The Role of Nanomechanics in Healthcare

Abstract

Nanomechanics has played a vital role in pushing our capability to detect, probe, and manipulate the biological species, such as proteins, cells, and tissues, paving way to a deeper knowledge and superior strategies for healthcare. Nanomechanical characterization techniques, such as atomic force microscopy, nanoindentation, nanotribology, optical tweezers, and other hybrid techniques have been utilized to understand the mechanics and kinetics of biospecies. Investigation of the mechanics of cells and tissues has provided critical information about mechanical characteristics of host body environments. This information has been utilized for developing biomimetic materials and structures for tissue engineering and artificial implants. This review summarizes nanomechanical characterization techniques and their potential applications in healthcare research. The principles and examples of label-free detection of cancers and myocardial infarction by nanomechanical cantilevers are discussed. The vital importance of nanomechanics in regenerative medicine is highlighted from the perspective of material selection and design for developing biocompatible scaffolds. This review interconnects the advancements made in fundamental materials science research and biomedical technology, and therefore provides scientific insight that is of common interest to the researchers working in different disciplines of healthcare science and technology.

Nanomechanics is playing a vital role in pushing our capability to detect, probe, and manipulate the biological species, such as proteins, cells and tissues, paving way to knowledge and strategies for superior healthcare. Nanomechanics has enabled early diagnosis of life-threatening diseases, as well as facilitated the development of biomimetic implants for tissue engineering and prosthesis.

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Organ Bioprinting: Are We There Yet?

Abstract

About 15 years ago, bioprinting was coined as one of the ultimate solutions to engineer vascularized tissues, which was impossible to accomplish using the conventional tissue fabrication approaches. With the advances of 3D-printing technology during the past decades, one may expect 3D bioprinting being developed as much as 3D printing. Unfortunately, this is not the case. The printing principles of bioprinting are dramatically different from those applied in industrialized 3D printing, as they have to take the living components into account. While the conventional 3D-printing technologies are actually applied for biological or biomedical applications, true 3D bioprinting involving direct printing of cells and other biological substances for tissue reconstruction is still in its infancy. In this progress report, the current status of bioprinting in academia and industry is subjectively evaluated. The progress made is acknowledged, and the existing bottlenecks in bioprinting are discussed. Recent breakthroughs from a variety of associated fields, including mechanical engineering, robotic engineering, computing engineering, chemistry, material science, cellular biology, molecular biology, system control, and medicine may overcome some of these current bottlenecks. For this to happen, a convergence of these areas into a systemic research area "3D bioprinting" is needed to develop bioprinting as a viable approach for creating fully functional organs for standard clinical diagnosis and treatment including transplantation.

Bioprinting involving direct printing of cells and other biological substances for tissue or organ reconstruction is still in its infancy. A transdisciplinary effort combining the best international expertise in biology, engineering, chemistry, optics, robotics, material science, medicine, noninvasive diagnostic imaging as well as computer-aided design, to name just the most obvious, is needed to hopefully generate the necessary innovations in this fascinating field.

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Workplace Phobic Anxiety as a Mental Health Phenomenon in the Job Demands-Resources Model

Purpose. Anxiety-related problems at work are a serious problem in the occupational context, as they come along with sick leave and problems in work participation. The aim of this study is to analyse workplace phobic anxiety in nonclinical context using the Job Demands-Resources model. Methods. The study involved a sample of 739 workers from a retail company, mostly with permanent contracts. Structural equation modelling analyses were performed using AMOS software. Results. Both the health impairment and motivational variables in the JD-R model were significantly related to workplace phobic anxiety and subsequently to absenteeism, specifically, exhaustion mediated between perceived job demands and workplace phobic anxiety and work engagement mediated between perceived job resources and workplace phobic anxiety. Moreover, workplace phobic anxiety was significantly positively related to absenteeism. Conclusions. Results suggest that workplace phobic anxiety is a specific concept and an important issue in organizations for both workers' health and the organizational costs linked to absenteeism. Supervisors and occupational physicians should be aware of workplace phobic anxiety, especially when workers are on sick leave often or for long periods.

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Is insomnia a risk factor for new-onset asthma? A population-based study in Taiwan

Objectives

To determine whether insomnia at baseline is a risk factor for new-onset asthma.

Methods

We recruited 48 871 patients with insomnia (insomnia group) newly diagnosed between 2002 and 2007, and 97 742 matched controls without insomnia (control group) from Taiwan's Longitudinal Health Insurance Database 2000. All of the patients were followed up for 4 years to see whether new-onset asthma developed. Patients with previous asthma or insomnia were excluded. The Poisson regression was used to estimate the incidence rate ratios (IRRs) and 95% CIs of asthma. Cox proportional hazard regression was used to calculate the risk of asthma between the two groups.

Results

After a 4-year follow-up, 424 patients in the insomnia group and 409 in the control group developed asthma. The incidence rate of asthma was significantly higher in the insomnia group (22.01vs10.57 per 10 000 person-years). Patients with insomnia have a higher risk of developing new-onset asthma during the 4-year follow-up (HR: 2.08, 95% CI 1.82 to 2.39). The difference remained significant after adjustment (adjusted HR: 1.89, 95% CI 1.64 to 2.17).

Conclusions

This large population-based study suggests that insomnia at baseline is a risk factor for developing asthma.

http://ift.tt/2AigKgg

Study of depression influencing factors with zero-inflated regression models in a large-scale population survey

Objectives

The number of depression symptoms can be considered as count data in order to get complete and accurate analyses findings in studies of depression. This study aims to compare the goodness of fit of four count outcomes models by a large survey sample to identify the optimum model for a risk factor study of the number of depression symptoms.

Methods

15 820 subjects, aged 10 to 80 years old, who were not suffering from serious chronic diseases and had not run a high fever in the past 15 days, agreed to take part in this survey; 15 462 subjects completed all the survey scales. The number of depression symptoms was the sum of the 'positive' responses of seven depression questions. Four count outcomes models and a logistic model were constructed to identify the optimum model of the number of depression symptoms.

Results

The mean number of depression symptoms was 1.37±1.55. The over-dispersion test statistic O was 308.011. The alpha dispersion parameter was 0.475 (95% CI 0.443 to 0.508), which was significantly larger than 0. The Vuong test statistic Z was 6.782 and the P value was <0.001, which showed that there were too many zero counts to be accounted for with traditional negative binomial distribution. The zero-inflated negative binomial (ZINB) model had the largest log likelihood and smallest AIC and BIC, suggesting best goodness of fit. In addition, predictive probabilities for many counts in the ZINB model fitted the observed counts best.

Conclusions

All fitting test statistics and the predictive probability curve produced the same findings that the ZINB model was the best model for fitting the number of depression symptoms, assessing both the presence or absence of depression and its severity.

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Impact of inhalational versus intravenous anaesthesia on early delirium and long-term survival in elderly patients after cancer surgery: study protocol of a multicentre, open-label, and randomised controlled trial

Introduction

Elderly patients who have solid organ cancer often receive surgery. Some of them may develop delirium after surgery and delirium development is associated with worse outcomes. Furthermore, despite all of the advances in medical care, the long-term survival in cancer patients is far from optimal. Evidences suggest that choice of anaesthetics during surgery, that is, either inhalational or intravenous anaesthetics, may influence outcomes. However, the impact of general anaesthesia type on the occurrence of postoperative delirium is inconclusive. Although retrospective studies suggest that propofol-based intravenous anaesthesia was associated with longer survival after cancer surgery when compared with inhalational anaesthesia, prospective studies as such are still lacking. The purposes of this randomised controlled trial are to test the hypotheses that when compared with sevoflurane-based inhalational anaesthesia, propofol-based intravenous anaesthesia may reduce the incidence of early delirium and prolong long-term survival in elderly patients after major cancer surgery.

Methods and analysis

This is a multicentre, open-label, randomised controlled trial with two parallel arms. 1200 elderly patients (≥65 years but <90 years) who are scheduled to undergo major cancer surgery (with predicted duration ≥2 hours) are randomised to receive either sevoflurane-based inhalational anaesthesia or propofol-based intravenous anaesthesia. Other anaesthetics and supplemental drugs including sedatives, opioids and muscle relaxants are administered in both arms according to routine practice. The primary early outcome is the incidence of 7-day delirium after surgery and the primary long-term outcome is the duration of 3-year survival after surgery.

Ethics and dissemination

The study protocol has been approved by the Clinical Research Ethics Committees of Peking University First Hospital (2015[869]) and all participating centres. The results of early and long-term outcomes will be analysed and reported separately.

Trial registration number

ChiCTR-IPR-15006209; NCT02662257; NCT02660411.

http://ift.tt/2AhvdJh

Protective effect of smoking against pterygium development in men: a nationwide longitudinal cohort study in South Korea

Objective

The present study aimed to evaluate the association between smoking and incident pterygium in adult Korean men.

Design

A retrospective nationwide longitudinal cohort.

Setting

National Health Insurance database of South Korea.

Participants

This study included Korean men (age range: 40–79 years) registered in the Korea National Health Insurance Service database from 2002 through 2013. We compared HRs for pterygium between 90 547 current/past and 90 547 never-smokers via 1:1 propensity-matched analysis.

Primary outcome measure

Incident cases of pterygium were identified from the database.

Results

Pterygium developed in 5389 (6.0%) never-smokers and 3898 (4.3%) past/current smokers (P<0.001). The incidence of pterygium per 1000 person-years in never-smokers and in past/current smokers was 6.5 and 4.7, respectively (age-adjusted HR, 0.73; 95% CI, 0.70 to 0.76). This protective effect was more pronounced among current smokers than among past smokers (for current smokers: HR, 0.68; 95% CI, 0.65 to 0.71 and for past smokers: HR, 0.85; 95% CI, 0.80 to 0.90). A longer duration of smoking and higher amounts of cigarette consumption were associated with a lower incidence of pterygium.

