Further evidence that de novo missense and truncating variants in ZBTB18 cause intellectual disability with variable features

ABSTRACT

Identification of rare genetic variants in patients with intellectual disability (ID) has been greatly accelerated by advances in next generation sequencing technologies. However, due to small numbers of patients, the complete phenotypic spectrum associated with pathogenic variants in single genes is still emerging. Among these genes is ZBTB18 (ZNF238), which is deleted in patients with 1q43q44 microdeletions who typically present with ID, microcephaly, corpus callosum (CC) abnormalities, and seizures. Here we provide additional evidence for haploinsufficiency or dysfunction of the ZBTB18 gene as the cause of ID in five unrelated patients with variable syndromic features who underwent whole exome sequencing revealing separate de novo pathogenic or likely pathogenic variants in ZBTB18 (two missense alterations and three truncating alterations). The neuroimaging findings in our cohort (CC hypoplasia seen in 4/4 of our patients who underwent MRI) lend further support for ZBTB18 as a critical gene for CC abnormalities. A similar phenotype of microcephaly, CC agenesis, and cerebellar vermis hypoplasia has been reported in mice with central nervous system-specific knockout of Zbtb18. Our five patients, in addition to the previously described cases of de novo ZBTB18 variants, add to knowledge about the phenotypic spectrum associated with ZBTB18 haploinsufficiency/dysfunction.

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Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Abstract

Brain extracellular matrix (ECM) is a highly organized system that consists of collagens, noncollagenous proteins, glycoproteins, hyaluronan, and proteoglycans. Recognized physiological roles of ECM include developmental regulation, tissue homeostasis, cell migration, cell proliferation, cell differentiation, neuronal plasticity, and neurite outgrowth. Aberrant ECM structure is associated with brain neurodegenerative conditions. This review focuses on two neurodegenerative conditions, schizophrenia and Alzheimer's disease, and summarizes recent findings of altered ECM components, including proteoglycans, glycosaminoglycans, proteins, and glycoproteins, and proteins and genes related to other brain components. The scope includes immunohistochemical, genomics, transcriptomics, proteomics, and glycomics studies, and a critical assessment of current state of proteomic studies for neurodegenerative disorders. The intent is to summarize the ECM molecular alterations associated with neurodegenerative pathophysiology.

Graphical Abstract

Brain extracellular matrix showing HSPGs, CSPGs, HA, collagens, and other glycoproteins.

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Acute β-Hydroxy-β-Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes

Abstract

Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine-derived metabolite β-hydroxy-β-methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB-treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator-activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP-activated protein kinase. As a result, HMB-treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.

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Comparison of efficacy of levofloxacin-metronidazole combination versus ceftriaxone in cases of moderate diabetic foot infection

2016-09-06T06-53-19Z
Source: International Journal of Basic & Clinical Pharmacology
Swati V. Patil, Roshan R. Mane.
Background: Foot ulcers are a significant complication of diabetes and are the most common cause of non-traumatic lower extremity amputations in the industrialized world. Diabetic foot infections can be treated effectively with cephalosporins and fluoroquinolnes. The purpose of this study was to compare the efficacy, safety and microbiological outcomes of ceftriaxone and combination of levofloxacin and metronidazole. Methods: This was a prospective, open labelled, randomized controlled trial study. Patients diagnosed of having diabetic foot infection were recruited for the study from the OPD and IPD of the surgery department of Govt. Medical College and Hospital, Miraj and PVP Govt. Hospital, Sangli from June 2007 to December 2007. Signed informed consents were obtained from the patients. The study complied with declaration of Helsinki. Enrolled patients were randomized in 2 groups. Group 1: ceftriaxone group: patients were hospitalized and received ceftriaxone 1 gm intravenously for 14 days. Group 2: levofloxacin and metronidazole group: patients were treated as out-patients and received Levofloxacin 500 mg orally once daily with metronidazole 400 mg orally thrice daily for 14 days. Detailed history and complete physical examination was done for all patients. Sequential measurement of the lesion was done, to assess the change in size. Bacteriological evaluation was done. Clinical and microbiological outcome and safety parameters were assessed after treatment. Results: The baseline characteristics in both the groups were comparable and were not significant with each other (p >0.05). In both the groups the most commonly isolated aerobe was staphylococci species followed by different species of enterobacteriacae and pseudomonas. Most commonly isolated anaerobe was bacteroides fragilis. Microbiological and clinical outcomes were assessed and the total no of patients recovered in both groups were almost similar. The percentage of wound healing in both the treatment groups was equal. None of the patients in both the groups had shown complete wound healing. The number of adverse effects associated with the therapies was also similar. The cost of therapies in both the groups were assessed and found the difference was highly significant. Conclusions: Even though combination of levofloxacin-metronidazole and ceftriaxone alone had similar outcomes in terms of efficacy, on contrary in comparison of cost and convenience, levofloxacin - metronidazole therapy was proved better than ceftriaxone in treatment of diabetic foot ulcers.


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Prevalence of anti-hepatitis C virus antibodies among indoor patients and blood donors attending a tertiary care hospital in North India

2016-09-06T06-51-05Z
Source: International Journal of Research in Medical Sciences
Noor Jahan, Vijay Gupta, Mariyam Sana, Sudhir Mehrotra, Razia Khatoon.
Background: Hepatitis C virus (HCV) causes acute as well as chronic hepatitis such as cirrhosis of liver and hepatocellular carcinoma. The virus is mainly transmitted through blood and blood products. Hence, in order to provide safe blood supply testing of each blood unit for markers of HCV has been made mandatory. The infection is detected by the presence of anti-HCV antibody in the patients serum. The objective of the present study was to determine the prevalence of anti-HCV antibodies among indoor patients and blood donors. Methods: A hospital based cross-sectional study was done from January to June 2016. A total of 1991 subjects comprising of 1649 indoor patients and 342 blood donors were included in the study whose blood samples were screened for presence of anti-Hepatitis C antibody using rapid HCV TRI-DOT and HCV Microlisa. Results: Out of 1649 indoor patients tested, 39 were found to be reactive, and out of 342 blood donors tested, 4 were found to be reactive, hence, the prevalence of anti-HCV antibody was found to be 2.4% among indoor patients and 1.2% among blood donors. The seroprevalence of anti-HCV antibody was found to be more among replacement donors (1.2%) as compared to voluntary donors (1.1%). Conclusions: As blood transfusion is an important mode of transmission of HCV, hence, prevention in the form of proper screening of every unit of blood prior to transfusion is mandatory. As voluntary donors are relatively safe, this should be encouraged by organizing frequent blood donation camps.


