Full-Term Small-for-Gestational-Age Newborns in the U.S.: Characteristics, Trends, and Morbidity

Abstract

Objectives The magnitude, characteristics, and morbidity of term (≥37 weeks gestation) newborns that are small-for-gestational-age (SGA) in the U.S. are underexplored. We sought to examine characteristics and trends for SGA-coded term newborns in the U.S. Methods Data were obtained from the Nationwide Inpatient Sample, a nationally representative database of hospital stays in the U.S. from 2002 to 2011. Term, singleton newborns with SGA codes were identified and examined over the study period. Demographic characteristics were compared for term newborns according to presence of SGA codes using χ² tests. Odds ratios (OR) were calculated to compare morbidities between the two groups, adjusting for relevant demographic and clinical variables. Results In 2011, 15 per 1000 term newborns in the U.S. were coded as SGA, a 29.9 % increase since 2002. Compared with other term newborns, SGA term newborns were significantly (p < 0.05) more likely to be female, receive public insurance, and reside in lower income zip codes. Comorbidities, including perinatal complications, metabolic disorders, central nervous system diseases, infection, and neonatal abstinence syndrome were more common among SGA-coded term newborns. These newborns also had higher odds of in-hospital death (OR = 3.0 95 % confidence interval: 2.0, 4.4), longer mean length of stay (3.7 vs. 2.3 days, p < 0.001), and higher mean hospital charges ($12,621 vs. $5012, p < 0.001). Conclusions for practice Term newborns coded as SGA have higher morbidity, mortality, and incur higher hospital charges than other term newborns. More research is needed to understand causes of SGA so its incidence and effects can be reduced.

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Paramedic - Lifeguard Ambulance Services

SUMMARY: Administers life support care to sick and injured persons in pre-hospital setting as authorized and directed by physician. Conducts advanced life support skills as allowed by the local, state and federal protocols and assists in the delivery of seriously ill or injured patients to appropriate medical facility personnel. Provides basic information relative to identification and condition of ...

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Erratum to: Psychosis in Parkinson’s Disease: Epidemiology, Pathophysiology, and Management

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Combination of glycolic acid peel and topical 20% azelaic acid cream in melasma patients: efficacy and improvement in quality of life

Summary

Background

Glycolic acid (GA) peel is one of the most versatile agents in the treatment of melasma. GA peeling alone or in combination with topical hypopigmenting agents has shown encouraging results. However, there is paucity of controlled trial demonstrating the efficacy of glycolic peel in conjunction with topical azelaic acid (AA). We therefore sought to highlight the efficacy and safety of this combination in melasma.

Objective

To assess the clinical efficacy, safety and reduction in melasma quality of life (MELASQOL) scores on combining serial GA peels with topical 20% AA cream in epidermal melasma.

Materials and method

Sixty patients of epidermal melasma were enrolled for 24 weeks. Patients were divided into two groups: (1) Study group received serial GA peel every 3 weeks with twice daily 20% AA cream, and (2) control group received only 20% AA cream. Clinical improvement was assessed objectively using Melasma Area Severity Index (MASI). Melasma-related quality of life was measured by MELASQOL scale in both groups. Side effects were observed at each visit.

Results

The improvement in MASI and percentage decrease in MASI scoring were statistically significant 12 weeks onwards in study group as compared to control group. There was also a significant reduction in MELASQOL scores in study group as compared to control group after treatment. Minor reversible side effects were observed in both groups, which did not require cessation of therapy.

Conclusion

GA peel enhances therapeutic efficacy of topical AA cream for treatment of melasma, with improvement in quality of life without serious side effects.

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Issue Information - Contents

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Cover Image

The cover image, by Fredrik Petersson et al., is based on the Case Report Minimally invasive carcinosarcoma ex pleomorphic adenoma: A case report and literature review with cytohistological correlation, DOI: 10.1002/hed.24462.

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Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non–human papillomavirus16 viral subtypes

Abstract

Background

The majority of human papillomavirus (HPV)-related oropharyngeal carcinomas (OPCs) are associated with HPV genotype 16; however, OPC can be associated with other high-risk non-HPV16 genotypes.

Methods

This was a retrospective analysis of patients with high-risk non-HPV16 OPC treated at a single tertiary institution. Sociodemographic and clinical information was obtained by chart review. HPV genotype was determined by polymerase chain reaction (PCR). Baseline data and outcomes were compared between HPV16 and high-risk non-HPV16 groups.

Results

High-risk non-HPV16 genotypes accounted for 9% of HPV-related OPC. Of the 27 total high-risk non-HPV16 OPCs, HPV35 was most prevalent (48%). High-risk non-HPV16 OPC presented at a slightly higher age (p = .021) and higher clinical T classification (p = .008) compared to HPV16 OPC, but there was no significant survival difference.

