Adaption and validation of the Rwandese version of the Young Mania Rating Scale to measure the severity of a manic or hypomanic episode.

BACKGROUND: Bipolar Disorder is one of the most incapacitating diseases among young persons, leading to cognitive and functional impairment and raised mortality, particularly death by suicide. Managing a manic episode and developing new and more effective treatment modalities requires sensitive and reliable instruments. This study aims to translate the English version of the YMRS questionnaire into Kinyarwanda, adapt it to the Rwandan context, and assess its validity. METHODS: The original English version of The Young Mania Rating Scale questionnaire was translated into Kinyarwanda. The translation process followed a standardized approach, including back-translation, cross-cultural adaptation, and final adjustments. A total of 130 inpatients with bipolar disorder in a manic episode from CARAES Ndera Teaching Hospital were included. The descriptive statistics and test-retest correlations were carried out, as well as the CFA for validation and Rasch-analysis. RESULTS: The Rwandese version of The Young mania rating scale had an adequate internal consistency (Cronbach's alpha = 0.90). Item 11 provided the lowest standardized loading in both ratings (0.51 and 0.55). The second lowest loading involved the highly correlated item pairs 5 & 9, with item 5 loading 0.51 in rating 1 and item 9 loading 0.57 in rating 2. The remaining loadings ranged from 0.59 to 0.79. This relatively narrow range indicated that a fit to a Rasch model was plausible if excluding item 11. CONCLUSION: The findings demonstrate that the translated YMRS, the R-YMRS, can be used as a reliable and valid instrument for assessing mania in the Rwandese population in clinical and research settings. However, the results supported using an unweighted total score of 32 and removing items 5, 9, and 11. Studies on this revised scale with an added interview guide for less-trained clinical staff are recommended.

Reactive molecular dynamics simulations of lithium-ion battery electrolyte degradation.

The development of reliable computational methods for novel battery materials has become essential due to the recently intensified research efforts on more sustainable energy storage materials. Here, we use a recently developed framework allowing to consistently incorporate quantum-mechanical activation barriers to classical molecular dynamics simulations to study the reductive solvent decomposition and formation of the solid electrolyte interphase for a graphite/carbonate electrolyte interface. We focus on deriving condensed-phase effective rates based on the elementary gas-phase reduction and decomposition energy barriers. After a short initial transient limited by the elementary barriers, we observe that the effective rate shows a transition to a kinetically slow regime influenced by the changing coordination environment and the ionic fluxes between the bulk electrolyte and the interface. We also discuss the impact of the decomposition on the ionic mobility. Thus, our work shows how elementary first-principles properties can be mechanistically leveraged to provide fundamental insights into electrochemical stability of battery electrolytes.

Adaption and validation of the Rwandese version of the Mood Disorder Questionnaire for the screening of bipolar disorder.

BACKGROUND: Bipolar disorder is challenging to diagnose. In Rwanda, a sub-Saharan country with a limited number of psychiatrists, the number of people with an undetected diagnosis of bipolar disorder could be high. Still, no screening tool for the disorder is available in the country. This study aimed to adapt and validate the Mood Disorder Questionnaire in the Rwandan population. METHODS: The Mood Disorder Questionnaire was translated into Kinyarwanda. The process involved back-translation, cross-cultural adaptation, field testing of the pre-final version, and final adjustments. A total of 331 patients with either bipolar disorder or unipolar major depression from two psychiatric outpatient hospitals were included. The statistical analysis included reliability and validity analyses and receiver operating characteristic curve (ROC) analysis. The optimal cut-off was chosen by maximizing Younden's index. RESULTS: The Rwandese version of The Mood Disorder Questionnaire had adequate internal consistency (Cronbach's alpha =0.91). The optimal threshold value was at least six positive items, which yielded excellent sensitivity (94.7%), and specificity (97.3%). The ROC area under the curve (AUC) was 0.99. CONCLUSION: The adapted tool showed good psychometric properties in terms of reliability and validity for the screening of bipolar disorder, with a recommended cutoff value of six items on the symptom checklist for a positive score and an exclusion of items 14 and 15. The tool has the potential to be a crucial instrument to identify otherwise undetected cases of bipolar disorder in Rwanda, improving access to mental health treatment, thus enhancing the living conditions of people with bipolar disorder.

Group psychoeducation for persons with bipolar disorder in Rwanda: a study protocol for a randomized controlled trial.