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Comparative evaluation of slide agglutination and Widal tube agglutination test in detecting enteric fever among patients attending a tertiary care hospital in North India

2016-09-06T06-51-05Z
Source: International Journal of Research in Medical Sciences
Noor Jahan, Razia Khatoon, Amrita, Sudhir Mehrotra, Swatantra Kumar.
Background: Enteric fever is a major public health problem with significant morbidity and mortality in developing countries. Although, isolation of causative organism from blood is the standard laboratory method, but due to frequent use of self-medication by patients, and its long turnaround time, it is seldom used, and enteric fever is usually diagnosed by using serological methods. Widal tube agglutination test is the standard serological test used, which is now a days replaced by slide agglutination test due to its convenience and rapidity. The present study was done to comparatively evaluate the slide agglutination and Widal tube agglutination test in detecting enteric fever. Methods: A hospital based cross-sectional study was done from January to June 2016. A total of 117 patients with clinical presentation suggestive of enteric fever were included in the study whose venous blood was collected and serum was tested by both slide agglutination and Widal tube agglutination test. Results: Out of 117 patients, slide agglutination test showed positive results in 39 (33.3%) samples, whereas, Widal tube agglutination test showed positive results in 23 (19.7%) samples only. The slide test had a sensitivity of 91.3%, specificity of 80.9%, positive predictive value of 53.8% and negative predictive value of 97.4% as compared to Widal tube agglutination test. Conclusions: Due to high false positivity shown by slide test, it is suggested that serological diagnosis should not be made solely on the basis of slide test rather its results should be confirmed by using Widal tube agglutination test.


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Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

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Is brain angio-MRI useful in infective endocarditis management?

Abstract

In infective endocarditis (IE), brain magnetic resonance imaging (MRI) is helpful to diagnose clinically silent neurological events. We assessed the usefulness of systematic early brain MRI in IE diagnosis and medico-surgical management. Over a period of 1 year, all patients admitted in one of the three hospitals participating in and fulfilling the Duke criteria for definite or possible IE underwent cerebral MRI within 7 days of IE suspicion. Eight panels of experts analyzed the records a posteriori. For each case, one record with and one record without the MRI results were randomly assigned to two panels, which determined the theoretical diagnosis and treatment. Paired comparisons were performed using a symmetry test. Thirty-seven brain MRIs were performed within a median of 5 days after inclusion. MRI was pathological in 26 patients (70 %), showing 62 % microischemia and 58 % microbleeds. The expert advice did not differ significantly between the two evaluations (with or without the MRI results). The therapeutic strategies determined diverged in five cases (13.5 %). Diagnosis differed in two cases (5.4 %), with an upgrading of diagnosis from possible to definite IE using MRI results. Early brain MRI did not significantly affect the IE diagnosis and medico-surgical treatment plan. These results suggest that systematic use of early brain MRI is irrelevant in IE. Further studies are necessary to define whether MRI is mandatory in IE management within a multidisciplinary approach, with particular attention paid to better timing and the subset of patients in whom this imaging examination could be beneficial.

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3,3´-diindolylmethane mitigates total body irradiation-induced hematopoietic injury in mice

Publication date: Available online 5 September 2016
Source:Free Radical Biology and Medicine
Author(s): Lu Lu, Jiali Dong, Deguan Li, Junling Zhang, Saijun Fan
We have reported that hematopoietic system injury induced by total body irradiation (TBI) leads to generation of intracellular reactive oxygen species (ROS) and DNA damage, which are ameliorated by antioxidant agents. In the present study, we reported that administration of DIM, a potent antioxidant agent, not only protected mice against TBI-induced lethality, also ameliorated TBI-induced hematopoietic injury. The latter effect was probably attributable to DIM's inhibition of TBI-induced increases in ROS production in hematopoietic stem cells (HSCs) and the phosphorylation of histone H2AX (γ-H2AX). In particular, DIM led to significant improvements in bone marrow (BM) HSC frequency, hematopoietic progenitor cell (HPC) clonogenic function, and multilineage engraftment after transplantation. A downregulation of NADPH oxidase 4 (NOX4) and an upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression were observed following DIM treatment. Notably, the anti-apoptotic potential of DIM was correlated with increased expression of the anti-apoptotic protein Bcl-2 and decreased expression of the pro-apoptotic protein Bax. These findings suggest that DIM attenuates TBI-induced hematopoietic injury through the inhibition of both oxidative stress in HSCs and hematopoietic cell apoptosis. Furthermore, we demonstrated that DIM protected BM hematopoietic cells against ionizing radiation and led to increased clonogenicity in vitro. Therefore, DIM has the potential to be used as an effective radioprotectant to ameliorate TBI-induced hematopoietic injury.

