Self-Templated Fabrication of MoNi4/MoO3-x Nanorod Arrays with Dual Active Components for Highly Efficient Hydrogen Evolution

A binder-free efficient MoNi₄/MoO_3-x nanorod array electrode with 3D open structure is developed by using Ni foam as both scaffold and Ni source to form NiMoO₄ precursor, followed by subsequent annealing in a reduction atmosphere. It is discovered that the self-templated conversion of NiMoO₄ into MoNi₄ nanocrystals and MoO_3-x as dual active components dramatically boosts the hydrogen evolution reaction (HER) performance. Benefiting from high intrinsic activity, high electrochemical surface area, 3D open network, and improved electron transport, the resulting MoNi₄/MoO_3-x electrode exhibits a remarkable HER activity with extremely low overpotentials of 17 mV at 10 mA cm⁻² and 114 mV at 500 mA cm⁻², as well as a superior durability in alkaline medium. The water–alkali electrolyzer using MoNi₄/MoO_3-x as cathode achieves stable overall water splitting with a small cell voltage of 1.6 V at 30 mA cm⁻². These findings may inspire the exploration of cost-effective and efficient electrodes by in situ integrating multiple highly active components on 3D platform with open conductive network for practical hydrogen production.

A MoNi₄/MoO_3-x nanorod array with dual active components is developed by self-templated conversion from NiMoO₄ host nanorods, which exhibits boosted activity and remarkable durability for hydrogen evolution with extremely low overpotentials of 114 mV at 500 mA cm⁻² in 1 M KOH. The assembled water–alkali electrolyzer outputs a current density of 30 mA cm⁻² at 1.6 V over long-term operation.

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Polymer Microstructures through Two-Photon Crosslinking

Two-photon crosslinking of polymers (2PC) is proposed as a novel method for the fabrication of freestanding microstructures via two-photon lithography. During this process in the confocal volume, two-photon absorption leads to (formal) C,H-insertion reactions, and consequently to a strictly localized crosslinking of the polymer. To achieve this, the polymer is coated as a solvent-free (glassy) film onto an appropriate substrate, and the desired microstructure is written by 2PC into this glass. In all regions outside of the focal volume where no two-photon process occurs, the polymer remains uncrosslinked and can be washed away during a developing process. Using a self-assembled monolayer containing the same photoreactive group allows covalent attachment of the forming freestanding structures to the substrate, and thus guarantees an improved stability of these structures against shear-induced detachment. As the two photon process is carried out in the glassy state, in a simple way, multilayer structures can be used to write structures having a varying chemical composition perpendicular to the surface. As an example, the 2PC process is used to build a structure from both protein-repellent and protein-adsorbing polymers so that the resulting 3D structure exhibits spatially controlled protein adsorption.

Two-photon crosslinking of polymers is a new method for the fabrication of microstructures via two-photon lithography. Here, in the confocal volume two-photon absorption leads to a (formal) C,H-insertion reaction. Using a self-assembled monolayer containing the same photoreactive group allows the forming freestanding structures to covalently attach to the substrate.

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“One Doesn’t Slap a Girl but…” Social Representations and Conditional Logics in Legitimization of Intimate Partner Violence

Abstract

The present research, which fits into the conceptual framework of social representations, aims to analyze the impact of gender and legitimizing ideologies on the evaluation of intimate partner violence (IPV). Using an inductive mixed methods approach, two studies were conducted in a French context. In Study 1, 24 participants were asked to express their views about a vignette describing an IPV case during semi-structured interviews. In Study 2, 123 participants completed a questionnaire which was based on the results of Study 1. They were asked to evaluate the severity and justification for this same IPV case in relation to several situations identified in interviews. They also completed two scales measuring adherence to ideologies legitimizing male dominance: the Ambivalent Sexism Inventory and the Domestic Violence Myth Acceptance Scale. Results show expressed ambivalence by participants between condemnation of IPV and the use of conditional logics in order to minimize or justify it. The expression of this reasoning was determined by social regulations such as the situations in which the violence occurred and adherence to legitimizing ideologies. Our results are relevant for campaigns raising awareness and educational programs that take into account social representations underlying IPV legitimization.

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Challenges in the anesthetic management of ambulatory patients in the MRI suites.

Purpose of review: MRI is becoming an indispensable diagnostic tool. The need for prolonged motion-free periods has substantially increased the need for deep sedation or anesthesia in a challenging environment. This review summarises recent literature with respect to pharmacological sedative strategies, nonpharmacological alternative approaches, airway management and safety issues in the ambulatory setting. Recent findings: Most literature researches the pediatric patient population. The American Society of Pediatrics published guidelines for monitoring and management of pediatric patients during sedation for diagnostic procedures. Dexmedetomidine is the most researched agent for sedation. It remains uncertain what the clinical implications are of the potential neurotoxicity of repeat sedation or anesthesia in young children. Airway strategies highlight the use of end-tidal carbon dioxide monitoring. Technical imaging advancement and nonpharmacological sedation alternatives allow for shorter procedures with a lower need for sedation. Summary: The anesthetic management of ambulatory patients in the MRI environment has its specific challenges and safety issues. However, the implementation of safety guidelines, new pharmacological and alternative nonpharmacological sedation strategies offer interesting perspectives to tackle these challenges. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Pediatric Emergency Department Utilization and Reliance by Insurance Coverage in the United States

Abstract

Objectives

For many children, the Emergency Department (ED) serves as the main destination for health care, whether it be for emergent or non-urgent reasons. Through examination of repeat utilization and ED reliance, in addition to overall ED utilization, we can identify subpopulations dependent on the ED as their primary source of health care.

Methods

Nationally representative data from the 2010-2014 Medical Expenditure Panel Survey (MEPS) were used to examine the annual ED utilization of children age 0-17 years by insurance coverage. Overall utilization, repeat utilization (≥2 ED visits), and ED reliance (percentage of all health care visits that occur in the ED) were examined using multivariate models, accounting for weighting and the complex survey design. High ED reliance was defined as having >33% of outpatient visits in a year being ED visits.

Results

A total of 47,926 children were included in the study. Approximately 12% of children visited an ED within a one-year period. A greater number of children with public insurance (15.2%) visited an ED at least once, compared to privately insured (10.1%) and uninsured (6.4%) children. Controlling for covariates, children with public insurance were more likely to visit the ED (adjusted odds ratio [aOR]: 1.55; 95% confidence interval [CI]: 1.40-1.73) than children with private insurance, whereas uninsured children were less likely (aOR: 0.64; 95% CI: 0.51-0.81). Children age three and under were significantly more likely to visit the ED than children age 15-17, whereas female children and Hispanic and non-Hispanic other race children were significantly less likely to visit the ED than male children and non-Hispanic white children. Among children with ED visits, 21% had two or more visits to the ED in a one-year period. Children with public insurance were more likely to have two or more visits to the ED (aOR: 1.53; 95% CI: 1.19-1.98) than children with private insurance whereas there was no significant difference in repeat ED utilization for uninsured children. Publicly insured (aOR: 1.70; 95% CI: 1.47-1.97) and uninsured children (aOR: 1.90; 95% CI: 1.49-2.42) were more likely to be reliant on the ED than children with private insurance.

Conclusions

Health insurance coverage was associated with overall ED utilization, repeat ED utilization, and ED reliance. Demographic characteristics, including gender, age, income, and race/ethnicity were important predictors of ED utilization and reliance.

This article is protected by copyright. All rights reserved.

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Change in Care Transition Practice for Patients with Non-Specific Chest Pain after ED Evaluation 2006-2012

Abstract

Objectives

From 2005-2010 healthcare financing shifts in the United States may have affected care transition practices for emergency department (ED) patients with non-specific chest pain (CP) after ED evaluation. Despite being less acutely ill than those with myocardial infarction, these patients' management can be challenging. The risk of missing acute coronary syndrome is considerable enough to often warrant admission. Diagnostic advances and reimbursement limitations on the use of inpatient admission are encouraging the use of alternative ED care transition practices. In the setting of these health care changes, we hypothesized there is a decline in inpatient admission rates for patients with non-specific CP after ED evaluation.

Methods

We retrospectively used the Nationwide ED Sample (NEDS) to quantify total and annual inpatient hospital admission rates from 2006-2012 for patients with a final ED diagnosis of non-specific CP. We assessed the change in admission rates over time, and stratified by facility characteristics including: safety-net hospital status, US geographic region, urban/teaching status, trauma-level designation, and hospital funding status.

Results

The admission rate for all patients with a final ED diagnosis of non-specific CP declined from 19.2% in 2006 to 11.3% in 2012. Variability across regions was observed, while metropolitan teaching hospitals and trauma centers reflected lower admission rates.

Conclusion

There was a 41.1% decline in inpatient-hospital admission for patients with non-specific CP after ED evaluation. This reduction is temporally associated with national policy changes affecting reimbursement for inpatient admissions.

This article is protected by copyright. All rights reserved.

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The pediatric submersion score predicts children at low risk for injury following submersions

Abstract

Introduction

Pediatric submersion victims often require admission. We wanted to identify a cohort of children at low risk for submersion-related injury who can be safely discharged from the emergency department (ED) after a period of observation.

