Factors associated with long hospitalisation for psychotic disorder patients in an acute ward: Tertiary care hospital.

Background: The average length of stay is often used to indicate health system efficiency; shorter stays are associated with reduced costs. In South Africa, mental healthcare expenditure is spent on inpatient care. Aim: To identify factors associated with a long stay in an acute psychiatric unit. Setting: A tertiary hospital. Methods: A case-control study review of inpatients diagnosed with psychotic symptoms was used. Sample was divided into two groups, length of stay (LOS) (LOS greater than 21 days, LOS less than 14 days). Total of 82 patients were divided into short stay group (SSG, n = 23) and long stay group (LSG) (n = 59). A comparison of demographic, clinical and system variables was conducted. Results: In demographics, LSG had fewer men compared to SSG (78.3%) and differed statistically from LSG with p = 0.05. Long stay groups were older in comparison to SSG with a p = 0.02. Illicit substance use in LSG was 44.1% and statistically less than SSG (73.91%; p = 0.02). A high proportion of LSG had medical or surgical and psychiatric comorbidities (67.8%) compared to SSG (43.5%) (p = 0.04). A total of 95% patients in SSG had family support. Conclusion: Longer stay was found to be associated with older females with primary psychotic disorders. Comorbidities with less availability of family support were associated with younger males presenting with psychotic symptoms that may be related to illicit substances that respond to rapid stabilisation. Contribution: Active surveillance of medical comorbidities amongst older female patients is necessary for early liaison services to reduce their length of stay.

Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org . Each genome was constructed using a novel assembly tool called Viridian ( https://github.com/iqbal-lab-org/viridian ), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

Bulk Nanostructure of Mixtures of Choline Arginate, Choline Lysinate, and Water.

Neutron diffraction with empirical potential structure refinement was used to investigate the bulk liquid nanostructure of mixtures of choline arginate (Ch[Arg]), choline lysinate (Ch[Lys]), and water at mole ratios of 1Ch[Arg]:1Ch[Lys]:6H2O (balanced), 1Ch[Arg]:1Ch[Lys]:20H2O (balanced dilute), 3Ch[Arg]:1Ch[Lys]:12H2O (Arg- rich), and 1Ch[Arg]:3Ch[Lys]:12H2O (Lys- rich). The Arg- and Lys- anions tend not to associate due to electrostatic repulsion between charge groups and weak anion-anion attractions. This means that the local ion structures around the anions in these mixtures resemble the parent single-component systems. The bulk liquid nanostructure varies with the Arg-:Lys- ratio. In the Lys--rich mixture (1Ch[Arg]:3Ch[Lys]:12H2O), Lys- side chains cluster into a continuous apolar domain separated from a charged domain of polar groups. In the balanced mixture (1Ch[Arg]:1Ch[Lys]:6H2O), Lys- side chains form discrete apolar aggregates within a continuous polar domain of Arg-, Ch+, and water, and in the Arg--rich mixture (3Ch[Arg]:1Ch[Lys]:12H2O), the distribution of Lys- and Arg- is nearly homogeneous. Finally, in the balance dilute system (1Ch[Arg]:1Ch[Lys]:20H2O), a percolating water domain forms.

Anaesthesia praCtice for Caesarean dElivery Snapshot Study (ACCESS): Protocol and baseline characteristics of registered centres.

