Neural Regeneration Research (Neural Regen Res)

Bridging larger gaps in peripheral nerves using neural prosthetics and physical therapeutic agents Muhammad Sana Ullah Sahar, Matthew Barton, Geoffrey Douglas Tansley Neural Regeneration Research 2019 14(7):1109-1115 Peripheral nerve injuries are relatively common and can be caused by a variety of traumatic events such as motor vehicle accidents. They can lead to long-term disability, pain, and financial burden, and contribute to poor quality of life. In this review, we systematically analyze the contemporary literature on peripheral nerve gap management using nerve prostheses in conjunction with physical therapeutic agents. The use of nerve prostheses to assist nerve regeneration across large gaps (> 30 mm) has revolutionized neural surgery. The materials used for nerve prostheses have been greatly refined, making them suitable for repairing large nerve gaps. However, research on peripheral nerve gap management using nerve prostheses reports inconsistent functional outcomes, especially when prostheses are integrated with physical therapeutic agents, and thus warrants careful investigation. This review explores the effectiveness of nerve prostheses for bridging large nerve gaps and then addresses their use in combination with physical therapeutic agents.

Magnesium: Pathophysiological mechanisms and potential therapeutic roles in intracerebral hemorrhage Jason J Chang, Rocco Armonda, Nitin Goyal, Adam S Arthur Neural Regeneration Research 2019 14(7):1116-1121 Intracerebral hemorrhage (ICH) remains the second-most common form of stroke with high morbidity and mortality. ICH can be divided into two pathophysiological stages: an acute primary phase, including hematoma volume expansion, and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion. To date, all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control, surgical evacuation, and hemostasis. However, none of these trials has resulted in improved clinical outcomes. Magnesium is a ubiquitous element that also plays roles in vasodilation, hemostasis, and blood-brain barrier preservation. Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms. Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume, hematoma expansion, and clinical outcome in patients with ICH. These associations, coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH, suggest that magnesium may be a viable target of study in future ICH studies.

Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration David Romeo-Guitart, Caty Casas Neural Regeneration Research 2019 14(7):1122-1128 Peripheral nerve injuries caused by accidents may lead to paralysis, sensory disturbances, anaesthesia, and lack of autonomic functions. Functional recovery after disconnection of the motoneuronal soma from target tissue with proximal rupture of axons is determined by several factors: motoneuronal soma viability, proper axonal sprouting across inhibitory zones and elongation toward specific muscle, effective synapse contact rebuilding, and prevention of muscle atrophy. Therapies, such as adjuvant drugs with pleiotropic effects, that promote functional recovery after peripheral nerve injury are needed. Toward this aim, we designed a drug discovery workflow based on a network-centric molecular vision using unbiased proteomic data and neural artificial computational tools. Our focus is on boosting intrinsic capabilities of neurons for neuroprotection; this is in contrast to the common approach based on suppression of a pathobiological pathway known to be associated with disease condition. Using our workflow, we discovered neuroheal, a combination of two repurposed drugs that promotes motoneuronal soma neuroprotection, is anti-inflammatory, enhances axonal regeneration after axotomy, and reduces muscle atrophy. This drug discovery workflow has thus yielded a therapy that is close to its clinical application.

Exogenous neural stem cell transplantation for cerebral ischemia Ling-Yi Liao, Benson Wui-Man Lau, Dalinda Isabel Sánchez-Vidaña, Qiang Gao Neural Regeneration Research 2019 14(7):1129-1137 Cerebral ischemic injury is the main manifestation of stroke, and its incidence in stroke patients is 70–80%. Although ischemic stroke can be treated with tissue-type plasminogen activator, its time window of effectiveness is narrow. Therefore, the incidence of paralysis, hypoesthesia, aphasia, dysphagia, and cognitive impairment caused by cerebral ischemia is high. Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction. Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue. Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years. This review discusses the treatment of ischemic stroke with neural stem cells, as well as the mechanisms of their involvement in stroke treatment.

Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage Hideki Kanamaru, Hidenori Suzuki Neural Regeneration Research 2019 14(7):1138-1143 Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities. Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure, followed by global cerebral ischemia. Post-subarachnoid hemorrhage ischemia, tissue injuries as well as extravasated blood components and the breakdown products activate microglia, astrocytes and Toll-like receptor 4, and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades. Once blood-brain barrier is disrupted, brain tissues are directly exposed to harmful blood contents and immune cells, which aggravate brain injuries furthermore. Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins. Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage, but the exact mechanisms remain unclear. Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage. This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.

Choroid plexus tumor necrosis factor receptor 1: A new neuroinflammatory piece of the complex Alzheimer's disease puzzle Sophie Steeland, Roosmarijn E Vandenbroucke Neural Regeneration Research 2019 14(7):1144-1147 Due to the aging of the population and despite the enormous scientific effort, Alzheimer’s disease remains one of the biggest medical and pharmaceutical challenges in current medicine. Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer’s disease. Tumor necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2, but that also regulates several brain functions in health and disease. However, clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer’s disease led to inconclusive results, partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1, but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these trials. We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer’s disease patients, signaling via tumor necrosis factor receptor 1. In agreement with this, choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer’s disease mouse models. Interestingly, both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer’s disease-associated inflammation, choroidal morphology and cognitive functioning. Here, we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in (early) Alzheimer’s disease, and the consequences this might have on the disease progression. As the main hypothesis in Alzheimer’s disease clinical trials is still based on the amyloid beta-cascade, the importance of Alzheimer’s disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer’s disease and prevent the irreversible neurodegeneration and resulting memory decline.

Transcriptional dysregulation in neurodegenerative diseases: Who tipped the balance of Yin Yang 1 in the brain? Zhefan Stephen Chen, Ho Yin Edwin Chan Neural Regeneration Research 2019 14(7):1148-1151 Yin Yang 1 (YY1) is a multi-functional transcription factor that regulates gene expression in a range of cell types, including neurons. It controls neuronal differentiation, as well as neuronal specification and migration during the development of the mammalian nervous system. Besides, YY1 also mediates the transcription of genes that are required for neuronal survival. An impairment of the transcriptional function of YY1 causes neuronal death. This review summarizes recent research findings that unveil the dysfunction of YY1 in multiple neurodegenerative disorders. The expression of disease proteins perturbs the function of YY1 via distinct molecular mechanisms, including recruitment to protein aggregates, protein degradation and aberrant nuclear/cytoplasmic shuttling. Understanding the pathogenic roles of YY1 will further broaden our knowledge of the disease mechanisms in distinct neurodegenerative disorders.

Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment Chao Ren, Yong-Qiang Ji, Hong Liu, Zhe Wang, Jia-Hui Wang, Cai-Yi Zhang, Li-Na Guan, Pei-Yuan Yin Neural Regeneration Research 2019 14(7):1152-1157 Stem cell transplantation has brought new hope for the treatment of neurological diseases. The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells. Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors, the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located. Accordingly, the optimal microenvironment for inducing stem cell differentiation is a hot topic. EGb761 is extracted from the leaves of the Ginkgo biloba tree. It is used worldwide and is becoming one of the focuses of stem cell research. Studies have shown that EGb761 can antagonize oxygen free radicals, stabilize cell membranes, promote neurogenesis and synaptogenesis, increase the level of brain-derived neurotrophic factors, and replicate the environment required during the differentiation of stem cells into nerve cells. This offers the possibility of using EGb761 to induce the differentiation of stem cells, facilitating stem cell transplantation. To provide a comprehensive reference for the future application of EGb761 in stem cell therapy, we reviewed studies investigating the influence of EGb761 on stem cells. These started with the composition and neuropharmacology of EGb761, and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

Amelioration of Alzheimer's disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer's disease Bridget Martinez, Philip V Peplow Neural Regeneration Research 2019 14(7):1158-1176 The most common age-related neurodegenerative disease is Alzheimer’s disease (AD) characterized by aggregated amyloid-β (Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles, together with loss of cholinergic neurons, synaptic alterations, and chronic inflammation within the brain. These lead to progressive impairment of cognitive function. There is evidence of innate immune activation in AD with microgliosis. Classically-activated microglia (M1 state) secrete inflammatory and neurotoxic mediators, and peripheral immune cells are recruited to inflammation sites in the brain. The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects. Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials. Treatment with immunomodulatory/anti-inflammatory agents early in the disease process, while not preventive, is able to inhibit the inflammatory consequences of both Aβ and tau aggregation. The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD. The majority of the animal studies reviewed had used transgenic models of early-onset AD. More effort needs to be given to creat models of late-onset AD. The effects of a combinational therapy involving two or more of the tested pharmaceutical agents, or one of these agents given in conjunction with one of the cell-based therapies, in an aged animal model of AD would warrant investigation.

Precision medicine in pantothenate kinase-associated neurodegeneration Mónica Alvarez-Cordoba, Marina Villanueva-Paz, Irene Villalón-García, Suleva Povea-Cabello, Juan M Suárez-Rivero, Marta Talaverón-Rey, Javier Abril-Jaramillo, Ana Belén Vintimilla-Tosi, José A Sánchez-Alcázar Neural Regeneration Research 2019 14(7):1177-1185 Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas, mainly the basal ganglia. The predominant clinical symptoms include spasticity, progressive dystonia, Parkinson’s disease-like symptoms, neuropsychiatric alterations, and retinal degeneration. Among the neurodegeneration with brain iron accumulation disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2 (PANK2) which catalyzed the first reaction of the coenzyme A biosynthesis pathway. Currently there is no effective treatment to prevent the inexorable course of these disorders. The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN. Recently, we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules, mitochondrial dysfunction and a pronounced increase of markers of oxidative stress. In addition, PKAN fibroblasts showed a morphological senescence-like phenotype. Interestingly, pantothenate supplementation, the substrate of the PANK2 enzyme, corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression. However, pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein. The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts. Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations. Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment. The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate. The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available, and monitoring its effect on the pathophysiological changes, can help for a better therapeutic strategy. In addition, these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.