Methods

This was a single-center retrospective derivation/validation cross-sectional study of children (0-18 years) who presented post-submersion to a tertiary-care, children's hospital ED from 2008-2015. We reviewed demographics, comorbidities, prehospital and ED course. Primary outcome was safe discharge at 8 hours' post-submersion: Normal mentation and vital signs. To identify potential scoring factors, any p-value ≤0.25 was included in binary logistic regression; p-values <0.05 were included in the final score. In the validation dataset, we generated a one-point scoring system for each normal ED item. Receiver operating characteristic curves with area under the curve (AUC) were generated to test sensitivity and specificity.

Results

The derivation dataset consisted of 356 patients and validation dataset of 89 patients. Five factors generated a safe discharge score at 8 hours: normal ED mentation, normal ED respiratory rate, absence of ED dyspnea, absence of need for airway support (Bag-valve-mask ventilation, intubation and CPAP), absence of ED systolic hypotension (Max. score: 5; Range 0-5). Only the 80 patients with values for all five factors were included in the sensitivity/specificity analysis. This resulted in an AUC = 0.81 (95% CI: 0.71–0.91; p-value<0.001). Based on the sensitivity/specificity analysis, the discriminative ability peaks at 75% with a score ≥3.5. A score of 4 or higher in the ED would suggest a safe discharge at 8 hours [Sensitivity: 88.2% (95% CI: 72.5% - 96.7%); Specificity is 62.9% (95% CI: 44.9% - 78.5%); Positive Predictive Value: 69.8% (95% CI: 53.9% - 82.8%); Negative Predictive Value: 84.6% (95% CI: 65.1% - 95.6%)].

Conclusions

A risk score can identify children at low risk for submersion-related injury who can be safely discharged from the ED after observation.

This article is protected by copyright. All rights reserved.

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Patient and System Factors Related to Missed Opportunities for Screening in an EMR-driven, Opt-out HIV Screening Program in the Emergency Department

Abstract

Objective

Emergency Departments (EDs) have implemented HIV screening using a variety of strategies. This study investigates how specific patient and health system factors in the ED impact who is and is not screened in a combined targeted and non-targeted, EMR-driven, opt-out, HIV screening program.

Methods

This was a retrospective, cross sectional study of ED visits where patients were determined eligible for HIV screening by an EMR algorithm between 11/18/2014 and 7/15/2015. The HIV screening workflow included three sequential events, all of which were required to get screened for HIV at the ED visit. The events were having a blood draw, being informed of the HIV screening policy by an ED nurse at the point of blood draw, and the patient consenting to the HIV test. Each event represented a dichotomous outcome and its association with six patient factors (age, gender, race/ethnicity, marital status, preferred language, and Emergency Severity Index (ESI)) and two health system factors (ED crowding and program phase) was investigated using multivariable modeling.

Results

A total of 15,918 ED visits were analyzed. Blood was drawn in 8,388 of 15,918 visits (53%). Of 8,388 visits where blood was drawn, there were 5,947 (71%) visits where ED nurses documented informing patients of the HIV screening policy. Of those visits, patient consent to the HIV test was documented at 3,815 (64%) visits. Patients between 13-19 years of age were significantly less likely to have blood drawn, to be informed of the screening policy, and to consent to the HIV test compared to other age groups. Both ED crowding and a patient's ESI were associated with decreased odds of having a blood draw and being informed of HIV screening by an ED nurse, but showed no association with patients consenting to the HIV test.

Conclusion

Many patients, particularly adolescents and young adults, are missed in ED HIV screening programs that require blood draw and depend on providers to obtain consent for testing. To ensure these patients are reached, future ED screening programs should strive to develop innovative workflows that allow for blood draws for HIV screening only and streamline the processes of obtaining informed consent and ordering tests for all eligible patients.

This article is protected by copyright. All rights reserved.

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Transmission as a basic process in microbial biology. Lwoff Award Prize Lecture

Abstract

Transmission is a basic process in biology and evolution, as it communicates different biological entities within and across hierarchical levels (from genes to holobionts) both in time and space. Vertical descent, replication, is transmission of information across generations (in the time dimension), and horizontal descent is transmission of information across compartments (in the space dimension). Transmission is essentially a communication process that can be studied by analogy of the classic information theory, based on 'emitters', 'messages' and 'receivers'. The analogy can be easily extended to the triad 'emigration', 'migration' and 'immigration'. A number of causes (forces) determine the emission, and another set of causes (energies) assures the reception. The message in fact is essentially constituted by 'meaningful' biological entities. A DNA sequence, a cell and a population have a semiotic dimension, are 'signs' that are eventually recognized (decoded) and integrated by receiver biological entities. In cis-acting or unenclosed transmission, the emitters and receivers correspond to separated entities of the same hierarchical level; in trans-acting or embedded transmission, the information flows between different, but frequently nested, hierarchical levels. The result (as in introgressive events) is constantly producing innovation and feeding natural selection, influencing also the evolution of transmission processes. This review is based on the concepts presented at the André Lwoff Award Lecture in the FEMS Microbiology Congress in Maastricht in 2015.

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Hypoalbuminemia is a Predictive Factor for Fistula Formation in Recurrent Cervical Cancer.

Objective: Antivascular endothelial growth factor monoclonal antibodies inhibit tumor angiogenesis, consequently impeding the recruitment of new vasculature to existing and new tumor lesions. We sought to evaluate toxicities in women with recurrent cervical cancer after receiving bevacizumab combination chemotherapy. Methods: A review was conducted of women with recurrent and metastatic cervical cancer who were treated with salvage chemotherapy with or without bevacizumab between 2005 and 2015. Clinicopathologic data and reasons for treatment discontinuation were recorded. Patients that were excluded had other histology than squamous or adenocarcinoma, received 1 cycle of salvage chemotherapy, single agent bevacizumab, currently on treatment, or noncompliant. Statistical analysis was performed using the Fishers Exact Test, logistic regression, and Kaplan-Meier Survival Analysis. Results: A total of 74 patients were included in analysis. Twenty-six patients were treated with bevacizumab (BEV) and chemotherapy and 48 patients with chemotherapy alone (chemotherapy). The progression free survival was significant with median 12 months versus 7 months for the BEV cohort (P

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Diversity of Ochrobactrum species in food animals, antibiotic resistance phenotypes and polymorphisms in the bla OCH gene

Abstract

Twenty-six lactose non-fermenting, oxidase, urease and citrate positive Gram negative rods, isolated from broiler chickens, pigs and cattle at slaughter, were subjected to MALDI-TOF mass spectrometry and 16S rDNA sequencing for identification. Susceptibility to 14 antimicrobials was determined by the disc diffusion method. Ochrobactrum isolates resistant to third generation cephalosporins were PCR-screened for the presence of the O. anthropi ampC gene (bla_OCH). A 547 bp internal segment of bla_OCH in the Ochrobactrum species was amplified with a newly designed primer set and a phylogenetic reconstruction based on the complete amino acid sequence of bla_OCH obtained from 9 Ochrobactrum strains in our collection and 20 O. anthropi available in the GenBank was undertaken. All the Ochrobactrum isolates were resistant to the expanded-spectrum beta-lactams and streptomycin. None of the isolates was resistant to imipenem while 41.7% to 50.0% of them were resistant to fluoroquinolones. The bla_OCH gene was detected in 16 (66.7%) and 20 (83.3%) of the 24 Ochrobactrum isolates using primers designed for O. anthropi and the newly designed primer set, respectively. Six AmpC variants grouped into two divergent clusters were identified. This is the first report of the complete nucleotide sequence of the non-Ochrobactrum anthropi species bla_OCH gene.

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Genome Analysis of Food-Processing Stressful- Resistant Probiotic Bifidobacterium animalis subsp. lactis BF052, and Its Potential Application in Fermented Soymilk

Abstract

In this study, Bifidobacterium animalis subsp. lactis BF052 was demonstrated the growth capability in soymilk and could be thus supplemented as a probiotic starter that employed soymilk as one of its food vehicles. The complete genome sequence of BF052 was therefore determined to understand the genetic basis of BF052 as a technological and functional probiotic starter. The whole genome sequence of BF052 consists of a circular genome of 1,938,624 bp with a G+C content of 60.50%. This research highlights relevant genes involving in its adaptive responses to industrial and/or environmental stresses and utilization of α-galacto-oligosaccharides in BF052 strain compared with other representative bifidobacterial genomes.

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Isolation of proteolytic bacteria from mealworm ( Tenebrio molitor ) exoskeletons to produce chitinous material

Abstract

The use of insects as a source of protein is becoming an important factor for feeding an increasing population. After protein extraction for food use, the insect exoskeleton may offer the possibility for the production of added value products. Here, the aim was to isolate bacteria from the surface of farmed mealworms (Tenebrio molitor Linnaeus, 1758) for the production of chitinous material from insect exoskeletons using microbial fermentation. Isolates were screened for proteases and acid production that may aid deproteination and demineralization of insects through fermentation to produce chitin. Selected isolates were used single-step (isolated bacteria only) or two-step fermentations with Lactobacillus plantarum (DSM 20174). Two-step fermentations with isolates from mealworm exoskeletons resulted in a demineralisation of 97.9 and 98.5% from deproteinated mealworm fractions. ATR-FTIR analysis showed that crude chitin was produced. However, further optimization is needed before the process can be upscaled. This is, to our knowledge, the first report using microbial fermentation for the extraction of chitin from insects.