BACKGROUND: The efficacy of psychoeducation as an add-on treatment to pharmacotherapy is well documented in treating symptoms and in relapse prevention for persons with bipolar disorder in western countries. Yet, no studies on psychosocial interventions for persons with bipolar disorder have been conducted in a low-income country in Africa. AIM: To develop a bipolar group psychoeducation program contextualized to the Rwandese setting, and determine its effect on symptom severity, medical adherence, and internalized stigma. METHODS: A culturally adapted guide manual was developed by local mental health professionals, including nurses, psychologists, and medical doctors. In-depth interviews with participants were held prior to and will be held following the intervention to address the cultural aspect of living with bipolar disease and the impact of the program. A two-armed randomized controlled trial has been set up at the tertiary mental health hospitals in Rwanda, with an intervention and a waiting list arm. A sample size of at least 50 in each arm was calculated as a requirement. The study's primary outcome measure will be the difference in relapse rate measured on the Young Mania Rating Scale and Hamilton Depression Scale-17. Differences in mean change on scales for medical adherence and internalized stigma will be secondary outcomes. Data will be analyzed according to the intention-to-treat principle. Participants will be assessed subsequently at baseline, at the end of the intervention period, and three months and 12 months post-intervention. DISCUSSION: This study will be one of the first intervention trials on bipolar disorder in a low-income country. If proven successful in reducing morbidity and increasing the quality of life in persons with bipolar disorder, it is anticipated that the psychoeducation program can be implemented at the district and community level and act as inspiration for other low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04671225. Registered on November 2020.

Intervention trials for adults with bipolar disorder in low-income and lower-middle-income countries: A systematic review.

BACKGROUND: The treatment gap for bipolar disorder is aggravated by economic inequality. Around half of the world's population live in a low-or lower-middle-income country, where research on treatment is scarce. Hence, this review aims to determine the number and types of intervention studies conducted on adults with bipolar disorder in low-income and lower-middle-income countries and analyze the effect of these interventions on symptom severity, medical adherence, and quality of life. METHODS: A systematic review was conducted in June and November 2021 using eight databases. Controlled intervention trials on adults with bipolar disorder on data from low-income and lower-middle-income countries at time of publication were included. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or The Risk Of Bias In Non-randomized Studies of Interventions assessment tool. RESULTS: Twenty-one studies met the inclusion criteria. These were divided into four subtypes based on the intervention; pharmacotherapy (=12), psychosocial (=7), electroconvulsive therapy (=1), and traditional medicine (=1). Three studies were from low-income countries. A high risk of bias characterized the studies; only four studies reported the procedures used for randomization. Most studies, however, identified a beneficial effect on symptom severity, and in addition, medical adherence could be improved with psychosocial interventions. LIMITATIONS: Heterogeneity across studies prevented any meaningful pooling of data to meta-analyses. CONCLUSION: Data for treatment interventions contextualized to the local setting for bipolar disorder remains sparse, particularly from low-resource settings. Further studies are urgently needed to target the treatment gap for bipolar disorder. TRIAL REGISTRATION: PROSPERO: CRD42020170953.

Detection of haplosporidian protistan parasites supports an increase to their known diversity, geographic range and bivalve host specificity.

Haplosporidian protist parasites are a major concern for aquatic animal health, as they have been responsible for some of the most significant marine epizootics on record. Despite their impact on food security, aquaculture and ecosystem health, characterizing haplosporidian diversity, distributions and host range remains challenging. In this study, water filtering bivalve species, cockles Cerastoderma edule, mussels Mytilus spp. and Pacific oysters Crassostrea gigas, were screened using molecular genetic assays using deoxyribonucleic acid (DNA) markers for the Haplosporidia small subunit ribosomal deoxyribonucleic acid region. Two Haplosporidia species, both belonging to the Minchinia clade, were detected in C. edule and in the blue mussel Mytilus edulis in a new geographic range for the first time. No haplosporidians were detected in the C. gigas, Mediterranean mussel Mytilus galloprovincialis or Mytilus hybrids. These findings indicate that host selection and partitioning are occurring amongst cohabiting bivalve species. The detection of these Haplosporidia spp. raises questions as to whether they were always present, were introduced unintentionally via aquaculture and or shipping or were naturally introduced via water currents. These findings support an increase in the known diversity of a significant parasite group and highlight that parasite species may be present in marine environments but remain undetected, even in well-studied host species.

A genomic Neolithic time transect of hunter-farmer admixture in central Poland.

