Electrical properties of disordered films of van der Waals semiconductor WS2 on paper.

One of the primary objectives in contemporary electronics is to develop sensors that are not only scalable and cost-effective but also environmentally sustainable. To achieve this goal, numerous experiments have focused on incorporating nanomaterial-based films, which utilize nanoparticles or van der Waals materials, on paper substrates. In this article, we present a novel fabrication technique for producing dry-abraded van der Waals films on paper, demonstrating outstanding electrical characteristics. We assess the quality and uniformity of these films by conducting a spatial resistivity characterization on a 5 × 5 cm2 dry-abraded WS2 film with an average thickness of 25 µm. Employing transfer length measurements with varying channel length-to-width ratios, we extract critical parameters, including sheet resistance and contact resistance. Notably, our findings reveal a resistivity approximately one order of magnitude lower than previous reports. The film's inherent disorder manifests as an asymmetric distribution of resistance values for specific geometries. We explore how this behavior can be effectively modeled through a random resistance network (RRN), which can reproduce the experimentally observed resistance distribution. Finally, we investigate the response of these devices under applied uniaxial strain and apply the RRN model to gain a deeper understanding of this process.

Are lead, cadmium and mercury risk factors for resistant hypertension?

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) AIMS: To compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. METHODS: Cross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. RESULTS: 46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7-5.2) vs. rHT 3.6 (IQR 2.8-6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07-0.80) vs. rHT 0.30 (IQR 0.07-0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8-12.9) vs. rHT 7.3 (IQR 4.6-13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84-14.10, p=0.086) for Pb, OR = 1.80 (0.39-8.24, p=0.451), for Cd and OR = 2.31 (0.59-9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8-200.2), p=0.072). CONCLUSION: A higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg.

Maternal Programming of Nursery Pig Performance and Gut Microbiome through Live Yeast Supplementation.

The supplementation of live yeast in pig diets is common in the post-weaning phase due to its prebiotic and probiotic effects, but little is known regarding the potential of feeding live yeast to gestating or lactating sows for transferring such benefits to their offspring through maternal programming. The objective of this study was to investigate the effects of live yeast supplementation in sow diets during late gestation and lactation on their reproductive performance and its impact on offspring performance and gut microbiomes in the post-weaning period. Three dietary treatments were imposed on 92 mixed-parity sows during late gestation and lactation based upon the inclusion level of live yeast in corn/soybean meal-based diets: Control (0% yeast), Low (0.1% yeast), and High (0.5% yeast). Nursery pigs in the Low group displayed the highest feed intake in the post-weaning period and greater total gain and average daily gain in comparison to pigs in the High group. The gut microbiomes of nursery pigs differed in composition according to maternal dietary treatment groups at days 4 and 28 post weaning, highlighting higher abundances of bacterial genera typically associated with fermentation roles in the gut microbiomes of offspring of yeast-fed sows. These results indicate that the supplementation of live yeast in sow diets, depending on the inclusion level, may result in beneficial performance and specific microbiome traits for their offspring in the post-weaning period.

Strain-Enhanced Large-Area Monolayer MoS2 Photodetectors.

In this study, we show a direct correlation between the applied mechanical strain and an increase in monolayer MoS2 photoresponsivity. This shows that tensile strain can improve the efficiency of monolayer MoS2 photodetectors. The observed high photocurrent and extended response time in our devices are indicative that devices are predominantly governed by photogating mechanisms, which become more prominent with applied tensile strain. Furthermore, we have demonstrated that a nonencapsulated MoS2 monolayer can be used in strain-based devices for many cycles and extensive periods of time, showing endurance under ambient conditions without loss of functionality. Such robustness emphasizes the potential of MoS2 for further functionalization and utilization of different flexible sensors.

Timing of dietary zinc additions during gestation for improved piglet survival.