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Anatomical Complications of Hysterectomy: A review

Abstract

Introduction: Hysterectomy is the most commonly performed gynecological procedure in the United States with three possible surgical approaches; vaginal, abdominal and laparoscopic. As with any surgical procedure, various anatomical complications can arise. These include injuries to anatomical structures such as the urinary bladder, ureter, intestines, rectum, anus and a multitude of nervous structures. Other complications include sexual dysfunction, vaginal cuff dehiscence and urinary incontinence.

Materials and Methods: Using standard search engines, the anatomical complications of hysterectomies are reviewed.

Conclusions: Surgeons who perform hysterectomies or are involved with post-operative hysterectomy patients should be familiar with the possible complications of this common procedure and the steps that can be taken to help reduce the risk of those complications. Clinicians should also inform their patients of the potential complications as they can affect lifestyle and comfort. This article is protected by copyright. All rights reserved.

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Magnetic Resonance imaging of the tensor vastus intermedius: A topographic study based on anatomical dissections

Abstract

The tensor of the vastus intermedius (TVI) is a newly described component of the extensor apparatus of the knee joint. The objective of this study was to evaluate the appearance of the TVI on magnetic resonance (MR) imaging and its association with the adjacent vastus lateralis (VL) and vastus intermedius (VI) muscles and to compare these findings with the corresponding anatomy.

MR images were analyzed from a cadaveric thigh where the TVI, as part of the extensor apparatus of the knee joint, had been dissected. The course of the TVI in relation to the adjacent VL and VI was studied.

The anatomic dissection and MR imaging revealed a multi-layered organization of the lateral extensor apparatus of the knee joint. The TVI is an intervening muscle between the VL and VI that combined into a broad flat aponeurosis in the mid-thigh and merged into the quadriceps tendon. Dorsally, the muscle fibers of the TVI joined those of the VL and VI and blended into the attachment at the lateral lip of the linea aspera. In this area, distinguishing between these three muscles was not possible macroscopically or virtually by MR imaging.

In the dorsal aspect the onion-like muscle layers of the VL, TVI and VI fuse to a hardly separable muscle mass indicating that these muscles work in conjunction to produce knee extension torque when knee joint action is performed. This article is protected by copyright. All rights reserved.

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Lung Ultrasound in the Critically Ill: The BLUE Protocol.

No abstract available

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Boring Is Beautiful in Preoperative Assessment.

No abstract available

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Association of STOP-Bang Questionnaire as a Screening Tool for Sleep Apnea and Postoperative Complications: A Systematic Review and Bayesian Meta-analysis of Prospective and Retrospective Cohort Studies.

BACKGROUND: The risk of postoperative complications increases with undiagnosed obstructive sleep apnea (OSA). The high-risk OSA (HR-OSA) patients can be easily identified using the STOP-Bang screening tool. The aim of this systematic review and meta-analysis is to determine the association of postoperative complications in patients screened as HR-OSA versus low-risk OSA (LR-OSA). METHODS: The following data bases were searched from January 1, 2008, to October 31, 2016, to identify the eligible articles: Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Cochrane Databases of Systematic Reviews, Medline-in-Process & other nonindexed citations, Google Scholar, Embase, Web of Sciences and Scopus. The search included studies with adult surgical patients screened for OSA with STOP-Bang questionnaire that reported at least 1 cardiopulmonary or any other complication requiring intensive care unit admission as diagnosis of outcome. We used a Bayesian random-effects analysis to evaluate the existing evidence of STOP-Bang in relation to OSA and to assess the association of postoperative complications with the identified HR-OSA patients by study design and methodologies. RESULTS: This systematic review and meta-analysis was conducted using 10 cohort studies: 23,609 patients (HR-OSA, 7877; LR-OSA, 15,732). The pooled odds of perioperative complications were higher in the HR-OSA versus LR-OSA patients (odds ratio 3.93, 95% credible interval, 1.85-7.77, P= .003; 6.86% vs 4.62%). The length of hospital stay was longer in HR-OSA by 2 days when compared with LR-OSA (5.0 +/- 4.2 vs 3.4 +/- 2.8 days; mean difference 2.01; 95% credible interval, 0.77-3.24; P= .005). Meta-regression to adjust for baseline confounding factors and subgroup analysis did not materially change the results. CONCLUSIONS: This systematic review and meta-analysis suggests that HR-OSA is related with higher risk of postoperative adverse events and longer length of hospital stay when compared with LR-OSA patients. Our findings support the implementation of the STOP-Bang screening tool for perioperative risk stratification. (C) 2017 International Anesthesia Research Society

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Impact of Simulator-Based Training in Focused Transesophageal Echocardiography: A Randomized Controlled Trial.

BACKGROUND: The aim of the study was to determine if training in transesophageal echocardiography (TEE) using a TEE simulator improves the ability of novice operators to perform and interpret a focused critical care TEE. METHODS: In this prospective, randomized, controlled study with blinded outcome assessment, 44 intensive care unit trainees were randomly assigned to a control group receiving 4 hours of lecture-based training only, or an intervention group which was additionally trained for 4 hours using a TEE simulator. After the training intervention, each participant performed 2 TEEs in intensive care unit patients which were evaluated by blinded assessors. The imaging quality of TEEs was measured using a predefined examination quality score ranging from 0 to 100 points. The correct quantification of pathologies and the interpretation of the TEEs were evaluated by blinded assessors using focused and comprehensive expert TEEs as comparators. RESULTS: A total of 114 TEEs were assessed. The mean examination quality score was 55.9 (95% confidence interval [CI], 50.3-61.5) for TEEs of the control group, 75.6 (95% CI, 70.1-81.0) for TEEs of the intervention group, and 88.5 (95% CI, 79.3-97.7) for TEEs in the expert group. The multiple comparisons revealed significant differences between all groups (19.7 [95% CI, 12.8-26.6], P

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Hypothermia Risk With Intraoperative Continuous Renal Replacement Therapy.

No abstract available

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Surveying the Literature: Synopsis of Recent Key Publications.

No abstract available

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A novel income security intervention to address poverty in a primary care setting: a retrospective chart review

Objective

To examine the development and implementation of a novel income security intervention in primary care.

Design

A retrospective, descriptive chart review of all patients referred to the Income Security Heath Promotion service during the first year of the service (December 2013–December 2014).

Setting

A multisite interdisciplinary primary care organisation in inner city Toronto, Canada, serving over 40 000 patients.

Participants

The study population included 181 patients (53% female, mean age 48 years) who were referred to the Income Security Health Promotion service and engaged in care.

Intervention

The Income Security Health Promotion service consists of a trained health promoter who provides a mixture of expert advice and case management to patients to improve income security. An advisory group, made up of physicians, social workers, a community engagement specialist and a clinical manager, supports the service.

Outcome measures

Sociodemographic information, health status, referral information and encounter details were collected from patient charts.

Results

Encounters focused on helping patients with increasing their income (77.4%), reducing their expenses (58.6%) and improving their financial literacy (26.5%). The health promoter provided an array of services to patients, including assistance with taxes, connecting to community services, budgeting and accessing free services. The service could be improved with more specific goal setting, better links to other members of the healthcare team and implementing routine follow-up with each patient after discharge.

Conclusions

Income Security Health Promotion is a novel service within primary care to assist vulnerable patients with a key social determinant of health. This study is a preliminary look at understanding the functioning of the service. Future research will examine the impact of the Income Security Health Promotion service on income security, financial literacy, engagement with health services and health outcomes.

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Novel Immunotherapies for Multiple Myeloma

Abstract

Purpose of Review

The treatment landscape of multiple myeloma is rapidly changing; however, despite improvement in patients' survival, it still remains a largely incurable disease. One hallmark of myeloma is substantial immune dysfunction leading to an increased infection rate and the inability of immune surveillance to detect neoplastic cells. Here, we critically analyze clinical approaches to harness the immune system to overcome this defect with a focus on antibody based and adoptive cellular therapies.

Recent Findings

Clinical trials exploring these immunotherapies to treat myeloma are now well underway and show promising results. In relapsed myeloma, monoclonal antibodies directed against plasma cell antigens and immune checkpoints have already shown substantial efficacy. In parallel, trials of adoptive cellular therapy have exciting promise in myeloma, having induced dramatic responses in a handful of early study participants.

Summary

Taken together, immunotherapeutic approaches hold enormous potential in the field of multiple myeloma and in the near future can be combined with or even replace the current standard of care.

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Erratum to: A novel tubulin polymerization inhibitor, MPT0B206, downregulates Bcr-Abl expression and induces apoptosis in imatinib-sensitive and imatinib-resistant CML cells

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New Horizons for Precision Medicine in Biliary Tract Cancers [Reviews]

Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review.

Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 1–20. ©2017 AACR.

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Enasidenib Approved for AML, but Best Uses Unclear [News in Brief]

Drug produces remissions in some patients, but researchers need to learn who will benefit.

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TCR signalling network organization at the immunological synapses of murine regulatory T cells

Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we characterized TCR signalling and recruitment of TCR signalling components to the immunological synapse (IS) in Treg cells and Tconv cells. With the exception of Themis which we detected in lower amounts in Treg cells, other major TCR signalling components were found equally abundant, however, their phosphorylation-status notably discriminates Treg cells from Tconv cells. Overall, this study identified 121 Treg cell-specific phosphorylations. Short-term triggering of T cell subsets via CD3 and CD28 widely harmonized these variations with the exception of eleven TCR signalling components that mainly regulate cytoskeleton dynamics and molecular transport. Accordingly, conjugation with B cells indeed caused variant cellular morphology and revealed a Treg cell-specific recruitment of TCR signalling components such as PKCθ, PLCγ1 and ZAP70 as well as B cell-derived CD86 into the IS. Together, results from this study support the existence of a Treg cell-specific IS and suggest Treg cell-specific cytoskeleton dynamics as a novel determinant for the unique functional properties of Treg cells.

