The Thiamine diphosphate dependent Enzyme Engineering Database: A tool for the systematic analysis of sequence and structure relations

<p>Abstract</p> <p>Background</p> <p>Thiamine diphosphate (ThDP)-dependent enzymes form a vast and diverse class of proteins, catalyzing a wide variety of enzymatic reactions including the formation or cleavage of carbon-sulfur, carbon-oxygen, carbon-nitrogen, and especially carbon-carbon bonds. Although very diverse in sequence and domain organisation, they share two common protein domains, the pyrophosphate (PP) and the pyrimidine (PYR) domain. For the comprehensive and systematic comparison of protein sequences and structures the Thiamine diphosphate (ThDP)-dependent Enzyme Engineering Database (TEED) was established.</p> <p>Description</p> <p>The TEED <url>http://www.teed.uni-stuttgart.de</url> contains 12048 sequence entries which were assigned to 9443 different proteins and 379 structure entries. Proteins were assigned to 8 different superfamilies and 63 homologous protein families. For each family, the TEED offers multisequence alignments, phylogenetic trees, and family-specific HMM profiles. The conserved pyrophosphate (PP) and pyrimidine (PYR) domains have been annotated, which allows the analysis of sequence similarities for a broad variety of proteins. Human ThDP-dependent enzymes are known to be involved in many diseases. 20 different proteins and over 40 single nucleotide polymorphisms (SNPs) of human ThDP-dependent enzymes were identified in the TEED.</p> <p>Conclusions</p> <p>The online accessible version of the TEED has been designed to serve as a navigation and analysis tool for the large and diverse family of ThDP-dependent enzymes.</p

Why did an effective Dutch complex psycho-social intervention for people with dementia not work in the German healthcare context? Lessons learnt from a process evaluation alongside a multicentre RCT

Contains fulltext : 97517.pdf (publisher's version ) (Open Access)Background The positive effects of the Dutch Community Occupational Therapy in Dementia programme on patients' daily functioning were not found in a multicentre randomised controlled trial (RCT) in Germany. Objectives To evaluate possible effect modification on the primary outcome within the German RCT with regard to (1) participant characteristics, (2) treatment performance and (3) healthcare service utilisation; and (4) to compare the design and primary outcome between the German and the original Dutch study. Methods (1) The impact of participant baseline data on the primary outcome was analysed in exploratory ANCOVA and regression analyses. (2) Therapists completed questionnaires on context and performance problems. The main problems were identified by a qualitative content analysis and focus-group discussion. Associations of the primary outcome with scores of participant adherence and treatment performance were evaluated by regression analysis. (3) Utilisation rates of healthcare services were controlled for significant group differences. (4) Differences in the Dutch and German study design were identified, and the primary outcome was contrasted at the item level. Results (1) Participant characteristics could not explain more than 5% of outcome variance. (2) The treatment performance of some active intervention components was poor but not significantly associated with the primary outcome. (3) There were no significant group differences in the utilisation of healthcare resources. (4) In contrast to the Dutch waiting-control group, the active intervention in the German control group may have reduced group differences in the current RCT. The German patients demonstrated a higher independence at baseline and less improvement in instrumental activities of daily living. Conclusion The differences in outcome may be explained by a more active control treatment, partially poor experimental treatment and less room for improvement in the German sample. Future cross-national transfers should be prepared by pilot studies assessing the applicability of the intervention and patient needs specific to the target country. Trial registration International Clinical Trials Registry Platform, DRKS00000053

Reactivation during sleep with incomplete reminder cues rather than complete ones stabilizes long-term memory in humans

Reactivation by reminder cues labilizes memories during wakefulness, requiring reconsolidation to persist. In contrast, during sleep, cued reactivation seems to directly stabilize memories. In reconsolidation, incomplete reminders are more effective in reactivating memories than complete reminders by inducing a mismatch, i.e. a discrepancy between expected and actual events. Whether mismatch is likewise detected during sleep is unclear. Here we test whether cued reactivation during sleep is more effective for mismatch-inducing incomplete than complete reminders. We first establish that only incomplete but not complete reminders labilize memories during wakefulness. When complete or incomplete reminders are presented during 40-min sleep, both reminders are equally effective in stabilizing memories. However, when extending the retention interval for another 7 hours (following 40-min sleep), only incomplete but not complete reminders stabilize memories, regardless of the extension containing wakefulness or sleep. We propose that, during sleep, only incomplete reminders initiate long-term memory stabilization via mismatch detection.Fil: Forcato, Cecilia. Instituto Tecnológico de Buenos Aires. Departamento de Investigación y Doctorado; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Klinzing, Jens G.. Eberhard Karls Universität Tübingen; Alemania. University of Princeton; Estados UnidosFil: Carbone, Julia. Eberhard Karls Universität Tübingen; AlemaniaFil: Radloff, Michael. Eberhard Karls Universität Tübingen; AlemaniaFil: Weber, Frederik D.. Radboud Universiteit Nijmegen. Donders Instituto Brain Cognition and Behavior. SNN Machine Learning Group; Países BajosFil: Born, Jan. Eberhard Karls Universität Tübingen; AlemaniaFil: Diekelmann, Susanne. Eberhard Karls Universität Tübingen; Alemani