Graphical abstract

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Reactions between Nitrosopersulfide and Heme Proteins

Publication date: Available online 5 September 2016
Source:Free Radical Biology and Medicine
Author(s): Crystal Bolden, S. Bruce King, Daniel B. Kim-Shapiro
When nitrosothiols react with excess hydrogen sulfide, H2S, they form several intermediates including nitrosopersulfide (SSNO^-). The stability and importance of this species has been debated. While some data suggest SSNO^- can be a relatively stable source of NO activity, others suggest that the species degrades too quickly. We find the species to be relatively stable in isolation. Due to the abundance and prominence of iron-containing proteins throughout the human body, it is important to establish the interaction of ferrous- and ferric-iron containing proteins with SSNO^-. Study of the reactions of SSNO^- with heme proteins can also provide information about the potential in vivo stability and spontaneous reactivity of this species. We have used time-resolved electron paramagnetic resonance and UV-Vis absorption spectroscopy to study the reactions of SSNO^- with heme proteins. Iron-nitrosyl hemoglobin is formed when SSNO^- is reacted with deoxyhemoglobin and deoxygenated methemoglobin, suggesting NO formation from SSNO^-. However, the yields of nitrosyl hemoglobin in reactions of SSNO^- with deoxyhemoglobin are much less than when SSNO^- is reacted with deoxygenated methemoglobin. Very little to no nitrosyl hemoglobin is formed when SSNO^-is reacted carboxyhemoglobin, HbCO, and when SSNO^- is reacted with oxygenated hemoglobin, minimal methemoglobin is formed Taken together, these data confirm the release of NO, but indicate a vacant heme is necessary to facilitate a direct heme-SSNO^- reaction to form substantial NO. These data also suggest that the ferric iron in methemoglobin potentiates SSNO^- reactivity. These results could potentially impact NO and sulfide bioavailability and reactivity.



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Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice

Publication date: Available online 5 September 2016
Source:Free Radical Biology and Medicine
Author(s): Mei-Yin Chien, Cheng-Hung Chuang, Chang-Ming Chern, Kou-Tong Liou, Der-Zen Liu, Yu-Chang Hou, Yuh-Chiang Shen
Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by compromising the activation of GSK3β and p25/Cdk5, which in turn upregulated β-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SalA blocks inflammatory responses by impairing NF-κB signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SalA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3β/Cdk5 activity to enhance the expression levels of β-catenin/DCX and Bcl-2 for neuroprotection.

Graphical abstract

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The suffering in silence of older parents whose child died of cancer: a qualitative study

As life expectancy grows, the death of an adult child becomes a highly prevalent problem for older adults. The present study is based on 9 interviews and explores the experience of parents (≥70 years) outliving an adult child. The bereaved parents described some silencing processes constraining their expression of grief. When an adult dies, the social support system nearly automatically directs its care towards the bereaved nuclear family. Parental grief at old age is therefore often not recognized and/or acknowledged. Health care providers should be sensitive to the silent grief of older parents both in geriatric and oncology care settings.

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Pain intensity in hospitalized adults: a multilevel analysis of barriers and facilitators of pain management

Background: Despite an enhanced interest and evolution in pain management, prevalence remains high. Interventions to optimize pain-related care can only be effective if barriers are identified and accounted for. Aim: To assess pain intensity and examine its association with patient-(including health literacy defined in this study as "requiring help to read health information"), nurse-, and system-related (including social capital defined as "the importance of network and norms at work") barriers/facilitators to pain management. Methods: A two-center, cross-sectional study was performed between October 2012 and April 2013. The study included patients and nurses of 39 noncritical wards of two hospitals in Belgium. Patients who were 18 years of age or older and without impaired cognition or consciousness were eligible to take part. All nurses working in the included ward were invited to participate. Pain intensity and patient-related barriers were collected by a structured and standardized questionnaire, completed in dialogue with the patient. Nurses completed the questionnaire on the nurse-and system-related barriers and the social capital scale. Multilevel analysis was used to analyze the data because of the hierarchical structure of the data. Results: The average pain of all patients across all wards on a 0-10 scale was 2.2 (SD = 3.6). The multilevel analysis indicates that pain intensity can be explained by variables at patient and ward levels. A significant independent association was found between higher pain intensity and younger age, receiving pain medication, the conviction of patients that pain medication does not improve pain, inadequate health literacy in patients, nurses without advanced education, and nurse's concerns about side effects. Social capital did not emerge as predictor of pain intensity. Discussion: Patient and nurse level factors should be taken into account in hospitals when setting up strategies to improve pain management.

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Insights into children's independent mobility for transportation cycling - which socio-ecological factors matter?

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A semi-automated FISH-based micronucleus-centromere assay for biomonitoring of hospital workers exposed to low doses of ionizing radiation

The aim of the present study was to perform cytogenetic analysis by means of a semi-automated micronucleus-centromere assay in lymphocytes from medical radiation workers. Two groups of workers receiving the highest occupational doses were selected: 10 nuclear medicine technicians and 10 interventional radiologists/cardiologists. Centromere-negative micronucleus (MNCM-) data, obtained from these two groups of medical radiation workers were compared with those obtained in matched controls. The blood samples of the matched controls were additionally used to construct a 'low-dose' (0-100 mGy) MNCM-dose-response curve to evaluate the sensitivity and suitability of the micronucleus-centromere assay as an 'effect' biomarker in medical surveillance programs. The physical dosimetry data of the 3 years preceding the blood sampling, based on single or double dosimetry practices, were collected for the interpretation of the micronucleus data. The in vitro radiation results showed that for small sized groups, semi-automated scoring of MNCM-enables the detection of a dose of 50 mGy. The comparison of MNCM-yields in medical radiation workers and control individuals showed enhanced MNCM-scores in the medical radiation workers group (P=0.15). The highest MNCM-scores were obtained in the interventional radiologists/cardiologists group, and these scores were significantly higher compared with those obtained from the matched control group (P=0.05). The higher MNCM-scores observed in interventional radiologists/cardiologists compared with nuclear medicine technicians were not in agreement with the personal dosimetry records in both groups, which may point to the limitation of 'double dosimetry' procedures used in interventional radiology/cardiology. In conclusion, the data obtained in the present study supports the importance of cytogenetic analysis, in addition to physical dosimetry, as a routine biomonitoring method in medical radiation workers receiving the highest occupational radiation burdens.