Conclusion

Clinical characteristics of high-risk non-HPV16 OPC were largely consistent with those of HPV16 OPC. Additional multi-institutional studies will be required to demonstrate conclusively that the favorable prognosis of patients with HPV16 applies to all high-risk HPV types. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1330–1337, 2016

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Minimally invasive carcinosarcoma ex pleomorphic adenoma: A case report and literature review with cytohistological correlation

Abstract

Background

Carcinosarcoma of the salivary glands is a rare neoplasm, and the minimally invasive form constitutes a subgroup with a more favorable prognosis. The cytomorphologic features of this neoplasm can be appreciated on fine-needle aspiration biopsy.

Methods and Results

We present a patient with a minimally invasive carcinosarcoma ex non-recurrent pleomorphic adenoma (Ca ex PA) who underwent initial fine-needle aspiration biopsy followed by surgical resection. The tumor was composed predominantly of a light microscopic pleomorphic high-grade sarcoma exhibiting partial myoepithelial immunohistochemical features, with a minor component of in situ and invasive salivary duct carcinoma (10%). A limited area with features of a hyalinized pleomorphic adenoma was identified.

Conclusion

This is the third case report of the cytological features of Ca ex PA of the salivary gland, with histologic correlation. It further illustrates the oncogenic relationship between epithelial and myoepithelial elements in the early stages of carcinosarcomatous transformation. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2483–E2489, 2016

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Brachytherapy after salvage surgery in cases with large isolated cervical recurrence of squamous cell carcinoma in the previously irradiated neck

Abstract

Background

Perioperative brachytherapy after salvage surgery is a therapeutic option in patients with cervical relapse of a primary, controlled, previously irradiated head and neck squamous cell carcinoma. The purpose of this study was to analyze the outcome of this treatment.

Methods

Between 2008 and 2013, 8 patients underwent cervical brachytherapy after neck dissection. The mean node size was 5.5 cm. Recurrence occurred in an irradiated field (median dose, 50 Gy). Brachytherapy was performed with ¹⁹²iridium and dosimetry in accord with the rules of the Paris system. The dose was 60 to 62.7 Gy on the reference isodose.

Results

The mean follow-up was 17 months. The median overall survival (OS) was 12 months. The OS was 19% at 2 years and 0% at 5 years. A grade 5 postoperative adverse event occurred in 1 patient. At 6 months, all patients had a grade 3 neck soft tissue fibrosis. One patient had a lethal hemorrhage at 56 months.

Conclusion

Brachytherapy is toxic in this population with poor OS. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2490–E2494, 2016

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Free anterolateral thigh flap and masseter nerve transfer for reconstruction of extensive periauricular defects: Surgical technique and clinical outcomes

Abstract

Background

Radical tumor ablation in the periauricular area often results in extensive soft tissue defects, including facial nerve sacrifice, bone and/or dura defects. Reconstruction of these defects should aim at restoring facial reanimation, wound closure, and facial and neck contours. We present our experience using free anterolateral thigh flap (ALT) in combination with masseter nerve to facial nerve transfer in managing complex defects in the periauricular area.

Methods

Between 2011 and 2015 six patients underwent a combined procedure of ALT flap reconstruction and masseter nerve transfer, to reconstruct extensive, post tumor resection, periauricular defects. The ALT flap was customized according to the defect. For smile restoration, the masseter nerve was transferred to the buccal branch of the facial nerve. If the facial nerve stump was preserved, interposition of nerve grafts to the zygomatic and frontal branches was performed to provide separate eye closure. The outcomes were analyzed by assessing wound closure, contour deformity, symmetry of the face, and facial nerve function.

Results

There were no partial or total flap losses. Stable wound closure and adequate volume replacement in the neck was achieved in all cases, as well as good facial tonus and symmetry. The mean follow-up time of clinical outcomes was 16.8 months. Smile restoration was graded as good or excellent in four cases, moderate in one and fair in one.

Conclusion

Extensive periauricular defects following oncologic resection could be adequately reconstructed in a combined procedure of free ALT flap and masseter nerve transfer to the facial nerve for smile restoration.

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GORE TIGRIS, a Third Generation Stent with Flexibility, Strength, Anti-Thrombus Technology, FDA Approved

W. L. Gore & Associates, better known as just Gore, won FDA approval for its GORE TIGRIS vascular stent. The device combines traditional nitinol metal with fluoropolymer interconnections. This gives it impressive strength and flexibility to resist the mechanical forces applied by either superficial femoral artery (SFA) or proximal popliteal artery (PPA), depending on the site of implantation. In a study that led to the FDA approval, the GORE TIGRIS had no fractures at all while 27% of the control devices experienced fractures.

The GORE TIGRIS also uses the firm's CBAS Heparin Surface, a blood thinning component that helps prevent thrombi from forming around the stent. This technology bonds the heparin to the stent while keeping the other side free to react with the blood passing by.