This article is protected by copyright. All rights reserved

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Minimally manipulated murine regulatory T cells purified by reversible Fab Multimers are potent suppressors for adoptive T cell therapy

The transfer of regulatory T cells, either freshly isolated, or modified, represents a promising therapeutic approach to dampen misdirected immune responses, like autoimmune diseases, chronic inflammatory syndromes and graft versus host disease. Clinical isolation of highly pure regulatory T cell (Treg) populations is still challenging and labeling reagents can influence their viability and functionality, potentially altering the potency of isolated Treg cell products. Here we show that reversible Fab multimer-based Treg purification can prevent conventional antibody label-induced interferences in vitro and in vivo. Remaining isolation reagents negatively interfere with Treg engraftment efficacy in C57BL/6 wildtype mice due to Fcγ-receptor- as well as IL-2 receptor-mediated mechanisms. Using a preclinical model for acute GvHD, we further show that purified 'label-freed' Tregs are protective at substantially lower cell numbers as compared to conventional non-reversible antibody staining, translating into significantly improved survival of mice treated with minimally manipulated Tregs. These findings have important clinical relevance for future Treg-based cell therapies.

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CXCR4 blockade with AMD3100 enhances Taxol chemotherapy to limit ovarian cancer cell growth.

The standard of care for ovarian cancer includes initial treatment with chemotherapy. Despite initial efficacy, over 70% of patients develop recurrence; thus, there is a need to identify novel approaches that can improve therapeutic outcomes. We evaluated AMD3100 (Plerixafor), an FDA-approved CXCR4 inhibitor, as a potential adjunctive therapy for low-dose Taxol (Paclitaxel) by assessing the impact on in-vitro ovarian cancer cell proliferation. Proliferation was a measure for both human TOV-112D and murine ID8 ovarian cancer cells incubated with AMD3100 and Taxol, either individually or in combination. Impact of treatment was first determined for the simultaneous administration of AMD3100 and Taxol. We next assessed a sequential application of AMD3100 pretreatment, followed by AMD3100, Taxol, or a combination to test for sensitization to Taxol. In addition, we measured the impact of AMD3100 and Taxol, individually and in combination, on colony formation, an in-vitro model assay of tumor growth. Expression data, as measured by flow cytometry, show that both ID8 and TOV-112D cells are positive for CXCR4, CXCR7, and CXCL12. Combination treatment with AMD3100 (

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Loss of the tumor suppressor STAG2 promotes telomere recombination and extends the replicative lifespan of normal human cells

Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The STAG2 gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how STAG2 loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in STAG2 mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres. Telomere maintenance in STAG2 mutant tumor cells occurred by either telomere recombination or telomerase activation mechanisms. Notably, these cells were refractory to telomerase inhibitors, indicating recombination can provide an alternative means of telomere maintenance. STAG2 silencing in normal human cells which lack telomerase led to increased recombination at telomeres, delayed telomere shortening and postponed senescence onset. Insofar as telomere shortening and replicative senescence prevent genomic instability and cancer by limiting the number of cell divisions, our findings suggest that extending the lifespan of normal human cells due to inactivation of STAG2 could promote tumorigenesis by extending the period during which tumor-driving mutations occur.

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PADI2-mediated citrullination promotes prostate cancer progression

Onset of castration-resistance prostate cancer (CRPC) after long-term androgen-deprivation therapy remains a major obstacle in the treatment of prostate cancer (PCa). The peptidylarginine deiminase PADI2 has been implicated in chronic inflammatory diseases and cancer. Here we show that PADI2 is an androgen-repressed gene and is upregulated in CRPC. PADI2 expression was required for survival and cell cycle progression of PCa cells, and PADI2 promoted proliferation of PCa cells under androgen-deprived or castration conditions in vitro and in vivo. Cytoplasmic PADI2 protected the androgen receptor (AR) against proteasome-mediated degradation and facilitated AR binding to its target genes after nuclear translocation and citrullination of histone H3 amino acid residue R26. By contrast, mutant PADI2 D180A failed to affect AR stability, nuclear translocation or transcriptional activity. PADI2 mediated AR control in a manner dependent on its enzymatic activity and nuclear localization, as correlated with increased histone H3 citrullination. Notably, co-administration of the PADI inhibitor Cl-amidine and the AR signaling inhibitor enzalutamide synergized in inhibiting CRPC cell proliferation in vitro and tumor growth in vivo. Overall, our results establish PADI2 as a key mediator for AR in PCa progression, especially CRPC, and they suggest PADI as novel therapeutic targets in this disease setting.

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Combination therapy with bispecific antibodies and PD-1 blockade enhances the antitumor potency of T cells

The DOCK-AND-LOCK (DNL®) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL® to generate a novel class of trivalent bispecific antibodies (bsAbs), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. Here we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2- and CEACAM5-expressing cancer cells, respectively. (E1)-3s and (14)-3s, in the presence of human T cells, killed target cells grown as monolayers at subnanomolar concentrations, with a similar potency observed for drug-resistant cells. Antitumor efficacy was demonstrated for (E1)-3s co-administered with human peripheral blood mononuclear cells (PBMC) in NOD/SCID mice harboring xenografts of MDA-MB-231, a triple-negative breast cancer line constitutively expressing Trop-2 and PD-L1. Growth inhibition was observed following treatment with (E1)-3s or (14)-3s combined with human PBMC in 3D spheroids generated from target cell lines to mimic the in vivo behavior and microenvironment of these tumors. Moreover, addition of an antagonistic anti-PD-1 antibody increased cell death in 3D spheroids and extended survival of MDA-MB-231-bearing mice. These preclinical results emphasize the potential of combining T cell-redirecting bsAbs with antagonists or agonists that mitigate T cell inhibition within the tumor microenvironment to improve immunotherapy of solid cancers in patients. They also support the use of 3D spheroids as a predictive alternative to in vivo models for evaluating T cell functions.

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Therapeutic targeting of the CBP/p300 bromodomain blocks the growth of castration-resistant prostate cancer

Resistance invariably develops to anti-androgen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here we report that the transcriptional co-activator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer.

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Trastuzumab Increases HER2 Uptake and Cross-Presentation by Dendritic Cells

Early phase clinical trials evaluating CD8+ T cell-eliciting, HER2-derived peptide vaccines administered to HER2-positive breast cancer patients in the adjuvant setting suggest synergy between the vaccines and trastuzumab, the monoclonal antibody targeting the HER2 protein. Among 60 patients enrolled on clinical trials evaluating the E75+GM-CSF and GP2+GM-CSF vaccines, there have been no recurrences in patients vaccinated after receiving trastuzumab as part of standard therapy in the per treatment analyses conducted after a median follow-up of greater than 34 months. Here we describe a mechanism by which this synergy may occur. Flow cytometry showed that trastuzumab facilitated uptake of HER2 by dendritic cells (DC), which was mediated by the Fc receptor and was specific to trastuzumab. In vitro, increased HER2 uptake by DC increased cross-presentation of E75, the immunodominant epitope derived from the HER2 protein; an observation confirmed in two in vivo mouse models. This increased E75 cross-presentation, mediated by trastuzumab treatment, enabled more efficient expansion of E75-specific cytotoxic T cells (E75-CTL). These results demonstrate a mechanism by which trastuzumab links innate and adaptive immunity by facilitating activation of antigen-specific T cells. Based on these data, we conclude that HER2-positive breast cancer patients that have been treated with trastuzumab may experience a more robust antitumor immune response by restimulation of T cells with the E75 peptide vaccine, thereby accounting for the improved disease-free survival observed with combination therapy.

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MRE11 promotes tumorigenesis by facilitating resistance to oncogene-induced replication stress

Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes. MRN binds DNA double strand breaks where it functions in repair and triggers cell cycle checkpoints via activation of the ataxia-telangiectasia mutated (ATM) kinase. To gain understanding of MRN in cancer, we engineered mice with B lymphocytes lacking MRN, or harboring MRN in which MRE11 lacks nuclease activities. Both forms of MRN deficiency led to hallmarks of cancer, including oncogenic translocations involving c-Myc and the immunoglobulin locus. These pre-neoplastic B lymphocytes did not progress to detectable B lineage lymphoma, even in the absence of p53. Moreover, Mre11 deficiencies prevented tumorigenesis in a mouse model strongly predisposed to spontaneous B cell lymphomas. Our findings indicate that MRN cannot be considered a standard tumor suppressor and instead imply that nuclease activities of MRE11 are required for oncogenesis. Inhibition of MRE11 nuclease activity increased DNA damage and selectively induced apoptosis in cells overexpressing oncogenes, suggesting MRE11 serves an important role in countering oncogene-induced replication stress. Thus, MRE11 may offer a target for cancer therapeutic development. More broadly, our work supports the idea that subtle enhancements of endogenous genome instability can exceed the tolerance of cancer cells and be exploited for therapeutic ends.