Mediterranean diet, alkaline water may be as effective as PPIs for laryngopharyngeal reflux

Alkaline water is water that's less acidic than regular tap water. This means it is rich in alkalizing compounds, including calcium, silica, potassium, magnesium, and bicarbonate.https://www.precisionnutrition.com/alkaline-water-legit-or-hoax

Seeing little relief with PPIs for patients, study author looked to dietary treatment for LPR

Treatment of laryngopharyngeal reflux (LPR) with alkaline water and the Mediterranean diet may be as effective as treatment with proton-pump inhibitors (PPIs), according to research published online in JAMA Otolaryngology–Head & Neck Surgery in September. Like gastroesophageal reflux disease, a similar condition, LPR occurs when acidic gastric juices in the stomach back up into the esophagus, but in LPR, the gastric juices reach the throat, resulting in symptoms such as hoarseness, sore throat, cough, and excessive mucous. 

In the study, researchers conducted a retrospective medical c­hart review comparing the change in Reflux Symptom Index (RSI) in two groups of patients, those treated between 2010 and 2012 with PPIs and standard reflux precautions and those treated between 2013 and 2015 with a plant-based Mediterranean diet and alkaline water that had a pH of at least 8. The team found that 54.1% of patients in the PPI group achieved a clinically meaningful reduction of at least 6 points, but 62.5% in the dietary group achieved similar results. Furthermore, those in the dietary group achieved a greater reduction in RSI: 39.8% compared with 27.2% in the PPI group.

"It's pretty clear that this data suggests that we, as health care professionals, need to start getting patients educated so they understand how important a role diet plays," said study lead author Craig H. Zalvan, MD, FACS, chief of otolaryngology and medical director at The Institute for Voice and Swallowing Disorders at Phelps Hospital in Sleepy Hollow, NY.

Zalvan said he thought to study dietary treatment for LPR after seeing that a sizable number of patients don't get much relief with PPIs.

"The standard of care for LPR has always been PPIs, and many of my patients got better with them, but a bunch didn't. At most it helps about 50% of patients," Zalvan said. "I looked at chronic diseases like heart disease, diabetes, and stroke, and their successful treatment with a plant-based diet, so I thought there's got to be a better way to treat LPR with diet [as well] and not have people constantly taking pills."

Zalvan added that the idea to incorporate alkaline water into treatment stemmed from prior research conducted by Jaime Koufman, MD, at the Voice Institute of New York in New York City, which suggests that alkaline water may benefit patients with reflux because it deactivates pepsin and acts as an acid buffer.

Zalvan said that as medication experts and readily accessible members of the health care team, pharmacists can help boost the signal about treatment options for LPR.

"Pharmacists can reinforce that PPIs are meant to be short-term medications for an acute problem, and that in order to get off them, diet will play a major part," Zalvan said. "If patients come to me and I say they should try diet, and then they go to the pharmacy and the pharmacist says they should try diet, patients are more likely to try diet."

For the full article, please visit www.pharmacytoday.org for the November 2017 issue of Pharmacy Today.

Clinical Thyroidology® for the Public – Highlighted Article

From Clinical Thyroidology^® for the Public: It is unclear if there is a link between hypothyroidism during pregnancy and the risk of asthma in children. The goal of this study is to examine whether hypothyroidism during pregnancy affected the risk of developing childhood asthma. Read More…

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Mutation profile of pfdhfr and pfdhps in Plasmodium falciparum among returned migrant workers in China from Africa [Epidemiology and Surveillance]

We evaluated markers of sulfadoxine-pyrimethamine (SP) resistance in P. falciparum among 254 returned migrant workers in China from Africa during 2013-2016. High prevalence of pfdhfr (97.2%) and pfdhps (96.5%) mutations were observed. The partially resistant genotype was homogeneously distributed in Africa with a modestly high prevalence (48%), whereas the super resistant genotype was only found in West Africa with a very low frequency (1.2%). The findings provided baseline data of molecular markers of SP resistance.

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Whole-genome sequencing analysis of multidrug-resistant serotype 15A Streptococcus pneumoniae in Japan and the emergence of a highly resistant serotype 15A-ST9084 clone [Mechanisms of Resistance]

Since the introduction of pneumococcal conjugate vaccines, an increase in the incidence of disease attributable to serotype 15A-ST63 pneumococci has been observed in many regions worldwide. We conducted a nationwide pediatric pneumococcal infection surveillance study between 2012 and 2014 in Japan. In the surveillance study, we detected multidrug-resistant serotype 15A-CC63 strains (resistant to macrolides, penicillin, cefotaxime and meropenem); in this study, we analyzed these resistant isolates to determine the dynamics and mechanism of resistance using whole-genome sequencing. In most of the penicillin-, cefotaxime- and meropenem-resistant strains, recombination occurred in the pbp2x region resulting in the acquisition of additional cefotaxime resistance to penicillin and meropenem. In the multidrug-resistant serotype 15A-CC63 strains, we identified a specific clone with ST9084, and all of the isolates were recovered from Yamaguchi prefecture in Japan. All of the serotype 15A-ST9084 isolates had a novel pbp2x-43 that was inserted by recombination events. The conserved amino acid motif profiles of pbp1a, pbp2b and pbp2x of the strains were identical to those in serotype 19A-ST320. A Bayesian analysis-based date estimation suggested that this clone emerged in approximately 2002 before the introduction of PCV in Japan. This clone should be monitored because serotype 15A is not contained in the currently used PCV13 and it was resistance to beta-lactams, which are often use in a clinical setting.

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Comparison of the Antiviral Activity of Bictegravir Against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants [Antiviral Agents]

We compared the activity of the integrase inhibitor bictegravir against HIV-1 and HIV-2 using a culture-based, single-cycle assay. EC₅₀ values ranged from 1.2 to 2.5 nM for nine HIV-1 isolates and 1.4 to 5.6 nM for 15 HIV-2 isolates. HIV-2 integrase mutants G140S/Q148R and G140S/Q148H were 34- and 110-fold resistant to bictegravir, respectively; other resistance-associated mutations conferred ≤5-fold changes in bictegravir susceptibility. Our findings indicate that bictegravir-based ART should be evaluated in HIV-2–infected individuals.

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Pharmacokinetics of levofloxacin in children treated for drug-resistant TB exposure [Clinical Therapeutics]

Levofloxacin is used to treat and prevent drug-resistant tuberculosis in children. We assessed levofloxacin serum drug concentrations for 24 children 2–10 years old receiving levofloxacin-based tuberculosis preventive therapy in Karachi, Pakistan. Only 9 (37.5%) children achieved adequate drug exposure. Target serum drug concentration was met in 4 (26.6%) of 15 children dosed consistently with World Health Organization recommendations, and 4 (80.0%) of 5 who received higher-than-recommended doses. Levofloxacin dosing recommendations may require reevaluation.

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A Nationwide Screen of carbapenem-resistant Klebsiella pneumoniae reveals an isolate with enhanced virulence and clinically undetected colistin-heteroresistance [Epidemiology and Surveillance]

The convergence of hypervirulence and multidrug-resistance in Klebsiella pneumoniae is a significant concern. We report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a US surveillance collection of carbapenem-resistant K. pneumoniae. We identified one hypermucoviscous isolate, encoding the KPC-3 carbapenemase among numerous resistance genes. The strain further exhibited colistin heteroresistance undetected by diagnostics. This convergence of diverse resistance mechanisms and increased virulence underscores the need for enhanced K. pneumoniae surveillance.

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Resistance Analysis of Bictegravir/Emtricitabine/Tenofovir Alafenamide in HIV-1 Treatment-Naïve Patients Through 48 Weeks [Antiviral Agents]

In Studies 1489 and 1490, bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), or DTG+F/TAF treatment achieved high rates of virologic suppression in HIV-1 treatment-naïve participants through Week 48. Pre-existing primary drug resistance was present at 1.3% INSTI resistance (-R), 2.7% NRTI-R, 14.1% NNRTI-R, and 3.5% PI-R in the 1274 participants from these studies. These mutations did not affect treatment outcomes. Resistance analyses in 13 virologic failures found no emergent resistance to study drugs.

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Serum Levels of Crushed Posaconazole Delayed Release Tablets [Letters]

Posaconazole (POS) delayed release tablets (DRT) are favored over the suspension formulation due to once-daily dosing and improved absorption....

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Fluoroquinolone efficacy against tuberculosis is driven by penetration into lesions and activity against resident bacterial populations [Pharmacology]

Fluoroquinolones are the pillar of multi-drug resistant tuberculosis (MDR-TB) treatment, with either moxifloxacin, levofloxacin or gatifloxacin being prescribed to MDR-TB patients. Recently, several clinical trials of 'universal' drug regimens, aiming to treat drug susceptible and resistant TB, have included a fluoroquinolone. In the absence of clinical data comparing their side-by-side efficacy in controlled MDR-TB trials, a pharmacological rationale is needed to guide the selection of the most efficacious fluoroquinolone. The present studies were designed to test the hypothesis that fluoroquinolone concentrations (pharmacokinetics) and activity (pharmacodynamics) at the site of infection are better predictors of efficacy than plasma concentrations and potency measured in standard growth inhibition assays, and to determine whether one of the fluoroquinolones outperforms the others in rabbits with active TB. We first measured the penetration of these fluoroquinolones in lung lesion compartments, and their potency against bacterial populations that reside in each compartment, to compute lesion-centric pharmacokinetic-pharmacodynamic (PK-/PD) parameters. PK modeling methods were used to quantify drug penetration from plasma to tissues at human-equivalent doses. Based on these metrics, moxifloxacin emerged with a clear advantage, whereas plasma-based PK/PD favored levofloxacin (plasma AUC/MIC range is 46-86 for moxifloxacin and 74-258 for levofloxacin). A comparative efficacy trial in the rabbit model of active TB demonstrated the superiority of moxifloxacin in reducing bacterial burden at the lesion level, and sterilizing cellular and necrotic lesions. Collectively, these results show that PK-PD at the site of infection is an adequate predictor of drug efficacy against TB, and constitute the baseline required to explore synergies, antagonism and drug-drug interactions in fluoroquinolone-containing regimens.