From GORE:

The evolution of peripheral stenting over the past decade has allowed for broader adoption of endovascular therapy for treating PAD. When physicians began placing stents in the SFA they were limited by first generation stent designs that had longitudinal metal connections which led to arterial stiffening, high fracture rates and poorer clinical outcomes. Improvements in second generation devices introduced helical interconnections to improve flexibility; however, their success in high flexion vessels, like the distal SFA and PPA, was still limited.* The introduction of third generation stents, including the GORE TIGRIS Vascular Stent, allow for better adherence in some of the more intricate vessels in the body.

Product page: GORE TIGRIS Vascular Stent…

Via: GORE…

This post GORE TIGRIS, a Third Generation Stent with Flexibility, Strength, Anti-Thrombus Technology, FDA Approved appeared first on Medgadget.

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Upper limb and trunk muscle activation during an unexpected descent on the outstretched hands in young and older women

Publication date: Available online 8 August 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Lauren J. Lattimer, Joel L. Lanovaz, Jonathan P. Farthing, Stéphanie Madill, Soo Kim, Cathy Arnold
Falling on the outstretched hands (FOOSH), a protective mechanism to arrest the body and avoid injury, requires upper limb and trunk motor control for effective body descent. The purpose of this study was to investigate muscle activity during three phases of an unexpected FOOSH in healthy older and younger women. Twenty young (mean age 22.9 yrs., SD±3.7) and 20 older females (mean age 68.1yrs., SD ±5.0) performed five trials of unexpected FOOSHs. Surface electromyography (EMG) determined muscle activations for left shoulder girdle, elbow and abdominal muscles during an unexpected FOOSH. Root mean squared EMG data were calculated during three phases: 1) baseline (BL; 500ms prior to release), 2) the preparatory phase (PRE; time between release and impact) (mean 257±37ms) and post-impact (POST; 200ms after impact). A mixed MANOVA determined differences between phases and age groups. There was a significant multivariate interaction effect of age and time phase on muscle activity (p=0.001). Younger women had significantly higher internal oblique/ transversus abdominus activity during PRE (p=0.006) as well as variations in muscle activity of shoulder girdle and elbow muscles. The age differences observed may lead to poorer preliminary trunk activation and greater arm bracing in older women, potentially increasing risk of fallrelated injury.



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Abstracts: 45th Annual Meeting of the Japanese Society for Wound Healing

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Mitochondrial genome erosion and the evolution of sex

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A purely predatory relationship… Really?

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Upper motor neuron evaluation in multiple sclerosis patients treated with Sativex®

Abstract

Background

Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST).

Objectives

To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex^® treatment.

Methods

Ten MS patients with spasticity ("cases") underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline.

Results

At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT (P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex^® resulted in a reduction of NRS for spasticity (P=.01).

Conclusions

We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex^® clinical effect.

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Approved oncology drugs lack in vivo activity against Trichuris muris despite in vitro activity

Abstract

Infections with soil-transmitted helminths (STHs) are considered among the most persistent global health problems. The few available drugs have limitations including low efficacy against Trichuris trichiura infections. As a starting point toward drug repositioning, we studied a set of FDA-approved oncology drugs for activity against Trichuris muris since targets relevant to cancer therapy might have a function in helminth biology. Drugs were tested in vitro on the larval and adult stage of T. muris. Compounds active in vitro were tested in the T. muris mouse model at single oral dosages of 200–400 mg/kg. Of the 114 drugs tested in vitro, 12 showed activity against T. muris larvae (>80 % drug effect at 50 μM). Ten of these drugs were also active on the adult worm stage (>80 % drug effect at 50 μM), of which six revealed IC₅₀ values between 1.8 and 5.0 μM. Except for tamoxifen citrate, all in vitro active drugs were protein kinase inhibitors. None of the drugs tested in vivo showed efficacy, revealing worm burden reductions of 0–24 % and worm expulsion rates of 0–7.9 %. The promising in vitro activities of protein kinases could not be confirmed in vivo. Drug discovery against STH should be strengthened including the definition of compound progression criteria. Follow-up structure-activity relationship studies with modified compounds might be considered.

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Humid Air Vortex Gun to Improve Airplane Comfort

At the Fraunhofer Institute for Building Physics in Germany, scientists have been working on improving the air we breathe when flying in airplanes. High flying airplanes are designed to reduce the internal air humidity to prevent moisture from sticking to the surfaces. This is because of the low pressure and cold temperature outside and the pressure regulation inside. The result are dry mucous membranes and flyer discomfort. A new vortex ring generator by the research team may be just the thing to increase the humidity for the flyers without raising the overall humidity inside the fuselage.

The generator spins up high humidity air and shoots it out toward a person's chest, creating a volume about the size of the head. The vortex then moves up toward the mouth and nose because of the warmth of the chest. Due to the laws of fluid dynamics, this vortex remains a lot more localized and stationary than simply blowing humid air out a vent. Since the amount of humidity expelled by the generator is pretty small compared to the size of the cabin, the windows should remain clear and surfaces dry.

To test the system, a dummy was recruited as a text subject whose nose has sensors that analyze incoming air. Instead of water vapor, more easily seen smoke was used. This allowed the team to tune their device to better target the dummy and prove that the concept is not just a bunch of humid air. Hopefully upcoming steps will involve working with airplane manufacturers to begin thinking of testing and later integrating the technology into the planes we fly.