Conclusions

Longitudinally, cigarette smoking was associated with a reduced risk of pterygium, and this protective effect was more pronounced among current smokers than among past smokers.

http://ift.tt/2iey1zT

Use of humour in medical education: a survey of students and teachers at a medical school in China

Objective

Humour is a powerful resource in medical education. The purpose of this study is to investigate what students and teachers think about the use of humour. What challenges do teachers face in using humour and how they address them are also the subject of the present study.

Design

Separate cross-sectional questionnaire surveys.

Setting

Tongji Medical College and Tongji Hospital in China.

Participants

327 students at Tongji Medical College and 165 physician teachers at Tongji Hospital in China.

Main outcome measures

The primary study outcome was assessed by proportion.

Results

87% of student and teacher respondents agreed with using humour in the didactic setting. They felt humour fostered a positive didactic atmosphere. Interesting clinical case was the most frequently used humour type by teachers and considered the most effective by students. Lack of humorous materials related to the lecture subject was the main challenge to humour use cited by teachers. Collecting humorous materials in teacher's daily work and life, observing teachers with a reputation for successfully using humour, and efficiently using the internet-enhanced humour use ability.

Conclusion

The present study confirms that most medical students and physician teachers support the use of humour in medical didactics, with particular strategies aiding its use and positive impact.

http://ift.tt/2AhUP92

Lived experience of women with gestational diabetes mellitus living in China: a qualitative interview study

Objective

To explore the lived experience of women with gestational diabetes mellitus (GDM) living in China in order to add knowledge about how the Chinese women suffer from GDM.

Design

A qualitative interpretive interview study. Data were collected with a snowball sampling technique. Phenomenological hermeneutics was used as the analysis method based on Ricoeur's phenomenological hermeneutical interpretation theory.

Setting

The study was performed at the participants' work places, or at the obstetric clinics or wards at two provincial hospitals and one municipal hospital in the southeast of China.

Participants

Inclusion criteria were age ≥18 years, diagnosis of GDM without other pregnancy complications, in 34th gestational weeks—postpartum 4th weeks and speaking Mandarin Chinese without speech impediment. 62 women, who met the inclusion criteria, took part in the study.

Results

The lived experience of the women with GDM living in China was formulated into a main theme: 'longing for caring care'. The main theme was derived from four themes: being stricken by GDM, wishing to receive caring GDM care, being left alone to struggle with GDM and trying to adjust and adapt to life with GDM.

Conclusion

The eagerness for caring care in China was highlighted. The lack of caring care could be one of the possible reasons why the professional–patient relations were deteriorating in China. It could be useful for health providers and health policymakers to receive education and training about caring care. Using the health metaphor of balance and 'patient participation' and 'patient-centred' approaches may benefit women with GDM and thus improve the quality of care in China.

http://ift.tt/2if9OcD

Postpartum management of hypertensive disorders of pregnancy: a systematic review

Objectives

Hypertensive disorders of pregnancy (HDP) affect one in ten pregnancies and often persist postpartum when complications can occur. We aimed to determine the effectiveness and safety of pharmacological interventions, other interventions and different care models for postpartum hypertension management.

Design

A systematic review was undertaken. Nine electronic databases, including Medline, were searched from inception to 16 March 2017. After duplicate removal, 4561 records were screened. Two authors independently selected studies, extracted study characteristics and data, and assessed methodological quality.

Setting

Randomised controlled trials, case–control studies and cohort studies from any country and healthcare setting.

Participants

Postnatal women with HDP.

Interventions

Therapeutic intervention for management of hypertension, compared with another intervention, placebo or no intervention.

Primary and secondary outcome measures

Outcome data were collected for maternal mortality and severe morbidity; systolic, diastolic and mean arterial blood pressure (BP) control; and safety data. Secondary outcome data collected included the length of postnatal hospital stay and laboratory values.

Results

39 studies were included (n=2901). Results were heterogeneous in terms of intervention, comparison and outcome requiring a narrative approach. There were insufficient data to recommend any single pharmacological intervention. 18 studies reported calcium-channel blockers, vasodilators and beta-blockers lowered BP postpartum. 12 of these reported safety data. Limited data existed regarding management in the weeks following hospital discharge. Neither loop diuretics (three studies) nor corticosteroids (one study) produced clinical benefit. Uterine curettage significantly reduced BP over the first 48 hours postpartum (range 6–13 mm Hg) compared with standard care (eight studies), with safety data only reported by four of eight studies.

Conclusion

There was insufficient evidence to recommend a particular BP threshold, agent or model of care, but three classes of antihypertensive appeared variably effective. Further comparative research, including robust safety data, is required. Curettage reduced BP, but without adequate reporting of harms, so it cannot currently be recommended.

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Protocol for the melatools skin self-monitoring trial: a phase II randomised controlled trial of an intervention for primary care patients at higher risk of melanoma

Introduction

Melanoma is the fifth most common cancer in the UK. Incidence rates have quadrupled over the last 30 years and continue to rise, especially among younger people. As routine screening of the general population is not currently recommended in the UK, a focus on secondary prevention through early detection and prompt treatment in individuals at increased risk of melanoma could make an important contribution to improve melanoma outcomes. This paper describes the protocol for a phase II, multisite, randomised controlled trial, in the primary care setting, for patients at increased risk of melanoma. A skin self-monitoring (SSM) smartphone 'App' was used to improve symptom appraisal and encourage help seeking in primary care, thereby promoting early presentation with skin changes suspicious of melanoma.

Methods and analysis

We aim to recruit 200 participants from general practice waiting rooms in the East of England. Eligible patients are those identified at higher melanoma risk (using a real-time risk assessment tool), without a personal history of melanoma, aged 18 to 75 years. Participants will be invited to a primary care nurse consultation, and randomised to the intervention group (standard written advice on skin cancer detection and sun protection, loading of an SSM 'App' onto the participant's smartphone and instructions on use including self-monitoring reminders) or control group (standard written advice alone). The primary outcomes are consultation rates for changes to a pigmented skin lesion, and the patient interval (time from first noticing a skin change to consultation). Secondary outcomes include patient sun protection behaviours, psychosocial outcomes, and measures of trial feasibility and acceptability.

Ethics and dissemination

NHS ethical approval has been obtained from Cambridgeshire and Hertfordshire research ethics committee (REC reference 16/EE/0248). The findings from the MelaTools SSM Trial will be disseminated widely through peer-reviewed publications and scientific conferences.

Trial registration number

ISCTRN16061621.

http://ift.tt/2ift5dU

Improving hearing and vision in dementia: protocol for a field trial of a new intervention

Introduction

Quality of life and other key outcomes may be improved by optimising hearing and vision function in people living with dementia. To date, there is limited research assessing the efficacy of interventions aimed at improving hearing and vision in people with dementia. Here, we outline a protocol to field test a newly developed home-based intervention, designed to optimise sensory functioning in people with dementia in three European sites. The results of this study will inform the design and conduct of a full-scale randomised controlled trial (RCT) in five European sites.

Methods and analysis

In this multisite, single arm, open label, feasibility study, participants with dementia (n=24) will be assessed for hearing and vision impairments and be prescribed a hearing aid and/or glasses. Each participant will have a study partner ('dyads'). A subset of dyads will receive 'sensory support' from a 'sensory support therapist', comprising home visits over 12 weeks. The therapist will offer the following intervention: adherence support for corrective devices; adaptations to the home environment to facilitate sensory function; communication training; and referral to community-based support services. The primary outcomes will be process measures assessing the feasibility, tolerability and acceptability of: (1) the intervention components; (2) the method of implementation of the intervention and (3) the study procedures, including outcome assessment measures. Quantitative data will be collected at baseline and follow-up. Qualitative data using semistructured interviews will be collected postintervention and weekly, using participant diaries. Finally, we will explore a model of cost-effectiveness to apply in the subsequent full-scale trial. This feasibility study is a necessary step in the development of a complex, individualised, psychosocial intervention. The data gathered will allow logistical and theoretical processes to be refined in preparation for a full-scale RCT.

Ethics and dissemination

Ethical approval was obtained in all three participating countries. Results of the field trial will be submitted for publication in a peer-reviewed journal.

http://ift.tt/2ifsYiu

A rapid review to identify physical activity accrued while playing golf

Objective

To identify physical activity (PA) accrued while playing golf and modifiers of PA accrued.

Design

A rapid review of primary research studies. Quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for cohort and cross-sectional studies.

Methods and outcomes

The following databases were searched from 1900 to March 2017: SPORTDiscus, Web of Science, PsycINFO, MEDLINE, Google Scholar, Google Advanced Search, ProQuest, WHO International Clinical Trials Registry Platform. All primary research investigating golf or golfers with any of the following outcomes was included: metabolic equivalent of task, oxygen uptake, energy expenditure, heart rate, step count, distance covered, strength, flexibility, balance, sedentary behaviour.

Results

Phase one searching identified 4944 citations and phase two searching identified 170 citations. In total, 19 articles met inclusion criteria. Golf is primarily a moderate intensity PA, but may be low intensity depending on the playing population and various modifiers. Less PA is accrued by those who ride a golf cart compared with those walking the course.

Conclusions

Golf can be encouraged in order to attain PA recommendations. Further research is required into the relationship between golf and strength and flexibility PA recommendations and how modifiers affect PA accrued.

PROSPERO registration number

CRD42017058237.

http://ift.tt/2Agc6PM

Review of systematic reviews of non-pharmacological interventions to improve quality of life in cancer survivors

Objectives

Over two million people in the UK are living with and beyond cancer. A third report diminished quality of life.

Design

A review of published systematic reviews to identify effective non-pharmacological interventions to improve the quality of life of cancer survivors.