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Resistance and virulence mechanisms of Escherichia coli selected by enrofloxacin in chicken [Mechanisms of Resistance]

This study aimed to investigate the genetic characteristics, antibiotic resistance patterns and novel mechanisms involved in fluoroquinolone (FQ) resistance in commensal Escherichia coli (E. coli). The E. coli were recovered from a previous clinical study and subjected to antimicrobial susceptibility testing and molecular typing. Known mechanisms of FQ resistance (target sites mutation, plasmid-mediated quinolone resistance (PMQR) genes, relative expression levels of efflux pumps and porins) were detected using DNA sequencing of PCR products and real-time qPCR. Whole genome shotgun sequencing was performed on 11 representative strains to screen for SNPs. The function of a key SNP (A1541G) was investigated by site-directed mutagenesis and allelic exchange. Results showed that long term enrofloxacin treatment selected multidrug resistant (MDR) E. coli in chicken gut and these E. coli isolates had diverse genetic backgrounds. Multiple genetic alterations including double mutations on GyrA (S83L and D87N), single mutation on ParC (S80I) and ParE (S458E), activation of efflux pumps and QnrS1 protein contributed to the high-level FQ resistance (MIC_ENR≥128 μg/mL), while the relative low-level FQ resistance (MIC_ENR=8 or 16 μg/mL) was commonly mediated by decreased expression of the porin OmpF, besides enhancement of the efflux pumps. No significant relationship was observed between resistance mechanisms and virulence genes. Introduction of A1541G mutation on aegA was able to increase the FQ susceptibility by 2-fold. This study contributed to better understanding of the development of MDR and differences underlying mechanisms of high-level and low-level FQ resistance in E. coli.

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Antibiotic treatment duration for bacteremia due to Enterobacteriaceae: A systematic review and meta-analysis [Clinical Therapeutics]

Background: The duration of antibiotic therapy for bacteremia due to Enterobacteriaceae is not well-defined. We sought to evaluate the clinical outcomes with shorter versus longer-course treatment.

Methods: We performed a systematic search of the PubMed and EMBASE databases through May 2018. Studies presenting comparative outcomes between patients receiving antibiotic treatment for ≤10 days ("short-course") and those treated for >10 days ("long-course") were considered eligible.

Results: Four retrospective cohort studies and one randomized controlled trial comprising 2,865 patients met the inclusion criteria. Short and long-course antibiotic treatment did not differ in 30-day all-cause mortality (1,374 patients, RR= 0.99, 95% CI (0.69-1.43)), 90-day all-cause mortality (1,750 patients, RR= 1.16 (95% CI, 0.81-1.66)), clinical cure (1,080 patients, RR= 1.02 (95% CI, 0.96-1.08)), or relapse at 90 days (1,750 patients, RR= 1.08 95% CI (0.69-1.67)).

Conclusions: In patients with bacteremia due to Enterobacteriaceae, short and long-course antibiotic treatment did not differ significantly in terms of clinical outcomes. Further well-designed studies are needed before treatment for 10 days or less is adopted in clinical practice.

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Measuring Antimicrobial Efficacy against Biofilms: A Meta-Analysis [Analytical Procedures]

Through a statistical meta-analysis of published data on antimicrobial efficacy against biofilms formed by two common bacterial species it was concluded that the particular experimental method used is the most important factor determining the outcome of the test. An expected dose-response behavior (greater killing with higher dose concentrations or longer treatment times) was observed for data sets derived from a single method, but was not observed when data from multiple studies using diverse methods were pooled. Method specific properties such as the surface area to volume ratio, areal biofilm cell density, and microbial species were shown to influence quantitative measurements of biofilm killing. A better appreciation of the method characteristics that affect anti-biofilm efficacy tests could aid decision-making related to investment in research and development and regulatory approvals for biofilm control strategies. These recommendations are offered to those working in research and development related to biofilm control: 1) report the log reduction, surface area to volume ratio, and biofilm areal cell density; 2) include data for a benchmark agent, making sure that this agent performs competitively at the dose tested; 3) measure a dose response, i.e., make measurements at multiple treatment concentrations or dose durations; and 4) use a standardized method in addition to research methods.

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Molecular characterization of multidrug-resistant Pseudomonas aeruginosa isolates in hospitals in Myanmar [Epidemiology and Surveillance]

The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa has become a serious worldwide medical problem. This study was designed to clarify the genetic and epidemiological properties of MDR P. aeruginosa strains isolated from hospitals in Myanmar. Forty-five MDR P. aeruginosa isolates obtained from different patients in seven hospitals in Myanmar were screened by the broth microdilution method. The whole genomes of the MDR isolates were sequenced by MiSeq (Illumina). Phylogenetic trees were constructed from single nucleotide polymorphism concatemers. Multilocus sequence types were deduced and drug resistance genes were identified. Of the 45 isolates, 38 harbored genes encoding carbapenemases, including DIM-1, IMP-1, NDM-1, VIM-2 and VIM-5; and nine had genes encoding 16S rRNA methylases, including RmtB, RmtD3, RmtE and RmtF2. Most strains of MDR P. aeruginosa isolated in Myanmar belonged to ST1047. This is the first molecular epidemiological analysis of MDR P. aeruginosa clinical isolates in Myanmar. These findings strongly suggest that P. aeruginosa ST1047 harboring carbapenemases, including DIM-, IMP-, NDM- and VIM-type metallo-β-lactamases, have been spreading throughout medical settings in Myanmar.

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NG-test Carba5 for rapid detection of carbapenemase-producing Enterobacterales from positive blood cultures [Mechanisms of Resistance]

The immunochromatographic assay, NG-test Carba5 (NG-biotech), has been evaluated for detection of carbapenemase-producing Enterobacterales (CPE) from spiked blood cultures (n=205). It detected and discriminated in less than 30 minutes KPC-, IMP-, VIM-, NDM- and OXA-48-like-producers with a sensitivity and specificity of 97.7% and 96.1%. Thus, it might help the rapid optimization of treatment of bloodstream infections due to CPE.

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Sitagliptin and Simvastatin Interaction Causing Rhabdomyolysis and AKI

We report a case of rhabdomyolysis and severe acute kidney injury (AKI) requiring dialysis in a 69-year-old male who was recently started on sitagliptin while on chronic simvastatin therapy. This potential interaction is not included in the package insert for sitagliptin. A comprehensive literature review revealed six previous reports of rhabdomyolysis due to drug interaction between sitagliptin and statins including simvastatin, lovastatin, and atorvastatin. Of these six cases, only two had developed rhabdomyolysis-associated AKI, none of which were severe enough to require dialysis. As patients are commonly prescribed statins and sitagliptin for treatment of dyslipidemia and diabetes, health care professionals should be aware of this potential drug interaction and closely monitor their patients for signs and symptoms of rhabdomyolysis and AKI. This case highlights the importance of conducting further studies on the risk of muscular toxicity of sitagliptin especially when administered concurrently with statins.

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Combination hyperbaric oxygen therapy and ustekinumab for severe hidradenitis suppurativa

Abstract

Hidradenitis suppurativa is a painful chronic inflammatory skin condition characterized by inflammatory nodules that can lead to sinus tracts and scarring. Numerous treatments have been reported, though none have reliable efficacy. Antiinflammatory agents, such as tumor necrosis factor‐alpha inhibitors and interleukin inhibitors, have been used as medical therapy for refractory cases. We describe here a case of severe hidradenitis suppurativa in a pediatric patient successfully treated with a combination of high‐dose ustekinumab and hyperbaric oxygen therapy.

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Vorgehen bei Schilddrüsenkarzinomen in einer medianen Halszyste

Laryngo-Rhino-Otol
DOI: 10.1055/a-0850-0154

Schilddrüsenkarzinome aus Residuen des Ductus thyreoglossus sind eine Seltenheit und werden meist als Zufallsbefund postoperativ festgestellt. Es gibt keine klaren Richtlinien für das korrekte therapeutische Vorgehen nach erfolgter Resektion, insbesondere bezüglich der Notwendigkeit einer totalen Thyroidektomie und Radioiodtherapie. Vor dem Hintergrund der aktuellen Literatur wird eine Fallserie von fünf Patienten mit Schilddrüsenkarzinomen in einer medianen Halszyste präsentiert. Es erfolgte eine retrospektive Analyse aller Patienten mit einem Schilddrüsenkarzinom in einer medianen Halszyste im Zeitraum zwischen 2002 und 2017.Von 578 Patienten, die aufgrund einer medianen Halszyste operiert wurden, konnte bei fünf dieser Patienten (3 Frauen, 2 Männer), im Alter von 16–73 Jahren (Altersmittelwert 51; Median 56 Jahre) ein Schilddrüsenkarzinom gesichert werden. Klinisch stellten sich alle Patienten mit einer schmerzlosen Schwellung im Bereich des Zungenbeins vor. Die Diagnose wurde in allen Fällen postoperativ gestellt, in einem Fall wurde in der präoperativen Bildgebung bereits ein Malignom vermutet. Histologisch zeigte sich in allen Fällen ein papilläres Schilddrüsenkarzinom. Vier Patienten erhielten im Intervall eine totale Thyroidektomie und Radioiodtherapie, zwei davon zusätzlich eine Neck dissection des medialen und lateralen Kompartiments, der fünfte Patient hat sich einer weiteren Diagnostik und Therapie entzogen. Es wurden in allen vier Fällen keine Karzinome der Schilddrüse oder Lymphknotenmetastasen nachgewiesen.Aufgrund der Seltenheit von Schilddrüsenkarzinomen in medianen Halszysten existiert derzeit kein standardisiertes therapeutisches Vorgehen. Es sollte eine Risikostratifizierung vorgenommen werden, um Patienten, die von einer zusätzlichen Thyroidektomie profitieren könnten, zu identifizieren. Die Prognose ist sehr gut.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2IzrnR7

Der neuartige Propel mini Stent – Indikationen, Operationstechnik und erste klinische Erfahrungen