Source: Fraunhofer…

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Dual structure evolution of a Ag(I) supramolecular framework triggered by anion-exchange: replacement of terminal ligand and switching of network interpenetration degree

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC05938D, Communication

Cheng-Peng Li, Si Wang, Wei Guo, Yan Yan, Miao Du
A 3-fold interpenetrated Ag(I) coordination framework can behave dual structure evolution driven by distinct anion-exchange courses in which irreversible single-crystal to single-crystal transformation occurs to result in a switching of...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Long-term preclinical MRI alterations in sporadic Creutzfeldt-Jakob disease

Abstract

An asymptomatic 74-year-old woman, on follow-up for a carotid body tumour, showed MRI focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion-weighted images revealed a bilateral cortical ribbon sign involving all lobes. After one month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within three months. Prion protein gene sequence, molecular and neuropathological studies confirm the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. This article is protected by copyright. All rights reserved.

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The cities of the future could be built by microbes

Today in Phys.org, Martyn Dade-Robertson explores the possibility of using microbes to produce natural cement. This process, called biomineralisation, was discovered deep under water off the coast of the Greek island of Zakynthos. Future implications for biomineralisation include self-healing ...

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Zika Virus in the USA

On this episode of Virus Watch we cover three Zika virus stories: the first human trial of a Zika virus vaccine, the first local transmission of infection in the United States, and whether the virus is a threat to participants in the 2016 Summer Olympic and Paralympic Games.

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Mosquito saliva enhances virus replication and disease

Mosquito saliva, which is injected into the host as a mosquito probes for a blood vessel, contains a collection of chemicals which include anticoagulants to prevent blood clotting, vasodilators to keep blood vessels wide, and anesthetics to prevent us from sensing the mosquito. Saliva also conta...

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The Effect of Bariatric Surgery on Mobility, Health-Related Quality of Life, Healthcare Resource Utilization, and Employment Status

Abstract

Background

A sub-study of the Ontario Bariatric Registry was conducted to evaluate the impact of bariatric surgery on mobility, health-related quality of life (HRQoL), healthcare resource utilization (HRU), and employment status.

Methods

The 1-year change in mobility following bariatric surgery was evaluated using the mobility domain of the EuroQOL-5D-5L (EQ-5D-5L), which was self-administered at baseline and 1 year after bariatric surgery along with questions on HRU. Another questionnaire was used to document employment status at time of surgery and 1 year later.

Results

The population included 304 individuals (mean age = 46 years; 85 % female). At baseline, 68 % of participants had some problems in walking compared to 14 % at 1 year following surgery (p < 0.001). The EQ-5D-5L health utility score increased from 0.73 to 0.90 (p < 0.001). The number of hospitalizations increased significantly before and after surgery (p = 0.021). Of the 304 study participants, 138 completed the questionnaire and responses indicated that more individuals reported a change in their employment status within 1 year following surgery (26 %) compared to 1 year prior to the surgery (9 %) (p < 0.001).

Conclusions

Within the limitations of this study, there is a suggestion that bariatric surgery has a major impact on mobility and HRQoL. More research is warranted to understand the benefits, costs, and cost-effectiveness of bariatric surgery in Canada.

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Rare case of gallbladder agenesis presenting with pancreatitis

Gallbladder agenesis (GA) is a rare congenital abnormality with an incidence of 0.01–0.09%. Majority of GA exist alone although it can be associated with other systemic malformations involving the gastrointestinal, genitourinary, cardiovascular and skeletal systems. It is thought that biliary and pancreatic pathologies coexist and this is the second case reported in the literature of GA presenting with pancreatitis.

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Cerebral venous thrombosis associated with thyrotoxicosis, the use of desmopressin and elevated factor VIII/von Willebrand factor

Cerebral venous thrombosis (CVT) is an uncommon disorder associated with diverse processes. We report a patient who, while receiving desmopressin and contraceptive pills (OCP), developed straight sinus thrombosis. Clinical assessment and laboratory investigations revealed untreated hyperthyroidism and a hypercoagulable state, characterised by high levels of von Willebrand factor, factor VIII coagulant activity and IgM cardiolipin antibody. The clinical picture improved with anticoagulation, treatment of hyperthyroidism and discontinuation of OCP and desmopressin. To the best of our knowledge, the association between the use of oral desmopressin and CVT has not been described. The multiple risk factors present in our case were probably additive in increasing the risk of CVT. Although this case represents a rare occurrence, practitioners should be alerted to the possible associations of desmopressin, oral contraceptives and Graves' disease with venous thrombosis.

