Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes.

BACKGROUND A discordant immune response (DIR) is a failure to satisfactorily increase CD4 counts on ART despite successful virological control. Literature on the clinical effects of DIR has not been systematically evaluated. We aimed to summarise the risk of mortality, AIDS and serious non-AIDS events associated with DIR with a systematic review. METHODS The protocol is registered with the Centre for Review Dissemination, University of York (registration number CRD42014010821). Included studies investigated the effect of DIR on mortality, AIDS, or serious non-AIDS events in cohort studies or cohorts contained in arms of randomised controlled trials for adults aged 16 years or older. DIR was classified as a suboptimal CD4 count (as defined by the study) despite virological suppression following at least 6 months of ART. We systematically searched PubMed, Embase, and the Cochrane Library to December 2015. Risk of bias was assessed using the Cochrane tool for assessing risk of bias in cohort studies. Two authors applied inclusion criteria and one author extracted data. Risk ratios were calculated for each clinical outcome reported. RESULTS Of 20 studies that met the inclusion criteria, 14 different definitions of DIR were used. Risk ratios for mortality in patients with and without DIR ranged between 1.00 (95% CI 0.26 to 3.92) and 4.29 (95% CI 1.96 to 9.38) with the majority of studies reporting a 2 to 3 fold increase in risk. CONCLUSIONS DIR is associated with a marked increase in mortality in most studies but definitions vary widely. We propose a standardised definition to aid the development of management options for DIR

Asthma Knowledge, Adherence, and Administration Techniques in Hispanic Caregivers of Pediatrics

7.5% of Hispanics in the United States suffer from asthma-related diseases, and Latino children are not as likely to use preventative asthma medications as compared with Caucasians. Educational interventions may reduce the number of visits to emergency-care. The reasons for non-adherence are currently unknown, and discovering these reasons will help to address the problem

Population Density and Reproductive Seasonality of Tryonia cheatumi (Gastropoda: Cochliopidae), the Phantom Tryonia

We studied population density, population size, and reproductive seasonality of the Phantom Tryonia, Tryonia cheatumi (Pilsbry, 1935). This endangered freshwater snail is found only in the San Solomon Spring system, a cienega, or karst-based, arid-land freshwater spring system, in western Texas, USA. We sampled populations at seven locations in the system seasonally over a 2-yr period. San Solomon Spring, the system\u27s largest spring and modified into a swimming pool, had the largest population of T. cheatumi, with an estimated 49 million individuals and a mean density as high as 23,626 ± 39,030 (individuals/m2 ± SD). There were seasonal differences in mean density (up to 25-fold) and median snail size at all sites, but consistent seasonal patterns of mean density or size were not observed. Median snail size among samples was not related to water temperature, and juveniles were present in most samples in all seasons. These results support continuous, aseasonal reproduction, as expected in thermally stable habitats, but differences in median size and mean density among seasons and sites suggest that other factors affect reproduction and seasonal variation in population size of T. cheatumi

The RCK1 domain of the human BK_(Ca) channel transduces Ca^(2+) binding into structural rearrangements

Large-conductance voltage- and Ca^(2+)-activated K^+ (BK_(Ca)) channels play a fundamental role in cellular function by integrating information from their voltage and Ca2+ sensors to control membrane potential and Ca^(2+) homeostasis. The molecular mechanism of Ca^(2+)-dependent regulation of BKCa channels is unknown, but likely relies on the operation of two cytosolic domains, regulator of K^+ conductance (RCK)1 and RCK2. Using solution-based investigations, we demonstrate that the purified BK_(Ca) RCK1 domain adopts an α/β fold, binds Ca^(2+), and assembles into an octameric superstructure similar to prokaryotic RCK domains. Results from steady-state and time-resolved spectroscopy reveal Ca^(2+)-induced conformational changes in physiologically relevant [Ca^(2+)]. The neutralization of residues known to be involved in high-affinity Ca^(2+) sensing (D362 and D367) prevented Ca^(2+)-induced structural transitions in RCK1 but did not abolish Ca^(2+) binding. We provide evidence that the RCK1 domain is a high-affinity Ca^(2+) sensor that transduces Ca^(2+) binding into structural rearrangements, likely representing elementary steps in the Ca^(2+)-dependent activation of human BK_(Ca) channels