Laryngo-Rhino-Otol
DOI: 10.1055/a-0839-5206

Hintergrund Die Therapie der chronischen Sinusitis frontalis stellt sich aufgrund des anatomisch engen Abflusses in die Nasenhaupthöhle häufig als problematisch dar. Neben konservativen Methoden wurden bisher auch viele chirurgische Therapieverfahren, sowohl mit als auch ohne Einsatz von Platzhaltern, jedoch ohne längerfristigen Therapieerfolg erprobt. Ziel dieser Arbeit war die klinische Testung der allgemeinen Praktikabilität und der kurz- sowie langfristige Therapieerfolg des neuartigen bioresorbierbaren Propel mini Stents. Material und Methoden In einer prospektiven Studie an 21 Patienten mit chronischer Rhinosinusitis mit Polyposis nasi wurde die chirurgische Therapie und das Einbringen des Stents dargestellt und die Degradation von insgesamt 31 Stents sowie der Erfolg dieser Therapieform über einen Zeitraum von 6 Monaten endoskopisch kontrolliert und analysiert. Ergebnisse Hinsichtlich chirurgischer Praktikabilität erwies sich der Stent mit Einführungstool als unkompliziertes und leicht bedienbares System. Alle Patienten haben die Stents gut toleriert. Die durchschnittliche, nachweisbare Materialabsorption überdauerte 28 Tage. Das Patientenkollektiv zeigte in 94 % der Fälle nach 3 Monaten und in 87 % der Fälle nach 6 Monaten einen vollständig sondierbares Neo-Ostium des Sinus frontalis. Schlussfolgerung Die Ergebnisse der prospektiven Studie zeigen insgesamt eine gute Akzeptanz bei den Patienten ohne Komplikationen sowie eine vollständige Stentdegradation. Auch die Follow-Up-Untersuchungen ergaben zufriedenstellende Ergebnisse über 6 Monate. Insbesondere unter dem Aspekt der endoskopischen Operation erwies sich das Stent-System als sehr praktikabel.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2TfJijL

High expression of MLANA in the plasma of patients with head and neck squamous cell carcinoma as a predictor of tumor progression

Background

There is a paucity of plasma‐based biomarkers that predict outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation therapy (CRT). Here, we evaluate the prognostic potential of plasma Melanoma‐Antigen Recognized by T‐cells 1 (MLANA) in this setting.

Methods

MLANA expression in HNSCC lines were evaluated by reverse transcription polymerase chain reaction, whereas plasma levels were quantified using ELISA in 48 patients with locally advanced HNSCC undergoing a phase 2 trial with CRT.

Results

MLANA is expressed at variable levels in a panel of HNSCC lines. In plasma, levels were elevated in patients with tumor relapse compared to those without (P < .004); 73.9% of the patients expressing high plasma MLANA levels progressed with recurrent disease (P = .020). Multivariate analysis showed that plasma MLANA levels and tumor resectability were independent prognostic factors for progression free survival.

Conclusion

Plasma MLANA expression appears to be an effective noninvasive biomarker for outcomes in patients treated with CRT, and could potentially guide therapeutic decisions in this context.

https://ift.tt/2BMVTBd

Bronchial hyperresponsiveness in children with allergic rhinitis and the associated risk factors

https://ift.tt/2EdAAcs

Localization and age distribution of telangiectases in children and adolescents with hereditary hemorrhagic telangiectasia: A retrospective cohort study

The location of telangiectases in hereditary hemorrhagic telangiectasia (HHT), as set forth in the consensus diagnostic (Curaçao) criteria, is based primarily on adults.

https://ift.tt/2Ti0y85

Dermoscopy of hyperkeratosis lenticularis perstans (Flegel disease)

https://ift.tt/2IB04G3

Psoriasis Effects on CV Risk May be Direct and Vary by Race

'It may still be an independent effect of the psoriasis, but acting through these other traditional risk factors,' said a researcher. Younger African-American adults seemed to be at special risk.
Medscape Medical News

https://ift.tt/2NukejN

Evaluation of major mite allergens from European standardized commercial extracts for in vivo diagnosis: addressing the need for precision medicine

Skin prick testing is the first-line interventional method to diagnose IgE mediated allergic diseases. Methodological differences in manufacturing processes and extract standardization may lead to variations i...

https://ift.tt/2Ew7RRe

Which imaging modality in cochlear implant candidates?

Abstract

Purpose

There is no guideline or consensus on preoperative radiologic imaging modality despite the fact that it has a vital importance in appropriate candidacy selection of cochlear implantation. We aimed to find out the role of high-resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) on surgical planning, intraoperative technique in cochlear implant candidates.

Methods

The clinical charts, imagings, and operative reports of patients who underwent cochlear implant surgery at a tertiary institution were retrospectively examined.

Results

611 patients (503 children and 108 adult) were enrolled into the study. We found 11 different pathologies in MRI which could not be seen in HRCT. However, we decided the side of surgery according to MRI in only three of them in which the pathology was cochlear nerve hypoplasia. Two patients with cochlear nerve hypoplasia were children with prelingual deafness and one was adult with perilingual deafness. Moreover, we changed the surgical planning of side according to both imaging modalities in nine patients. Seven of them were children and two were adult. One of these adults had cochlear anomaly, and another had bilateral temporal bone fracture.

Conclusions

We suggest both imaging modalities in pediatric candidates. However, in adults, we think that superiority of either imaging modalities is still contradictive. We had only three adult patients and the decision of the side of surgery was made according to MRI in one of them and to both imaging modalities in the other two adults.

https://ift.tt/2BOjrpe

Adjuvant Radiotherapy in Early Stage Oral Cancers

Conditions:   Cancer of Mouth;   Cancer of the Tongue;   Cancer of the Head and Neck;   Buccal Mucosa Cancer;   Floor of Mouth Carcinoma
Intervention:   Radiation: Post-operative adjuvant radiotherapy
Sponsor:   Tata Memorial Hospital
Recruiting

https://ift.tt/2TeK4xp

A Phase Ib/II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, for Advanced Solid Tumors or With mXELOX as First-line Therapy for Advanced Gastric or GEJ Adenocarcinoma

Conditions:   Gastric Adenocarcinoma;   Advanced Solid Tumors;   Gastroesophageal Junction Adenocarcinoma
Interventions:   Biological: AK104;   Drug: Oxaliplatin;   Drug: Capecitabine
Sponsors:   Akeso;   Akeso Pharmaceuticals, Inc.
Recruiting

https://ift.tt/2Iz6Mwc

Crowd Spatial Patterns at Bus Stops: Security Implications and Effects of Warning Messages

Solymosi, R; Borrion, H; Fujiyama, T; (2015) Crowd Spatial Patterns at Bus Stops: Security Implications and Effects of Warning Messages. In: Newton, A and Ceccato, V, (eds.) Safety and Security in Transit Environments: An Interdisciplinary Approach. (pp. 156-178). Palgrave Macmillan: London, UK. Green open access

https://ift.tt/2SnhDZH

Numerical analysis of the in-plane behaviour of three-leaf stone masonry panels consolidated with grout injection

Silva, BQ; Pappas, A; Guedes, JM; da Porto, F; Modena, C; (2017) Numerical analysis of the in-plane behaviour of three-leaf stone masonry panels consolidated with grout injection. Bulletin of Earthquake Engineering , 15 (1) pp. 357-383. 10.1007/s10518-016-9969-5 . Green open access

https://ift.tt/2XouZZB

Late Antiquity

Salway, B; (2014) Late Antiquity. In: Bruun, C and Edmondson, J, (eds.) The Oxford Handbook of Roman Epigraphy. (pp. 364-393). Oxford University Press: Oxford, UK.

https://ift.tt/2SrkFMC

Early risk factors for depression, anxiety and post-traumatic distress after hospital admission for unintentional injury: Multicentre cohort study

Kendrick, D; Baker, R; Hill, T; Beckett, K; Coupland, C; Kellezi, B; Joseph, S; ... Morriss, R; + view all Kendrick, D; Baker, R; Hill, T; Beckett, K; Coupland, C; Kellezi, B; Joseph, S; Barnes, J; Sleney, J; Christie, N; Morriss, R; - view fewer (2018) Early risk factors for depression, anxiety and post-traumatic distress after hospital admission for unintentional injury: Multicentre cohort study. Journal of Psychosomatic Research , 112 pp. 15-24. 10.1016/j.jpsychores.2018.06.008 .

https://ift.tt/2Xov6nZ

Cybersecurity: Policy

Chung, AS; Dawda, S; Hussain, A; Shaikh, SA; Carr, M; (2018) Cybersecurity: Policy. In: Shapiro, LR and Maras, M-H, (eds.) Encyclopedia of Security and Emergency Management. Springer Nature: Cham, Switzerland.

https://ift.tt/2SqFjMJ

The ’Good Workplace’: The Role of Joint Consultative Committees, Unions and HR Policies in Employee Ratings of Workplaces in Britain

Bryson, A; Barry, M; Gomez, R; Lomas, G; Kaufman, B; Wilkinson, A; (2019) The 'Good Workplace': The Role of Joint Consultative Committees, Unions and HR Policies in Employee Ratings of Workplaces in Britain. Journal of Participation and Employee Ownership (In press).

https://ift.tt/2XouQFx

Feasibility of using a novel non-invasive ambulatory tibial nerve stimulation device for the home-based treatment of overactive bladder symptoms

Seth, JH; Gonzales, G; Haslam, C; Pakzad, M; Vashisht, A; Sahai, A; Knowles, C; ... Panicker, J; + view all Seth, JH; Gonzales, G; Haslam, C; Pakzad, M; Vashisht, A; Sahai, A; Knowles, C; Tucker, A; Panicker, J; - view fewer (2018) Feasibility of using a novel non-invasive ambulatory tibial nerve stimulation device for the home-based treatment of overactive bladder symptoms. Translational Andrology and Urology , 7 (6) pp. 912-919. 10.21037/tau.2018.09.12 .

https://ift.tt/2SpQHIX

Vacant land in London: a planning tool to create land for growth

Freire Trigo, S; (2019) Vacant land in London: a planning tool to create land for growth. International Planning Studies 10.1080/13563475.2019.1585231 . (In press).