BACKGROUND: Specific guidelines to manage caesarean delivery anaesthesia are lacking. A European multicentre study, ACCESS investigates caesarean delivery anaesthesia management in European centres. In order to identify ACCESS participating centres, a registration survey was created. OBJECTIVE: The aim of the current report is to describe the characteristics of ACCESS study participating centres, the rationale for the ACCESS study and the study methodology. DESIGN AND SETTING: The ACCESS study is a European multicentre cross-sectional study to describe anaesthesia management for caesarean delivery (CD) using a snapshot (2-week) design. The ACCESS registration survey gathered: contact details for National Coordinators (NC); Lead Investigators (LI) per centre; centre annual CD volume; expected no. of CD during 2-week snapshot window; centre practice information; data collection language. The ACCESS registration survey was launched July 2022 (Google Forms, Google Inc., Mountain View, CA, USA) and distributed through personal connections, national and international societies, social media networks, during Euroanaesthesia 2023, through the European Society of Anaesthesiology and Intensive Care newsletter. RESULTS: The ACCESS registration survey identified Lead Investigators for 418 centres, in 32 countries, representing an anticipated number of 15,073 CD cases over the planned 12-month study period. A median (range) of 20 (2 to 400) CD cases are anticipated per centre during the 2-week snapshot window. Most 366/418 (87.6%) centres are small, ≤2000 annual CD cases, 42 are medium 2000-5000 cases and 10 are large, ≥5000 annual CD cases. Registered centres reported in 134 (32.0%) centres that anaesthesia for caesarean delivery is performed mostly by a specialist obstetric anaesthesiologist. CONCLUSION: The ACCESS registration survey revealed variability in volume and CD practice as well as training-levels and staffing among European countries. The ACCESS study (https://www.access-study.org/) aims to generate practice data to guide CD anaesthetic management strategies.

The role of environmental gradients and microclimates in structuring communities and functional groups of lizards in a rainforest-savanna transition area.

Environmental heterogeneity poses a significant influence on the functional characteristics of species and communities at local scales. Environmental transition zones, such as at the savanna-forest borders, can act as regions of ecological tension when subjected to sharp variations in the microclimate. For ectothermic organisms, such as lizards, environmental temperatures directly influence physiological capabilities, and some species use different thermoregulation strategies that produce varied responses to local climatic conditions, which in turn affect species occurrence and community dynamics. In the context of global warming, these various strategies confer different types of vulnerability as well as risks of extinction. To assess the vulnerability of a species and understand the relationships between environmental variations, thermal tolerance of a species and community structure, lizard communities in forest-savanna transition areas of two national parks in the southwestern Amazon were sampled and their thermal functional traits were characterized. Then, we investigated how community structure and functional thermal variation were shaped by two environmental predictors (i.e., microclimates estimated locally and vegetation structure estimated from remote sensing). It was found that the community structure was more strongly predicted by the canopy surface reflectance values obtained via remote sensing than by microclimate variables. Environmental temperatures were not the most important factor affecting the occurrence of species, and the variations in ecothermal traits demonstrated a pattern within the taxonomic hierarchy at the family level. This pattern may indicate a tendency for evolutionary history to indirectly influence these functional features. Considering the estimates of the thermal tolerance range and warming tolerance, thermoconformer lizards are likely to be more vulnerable and at greater risk of extinction due to global warming than thermoregulators. The latter, more associated with open environments, seem to take advantage of their lower vulnerability and occur in both habitat types across the transition, potentially out-competing and further increasing the risk of extinction and vulnerability of forest-adapted thermoconformer lizards in these transitional areas.

Imaging spectrum of atraumatic muscle disorders: a radiologist's guide.

Atraumatic muscle disorders comprise a very wide range of skeletal muscle diseases, including metabolic, inflammatory, autoimmune, infectious, ischemic, and neoplastic involvement of the muscles. Therefore, one must take clinical and laboratory data into consideration to elucidate the differential diagnoses, as well as the distribution of the muscle compromise along the body-whether isolated or distributed along the body in a symmetric or asymmetrical fashion. Assessment of muscular disorders often requires imaging investigation before image-guided biopsy or more invasive procedures; therefore, radiologists should understand the advantages and limitations of imaging methods for proper lesion evaluation and be aware of the imaging features of such disorders, thus contributing to proper decision-making and good patient outcomes. In this review, we propose a systematic approach for the assessment of muscle disorders based on their main imaging presentation, dividing them into patterns that can be easily recognized.

Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Pathophysiology of chikungunya virus infection associated with fatal outcomes.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.

Present and Future of Blood-Based Biomarkers of Alzheimer's Disease: Beyond the Classics.