Demand satisfied by modern contraceptive among married women of reproductive age in Kenya

Background: Demand for family planning met/satisfied with modern contraceptive methods (mDFPS) has been proposed to track progress in Family Planning (FP) programs for Sustainable Development Goals. This study measured mDFPS among married women of reproductive age (MWRA) in Kenya to identify which groups were not being reached by FP programs. Materials and methods: Performance, Monitoring and Accountability 2020 (PMA2020) survey data from 2014–2018 was used. PMA2020 surveys are cross-sectional including women 15–49 years. PMA2020 used a 2-stage cluster design with urban/rural regions as strata with random selection of households. Univariate and multivariate analysis was done using stata V15. Results: Of the 34,832 respondents interviewed from 2014 to 2018, 60.2% were MWRA. There was a significant decrease in demand for FP from 2014 to 2018, p = 0.012. Lowest demand was among 15–19 and 45–49 years old women. Overall, modern contraceptive prevalence rate increased significantly from 54.6% to 60.8%, p = 0.004, being higher for women from urban areas, home visits by health care worker (HCW), educated, wealthy, visited health facilities and exposed to mass media. Unmet need for FP decreased from 23.0–13.8% over the 5-years, p\u3c0.001. Married adolescent 15–19 had the highest unmet need and those from rural areas, poor, uneducated and not exposed to mass media. mDFPS increased significantly from 69.7–79.4% over the 5-years, p\u3c0.001, with increase in long acting reversible contraception/permanent methods from 19.9–37.2% and decrease in short acting methods from 49.9–42.2%. Significant determinants of mDFPS were age, rural/urban residence, education, wealth, health facility visitation, exposure to FP messages via mass media in the last 12 months, year of study and county of residence. Conclusions: Results show a good progress in key FP indicators. However, not all MWRA are being reached and should be reached if Kenya is to achieve the desired universal health coverage as well as Sustainable Development Goals. Targeted home visits by HCW as well increase in mass media coverage could be viable interventions

Implementation of respondent driven sampling in Nairobi, Kenya, for tracking key family planning indicators among adolescents and youth: lessons learnt

Objective: Adolescents and youth constitute a significant proportion of the population in developing nations. Conventional survey methods risk missing adolescents/youth because their family planning/contraception (FP/C) behavior is hidden. Respondent-driven sampling (RDS), a modified chain-referral recruitment sampling approach, was used to reach unmarried adolescents/youth aged 15–24 in Nairobi, Kenya to measure key FP/C indicators. Seeds were selected and issued with three coupons which they used to invite their peers, male or female, to participate in the study. Referred participants were also given coupons to invite others till sample size was achieved. We report on key implementation parameters following standard RDS reporting recommendations. Results: A total of 1674 coupons were issued to generate a sample size of 1354. Coupon return rate was 82.7%. Study participants self-administered most survey questions and missing data was low. Differential enrolment by gender was seen with 56.0% of females recruiting females while 44.0% of males recruited males. In about two months, it was possible to reach the desired sample size using RDS methodology. Implementation challenges included presentation of expired coupons, recruitment of ineligible participants and difficulty recruiting seeds and recruits from affluent neighborhoods. Challenges were consistent with RDS implementation in other settings and populations. RDS can complement standard surveillance/survey approaches, particularly for mobile populations like adolescents/youth

Missed opportunities for family planning counselling among postpartum women in eleven counties in Kenya