Extraneous color affects female macaques’ gaze preference for photographs of male conspecifics

Humans find members of the opposite sex more attractive when their image is spatially associated with the color red. This effect even occurs when the red color is not on the skin or clothing (i.e. is extraneous). We hypothesize that this extraneous color effect could be at least partially explained by a low-level and biologically innate generalization process, and so similar extraneous color effects should be observed in non-humans. To test this possibility, we examined the influence of extraneous color in rhesus macaques (Macaca mulatta). Across two experiments, we determined the influence of extraneous red on viewing preferences (assessed by looking time) in free-ranging rhesus monkeys. We presented male and female monkeys with black and white photographs of the hindquarters of same and opposite sex conspecifics on either a red (experimental condition) or blue (control condition) background. As a secondary control, we also presented neutral stimuli (photographs of seashells) on red and blue backgrounds. We found that female monkeys looked longer at a picture of a male scrotum, but not a seashell, on a red background (Experiment 1), while males showed no bias. Neither male nor female monkeys showed an effect of color on looking time for female hindquarters or seashells (Experiment 2). The finding for females viewing males suggests that extraneous color affects preferences among rhesus macaques. Further, it raises the possibility that evolutionary processes gave rise to extraneous color effects during human evolution

Healthy ageing, appetite, frailty and sarcopenia: a brief overview

In many societies the population is getting older, such that in some western countries it is expected that those over 80 years of age will make up 30% of the population (1-2). In the modern era, due to improved health and better medical support/treatment, many people may spend as many years retired as they did working. Unfortunately, as one ages, the burden of disease increases (2.9 million people in England have >1 long-term condition), longevity is compromised by disability; therefore the drive must be to add life to years rather than just years to life. When people live long, the media often asks “what is the success associated with longevity or successful (healthy) ageing?” Is it a success to live a long life, or is successful ageing the key? Healthy ageing, is defined as a state, where the effect of frailty, sarcopenia, disease and disability have been minimised. Farpour et al (3) discuss the effect that aging has on Iranian people, and Liang et al discuss the findings of a systematic review looking at traditional Chinese’ medicine and subhealth (4), which could be aligned to prefrailty. In 2015 the WHO defined Health as “a state of complex physical, mental and social well-being and not merely absence of disease” (5). Healthy ageing was also defined as “the process of developing and maintaining the functional ability that enables well-being in older age”. Rowe and Khan (1987) commented that to age successfully one must avoid disease, remain engaged with life and maintain a high level of physical and cognitive function (6). Healthy ageing is, therefore, a complex interplay between physical, cognitive and social factors, and perhaps is dependent on how we individually respond to the internal and external forces at play (table 1). The definition of what is normal and what is abnormal is fraught with difficulty; what is acceptable and what is not? There is a risk that where normative parameters (for younger adults) are exceeded there will be a medicalisation of “older age”! What ultimately matters is the preservation of functional ability, which the majority (75%) of very old people are able to do and live relatively independent lives (6). This paper will discuss the interdependency between healthy ageing, appetite, frailty and sarcopenia and their impact on functional ability

The impact on sleep of a multidisciplinary cognitive behavioural pain management programme: a pilot study