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Therapeutic effects of XPO1 inhibition in thymic epithelial tumors

Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export (SINE) compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins (TSP) including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells and induces p53-dependent and -independent antitumor activity in vitro. Selinexor suppressed the growth of TET xenograft tumors in athymic nude mice via inhibition of cell proliferation and induction of apoptosis. Loss of p53 activity or amplification of XPO1 may contribute to resistance to XPO1 inhibitor in TET. Using mass spectrometry-based proteomics analysis, we identified a number of proteins whose abundances in the nucleus and cytoplasm shifted significantly following selinexor treatment in the TET cells. Furthermore, we found that XPO1 was highly expressed in aggressive histotypes and advanced stages of human TET, and high XPO1 expression was associated with poorer patient survival. These results underscore an important role of XPO1 in the pathogenesis of TET and support clinical development of XPO1 inhibitor for the treatment of patients with this type of tumors.

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{beta}-adrenergic signaling in mice housed at standard temperatures suppresses an effector phenotype in CD8+ T cells and undermines checkpoint inhibitor therapy

The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8+ T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models. Reducing β-AR signaling facilitated conversion of tumors to an immunologically active tumor microenvironment with increased intra-tumoral frequency of CD8+ T cells with an effector phenotype and decreased expression of PD-1, in addition to an elevated effector CD8+ T cell to CD4+ regulatory T cell ratio (IFN-γ+CD8+:Treg). Moreover, this conversion significantly increased the efficacy of anti-PD-1 checkpoint blockade. These data highlight the potential of adrenergic stress and norepinephrine-driven β-adrenergic receptor signaling to regulate the immune status of the tumor microenvironment and supports the strategic use of clinically available β-blockers in patients to improve responses to immunotherapy.

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Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer

The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified based on the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients.

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Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine

Parenteral artesunate is the treatment of choice for severe malaria. Recently, haemolytic anaemia occurring 1 to 3 weeks after artesunate treatment of falciparum malaria has been reported in returning travellers ...

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Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Örebro, Sweden, 1963-2010

Summary

Background

Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown.

Aim

To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010.

Methods

Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Örebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005.

Results

The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P < .01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P < .01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P < .01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P < .01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P < .01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02).

Conclusion

The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.

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Hepatoprotective and antioxidant effects of single clove garlic against CCl4-induced hepatic damage in rabbits

The increase in demand and consumption of single clove garlic or 'Solo garlic' (Allium sativum) has resulted in an increase in research on its therapeutic properties. The present study aims to evaluate the antiox...

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Neuroprotective properties of curcumin in toxin-base animal models of Parkinson’s disease: a systematic experiment literatures review

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective ...

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FMNL2 destabilises COMMD10 to activate NF-κB pathway in invasion and metastasis of colorectal cancer

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MDM2 promotes epithelial–mesenchymal transition and metastasis of ovarian cancer SKOV3 cells

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Influence of dietary insulin scores on survival in colorectal cancer patients

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History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report

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Evaluating the effect of immune cells on the outcome of patients with mesothelioma

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Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study

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Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228)

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Phase-variable methylation and epigenetic regulation by type I restriction–modification systems

Abstract

Epigenetic modifications in bacteria, such as DNA methylation, have been shown to affect gene regulation, thereby generating cells that are isogenic but with distinctly different phenotypes. Restriction–modification (RM) systems contain prototypic methylases that are responsible for much of bacterial DNA methylation. This review focuses on a distinctive group of type I RM loci that , through phase variation, can modify their methylation target specificity and can thereby switch bacteria between alternative patterns of DNA methylation. Phase variation occurs at the level of the target recognition domains of the hsdS (specificity) gene via reversible recombination processes acting upon multiple hsdS alleles. We describe the global distribution of such loci throughout the prokaryotic kingdom and highlight the differences in loci structure across the various bacterial species. Although RM systems are often considered simply as an evolutionary response to bacteriophages, these multi-hsdS type I systems have also shown the capacity to change bacterial phenotypes. The ability of these RM systems to allow bacteria to reversibly switch between different physiological states, combined with the existence of such loci across many species of medical and industrial importance, highlights the potential of phase-variable DNA methylation to act as a global regulatory mechanism in bacteria.

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Editorial: Lactic acid bacteria—a continuing journey in science and application

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Using murine colitis models to analyze probiotics–host interactions

Abstract

Probiotics are defined as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. So, to consider a microorganism as a probiotic, a demonstrable beneficial effect on the health host should be shown as well as an adequate defined safety status and the capacity to survive transit through the gastrointestinal tract and to storage conditions. In this review, we present an overview of the murine colitis models currently employed to test the beneficial effect of the probiotic strains as well as an overview of the probiotics already tested. Our aim is to highlight both the importance of the adequate selection of the animal model to test the potential probiotic strains and of the value of the knowledge generated by these in vivo tests.

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Bacteriocins and bacteriophage; a narrow-minded approach to food and gut microbiology

Abstract

Bacteriocins and bacteriophage (phage) are biological tools which exhibit targeted microbial killing, a phenomenon which until recently was seen as a major drawback for their use as antimicrobial agents. However, in an age when the deleterious consequences of broad-spectrum antibiotics on human health have become apparent, there is an urgent need to develop narrow-spectrum substitutes. Indeed, disruption of the microbial communities which exist on and in our bodies can generate immediate and long-term negative effects and this is particularly borne out in the gut microbiota community whose disruption has been linked to a number of disorders reaching as far as the brain. Moreover, the antibiotic resistance crisis has resulted in our inability to treat many bacterial infections and has triggered the search for damage-limiting alternatives. As bacteriocins and phage are natural entities they are relatively easy to isolate and characterise and are also ideal candidates for improving food safety and quality, forfeiting the need for largely unpopular chemical preservatives. This review highlights the efficacy of both antimicrobial agents in terms of gut health and food safety and explores the body of scientific evidence supporting their effectiveness in both environments.

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The Evolution of gene regulation research in Lactococcus lactis

Abstract

Lactococcus lactis is a major microbe. This lactic acid bacterium (LAB) is used worldwide in the production of safe, healthy, tasteful and nutritious milk fermentation products. Its huge industrial importance has led to an explosion of research on the organism, particularly since the early 1970s. The upsurge in the research on L. lactis coincided not accidentally with the advent of recombinant DNA technology in these years. The development of methods to take out and re-introduce DNA in L. lactis, to clone genes and to mutate the chromosome in a targeted way, to control (over)expression of proteins and, ultimately, the availability of the nucleotide sequence of its genome and the use of that information in transcriptomics and proteomics research have enabled to peek deep into the functioning of the organism. Among many other things, this has provided an unprecedented view of the major gene regulatory pathways involved in nitrogen and carbon metabolism and their overlap, and has led to the blossoming of the field of L. lactis systems biology. All of these advances have made L. lactis the paradigm of the LAB. This review will deal with the exciting path along which the research on the genetics of and gene regulation in L. lactis has trodden.

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Oenococcus oeni and the genomic era

Abstract

Oenococcus oeni is the main lactic acid bacteria species associated with grapes and wine. It is a bacterium that has adapted itself to the harsh conditions of wine, and demonstrated its importance in the production of quality wines. It has a small genome (1.8 Mb); over 200 strains have had their genome sequenced. Genomic analyses have proposed that there are two major branches of O. oeni strains that might be linked to wine style (sparkling wine versus white and red) and metagenomic studies have suggested a possible influence of terroir. This review explores recent developments of O. oeni including genomic studies examining O. oeni diversity and how this might shape future regional-specific commercial O. oeni starter strains.

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Physiology, ecology and industrial applications of aroma formation in yeast

Abstract

Yeast cells are often employed in industrial fermentation processes for their ability to efficiently convert relatively high concentrations of sugars into ethanol and carbon dioxide. Additionally, fermenting yeast cells produce a wide range of other compounds, including various higher alcohols, carbonyl compounds, phenolic compounds, fatty acid derivatives and sulfur compounds. Interestingly, many of these secondary metabolites are volatile and have pungent aromas that are often vital for product quality. In this review, we summarize the different biochemical pathways underlying aroma production in yeast as well as the relevance of these compounds for industrial applications and the factors that influence their production during fermentation. Additionally, we discuss the different physiological and ecological roles of aroma-active metabolites, including recent findings that point at their role as signaling molecules and attractants for insect vectors.

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Lifestyles in transition: evolution and natural history of the genus Lactobacillus

Abstract

Lactobacillus species are found in nutrient-rich habitats associated with food, feed, plants, animals and humans. Due to their economic importance, the metabolism, genetics and phylogeny of lactobacilli have been extensively studied. However, past research primarily examined lactobacilli in experimental settings abstracted from any natural history, and the ecological context in which these bacteria exist and evolve has received less attention. In this review, we synthesize phylogenetic, genomic and metabolic metadata of the Lactobacillus genus with findings from fine-scale phylogenetic and functional analyses of representative species to elucidate the evolution and natural history of its members. The available evidence indicates a high level of niche conservatism within the well-supported phylogenetic groups within the genus, with lifestyles ranging from free-living to strictly symbiotic. The findings are consistent with a model in which host-adapted Lactobacillus lineages evolved from free-living ancestors, with present-day species displaying substantial variations in terms of the reliance on environmental niches and the degree of host specificity. This model can provide a framework for the elucidation of the natural and evolutionary history of Lactobacillus species and valuable information to improve the use of this important genus in industrial and therapeutic applications.