Ancient DNA genome-wide analyses of Neolithic individuals from central and southern Europe indicate an overall population turnover pattern in which migrating farmers from Anatolia and the Near East largely replaced autochthonous Mesolithic hunter-gatherers. However, the genetic history of the Neolithic transition in areas lying north of the European Neolithic core region involved different levels of admixture with hunter-gatherers. Here we analyse genome-wide data of 17 individuals spanning from the Middle Neolithic to the Early Bronze Age (4300-1900 BCE) in order to assess the Neolithic transition in north-central Poland, and the local impacts of hunter-farmer contacts and Late Neolithic steppe migrations. We evaluate the influence of these on local populations and assess if and how they change through time, reporting evidence of recurrent hunter-farmer admixture over three millennia, and the co-existence of unadmixed hunter-gatherers as late as 4300 BCE. During the Late Neolithic we report the appearance of steppe ancestry, but on a lesser scale than previously described for other central European regions, with evidence of stronger affinities to hunter-gatherers than to steppe pastoralists. These results help understand the Neolithic palaeogenomics of another central European area, Kuyavia, and highlight the complexity of population interactions during those times.

High prevalence of Seoul hantavirus in a breeding colony of pet rats.

As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.

Psychoeducational groups for adults with ADHD and their significant others (PEGASUS): A pragmatic multicenter and randomized controlled trial.

OBJECTIVE: To examine the feasibility, efficacy, and effectiveness of PEGASUS, a group-based structured psychoeducation for adults with ADHD and their significant others. METHOD: A pragmatic parallel group add-on design multicenter randomized controlled trial was conducted, comparing an 8-session treatment with PEGASUS (allocated n=97; 48 with ADHD and 49 with significant others) to treatment as usual (TAU, allocated n=82; 39 with ADHD and 43 significant others). Participants (individuals with ADHD and significant others) were recruited from five psychiatric outpatient departments and block randomized to PEGASUS or TAU. Knowledge about ADHD was measured using the ADHD 20 scale pre- and post-intervention and served as primary outcome. RESULTS: Knowledge about ADHD (d=0.97 [95% CI: 0.61-1.31]) increased following PEGASUS participation compared to TAU. Improvements were also observed in secondary outcomes e.g. global life satisfaction (d=0.25 [95% CI: from -0.09 to 0.59]). Overall treatment satisfaction was good. Over 90% of the participants completed the program. Post-intervention data was obtained from n=89 in PEGASUS group and n=70 in TAU group and analyses were conducted per protocol. No important adverse effects or side effects were observed. CONCLUSIONS: Group-based structured psychoeducation PEGASUS for adults with ADHD and their significant others is a feasible, efficacious, and effective treatment option to increase ADHD knowledge and general life satisfaction in psychiatric outpatient care.

An eDNA assay for Irish Petromyzon marinus and Salmo trutta and field validation in running water.

This pilot study presents an environmental DNA (eDNA) assay for sea lamprey Petromyzon marinus and brown trout Salmo trutta, two species of economic and conservation importance in the Republic of Ireland. The results demonstrate the effectiveness of eDNA for assessing presence of low-abundance taxa (here, P. marinus) for environmental managers, and they highlight the potential for assessing relative abundance of rare or invasive freshwater species.

Influence of grazing management on claw disorders in Swedish freestall dairies with mandatory grazing.

Our hypothesis was that grazing time, the number of days (duration) and number of hours per day, affected claw health. From Swedish freestall herds that fulfilled our criteria of claw-trimming routines, 201 herds were randomly selected for a telephone interview regarding grazing management. Herd data were retrieved from the Swedish Official Milk Recording Scheme. Claw disorders to be analyzed were recorded at maintenance claw trimming before and after the grazing period and included mild and severe dermatitis, severe heel-horn erosion, and sole ulcer (including severe sole hemorrhage). Any remark included one or more of these recorded disorders. The odds for having a recorded claw disorder at the autumn trimming in relation to grazing management, as well as to herd- and cow-related parameters, was tested using multilevel logistic regression models. The final statistical analysis included 17,600 cows in 174 herds, which were distributed from the south to the north of Sweden with decreasing length of mandatory grazing period because of climate. Grazing duration was statistically associated with the risk of sole ulcer, but it was not linear. However, grazing duration was not statistically associated with the odds for any remark, dermatitis, or heel-horn erosion. The odds for dermatitis were lower with access to pasture for 24 h compared with either day or night access. Otherwise, the number of hours that the animals had access to grazing per day was not significantly associated with any of the other analyzed claw disorders. Higher pasture stocking density (number of cow hours per day per hectare) was associated with a higher odds for dermatitis and sole ulcer. For all recorded claw disorders, the highest odds for having a disorder after the grazing period were consistently when the cow had the same claw disorder before the release to pasture. The positive effects of grazing on claw health were less than expected, and the previous known effects of breed, days in milk, parity, production system, housing environment, and management were verified for most claw disorders. If cows in today's loose housing systems have a more restrictive grazing than cows in tie-stall herds previously experienced, one cannot expect as strong an effect even if grazing is mandatory in all Swedish dairy cattle. Despite some positive effects of grazing, good stall environment and management during the housing period seem to be more important to obtain good claw health.