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Successful treatment of recurrent pleural and pericardial effusions with tocilizumab in a patient with systemic lupus erythematous

A 22-year-old Caucasian man presented to hospital with pleuritic chest pain. He had had a history of a sun-sensitive rash a year prior. Workup revealed normal cardiac enzymes and chest X-ray. However, electrocardiogram revealed ST elevation and PR depression, and echocardiogram revealed a slight pericardial effusion without other findings. A diagnosis of pericarditis was made. Subsequently, he was found to be positive for antinuclear antibodies (ANAs), as well as antibodies to SSA, SSB and double-stranded DNA; C3 was low, and C4 was undetectable. A diagnosis of systemic lupus erythematosus was made. The patient initially responded to high-dose ibuprofen. One month later, he developed a new pericardial effusion, this time with concomitant massive left-sided pleural effusion, requiring three separate thoracenteses draining a total of 6 L of pleural fluid. The recurrent effusion failed to respond to high-dose corticosteroid treatment. Owing to the severity and rapidity of the recurrence of pleural and pericardial effusion, intravenous tocilizumab was administered. The patient had excellent clinical and radiographic improvement. This case shows that tocilizumab may have a role in the treatment of intractable pleuropericardial effusion and other forms of lupus-associated serositis.

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Maternal uniparental disomy for chromosome 6 in a patient with IUGR, ambiguous genitalia, and persistent mullerian structures

Maternal uniparental disomy of chromosome 6 [upd(6)mat] is rare and has only been previously reported 13 times with the main associated phenotype being IUGR. We present a case of a male patient with isodisomy upd(6)mat resulting in severe IUGR and ambiguous genitalia, a phenotype not previously described in association with this chromosome finding. The patient initially presented prenatally with IUGR at 19 weeks gestation with placental dysfunction and ambiguous genitalia noted at 27 weeks. Postnatally, the patient had external genital abnormalities, the gonads were in the inguinal canal and there was a rudimentary appearing vagina and uterus. Karyotype is 46, XY and SNP array revealed maternal isodisomy of 171 Mb at 6p25.3q27 with no pathogenic copy number variants. To our best knowledge, this is the first case of an XY patient with upd(6)mat with IUGR and ambiguous genitalia, further supporting previous reports regarding an association between upd(6)mat and IUGR. This patient also presented with a disorder of sex development (46, XY DSD) with the sex chromosome being male and positive for the SRY gene, testicular gonadal sex and abnormal external and internal genitalia. © 2016 Wiley Periodicals, Inc.

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Erratum to: The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b + Ly6C hi cells to tumor tissue reduces tumor growth

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Erratum to: Conformational changes and translocation of tissue-transglutaminase to the plasma membranes: role in cancer cell migration

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Diagnostic accuracy of intracranial translucency in detecting spina bifida: a systematic review and meta-analysis

Abstract

Objective

To evaluate the diagnostic accuracy of intracranial translucency(IT) in the detection of spina bifida in the first trimester of pregnancy

Methods

We included study assessing the accuracy of sonographic measurements of IT in a mid-sagittal view of the fetal face in prediction of spina bifida in the first trimester of pregnancy. The primary outcome was the accuracy of IT in prediction of spina bifida. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR + andLR–) and diagnostic odds ratio (DOR) for the overall predictive accuracy of IT were computed.

Results

9studies(21,070fetuses)were included in the analysis. IT was successfully assessed in the majority of fetuses 97.8% (95%CI 97.6-98.0). The diagnostic performance of IT in detecting spina bifida was as follows: sensitivity:53.5% (95%CI42.4-64.3); specificity:99.7% (95%CI99.6-99.8); LR+:62.1 (95%CI12.2-317); LR-:0.55 (95%CI0.45-0.68); DOR: 223 (95%CI25-2039).

Conclusions

IT had low diagnostic accuracy in prediction of open spina bifida thus questioning its role as a screening marker for OSB in an unselected population. When looking at the individual study data, it appears that IT assessment for OSB prediction can be affected by a high rate of false positive results potentially leading to unnecessary parental anxiety.

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A genotype-phenotype correlation study reveals a non-coding RNA might be associated with cardiovascular anomalies in WHS fetuses

Abstract

Wolf-Hirschhorn syndrome (OMIM#194190) is a rare genetic disease caused by a partial deletion from the short arm of chromosome 4. It consists of a broad range of clinical manifestations, including a characteristic craniofacial appearance, growth retardation, intellectual disability, seizures, and structural abnormalities, etc. ^1,2 The deletion size also varies greatly and is reported to range from 67 kb to 37 Mb. ^3,4 Two WHS critical regions (WHSCR and WHSCR-2) have been postulated by researchers, containing candidate genes such as WHSC1, WHSC2 and LETM1. ^5,6,7 However, WHS critical regions are insufficient to elucidate the complex clinical presentations. Although many genotype-phenotype correlation studies have been performed, few clear-cut clinical-genetic correlations could be easily established due to the complexity of WHS etiology. Here we present two fetuses with WHS to provide further insight into the pathogenesis of WHS, both with similar deletions but with different clinical manifestations.