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Haptic simulation framework for determining virtual dental occlusion

Abstract

Purpose

The surgical treatment of many dentofacial deformities is often complex due to its three-dimensional nature. To determine the dental occlusion in the most stable position is essential for the success of the treatment. Computer-aided virtual planning on individualized patient-specific 3D model can help formulate the surgical plan and predict the surgical change. However, in current computer-aided planning systems, it is not possible to determine the dental occlusion of the digital models in the intuitive way during virtual surgical planning because of absence of haptic feedback. In this paper, a physically based haptic simulation framework is proposed, which can provide surgeons with the intuitive haptic feedback to determine the dental occlusion of the digital models in their most stable position.

Methods

To provide the physically realistic force feedback when the dental models contact each other during the searching process, the contact model is proposed to describe the dynamic and collision properties of the dental models during the alignment. The simulated impulse/contact-based forces are integrated into the unified simulation framework.

Results

A validation study has been conducted on fifteen sets of virtual dental models chosen at random and covering a wide range of the dental relationships found clinically. The dental occlusions obtained by an expert were employed as a benchmark to compare the virtual occlusion results. The mean translational and angular deviations of the virtual occlusion results from the benchmark were small.

Conclusions

The experimental results show the validity of our method. The simulated forces can provide valuable insights to determine the virtual dental occlusion. The findings of this work and the validation of proposed concept lead the way for full virtual surgical planning on patient-specific virtual models allowing fully customized treatment plans for the surgical correction of dentofacial deformities.

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Radiocaesium in Cortinarius spp. mushrooms in the regions of the Reggio Emilia in Italy and Pomerania in Poland

Abstract

Activity concentrations of ¹³⁴Cs and ¹³⁷Cs have been determined in 23 species of mushrooms of the genus Cortinarius (59 individual samples) collected from the Reggio Emilia in Italy 1992–1999 and in 4 species (16 composite samples and 413 individuals) from the Pomerania region in Poland from 1996 to 2015. Across all the Cortinarius species from the Reggio Emilia, the activity concentrations were relatively high in Cortinarius alboviolaceus, Cortinarius duracinus, Cortinarius orellanus, Cortinarius rapaceus, and Cortinarius subannulatus, in which ¹³⁷Cs was at 10,000 ~ 100,000 Bq kg⁻¹ dry biomass (db) in 1994. Smaller activity concentrations were found in Cortinarius bivelus, Cortinarius bulliardii, Cortinarius cotoneus, Cortinarius largus, Cortinarius lividoviolaceus, Cortinarius purpureus, Cortinarius rufo-olivaceus, Cortinarius torvus, and Cortinarius venetus with levels at 1000 ~ 6000 Bq kg⁻¹ db from 1992 to 1994, and further in Cortinarius anserinus, Cortinarius auroturbinatus, C. largus, Cortinarius praestans, Cortinarius purpurascens, Cortinarius scaurus, Cortinarius sebaceous, Cortinarius talus, and Cortinarius variecolor with activity concentrations at 100 ~ 600 Bq kg⁻¹ db in 1994. All the data were calculated for dehydrated fungal material corrected back to the exact date samples of collection. The greatest activity concentrations of ¹³⁷Cs both in Italy (1992–1999) and Poland (1996–2010) were found in the popular Cortinarius caperatus, confirming its very high capacity of radiocaesium accumulation. Besides ¹³⁷Cs, the isotope ¹³⁴Cs was detected in some species from the Reggio Emilia. An average calculated ratio of activities of ¹³⁴Cs to ¹³⁷Cs referenced to 1986 was equal to 0.38 in mushrooms from the Reggio Emilia, and this value slightly differ from that specific for Chernobyl fallout, which was 0.54. It was calculated that ¹³⁷Cs originating from Chernobyl accident constituted about 68 % of the total activity concentration of the isotope in Reggio Emilia in 1986, while as much as 32 % of ¹³⁷Cs in mushrooms were from the global fallout from nuclear bomb testing.

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Short-term contributions of cover crop surface residue return to soil carbon and nitrogen contents in temperate Australia

Abstract

Cover crop species are usually grown to control weeds. After cover crop harvest, crop residue is applied on the ground to improve soil fertility and crop productivity. Little information is available about quantifying the contributions of cover crop application to soil total carbon (C) and nitrogen (N) contents in temperate Australia. Here, we selected eight cover crop treatments, including two legume crops (vetch and field pea), four non-legume crops (rye, wheat, Saia oat, and Indian mustard), a mixture of rye and vetch, and a nil-crop control in temperate Australia to calculate the contributions of cover crops (crop growth + residue decomposition) to soil C and N contents. Cover crops were sown in May 2009 (autumn). After harvest, the crop residue was placed on the soil surface in October 2009. Soil and crop samples were collected in October 2009 after harvest and in May 2010 after 8 months of residue decomposition. We examined cover crop residue biomass, soil and crop total C and N contents, and soil microbial biomass C and N contents. The results showed that cover crop application increased the mean soil total C by 187–253 kg ha⁻¹ and the mean soil total N by 16.3–19.1 kg ha⁻¹ relative to the nil-crop treatment, except for the mixture treatment, which had similar total C and N contents to the nil-crop control. Cover crop application increased the mean soil microbial biomass C by 15.5–20.9 kg ha⁻¹ and the mean soil microbial biomass N by 4.5–10.2 kg ha⁻¹. We calculated the apparent percentage of soil total C derived from cover crop residue C losses and found that legume crops accounted for 10.6–13.9 %, whereas non-legume crops accounted for 16.4–18.4 % except for the mixture treatment (0.2 %). Overall, short-term cover crop application increased soil total C and N contents and microbial biomass C and N contents, which might help reduce N fertilizer use and improve sustainable agricultural development.

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Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity

Abstract

Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69–86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This implies that a further optimization of advanced wastewater treatment is needed that goes beyond combining available technologies.

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The Rest of the Story: A Qualitative Study of Complementing Standardized Assessment Data with Informal Interviews with Older Patients and Families

Abstract

Background

While standardized health assessments capture valuable information on patients' demographic and diagnostic characteristics, health conditions, and physical and mental functioning, they may not capture information of most relevance to individual patients and their families. Given that patients and their informal caregivers are the experts on that patient's unique context, it is important to ensure they are able to convey all relevant personal information to formal healthcare providers so that high-quality, patient-centered care may be delivered. This study aims to identify information that older patients and families consider important but that might not be included in standardized assessments.