The field of blood-based biomarkers for Alzheimer's disease (AD) has advanced at an incredible pace, especially after the development of sensitive analytic platforms that can facilitate large-scale screening. Such screening will be important when more sophisticated diagnostic methods are scarce and expensive. Thus, blood-based biomarkers can potentially reduce diagnosis inequities among populations from different socioeconomic contexts. This large-scale screening can be performed so that older adults at risk of cognitive decline assessed using these methods can then undergo more complete assessments with classic biomarkers, increasing diagnosis efficiency and reducing costs to the health systems. Blood-based biomarkers can also aid in assessing the effect of new disease-modifying treatments. This paper reviews recent advances in the area, focusing on the following leading candidates for blood-based biomarkers: amyloid-beta (Aß), phosphorylated tau isoforms (p-tau), neurofilament light (NfL), and glial fibrillary acidic (GFAP) proteins, as well as on new candidates, Neuron-Derived Exosomes contents (NDEs) and Transactive response DNA-binding protein-43 (TDP-43), based on data from longitudinal observational cohort studies. The underlying challenges of validating and incorporating these biomarkers into routine clinical practice and primary care settings are also discussed. Importantly, challenges related to the underrepresentation of ethnic minorities and socioeconomically disadvantaged persons must be considered. If these challenges are overcome, a new time of cost-effective blood-based biomarkers for AD could represent the future of clinical procedures in the field and, together with continued prevention strategies, the beginning of an era with a lower incidence of dementia worldwide.

Amazonian useful plants described in the book "Le Pays des Amazones" (1885) of the Brazilian propagandist Baron de Santa-Anna Nery: a historical and ethnobotanical perspective.

BACKGROUND: Frederico José de Santa-Anna Nery (1848-1901) was a Brazilian Baron who referred to himself as a "volunteer propagandist" for Brazil in Europe, serving as an immigration agent to publicize the living conditions in the Amazon region, advocating for its development and modernization at the end of the nineteenth century. Santa-Anna Nery's most famous book is "Le Pays des Amazones" (The Lands of the Amazons), first published in 1885, which the author dedicated a chapter to introduce and report on the Amazonian useful plant species and its relationship with humans. The aim of this work is to understand the historical context and ethnobotanical value of the plant species in the Brazilian Amazon at the end of the nineteenth century through an analysis of the book "Le Pays des Amazones" (1885) by Baron de Santa-Anna Nery, as well as to bring to light the historical importance of this very influential propagandist, who has been forgotten nowadays. METHODS: The original book "Le Pays des Amazones" (1885), as well as the original 3rd edition and its translated version into Portuguese, was carefully analyzed and all information about plants was systematized, with botanical names being updated. Finally, using the scientific name of medicinal plants alone or in combination with their traditional use, a search was carried out in databases in order to indicate current pharmacological studies that provide evidence about the described traditional uses. RESULTS: A total of 156 plant species were identified in the book, although 132 species had their scientific names updated. These species belong to 45 different families, with Fabaceae and Arecaceae the most represented, and 109 plants are Brazilian native. Considering only the 36 medicinal plants, the main medicinal indications reported were astringent, purgative/laxative, stimulant and tonic, vermifuge, febrifuge, sudorific, emetic, diuretic and antidysenteric. Regarding other useful plants (non-medicinal), 97 species were cited for food, constructions and buildings, spices and condiments, ornaments and objects, carpentry, textile fibers, gums, oils, balms and essences, pigments and tanning, hunting and fishing. CONCLUSIONS: When the book "Le Pays des Amazones" is analyzed from a timeless perspective, with a particular focus on historical ethnobotany, it is possible to observe the economic, social, and political importance of many useful plants for the Amazon at the end of the nineteenth century and how the relationship between local people, indigenous communities, and immigrants was established with plant biodiversity.

Probabilistic Intersection-Over-Union for Training and Evaluation of Oriented Object Detectors.