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Stigmatization toward irritable bowel syndrome and inflammatory bowel disease in an online cohort

Abstract

Background

Stigma is associated with many negative health outcomes. Research has examined perceived and internalized stigma in individuals with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), but less has been done to evaluate levels of enacted stigma associated with these conditions. The aim of this study was to evaluate the presence of enacted stigma toward IBS and IBD in the general population compared to an adult-onset asthma (AOA) control group.

Methods

Participants were recruited via social media and a research-dedicated website and completed all measures online. Participants were randomized to one of six clinical vignettes: (i) IBD male, (ii) IBD female, (iii) IBS male, (iv) IBS female, (v) AOA male, or (vi) AOA female. Participants read the assigned vignette and then completed measures of emotional empathy, level of familiarity, and enacted stigma.

Key Results

Participants reported higher levels of enacted stigma toward IBS compared to both IBD and AOA. No differences in stigma were found between IBD and AOA. Higher levels of familiarity were most strongly correlated with reduced IBD-related stigma, with weaker but still significant correlations between level of familiarity and IBS and AOA. Higher levels of emotional empathy were associated with reduced stigma for IBD, IBS, and AOA.

Conclusions & Inferences

Individuals with IBS experience greater levels of enacted stigma compared to IBD and AOA. This finding is consistent with previous research that has shown greater levels of perceived and internalized stigma in IBS compared to IBD.

Stigma toward chronic illness is a pervasive public health issue. This is the first study to evaluate stigmatizing beliefs toward IBS and IBD.

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Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma

ABSTRACT

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non-Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV-infected patients with diffuse large B-cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV-infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004-May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon-based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% v 72%; p=0.07) and upper gastrointestinal (GI; 42% v 24%; p=0.004) involvement. Cases never given AVT had DLBCL more refractory to first-line chemotherapy than that in the controls (33% v 17%; p=0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% v 32%; p=0.09) or cases given AVT (50% v 27%; p=0.06). Cases never given AVT had worse 5-year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01-5.3]; p=0.04). Furthermore, AVT improved 5-year OS rates among cases in both univariate (median [Interquartile range]: 39 [26-56] v 16 [6-41] months, p=0.02) and multivariate analyses (HR=0.21 [95% CI, 0.06-0.69]; p=0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5-year OS. This article is protected by copyright. All rights reserved.

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Anti-tumor Activity of the ATR Inhibitor AZD6738 in HER2 positive Breast Cancer Cells

ABSTRACT

Ataxia telangiectasia and Rad3-related (ATR) proteins are sensors of DNA damage, which induces homologous recombination (HR)-dependent repair. ATR is a master regulator of DNA damage repair (DDR), signaling to control DNA replication, DNA repair, and apoptosis. Therefore, the ATR pathway might be an attractive target for developing new drugs. This study was designed to investigate the antitumor effects of the ATR inhibitor, AZD6738 and its underlying mechanism in human breast cancer cells. Growth inhibitory effects of AZD6738 against human breast cancer cell lines were studied using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (methyl thiazolyl tetrazolium, MTT) assay. Cell cycle analysis, Western blotting, immunofluorescence, and comet assays were also performed to elucidate underlying mechanisms of AZD6738 action. Anti-proliferative and DDR inhibitory effects of AZD6738 were demonstrated in human breast cancer cell lines. Among 13 cell lines, the IC₅₀ values of 9 cell lines were less than 1 μmol/L using MTT assay. Two cell lines, SK-BR-3 and BT-474, were chosen for further evaluation focused on human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. Sensitive SK-BR-3 but not the less sensitive BT-474 breast cancer cells showed increased level of apoptosis and S phase arrest and reduced expression levels of phosphorylated check-point kinase 1 (CHK1) and other repair markers. Decreased functional CHK1 expression induced DNA damage accumulation due to HR inactivation. AZD6738 showed synergistic activity with cisplatin. Understanding the antitumor activity and mechanisms of AZD6738 in HER2-positive breast cancer cells creates the possibility for future clinical trials targeting DDR in HER2-positive breast cancer treatment. This article is protected by copyright. All rights reserved.

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Robust Underwater Oil-Repellent Material Inspired by Columnar Nacre

Inspired by natural columnar nacre, artificial montmorillonite/hydroxyethyl cellulose columnar nacre-like materials with a site-specific layered structure in the interior and a hierarchical columnar structure on the surface are prepared. The materials exhibited improved tensile strength, good chemical stability in seawater, superior resistance to sand grain impingement, and robust underwater low adhesive superoleophobicity.

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Dual-Template Synthesis of 2D Mesoporous Polypyrrole Nanosheets with Controlled Pore Size

The first synergistic dual-template self-assembly approach is presented for bottom-up construction of 2D mesoporous polypyrrole nanosheets based on different supramolecular assemblies, which feature a double-layered architecture, controlled pore sizes, ultrathin thickness, and large surface area. The unique structure rends them with superior reversible discharge capability, rate performance, and stable cyclability when serving as the cathode materials for Na-ion batteries.