https://ift.tt/2XouIG3

Bistatic Cross Section of Ships Between P and S Band

Stove, A; Antoniou, M; Tzagkas, D; Ritchie, M; (2018) Bistatic Cross Section of Ships Between P and S Band. In: 2018 International Conference on Radar (RADAR). IEEE: Brisbane, Australia. Green open access

https://ift.tt/2Sm4XT7

Why the current Peak in Populism in the US and Europe? Populism as a Deviation in the Median Voter Theorem

Figueira, F; (2018) Why the current Peak in Populism in the US and Europe? Populism as a Deviation in the Median Voter Theorem. European Journal of Government and Economics , 7 (2) pp. 154-170. 10.17979/ejge.2018.7.2.4423 . Green open access

https://ift.tt/2XmEGHY

Improvisation and Transformation: Yes to the Mess

Barrett, FJ; Huffaker, J; Fisher, CM; Burgaud, D; (2018) Improvisation and Transformation: Yes to the Mess. In: Neal, J, (ed.) Handbook of Personal and Organizational Transformation. Springer: New York, NY, USA.

https://ift.tt/2Sm4QXH

Why Would the Rise of Social Media Increase the Influence of Traditional Media on Collective Judgments? A Response to Blevins and Ragozzino

Ravasi, D; Etter, M; Colleoni, E; (2019) Why Would the Rise of Social Media Increase the Influence of Traditional Media on Collective Judgments? A Response to Blevins and Ragozzino. Academy of Management Review , 44 (1) pp. 222-226. 10.5465/amr.2018.0065 .

https://ift.tt/2Xouwqj

Research on Uncertainty

Pratt, D; Kazak, S; (2018) Research on Uncertainty. In: Ben-Zvi, D and Makar, K and Garfiled, J, (eds.) International Handbook of Research in Statistics Education. (pp. 193-228). Springer: Cham, Switzerland.

https://ift.tt/2Sm4IaF

Lazarillo de Tormes and the dream of a world without poverty

Samson, A; (2015) Lazarillo de Tormes and the dream of a world without poverty. In: Garrido Ardila, JA, (ed.) The Picaresque Novel in Western Literature: From the Sixteenth Century to the Neopicaresque. (pp. 24-39). Cambridge University Press: Cambridge, UK. Green open access

https://ift.tt/2XjK0Ma

Opto‐epigenetic modulation of DNA methylation with a photo‐responsive small‐molecule approach

Nguyen, HP; Stewart, S; Kukwikila, MN; Jones, SF; Offenbartl-Stiegert, D; Mao, S; Balasubramanian, S; ... Howorka, S; + view all Nguyen, HP; Stewart, S; Kukwikila, MN; Jones, SF; Offenbartl-Stiegert, D; Mao, S; Balasubramanian, S; Beck, S; Howorka, S; - view fewer (2019) Opto‐epigenetic modulation of DNA methylation with a photo‐responsive small‐molecule approach. Angewandte Chemie International Edition 10.1002/anie.201901139 . (In press).

https://ift.tt/2StNng4

Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature

Antony, D; Nampoory, N; Bacchelli, C; Melhem, M; Wu, K; James, CT; Beales, PL; ... Alsmadi, O; + view all Antony, D; Nampoory, N; Bacchelli, C; Melhem, M; Wu, K; James, CT; Beales, PL; Hubank, M; Thomas, D; Mashankar, A; Behbehani, K; Schmidts, M; Alsmadi, O; - view fewer (2017) Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature. [Review]. European Journal of Medical Genetics , 60 (12) pp. 658-666. 10.1016/j.ejmg.2017.08.019 . Green open access

https://ift.tt/2XmEGYu

Quality of Life in Head and Neck Cancer Patients

Abstract

To assess the quality of life in head and neck cancer patients and the various factors which affect the quality of life in head and neck cancer patients was the main aim of the study. A prospective longitudinal study with a sample size of 130 patients was done within the time period of one and a half years. Patients with biopsy proven squamous cell carcinoma of the head and neck were treated as per their treatment protocol either by combined modality or single modality. Follow up at the completion of treatment was done and the quality of life questionnaire was filled out. QoL was assessed pre-treatment and at 4 times at different stages of follow up period. Demographic data was also taken into consideration for comparison which showed that head and neck cancer is more common in the males (80%) between the age group of 35–50 years, chronic tobacco chewers (45%) with most common site of cancer being the oral cavity (61%). Majority of the patients presented at Stage IV of their disease (35%) with largest HRQoL changes seen within the first three months after commencement of treatment. The most debilitating modality of treatment was Surgery + CTRT. Detailed assessment of the various factors which hamper the QoL in head and neck cancer patients should be done by which we can provide quality care and a completely new view into the health care experience and improving patient satisfaction.

https://ift.tt/2VkKno0

A population pharmacokinetic model of AT9283 in adults and children to predict the maximum tolerated dose in children with leukaemia

Duong, JK; Griffin, MJ; Hargrave, D; Vormoor, J; Edwards, D; Boddy, AV; (2017) A population pharmacokinetic model of AT9283 in adults and children to predict the maximum tolerated dose in children with leukaemia. British Journal of Clinical Pharmacology , 83 (8) pp. 1713-1722. 10.1111/bcp.13260 . Green open access

https://ift.tt/2SmEp40

Improving Mouse Models for Dementia. Are All the Effects in Tau Mouse Models Due to Overexpression?

Joel, Z; Izquierdo, P; Salih, DA; Richardson, JC; Cummings, DM; Edwards, FA; (2019) Improving Mouse Models for Dementia. Are All the Effects in Tau Mouse Models Due to Overexpression? Cold Spring Harbor Symposia on Quantitative Biology 10.1101/sqb.2018.83.037531 . (In press). Green open access

https://ift.tt/2Xqwq9E

Non-alcoholic fatty liver disease (NAFLD) and the quest for effective treatments

Thanapirom, K; Tsochatzis, EA; (2019) Non-alcoholic fatty liver disease (NAFLD) and the quest for effective treatments. Hepatobiliary Surgery and Nutrition , 8 (1) pp. 77-79. 10.21037/hbsn.2018.11.06 .

https://ift.tt/2SsZjOQ

Loss of trefoil factor 2 1 sensitizes rat pups to systemic infection with the neonatal pathogen Escherichia coli K1

McCarthy, A; Birchenough, GMH; Taylor, P; (2019) Loss of trefoil factor 2 1 sensitizes rat pups to systemic infection with the neonatal pathogen Escherichia coli K1. Infection and Immunity (In press).

https://ift.tt/2XlSHp8

Quality of Life in Head and Neck Cancer Patients

Abstract

To assess the quality of life in head and neck cancer patients and the various factors which affect the quality of life in head and neck cancer patients was the main aim of the study. A prospective longitudinal study with a sample size of 130 patients was done within the time period of one and a half years. Patients with biopsy proven squamous cell carcinoma of the head and neck were treated as per their treatment protocol either by combined modality or single modality. Follow up at the completion of treatment was done and the quality of life questionnaire was filled out. QoL was assessed pre-treatment and at 4 times at different stages of follow up period. Demographic data was also taken into consideration for comparison which showed that head and neck cancer is more common in the males (80%) between the age group of 35–50 years, chronic tobacco chewers (45%) with most common site of cancer being the oral cavity (61%). Majority of the patients presented at Stage IV of their disease (35%) with largest HRQoL changes seen within the first three months after commencement of treatment. The most debilitating modality of treatment was Surgery + CTRT. Detailed assessment of the various factors which hamper the QoL in head and neck cancer patients should be done by which we can provide quality care and a completely new view into the health care experience and improving patient satisfaction.

https://ift.tt/2VkKno0

Phacomorphic glaucoma in a high myope with phakic intraocular lens

We report a case of a young, one-eyed woman with high myopia who presented to our emergency department with sudden onset painful diminution of vision in the right eye after undergoing laser treatment. Her right eye had a phakic intraocular lens (pIOL) implantation 4 years back and her left eye had absent light perception. She was diagnosed as right eye lens induced secondary angle closure glaucoma with pIOL touching the corneal endothelium and left eye atrophic bulbi. She was admitted under eye emergency for medical intraocular pressure control followed by pIOL explantation with lens aspiration of the cataractous lens and posterior chamber intraocular lens implantation.

https://ift.tt/2Tj6L3C

"Fungating" tumour? No, its bacterial!

A fit and healthy 26-year-old woman presented to the general surgical team with epigastric pain and weight loss of 2 stones over 6 months. She has also a positive family history of ulcerative colitis. As her oesophagogastroduodenoscopy and colonoscopy were normal, a contrasted CT was requested, and it detected an inflammatory mass with fat streaking around her transverse colon. An intrauterine contraceptive device (IUCD) was noted. In light of the CT findings, she underwent a diagnostic laparoscopy. As the inflammatory mass was not separable from the transverse colon, a segmental transverse colectomy was proceeded. The histology revealed multiple actinomycosis abscesses in the mesentery. Subsequently, we learnt that her IUCD had been in situ for the last 7 years, and the source of actinomycosis abscesses is likely from her IUCD. The patient was recommended to have the coil removed and commenced on a 6 months course of amoxicillin.

https://ift.tt/2NuxpkB

Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5–10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13–1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30–100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient's hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

https://ift.tt/2NtQROo

Urinary tract bleeding from a urethral caruncle mimicking genital tract bleeding

A 69-year-old Japanese woman with a post-hysterectomy status came to our primary care clinic. She presented with vaginal bleeding for the past 3 days which had developed after defecation. There was a palpable mass measuring approximately 2 cm on pelvic exam; however, heavy bleeding prevented in-depth observation. CT and MRI scans revealed that the mass was inside the urethral meatus and not in the vagina. She underwent surgical resection of the urethral tumour, and the pathological report showed no malignancy. A final diagnosis of urethral caruncle was made. Vaginal bleeding is commonly encountered in the primary care practice and is usually attributed to gynaecological diseases. However, patients and physicians may falsely regard urinary or gastrointestinal tract bleeding as one involving the genital tract. We present a case wherein vaginal bleeding was initially considered but was later identified to be due to a urethral caruncle.

https://ift.tt/2Tiwjhl

Sentinel bruising as a presentation of metastatic melanoma

A 46-year-old man presented with a 4-week history of bruising with subcutaneous nodules and weight loss. He also had a 2-week history of progressive back and hip pain. He had been diagnosed with stage Ib cutaneous melanoma 30 months previously, which had been fully excised. A sentinel lymph node biopsy was negative. On examination, there were five skin lesions at different stages. Each had spontaneously appeared as a bruise with a central subcutaneous nodule, and the bruising then faded to leave a persistent subcutaneous nodule. Excision of one of the nodules demonstrated a 4.5 mm diameter partly necrotic melanoma deposit in the dermis. CT scan of the head, chest, abdomen and pelvis showed widespread metastases. This rare presentation of cutaneous malignant melanoma metastases has been termed 'sentinel bruising'. There are fewer than 10 cases reported in the literature.

https://ift.tt/2Ntqlop

How does knowledge of the blood supply to an intracardiac tumour help?