Oriented object detection is a challenging and relatively new problem. Most existing approaches are based on deep learning and explore Oriented Bounding Boxes (OBBs) to represent the objects. They are typically based on adaptations of traditional detectors that work with Horizontal Bounding Boxes (HBBs), which have been exploring IoU-like loss functions to regress the HBBs. However, extending this idea for OBBs is challenging due to complex formulations or requirement for customized backpropagation implementations. Furthermore, using OBBs presents limitations for irregular or roughly circular objects, since the definition of the ideal OBB is an ambiguous and ill-posed problem. In this work, we jointly tackle the problem of training, representing, and evaluating oriented detectors. We explore Gaussian distributions-called Gaussian Bounding Boxes (GBBs)-as fuzzy representations for oriented objects and propose using a similarity metric between two GBBs based on the Hellinger distance. We show that this metric leads to a differentiable closed-form expression that can be directly used as a localization loss term to train OBB object detectors. We also show that GBBs present a natural representation as elliptical regions (called EBBs), which inherently mitigate ambiguity representation for circular objects. Finally, we empirically show that the proposed similarity metric computed between two GBBs strongly correlates with the IoU between the corresponding EBBs, motivating the name Probabilistic Intersection-over-Union (ProbIoU). Our experiments show that results using ProbIoU as a regression loss are competitive with state-of-the-art alternatives without requiring additional hyperparameters or customized implementations, and that ProbIoU is a promising alternative to evaluate oriented object detectors. Our code is available at https://github.com/ProbIOU/.

Negative allosteric modulation of CB1 cannabinoid receptor signaling decreases intravenous morphine self-administration and relapse in mice.

The endocannabinoid system interacts with the reward system to modulate responsiveness to natural reinforcers, as well as drugs of abuse. Previous preclinical studies suggested that direct blockade of CB1 cannabinoid receptors (CB1R) could be leveraged as a potential pharmacological approach to treat substance use disorder, but this strategy failed during clinical trials due to severe psychiatric side effects. Alternative strategies have emerged to circumvent the side effects of direct CB1 binding through the development of allosteric modulators. We hypothesized that pharmacological inhibition of CB1R signaling through negative allosteric modulation (NAM) would reduce the reinforcing properties of morphine and decrease opioid addictive behaviors. By employing i.v. self-administration in mice, we studied the effects of the CB1-biased NAM GAT358 on morphine intake, relapse-like behavior, and motivation to work for morphine infusions. Our data revealed that GAT358 reduced morphine infusion intake during the maintenance phase of morphine self-administration under fixed ratio 1 schedule of reinforcement. GAT358 decreased morphine-seeking behavior after forced abstinence. Moreover, GAT358 dose-dependently decreased the motivation to obtain morphine infusions in a progressive ratio schedule of reinforcement. Strikingly, GAT358 did not affect the motivation to work for food rewards in an identical progressive ratio task, suggesting that the effect of GAT358 in decreasing opioid self-administration is reward specific. Furthermore, GAT58 did not produce motor ataxia in the rota-rod test. Our results suggest that CB1R NAMs reduced the reinforcing properties of morphine and could represent a viable therapeutic route to safely decrease opioid-addicted behaviors.

Kinematic variations in the barbell back squat under different footwear conditions in female college athletes.

BACKGROUND: The barbell back squat is one of the most performed exercises, being important for the strengthening of lower limbs and trunk. Recently, it has become popular to train under different conditions of footwear or without it, and some investigations have analyzed the changes that this brings, with some contradictions in this regard. The purpose of this study was to analyze the kinematic variations under different shoe conditions (running shoes, barefoot and barefoot with heel raised) in the back squat in female university athletes. METHODS: Fifteen athletes in the three conditions with a load equal to 70% of their one-maximum repetition (1RM), were recorded and analyzed to determine the angles of the ankle, knee, hip and trunk by five movements in each condition. RESULTS: The use of enhancement significantly increased (P<0.05) the dorsal flexion angle of the ankle, against the footwear condition and barefoot without enhancement (109.6±11.1° vs. 99.1±9.0° vs. 101.3±11.5°). No significant differences were observed in any of the other variables. CONCLUSIONS: An optimal squat technique is important for preventing injuries, optimal rehabilitation and for improving sports performance. Increased dorsal ankle flexion angle may protect distal tibiofibular joint.