The objectives of this study were to determine a practical approach to feeding elevated dietary zinc (Zn) to gestating sows in a commercial setting and to confirm preweaning mortality could be reduced by feeding high Zn to sows during different periods of gestation. The study was conducted at a commercial sow farm in the upper Midwest. Mixed parity sows (n = 267) over three consecutive weekly farrowing groups (sows farrowing within 1 wk) were assigned randomly to one of the three dietary treatments within parity. Treatments consisted of: (1) control sows fed a corn-soybean meal diet containing 206 mg/kg total supplemental Zn supplied by zinc hydroxychloride; (2) breed-to-farrow: as control + 147 mg/kg supplemental Zn as ZnSO4 (353 mg/kg total supplemental Zn) fed from 5 d after breeding to farrowing; and (3) day 110-to-farrow: as control fed from breeding to farrowing + 4,079 mg/kg supplemental Zn as ZnSO4 (4,285 mg/kg total supplemental Zn) starting day 110 of gestation until farrowing. At farrowing, individual piglets were weighed and identified within 12 h of birth. Data were analyzed using PROC GLIMMIX of SAS and the model considered the fixed effect of dietary treatment and random effect of farrowing group. Dietary treatments did not affect number of total pigs born per litter. For breed-to-farrow sows, there was an increase in the percentage of pigs born alive compared to sows fed the control and day 110-to-farrow treatments (P < 0.001). The number of stillborn pigs expressed as a percentage of total litter size at birth decreased for breed-to-farrow sows (P < 0.001) compared with control or day 110-to-farrow sows. Mortality of low birth weight piglets from birth to weaning did not differ among dietary treatments (P = 0.305); however, a trend for decreasing post-natal mortality (P = 0.068) of normal birth weight pigs was observed for pigs born to sows fed elevated Zn 5 d before farrowing. In conclusion, feeding elevated Zn to sows throughout gestation increased the proportion of pigs born alive suggesting that elevated gestational Zn intake makes piglets more robust to endure the stresses of farrowing and decreases intrapartum mortality. Under the conditions of this study, elevated Zn intake of sows did not influence piglet post-natal survival. However, feeding high zinc throughout gestation may decrease piglet mortality during the parturition process.

Interactions between maternal parity and feed additives drive the composition of pig gut microbiomes in the post-weaning period.

BACKGROUND: Nursery pigs undergo stressors in the post-weaning period that result in production and welfare challenges. These challenges disproportionately impact the offspring of primiparous sows compared to those of multiparous counterparts. Little is known regarding potential interactions between parity and feed additives in the post-weaning period and their effects on nursery pig microbiomes. Therefore, the objective of this study was to investigate the effects of maternal parity on sow and offspring microbiomes and the influence of sow parity on pig fecal microbiome and performance in response to a prebiotic post-weaning. At weaning, piglets were allotted into three treatment groups: a standard nursery diet including pharmacological doses of Zn and Cu (Con), a group fed a commercial prebiotic only (Preb) based on an Aspergillus oryzae fermentation extract, and a group fed the same prebiotic plus Zn and Cu (Preb + ZnCu). RESULTS: Although there were no differences in vaginal microbiome composition between primiparous and multiparous sows, fecal microbiome composition was different (R2 = 0.02, P = 0.03). The fecal microbiomes of primiparous offspring displayed significantly higher bacterial diversity compared to multiparous offspring at d 0 and d 21 postweaning (P < 0.01), with differences in community composition observed at d 21 (R2 = 0.03, P = 0.04). When analyzing the effects of maternal parity within each treatment, only the Preb diet triggered significant microbiome distinctions between primiparous and multiparous offspring (d 21: R2 = 0.13, P = 0.01; d 42: R2 = 0.19, P = 0.001). Compositional differences in pig fecal microbiomes between treatments were observed only at d 21 (R2 = 0.12, P = 0.001). Pigs in the Con group gained significantly more weight throughout the nursery period when compared to those in the Preb + ZnCu group. CONCLUSIONS: Nursery pig gut microbiome composition was influenced by supplementation with an Aspergillus oryzae fermentation extract, with varying effects on performance when combined with pharmacological levels of Zn and Cu or for offspring of different maternal parity groups. These results indicate that the development of nursery pig gut microbiomes is shaped by maternal parity and potential interactions with the effects of dietary feed additives.

Pros and cons of narrow- versus wide-compartment rotarod apparatus: An experimental study in mice.