Myxoma is a common benign tumour found in the heart. On reviewing literature, we found some left atrial myxomas receive blood supply from the right coronary artery. Performing a coronary angiogram in a cardiac tumour has the following uses: (1) it shows the vascularity that can be ligated by the surgeon at operation; (2) if there is a blood supply visible, it may not be an intracardiac thrombus; (3) the coronary angiogram may detect a myxoma even before an echocardiogram does so; (4) some myxomas may bleed into the right atrium or left atrium and this may be seen on coronary angiography. We show here the neovascularity of a left atrial myxoma and its blood supply from the right coronary artery. We recommend that all routine coronary angiograms be reviewed carefully for any signs of tumour vascularity or tumour blush as this would prevent missing early myxomas. Echocardiography is the gold standard for detection of myxomas but literature has a number of intracardiac tumours that were detected only by the tumour blush. Some left atrial tumours have been treated by occluding their blood supply.The absence of a blood supply on coronary angiography could rule out a benign cardiac tumour that usually has a blood supply.

https://ift.tt/2TdbVhH

Rare cause of subarachnoid haemorrhage

https://ift.tt/2NtQJyo

Extrapulmonary uterine lymphangioleiomyomatosis (LAM) and dysfunctional uterine bleeding: the first presentation of LAM in a tuberous sclerosis complex patient

Lymphangioleiomyomatosis (LAM) is a rare disease that typically affects women of childbearing age. It most commonly affects the lungs (P-LAM) but can occasionally occur in extra-pulmonary sites (E-LAM). There is a strong association between LAM and the tuberous sclerosis complex (TSC). We report a case of a 42-year-old female TSC sufferer who presented with dysfunctional uterine bleeding. She was not known to have LAM. An endometrial biopsy revealed a spindled-cell lesion suspicious of leiomyosarcoma, which correlated with cross-sectional imaging. She underwent a hysterectomy that showed a bizarre (symplastic) leiomyomatous endometrial polyp with background uterine LAM. We discuss the clinical and pathological implications of this unusual case of E-LAM and the importance of clinicopathological correlation in TSC sufferers. The association of uterine LAM with TSC is important and LAM should be considered as a differential of dysfunctional uterine bleeding and a benign mimic to uterine leiomyosarcoma in patients with TSC.

https://ift.tt/2Ud6AnX

Regulatory aspects of prospective and retrospective clinical research in France in 2018

Publication date: Available online 23 February 2019

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): P. Gorphe, C. Jannin

Abstract

In France, the so-called "Jardé law" (named for its proposer) on human research, implemented since 2016, defines the regulatory and legal framework for "prospective" studies, formerly known as "biomedical research" or "common care". Three categories are distinguished: type 1 is at-risk drug or non-drug interventional research, type 2 is low-risk, low-burden interventional research, and type 3 is non-interventional research. The decrees of April 12, 2018 precisely define a list of research categories for types 2 and 3, thereby clarifying the regulatory procedures. The Sponsor registers the trial on the database of the National Drug Safety Agency (ANSM), or the European EudraCT database for drug studies, to obtain an identification number. Regulatory procedures are undertaken with the IRB and ANSM and then the Data Protection Commission (CNIL). Retrospective research on previously collected data (other than genetic) does not come under the Jardé law, and is governed by the 1978 data protection law, updated by the application decree of December 2016 and the law No. 2018-493 of June 20, 2018 on protection of personal data. This article presents a clarification of the key methodologic and regulatory steps.

https://ift.tt/2TitI75

Vestibular Infant Screening – Flanders: the implementation of a standard vestibular screening protocol for hearing-impaired children in Flanders

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Sarie Martens, Ingeborg Dhooge, Cleo Dhondt, Laura Leyssens, Marieke Sucaet, Saartje Vanaudenaerde, Lotte Rombaut, Leen Maes

Abstract

Objectives

The Vestibular Infant Screening – Flanders (VIS-Flanders) project aims to implement and refine a vestibular screening protocol for all children with neonatal hearing loss in Flanders (Belgium) to limit the impact of a vestibular dysfunction on the motor, cognitive and psychosocial development of hearing-impaired children.

Methods

Each child with a confirmed neonatal hearing loss in Flanders will undergo a vestibular screening at the age of 6 months in the reference centers involved in the neonatal hearing screening program. The cervical Vestibular Evoked Myogenic Potential (cVEMP) test will be used as a screening tool. The test is short, child-friendly, feasible at a young age and highly correlated with motor and balance performance. The results of an extensive follow-up protocol at the Ghent University Hospital will enable further refinement of the screening protocol.

Results

Data collection in all reference centers has started since June 2018. This paper outlines the rationale for the screening and the set-up of this four-year project.

Conclusions

Current available literature strongly favors vestibular assessment in congenitally hearing-impaired children. A standard vestibular screening for these children should lead to early identification of vestibular deficits and subsequent prompt referral for further motor assessment and rehabilitation, in order to limit the impact of a vestibular dysfunction in developing children and improve their quality of life.

https://ift.tt/2GKz994

Recurrent Periorbital Cellulitis Associated with Rhinosinusitis in Children: Characteristics, Course of Disease, and Management Paradigm

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Sharon Tzelnick, Ethan Soudry, Eyal Raveh, Dror Gilony

Abstract

Background

Recurrent periorbital cellulitis (RPOC) associated with rhinosinusitis is rarely noted and scarcely discussed in the literature. The aim of our study was to analyze the characteristics and disease course of a group of pediatric patients with RPOC.

Methods

The medical records of all pediatric patients with a diagnosis of RPOC treated in a tertiary children's hospital were retrieved. Included were patients with a history of two or more episode of RPOC.

Results

A total of 14 children were included. Mean follow up was 3 years (SD ±2.5). Median age of first POC episode was 12 months (range 5 months – 12 years). Overall, 75 events of RPOCs were documented. A median of 3 events per patient was noted (range 2-16). Preseptal cellulitis was diagnosed in all but five patients, in whom orbital cellulitis or subperiosteal abscess were identified, one following failure of conservative treatment, and the remaining at first presentation or recurrence. Rhinorrhea was present in only five patients (35%). The majority of patients were treated with intra-venous antibiotics. Imaging studies were performed in all patients revealing ethmoidal sinusitis in all patients, with lamina papyracea dehiscence in two patients. Immune deficiency was diagnosed in one patient. Endoscopic sinus surgery was performed in seven patients, in four as preventive procedure and in three during an acute phase. Post-operative recurrent disease was noted in two patients that were operated during the acute phase.

Conclusions

RPOC is a rare entity. Rhinosinusitis should be suspected in events of recurrent preseptal cellulitis even in the absence of nasal symptoms. CT scan is diagnostic for sinus origin of disease and possible anatomical abnormalities. In the majority of patients no evident etiology was identified. Elective Surgery or prophylactic antibiotic treatment should be strongly considered in this subgroup of patients as it seems beneficial.

https://ift.tt/2NstF3f

Serious complications due to acute rhinosinusitis in children up to five years old in Stockholm, Sweden – still a challenge in the pneumococcal conjugate vaccine era

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): S.Hultman Dennison, L.Schollin Ask, M. Eriksson, A. Granath, O. Hertting, R. Bennet, A. Lindstrand, P. Masaba, P. Dimitriou, P. Stjärne

Abstract

Objectives

The aim of this study was to analyze the rate of admissions, the rate of serious complications (postseptal orbital complications and surgery) and the bacterial etiology of acute rhinosinusitis in hospitalized children under five years old in Stockholm County, eight years after the introduction of the pneumococcal conjugate vaccine (PCV). The secondary aim was to compare this period with the period four years prior to the vaccine's introduction.

Methods

This was a population-based, descriptive observational study with retrospectively collected data from 1 July 2008 to 30 June 2016 in Stockholm County. Hospital admissions of children with a discharge diagnosis of rhinosinusitis and related complications were reviewed and compared to the pre-PCV period of 2003 to 2007.

Results

A total of 215 children were admitted, for a yearly incidence of 18.8 per 100 000 children (22.8 for boys, 14.6 for girls). Computer tomography-verified postseptal orbital complications occurred in 29 cases (13.5%) and surgery was necessary in nine (4.2%). Pathogens other than Streptococcus pneumoniae were found in the cases with postseptal complication or surgery (Streptococcus pyogenes in four, Haemophilus influenzae in three and Staphylococcus aureus in one case). In comparison to the four years pre-PCV, the incidence of admission decreased from 43.81 to 20.31 and 17.45 per 100 000/year for the two four-year periods after vaccine introduction. The incidence of CT-verified postseptal complication increased slightly from 1.51 to 2.34 and 2.74 per 100 000/year. The incidence of surgeries increased marginally but continued to be very low, from 0.22 to 0.54 and 1.03 per 100 000/year.