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Practical considerations for large-scale gut microbiome studies

Abstract

First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and characterisation of the multiple influencing factors and their relative contribution. In order to guide future research projects and standardisation efforts, we here review currently applied collection and preservation methods for gut microbiome research. We discuss aspects such as sample quality, applicable omics techniques, user experience and time and cost efficiency. In addition, we evaluate the protocols of a large-scale microbiome cohort initiative, the Flemish Gut Flora Project, to give an idea of perspectives, and pitfalls of large-scale faecal sampling studies. Although cryopreservation can be regarded as the gold standard, freezing protocols generally require more resources due to cold chain management. However, here we show that much can be gained from an optimised transport chain and sample aliquoting before freezing. Other protocols can be useful as long as they preserve the microbial signature of a sample such that relevant conclusions can be drawn regarding the research question, and the obtained data are stable and reproducible over time.

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Unexpected complexity in the lactate racemization system of lactic acid bacteria

Abstract

Analysis of lactate racemase (Lar) in lactic acid bacteria (LAB) has been a scientific challenge for many years, as indicated by the numerous contradictory reports on this activity. Recently, genetic and biochemical studies of the Lar system of Lactobacillus plantarum have unveiled the complexity of this particular enzymatic system. Lar activity is associated with LarA and its nickel-containing cofactor, synthesized from nicotinic acid adenine dinucleotide by the three biosynthetic enzymes: LarB, LarC, and LarE. In addition to these core Lar enzymes, a nickel transporter (Lar(MN)QO), a lactic acid channel (LarD) and a transcriptional regulator (LarR) which promotes expression of the lar genes in the presence of excess L-lactate are also part of the Lar system of Lb. plantarum and of many other LAB. These proteins promote racemization of external L-lactate, in addition to carrying out intracellular racemization. This additional outcome suggests that racemization of L-lactate is not only required for cell wall biosynthesis, as reported before, but may have additional roles in lactate production and utilization in LAB. Finally, bioinformatics analyses indicate that some Lar homologs probably catalyze reactions other than lactate racemization.

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Host recognition by lactic acid bacterial phages

Abstract

Bacteriophage infection of lactic acid bacteria (LAB) is one of the most significant causes of inconsistencies in the manufacture of fermented foods, affecting production schedules and organoleptic properties of the final product. Consequently, LAB phages, and particularly those infecting Lactococcus lactis, have been the focus of intensive research efforts. During the past decade, multidisciplinary scientific approaches have uncovered molecular details on the exquisite process of how a lactococcal phage recognises and binds to its host. Such approaches have incorporated genomic/molecular analyses and their partnership with phage structural analysis and host cell wall biochemical studies are discussed in this review, which will also provide our views on future directions of this research field.

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Polysaccharide production by lactic acid bacteria: from genes to industrial applications

Abstract

The ability to produce polysaccharides with diverse biological functions is widespread in bacteria. In lactic acid bacteria (LAB), production of polysaccharides has long been associated with the technological, functional and health-promoting benefits of these microorganisms. In particular, the capsular polysaccharides and exopolysaccharides have been implicated in modulation of the rheological properties of fermented products. For this reason, screening and selection of exocellular polysaccharide-producing LAB has been extensively carried out by academia and industry. To further exploit the ability of LAB to produce polysaccharides, an in-depth understanding of their biochemistry, genetics, biosynthetic pathways, regulation and structure–function relationships is mandatory. Here, we provide a critical overview of the latest advances in the field of glycosciences in LAB. Surprisingly, the understanding of the molecular processes involved in polysaccharide synthesis is lagging behind, and has not accompanied the increasing commercial value and application potential of these polymers. Seizing the natural diversity of polysaccharides for exciting new applications will require a concerted effort encompassing in-depth physiological characterization of LAB at the systems level. Combining high-throughput experimentation with computational approaches, biochemical and structural characterization of the polysaccharides and understanding of the structure–function–application relationships is essential to achieve this ambitious goal.

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Experimental evolution and the adjustment of metabolic strategies in lactic acid bacteria

Abstract

Experimental evolution of microbes has gained lots of interest in recent years, mainly due to the ease of strain characterisation through next-generation sequencing. While evolutionary and systems biologists use experimental evolution to address fundamental questions in their respective fields, studies with lactic acid bacteria are often more directed by applied questions. Insight into population and genome dynamics are valuable for experimental design and data interpretation, and it is becoming increasingly apparent how different constraints limit and govern the outcome of microbial adaptation to a selective environment. Examples for such constraints are the finite membrane and cellular space which can lead to trade-offs between cellular strategies. A powerful perspective is that of resource allocation, which allows cells to maximise fitness. This impacts on metabolic strategies that have different protein/resource demands. This review focuses on parameters and forces that shape cellular optimisation processes and that are determining for the outcome of laboratory evolution experiments. Phenotypic changes of experimentally evolved lactic acid bacteria will be discussed in the light of the selection conditions and the prevailing constraints.

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Exploring Potential Germline Associated Roles of the TRIM-NHL Protein NHL-2 Through RNAi Screening

TRIM-NHL proteins are highly conserved regulators of developmental pathways in vertebrates and invertebrates. The TRIM-NHL family member, NHL-2 in Caenorhabditis elegans functions as a miRNA cofactor to regulate developmental timing. Similar regulatory roles have been reported in other model systems, with the mammalian orthologue in mice, TRIM32, contributing to muscle and neuronal cell proliferation via miRNA activity. Given the interest associated with TRIM-NHL family proteins, we aimed to further investigate the role of NHL-2 in C. elegans development by using a synthetic RNAi screening approach. Using the ORFeome library, we knocked down 11,942 genes in wild-type animals and nhl-2 null mutants. In total, we identified 42 genes that produced strong reproductive synthetic phenotypes when knocked down in nhl-2 null mutants, with little or no change when knocked down in wild-type animals. These included genes associated with transcriptional processes, chromosomal integrity and key cofactors of the germline small 22G RNA pathway.

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Systematic Identification of Determinants for Single Strand Annealing Mediated Deletion Formation in Saccharomyces cerevisiae

To ensure genomic integrity, living organisms have evolved diverse molecular processes for sensing and repairing damaged DNA. If improperly repaired, DNA damage can give rise to different types of mutations, an important class of which are the genomic structural variants (SVs). In spite of their importance for phenotypic variation and genome evolution, potential contributors to SV formation in Saccharomyces cerevisiae (budding yeast), a highly tractable model organism, are not fully recognized. Here we developed and applied a genome-wide assay to identify yeast gene knock-out mutants associated with de novo deletion formation, in particular single strand annealing (SSA) -mediated deletion formation in a systematic manner. In addition to genes previously linked to genome instability, our approach implicates novel genes involved in chromatin remodelling and meiosis in affecting the rate of SSA-mediated deletion formation in the presence or absence of stress conditions induced by DNA damaging agents. We closely examined two candidate genes, the chromatin remodelling gene IOC4 and the meiosis-related gene MSH4, which when knocked-out resulted in gene expression alterations affecting genes involved in cell division and chromosome organization, as well as DNA repair and recombination, respectively. Our high-throughput approach facilitates the systematic identification of processes linked to the formation of a major class of genetic variation.

http://ift.tt/2uNj4d3

The use of genetic markers to estimate relationships between dogs in the course of criminal investigations

Attacks on humans by dogs in a pack, though uncommon, do happen, and result in severe, sometimes fatal, injuries. We describe the role that canine genetic markers played during the investigation of a fatal dog...

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Case report: value of gene expression profiling in the diagnosis of atypical neuroblastoma

Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, e...

http://ift.tt/2vNpKFi

Severe neutropenia revealing a rare presentation of dengue fever: a case report

Arboviruses are a common cause of fever in the returned traveler often associated with leucopenia, especially lymphopenia and thrombocytopenia. Transient neutropenia has been described in a few cases of arbovi...

http://ift.tt/2w71VL9

Subclinical Hypothyroidism and Low-Normal Thyroid Function are Associated with Nonalcoholic Steatohepatitis and Fibrosis

Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD).

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Sagittal plane deformity: Evaluation and Management

Publication date: Available online 14 August 2017
Source:Seminars in Spine Surgery
Author(s): Alexander M. Satin, Yen H. Chen, Jeff Silber, David Essig
Sagittal alignment is a critical component of the evaluation and management of adult spinal deformities. Loss of sagittal alignment may be the result of iatrogenic induced deformity, metabolic bone problems, progression of idiopathic or neuromuscular deformities, post traumatic, or de novo. Goals of reconstruction involve restoration of global sagittal balance and lumbopelvic harmony. Treating the deformity often involves long construct fusion to the sacropelvis. Often times, multilevel osteotomies as well as circumferential approaches are needed to adequately address the deformity. Failure to address sagittal plane deformities has been linked to poor patient reported outcomes from surgical management. However, even with correction, postoperative complications are common. These included proximal and distal junctional failure, pseudoarthrosis, and the need for future surgery.