Methods

Transcripts were analyzed from 29 interviews relating to eight patients with hip fractures from three sites (large urban, smaller urban, rural) in two provinces in Canada. These interviews were conducted as part of a larger ethnographic study. Each transcript was analyzed by two researchers using content analysis. Results were reviewed in two focus group interviews with older adults and family caregivers. Identified themes were compared with items from two standardized assessments used in healthcare settings.

Results

Three broad themes emerged from the qualitative analysis that were not covered in the standardized assessments: informal caregiver and family considerations, insider healthcare knowledge, and patients' healthcare attitudes and experiences. The importance of these themes was confirmed through focus group interviews. Focus group participants also emphasized the importance of conducting assessments in a patient-centered way and the importance of open-ended questions.

Conclusions

A less structured interview approach may yield information that would otherwise be missed in standardized assessments. Combining both sources could yield better-informed healthcare planning and quality-improvement efforts.

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Silencing transposable elements in the Drosophila germline

Abstract

Transposable elements or transposons are DNA pieces that can move around within the genome and are, therefore, potential threat to genome stability and faithful transmission of the genetic information in the germline. Accordingly, self-defense mechanisms have evolved in the metazoan germline to silence transposons, and the primary mechanism requires the germline-specific non-coding small RNAs, named Piwi-interacting RNA (piRNAs), which are in complex with Argonaute family of PIWI proteins (the piRNA–RISC complexes), to silence transposons. piRNA-mediated transposon silencing occurs at both transcriptional and post-transcriptional levels. With the advantages of genetic manipulation and advances of sequencing technology, much progress has been made on the molecular mechanisms of piRNA-mediated transposon silencing in Drosophila melanogaster, which will be the focus of this review. Because piRNA-mediated transposon silencing is evolutionarily conserved in metazoan, model organisms, such as Drosophila, will continue to be served as pioneer systems towards the complete understanding of transposon silencing in the metazoan germline.

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In situ formation of the first proteinogenically functionalized [TeW6O24O2(Glu)]7- structure reveals unprecedented chemical and geometrical features of the Anderson-type cluster

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC07004C, Communication

Christian Molitor, Aleksandar Bijelic, Annette Rompel
The chemistry of polyoxometalates (POMs) in a protein environment is an almost unexplored but highly relevant research field as important biological and pharmacological attributes of certain POMs are based on...
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OTUB1 triggers lung cancer development by inhibiting RAS monoubiquitination

Activation of the RAS oncogenic pathway, frequently ensuing from mutations in RAS genes, is a common event in human cancer. Recent reports demonstrate that reversible ubiquitination of RAS GTPases dramatically affects their activity, suggesting that enzymes involved in regulating RAS ubiquitination may contribute to malignant transformation. Here, we identified the de-ubiquitinase OTUB1 as a negative regulator of RAS mono- and di-ubiquitination. OTUB1 inhibits RAS ubiquitination independently of its catalytic activity resulting in sequestration of RAS on the plasma membrane. OTUB1 promotes RAS activation and tumorigenesis in wild-type RAS cells. An increase of OTUB1 expression is commonly observed in non-small-cell lung carcinomas harboring wild-type KRAS and is associated with increased levels of ERK1/2 phosphorylation, high Ki67 score, and poorer patient survival. Our results strongly indicate that dysregulation of RAS ubiquitination represents an alternative mechanism of RAS activation during lung cancer development.

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State of affairs of osteopathy in the Benelux: Benelux Osteosurvey 2013

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The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.

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Synthesis, in vitro and in vivo small-animal SPECT evaluation of novel technetium labeled bile acid analogues to study (altered) hepatic transporter function

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The easiest way to predict adverse drug reactions in older persons: reply

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Synchrotron radiation induced X-ray microfluorescence analysis

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Ileostomy reversal with handsewn techniques. Short-term outcomes in a teaching hospital

Abstract

Introduction

Fecal diversion is considered an effective procedure to protect bowel anastomosis at high risk for leak. Some concerns exist regarding the risk for a significant morbidity associated to ileostomy creation itself and moreover to its closure. Surgical expertise and closure techniques are considered potential factors influencing morbidity. Aim of the study is to present a single-institution experience with ileostomy closures, in a teaching hospital, whereas ileostomy reversal is mainly performed by young residents.

Methods

A prospective database was investigated to extract data of patients who underwent loop ileostomy closure between January 2005 and December 2014. Ileostomy reversion was always realized in a handsewn fashion, performing either a direct closure (DC) or a resection plus end-to-end anastomosis (EEA). Postoperative morbidity was graded according to Clavien-Dindo classification. Outcomes after DC and EEA were compared by Fisher's exact test and Wilcoxon rank-sum test.

Results

Two hundred ninety-eight patients were included. Ileostomy reversal was performed by EEA in 236 patients (79.19 %) and by DC in 62 patients (20.81 %). Surgery was performed with a peristomal access in 296 cases (99.33 %). Incidence of anastomotic leak was 0.67 % (2/298). Overall reoperation rate was 0.34 % (1/298). Short-term overall morbidity rate was 20.47 %; but major complications (≥ grade III) occurred in only one patient (0.34 %). Mortality was nil. No significant differences in postoperative morbidity were found between the DC and EEA group.

Conclusion

Loop ileostomy reversal is a safe procedure, associated to a low major morbidity and excellent results, even if performed with a handsewn technique by supervised trainee surgeons.

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Rectal prolapse traumatizes rectal neuromuscular microstructure explaining persistent rectal dysfunction

Abstract

Purpose

Internal rectal prolapse is common and correlates with age. It causes a plug-like physical obstruction and is a major cause of defecation disorder. The progressive distortion of the prolapsing rectum likely causes secondary defects in the rectal wall, which may exacerbate rectal dysfunction. We undertook a prospective observational study to detect and quantify the neurologic and histopathologic changes in the rectal wall.