Integrative species delimitation uncovers hidden diversity within the Pithecopus hypochondrialis species complex (Hylidae, Phyllomedusinae) and its phylogeography reveals Plio-Pleistocene connectivity among Neotropical savannas.

Despite their limited vagility and pronounced habitat heterogeneity in the tropics, many anuran species have unexpectedly extensive geographic ranges. One prominent example of this phenomenon is Pithecopus hypochondrialis, which is found in the Cerrado, Guianan savanna, and Llanos domains, as well as isolated tracts of savanna and open habitat within the Amazon Forest. The present study employs an integrative species delimitation approach to test the hypothesis that P. hypochondrialis is in fact a species complex. We also reconstruct the relationships among the lineages delimited here and other Pithecopus species. In this study, we employ Ecological Niche Modelling (ENM) and spatiotemporal phylogeographic reconstruction approaches to evaluate a multitude of scenarios of connectivity across the Neotropical savannas. We identified three divergent lineages, two of which have been described previously. The lineages were allocated to a lowland Pithecopus clade, although the relationships among these lineages are weakly supported. Both the ENM and the phylogeographic reconstruction highlight the occurrence of periods of connectivity among the Neotropical savannas over the course of the Pliocene and Pleistocene epochs. These processes extended from eastern Amazonia to the northern coast of Brazil. The findings of the present study highlight the presence of hidden diversity within P. hypochondrialis, and reinforce the need for a comprehensive taxonomic review. These findings also indicate intricate and highly dynamic patterns of connectivity across the Neotropical savannas that date back to the Pliocene.

Systematic review of reverse vaccinology and immunoinformatics data for non-viral sexually transmitted infections.

Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium's genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis.

Triclabendazole and clofazimine reduce replication and spermine uptake in vitro in Toxoplasma gondii.

Toxoplasmosis is a worldwide zoonosis caused by the protozoan parasite Toxoplasma gondii. Although this infection is generally asymptomatic in immunocompetent individuals, it can cause serious clinical manifestations in newborns with congenital infection or in immunocompromised patients. As current treatments are not always well tolerated, there is an urgent need to find new drugs against human toxoplasmosis. Drug repurposing has gained considerable momentum in the last decade and is a particularly attractive approach for the search of therapeutic alternatives to treat rare and neglected diseases. Thus, in this study, we investigated the antiproliferative effect of several repurposed drugs. Of these, clofazimine and triclabendazole displayed a higher selectivity against T. gondii, affecting its replication. Furthermore, both compounds inhibited spermine incorporation into the parasite, which is necessary for the formation of other polyamines. The data reported here indicate that clofazimine and triclabendazole could be used for the treatment of human toxoplasmosis and confirms that drug repurposing is an excellent strategy to find new therapeutic targets of intervention.

Musculoskeletal manifestations of COVID-19.

During the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected millions of people worldwide, with acute respiratory distress syndrome (ARDS) being the most common severe condition of pulmonary involvement. Despite its involvement in the lungs, SARS-CoV-2 causes multiple extrapulmonary manifestations, including manifestations in the musculoskeletal system. Several cases involving bone, joint, muscle, neurovascular and soft tissues were reported shortly after pandemic onset. Even after the acute infection has resolved, many patients experience persistent symptoms and a decrease in quality of life, a condition known as post-COVID syndrome or long COVID. COVID-19 vaccines have been widely available since December 2020, preventing millions of deaths during the pandemic. However, adverse reactions, including those involving the musculoskeletal system, have been reported in the literature. Therefore, the primary goal of this article is to review the main imaging findings of SARS-CoV-2 involvement in the musculoskeletal system, including acute, subacute, chronic and postvaccination manifestations.