Data sources

Databases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO.

Study selection

Published systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data.

Outcomes

The primary outcome of interest was any measure of global (overall) quality of life.

Analytical methods

Quality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components.

Results

Of 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life.

Conclusions

Exercise-based interventions were effective in the short (less than 3–8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal.

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An immune-molecular hypothesis supporting infectious aetiopathogenesis of Kawasaki disease in children

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CXCL4 is a novel inducer of human Th17 cells and correlates with IL-17 and IL-22 in psoriatic arthritis

Abstract

CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17-associated rheumatic diseases. However, whether CXCL4 plays a direct role in the induction of IL-17 production by human CD4 T cells is currently unclear. Here, we demonstrated that CXCL4 induced human CD4 T cells to secrete IL-17 that co-expressed IFNγ and IL-22, and differentiated naïve CD4 T cells to become Th17-cytokine producing cells. In a co-culture system of human CD4 T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17 production upon triggering by superantigen. Moreover, when monocyte-derived dendritic cells were differentiated in the presence of CXCL4, they orchestrated increased levels of IL-17, IFNγ, and proliferation by CD4 T cells. Furthermore, the CXCL4 levels in synovial fluid from psoriatic arthritis patients strongly correlated with IL-17 and IL-22 levels. A similar response to CXCL4 of enhanced IL-17 production by CD4 T cells was also observed in patients with psoriatic arthritis. Altogether, we demonstrate that CXCL4 boosts pro-inflammatory cytokine production especially IL-17 by human CD4 T cells, either by acting directly or indirectly via myeloid antigen presenting cells, implicating a role for CXCL4 in PsA pathology.

This article is protected by copyright. All rights reserved

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Northern Pig-tailed Macaques (Macaca leonina) maintain superior CD4+ T cell homeostasis during SIVmac239 infection

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A case report of brown tumor in a patient with chronic renal failure and renal cell carcinoma

We report a case of a 72 year old male with hyperparathyroidism secondary to end stage diabetic renal disease and coexisting bilateral chromophobe renal cell carcinomas. The patient presented with back and groin pain, right pelvic hemorrhage, and multiple lytic bone lesions concerning for metastatic renal cell carcinoma. Fine needle aspiration cytology demonstrated benign appearing osteoclasts and spindled cells. A concurrent core biopsy showed foci of spindled cell proliferation populated by osteoclast-like giant cells with stromal hemorrhage without evidence of metastatic carcinoma. The cytologic and histologic findings, in correlation with the clinical history, radiographic features, markedly increased parathyroid hormone levels and other serologic studies, were diagnostic of the reactive lesion seen in brown tumor of hyperparathyroidism secondary to chronic renal failure.

http://ift.tt/2Agp93N

Interaction-Dominant Causation in Mind and Brain, and Its Implication for Questions of Generalization and Replication

Abstract

The dominant assumption about the causal architecture of the mind is, that it is composed of a stable set of components that contribute independently to relevant observables that are employed to measure cognitive activity. This view has been called component-dominant dynamics. An alternative has been proposed, according to which the different components are not independent, but fundamentally interdependent, and are not stable basic properties of the mind, but rather an emergent feature of the mind given a particular task context. This view has been called interaction-dominant dynamics. In this paper, we review evidence for interaction-dominant dynamics as the causal architecture of the mind. We point out, that such an architecture is consistent with problems of convergence in research on the level of results and theorizing. Moreover, we point out that if interaction-dominant dynamics as the causal architecture of the mind were to be true, this would naturally lead to (some degree of) problems with generalization and replicability in sciences of the mind and brain, and would probably warrant changes in the scientific practice with regard to study-design and data analysis.

http://ift.tt/2nf5qvZ

The nuclear factor-kappa B pathway and response to treatment in breast cancer

Pharmacogenomics, Ahead of Print.


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Synechococcus plasticity under environmental changes

Abstract

Cyanobacteria are among the oldest photoautotrophic organisms on Earth, and have contributed to shaping the planet's biogeochemistry with their significant biomass and key metabolic activities. Synechococcus, the focus of this review, is one of the prevalent genera in the order Chroococcales, common in oceans and lakes and characterized by a coccoid unicellular or microcolony morphology. The evolution of its phycobilisomes is the key of the adaptation of this tiny photosynthetic cell to different light regimes and environmental conditions. Furthermore, Synechococcus strains are widely distributed from the equator to the poles, showing an extreme adaptability to high and low temperatures. Because of their structural plasticity and ecological adaptability, these cyanobacteria are particularly interesting in the current condition of fast climate change. Moreover, picocyanobacteria of the Synechococcus genus have a potentially vast impact on global cycles thanks to their significant role in the biogeochemical cycles of aquatic ecosystems. As increasing abundances are predicted for this genus worldwide, and in light of the connection between cyanobacteria and global change events, a better characterization of these organisms promises important and timely ecological insights. Here, I will summarize the morphological and genetic characteristics of Synechococcus strains and their distribution in freshwater lakes, also considering its marine counterpart.

http://ift.tt/2gVsAoI

Antibiotic treatment disrupts bacterial communities in the colon and rectum of simian immunodeficiency virus-infected macaques

Abstract

Antibiotic therapies are known to disrupt gastrointestinal (GI) bacterial communities. HIV and pathogenic simian immunodeficiency virus (SIV) infections have also been associated with disrupted GI bacterial communities. We administered a combination antibiotic therapy to six SIV-infected rhesus macaques and collected colon biopsies, stool samples and rectal swabs before and after antibiotics, and evaluated the bacterial communities at each sample site using high-throughput 16S rRNA gene sequencing. The colon mucosa and stool samples displayed different bacterial communities, while the rectal swabs showed a mixture of the mucosal and stool-associated bacteria. Antibiotics disrupted the native bacterial communities at each sample site. The colon mucosa showed depleted abundances of the dominant Helicobacteraceae, while we found depleted abundances of the dominant Ruminococcaceae sp. in the stool. The rectal swabs showed similar trends as the colon mucosa, but were more variable. After the antibiotic treatment, there were increased abundances of similar taxa of facultative anaerobic bacteria, including Lactobacillaceae and Enterobacteriaceae at each sample site.

http://ift.tt/2y9yNoo

Pretreatment C-reactive protein/albumin ratio is associated with poor survival in patients with stage IB-IIA cervical cancer

Abstract

Previous studies have shown that the C-reactive protein/albumin ratio (CAR) is a prognostic indicator in multiple types of carcinomas. This study is the first to evaluate the prognostic significance of CAR in stage IB-IIA cervical cancer patients treated with radical surgery, as well as that of several other inflammation-based factors, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI). A total of 235 patients were enrolled in this study. The optimal cut-off values of CAR and other inflammation-based factors were determined by receiver operating characteristic curves. The Kaplan–Meier method and Cox regression model analysis were performed to determine the independent predictors of progression-free survival (PFS) and overall survival (OS). At a cut-off value of 0.15, patients with a high CAR had significantly shorter PFS and OS than those with a lower CAR (P < 0.001). A higher CAR was significantly associated with elevated scores of NLR and PLR and a decreased PNI (P < 0.001). Univariate analyses showed that elevated CAR preoperatively was significantly associated with poor survival; a similar trend was also noted for the NLR, PLR, and PNI. Multivariate analyses demonstrated that only CAR was an independent indicator for PFS (hazard ratio [HR]: 5.164; 95% confidence interval [CI]: 2.495–10.687; P < 0.001) and OS (HR: 4.729; 95% CI: 2.263–9.882; P < 0.001). In conclusion, preoperative CAR is a novel and superior predictor of poor survival in patients with stage IB-IIA cervical cancer.

This paper intends to elaborate the relationship between C-reactive protein/albumin ratio (CAR) and prognosis of stage IB-IIA cervical cancer and found that the preoperativeCAR is a novel and superior prognostic factor in stage IB-IIA cervical cancer patients who undergo radical hysterectomy.

http://ift.tt/2BvTNDR

An investigation of survivorship clinic attendance among childhood cancer survivors living in a five-state rural region

Abstract

Purpose

Cancer survivorship clinics manage cancer-related health complications and are available primarily in urban areas. We examine how demographic, clinical, and geographic-based characteristics are associated with attendance at the only pediatric survivorship clinic in a largely rural, multistate region.

Methods

One thousand eight hundred sixteen cancer survivors were diagnosed at age ≤ 25 from 1986 to 2005 while living in the region. Cox models incorporating death as a competing risk and generalized estimating equations calculated hazards ratios (HR) for characteristics measured at the clinic's opening. Subjects were followed from the clinic opening their first visit, death, emigration from the catchment area, or December 31, 2014.

Results

Five percent of survivors visited the clinic. Attendance is positively associated with a leukemia or lymphoma diagnosis (HR = 3.32, 95% confidence interval [CI] = 1.72–6.78 vs CNS tumors), previous relapse (HR = 1.78, 95% CI = 1.00–3.19), and residing >100 mi from the clinic (HR = 2.05, 95% CI 1.03–4.10). Survivors aged ≥ 31 years at clinic opening (HR = 0.19, 95% CI = 0.07–0.54) are less likely to attend than younger survivors. Residence between 16 and 100 mi had an inverse association with attendance, although not significant.

Conclusion

Survivorship clinics are not widely attended by survivors in this catchment region. Efforts should be made to recruit survivors aged ≥ 31 and diagnosed with CNS tumors. Distance has a complex association with attendance, which could be attributed to the limited availability of preventative services in regions > 100 mi from the clinic.