Methods

We examined dorsal and ventral rectal wall specimens from consecutive patients with internal rectal prolapse undergoing stapled transanal rectal resection (STARR). We subjected specimens to histopathologic and neuropathologic assessment, including immunohistochemistry. We also recorded patients' clinical and demographic characteristics and sought correlations between these and the pathologic findings.

Results

We examined 100 specimens. The severity of rectal prolapse and the extent of descent of the perineum correlated significantly with age. Concomitant hemorrhoidal prolapse was noted in all male patients and in 79 % of female patients. Muscular and neuronal defects were detected in 94 and 90 % of the specimens, respectively. Only four specimens (4 %) were free of significant structural defects.

Conclusion

Rectal prolapse traumatizes the rectum causing neuromuscular defects. The tissue trauma is due to shearing forces and ischemia caused by the intussusception. This initiates a self-reinforcing vicious circle of physical and functional obstruction, further impairing rectal evacuation and causing constipation and incontinence. The correlation between extent of prolapse and age suggests that internal rectal prolapse can be considered a degenerative disorder. Neural and motor defects in the wall of the rectum caused by rectal prolapse are likely irreversible.

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Robot-assisted versus laparoscopic surgery for lower rectal cancer: the impact of visceral obesity on surgical outcomes

Abstract

Purpose

The purpose of this study was to evaluate the advantages of robot-assisted laparoscopic surgery (RALS) for lower rectal cancer and for visceral obesity cases, which have been regarded as challenging situations in rectal cancer surgery, comparing their surgical outcomes with those of conventional laparoscopic surgery (CLS).

Methods

Patients who underwent robotic or laparoscopic total mesorectal excision for rectal cancer were included in this retrospective study. Surgical outcomes including perioperative, postoperative, and pathological data were compared between the RALS and CLS groups. Patients were stratified into obese and non-obese groups according to visceral fat area (VFA). Obesity was defined by VFA ≥130 cm².

Results

Two hundred thirty-six patients were enrolled, including 127 cases in the RALS group and 109 cases in the CLA group. A total of 82 (34.7 %) cases were categorized as VFA obese, including 52 cases in the RALS and 30 cases in the CLS groups. RALS for lower rectal cancer was associated with less blood loss (p = 0.007), a lower overall complication rate (9.4 % in RALS vs 23.9 % in CLS, p = 0.003), and shorter postoperative stay (p < 0.01) than CLS, with similar operative time and pathological results. The overall complication rate was significantly lower in the RALS group with VFA obesity; blood loss was significantly less and the postoperative stay was shorter in the RALS group with visceral obesity.

Conclusions

The present study demonstrated that RALS has some advantages in terms of surgical outcomes over CLS in challenging situations of rectal cancer surgery, such as lower rectal cancer cases and visceral obesity cases.

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Intramolecular Cycloaddition in the (Diyne)iridium Complexes [Cp*Ir(CO)(η2-ArC≡CC≡CAr)]: An Experimental and Computational Study

The diyne complex [Cp*Ir(CO)(η²-ArC≡CC≡CAr)] reacts with two-electron donor ligands to form the iridacyclobutenone [Cp*Ir(L){C(C≡CAr)=C(Ar)C=O}]. Kinetic measurements and computational studies support the proposal that the reaction pathway involves alkyne insertion followed by coordination of the two-electron donor ligand.

The diyne species [Cp*Ir(CO)(η²-ArC≡CC≡CAr)] undergoes intramolecular cycloaddition in the presence of two-electron donor ligands to afford iridacyclobutenone complexes. Kinetic measurements and a computational study suggest that the reaction proceeds through an alkyne insertion reaction followed by rate-limiting ligand association.

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Inverted erythrocyte membranes as a novel model for studying the antiphospholipid syndrome

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IgG/IgM antiphospholipid antibodies present in the classification of the antiphospholipid syndrome: a critical review of their association with thrombosis

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Influence of platelet count in platelet rich plasma for adenosine triphosphate release assay

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Mesenchymal Stem Cells Contribute to Hepatic Maturation of Human Induced Pluripotent Stem Cells

Background: Induced pluripotent stem cells (iPSCs) are human somatic cells that have been reprogrammed to a pluripotent state. Several methods have been used to generate hepatocyte-like cells from iPSCs. However, these hepatic cells have limited clinical application because of their immature function compared to primary hepatocytes. Mesenchymal stem cells (MSCs) have been reported to inhibit apoptosis of hepatic cells and to improve hepatic regeneration in acute liver injury. Therefore, we expected that MSCs had the potential to positively contribute to the maturation of hepatic cells. Here we demonstrate the effect of MSCs on the maturation of hepatoblasts derived from human iPSCs. Methods: MSCs were isolated from human bone marrow and cultured to 70-80% confluence. MSC-conditioned medium (MSC-CM) was collected 48 h after culture in hepatic maturation medium. Human iPSC-derived hepatoblasts were then cultured for 6 days with MSC-CM. Hepatic functions were analyzed and compared to those from cells cultured in general maturation medium. Results: Cells in both groups had a cuboidal morphology typical of hepatocytes. The proportion of Oct4-positive cells was decreased and those of albumin- and alpha-fetoprotein-positive cells were increased in the MSC-CM group. Albumin secretion and urea synthesis as well as cytochrome P450 (CYP) 3A4 activity were enhanced in the MSC-CM group. The gene expressions of some CYP enzymes were upregulated as demonstrated by RT-PCR. Conclusion: Secreted molecules from human MSCs could enhance the hepatic function of human iPSC-derived hepatocyte-like cells. Although more technological innovations are needed, MSC-CM will be useful as a novel efficient strategy for clinically relevant hepatic cell maturation.
Eur Surg Res 2017;58:27-39

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Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2 -negative patients with early-onset breast cancer

Abstract

Background

Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms.

Methods

Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing.

Results

A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases.