Background: Reduced sleep quality is a common complaint among patients with chronic pain, with 50-80% of patients reporting sleep disturbance. Improvements in pain and quality of life measures have been achieved using a multidisciplinary cognitive behavioural therapy pain management programme (CBT-PMP) that aims to recondition attitudes to pain, and improve patients' self-management of their condition. Despite its high prevalence in patients with chronic pain, there is very limited objective evidence for the effect of this intervention on sleep quality. The primary research objective is to investigate the short-term effect of a multidisciplinary CBTPMP on subjective (measured by Pittsburg Sleep Quality Index) and objective sleep quality (measured by Actigraphy) in patients with chronic pain by comparison with a control group. The secondary objectives will investigate changes in function and mood, and then explore the relationship between objective and subjective sleep quality and physical and psychological outcome measures. Methods/Design: Patients who fulfil the inclusion criteria for attendance on the multidisciplinary CBT-PMP in the Adelaide and Meath Hospital, Tallaght, Dublin and are currently listed on the PMP waiting list will be invited to participate in this pilot study. Potential patients will be screened for sleep disturbance [determined by the Pittsburgh Sleep Quality Index (PSQI)]. Those patients with a sleep disturbance (PSQI >5) will be assigned to either the intervention group (immediate treatment), or control group (deferred treatment, i.e. the PMP they are listed for is more than six months away) based on where they appear on the waiting list. Baseline measures of sleep, function, and mood will be obtained using a combination of self-report questionnaires (the Hospital Anxiety and Depression Scale, the Short Form 36 health survey, the Pittsburgh Sleep Quality Index, the Tampa Scale for Kinesiophobia), and functional outcome measures. Sleep will be measured for seven days using actigraphy (Actiwatch 7). These measures will be repeated after the four week multidisciplinary cognitive behavioural therapy pain management programme, and at a two month follow-up. The waiting list control group will be assessed at baseline, and two months later. Analysis for the primary outcome will include between group differences of subjective and objective sleep parameters from baseline to follow-up using Independent T-tests or Mann-Whitney U tests. The secondary outcomes establishing relationships between the sleep variables and physical and psychological outcome measures will be established using multiple linear regression models. Discussion: This pilot study will evaluate the impact of a multidisciplinary CBT-PMP on both subjective and objective measures of sleep in patients with chronic pain and provide guidance for a larger clinical trial. Trial Registration: Current controlled trial ISRCTN: ISRCTN7491359

A survey and panel discussion of the effects of the COVID-19 pandemic on paediatric urological productivity, guideline adherence and provider stress

Introduction The COVID-19 pandemic has led to an unprecedented need to re-organise and re-align priorities for all surgical specialties. Despite the current declining numbers globally, the direct effects of the pandemic on institutional practices and on personal stress and coping mechanisms remains unknown. The aims of this study were to assess the effect of the pandemic on daily scheduling and work balances, its effects on stress, and to determine compliance with guidelines and to assess whether quarantining has led to other areas of increased productivity. Methods A trans-Atlantic convenience sample of paediatric urologists was created in which panellists (Zoom) discussed the direct effects of the COVID-19 pandemic on individual units, as well as creating a questionnaire using a mini-Delphi method to provide current semi-quantitative data regarding practice, and adherence levels to recently published risk stratification guidelines. They also filled out a Perceived Stress Scale (PSS) questionnaire to assess contemporary pandemic stress levels. Results There was an 86% response rate from paediatric urologists. The majority of respondents reported near complete disruption to planned operations (70%), and trainee education (70%). They were also worried about the effects of altered home-lives on productivity (<= 90%), as well as a lack of personal protective equipment (57%). The baseline stress rate was measured at a very high level (PSS) during the pandemic. Adherence to recent operative guidelines for urgent cases was 100%. Conclusion This study represents a panel discussion of a number of practical implications for paediatric urologists, and is one of the few papers to assess more pragmatic effects and combines opinions from both sides of the Atlantic. The impact of the pandemic has been very significant for paediatric urologists and includes a decrease in the number of patients seen and operated on, decreased salary, increased self-reported stress levels, substantially increased telemedicine usage, increased free time for various activities, and good compliance with guidelines and hospital management decisions