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Proximal Renal Tubular Acidosis (Fanconi syndrome) Induced by Apremilast: A Case Report

Apremilast is a recently developed phosphodiesterase 4–inhibitory medication approved for use to treat psoriasis and psoriatic arthritis. We report a case of Fanconi syndrome and proximal renal tubular acidosis that was associated with this medication. Our patient was started on treatment with apremilast 2 weeks before his admission. On arrival, laboratory test results were significant for hypokalemia, hyperchloremic metabolic acidosis, low uric acid concentration, positive urine anion gap, and proteinuria, which resolved on discontinuation of the drug.

http://ift.tt/2w6GPN1

Risk of Venous Thromboembolism in Patients by Albuminuria and Estimated GFR

The risk for venous thromboembolism (VTE) is elevated with albuminuria or a low estimated glomerular filtration rate (eGFR). However, the VTE risk due to the combined effects of eGFR and albuminuria are unknown.

http://ift.tt/2vN748I

Predictors of Health Deterioration Among Older Adults After 12 Months of Dialysis Therapy: A Longitudinal Cohort Study From New Zealand

Involving patients in dialysis decision making is crucial, yet little is known about patient-reported experiences and patient-reported outcomes of dialysis.

http://ift.tt/2w6S349

Association Between Sonographically Diagnosed Nephrolithiasis and Subclinical Coronary Artery Calcification in Adults

Although recent studies suggest an association between nephrolithiasis and clinical cardiovascular events, this association has been underexplored.

http://ift.tt/2vNiol8

High-Grade Neuroendocrine Carcinoma of the Urachus - Report of 3 Cases

The majority of urachal malignancies are composed of pure adenocarcinoma with mucin production. Urachal neuroendocrine carcinoma (NEC) is extremely rare, with only a few cases reported in the literature. Here we report 3 cases of urachal NEC, the largest series of this rare disease from a single institution. The patients were young, with a mean age of 27years (range, 23–34). The urachal tumors showed 2 distinct components, high-grade NEC and enteric-type adenocarcinoma. The urachal NECs were composed of small cell carcinoma (n=2) or large cell NEC (n=1).

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A Study of Appendiceal Crypt Cell Adenocarcinoma (So-Called Goblet Cell Carcinoid and Its Related Adenocarcinoma)

Goblet cell carcinoids (GCCs) of the appendix are rare tumors, characterized by a carcinoid-like organoid growth pattern. Despite the term carcinoid, neuroendocrine features are inconspicuous, and its behavior is distinct from carcinoid. Its high grade counterpart is designated as adenocarcinoma ex GCC. We conducted a retrospective study of 105 tumors to find prognostic values of a variety of clinico-pathologic features.The tumors were subclassified as low grade, equivalent to classic type, and high grade, defined as loss of organoid pattern, and a proportion (%) of low and high grades were documented in each tumor.

http://ift.tt/2x8UG27

Histopathological evidence of neoplastic progression of von Meyenburg complex to intrahepatic cholangiocarcinoma

Von Meyenburg complex (VMC) is generally thought to be benign, although its preneoplastic potential for intrahepatic cholangiocarcinoma (iCC) has been a subject of contention. We retrospectively reviewed 86 hepatectomy specimens with a diagnosis of iCC. Morphologically, an association between iCC and VMC was appreciated in 35% of cases that illustrated a gradual neoplastic progression from benign VMC to dysplasia and then to iCC. Among them, 24 cases had VMC lined by epithelial cells with low-grade biliary dysplasia and 13 with high-grade biliary dysplasia.

http://ift.tt/2weSdqz

MicroRNA-139: a potential diagnostic and therapeutic target for cancers

MicroRNA-139-5p/3p (miR-139-5p/3p) and their different target genes have been reported to be associated with tumorigenesis by participating in multiple biological processes via the modulation of various aspects of cell biology, such as cell growth, proliferation and signal transduction. However, the miR-139-5p/3p expression signatures and function profiles in human breast cancer are still largely elusive. Surprisingly, we read with great interest the recently published work by Dai et al. [1], demonstrating that miR-139-5p tissue expression level is significantly down-regulated in breast cancer patients and correlated with higher tumor grade, estrogen receptor negativity, progesterone receptor negativity, greater proliferation, or larger size.

http://ift.tt/2x9eVNu

Pulmonary Invasive Mucinous Adenocarcinoma and Mixed Invasive Mucinous/Non-Mucinous Adenocarcinoma- A Clinicopathological and Molecular Genetic Study with Survival Analysis

Invasive mucinous adenocarcinoma is a variant of lung adenocarcinoma, which may be mixed with non-mucinous adenocarcinoma. KRAS mutations are common, but other clinical and genetic features are not clearly established. Lung adenocarcinomas (n=760) with ≥5years follow-up comprised 3 non-overlapping cohorts for survival analysis. Mucinous tumors were evaluated with Ion AmpliSeq™ Cancer Hotspot Panel v2. Cases without detected mutations were tested for ALK, ROS1, and by OncoScan array. Fifty-seven invasive mucinous adenocarcinomas and 54 mixed mucinous/non-mucinous adenocarcinomas were identified.

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The histologic evolution of revealed, acute abruptions

There is considerable interest in using pathology to confirm acute abruptions. It has been suggested that pathologic findings can help to determine the timing of abruptions. Because of the dearth of evidence in the literature supporting this claim and its medicolegal implications, we undertook this study to explore further the possibility of timing abruptions by histopathology. We sought to correlate bleeding interval (duration from maternal presentation with vaginal bleeding (revealed abruption) to placental delivery) with placental histopathologic findings.

http://ift.tt/2x9p38Q

Immunohistochemical prognostic markers of esophageal squamous cell carcinoma: a systematic review

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the p...

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Estimates of cancer incidence and mortality in China, 2013

Population-based cancer registration data are collected by the National Central Cancer Registry in China every year. Cancer incident cases and cancer deaths in 2013 were analyzed.

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Minimum operational standards for 24/7 available emergency departments in the Netherlands: a first step taken by emergency physicians using an e-Delphi approach.

Objective: The objective of this study was to effectuate a consensus of emergency physicians on minimum requirements for facility, diagnostic, and medical specialist availability as a first step toward minimum operational standards for 24/7 available emergency departments (EDs) in the Netherlands. Patients and methods: A two-part e-Delphi through online survey was performed between January 2015 and May 2016, using a panel of 20 experts in emergency medicine. The aim of part I was to reach an agreement on a list of possible ED elements and their definitions. The second part addressed the actual study objective to reach consensus on operational standards. Successive rounds were submitted to the members of the panel online using SurveyMonkey. Results of each survey round were discussed and interpreted in agreement with all authors in preparation for the next round. Reaching consensus, defined as 70% or more agreement or disagreement among the panel, on the level of all items was the endpoint of this study. Results: Both parts I and II required five rounds. The dropout rate of the expert panel remained zero. The availability of 52 facilities and diagnostic functionalities and the manner in which 17 medical specialties should be available to every 24/7 ED were agreed upon by the expert panel. Conclusion: An expert panel agreed upon minimum operational standards for EDs in the Netherlands. These results are helpful as a first step toward a more widely supported standard for future 24/7 available EDs in the Netherlands and in addition to this other urgent care facilities. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of poly-hexamethylene biguanide hydrochloride (PHMB) treated non-sterile medical gloves upon the transmission of Streptococcus pyogenes, carbapenem-resistant E. coli, MRSA and Klebsiella pneumoniae from contact surfaces

Reduction of accidental contamination of the near-patient environment has potential to reduce acquisition of healthcare-associated infection(s). Although medical gloves should be removed when soiled or touchin...

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Author's Reply: "How to Report and Interpret Bioequivalence Data in Solid Organ Transplant Recipients".

No abstract available

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Summary of the British Transplantation Society UK Guidelines for Hepatitis E and Solid Organ Transplantation.

The incidence and prevalence of hepatitis E virus (HEV) infection has increased in many developed countries over the last decade, predominantly due to infection with genotype 3 (G3) HEV. Infection with HEV G3 is important in transplant recipients because it can persist in immunosuppressed individuals, leading if untreated to the development of chronic hepatitis and significant liver fibrosis. The British Transplantation Society (BTS) has developed Guidelines for "Hepatitis E & Solid Organ Transplantation" to inform clinical teams and patients about hepatitis E, to help increase the recognition of persistent hepatitis E infection, and to provide clear guidance on its management. This guideline was published on the BTS website in June 2017 and aims to review the evidence relating to the diagnosis and management of persistent hepatitis E in solid organ transplant recipients, and the methods of prevention of HEV infection. In line with previous guidelines published by the BTS, the guideline has used the GRADE system to rate the strength of evidence and recommendations. This article includes a summary overview of hepatitis E and transplantation with key references, and the statements of recommendation contained within the guideline. It is recommended that the full guideline document is consulted for complete details of the relevant references and evidence base. This may be accessed at http://ift.tt/2w6lROe Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Everolimus is Associated With Less Weight Gain Than Tacrolimus 2 Years Following Liver Transplantation: Results of a Randomized Multicenter Study.

Background: Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mTOR inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study. Methods: Following a run-in period, patients (N = 719) were randomized at 30+/-5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC)(n=245); (ii) TAC control (n=243) or (iii) TAC elimination (n=231). In this posthoc analysis, weight change at 12 and 24 months was compared between groups. Vital signs, lipids and laboratory parameters at 12 and 24 months and rates of PTMS were assessed. Results: Mean increase in weight from baseline was higher at month 12 in the TAC control arm (8.15 +/- 9.27 kg) than in the EVR + reduced TAC (5.88 +/- 12.60 kg, P=0.056) and the TAC elimination arms (4.76 +/- 9.94 kg, P=0.007). At month 24, the TAC control arm displayed a significantly greater weight increase (9.54 +/- 10.21 kg) than either the EVR + reduced TAC (6.69 +/- 8.37 kg, P=0.011) or the TAC elimination groups (6.01 +/- 9.98 kg, P=0.024). Rates of PTMS were similar for the EVR + reduced TAC (71.8%), TAC elimination (70.3%) and TAC control (67.4%) arms (P=NS). Conclusions: EVR with reduced-exposure TAC attenuated weight gain at 1 and 2 years posttransplant compared to a standard tacrolimus immunosuppression regimen. Rates of PTMS were comparable between EVR-containing and TAC control regimens. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Synthesis of Infectious Bacteriophages in an E. coli-based Cell-free Expression System

A new generation of cell-free transcription-translation platforms has been engineered to construct biochemical systems in vitro through the execution of gene circuits. In this article, we describe how bacteriophages, such as MS2, ΦΧ174, and T7, are synthesized from their genome using an all E. coli cell-free TXTL system.