Background: Mothers may access medical facilities for their babies and miss opportunities to access family planning (FP) services. This study was undertaken to describe missed opportunities for FP among women within the extended (0–11months) postpartum period from counties participating in Performance Monitoring and Accountability 2020 (PMA2020) surveys. Design and setting: This study analysed cross-sectional household survey data from 11 counties in Kenya between 2014 and 2018. PMA2020 uses questions extracted from the Demographic and Health survey (DHS) and DHS defnitions were used. Multivariable logistic regression was used for inferential statistics with p-value of \u3c0.05 considered to be signifcant. Participants: Women aged 15-49 years from the households visited. Primary outcome measure: Missed opportunity for family planning/contraceptives (FP/C) counselling. Results: Of the 34,832 women aged 15-49 years interviewed, 10.9% (3803) and 10.8% (3746) were in the period 0–11months and 12–23months postpartum respectively, of whom, 38.8 and 39.6% respectively had their previous pregnancy unintended. Overall, 50.4% of women 0-23months postpartum had missed opportunities for FP/C counselling. Among women who had contact with health care at the facility, 39.2% of women 0-11months and 44.7% of women 12-23months had missed opportunities for FP/C counselling. Less than half of the women 0-11months postpartum (46.5%) and 64.5% of women 12 – 23months postpartum were using highly efcacious methods. About 27 and 18% of the women 0-11months and 12 – 23months postpartum respectively had unmet need for FP/C. Multivariable analysis showed that being low parity and being from the low wealth quintile signifcantly increased the odds of missed opportunities for FP/C counselling among women in the extended postpartum period, p\u3c0.05. Conclusions: A large proportion of women have missed opportunities for FP/C counselling within 2 years postpartum. Programs should address these missed opportunities

Reproductive Biology of the Cape Honeybee: A Critique of Beekman et al: A critique of "Asexually Produced Cape Honeybee Queens (Apis mellifera capensis) Reproduce Sexually,” authors: Madeleine Beekman, Michael H. Allsopp, Julianne Lim, Frances Goudie, and Benjamin P. Oldroyd. Journal of Heredity. 2011:102(5):562-566

Laying workers of the Cape honeybee parthenogenetically produce female offspring, whereas queens typically produce males. Beekman et al. confirm this observation, which has repeatedly been reported over the last 100 years including the notion that natural selection should favor asexual reproduction in Apis mellifera capensis. They attempt to support their arguments with an exceptionally surprising finding that A. m. capensis queens can parthenogenetically produce diploid homozygous queen offspring (homozygous diploid individuals develop into diploid males in the honeybee). Beekman et al. suggest that these homozygous queens are not viable because they did not find any homozygous individuals beyond the third larval instar. Even if this were true, such a lethal trait should be quickly eliminated by natural selection. The identification of sex (both with molecular and morphological markers) is possible but notoriously difficult in honeybees at the early larval stages. Ploidy is however a reliable indicator, and we therefore suggest that these "homozygous” larvae found in queen cells are actually drones reared from unfertilized eggs, a phenomenon well known by honeybee queen breeder

A proposal for the retrospective identification and categorization of older people with functional impairments in scientific studies : recommendations of the Medication and Quality of Life in Frail Older Persons (MedQoL) research group

When treating older adults, a main factor to consider is physical frailty. Because specific assessments in clinical trials are frequently lacking, critical appraisal of treatment evidence with respect to functional status is challenging. Our aim was to identify and categorize assessments for functional status given in clinical trials in older adults to allow for a retrospective characterization and indirect comparison of treatment evidence from these cohorts. We conducted 4 separate systematic reviews of randomized and nonrandomized controlled clinical trials in older people with hypertension, diabetes, depression, and dementia. All assessments identified that reflected functional status were analyzed. Assessments were categorized across 4 different functional status levels. These levels span from functionally not impaired, slightly impaired, significantly impaired, to severely impaired/disabled. If available from the literature, cut-offs for these 4 functioning levels were extracted. If not, or if the existing cut-offs did not match the predefined functional levels, cut-off points were defined by an expert group composed of geriatricians, pharmacists, pharmacologists, neurologists, psychiatrists, and epidemiologists using a patient-centered approach. We identified 51 instruments that included measures of functional status. Although some of the assessments had clearly defined cut-offs across our predefined categories, many others did not. In most cases, no cut-offs existed for slightly impaired or severely impaired older adults. Missing cut-offs or values to adjust were determined by the expert group and are presented as described. The functional status assessments that were identified and operationalized across 4 functional levels could now be used for a retrospective characterization of functional status in randomized controlled trials and observational studies. Allocated categories only serve as approximations and should be validated head-to-head in future studies. Moreover, as general standard, upcoming studies involving older adults should include and explicitly report functional impairment as a baseline characteristic of all participants enrolled

Retardation of arsenic transport through a Pleistocene aquifer

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic. Holocene aquifers are the source of widespread arsenic poisoning across the region. In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up