Seoul hantavirus in brown rats in the Netherlands: implications for physicians--Epidemiology, clinical aspects, treatment and diagnostics.

The recent discovery of Seoul hantavirus (SEOV) presence in wild rat populations in the Netherlands has direct implications for Dutch clinicians and hantavirus diagnostics. SEOV is amongst the Old World hantaviruses which cause haemorrhagic fever and renal syndrome (HFRS) in humans. HFRS is characterised by a classical triad of fever, acute kidney injury and haemorrhage, but can show different signs and symptoms in specific cases. SEOV is transmitted from infected rats to humans by inhalation of aerosolised excreta. When compared with the known circulating hantaviruses in the Netherlands, Puumala (PUUV) and Tula (TULV), SEOV causes a more severe form of HFRS. Data from cohort studies undertaken in China and Northern Europe show differences in signs and symptoms at onset of disease, (haemorrhagic) complications and mortality. Furthermore, routine diagnostics currently available for hantavirus diagnosis in the Netherlands are not optimised for SEOV detection. The clinical outcome of an SEOV and PUUV infection will greatly benefit from an early diagnosis which will reduce the costs of unnecessary tests and treatments as well. The discovery of SEOV circulation in the Netherlands follows recent findings of SEOV infections in both rodents and humans in England, Wales, France, Belgium and Sweden, indicating the emerging character of SEOV and a high importance of this hantavirus for Public Health in large areas of Europe. Here, we review the current knowledge on the clinical manifestation of SEOV versus PUUV infections in humans, the treatment of clinical cases and diagnostics.

Isolation and characterization of 13 polymorphic microsatellite loci in Hypostomus ancistroides (Teleostei, Loricariidae) and cross-amplification in related species.

This study details 13 novel polymorphic microsatellite loci in the armoured catfish Hypostomus ancistroides, and assesses their utility for population genetic studies. The analysis of 30 individuals revealed a total of 99 different alleles (ranging from two to 15 alleles per locus), with an average of 7·62 alleles per locus, with observed and expected heterozygosities ranging from 0·103 to 0·931 and from 0·102 to 0·906, respectively. One of the 13 loci showed significant deviations from Hardy-Weinberg equilibrium, probably due to the presence of null alleles, inferred from the excess of homozygotes.

Prognostic significance of YWHAZ expression in localized prostate cancer.

BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa. METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were used to assess the prognostic value of YWHAZ intensity. RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P < 0.001) and PSA relapse (P = 0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P = 0.002) and reduced survival time (P = 0.002). CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.

The hanta hunting study: underdiagnosis of Puumala hantavirus infections in symptomatic non-travelling leptospirosis-suspected patients in the Netherlands, in 2010 and April to November 2011.

Leptospirosis and haemorrhagic fever with renal syndrome (HFRS) are hard to distinguish clinically since these two important rodent-borne zoonoses share hallmark symptoms such as renal failure and haemorrhage. Leptospirosis is caused by infection with a spirochete while HFRS is the result of an infection with certain hantaviruses. Both diseases are relatively rare in the Netherlands. Increased incidence of HFRS has been observed since 2007 in countries that border the Netherlands. Since a similar rise in incidence has not been registered in the Netherlands, we hypothesise that due to overlapping clinical manifestations, hantavirus infections may be confused with leptospirosis, leading to underdiagnosis. Therefore, we tested a cohort of non-travelling Dutch patients with symptoms compatible with leptospirosis, but with a negative diagnosis, during 2010 and from April to November 2011. Sera were screened with pan-hantavirus IgG and IgM enzyme-linked immunosorbent assays (ELISAs). Sera with IgM reactivity were tested by immunofluorescence assay (IFA). ELISA (IgM positive) and IFA results were confirmed using focus reduction neutralisation tests (FRNTs). We found hantavirus-specific IgG and/or IgM antibodies in 4.3% (11/255) of samples taken in 2010 and in 4.1% (6/146) of the samples during the 2011 period. After FRNT confirmation, seven patients were classed as having acute Puumala virus infections. A review of hantavirus diagnostic requests revealed that at least three of the seven confirmed acute cases as well as seven probable acute cases of hantavirus infection were missed in the Netherlands during the study period.

Serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants.

BACKGROUND AND PURPOSE: Although serine proteases and agonists of protease-activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of proteases that are activated by proinflammatory and algesic stimuli and their contribution to inflammatory pain are uncertain. EXPERIMENTAL APPROACH: Enzymic assays and selective inhibitors were used to characterize protease activity in mice after intraplantar injections of formalin, bradykinin, PAR2 activating peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was determined. Protease inhibitors and par2 (-/-) mice were used to assess the contributions of proteases and PAR2 to pain and inflammation. KEY RESULTS: Intraplantar injection of formalin, bradykinin or PAR2-AP led to the activation of proteases that were susceptible to the serine protease inhibitor melagatran but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved PAR2-derived peptides. These proteases and trypsin 4 increased [Ca(2+) ]i in PAR2-transfected but not in untransfected cells, and melagatran suppressed this activity. Melagatran or PAR2 deletion suppressed oedema and mechanical hypersensitivity induced by intraplantar formalin, bradykinin and PAR2-AP, but had no effect on capsaicin-induced pain. CONCLUSIONS AND IMPLICATIONS: Diverse proinflammatory and algesic agents activate melagatran-sensitive serine proteases that cause inflammation and pain by a PAR2-mediated mechanism. By inducing self-activating proteases, PAR2 amplifies and sustains inflammation and pain. Serine protease inhibitors can attenuate the inflammatory and algesic effects of diverse stimuli, representing a useful therapeutic strategy.

The health status of mussels, Mytilus spp., in Ireland and Wales with the molecular identification of a previously undescribed haplosporidian.

Both wild and cultured mussels (Mytilus edulis, Mytilus galloprovincialis and hybrids), are found along most of the Irish coastline. M. edulis is widespread along all Irish coasts and is the only mussel species present on both the east coast of Ireland and the Welsh coast in the Irish Sea. M. galloprovincialis and hybrids are found along the Irish coastline except for the east coast. Samples of Mytilus spp. were collected from twenty-four sites, encompassing all coasts of Ireland and the Welsh coast, at different times of the year and over several years (2008-2011). In total, 841 mussels were examined histologically to assess their health status and the presence of any parasites or commensals. Mussels from 14 of the 24 sites were screened using polymerase chain reaction (PCR) to determine which mytilid species were present. A range of parasites were observed, generally at low levels. The most diverse community of parasites was observed at a sheltered site with poor water quality. Of significance, a previously undescribed haplosporidian was detected in a single mussel sample in the Menai Strait, Wales, by PCR and was confirmed by direct sequencing and is most closely related to Minchina chitonis and a haplosporidian of the Florida marsh clam Cyrenoida floridana. While M. edulis were infected by a variety of micro- and macro-parasites, only trematodes were observed in M. galloprovincialis and hybrids. Habitat description and the environmental factors influencing the study sites, including water quality and exposure, were recorded.

Rapid, economical single-nucleotide polymorphism and microsatellite discovery based on de novo assembly of a reduced representation genome in a non-model organism: a case study of Atlantic cod Gadus morhua.

By combining next-generation sequencing technology (454) and reduced representation library (RRL) construction, the rapid and economical isolation of over 25 000 potential single-nucleotide polymorphisms (SNP) and >6000 putative microsatellite loci from c. 2% of the genome of the non-model teleost, Atlantic cod Gadus morhua from the Celtic Sea, south of Ireland, was demonstrated. A small-scale validation of markers indicated that 80% (11 of 14) of SNP loci and 40% (6 of 15) of the microsatellite loci could be amplified and showed variability. The results clearly show that small-scale next-generation sequencing of RRL genomes is an economical and rapid approach for simultaneous SNP and microsatellite discovery that is applicable to any species. The low cost and relatively small investment in time allows for positive exploitation of ascertainment bias to design markers applicable to specific populations and study questions.

Extracting insights from the shape of complex data using topology.

This paper applies topological methods to study complex high dimensional data sets by extracting shapes (patterns) and obtaining insights about them. Our method combines the best features of existing standard methodologies such as principal component and cluster analyses to provide a geometric representation of complex data sets. Through this hybrid method, we often find subgroups in data sets that traditional methodologies fail to find. Our method also permits the analysis of individual data sets as well as the analysis of relationships between related data sets. We illustrate the use of our method by applying it to three very different kinds of data, namely gene expression from breast tumors, voting data from the United States House of Representatives and player performance data from the NBA, in each case finding stratifications of the data which are more refined than those produced by standard methods.