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Compensated Ferrimagnetic Tetragonal Heusler Thin Films for Antiferromagnetic Spintronics

Fully compensated ferrimagnets with tetragonal crystal structure have the potential for large spin-polarization and strong out-of-plane magnetic anisotropy; hence, they are ideal candidates for high-density-memory applications. Tetragonal Heusler thin films with compensated magnetic state are realized by substitution of Pt in Mn_3−xPt_xGa. Furthermore, the bilayer formed from compensated/uncompensated Mn–Pt–Ga layers is utilized to accomplish exchange bias up to room temperature.

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Recent Advances in Doping of Molybdenum Disulfide: Industrial Applications and Future Prospects

Owing to their excellent physical properties, atomically thin layers of molybdenum disulfide (MoS₂) have recently attracted much attention due to their nonzero-gap property, exceptionally high electrical conductivity, good thermal stability, and excellent mechanical strength, etc. MoS₂-based devices exhibit great potential for applications in optoelectronics and energy harvesting. Here, a comprehensive review of various doping strategies is presented, including wet doping and dry doping of atomically crystalline MoS₂ thin layers, and the progress made so far for their doping-based prospective applications is also discussed. Finally, several significant research issues for the prospects of doped-MoS₂ in industry, as a guide for 2D material community, are also provided.

Various strategies for doping of molybdenum disulfide are comprehensively reviewed, including wet doping and dry doping of MoS₂ thin layers and the progress made so far for their doping-based industrial applications. Finally, a few important opening study directions for future prospects of doped atomically crystalline MoS₂ layers in optoelectronics and energy harvesting, as a guide for the 2D material community, are also provided.

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Photon Upconversion at Crystalline Organic–Organic Heterojunctions

Triplet transfer across a surface-anchored metal–organic-framework heterojunction is demonstrated by the observation of triplet–triplet annihilation photon ­upconversion in a sensitizer–emitter heterostructure. Upconversion thresholds under 1 mW cm⁻² are achieved. In the broader context, the double-electron-exchange mechanism of triplet transfer indicates that the heterojunction quality is sufficient for electrons to move between layers in this solution-processed crystalline heterostructure.

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High-Performance Photovoltaic Polymers Employing Symmetry-Breaking Building Blocks

Two 1D–2D asymmetric benzodithiophenes (BDTs) as donor building blocks are designed and synthesized, combining the advantages of both 1D and 2D symmetric BDTs. The photovoltaic properties of the asymmetric BDT-based polymers are improved greatly in comparison with corresponding symmetric BDT-based polymers. This work provides a new approach to design prospective organic optoelectronic materials employing the symmetry-breaking strategy.

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A Vinylene-Bridged Perylenediimide-Based Polymeric Acceptor Enabling Efficient All-Polymer Solar Cells Processed under Ambient Conditions

All-polymer solar cells with 7.57% power conversion efficiency are achieved via a new perylenediimide-based polymeric acceptor. Furthermore, the device processed in ambient air without encapsulation can still reach a high power conversion efficiency (PCE) of 7.49%, which is a significant economic advantage from an industrial processing perspective. These results represent the highest PCE achieved from perylenediimide-based polymers.

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Controlling Molecular Ordering in Aqueous Conducting Polymers Using Ionic Liquids

The molecular ordering of aqueous conducting polymers is controlled using a rational method. By introducing various ionic liquids, which have designed electrostatic interactions to PEDOT:PSS solutions, the evolution of the molecular ordering of the PEDOT is manipulated. Consequently, highly ordered nanostructures are achieved with a reduced π–π stacking distance of ≈3.38 Å and, thus, a maximum σ_dc of ≈2100 S cm^–1.

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Family-centered care in children with epilepsy: Evaluating the Measure of Processes of Care (MPOC-20)

Summary

Objective

The objective was to test whether the five-domain structure of the Measure of Processes of Care (MPOC-20) was observed in a sample of children with epilepsy and, if not, to propose adaptations to improve its utility in this population.

Methods

Data came from the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES)—a multicenter prospective cohort study (n = 374) following children 4–12 years of age for 2 years after diagnosis. Confirmatory factor analysis (CFA) tested the applicability of the five domains/factors in a sample of children with epilepsy approximately 6 months following diagnosis (n = 311). Goodness-of-fit statistics were used to examine sources of ill model fit, and modification indices guided the model modification process where there was strong theoretical rationale for changes.

Results

The five-factor model described by the originators of the MPOC-20 was found to be inadmissible in children with epilepsy, with four of the five factors demonstrating high correlations (r > 0.85). Upon merging the intercorrelated factors, a two-factor solution with a mediocre fit emerged (Root Mean Square Error of Approximation (RMSEA) = 0.080, Comparative Fit Index (CFI) = 0.902, Standardized Root Mean Square Residual (SRMR) = 0.060). Modification indices identified four items as the source of poor model fit. Removing these four items and reperforming the CFA resulted in an adequate model fit and a revised 16-item MPOC (RMSEA = 0.057, CFI = 0.958, SRMR = 0.036). The two factors are "Family/Care Provider Interaction" and "Providing Information."

