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Abstract Background Epilepsy contributes to a significant disease burden in children and adolescents worldwide. The incidence of childhood epilepsy is threefold higher in low and middle income countries compared in high-income countries. Epilepsy is a serious neurological condition associated with stigma and discrimination, an impaired quality of life, and other mental health related problems. Objective This study is aimed to synthesize existing evidence and estimate the pooled prevalence and incidence of epilepsy in children and adolescents in Africa. Methods A comprehensive and systematic search of relevant databases was conducted. The quality of each study was assessed using the Newcastle-Ottawa Quality Assessment Scale adapted for meta-analysis. Two reviewers screened retrieved articles, conducted critical appraisals, and extracted the data. Heterogeneity between studies was assessed by visual inspection of forest plots and statistically using Cochran’s Q statistics and the I2 test. Publication bias was checked by visual inspection of funnel plots as well as statistically using Egger’s correlation and Begg’s regression tests. Finally, the pooled prevalence and incidence of childhood epilepsy were computed with 95% confidence intervals. Result In this review and meta-analysis 42 studies with 56 findings were included to compute the pooled prevalence of childhood epilepsy. On the other hand, 6 studies were included to estimate the combined incidence. The pooled prevalence of cumulative epilepsy was 17.3 per 1000 children. Whereas the pooled prevalence of active and lifetime epilepsy was 6.8 and 18.6 per 1000 children respectively. The pooled incidence of childhood epilepsy was 2.5 per 1000 children. Conclusion Nearly 1 in 50 children are suffering from epilepsy in Africa. However, little attention has been paid to the prevention and treatment of childhood epilepsy. Mass epilepsy screening, scaling up treatment coverage, and designing strict treatment follow up and monitoring mechanisms are recommended.

Objectives Diabetes is the leading cause of disability-adjusted life years in Mexico, and cost-effective care models are needed to address the epidemic. We sought to evaluate the cost and cost-effectiveness of a novel community-based model of diabetes care in rural Mexico, compared with usual care.Design We performed time-driven activity-based costing to estimate annualised costs associated with typical diabetes care in Chiapas, Mexico, as well as a novel diabetes care model known as Compañeros En Salud Programa de Enfermedades Crónicas (CESPEC). We conducted Markov chain analysis to estimate the cost-effectiveness of CESPEC compared with usual care from a societal perspective. We used patient outcomes from CESPEC in 2016, as well as secondary data from existing literature.Setting Rural primary care clinics in Chiapas, Mexico.Participants Adults with diabetes.Interventions CESPEC is a novel, comprehensive, diabetes care model that integrates community health workers, provider education, supply chain management and active case finding.Outcome measure The primary outcome was the incremental cost-effectiveness of CESPEC compared with care as usual, per quality-adjusted life year (QALY) gained, expressed in 2016 US dollars.Results The economic cost of the CESPEC diabetes model was US$144 per patient per year, compared with US$125 for diabetes care as usual. However, CESPEC care was associated with 0.13 additional years of health-adjusted life expectancy compared with usual care and 0.02 additional years in the first 5 years of treatment. This translated to an incremental cost-effectiveness ratio (ICER) of US$2981 per QALY gained over a patient’s lifetime and an ICER of US$10 444 over the first 5 years. Findings were robust to multiple sensitivity analyses.Conclusions CESPEC is a cost-effective, community-based model of diabetes care for patients in rural Mexico. Given the high prevalence and significant morbidity associated with diabetes in Mexico and other countries in Central America, this model should be considered for broader scale up and evaluation.

The article presents a case study of a 5-month-old boy with nonbloody, nonbilious emesis after every meal. Topics discussed include abnormal eye movements and inconsolable fussiness has been reported and was diagnosed with right eye esotropia and bulging fontanelle; computed tomography scan of his head revealed bilateral subdural fluid collections and increased intracranial pressure; and diagnosis of nonaccidental trauma.

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug.

O presente trabalho teve por objetivo validar métodos por espectrofotometria UV-Vis e por CLAE para a análise quantitativa de um derivado do tiofeno, o 2-[(3,4-dicloro-benzilideno)-amino]-5,6-diidro-4H-ciclopen-ta[b]tiofeno-3-carbonitrila (5CN05) e aplicá-los no doseamento da molécula contida em microemulsões, Os métodos propostos foram validados conforme a Resolução 899/2003 da Agência Nacional de Vigilância Sanitária (ANVISA), O comprimento de onda de máxima absorção do fármaco 5CN05 foi detectado em ?max= 387nm, O método espectrofotométrico validado mostrou-se seletivo, apresentando linearidade na faixa de 3 a 16 µg.mL-1, coeficiente de correlação (r) igual a 0,9998 e limites de detecção e quantificação de 0,12 µg.mL-1 e 0,41 µg.mL-1, respectivamente, Para o método CLAE, observou-se linearidade na faixa de 0,1 a 3,0 µg.mL-1, r = 0,99915, limites de detecção e quantificação de 0,07 µg.mL-1 e 0,10 µg.mL-1 respectivamente, Para ambos os métodos, os parâmetros precisão, exatidão e robustez mostraram-se adequados para o uso pretendido, As metodologias propostas podem ser seguramente aplicadas para quantificação do 5CN05 em produtos farmacêuticos como microemulsões.

Describes a case of doramectin toxicity in a collie. Background on the drug doramectin, a new avermectin approved for use in cattle and swine; Cases of ivermectin toxicity in collies and other dog breeds; Association of the toxicity with diffuse cerebral and cerebellar dysfunction; Medical condition of the dog; Physical and neurological examination of the dog; Results of laboratory tests performed.