Implications for Cancer Survivors

Survivors living in this catchment region may not be receiving care necessary to prevent severe late effects.

http://ift.tt/2ik8Xr7

Fungal 7-epi-10-deacetyltaxol produced by an endophytic Pestalotiopsis microspora induces apoptosis in human hepatocellular carcinoma cell line (HepG2)

Paclitaxel (taxol) is a potent anticancer drug that is used in the treatment of a wide variety of cancerous. In the present study, we identified a taxol derivative named 7-epi-10-deacetyltaxol (EDT) from the cult...

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Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis

Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and l...

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Extracts of Zuo Jin Wan, a traditional Chinese medicine, phenocopies 5-HTR1D antagonist in attenuating Wnt/β-catenin signaling in colorectal cancer cells

In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a herbal formula of traditional Chinese medicine (TCM), possessed anticancer properties. However, the underlying mechanism for the action of ZJW ...

http://ift.tt/2i1aKO8

TEM8/ANTXR1-specific CAR T cells as a targeted therapy for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive disease lacking targeted therapy. In this study, we developed a CAR T cell-based immunotherapeutic strategy to target TEM8, a marker initially defined on endothelial cells in colon tumors that was discovered recently to be upregulated in TNBC. CAR T cells were developed that upon specific recognition of TEM8 secreted immunostimulatory cytokines and killed tumor endothelial cells as well as TEM8-positive TNBC cells. Notably, the TEM8 CAR T cells targeted breast cancer stem-like cells, offsetting the formation of mammospheres relative to non-transduced T cells. Adoptive transfer of TEM8 CAR T cells induced regression of established, localized patient-derived xenograft tumors (PDX) as well as lung metastatic TNBC cell line-derived xenograft tumors, by both killing TEM8+ TNBC tumor cells and targeting the tumor endothelium to block tumor neovascularization. Our findings offer a preclinical proof of concept for immunotherapeutic targeting of TEM8 as a strategy to treat TNBC.

http://ift.tt/2igNxLJ

Short dental implants as compared to maxillary sinus augmentation procedure for the rehabilitation of edentulous posterior maxilla: Three-year results of a randomized clinical study

Abstract

Background

Several treatment options exist for the implant-supported rehabilitation of edentulous posterior maxilla.

Purpose

To compare maxillary sinus floor augmentation associated to standard length implants, with direct placement of implants of reduced length in the available residual bone.

Materials and Methods

Patients with edentulous posterior maxilla and a residual height of 4-7 mm were randomly allocated to the test (short implants [SIs], 6.5 to 8.5mm long) or the control (sinus augmentation [SA] and implants ≥10mm long) group. Anorganic bovine bone was the grafting material for the control group. In both groups pure platelet-rich plasma was used to bioactivate implant surface prior to insertion. Implant and prosthesis survival, clinical variables, radiographic bone level change, quality of life, and patient satisfaction were assessed.

Results

Twenty-five patients were treated in the control group (58 standard length implants) and 27 in the test group (42 SIs). After 3 years of follow-up no implant failure and biological or mechanical complications were recorded. Marginal bone loss, soft tissue, and oral hygiene parameters were similar in the 2 groups at both 1 and 3 years' follow-up. Postoperative pain, swelling and other symptoms and daily activities were better in the SIs group than in the SA group, while patients' satisfaction after 1 year was similar.

Conclusions

In spite of comparable medium-term clinical and radiographic outcomes, when the residual ridge height is sufficient for a safe placement, SIs may be preferred due to simplified protocol, less invasiveness, shorter treatment time, and reduced postoperative discomfort as compared to SA.

http://ift.tt/2zzjYrX

Challenges to discussing palliative care with people experiencing homelessness: a qualitative study

Objectives

To explore the views and experiences of people who are homeless and those supporting them regarding conversations and approaches to palliative care

Setting

Data were collected between October 2015 and October 2016 in homeless hostels and day centres and with staff from primary and secondary healthcare providers and social care services from three London boroughs.

Participants

People experiencing homelessness (n=28), formerly homeless people (n=10), health and social care providers (n=48), hostel staff (n=30) and outreach staff (n=10).

Methods

In this qualitative descriptive study, participants were recruited to interviews and focus groups across three London boroughs. Views and experiences of end-of-life care were explored with people with personal experience of homelessness, health and social care professionals and hostel and outreach staff. Saturation was reached when no new themes emerged from discussions.

Results

28 focus groups and 10 individual interviews were conducted. Participants highlighted that conversations exploring future care preferences and palliative care with people experiencing homelessness are rare. Themes identified as challenges to such conversations included attitudes to death; the recovery focused nature of services for people experiencing homelessness; uncertainty regarding prognosis and place of care; and fear of negative impact.

Conclusions

This research highlights the need for a different approach to supporting people who are homeless and are experiencing advanced ill health, one that incorporates uncertainty and promotes well-being, dignity and choice. We propose parallel planning and mapping as a way of working with uncertainty. We acknowledge that these approaches will not always be straightforward, nor will they be suitable for everyone, yet moving the focus of conversations about the future away from death and dying, towards the present and the future may facilitate conversations and enable the wishes of people who are homeless to be known and explored.

http://ift.tt/2Bk6ock

Impact of tumour histology on survival in advanced cervical carcinoma: an NRG Oncology/Gynaecologic Oncology Group Study

Impact of tumour histology on survival in advanced cervical carcinoma: an NRG Oncology/Gynaecologic Oncology Group Study

Impact of tumour histology on survival in advanced cervical carcinoma: an NRG Oncology/Gynaecologic Oncology Group Study, Published online: 28 November 2017; doi:10.1038/bjc.2017.400

Impact of tumour histology on survival in advanced cervical carcinoma: an NRG Oncology/Gynaecologic Oncology Group Study

http://ift.tt/2na4FUS

Variation in ‘fast-track’ referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites

Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites

Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites, Published online: 28 November 2017; doi:10.1038/bjc.2017.381

Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites

http://ift.tt/2na4E3g

Phosphate-Binder Use in US Dialysis Patients: Prevalence, Costs, Evidence, and Policies

Medicare costs for phosphate binders for US dialysis patients and patients with chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015. Previous data have shown that Part D costs for mineral and bone disorder medications increased faster than costs for all Part D medications for dialysis patients. Despite extensive use of phosphate binders and escalating costs, conclusive evidence is lacking that they improve important clinical end points in dialysis patients or non–dialysis-dependent patients with chronic kidney disease.

http://ift.tt/2j0Nwsp

Impact of tumour histology on survival in advanced cervical carcinoma: an NRG Oncology/Gynaecologic Oncology Group Study

http://ift.tt/2AeoMWQ

Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies

CSP is the target of protective antibodies against the malaria parasite Plasmodium falciparum (Pf). Here, Triller and Scally et al. identified potent Pf-inhibitory human anti-CSP memory B cell antibodies induced by natural exposure and unveiled the molecular details of antigen binding to two protective CSP repeat epitopes.

http://ift.tt/2zxm8sf

Variation in ‘fast-track’ referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites

http://ift.tt/2BvkvN6

Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies

The architecture of protein complexes is essential for their function. Combining various mass spectrometric techniques proved powerful to study their assembly. We provide protocols for chemical cross-linking and native mass spectrometry and show how these complementary techniques help to elucidate the architecture of multi-subunit protein assemblies.

http://ift.tt/2AiiyU5

Selective Serotonin Reuptake Inhibitors and Serotonin–Norepinephrine Reuptake Inhibitors Are Not Associated With Bleeding or Transfusion in Cardiac Surgical Patients

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) and serotonin–norepinephrine reuptake inhibitor (SNRI) use is known to alter platelet activation and aggregation leading to impairment in hemostasis. Previous studies are ambiguous with regard to bleeding, transfusion, and perioperative complications in patients undergoing cardiac surgery. The purpose of this study was to evaluate the risk of perioperative bleeding, transfusion, morbidity, and mortality in cardiac surgical patients taking SSRI/SNRIs compared with propensity-matched controls. METHODS: Adult patients undergoing cardiac surgery with cardiopulmonary bypass at our institution between January 1, 2004, and December 31, 2014, were eligible for study inclusion. Patients taking SSRI/SNRI medications at the time of surgery were identified and compared against all other patients not taking SSRI/SNRI medications to produce well-matched groups via propensity score analysis. Patients taking SSRI/SNRI medications were matched in a 1:1 ratio to control patients not taking these medications based on an internally estimated propensity score. Primary outcomes included perioperative blood transfusion, chest tube output, and reoperation for bleeding. Secondary outcomes included postoperative complications (renal failure, stroke or transient ischemic accident, prolonged mechanical ventilation, and perioperative myocardial infarction), intensive care unit (ICU) and hospital length of stay (LOS), and 30-day mortality. RESULTS: A total of 1417 pairs of SSRI/SNRI patients and matched controls were retained for analysis. Between SSRI/SNRI patients and matched controls, there was no significant difference in postoperative chest tube output (median, 750.0 vs 750.0 mL; P = .860) or reoperation for bleeding (2.8% vs 2.5%; P = .892). Perioperative transfusion rates across all time points and blood product type were not significantly different between groups, with the overall perioperative transfusion rate for SSRI/SNRI patients 66.5% vs 64.9% for matched controls (P = .697). Patients in the SSRI/SNRI group had a higher rate of prolonged mechanical ventilation (13.1% vs 8.6%; P = .002), longer ICU LOS (median, 25.5 vs 23.8 hours; P

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Nonhuman Primates in Anesthesia Research: Have We Reached the End of the Road?