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FDA Approves Nivolumab for Some Metastatic Colorectal Cancers

FDA has granted accelerated approval to the immunotherapy drug nivolumab (Opdivo®) for patients with metastatic colorectal cancer whose tumors have alterations that affect DNA repair.

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Experimental Methods for Trapping Ions Using Microfabricated Surface Ion Traps

This paper presents a microfabrication methodology for surface ion traps, as well as a detailed experimental procedure for trapping ytterbium ions in a room-temperature environment.

http://ift.tt/2w6jElV

Clarius Wireless Ultrasound Scanners now available with advanced features

VANCOUVER — Clarius Mobile Health, a healthcare technology company, has released advanced features and options for its wireless handheld ultrasound scanner for medical professionals on the go. The Clarius App 3.1 Eclipse with the enhancements is available now on the App Store and Google Play. Clarius Ultrasound Scanners are intended for use as a visual stethoscope for clinicians to conduct quick ...

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Rescue crew uses drones to help save man trapped across river

The drones were used to "make sure there were no hazards" that the crew members didn't see

http://ift.tt/2iaEGdl

Soft Lithographic Procedure for Producing Plastic Microfluidic Devices with View-ports Transparent to Visible and Infrared Light

A protocol for the fabrication of plastic microfluidic devices with transparent view-ports for visible and infrared light imaging is described.

http://ift.tt/2vHfuQJ

Echocardiographic Assessment of Right Ventricle Dimensions and Function After Exposure to Extreme Altitude: Is an Expedition to 8000 m Hazardous for Right Ventricular Function?

High Altitude Medicine & Biology , Vol. 0, No. 0.


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Method and Instrumented Fixture for Femoral Fracture Testing in a Sideways Fall-on-the-Hip Position

In this manuscript, we present a protocol to fracture test cadaveric proximal femora in a sideways fall on the hip configuration using instrumented fixtures mounted on a standard servo hydraulic frame. Nine digitized signals comprising forces, moments, and displacement along with two high speed video streams are acquired during testing.

http://ift.tt/2i9tuOa

Rescue crew uses drones to help save man in river

The drones were used to "make sure there were no hazards" that the crew members didn't see

http://ift.tt/2w53Z6y

Projected increase in obesity and non-alcoholic steatohepatitis-related liver transplantation waitlist additions in the United States

Abstract

Non-alcoholic steatohepatitis (NASH) cirrhosis is the fastest growing indication for liver transplantation (LT) in the US. We aimed to determine the temporal trend behind the rise in obesity and NASH-related additions to the LT waitlist in the US and make projections for future NASH burden on the LT waitlist. We used data from the Organ Procurement and Transplantation Network database from 2000-2014 to obtain the number of NASH-related LT waitlist additions. The obese population in the US from 2000-2014 was estimated using data from the US Census Bureau and the National Health and Nutrition Examination Survey. Based on obesity trends, we established a time lag between obesity prevalence and NASH-related waitlist additions. We used data from the US Census Bureau on population projections from 2016-2030 to forecast obesity estimates and NASH-related LT waitlist additions. From 2000-2014, the proportion of obese individuals significantly increased 44.9% and the number of NASH-related annual waitlist additions increased from 391 to 1605. Increase in obesity prevalence was strongly associated with LT waitlist additions 9 years later in derivation and validation cohorts (R²=0.9). Based on these data, annual NASH-related waitlist additions are anticipated to increase by 55.4% (1,354 to 2,104) between 2016 and 2030. There is significant regional variation in obesity rates and in the anticipated increase in NASH-related waitlist additions (p<0.01). Conclusion: We project a marked increase in demand for LT for NASH given population obesity trends. Continued public health efforts to curb obesity prevalence are needed to reduce the projected future burden of NASH. This article is protected by copyright. All rights reserved.

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A Randomized, Placebo-Controlled Trial of Cenicriviroc for Treatment of Nonalcoholic Steatohepatitis with Fibrosis

Abstract

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis.

A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score [NAS] ≥4, and liver fibrosis (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of steatohepatitis. Biomarkers of inflammation and adverse events were assessed.

Full study recruitment was achieved. The primary end point of NAS improvement in the intent-to-treat population and resolution of steatohepatitis was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144) (16% vs 19%, P = 0.52 and 8% vs 6%, P = 0.49, respectively). However, the fibrosis end point was met in significantly more subjects on CVC than placebo (20% vs 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo.

Conclusions: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of steatohepatitis compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation. ClinicalTrials.gov no: NCT02217475 (CENTAUR). This article is protected by copyright. All rights reserved.

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Hepatic function of FcRn revealed: Implications for overcoming drug-mediated hepatotoxicity

http://ift.tt/2vGcBiS

Increased tumor-infiltrating CD45RA−CCR7− regulatory T-cell subset with immunosuppressive properties foster gastric cancer progress

Increased tumor-infiltrating CD45RA−CCR7− regulatory T-cell subset with immunosuppressive properties foster gastric cancer progress

Cell Death and Disease 8, e3002 (August 2017). doi:10.1038/cddis.2017.388

Authors: Fang-yuan Mao, Hui Kong, Yong-liang Zhao, Liu-sheng Peng, Weisan Chen, Jin-yu Zhang, Ping Cheng, Ting-ting Wang, Yi-pin Lv, Yong-sheng Teng, Xiao-long Fu, Yu-gang Liu, Xiao-long Wu, Chuan-jie Hao, Nan You, Ping Luo, Pei-wu Yu, Quan-ming Zou, Gang Guo & Yuan Zhuang

http://ift.tt/2uUvtrI

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage

Cell Death and Disease 8, e3003 (August 2017). doi:10.1038/cddis.2017.381

Authors: Seung-Jun Yoo, Bongki Cho, Deokho Lee, Gowoon Son, Yeong-Bae Lee, Hyung Soo Han, Eunjoo Kim, Chanil Moon & Cheil Moon

http://ift.tt/2uUdul4

Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway

Total tanshinones exhibits anti-inflammatory effects through blocking TLR4 dimerization via the MyD88 pathway

Cell Death and Disease 8, e3004 (August 2017). doi:10.1038/cddis.2017.389

Authors: Hongwei Gao, Xin Liu, Wen Sun, Naixin Kang, Yanli Liu, Shilin Yang, Qiong-ming Xu, Chunming Wang & Xiuping Chen

http://ift.tt/2wjrOXP

Ossicular Chain Reconstruction: A Home Run for Leslie Horne After a Devastating Auto Accident

Two weeks before her wedding, 27-year-old Leslie Horne was driving from her new home in Fulshear to a friend's house... Read the full article...

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Three ORL Specialists Named to H Texas Magazine Top Doctors List for 2017

Three members of the Department of Otorhinolaryngology-Head and Neck Surgery at McGovern Medical School at UTHealth were named by local... Read the full article...

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Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins

Zika virus infects neural stem cells and causes microcephaly. In this study, Yoon et al. showed that NS2A protein encoded by Zika virus, but not by Dengue virus, impairs proliferation of radial glial cells in both embryonic mouse cortex and human forebrain organoids. Mechanistically, ZIKV-NS2A disrupts adherens junction formation.

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Introducing navigation during melanoma-related sentinel lymph node procedures in the head-and-neck region

Abstract

Background

Intraoperative sentinel node (SN) identification in patients with head-and-neck malignancies can be challenging due to unexpected drainage patterns and anatomical complexity. Here, intraoperative navigation-based guidance technologies may provide outcome. In this study, gamma camera-based freehandSPECT was evaluated in combination with the hybrid tracer ICG-^99mTc-nanocolloid.

Materials and methods

Eight patients with melanoma located in the head-and-neck area were included. Indocyanine green (ICG)-^99mTc-nanocolloid was injected preoperatively, whereafter lymphoscintigraphy and SPECT/CT imaging were performed in order to define the location of the SN(s). FreehandSPECT scans were generated in the operation room using a portable gamma camera. For lesion localization during surgery, freehandSPECT scans were projected in an augmented reality video-view that was used to spatially position a gamma-ray detection probe. Intraoperative fluorescence imaging was used to confirm the accuracy of the navigation-based approach and identify the exact location of the SNs.

Results

Preoperatively, 15 SNs were identified, of which 14 were identified using freehandSPECT. Navigation towards these nodes using the freehandSPECT approach was successful in 13 nodes. Fluorescence imaging provided optical confirmation of the navigation accuracy in all patients. In addition, fluorescence imaging allowed for the identification of (clustered) SNs that could not be identified based on navigation alone.

Conclusions

The use of gamma camera-based freehandSPECT aids intraoperative lesion identification and, with that, supports the transition from pre- to intraoperative imaging via augmented reality display and directional guidance.

http://ift.tt/2uUh1je