Burden, coping, physical symptoms and psychological morbidity in caregivers of functionally dependent family members

Objectives: this study assessed burden, coping, physical symptoms and psychological morbidity in caregivers of functionally dependent family members. Methods: fifty family caregivers completed self-reported measures of burden, physical symptoms, psychological morbidity and coping strategies. Results: there was a significant negative correlation between coping strategies and the different clinical variables, as well as a significant positive correlation between coping strategies and duration of care. It appears that the stronger bond between caregiver and family member leads to a poorer use of adaptive coping strategies. It also appears that the deterioration of the relationship between them and the lower perceived self-efficacy are more prominente in caregivers of family members with cognitive impairment, indicating that caregivers with family members without cognitive impairment face fewer difficulties. Conclusion: these results emphasize the need for interventions to include coping strategies, since they are important in reducing caregivers’ burden, psychological morbidity and physical symptoms

Both habitat change and local lek structure influence patterns of spatial loss and recovery in a black grouse population

The final publication is available at Springer via http://dx.doi.org/10.1007/s10144-015-0484-3Land use change is a major driver of declines in wildlife populations. Where human economic or recreational interests and wildlife share landscapes this problem is exacerbated. Changes in UK black grouse Tetrao tetrix populations are thought to have been strongly influenced by upland land use change. In a long-studied population within Perthshire, lek persistence is positively correlated with lek size, and remaining leks clustered most strongly within the landscape when the population is lowest, suggesting that there may be a demographic and/or spatial context to the reaction of the population to habitat changes. Hierarchical cluster analysis of lek locations revealed that patterns of lek occupancy when the population was declining were different to those during the later recovery period. Response curves from lek-habitat models developed using MaxEnt for periods with a declining population, low population, and recovering population were consistent across years for most habitat measures. We found evidence linking lek persistence with habitat quality changes and more leks which appeared between 1994 and 2008 were in improving habitat than those which disappeared during the same period. Generalised additive models (GAMs) identified changes in woodland and starting lek size as being important indicators of lek survival between declining and low/recovery periods. There may also have been a role for local densities in explaining recovery since the population low point. Persistence of black grouse leks was influenced by habitat, but changes in this alone did not fully account for black grouse declines. Even when surrounded by good quality habitat, leks can be susceptible to extirpation due to isolation

A feasibility study for NOn-Traditional providers to support the management of Elderly People with Anxiety and Depression: the NOTEPAD study Protocol

BACKGROUND: Anxiety and depression are common among older people, with up to 20% reporting such symptoms, and the prevalence increases with co-morbid chronic physical health problems. Access to treatment for anxiety and depression in this population is poor due to a combination of factors at the level of patient, practitioner and healthcare system. There is evidence to suggest that older people with anxiety and/or depression may benefit both from one-to-one interventions and group social or educational activities, which reduce loneliness, are participatory and offer some activity. Non-traditional providers (support workers) working within third-sector (voluntary) organisations are a valuable source of expertise within the community but are under-utilised by primary care practitioners. Such a resource could increase access to care, and be less stigmatising and more acceptable for older people. METHODS: The study is in three phases and this paper describes the protocol for phase III, which will evaluate the feasibility of recruiting general practices and patients into the study, and determine whether support workers can deliver the intervention to older people with sufficient fidelity and whether this approach is acceptable to patients, general practitioners and the third-sector providers. Phase III of the NOTEPAD study is a randomised controlled trial (RCT) that is individually randomised. It recruited participants from approximately six general practices in the UK. In total, 100 participants aged 65 years and over who score 10 or more on PHQ9 or GAD7 for anxiety or depression will be recruited and randomised to the intervention or usual general practice care. A mixed methods approach will be used and follow-up will be conducted 12 weeks post-randomisation. DISCUSSION: This study will inform the design and methods of a future full-scale RCT. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN16318986 . Registered 10 November 2016. The ISRCTN registration is in line with the World Health Organization Trial Registration Data Set. The present paper represents the original version of the protocol. Any changes to the protocol will be communicated to ISRCTN

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Characterization and Regulation of the Osmolyte Betaine Synthesizing Enzymes GSMT and SDMT from Halophilic Methanogen Methanohalophilus portucalensis

The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize the osmolyte betaine de novo in response to extracellular salt stress. Betaine is generated by the stepwise methylation of glycine to form sarcosine, N, N-dimethylglycine and betaine by using S-adenosyl-L-methionine (AdoMet) as the methyl donor. The complete gene cluster of Mpgsmt-sdmt was cloned from Southern hybridization and heterologous expressed in E. coli respectively. The recombinant MpGSMT and MpSDMT both retained their in vivo functional activities in E. coli BL21(DE3)RIL to synthesize and accumulate betaine and conferred elevated survival ability in betaine transport deficient mutant E. coli MKH13 under high salt stress. The dramatic activating effects of sodium and potassium ions on the in vitro methyltransferase activities of MpGSMT, but not MpSDMT or bacterial GSMT and SDMT, revealed that GSMT from halophilic methanoarchaeon possesses novel regulate mechanism in betaine biosynthesis pathway. The circular dichroism spectra showed the fluctuated peaks at 206 nm were detected in the MpGSMT under various concentrations of potassium or sodium ions. This fluctuated difference may cause by a change in the β-turn structure located at the conserved glycine- and sarcosine-binding residue Arg167 of MpGSMT. The analytical ultracentrifugation analysis indicated that the monomer MpGSMT switched to dimeric form increased from 7.6% to 70% with KCl concentration increased from 0 to 2.0 M. The level of potassium and sodium ions may modulate the substrate binding activity of MpGSMT through the conformational change. Additionally, MpGSMT showed a strong end product, betaine, inhibitory effect and was more sensitive to the inhibitor AdoHcy. The above results indicated that the first enzymatic step involved in synthesizing the osmolyte betaine in halophilic archaea, namely, GSMT, may also play a major role in coupling the salt-in and compatible solute (osmolyte) osmoadaptative strategies in halophilic methanogens for adapting to high salt environments