No abstract available

http://ift.tt/2jt8fEu

ECMO in the Adult Patient: Core Critical Care

No abstract available

http://ift.tt/2hZcF5N

Predicting Severity of Acute Pain After Cesarean Delivery: A Narrative Review

Cesarean delivery is one of the most common surgical procedures in the United States, with over 1.3 million performed annually. One-fifth of women who undergo cesarean delivery will experience severe pain in the acute postoperative period, increasing their risk of developing chronic pain and postpartum depression, and negatively impacting breastfeeding and newborn care. A growing body of research has investigated tools to predict which patients will experience more severe pain and have increased analgesic consumption after cesarean delivery. These include quantitative sensory testing, assessment of wound hyperalgesia, response to local anesthetic infiltration, and preoperative psychometric evaluations such as validated psychological questionnaires and simple screening tools. For this review, we searched MEDLINE, the Cochrane database, and Google Scholar to identify articles that evaluated the utility of various tools to predict severe pain and/or opioid consumption in the first 48 hours after cesarean delivery. Thirteen articles were included in the final review: 5 utilizing quantitative sensory testing, including patient responses to pressure, electrical, and thermal stimuli; 1 utilizing hyperalgesia testing; 1 using response to local anesthetic wound infiltration; 4 utilizing preoperative psychometric evaluations including the State-Trait Anxiety Inventory, the Pain Catastrophizing Scale, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and simple questionnaires; and 2 utilizing a combination of quantitative sensory tests and psychometric evaluations. A number of modalities demonstrated statistically significant correlations with pain outcomes after cesarean delivery, but most correlations were weak to modest, and many modalities might not be clinically feasible. Response to local anesthetic infiltration and a tool using 3 simple questions enquiring about anxiety and anticipated pain and analgesic needs show potential for clinical use, but further studies are needed to evaluate the utility of these predictive tests in clinical practice. Accepted for publication October 9, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Ashraf S. Habib, MBBCh, MSc, MHSc, FRCA, Duke University Medical Center, Box 3094, Durham, NC 27710. Address e-mail to ashraf.habib@dm.duke.edu. © 2017 International Anesthesia Research Society

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Management of 1-Lung Ventilation—Variation and Trends in Clinical Practice: A Report From the Multicenter Perioperative Outcomes Group

BACKGROUND: Lung-protective ventilation (LPV) has been demonstrated to improve clinical outcomes in surgical patients. There are very limited data on the current use of LPV for patients undergoing 1-lung ventilation (1LV) despite evidence that 1LV may be a particularly important setting for its use. In this multicenter study, we report trends in ventilation practice for patients undergoing 1LV. METHODS: The Multicenter Perioperative Outcomes Group database was used to identify patients undergoing 1LV. We retrieved and calculated median initial and overall tidal volume (VT) for the cohort and for high-risk subgroups (female sex, obesity [body mass index >30 kg/m2], and short stature), percentage of patients receiving positive end-expiratory pressure (PEEP) ≥5 cm H2O, LPV during 1LV (VT ≤ 6 mL/kg predicted body weight [PBW] and PEEP ≥5 cm H2O), and ventilator driving pressure (ΔP; plateau airway pressure − PEEP). RESULTS: Data from 5609 patients across 4 institutions were included in the analysis. Median VT was calculated for each case and since the data were normally distributed, the mean is reported for the entire cohort and subgroups. Mean of median VT during 1LV for the cohort was 6.49 ± 1.82 mL/kg PBW. VT (mL/kg PBW) for high-risk subgroups was significantly higher; 6.86 ± 1.97 for body mass index ≥30 kg/m2, 7.05 ± 1.92 for female patients, and 7.33 ± 2.01 for short stature patients. Mean of the median VT declined significantly over the study period (from 6.88 to 5.72; P

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Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System

BACKGROUND: Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs. METHODS: With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I–III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS. RESULTS: Data were analyzed for 127 patients, of median (range) age 64 (22–86) years, undergoing surgical procedures lasting 105 (9–348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2–27.7) in phase I and 14.6 (11.6–20.7) in phase II (median difference, −3.25; 95% confidence interval, −6.35 to −0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6–90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1–93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1–6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II. CONCLUSIONS: Adding closed-loop control of remifentanil improved overall controller performance. This controller design offers a robust method to optimize the control of 2 drugs using a single sensor. The infusion safety system is an important component of a robust automated anesthesia system, but further research is required to determine the optimal constraints for these safe conditions. Accepted for publication September 27, 2017. Funding: This work was supported by funds received from the Collaborative Health Research Projects (CHRP 446511–13) (Principal Investigator: G.A.D.), a joint initiative between the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research. NeuroWave Systems Inc provided loan equipment for use in this study. Conflicts of Interest: See Disclosures at the end of the article. Trial Registration: clinicaltrials.gov (NCT01771263). Reprints will not be available from the authors. Address correspondence to Nicholas West, MSc, Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, V3-350, Clinical Support Bldg, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. Address e-mail to nicholas.west@cw.bc.ca. © 2017 International Anesthesia Research Society

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Technical Solutions and the Safety Big Picture

No abstract available

http://ift.tt/2i0CVwC

Failure of the Oxygen Gauge to Accurately Reflect the Pressure in the Oxygen Tank

No abstract available

http://ift.tt/2jt7hYS

Effect of Remote Ischemic Preconditioning on Outcomes in Adult Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Studies

BACKGROUND: Remote ischemic preconditioning (RIPC) has been demonstrated to prevent organ dysfunction in cardiac surgery patients. However, recent large, prospective, multicenter, randomized controlled trials (RCTs) had controversial results. Thus, a meta-analysis of RCTs was performed to investigate whether RIPC can reduce the incidence of acute myocardial infarction (AMI), acute kidney injury (AKI), and mortality in adult cardiac surgery patients. METHODS: Study data were collected from Medline, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. RCTs involving the effect of RIPC on organ protection in cardiac surgery patients, which reported the concentration or total release of creatine kinase-myocardial band, troponin I/troponin T (TNI/TNT) after operation, or the incidence of AMI, AKI, or mortality, were selected. Two reviewers independently extracted data using a standardized data extraction protocol where TNI or TNT concentrations; total TNI released after cardiac surgery; and the incidence of AKI, AMI, and mortality were recorded. Review Manager 5.3 software was used to analyze the data. RESULTS: Thirty trials, including 7036 patients were included in the analyses. RIPC significantly decreased the concentration of TNI/TNT (standard mean difference [SMD], −0.25 ng/mL; 95% confidence interval [CI], 0.12 to −0.04 ng/mL; P = .004), creatine kinase-myocardial band (SMD, −0.22; 95% CI, 0.07–0.35 ng/mL; P = .46), and the total TNI/TNT release (SMD, −0.49 ng/mL; 95% CI, 0.93 to −0.55 ng/mL; P = .03) in cardiac surgery patients after a procedure. However, RIPC could not reduce the incidence of AMI (relative risk, 0.89; 95% CI, 0.77–1.03; P = .12) and AKI (relative risk, 0.88; 95% CI, 0.72–1.06; P = .18), and there was also no effect of RIPC on mortality in adult cardiac surgery patients. Interestingly, subgroup analysis showed that RIPC reduced mortality of cardiac surgery patients who received volatile agent anesthesia. CONCLUSIONS : Our meta-analysis demonstrated that RIPC reduced TNI/TNT release after cardiac surgery. RIPC did not significantly reduce the incidence of AKI, AMI, and mortality. However, RIPC could reduce mortality in patients receiving volatile inhalational agent anesthesia. Accepted for publication October 10, 2017. Funding: Supported by Clinical Medicine Science and Technology program of Jiangsu Province (BL2013030). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Haibo Qiu, MD, PhD, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Address e-mail to haiboq2000@163.com. © 2017 International Anesthesia Research Society

http://ift.tt/2hYNksu

Total Intravenous Anesthesia and Target Controlled Infusions: A Comprehensive Global Anthology

No abstract available

http://ift.tt/2jsk5in

Perioperative Steroid Use for Tonsillectomy and Its Association With Reoperation for Posttonsillectomy Hemorrhage: A Retrospective Cohort Study

BACKGROUND: Steroids reduce postoperative complications after tonsillectomy such as nausea and vomiting, pain, and delayed recovery. However, steroids may also increase the risk of severe posttonsillectomy bleeding requiring reoperation. METHODS: To evaluate the risk of postoperative bleeding requiring reoperation related to perioperative steroid use, we conducted a retrospective cohort study of 6149 patients treated at 68 hospitals using a hospital-based claims database. The primary outcome was reoperation for bleeding within 14 postoperative days. We estimated odds ratios (ORs) between perioperative steroid use and reoperation by multivariable logistic regression analysis adjusted for confounders. We also estimated differences in the adjusted risk. Subgroup analyses after dividing patients into adults and children were also performed. RESULTS: The incidence of reoperation did not differ significantly between patients who received steroids on the day of tonsillectomy and those who did not (1.8%, n = 15 vs 1.5%, n = 79; adjusted OR 0.81, 95% confidence interval [CI], 0.45–1.43; P = .46). We also found nonsignificant associations in both adults (OR, 0.73; 95% CI, 0.38–1.38; P = .33) and children (OR, 1.18; 95% CI, 0.34–4.11; P = .80). The adjusted risk differences estimated by the logistic regression model were −0.30% (95% CI, −1.05 to 0.45) in all patients, −0.64% (95% CI, −1.82 to 0.54) in adults, and 0.13% (95% CI, −0.93 to 1.19) in children. CONCLUSIONS: Steroid use on the day of tonsillectomy was not associated with an increased risk of reoperation for bleeding. Although the wide range of CIs for the ORs could not eliminate the possibility of increased risk, especially in children, the incremental risks of reoperation for steroid use were within an acceptable range for both adults and children. Our results support the safety of perioperative steroid use for tonsillectomy, considering the magnitude of risk of reoperation because of bleeding. Accepted for publication October 20, 2017. Funding: Support was provided solely from institutional and/or departmental sources. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Yoshihisa Miyamoto, MD, MPH, is currently affiliated with the Department of Anesthesia, Kanagawa Children's Medical Center, Yokohama, Japan. Maki Shinzawa, MD, PhD, is currently affiliated with the Department of Nephrology, Graduate School of Medicine, Osaka University, Suita, Japan. Shiro Tanaka, PhD, is currently affiliated with the Department of Clinical Biostatistics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Sachiko Tanaka-Mizuno, PhD, is currently affiliated with the Department of Medical Statistics, Shiga University of Medical Science, Otsu, Japan. Reprints will not be available from the authors. Address correspondence to Koji Kawakami, MD,hD, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoecho, Sakyo-ku, Kyoto 606–8501, Japan. Address e-mail to kawakami.koji.4e@kyoto-u.ac.jp. © 2017 International Anesthesia Research Society

