Abstract
Cosponsoring Associations:
The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the ...Endocrine Society.
Objective:
To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA).
Participants:
The participants include an Endocrine Society–appointed task force of eight experts, a methodologist, and a medical writer.
Evidence:
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
Consensus Process:
One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline.
Conclusions:
FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.
FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof.
The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing ...combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures.
In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases.
Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting.
We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings.
COVID-19 Genomics UK (supported by UK Research and Innovation, the National Institute of Health Research, the Wellcome Sanger Institute), the Wellcome Trust, the Academy of Medical Sciences and the Health Foundation, and the National Institute for Health Research Cambridge Biomedical Research Centre.
The reliability and reproducibility of science are under scrutiny. However, a major cause of this lack of repeatability is not being considered: the wide sample-to-sample variability in the P value. ...We explain why P is fickle to discourage the ill-informed practice of interpreting analyses based predominantly on this statistic.
Palm oil is the most widely sold oil across the globe. The production of palm oil results in vast amounts of biomass waste. The palm kernel shells (PKS) can be used for energy production through ...gasification or combined heat and power (CHP). After gasification, some PKS remains as charred residue. In this manuscript, briquettes/pellets are produced from these biochars. The palm kernel shell biochars (PKSB) show very high calorific value exceeding typical values for biomass. The effects of water content, compaction pressure, feed particle size, compaction retention time, and the use of starch as a binder have been studied. The tensile crushing strength, impact resistance, and water resistance (immersion tests) show that the starch binder is imperative for suitable briquette quality. The use of starch increases the tensile crushing strength from less than 40 kN m−2 to more than 800 kN m−2 in the weakest (longitudinal) orientation. The tensile crushing strength of the starch-bound briquettes increases as their water content evaporates during storage and curing. It is speculated that the evaporation of water from the starch-bound sample allows for better cementing of the starch and PKSB particles.
•Palm kernel shell residues from a gasifier have been collected and reused.•The palm kernel shell biochar (PKSB) exhibits very high calorific value.•The PKSB is compacted with the use of starch binder.•The optimum densification pressure depends on the moisture content.•The briquette becomes stronger with prolonged curing time.
It has been hypothesized that cytoskeletal tension prevents large-scale phase separation within cell plasma membranes. Here, we microaspirate giant unilamellar vesicles to determine the effect of ...mechanical stress on the liquid/liquid miscibility temperature of a membrane composed of a ternary lipid mixture. An increase in tension of 0.1 mN/m induces a decrease in miscibility temperature on the order of a few tenths of a degree K, which validates recent theoretical predictions.
Malnutrition predicts poorer clinical outcomes for people with cancer. Older adults with cancer are a complex, growing population at high risk of weight-losing conditions. A number of malnutrition ...screening tools exist, however the best screening tool for this group is unknown. The aim was to systematically review the published evidence regarding markers and measures of nutritional status in older adults with cancer (age ≥ 70). A systematic search was performed in Ovid Medline, EMBASE, Web of Science, CINAHL, British Nursing Database and Cochrane CENTRAL; search terms related to malnutrition, cancer, older adults. Titles, abstracts and papers were screened and quality-appraised. Data evaluating ability of markers of nutritional status to predict patient outcomes were subjected to meta-analysis or narrative synthesis. Forty-two studies, describing 15 markers were included. Meta-analysis found decreased food intake was associated with mortality (OR 2.15 2.03-4.20 p = < 0.00001) in univariate analysis. Prognostic Nutritional Index (PNI) was associated with overall survival (HR 1.89 1.03-3.48 p = 0.04). PNI markers (albumin, total lymphocyte count) could be seen as markers of inflammation rather than nutrition. There a suggested relationship between very low body mass index (BMI) (<18 kg/m
) and clinical outcomes. No tool was identified as appropriate to screen for malnutrition, as distinct from inflammatory causes of weight-loss. Risk of cancer-cachexia and sarcopenia in older adults with cancer limits the tools analysed. Measures of food intake predicted mortality and should be included in clinical enquiry. A screening tool that distinguishes between malnutrition, cachexia and sarcopenia in older adults with cancer is needed.
Recent evidence has shown support for the United Nations Development Programme (UNDP) accelerator concept, which highlights the need to identify interventions or programmatic areas that can affect ...multiple sustainable development goals (SDGs) at once to boost their achievement. These data have also clearly shown enhanced effects when interventions are used in combination, above and beyond the effect of single interventions. However, detailed knowledge is now required on optimum combinations and relative gain in order to derive policy guidance. Which accelerators work for which outcomes, what combinations are optimum, and how many combinations are needed to maximise effect? The current study utilised pooled data from the Young Carers (n = 1402) and Child Community Care (n = 446) studies. Data were collected at baseline (n = 1848) and at a 1 to 1.5- year follow-up (n = 1740) from children and young adolescents aged 9-13 years, living in South Africa. Measures in common between the two databases were used to generate five accelerators (caregiver praise, caregiver monitoring, food security, living in a safe community, and access to community-based organizations) and to investigate their additive effects on 14 SDG-related outcomes. Predicted probabilities and predicted probability differences were calculated for each SDG outcome under the presence of none to five accelerators to determine optimal combinations. Results show that various accelerator combinations are effective, though different combinations are needed for different outcomes. Some accelerators ramified across multiple outcomes. Overall, the presence of up to three accelerators was associated with marked improvements over multiple outcomes. The benefit of targeting access to additional accelerators, with additional costs, needs to be weighed against the relative gains to be achieved with high quality but focused interventions. In conclusion, the current data show the detailed impact of various protective factors and provides implementation guidance for policy makers in targeting and distributing interventions to maximise effect and expenditure. Future work should investigate multiplicative effects and synergistic interactions between accelerators.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
8.