Fibroid explants reveal a higher sensitivity against MDM2-inhibitor nutlin-3 than matching myometrium

<p>Abstract</p> <p>Background</p> <p>Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets.</p> <p>Methods</p> <p>We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14^Arfand used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's <it>t </it>test.</p> <p>Results</p> <p>An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14^Arfin the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of <it>BAX </it>as well as of <it>p21</it>, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers <it>BAX </it>and <it>p21</it>. Because as a rule fibroids express much higher levels of p14^Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium.</p> <p>Conclusions</p> <p>The results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.</p

An in silico model of the ubiquitin-proteasome system that incorporates normal homeostasis and age-related decline

BACKGROUND: The ubiquitin-proteasome system is responsible for homeostatic degradation of intact protein substrates as well as the elimination of damaged or misfolded proteins that might otherwise aggregate. During ageing there is a decline in proteasome activity and an increase in aggregated proteins. Many neurodegenerative diseases are characterised by the presence of distinctive ubiquitin-positive inclusion bodies in affected regions of the brain. These inclusions consist of insoluble, unfolded, ubiquitinated polypeptides that fail to be targeted and degraded by the proteasome. We are using a systems biology approach to try and determine the primary event in the decline in proteolytic capacity with age and whether there is in fact a vicious cycle of inhibition, with accumulating aggregates further inhibiting proteolysis, prompting accumulation of aggregates and so on. A stochastic model of the ubiquitin-proteasome system has been developed using the Systems Biology Mark-up Language (SBML). Simulations are carried out on the BASIS (Biology of Ageing e-Science Integration and Simulation) system and the model output is compared to experimental data wherein levels of ubiquitin and ubiquitinated substrates are monitored in cultured cells under various conditions. The model can be used to predict the effects of different experimental procedures such as inhibition of the proteasome or shutting down the enzyme cascade responsible for ubiquitin conjugation. RESULTS: The model output shows good agreement with experimental data under a number of different conditions. However, our model predicts that monomeric ubiquitin pools are always depleted under conditions of proteasome inhibition, whereas experimental data show that monomeric pools were depleted in IMR-90 cells but not in ts20 cells, suggesting that cell lines vary in their ability to replenish ubiquitin pools and there is the need to incorporate ubiquitin turnover into the model. Sensitivity analysis of the model revealed which parameters have an important effect on protein turnover and aggregation kinetics. CONCLUSION: We have developed a model of the ubiquitin-proteasome system using an iterative approach of model building and validation against experimental data. Using SBML to encode the model ensures that it can be easily modified and extended as more data become available. Important aspects to be included in subsequent models are details of ubiquitin turnover, models of autophagy, the inclusion of a pool of short-lived proteins and further details of the aggregation process

Modeling fomite-mediated SARS-CoV-2 exposure through personal protective equipment doffing in a hospital environment

Self-contamination during doffing of personal protective equipment (PPE) is a concern for healthcare workers (HCW) following SARS-CoV-2-positive patient care. Staff may subconsciously become contaminated through improper glove removal; so, quantifying this exposure is critical for safe working procedures. HCW surface contact sequences on a respiratory ward were modeled using a discrete-time Markov chain for: IV-drip care, blood pressure monitoring, and doctors’ rounds. Accretion of viral RNA on gloves during care was modeled using a stochastic recurrence relation. In the simulation, the HCW then doffed PPE and contaminated themselves in a fraction of cases based on increasing caseload. A parametric study was conducted to analyze the effect of: (1a) increasing patient numbers on the ward, (1b) the proportion of COVID-19 cases, (2) the length of a shift, and (3) the probability of touching contaminated PPE. The driving factors for the exposure were surface contamination and the number of surface contacts. The results simulate generally low viral exposures in most of the scenarios considered including on 100% COVID-19 positive wards, although this is where the highest self-inoculated dose is likely to occur with median 0.0305 viruses (95% CI =0–0.6 viruses). Dose correlates highly with surface contamination showing that this can be a determining factor for the exposure. The infection risk resulting from the exposure is challenging to estimate, as it will be influenced by the factors such as virus variant and vaccination rates

Contrasting Genetic Structure in Two Co-Distributed Species of Old World Fruit Bat

The fulvous fruit bat (Rousettus leschenaulti) and the greater short-nosed fruit bat (Cynopterus sphinx) are two abundant and widely co-distributed Old World fruit bats in Southeast and East Asia. The former species forms large colonies in caves while the latter roots in small groups in trees. To test whether these differences in social organization and roosting ecology are associated with contrasting patterns of gene flow, we used mtDNA and nuclear loci to characterize population genetic subdivision and phylogeographic histories in both species sampled from China, Vietnam and India. Our analyses from R. leschenaulti using both types of marker revealed little evidence of genetic structure across the study region. On the other hand, C. sphinx showed significant genetic mtDNA differentiation between the samples from India compared with China and Vietnam, as well as greater structuring of microsatellite genotypes within China. Demographic analyses indicated signatures of past rapid population expansion in both taxa, with more recent demographic growth in C. sphinx. Therefore, the relative genetic homogeneity in R. leschenaulti is unlikely to reflect past events. Instead we suggest that the absence of substructure in R. leschenaulti is a consequence of higher levels of gene flow among colonies, and that greater vagility in this species is an adaptation associated with cave roosting