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Developing Reflective Practice: A Guide for Medical Students, Doctors, and Teachers

No abstract available

http://ift.tt/2jtb2O4

In Response: Investigation of 2 Prototypes of Novel Noncontact Technologies for Automated Real-Time Capture of Incremental Drug Administration Data From Syringes

No abstract available

http://ift.tt/2i0CthU

Large Variability in the Diversity of Physiologically Complex Surgical Procedures Exists Nationwide Among All Hospitals Including Among Large Teaching Hospitals

BACKGROUND: Multiple previous studies have shown that having a large diversity of procedures has a substantial impact on quality management of hospital surgical suites. At hospitals with substantial diversity, unless sophisticated statistical methods suitable for rare events are used, anesthesiologists working in surgical suites will have inaccurate predictions of surgical blood usage, case durations, cost accounting and price transparency, times remaining in late running cases, and use of intraoperative equipment. What is unknown is whether large diversity is a feature of only a few very unique set of hospitals nationwide (eg, the largest hospitals in each state or province). METHODS: The 2013 United States Nationwide Readmissions Database was used to study heterogeneity among 1981 hospitals in their diversities of physiologically complex surgical procedures (ie, the procedure codes). The diversity of surgical procedures performed at each hospital was quantified using a summary measure, the number of different physiologically complex surgical procedures commonly performed at the hospital (ie, 1/Herfindahl). RESULTS: A total of 53.9% of all hospitals commonly performed 3-fold larger diversity (ie, >30 commonly performed physiologically complex procedures). Larger hospitals had greater diversity than the small- and medium-sized hospitals (P 30 procedures (lower 99% CL, 71.9% of hospitals). However, there was considerable variability among the large teaching hospitals in their diversity (interquartile range of the numbers of commonly performed physiologically complex procedures = 19.3; lower 99% CL, 12.8 procedures). CONCLUSIONS: The diversity of procedures represents a substantive differentiator among hospitals. Thus, the usefulness of statistical methods for operating room management should be expected to be heterogeneous among hospitals. Our results also show that "large teaching hospital" alone is an insufficient description for accurate prediction of the extent to which a hospital sustains the operational and financial consequences of performing a wide diversity of surgical procedures. Future research can evaluate the extent to which hospitals with very large diversity are indispensable in their catchment area. Accepted for publication October 3, 2017. Funding: Departmental funding. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). The Division of Management Consulting, Department of Anesthesia, University of Iowa, performs the calculations described in the Introduction and Discussion of this article. F.D. receives no funds personally other than his salary and allowable expense reimbursements from the University of Iowa and has tenure with no incentive program. He and his family have no financial holdings in any company related to his work, other than indirectly through mutual funds for retirement. Income from the Division's consulting work is used to fund Division research. Reprints will not be available from the authors. Address correspondence to Franklin Dexter, MD, PhD, Division of Management Consulting, Department of Anesthesia, University of Iowa, 200 Hawkins Drive, 6 JCP, Iowa City, IA 52242. Address e-mail to Franklin-Dexter@UIowa.edu. © 2017 International Anesthesia Research Society

http://ift.tt/2hXGFiv

A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells

Abstract

Numerous approaches suggested that compounds with conjugated triazole moieties or benzoxazone pharmacores are effective to antagonize proliferation of human tumors. The current study reported that a synthetic triazole-conjugated benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H-benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug concentrations. More evidence supported that the induced reactive oxygen species lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic pathway as elucidated involved tumor suppressor p53 activation and LC3-1 conversion followed by PARP and procaspase-3 cleavage. Autophagy inhibition reverted apoptotic death and restored cell viabilities. BTO suppressed the development of A549 cell xenograft tumors by activating autophagy and apoptosis simultaneously. As an efficient tumor growth inhibitor with relatively small molecular weight, BTO is a viable addition to the existing list of lung cancer treatment.

http://ift.tt/2AeAmBY

Could mouthwash be putting you at risk of diabetes?

It might help to reduce bad breath and tooth decay, but a surprising new study suggests that mouthwash could also increase the risk of diabetes.

http://ift.tt/2AdZ8Sn

EMCrit – Critical Hyperkalemia by H. Pendell Meyers, EMCrit Intern

Critical Hyperkalemia ?s based on a recent publication

EMCrit by Guest Author.

http://ift.tt/2zOFjSo

Fabrication of Fine Electrodes on the Tip of Hypodermic Needle Using Photoresist Spray Coating and Flexible Photomask for Biomedical Applications

The fabrication method for fine interdigitated electrodes (gap and width: 20 µm) at the tip of a hypodermic needle (diameter: 720 µm) is demonstrated using a spray coating and flexible film photomask in the photolithography process.

http://ift.tt/2zAHgxL

Biotin (Vitamin B7): Safety Communication - May Interfere with Lab Tests

Audience: Laboratory, Health Professional, Patient [Posted 11/28/2017] ISSUE: The FDA is alerting the public, health care providers, lab personnel, and lab test developers that biotin can significantly interfere with certain lab tests and cause...

http://ift.tt/2ne2f7K

Preparation of Large-area Vertical 2D Crystal Hetero-structures Through the Sulfurization of Transition Metal Films for Device Fabrication

Through the sulfurization of pre-deposited transition metals, large-area and vertical 2D crystal hetero-structures can be fabricated. The film transferring and device fabrication procedures are also demonstrated in this report.

http://ift.tt/2i0A9HR

In Vivo Assay for Detection of Antigen-specific T-cell Cytolytic Function Using a Vaccination Model

The goal of this protocol is to allow for detection of in vivo antigen-specific killing of a target cell in a murine model.

http://ift.tt/2AdShIq

Bayesian fault detection and isolation using Field Kalman Filter

Fault detection and isolation is crucial for the efficient operation and safety of any industrial process. There is a variety of methods from all areas of data analysis employed to solve this kind of task, suc...

http://ift.tt/2jsYl5S

Experimental study of delivery of humidified-warm carbon dioxide during open abdominal surgery

Background

The aim of this study was to monitor the effect of humidified-warm carbon dioxide (HWCO₂) delivered into the open abdomen of mice, simulating laparotomy.

Methods

Mice were anaesthetized, ventilated and subjected to an abdominal incision followed by wound retraction. In the experimental group, a diffuser device was used to deliver HWCO₂; the control group was exposed to passive air flow. In each group of mice, surgical damage was produced on one side of the peritoneal wall. Vital signs and core temperature were monitored throughout the 1-h procedure. The peritoneum was closed and mice were allowed to recover for 24 h or 10 days. Tumour cells were delivered into half of the mice in each cohort. Tissue was then examined using scanning electron microscopy and immunohistochemistry.

Results

Passive air flow generated ultrastructural damage including mesothelial cell bulging/retraction and loss of microvilli, as assessed at 24 h. Evidence of surgical damage was still measurable on day 10. HWCO₂ maintained normothermia, whereas open surgery alone led to hypothermia. The degree of tissue damage was significantly reduced by HWCO₂ compared with that in controls. Peritoneal expression of hypoxia inducible factor 1α and vascular endothelial growth factor A was lowered by HWCO₂. These effects were also evident at the surgical damage sites, where protection from tissue trauma extended to 10 days. HWCO₂ did not reduce tumorigenesis in surgically damaged sites compared with passive air flow.

Conclusion

HWCO₂ diffusion into the abdomen in the context of open surgery afforded tissue protection and accelerated tissue repair in mice, while preserving normothermia.

Surgical relevance

Damage to the peritoneum always occurs during open abdominal surgery, by exposure to desiccating air and by mechanical trauma/damage owing to the surgical intervention. Previous experimental studies showed that humidified-warm carbon dioxide (HWCO₂) reduced peritoneal damage during laparoscopic insufflation. Additionally, this intervention decreased experimental peritoneal carcinomatosis compared with the use of conventional dry-cold carbon dioxide.

In the present experimental study, the simple delivery of HWCO₂ into the open abdomen reduced the amount of cellular damage and inflammation, and accelerated tissue repair. Sites of surgical intervention serve as ideal locations for cancer cell adhesion and subsequent tumour formation, but this was not changed measurably by the delivery of HWCO₂.

http://ift.tt/2zxR2QZ

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent

Background

The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection.

Methods

Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed.

Results

A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019).

Conclusion

Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

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Comparison of gaze behaviour of trainee and experienced surgeons during laparoscopic gastric bypass

Background

Eye tracking presents a novel tool that could be used to profile skill levels in surgery objectively. The primary aim of this study was to identify differences in gaze behaviour between expert and junior surgeons performing a laparoscopic Roux-en-Y gastric bypass (LRYGB) for obesity.

Methods

This prospective observational study used a lightweight eye-tracking apparatus to determine the difference in gaze behaviours between expert (more than 75 procedures) and junior (75 or fewer procedures) surgeons at defined stages of LRYGB. Primary endpoints were normalized dwell time and fixation frequency. Secondary endpoints were blink rate, maximum pupil size and rate of pupil change.