Conclusions

These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

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Reactivation of mutant p53 by capsaicin, the major constituent of peppers

Abstract

Background

Mutations in the p53 oncosuppressor gene are highly frequent in human cancers. These alterations are mainly point mutations in the DNA binding domain of p53 and disable p53 from transactivating target genes devoted to anticancer activity. Mutant p53 proteins are usually more stable than wild-type p53 and may not only impair wild-type p53 activity but also acquire pro-oncogenic functions. Therefore, targeting mutant p53 to clear the hyperstable proteins or change p53 conformation to reactivate wild-type p53 protein functions is a powerful anticancer strategy. Several small molecules have been tested for p53 reactivation in mutant p53-carrying cells while studies exploiting the effect of natural compounds are limited. Capsaicin (CPS) is the major constituent of peppers and show antitumor activity by targeting several molecular pathway, however, its effect on mutant p53 reactivation has not been assessed yet. In this study we aimed at investigating whether mutant p53 could be a new target of capsaicin-induced cell death and the underlying mechanisms.

Methods

p53 levels were analysed by western blot upon capsaicin treatment in the presence of the autophagy inhibitor chloroquine. The mutant p53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) assay and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The specific wild-type p53 activation was determined by using the inhibitor of p53 transactivation function, pifithrin-α and siRNA for p53.

Results

Here, we show that capsaicin induced autophagy that was, at least in part, responsible of mutant p53 protein degradation. Abrogation of mutant p53 by capsaicin restored wild-type p53 activities over mutant p53 functions, contributing to cancer cell death. Similar effects were confirmed in cancer cells bearing tumor-associated p53 mutations and in H1299 (p53 null) with overexpressed p53R175H and p53R273H mutant proteins.

Conclusion

These findings demonstrate for the first time that capsaicin may reduce mutant p53 levels and reactivate wild-type p53 protein in mutant p53-carrying cells and the p53 reactivation contributes to capsaicin-induced cell death.

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Inhibition of YAP suppresses CML cell proliferation and enhances efficacy of imatinib in vitro and in vivo

Abstract

Background

Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified.

Methods

The expression of YAP in CML cells was determined by western blotting. Next, the effects of YAP knockdown and YAP inhibitor on CML cells were evaluated by MTT assay, flow cytometry (FCM) and Wright's staining. Moreover, K562 induced mice model was employed to further investigate the role of YAP in vivo.

Results

YAP was overexpressed in CML cells. Knockdown of YAP by si-RNA or inhibition the function of YAP using verteporfin (VP) not only inhibited the proliferation, induced the apoptosis of CML cells but also reduced the expression of YAP target genes c-myc and survivin. Additionally, VP enhanced the efficacy of imatinib (IM) in vitro and suppressed leukemogenesis in vivo.

Conclusion

Our results indicate that YAP may play an important role in the proliferation and leukemogenesis of CML cells. Genetic or pharmacological inhibition of YAP provides a novel treatment strategy for CML.

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Copper-catalyzed N-thioetherification of sulfoximines using disulfides

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC06359D, Communication

Hui Zhu, Jin-Tao Yu, Jiang Cheng
A novel copper-catalyzed N-thioetherification of sulfoximines under mild reaction conditions was developed. In this procedure, the N-S bond formation was achieved using readily available disulfides as sulfur source.
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Affinity modulation of photoresponsive hosts for fullerenes. Light-gated corannulene tweezers

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC06445K, Communication

Hector Barbero, Sergio Ferrero, Lucia Alvarez-Miguel, Patricia Gomez Iglesias, Daniel Miguel, Celedonio M. Alvarez
Six azobenzene derivatives bearing polyaromatic fragments have been prepared and their reversible photoisomerization has been assessed. Corannulene-functionalized molecules have demonstrated excellent switchable hosting abilities towards fullerenes in which an interesting...
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Comparison of self-reported quality of vision outcomes after myopic LASIK with two femtosecond lasers: a prospective, eye-to-eye study

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Association of serum vitamin D with acute lower respiratory infection in Indian children under 5 years: A case control study

2016-09-06T05-11-47Z
Source: International Journal of Contemporary Pediatrics
Deepandra Garg, Vikas K. Sharma, B. S. Karnawat.
Introduction: Acute lower respiratory infection (ALRI), primarily pneumonia and bronchiolitis, is a substantial cause of morbidity and mortality in children


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Assessment of incidence, determinants and co-morbidities associated with meconium aspiration syndrome: a hospital based study

2016-09-06T05-11-47Z
Source: International Journal of Contemporary Pediatrics
Suhaim Afsar, Naresh P. Motwani*, Sudhakar C., Uma Chaturvedi.
Background: Meconium aspiration syndrome (MAS) was found to be major contributing factor towards perinatal morbidity and mortality. This condition is mainly accompanied with respiratory failure, pulmonary air leaks and pulmonary hypertension in neonates. A conservative approach of obstetrician-paediatrician combination moderates incidence of MAS and its complications. The objective of the study was to determine the incidence, determinants and co-morbidities associated with MAS in both intramural and out born admitted to the NICU and SNICU of a Chandulal Chandrakar memorial hospital located in Bhilai, Chattisgarh, India. Methods: This was a prospective study conducted in Chandulal Chandrakar memorial hospital, Bhilai from 1st September 2013 to 31st February 2015, in newborns with history of meconium stained amniotic fluid (MSAF) in both out-born and inborn units. Neonates who met inclusion criteria they were included in the study. The data were recorded in predesigned proforma. The data was analyzed using Chi square test. Level of significance of this data was set at p 2.5 kgs (80%) and common in primiparous mothers (60%) with lower segmental caesarian sections. MAS commonly seen in post -term babies (53.33%) than those of term (36.66%) or pre-term (10%) gestation. Fetal distress was the common complication observed in most of the cases (91.1%) and one death related to this was noted. At the end of 1 year there were predominantly more children (40%) who developed respiratory morbidities. Delayed development was seen among 13.3% children and transient tone abnormalities were noted in about 2% of infants. Conclusions: The overall incidence of MAS was found to have been 30% among cases of MSAF, which was relatively higher due to delayed referral. This percentage could have been reduced along with associated co-morbidities with appropriate antenatal check-ups and timely referral.