The rotarod test, a sensorimotor assessment that allows for quantitative evaluation of motor coordination in rodents, has extensive application in many research fields. The test results exhibit extreme between-study variability, sometimes making it challenging to conclude the validity of certain disease models and related therapeutic effects. Although the variation in test paradigms may account for this disparity, some features of rotarod apparatus including rod diameter make differences. However, it is unknown whether the width of animal compartment has a role in rotarod performance. Here we comprehensively evaluated the active rotarod performance and adverse incidents in multiple strains of mice on an 11-cm- or a 5-cm-wide compartment apparatus. We found that mouse behaviors on these apparatuses were surprisingly different. It took a markedly longer time to train mice on the narrow- than wide-compartment rotarod. Further, non-transgenic B6129S and tau knockout mice aged 11 months and beyond showed different levels of improvement based on the compartment width. These mice had no overt improvements on accelerating rotarod over 4-5 training sessions on the narrow compartment, contrary to marked progress on the wide counterpart. The incidents of mice passively somersaulting round and fragmented running occurred significantly more on the wide than narrow compartment during accelerating rotarod sessions. Mice fell off rod more frequently on narrow than wide compartments upon attempt to turn around and when moving backward on rod. The pros and cons of narrow versus wide compartments are informative as to how to choose a rotarod apparatus that best fits the animal models used.

Understanding the role of AMPA receptors in autism: insights from circuit and synapse dysfunction.

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the cerebro-cerebellar circuit, particularly in genetic autism related to SHANK3 or SYNGAP1 protein dysfunction function and autism associated with in utero exposure to the anti-seizure medications valproic acid and topiramate, may contribute to the disease presentation. Initially, a discussion contextualizing AMPAr signaling in the cerebro-cerebellar circuitry and microstructural circuit considerations is offered. Subsequently, a detailed review of the literature implicating mutations or deletions of SHANK3 and SYNGAP1 in disrupted AMPAr signaling reveals how bidirectional pathogenic modulation of this key circuit may contribute to autism. Finally, how pharmacological exposure may interact with this pathway, via increased risk of autism diagnosis with valproic acid and topiramate exposure and potential treatment of autism using AMPAr modulator perampanel, is discussed. Through the lens of the review, we will offer speculation on how neuromodulation may be used as a rational adjunct to therapy. Together, the present review seeks to synthesize the disparate considerations of circuit understanding, genetic etiology, and pharmacological modulation to understand the mechanistic interaction of this important and complex disorder.

EPITRANS. Quality assessment of the epilepsy transition process.

OBJECTIVE: To analyze the differences in clinical management during the epilepsy transition process from pediatric to adult care and to determine the quality of life and degree of satisfaction of patients and caregivers during the transition. METHODS: This is a longitudinal study including patients with epilepsy transferred from pediatric to adult epilepsy care between 2013 and 2017. Patients had a minimum follow-up of 3 years before the transition visit and at least 3 years consulting in the adults section. Clinical characteristics were retrieved from the medical chart. Quality of life and satisfaction questionnaires were administered by online access to patients and caregivers at the end of the adult follow-up period. RESULTS: 99 patients (50.5 % women, mean transition age 16.5 ± 1 years old) were included. Before the transition visit, 90 % of patients received a transition discussion and 88 % had a formal clinical report. In the pediatric period, patients were visited more frequently, had more EEGs and genetic studies, and were seen by the same neuropediatrician (P<0.05). In the adult period, patients underwent a larger number of prolonged video EEGs and were prescribed polytherapy more often (P<0.05). Quality of life remained steady during the entire transition, but satisfaction with the care received was significantly higher during the pediatric period. CONCLUSIONS: Significant differences were seen in epilepsy care during transition from pediatric to adult management, and this had an impact on the degree of satisfaction reported by patients and caregivers. Our results provide evidence of the potential value of development and early implementation of a protocolled transition program.

Effects of Horseback Riding on the Postural Control of Autistic Children: A Multiple Baseline Across-subjects Design.