Results

A total of 20 procedures (12 junior, 8 expert) were analysed. Compared with juniors, experts showed a prolonged dwell time on the screen during angle of His dissection (median (range) 91·20 (83·40–94·40) versus 68·95 (59·80–87·60) per cent; P = 0·001), formation of the retrogastric tunnel (91·50 (85·80–95·50) versus 73·60 (34·60–90·50) per cent; P = 0·001) and gastric pouch formation (86·95 (83·60–90·20) versus 67·60 (37·10–80·00) per cent P < 0·001). Juniors had a greater blink frequency throughout all recorded segments (P < 0·010) and had a larger maximum pupil size during all recorded operative segments (P < 0·010). Rate of pupil change was greater in juniors in all analysed segments (P < 0·010).

Conclusion

These results suggest that experts display more focused attention on significant stimuli, alongside experiencing a reduced mental workload and having increased concentration. This has the potential for future use in validation of surgical skill in high-stakes assessment.

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Proton pump inhibitors and the risk for gastric cancer: possible confounding by serum vitamin B12

We read with interest the article by Cheung et al1 reporting an increased risk of gastric cancer with long-term exposure to proton pump inhibitors (PPI) following Helicobacter pylori (HP) eradication. Several recent reports and a meta-analysis have also demonstrated this association.2 3 The present study, using strict exclusion criteria, was able to adjust for the confounding effect of previous HP infection and eradication, demonstrating a PPI exposure-dependent escalating risk for non-cardia gastric cancer (NCGC) in previously infected patients. The authors suggest that the profound acid suppression by PPIs worsens the atrophic gastritis induced by HP infection, increasing the risk. We wish to address another confounder not taken into consideration in the present study as well as in the previous ones,1–3 namely vitamin B₁₂.

B vitamins are essential for methylation reactions, DNA stability and repair, while intact gastric mucosa and...

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An Important Moment in Tobacco Control

November 26, 2017, marked a unique moment in US public health history, with the major US tobacco companies issuing the first in a series of court-ordered "corrective statements" about their products.

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Biotin (Vitamin B7): Safety Communication - May Interfere with Lab Tests

Audience: Laboratory, Health Professional, Patient [Posted 11/28/2017] ISSUE: The FDA is alerting the public, health care providers, lab personnel, and lab test developers that biotin can significantly interfere with certain lab tests and cause...

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TGF-β signaling pathway in early mouse development and embryonic stem cells

Abstract

TGF-β superfamily signaling pathways essentially contribute to the broad spectrum of early developmental events including embryonic patterning, cell fate determination and dynamic movements. In this review, we first introduced some key developmental processes that require TGF-β signaling to show the fundamental importance of these pathways. Then we discuss how their activities are regulated, and new findings about how the TGF-β superfamily ligands bind to the chromatin to regulate transcription during embryo development.

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The role of TGF-β superfamily signaling in neurological disorders

Abstract

The TGF-β superfamily signaling is involved in a variety of biological processes during embryogenesis and in adult tissue homeostasis. Faulty regulation of the signaling pathway that transduces the TGF-β superfamily signals accordingly leads to a number of ailments, such as cancer and cardiovascular, metabolic, urinary, intestinal, skeletal, and immune diseases. In recent years, a number of studies have elucidated the essential roles of TGF-βs and BMPs during neuronal development in the maintenance of appropriate innervation and neuronal activity. The new advancement implicates significant roles of the aberrant TGF-β superfamily signaling in the pathogenesis of neurological disorders. In this review, we compile a number of reports implicating the deregulation of TGF-β/BMP signaling pathways in the pathogenesis of cognitive and neurodegenerative disorders in animal models and patients. We apologize in advance that the review falls short of providing details of the role of TGF-β/BMP signaling or mechanisms underlying the pathogenesis of neurological disorders. The goal of this article is to reveal a gap in our knowledge regarding the association between TGF-β/BMP signaling pathways and neuronal tissue homeostasis and development and facilitate the research with a potential to develop new therapies for neurological ailments by modulating the pathways.

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Quantitative single-molecule study of TGF-β/Smad signaling

Abstract

TGF-β/Smad signaling pathway triggers diverse cellular responses among different cell types and environmental conditions. Quantitative analysis of protein-protein interactions involved in TGF-β/Smad signaling is demanded for understanding the molecular mechanism of this signaling pathway. Live-cell single-molecule microcopy with high spatiotemporal resolution is a new tool to monitor key molecular events in a real-time manner. In this review, we mainly presented the recent work on the quantitative characterization of TGF-β/Smad signaling proteins by single-molecule method, and showed how it enabled us to obtain new insights about this canonical signaling process.

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TGF-β signaling in cancer metastasis

Abstract

The transforming growth factor (TGF)-β signaling events are well known to control diverse processes and numerous responses, such as cell proliferation, differentiation, apoptosis, and migration. TGF-β signaling plays context-dependent roles in cancer: in pre-malignant cells TGF-β primarily functions as a tumor suppressor, while in the later stages of cancer TGF-β signaling promotes invasion and metastasis. Recent studies have also suggested that the cross-talk between TGF-β signaling and other signaling pathways, such as Hippo, Wnt, EGFR/RAS, and PI3K/AKT pathways, may substantially contribute to our current understanding of TGF-β signaling and cancer. As a result of the wide-ranging effects of TGF-β, blockade of TGF-β and its downstream signaling components provides multiple therapeutic opportunities. Therefore, the outlook for anti-TGF-β signaling therapy for numerous diseases appears bright and will provide valuable information and thinking on the drug molecular design. In this review, we focus on recent insights into the regulation of TGF-β signaling in cancer metastasis which may contribute to the development of novel cancer-targeting therapies.

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Crosstalk between TGF-β signaling and epigenome

Abstract

The transforming growth factor beta (TGF-β) family of ligands plays major roles in embryonic development, tissue homeostasis, adult immunity, and wound repair. Dysregulation of TGF-β signaling pathway leads to severe diseases. Its key components have been revealed over the past two decades. This family of cytokines acts by activating receptor activated SMAD (R-SMAD) transcription factors, which in turn modulate the expression of specific sets of target genes. Cells of a multicellular organism have the same genetic information, yet they show structural and functional differences owing to differential expression of their genes. Studies have demonstrated that epigenetic regulation, an integral part of the TGF-β signaling, enables cells to sense and respond to TGF-β signaling in a cell context-dependent manner. R-SMAD, as the central transcription factor of TGF-β signaling, can recruit various epigenetic regulators to shape the transcriptome. In this review, we focus on epigenetic regulatory mechanisms in the TGF-β signaling during mammalian development and diseases and discuss the central role of the interaction between R-SMAD and various epigenetic regulators in this epigenetic regulation. The crosstalk between TGF-β signaling and the epigenome could serve as a versatile fine-tuning mechanism for transcriptional regulation during embryonic development and progression of diseases, particularly cancer.

http://ift.tt/2k8fjKK

The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages

Inflammasomes elicit pyroptosis or cell hyperactivation, with the latter defined as living cells that release IL-1. Evavold et al report that the pore-forming protein gasdermin D regulates IL-1 release from hyperactive macrophages. Cell- and liposome-based assays revealed that gasdermin D pores permit IL-1 passage across intact lipid bilayers.

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Ankle muscle tenotomy does not alter ankle flexor muscle recruitment bias during locomotor-related repetitive limb movement in late-stage chick embryos

Abstract

In ovo, late-stage chick embryos repetitively step spontaneously, a locomotor-related behavior also identified as repetitive limb movement (RLM). During RLMs, there is a flexor bias in recruitment and drive of leg muscle activity. The flexor biased activity occurs as embryos assume an extremely flexed posture in a spatially restrictive environment 2–3 days before hatching. We hypothesized that muscle afferent feedback under normal mechanical constraint is a significant input to the flexor bias observed during RLMs on embryonic day (E) 20. To test this hypothesis, muscle afference was altered either by performing a tenotomy of ankle muscles or removing the shell wall restricting leg movement at E20. Results indicated that neither ankle muscle tenotomy nor unilateral release of limb constraint by shell removal altered parameters indicative of flexor bias. We conclude that ankle muscle afference is not essential to ankle flexor bias characteristic of RLMs under normal postural conditions at E20.

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Clinical and molecular characterization of an emerging chromosome 22q13.31 microdeletion syndrome

Microdeletion of chromosome 22q13.31 is a very rare condition. Fourteen patients have been annotated in public databases but, to date, a clinical comparison has not been done and, consequently, a specific phenotype has not been delineated yet. We describe a patient showing neurodevelopmental disorders, dysmorphic features, and multiple congenital anomalies in which SNP array analysis revealed an interstitial 3.15 Mb de novo microdeletion in the 22q13.31 region encompassing 21 RefSeq genes and seven non-coding microRNAs. To perform an accurate phenotype characterization, clinical features observed in previously reported cases of 22q13.31 microdeletions were reviewed and compared to those observed in our patient. To the best of our knowledge, this is the first time that a comparison between patients carrying overlapping 22q13.31 deletions has been done. This comparison allowed us to identify a distinct spectrum of clinical manifestations suggesting that patients with a de novo interstitial microdeletion involving 22q13.31 have an emerging syndrome characterized by developmental delay/intellectual disability, speech delay/language disorders, behavioral problems, hypotonia, urogenital, and hands/feet anomalies. The microdeletion identified in our patient is the smallest reported so far and, for this reason, useful to perform a detailed genotype-phenotype correlation. In particular, we propose the CELSR1, ATXN10, FBLN1, and UPK3A as candidate genes in the onset of the main clinical features of this contiguous gene syndrome. Thus, the patient reported here broadens our knowledge of the phenotypic consequences of 22q13.31 microdeletions facilitating genotype-phenotype correlations. Additional cases are needed to corroborate our hypothesis and confirm genotype–phenotype correlations of this emerging syndrome.