Significance

Results suggest that the MPOC-16 better reflects family-centered care (FCC) in children with epilepsy than the original MPOC-20. The benefit of having fewer factors is that scoring is simpler and the interpretation of the results is easier. This was the first investigation of the factor structure of the MPOC-20 on a sample entirely composed of children with epilepsy. These results add to evidence that the factor structure (and how family-centered care is delivered and perceived) differs across treatment environments and treatment populations.

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Midazolam–ketamine dual therapy stops cholinergic status epilepticus and reduces Morris water maze deficits

Summary

Objective

Pharmacoresistance remains an unsolved therapeutic challenge in status epilepticus (SE) and in cholinergic SE induced by nerve agent intoxication. SE triggers a rapid internalization of synaptic γ-aminobutyric acid A (GABA_A) receptors and externalization of N-methyl-d-aspartate (NMDA) receptors that may explain the loss of potency of standard antiepileptic drugs (AEDs). We hypothesized that a drug combination aimed at correcting the consequences of receptor trafficking would reduce SE severity and its long-term consequences.

Methods

A severe model of SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABA_A receptor agonist midazolam, the NMDA receptor antagonist ketamine, and/or the AED valproate were injected 40 min after SE onset in combination or as monotherapy. Measures of SE severity were the primary outcome. Secondary outcomes were acute neuronal injury, spontaneous recurrent seizures (SRS), and Morris water maze (MWM) deficits.

Results

Midazolam–ketamine dual therapy was more efficient than double-dose midazolam or ketamine monotherapy or than valproate–midazolam or valproate–ketamine dual therapy in reducing several parameters of SE severity, suggesting a synergistic mechanism. In addition, midazolam–ketamine dual therapy reduced SE-induced acute neuronal injury, epileptogenesis, and MWM deficits.

Significance

This study showed that a treatment aimed at correcting maladaptive GABA_A receptor and NMDA receptor trafficking can stop SE and reduce its long-term consequences. Early midazolam–ketamine dual therapy may be superior to monotherapy in the treatment of benzodiazepine-refractory SE.

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A computational biomarker of idiopathic generalized epilepsy from resting state EEG

Summary

Epilepsy is one of the most common serious neurologic conditions. It is characterized by the tendency to have recurrent seizures, which arise against a backdrop of apparently normal brain activity. At present, clinical diagnosis relies on the following: (1) case history, which can be unreliable; (2) observation of transient abnormal activity during electroencephalography (EEG), which may not be present during clinical evaluation; and (3) if diagnostic uncertainty occurs, undertaking prolonged monitoring in an attempt to observe EEG abnormalities, which is costly. Herein, we describe the discovery and validation of an epilepsy biomarker based on computational analysis of a short segment of resting-state (interictal) EEG. Our method utilizes a computer model of dynamic networks, where the network is inferred from the extent of synchrony between EEG channels (functional networks) and the normalized power spectrum of the clinical data. We optimize model parameters using a leave-one-out classification on a dataset comprising 30 people with idiopathic generalized epilepsy (IGE) and 38 normal controls. Applying this scheme to all 68 subjects we find 100% specificity at 56.7% sensitivity, and 100% sensitivity at 65.8% specificity. We believe this biomarker could readily provide additional support to the diagnostic process.

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Prehospital use of ketamine

Watch this video about the mechanism of action, indications and administration routes for prehospital use of ketamine.  After watching read the Ketamine Drug Why article and three reasons to use ketamine for prehospital analgesia. 

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Downregulation of nucleophosmin expression inhibited proliferation and induced apoptosis in salivary gland adenoid cystic carcinoma

Background

This study aimed to explore the relationship between nucleophosmin (NPM1) and patient clinical characteristics. Moreover, we investigated the effect of NPM1 in tumor proliferation and apoptosis of salivary gland adenoid cystic carcinoma (SACC).

Materials and methods

NPM1 expression was examined in 74 specimens of SACC and 31 non-cancerous epithelium adjacent to carcinoma (NCEAC) by immunohistochemistry (IHC). RNA interference technology was used to silence NPM1 expression in SACC cells. We used transwell culture assay, cell counting kit-8 tests, and colony formation assay to test the proliferation, cisplatin resistance, migration, and invasiveness of SACC cells.

Results

The nuclear and cytoplasmic expression of NPM1 in SACC tissue was overexpressed and was tightly linked to perineural invasion and lymph node metastasis. The downregulation of NPM1 inhibited proliferation and induced apoptosis in SACC cells. Knockdown of NPM1 expression had no effect on chemoresistance migration, or invasiveness.

Conclusions

NPM1 may play an important role in tumor progress in SACC and is a potential biomarker for SACC.

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Issue Information - TOC

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Prehospital use of ketamine

Watch this video about the mechanism of action, indications and administration routes for prehospital use of ketamine.  After watching read the Ketamine Drug Why article and three reasons to use ketamine for prehospital analgesia. 

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