The aim of this research was to study the effect of a horseback-riding programme on postural control in a group of autistic children (ASD). Nine children aged 9 to 12 years participated in this study through a multiple baseline across subjects design. The whole programme took place over nine months. Participants followed a previously developed specific horseback-riding programme, consisting of 45-minute sessions held twice a week for at least three months. To evaluate postural control, the average velocity of the centre of pressure displacement was measured by means of a posturographic platform. Results indicated that this intervention with horses had a positive effect on the postural control in children with ASDs.

Infection outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study.

OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.

Child-to-adult transition: a survey of current practices within the European Reference Network for Rare Neurological Diseases (ERN-RND).

BACKGROUND: Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. AIM: To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). METHODS: Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. RESULTS: Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18 years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40 years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. CONCLUSIONS: This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.

Malignancy outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study.

OBJECTIVE: To evaluate the risk of malignancy (overall, breast, lung, and lymphoma) in patients with rheumatoid arthritis treated with abatacept, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), and other biologic/targeted synthetic (b/ts)DMARDs in clinical practice. METHODS: Four international observational data sources were included: ARTIS (Sweden), RABBIT (Germany), FORWARD (USA), and BC (Canada). Crude incidence rates (IRs) per 1000 patient-years of exposure with 95% confidence intervals (CIs) for a malignancy event were calculated; rate ratios (RRs) were estimated and adjusted for demographics, comorbidities, and other potential confounders. RRs were then pooled in a random-effects model. RESULTS: Across data sources, mean follow-up for patients treated with abatacept (n = 5182), csDMARDs (n = 73,755), and other b/tsDMARDs (n = 37,195) was 3.0-3.7, 2.9-6.2, and 3.1-4.7 years, respectively. IRs per 1000 patient-years for overall malignancy ranged from 7.6-11.4 (abatacept), 8.6-13.2 (csDMARDs), and 5.0-11.8 (other b/tsDMARDs). IRs ranged from: 0-4.4, 0-3.3, and 0-2.5 (breast cancer); 0.1-2.8, 0-3.7, and 0.2-2.9 (lung cancer); and 0-1.1, 0-0.9, and 0-0.6 (lymphoma), respectively, for the three treatment groups. The numbers of individual cancers (breast, lung, and lymphoma) in some registries were low; RRs were not available. There were a few cases of lymphoma in some of the registries; ARTIS observed an RR of 2.8 (95% CI 1.1-6.8) with abatacept versus csDMARDs. The pooled RRs (95% CIs) for overall malignancy with abatacept were 1.1 (0.8-1.5) versus csDMARDs and 1.0 (0.8-1.3) versus b/tsDMARDs. CONCLUSIONS: This international, post-marketing observational safety study did not find any statistically significant increase in the risk of overall malignancies in pooled data in patients treated with abatacept compared with csDMARDs or with other b/tsDMARDs. Assessment of larger populations is needed to further evaluate the risks for individual cancers, especially lymphoma.

Developmental epileptic encephalopathy in DLG4-related synaptopathy.

OBJECTIVE: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy. METHODS: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. RESULTS: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants. SIGNIFICANCE: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG.

Profiling pathogenic protozoan and their functional pathways in wastewater using 18S rRNA and shotgun metagenomics.