Disorders of synaptic vesicle fusion machinery Melland, Holly; Carr, Elysa M.; Gordon, Sarah L.
Journal of neurochemistry,
April 2021, 2021-04-00, 20210401, Letnik:
157, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The revolution in genetic technology has ushered in a new age for our understanding of the underlying causes of neurodevelopmental, neuromuscular and neurodegenerative disorders, revealing that the ...presynaptic machinery governing synaptic vesicle fusion is compromised in many of these neurological disorders. This builds upon decades of research showing that disturbance to neurotransmitter release via toxins can cause acute neurological dysfunction. In this review, we focus on disorders of synaptic vesicle fusion caused either by toxic insult to the presynapse or alterations to genes encoding the key proteins that control and regulate fusion: the SNARE proteins (synaptobrevin, syntaxin‐1 and SNAP‐25), Munc18, Munc13, synaptotagmin, complexin, CSPα, α‐synuclein, PRRT2 and tomosyn. We discuss the roles of these proteins and the cellular and molecular mechanisms underpinning neurological deficits in these disorders.
Disruption to the synaptic vesicle fusion machinery is increasingly being identified in the pathogenesis of neurodevelopmental, neuromuscular and neurodegenerative disorders. In this review, we cover disorders of synaptic vesicle fusion caused either by toxic insult to the presynapse or genetic mutation of the key proteins that control and regulate fusion: the SNARE proteins (synaptobrevin, syntaxin‐1 and SNAP‐25), Munc18, Munc13, synaptotagmin, complexin, CSPα, α‐synuclein, PRRT2 and tomosyn. We discuss the roles of these proteins and the cellular and molecular mechanisms underpinning neurological deficits in these disorders.
The membranes of the first protocells on the early Earth were likely self-assembled from fatty acids. A major challenge in understanding how protocells could have arisen and withstood changes in ...their environment is that fatty acid membranes are unstable in solutions containing high concentrations of salt (such as would have been prevalent in early oceans) or divalent cations (which would have been required for RNA catalysis). To test whether the inclusion of amino acids addresses this problem, we coupled direct techniques of cryoelectron microscopy and fluorescence microscopy with techniques of NMR spectroscopy, centrifuge filtration assays, and turbidity measurements. We find that a set of unmodified, prebiotic amino acids binds to prebiotic fatty acid membranes and that a subset stabilizes membranes in the presence of salt and Mg2+. Furthermore, we find that final concentrations of the amino acids need not be high to cause these effects; membrane stabilization persists after dilution as would have occurred during the rehydration of dried or partially dried pools. In addition to providing a means to stabilize protocell membranes, our results address the challenge of explaining how proteins could have become colocalized with membranes. Amino acids are the building blocks of proteins, and our results are consistent with a positive feedback loop in which amino acids bound to self-assembled fatty acid membranes, resulting in membrane stabilization and leading to more binding in turn. High local concentrations of molecular building blocks at the surface of fatty acid membranes may have aided the eventual formation of proteins.
Abstract
Background
Care homes are complex settings to undertake intervention research. Barriers to research implementation processes can threaten studies’ validity, reducing the value to residents, ...staff, researchers and funders. We aimed to (i) identify and categorise contextual factors that may mediate outcomes of complex intervention studies in care homes and (ii) provide recommendations to minimise the risk of expensive research implementation failures.
Methods
We conducted a systematic review using a framework synthesis approach viewed through a complex adaptive systems lens. We searched: MEDLINE, Embase, CINAHL, ASSIA databases and grey literature. We sought process evaluations of care home complex interventions published in English. Narrative data were indexed under 28 context domains. We performed an inductive thematic analysis across the context domains.
Results
We included 33 process evaluations conducted in high-income countries, published between 2005 and 2019. Framework synthesis identified barriers to implementation that were more common at the task and organisational level. Inductive thematic analysis identified (i) avoiding procedural drift and (ii) participatory action and learning as key priorities for research teams. Research team recommendations include advice for protocol design and care home engagement. Care home team recommendations focus on internal resources and team dynamics. Collaborative recommendations apply to care homes’ individual context and the importance of maintaining positive working relationships.
Discussion
Researchers planning and undertaking research with care homes need a sensitive appreciation of the complex care home context. Study implementation is most effective where an intervention is co-produced, with agreed purpose and adequate resources to incorporate within existing routines and care practices.
PDF