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Evaluation of neuro-developmental outcome among babies with meconium aspiration syndrome

2016-09-06T05-11-47Z
Source: International Journal of Contemporary Pediatrics
Suhaim Afsar, Naresh P. Motwani*, Sudhakar C., Uma Chaturvedi.
Background: Meconium aspiration syndrome (MAS) is respiratory distress in a neonates caused by the presence of meconium in the tracheobronchial airways. Despite adequate management, there is a high risk of morbidity in the form of seizures, cerebral palsy, mental retardation, respiratory problems of childhood and mortality. Hence, this study was performed in view of developmental issues concerning young infants and pre-school children as maximum brain growth happens in the first three years of life. Methods: This was a prospective study conducted in Chandulal Chandrakar memorial hospital, Bhilai from 1st September 2013 to 31st February 2015, with history of meconium stained amniotic fluid (MSAF) in both out-born and in-born neonates. Neonates after meeting inclusion criteria were included in the study. The data were recorded in pre-designed proforma. The data were analyzed using appropriate Chi square test. Level of significance was set at p 2.5 kgs (80%) and common in primiparous mothers (60%) with lower segmental caesarian sections. MAS commonly seen in post -term babies (53.33%) than those of term (36.66%) or pre-term (10%) gestation. Fetal distress was the common complication observed in most of the cases (91.1%) and one death related to this was noted. At the end of 1 year there were predominantly more children (40%) who developed respiratory morbidities. Delayed development was seen among 13.3% children, transient tone abnormalities were noted in about 2% of infants. Conclusions: The findings of the present study suggest that neonates diagnosed with MAS displayed neuro-developmental delay in13% cases. This study gave an overview of all meconium aspiration cases and the neuro-developmental outcome in these babies. However further research should be done with large sample size to confirm these findings.


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In vivo and in vitro inhibitory activity of an ethanolic extract of Sargassum fulvellum and its component grasshopper ketone on atopic dermatitis

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Bo-Kyeong Kang, Min-Ji Kim, Koth-Bong-Woo-Ri Kim, Dong-Hyun Ahn
The present study investigated the effect of Sargassum fulvellum ethanol extract (SFEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice. The severity of skin dermatitis, production of cytokines, and total IgE content were measured, and the histopathological features were analyzed. SFEE decreased the severity of DNCB-induced dermatitis and suppressed the serum levels of total immunoglobulin E (IgE), tumor necrosis factor (TNF)-α, and interleukin (IL)-4. In addition, SFEE reduced the production of IL-4, IL-5, and IL-13 in mice splenocytes. However, the levels of IL-10 and interferon (IFN)-γ significantly increased in mice sera and splenocytes. Histological examination revealed decreased dermal thickness and infiltration by mast cells after treatment with SFEE. Furthermore, grasshopper ketone, a compound isolated from SFEE, was found to significantly decrease cytokine production in concanavalin A-stimulated splenocytes from BALB/c mice with no cytotoxicity. Taken together, these results indicate that SFEE and the isolated grasshopper ketone have an inhibitory effect on AD by regulating immune mediators and cells and may be a potential effective alternative therapy for AD.



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Tumor-associated macrophages promote invasion via Toll-like receptors signaling in patients with ovarian cancer

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Xing Ke, Shuping Zhang, Meng Wu, Jianfang Lou, Jiexin Zhang, Ting Xu, Lei Huang, Peijun Huang, Fang Wang, Shiyang Pan
Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes recruit into tumor microenvironment and display functions associated with tumor progression. The mechanisms by which TAMs display roles that associated with the invasion ability of ovarian cancer have not been well investigated. In our research, we found abundant TAMs infiltrate in ovarian cancer compared with benign ovarian tumor tissues. Levels of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-10, and Toll-like receptors (TLRs) signaling proteins were evaluated in ovarian cancer. The high level of TAMs was associated with metastasis and advance of patients with ovarian cancer. TAMs and ovarian cancer cell line SKOV3 were cocultured in vitro, MMPs level and the invasion ability of SKOV3 cells were significantly up-regulated. The coculture process was correlated with the activation of TLRs signaling and downstream nuclear factor (NF)-κB p65 and microtubule-associated proteins (MAPs) kinases pathway in SKOV3. In addition, pre-incubation with TLRs signaling inhibitors remarkably suppressed invasion ability of SKOV3. Levels of TLRs signaling pathways proteins were also down-regulated in this blocking process. These findings demonstrated that TAMs promoted up-regulation of MMP-2, MMP-9 and MMP-10 expressions and enhanced ovarian cancer cells invasion via TLRs signaling pathway. We conclude that TAMs could enhance ovarian cancer cells invasion and ultimately promote ovarian cancer progression.



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Transient receptor potential channels in intestinal inflammation: what is the impact of cigarette smoking?

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STOPP/START version 2-development of software applications: easier said than done?

Explicit criteria, such as the STOPP/START criteria, are increasingly used both in clinical practice and in research to identify potentially inappropriate prescribing in older people. In an article on the STOPP/START criteria version 2, O'Mahony et al. have pointed out the advantages of developing computerised criteria. Both clinical decision support systems to support healthcare professionals and software applications to automatically detect inappropriate prescribing in research studies can be developed. In the process of developing such tools, difficulties may occur. In the context of a research study, we have developed an algorithm to automatically apply STOPP/START criteria version 2 to our research database. We comment in this paper on different kinds of difficulties encountered and make suggestions that could be taken into account when developing the next version of the criteria.

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Exposure to positively- and negatively-charged plasma cluster ions impairs IgE-binding capacity of indoor cat and fungal allergens

Environmental control to reduce the amount of allergens in a living place is thought to be important to avoid sensitization to airborne allergens. However, efficacy of environmental control on inactivation of ...

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