Despite extensive research, little is known about the composition of eukaryotic protists in environmental samples. This is due to low parasite concentrations, the complexity of parasite diversity, and a lack of suitable reference databases and standardized protocols. To bridge this knowledge gap, this study used 18S rRNA short amplicon and shotgun metagenomic sequencing approaches to profile protozoan microbial communities as well as their functional pathways in treated and untreated wastewater samples collected from different regions of South Africa. Results demonstrated that protozoan diversity (Shannon index P-value = 0.03) and taxonomic composition (PERMANOVA, P-value = 0.02) was mainly driven by the type of wastewater samples (treated & untreated) and geographic location. However, these WWTPs were also found to contain a core community of protozoan parasites. The untreated wastewater samples revealed a predominant presence of free-living, parasitic, and potentially pathogenic protists typically found in humans and animals, ranging from Alveolata (27 %) phylum (Apicomplexa and Ciliophora) to Excavata (3.88 %) (Discoba and Parasalia) and Amoebozoa (2.84 %) (Entamoeba and Acanthamoeba). Shotgun metagenomics analyses in a subset of the untreated wastewater samples confirmed the presence of public health-importance protozoa, including Cryptosporidium species (3.48 %), Entamoeba hystolitica (6.58 %), Blastocystis hominis (2.91 %), Naegleria gruberi (2.37 %), Toxoplasma gondii (1.98 %), Cyclospora cayetanensis (1.30 %), and Giardia intestinalis (0.31 %). Virulent gene families linked to pathogenic protozoa, such as serine/threonine protein phosphatase and mucin-desulfating sulfatase were identified. Additionally, enriched pathways included thiamine diphosphate biosynthesis III, heme biosynthesis, Methylerythritol 4-Phosphate Pathway, methyl erythritol phosphate (MEP), and pentose phosphate pathways. These findings suggest that protozoan pathogens may possess metabolic and growth potential within WWTPs, posing a severe risk of transmission to humans and animals if inadequately disinfected before release. This study provides a baseline for the future investigation of diverse protozoal communities in wastewater, which are of public health importance.

Ischemic Stroke During Dengue Infection: A Report of 2 Cases.

BACKGROUND Involvement of the central nervous system during infection with dengue virus (DENV) is recognized. However, ischemic stroke is rarely reported. Herein are described 2 cases of patients with ischemic stroke in which DENV infection was demonstrated. CASE REPORT The first patient was a 51-year-old woman that presented altered consciousness, monoparesis, facial palsy, dysarthria, Babinski sign, and syncope 7 days from the onset of fever. She had a history of carotid artery atherothrombosis and previous stroke. Magnetic resonance imaging (MRI) showed an acute infarction of the right middle cerebral artery. DENV was confirmed by the presence of NS1 and IgM in serum. The patient was treated with intravenous fluids and recovered well, with only right facial paresis still present at discharge. The second patient was a 50-year-old man who presented with headache, altered consciousness, and mutism after a febrile episode 1 week prior. This patient had a previous history of stroke, glioblastoma resection, epilepsy, hypothyroidism, and diabetes. MRI demonstrated a subacute ischemic event. The diagnosis of dengue was confirmed by serum NS1 and IgM and by RT-PCR in serum and cerebrospinal fluid. DENV-1 serotype was observed in serum and cerebrospinal fluid. The patient was treated with intravenous fluids and was discharged in good condition. In both patients, thrombocytopenia and leukopenia was demonstrated, and hemoconcentration was demonstrated in the second patient. CONCLUSIONS In tropical and subtropical countries, DENV infection can represent a potential cause of ischemic stroke in patients with a history of comorbidities, including stroke.

The Medical Action Ontology: A tool for annotating and analyzing treatments and clinical management of human disease.

BACKGROUND: Navigating the clinical literature to determine the optimal clinical management for rare diseases presents significant challenges. We introduce the Medical Action Ontology (MAxO), an ontology specifically designed to organize medical procedures, therapies, and interventions. METHODS: MAxO incorporates logical structures that link MAxO terms to numerous other ontologies within the OBO Foundry. Term development involves a blend of manual and semi-automated processes. Additionally, we have generated annotations detailing diagnostic modalities for specific phenotypic abnormalities defined by the Human Phenotype Ontology (HPO). We introduce a web application, POET, that facilitates MAxO annotations for specific medical actions for diseases using the Mondo Disease Ontology. FINDINGS: MAxO encompasses 1,757 terms spanning a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. These terms annotate phenotypic features associated with specific disease (using HPO and Mondo). Presently, there are over 16,000 MAxO diagnostic annotations that target HPO terms. Through POET, we have created 413 MAxO annotations specifying treatments for 189 rare diseases. CONCLUSIONS: MAxO offers a computational representation of treatments and other actions taken for the clinical management of patients. Its development is closely coupled to Mondo and HPO, broadening the scope of our computational modeling of diseases and phenotypic features. We invite the community to contribute disease annotations using POET (https://poet.jax.org/). MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO). FUNDING: NHGRI 1U24HG011449-01A1 and NHGRI 5RM1HG010860-04.