Conclusions

Complications due to acute rhinosinusitis in children living in Stockholm County continues to be very rare after the introduction of pneumococcal vaccine. Hospitalization has decreased for children under five years old after PCV introduction, but the incidence or postseptal complications and surgery in the same population increased slightly. Predominantly bacteria other than Streptococcus pneumoniae was found. There is a need of larger studies to determine trends, and a need of prospective studies to elucidate the bacterial etiology, of serious complications due to acute rhinosinusitis in children.

https://ift.tt/2GKz2dE

Identification and mutational analysis of continuous, immunodominant epitopes of the major oyster allergen Crag 1

Publication date: Available online 23 February 2019

Source: Clinical Immunology

Author(s): Lei Fang, Guoming Li, Jiangtao Zhang, Ruizeng Gu, Muyi Cai, Jun Lu

Abstract

Shellfish, including oysters, often cause allergic reactions in children and adults. Oysters are inevitably consumed because of its delicacy and nutritional benefit, leading to frequent occurrence of severe clinical symptoms observed in patients with oyster hypersensitivity. We aimed to identify the immunodominant epitopes of oyster tropomyosin and crucial amino acids for IgE binding, which will help us to further understand the immunochemical characteristics of Cra g 1. The potential epitopes were predicted by immunoinformatics tools and the resultant immunodominant epitopes were identified by inhibition ELISA with pooled sera and individual serum from oyster allergic patients. Surprisingly, homologous substitution of multiple amino acids led to obviously decrease affinity of IgE antibodies, but this manner did not abrogate binding completely. Five major linear epitopes were evenly distributed on the surface of homology-based Cra g 1 model and hydrophilic residues appeared to be the most important for IgE binding. These results not only offer a better understanding of the molecular mechanism of interaction between Cra g 1 and oyster-specific IgE but also have significance in clinical diagnosis and immunotherapy.

https://ift.tt/2VoheIF

Micronutrients: Speculation on Inborn Errors, Nutrigenomics, Evolution, the Microbiome, and Nutritional Immunity

Clayton, PT; Mills, PB; (2018) Micronutrients: Speculation on Inborn Errors, Nutrigenomics, Evolution, the Microbiome, and Nutritional Immunity. Journal of Inborn Errors of Metabolism and Screening , 6 (1-5) 10.1177/2326409818765011 . Green open access

https://ift.tt/2GZvmE5

Findings of Impaired Hearing in Patients With Nonfluent/Agrammatic Variant Primary Progressive Aphasia

Hardy, CJD; Frost, C; Sivasathiaseelan, H; Johnson, JCS; Agustus, JL; Bond, RL; Benhamou, E; ... Warren, JD; + view all Hardy, CJD; Frost, C; Sivasathiaseelan, H; Johnson, JCS; Agustus, JL; Bond, RL; Benhamou, E; Russell, LL; Marshall, CR; Rohrer, JD; Bamiou, D-E; Warren, JD; - view fewer (2019) Findings of Impaired Hearing in Patients With Nonfluent/Agrammatic Variant Primary Progressive Aphasia. JAMA Neurology 10.1001/jamaneurol.2018.4799 . (In press). Green open access

https://ift.tt/2tKWVJH

Sand dunes and ventifacts on the coast of South Africa

Knight, J; Burningham, H; Sand dunes and ventifacts on the coast of South Africa. Aeolian Research (In press).

https://ift.tt/2GZvfZb

The European trade ban on wild birds reduced invasion risks

Cardador -Bergua, L; Tella, JL; Anadón, JD; Abellán, P; Carrete, M; (2019) The European trade ban on wild birds reduced invasion risks. [Letter]. Conservation Letters 10.1111/conl.12631 . (In press). Green open access

https://ift.tt/2tEsIMi

Comparative Effectiveness of Tumor Response Assessment Methods: Standard of Care Versus Computer-Assisted Response Evaluation

Allen, BC; Florez, E; Sirous, R; Lirette, ST; Griswold, M; Remer, EM; Wang, ZJ; ... Smith, AD; + view all Allen, BC; Florez, E; Sirous, R; Lirette, ST; Griswold, M; Remer, EM; Wang, ZJ; Bieszczad, JE; Cox, KL; Goenka, AH; Howard-Claudio, CM; Kang, HC; Nandwana, SB; Sanyal, R; Shinagare, AB; Henegan, JC; Storrs, J; Davenport, MS; Ganeshan, B; Vasanji, A; Rini, B; Smith, AD; - view fewer (2017) Comparative Effectiveness of Tumor Response Assessment Methods: Standard of Care Versus Computer-Assisted Response Evaluation. JCO Clinical Cancer Informatics , 1 pp. 1-16. 10.1200/CCI.17.00026 . Green open access

https://ift.tt/2GZvbIV

Dynamic Causal Modelling of Dynamic Dysfunction in NMDA-Receptor Antibody Encephalitis

Rosch, ER; Cooray, G; Friston, KJ; (2017) Dynamic Causal Modelling of Dynamic Dysfunction in NMDA-Receptor Antibody Encephalitis. In: Erdi, P and Bhattacharya, BS and Cochran, A, (eds.) Computational Neurology and Psychiatry. (pp. 121-148). Springer: Cham, Switzerland. Green open access

https://ift.tt/2tF32ig

Supporting Teachers in Developing Their RiTPACK Through Using Video Cases in an Online Course

Crisan, C; (2018) Supporting Teachers in Developing Their RiTPACK Through Using Video Cases in an Online Course. In: Silverman, J and Hoyos, V, (eds.) Distance Learning, E-Learning and Blended Learning of Mathematics: International Trends in Research and Development. (pp. 165-181). Springer: Cham, Switzerland.

https://ift.tt/2GZv5kx

Effective Territorial Control by Non-State Armed Groups and the Right to Self-Defence

Urs, P; (2017) Effective Territorial Control by Non-State Armed Groups and the Right to Self-Defence. Zeitschrift für ausländisches öffentliches Recht und Völkerrecht , 77 (1) pp. 31-34.

https://ift.tt/2tD7IFt

Gold Standard, Evidence-Based Approach to Diagnosing APD

Iliadou, VV; Chermak, GD; Bamiou, DE; Musiek, FE; (2019) Gold Standard, Evidence-Based Approach to Diagnosing APD. Hearing Journal , 72 (2) pp. 42-46. 10.1097/01.HJ.0000553582.69724.78 .

https://ift.tt/2GXNnCO

Estimating Real-Time Highstreet Footfall from Wi-Fi Probe Requests

Soundararaj, B; Cheshire, J; Longley, P; (2019) Estimating Real-Time Highstreet Footfall from Wi-Fi Probe Requests. International Journal of Geographical Information Science (In press).

https://ift.tt/2tAKxvx

The experiences of parents with children with disabilities travelling on planes: An exploratory study

Davies, A; Christie, N; (2018) The experiences of parents with children with disabilities travelling on planes: An exploratory study. Journal of Transport & Health , 11 pp. 122-129. 10.1016/j.jth.2018.10.002 .

https://ift.tt/2GXNjmy

Scalable 3D Printed Molds for Human Tissue Engineered Skeletal Muscle

Capel, A; Rimington, R; Fleming, J; Player, D; Baker, L; Turner, M; Jones, J; ... Lewis, M; + view all Capel, A; Rimington, R; Fleming, J; Player, D; Baker, L; Turner, M; Jones, J; Martin, N; Ferguson, R; Mudera, V; Lewis, M; - view fewer (2019) Scalable 3D Printed Molds for Human Tissue Engineered Skeletal Muscle. Frontiers in Bioengineering and Biotechnology , 7 , Article 20. 10.3389/fbioe.2019.00020 . Green open access

https://ift.tt/2tzVwFH

Let’s take the heat out of the CKDu debate: more evidence is needed

Pearce, N; Caplin, B; Let's take the heat out of the CKDu debate: more evidence is needed. Occupational and Environmental Medicine (In press).

https://ift.tt/2GXNb6y

Ignition and Oxidation of Core-Shell Al/Al2O3 Nanoparticles in an Oxygen Atmosphere: Insights from Molecular Dynamics Simulation

Chu, Q; Shi, B; Liao, L; Luo, KH; Wang, N; Huang, C; (2018) Ignition and Oxidation of Core-Shell Al/Al2O3 Nanoparticles in an Oxygen Atmosphere: Insights from Molecular Dynamics Simulation. Journal of Physical Chemistry C , 122 (51) pp. 29620-29627. 10.1021/acs.jpcc.8b09858 .

https://ift.tt/2tE6auS

Diffuse optical tomography for the detection of perinatal stroke at the cot side: a pilot study

Chalia, M; Dempsey, LA; Cooper, RJ; Lee, C-W; Gibson, AP; Hebden, JC; Austin, T; (2019) Diffuse optical tomography for the detection of perinatal stroke at the cot side: a pilot study. Pediatric Research 10.1038/s41390-018-0263-x . (In press). Green open access

https://ift.tt/2GYARTo

Semantic Representation and Location Provenance of Cultural Heritage Information: the National Gallery Collection in London

Padfield, J; Kontiza, K; Bikakis, A; Vlachidis, A; (2019) Semantic Representation and Location Provenance of Cultural Heritage Information: the National Gallery Collection in London. Heritage , 2 (1) pp. 648-665. 10.3390/heritage2010042 . Green open access

https://ift.tt/2tDKtLr

Response of heat release to equivalence ratio variations in high Karlovitz premixed H2/air flames at 20 atm

Wang, X; Jin, T; Luo, KH; (2019) Response of heat release to equivalence ratio variations in high Karlovitz premixed H2/air flames at 20 atm. International Journal of Hydrogen Energy , 44 (5) pp. 3195-3207. 10.1016/j.ijhydene.2018.12.027 .

https://ift.tt/2GZulMh

Modelling the spatial decision making of terrorists: The discrete choice approach

Marchment, Z; Gill, P; (2019) Modelling the spatial decision making of terrorists: The discrete choice approach. Applied Geography , 104 pp. 21-31. 10.1016/j.apgeog.2019.01.009 . (In press).

https://ift.tt/2tDKsqR

CKD of undetermined aetiology: Tens of thousands of premature deaths yet too many unknowns remain.