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Clinical and genetic characterization of AP4B1-associated SPG47

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of disorders characterized by degeneration of the corticospinal and spinocerebellar tracts leading to progressive spasticity. One subtype, spastic paraplegia type 47 (SPG47 or HSP-AP4B1), is due to bi-allelic loss-of-function mutations in the AP4B1 gene. AP4B1 is a subunit of the adapter protein complex 4 (AP-4), a heterotetrameric protein complex that regulates the transport of membrane proteins. Since 2011, 11 individuals from six families with AP4B1 mutations have been reported, nine of whom had homozygous mutations and were from consanguineous families. Here we report eight patients with AP4B1-associated SPG47, the majority born to non-consanguineous parents and carrying compound heterozygous mutations. Core clinical features in this cohort and previously published patients include neonatal hypotonia that progresses to spasticity, early onset developmental delay with prominent motor delay and severely impaired or absent speech development, episodes of stereotypic laughter, seizures including frequent febrile seizures, thinning of the corpus callosum, and delayed myelination/white matter loss. Given that some of the features of AP-4 deficiency overlap with those of cerebral palsy, and the discovery of the disorder in non-consanguineous populations, we believe that AP-4 deficiency may be more common than previously appreciated.

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Oligonephronia and Wolf-Hirschhorn syndrome: A further observation

Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by a partial deletion of chromosome 4 (4p16.3p16.2). We describe a case of a male 9 years old children with WHS proteinuria and hypertension. Laboratory data showed creatinine 1.05 mg/dl, GFR 65.9 ml/min/1.73 m², cholesterol 280 mg/dl, triglyceride 125 mg/dl with electrolytes in the normal range. Urine collection showed protein 2.72 g/L with a urine protein/creatinine ratio (U_P/U_Cr ratio) of 4.2 and diuresis of 1,100 ml. Renal ultrasound showed reduced kidney dimensions with diffusely hyperechogenic cortex and poorly visualized pyramids. Renal biopsy showed oligonephronia with focal segmental glomerulosclerosis associated with initial tubulointerstitial sclerotic atrophy. The child began therapy with Angiotensin-converting enzyme inhibitors (ACE-inhibitors) to reduce proteinuria and progression of chronic kidney disease. In the literature the anomalies of number of glomeruli oligonephronia and oligomeganephronia (OMN) are described in two forms, one without any associated anomalies, sporadic, and solitary and the other with one or more anomalies. Our review of the literature shows that the pathogenesis of this anomaly is unknown but the role of chromosome 4 is very relevant. Many cases of OMN are associated with anomalies on this chromosome, in the literature cases series we observed this association in 14/48 cases (29.2%) and in 7 of these 14 cases with WHS. Our case and the review of literature demonstrate how periodic urinalysis and renal ultrasound monitoring is recommended in patients affected by WHS and the renal biopsy must be performed when there is the onset of proteinuria.

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Cognitive and behavioral phenotype of children with pseudohypoparathyroidism type 1A

Pseudohypoparathyroidism 1A (PHP1A) is a rare, genetic disorder. Most patients with PHP1A have cognitive impairment but this has not been systematically studied. We hypothesized that children with PHP1A would have lower intelligent quotient (IQ) scores than controls. To evaluate cognition and behavior, we prospectively enrolled children with PHP1A, one unaffected sibling (when available) and controls matched on BMI/age/gender/race. Evaluations included cognitive and executive function testing. Parents completed questionnaires on behavior and executive function. We enrolled 16 patients with PHP1A, 8 unaffected siblings, and 15 controls. Results are presented as mean (SD). The PHP1A group had a composite IQ of 85.9 (17.2); 25% had a composite IQ < −2 SD. The PHP1A group had significantly lower IQs than matched controls (composite IQ −17.3, 95%CI −28.1 to −6.5, p < 0.01) and unaffected siblings (composite IQ −21.5, 95%CI −33.9 to −9.1, p < 0.01). Special education services were utilized for 93% of the patients with PHP1A. Deficits were observed in executive function and parents reported delayed adaptive behavior skills and increased rates of attention deficit hyperactivity disorder. In conclusion, children with PHP1A have lower intelligence quotient scores, poorer executive function, delayed adaptive behavior skills, and increased behavior problems.

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Linear ubiquitin chain induces apoptosis and inhibits tumor growth

Abstract

Ubiquitination of proliferating cell nuclear antigen (PCNA) plays an important role in DNA damage response. Ectopic expression of PCNA fused at either terminus with ubiquitin (Ub) lacking two C-terminal glycine residues induces translesion DNA synthesis which resembles synthesis mediated by PCNA monoubiquitination. PCNA fused with Ub containing the C-terminal Gly residues at the C-terminus can be further polyubiquitinated in a Gly-dependent manner, which inhibits cell proliferation and induces ATR-dependent replication checkpoint. In this study, we surprisingly found that PCNA fused to a head-to-tail linear Ub chain induces apoptosis in a Ub chain length-dependent manner. Further investigation revealed that the apoptotic effect is actually induced by the linear Ub chain independently from PCNA, as the Ub chain fused to GFP or an epitope tag still efficiently induces apoptosis. It is revealed that the artificial linear Ub chain differs from endogenously encoded linear Ub chains in that its Ubs contain a Ub-G76S substitution, making the Ub chain resistant to cleavage by deubiquitination enzymes. We demonstrated in this study that ectopic expression of the artificial Ub chain alone in cultured human cancer cells is sufficient to inhibit tumor growth in a xenograft mouse model, making the linear Ub chain a putative anti-cancer agent.

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Lung cancer incidence and the strength of municipal smoke-free ordinances

BACKGROUND

Smoke-free laws reduce disease prevalence. The impact of municipal smoke-free laws on lung cancer incidence in Kentucky was examined. The authors hypothesized that lung cancer incidence rates would be associated with the strength of smoke-free laws.

METHODS

This was a secondary analysis of 83,727 Kentucky residents aged ≥ 50 years who were newly diagnosed with lung cancer from 1995 to 2014. In 2014, 33 municipalities had 1 or more smoke-free laws. County-level characteristics included adult smoking rate, sex, race/ethnicity, income, physician supply, observed radon values, and rurality.

RESULTS

Individuals living in communities with comprehensive smoke-free laws were 7.9% less likely than those living in communities without smoke-free protections to be diagnosed with lung cancer. The difference in lung cancer incidence between counties with moderate/weak laws and those without laws was not significant.

CONCLUSIONS

Comprehensive smoke-free laws were associated with fewer new cases of lung cancer, whereas weak or moderate smoke-free laws did not confer the same benefit. One hundred percent smoke-free laws, covering all workers and the public with few or no exceptions, may be key in reducing new cases of lung cancer. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society.

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The life-saving power of policy: Lessons from Kentucky

Data from Kentucky clearly link comprehensive smoke-free ordinances to lower rates of lung cancer. Uniform smoke-free policies protect nonsmokers from secondhand smoke, encourage cessation in those who are still smoking, and save lives. See also pages 000-000.

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Downregulation of DYRK2 promotes tumor cell proliferation and invasion by enhancing CDK14 expression in breast cancer

Abstract

Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation, and apoptosis. However, little is known about the mechanisms of transcriptional regulation by DYRK2 in cancer progression, particularly with respect to cancer proliferation and invasion. Here, we show that cyclin-dependent kinase 14 (CDK14) is identified as a target of DYRK2 using a comprehensive expression profiling approach. We found that reduced DYRK2 expression increases CDK14 expression, which promotes cancer cell proliferation and invasion in vitro, in addition to tumorigenicity in vivo. CDK14 and DYRK2 expression inversely correlated in human breast cancer tissues. We further identified androgen receptor (AR) as a candidate of DYRK2-dependent transcription factors regulating CDK14. Taken together, our findings suggest a mechanism by which DYRK2 controls CDK14 expression to regulate tumor cell proliferation and invasion in breast cancer. Targeting of this pathway may be a promising therapeutic strategy for treating breast cancer.

This article is protected by copyright. All rights reserved.

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Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians

Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretro...

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Why is my tongue tingling?

We look at a range of causes for a tingling tongue, including dental injuries, migraine, multiple sclerosis, and allergies. Learn more.

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Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development [RESEARCH REPORT]

Celeste M. Nelson, Jason P. Gleghorn, Mei-Fong Pang, Jacob M. Jaslove, Katharine Goodwin, Victor D. Varner, Erin Miller, Derek C. Radisky, and Howard A. Stone

Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses. Time-lapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between different tissues to control the development of the embryonic lung.

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Phyllotactic regularity requires the Paf1 complex in Arabidopsis [RESEARCH ARTICLE]

Kateryna Fal, Mengying Liu, Assem Duisembekova, Yassin Refahi, Elizabeth S. Haswell, and Olivier Hamant

In plants, aerial organs are initiated at stereotyped intervals, both spatially (every 137° in a pattern called phyllotaxis) and temporally (at prescribed time intervals called plastochrons). To investigate the molecular basis of such regularity, mutants with altered architecture have been isolated. However, most of them only exhibit plastochron defects and/or produce a new, albeit equally reproducible, phyllotactic pattern. This leaves open the question of a molecular control of phyllotaxis regularity. Here, we show that phyllotaxis regularity depends on the function of VIP proteins, components of the RNA polymerase II-associated factor 1 complex (Paf1c). Divergence angles between successive organs along the stem exhibited increased variance in vip3-1 and vip3-2 compared with the wild type, in two different growth conditions. Similar results were obtained with the weak vip3-6 allele and in vip6, a mutant for another Paf1c subunit. Mathematical analysis confirmed that these defects could not be explained solely by plastochron defects. Instead, increased variance in phyllotaxis in vip3 was observed at the meristem and related to defects in spatial patterns of auxin activity. Thus, the regularity of spatial, auxin-dependent, patterning at the meristem requires Paf1c.

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