Mahalingasivam, V; Caplin, B; (2019) CKD of undetermined aetiology: Tens of thousands of premature deaths yet too many unknowns remain. Nephrology Dialysis Transplantation 10.1093/ndt/gfz014 . (In press).

https://ift.tt/2H2lp98

Main and interactive effects of inflammation and perceived neighbourhood cohesion on psychological distress: Results from a population-based study in the UK

Papachristou, E; Flouri, E; Kokosi, T; Francesconi, M; (2019) Main and interactive effects of inflammation and perceived neighbourhood cohesion on psychological distress: Results from a population-based study in the UK. Quality of Life Research 10.1007/s11136-019-02143-7 . (In press).

https://ift.tt/2tCquNt

Polymorphism in GRHL2 gene may contribute to noise-induced hearing loss susceptibility: a meta-analysis

Publication date: Available online 23 February 2019

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Xin Li, Zhengping Zhu, Wei Li, Li Wei, Baocheng Zhao, Zheng Hao

Abstract

Instruction

Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting.

Objective

The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss.

Methods

A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association.

Results

Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594–0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062–1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514–0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054–1.379).

Conclusion

Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

Resumo

Introdução

Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes.

Objetivo

O objetivo deste estudo foi identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído.

Método

Uma pesquisa abrangente foi realizada para coletar dados até 8 de julho de 2018. No final, quatro artigos elegíveis foram incluídos nesta meta-análise, abrangendo 2410 indivíduos. Os odds ratios agrupados com intervalos de confiança de 95% foram utilizados para avaliar a força da associação.

Resultados

Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379).

Conclusão

O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

https://ift.tt/2NshMKF

Diagnosing acquired syphilis through oral lesions: the 12 year experience of an Oral Medicine Center

Publication date: Available online 23 February 2019

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Michelle Danielle Porto Matias, Alessandro Oliveira de Jesus, Renata Gonçalves Resende, Patrícia Carlos Caldeira, Maria Cássia Ferreira de Aguiar

Abstract

Introduction

A resurgence of syphilis in Brazil has been reported in recent years.

Objective

With this in mind, the present study sought to investigate the frequency, demographics, and clinical characteristics of patients with acquired syphilis with oral involvement who received medical care at an Oral Medicine Reference Center in a Brazilian Public Hospital.

Methods

A retrospective study, spanning a period of 12 years, was performed to identify changing trends in syphilis over time. Medical records from all patients diagnosed with acquired syphilis who received medical care at the Hospital's Oral Medicine Clinic from 2005 to 2016 were reviewed, and the demographic and clinical data were collected.

Results

A total of 85 patients had been diagnosed with acquired syphilis, with a significant increase in the number of cases over the past 5 years. Patients ranged from 16 to 76 years of age, with a peak in the third and fourth decades. Forty-eight cases affected males (56.5%), while 37 cases affected females (43.5%). Most of the oral lesions appeared as unique ulcers or plaques, with the lips and tongue representing the most affected sites. All cases were positive for Venereal Disease Research Laboratory or Fluorescent Treponemal Antibody Absorption, and treatment was performed with Penicillin G benzathine in most cases (84.7%).

Conclusion

The frequency of oral syphilis has been rising over time and oral lesions may well represent a diagnostic clue; therefore, oral health professionals must be made aware and properly trained in an attempt to develop a high degree of clinical suspicion in the diagnosis of syphilis.

Resumo

Introdução

Um ressurgimento da sífilis no Brasil tem sido relatado nos últimos anos.

Objetivo

Nesse sentido, o presente estudo buscou investigar a frequência, características demográficas e clínicas dos pacientes com sífilis adquirida com envolvimento oral que receberam atendimento médico em um centro de referência em medicina oral em um hospital público brasileiro.

Método

Trata-se de um estudo retrospectivo, abrangendo um período de 12 anos, realizado para identificar tendências de mudança na sífilis ao longo do tempo. Registros médicos de todos os pacientes diagnosticados com sífilis adquirida que receberam atendimento médico na clínica de medicina oral do hospital de 2005 a 2016 foram revisados, e os dados demográficos e clínicos foram coletados.

Resultados

Um total de 85 pacientes foi diagnosticado com sífilis adquirida, com um aumento significativo no número de casos nos últimos 5 anos. A idade dos pacientes variou de 16 a 76 anos de idade, com pico na terceira e quarta décadas. Quarenta e oito casos eram do sexo masculino (56,5%) e 37 casos do sexo feminino (43,5%). A maioria das lesões orais apareceu como úlceras ou placas únicas, com os lábios e a língua representando os locais mais afetados. Todos os casos foram positivos para Venereal Disease Research Laboratory e Fluorescent Treponemal Antibody Absorption Test, e o tratamento foi realizado com Penicilina G benzatina na maioria dos casos (84,7%).

Conclusão

A frequência da sífilis oral tem aumentado com o tempo e as lesões orais podem representar uma pista diagnóstica; portanto, os profissionais de saúde bucal devem ser conscientizados e devidamente treinados na tentativa de desenvolver um alto grau de suspeição clínica no diagnóstico da sífilis.

https://ift.tt/2GJOzKH

Marine Bromophenols as an effective inhibitor of virulent proteins (Peptidyl Arginine Deiminase, Gingipain R and Hemagglutinin A) in Porphyromas gingivalis

Publication date: Available online 23 February 2019

Source: Archives of Oral Biology

Author(s): Chikoo Cherian, J. Jannet Vennila, Leena Sharan

Abstract

Objectives

Porphyromonas gingivalis, is one of the major oral pathogen that produce virulent proteins which mediate periodontal tissue inflammation and infection. Marine algae have recently gained popularity for its bioactive molecules and their oral applications. Marine bromophenols (MBs) is abundant in red algae which are reported to have wide medicinal properties. The current research primarily focuses to elucidate the bioactivity of MBs against the virulent proteins produced by P. gingivalis.

Materials and methods

Potent MBs which effectively binds and inhibits the virulent proteins peptidyl arginine deiminase (PPAD), gingipain R (Rgp) and hemagglutinin A (HgA) was identified through molecular docking and molecular simulation approach. MBs were extracted from Kappaphycus alvarezii (KAB), marine red algae found in India. The efficacy of this MB was studied against P. gingivalis by employing antibacterial activity assays, gingipain assay, hemagglutination inhibition assay (HIA) and mRNA expression analysis (q RT PCR).

Results

MBs with benzene, methyl and glycosyl substitutions demonstrated significant docking score, with good stability and pharmacokinetic properties. In addition to the antibacterial activities against P. gingivalis, KAB was also found to inhibit the gingipain and hemagglutination activities. Exposure of KAB to the virulent genes in P. gingivalis resulted in low mRNA levels of these genes, which suggested the down regulation functions induced by the MBs

Conclusion

Biochemical investigations revealed that KAB is a potent natural metabolite that can inhibit and control the virulent proteins produced by P. gingivalis. This study recommends future research to direct towards applicability of MBs in commercial dental products.

Graphical abstract

https://ift.tt/2ViBKuc

Recurrent retroperitoneal abscess after biliary tract surgery in an elderly patient: a minimally invasive nonsurgical approach and its consequences: a case report

Hepatic abscess can be defined as an encapsulated collection of suppurative material within the liver parenchyma. Hepatic abscess can be distinguished as pyogenic, amebic, or fungal. Biliary tract disease rema...

https://ift.tt/2Xny787

Rapid Onset of Effect of Benralizumab on Morning Peak Expiratory Flow in Severe, Uncontrolled Asthma

Publication date: Available online 23 February 2019

Source: Annals of Allergy, Asthma & Immunology

Author(s): Geoffrey Chupp, Njira L. Lugogo, Joel N. Kline, Gary T. Ferguson, Ian Hirsch, Mitchell Goldman, James G. Zangrilli, Frank Trudo

https://ift.tt/2NsBjdZ

Epidemiology of otorhinolaryngologic emergencies in a secondary hospital: analysis of 64,054 cases

Abstract

Purpose

To determine the incidence and distribution of care in relation to urgent otorhinolaryngologic pathologies by the different medical specialist units.

Methods

A descriptive, observational and retrospective study was conducted of patients seen by the Emergency Service at a secondary hospital over the course of 7 years (2011–2017).

Results

A total of 546,701 patients were seen during the period in question, of which 64,054 presented with otorhinolaryngologic symptoms. The attendance rate was 450/1000 inhabitants/year. The most frequent diagnoses were upper respiratory tract infection, with 13,639 cases (21.3%), tonsillopharyngitis, with 10,150 cases (15.8%) and vertigo/dizziness with 8761 cases (13.7%). Patients seen by the Hospital Emergency Service physicians and those referred to the Otorhinolaryngology or Paediatric Units were analysed both together and separately. The Hospital Emergency Service dealt with 77.1% of the cases, and referred 15.4% to the Otorhinolaryngology Unit and 7.5% to the Paediatrics Unit. Within the subgroup of patients referred to the Otorhinolaryngology Unit, the most frequent diagnoses were problems related to inflammatory ear disease (25.6%), followed by cervicofacial trauma (15.4%) and bleeding with otorhinolaryngologic symptoms (12.5%). The percentage of hospital admissions for the entire sample was 3%, while for patients referred to the Otorhinolaryngology Unit this figure was 6.8%.

Conclusions

A large percentage of patients presenting at the Hospital Emergency Service do so with otorhinolaryngologic symptoms, and the vast majority are treated effectively by the physicians in that service and are referred to the specialist services on the basis of sound criteria.

https://ift.tt/2H0Q46z

Depth of invasion alone as an indication for postoperative radiotherapy in small oral squamous cell carcinomas: An International Collaborative Study

Abstract

Background

We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC).

Methods

Retrospective analysis of DOI (<5, 5 to <10, ≥10 mm) and disease‐specific survival (DSS) in a multi‐institutional international cohort of 1409 patients with oral SCC ≤4 cm in size treated between 1990‐2011.

Results

In patients without other adverse factors (nodal metastases; close [<5 mm] or involved margins), there was no association between DOI and DSS, with an excellent prognosis irrespective of depth. In the absence of PORT, the 5‐year disease‐specific mortality was 10% with DOI ≥10 mm, 8% with DOI 5‐10 mm, and 6% with DOI <5 mm (P = .169), yielding an absolute risk difference of only 4%.

Conclusion

The deterioration in prognosis with increasing DOI largely reflects an association with other adverse features. In the absence of these, depth alone should not be an indication for PORT outside a clinical trial.

https://ift.tt/2TlrgNm