A new method using a magnetic nanoparticle-based colorimetric biosensing assay (NCBA) was compared with sputum smear microscopy (SSM) for the detection of pulmonary tuberculosis (PTB) in sputum samples. Studies were made to compare the NCBA against SSM using sputum samples collected from PTB patients prior to receiving treatment. Experiments were also conducted to determine the appropriate concentration of glycan-functionalized magnetic nanoparticles (GMNP) used in the NCBA and to evaluate the optimal digestion/decontamination solution to increase the extraction, concentration and detection of acid-fast bacilli (AFB). The optimized NCBA consisted of a 1:1 mixture of 0.4% NaOH and 4% N-acetyl-L-cysteine (NALC) to homogenize the sputum sample. Additionally, 10 mg/mL of GMNP was added to isolate and concentrate the AFB. All TB positive sputum samples were identified with an increased AFB count of 47% compared to SSM, demonstrating GMNP’s ability to extract and concentrate AFB. Results showed that NCBA increased AFB count compared to SSM, improving the grade from “1+„ (in SSM) to “2+„. Extending the finding to paucibacillary cases, there is the likelihood of a “scant„ grade to become “1+„. The assay uses a simple magnet and only costs $0.10/test. NCBA has great potential application in TB control programs.

α,β Amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has shown a variety of pharmacological properties, including anti-inflammatory effect. ABAM is isolated from Burseraceae oilresins, especially from the Protium species, which is commonly found in the Brazilian Amazon. This work aimed to develop solid dispersions (SD) of ABAM with the following hydrophilic polymers: polyvinylpyrrolidone (PVP-K30), polyethylene glycol (PEG-6000) and hydroxypropylmethylcellulose (HPMC). The SDs were prepared by physical mixture (PM), kneading (KND) and rotary evaporation (RE) methods. In order to verify any interaction between ABAM and the hydrophilic polymers, physicochemical characterization was performed by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC) analysis. Furthermore, an in vitro anti-inflammatory assay was performed with ABAM alone and as SDs with the hydrophilic polymers. The results from the characterization analysis show that the SDs were able to induce changes in the physicochemical properties of ABAM, which suggests interaction with the polymer matrix. In vitro anti-inflammatory assay showed that the SDs improved the anti-inflammatory activity of ABAM and showed no cytotoxicity. In conclusion, this study showed the potential use of SDs as an efficient tool for improving the stability and anti-inflammatory activity of ABAM without cytotoxicity.

Effective visualization is central to the exploration and comprehension of brain imaging data. While MRI data are acquired in three-dimensional space, the methods for visualizing such data have rarely taken advantage of three-dimensional stereoscopic technologies. We present here results of stereoscopic visualization of clinical data, as well as an atlas of whole-brain functional connectivity. In comparison with traditional 3D rendering techniques, we demonstrate the utility of stereoscopic visualizations to provide an intuitive description of the exact location and the relative sizes of various brain landmarks, structures and lesions. In the case of resting state fMRI, stereoscopic 3D visualization facilitated comprehension of the anatomical position of complex large-scale functional connectivity patterns. Overall, stereoscopic visualization improves the intuitive visual comprehension of image contents, and brings increased dimensionality to visualization of traditional MRI data, as well as patterns of functional connectivity.

Although sleep abnormalities in general and sleep related breathing disorders (SBD) in particular are quite common in healthy children, their presence is notably under-recognized. Impaired sleep is a frequent problem in subjects with Inborn Errors of Metabolism (IEM) as well as in a variety of genetic disorders; however, they are commonly either missed or underestimated. Moreover, the complex clinical presentation and the frequently life threatening symptoms are so overwhelming that sleep and its quality may easily dismissed. Even centers which specialize in rare genetic-metabolic disorders are expected to see only few patients with a particular syndrome, a fact that significantly contributes to the under-diagnosis and treatment of impaired sleep in this particular population. Many of those patients suffer from reduced life quality associated with a variable degree of cognitive impairment which may be worsened by poor sleep and abnormal ventilation during sleep, abnormalities which can be alleviated by proper treatment. Even when such problems are detected, there is a paucity of publications on sleep and breathing characteristics of such patients that the treating physician can refer to. In the present paper we provide an overview of sleep and breathing characteristics in a number of rare genetic-metabolic disorders with the hope that it will serve as a reminder for the medical profession to look for possible impaired sleep and SBD in their patients and when present to apply the appropriate evaluation and treatment options .

Motor inhibition is among the most commonly studied executive functions in Attention-Deficit/Hyperactivity Disorder (ADHD). Imaging studies using probes of motor inhibition such as the Stop Signal Task (SST) consistently demonstrate ADHD-related dysfunction within a right-hemisphere fronto-striatal network that includes inferior frontal gyrus and pre-supplementary motor area (pre-SMA). Beyond findings of focal hypo- or hyper-function, emerging models of ADHD psychopathology highlight disease-related changes in functional interactions between network components. Resting state fMRI (R-fMRI) approaches have emerged as powerful tools for mapping such interactions (i.e., resting state functional connectivity, RSFC), and for relating behavioral and diagnostic variables to network properties. We used R-fMRI data collected from 17 typically developing controls (TDC) and 17 age-matched children with ADHD (aged 8-13 years) to identify neural correlates of SST performance measured outside the scanner. We examined two related inhibition indices: stop signal reaction time (SSRT), indexing inhibitory speed, and stop signal delay (SSD), indexing inhibitory success. Using 11 fronto-striatal seed regions-of-interest, we queried the brain for relationships between RSFC and each performance index, as well as for interactions with diagnostic status. Both SSRT and SSD exhibited connectivity-behavior relationships independent of diagnosis. At the same time, we found differential connectivity-behavior relationships in children with ADHD relative to TDC. Our results demonstrate the utility of RSFC approaches for assessing brain/behavior relationships, and for identifying pathology-related differences in the contributions of neural circuits to cognition and behavior.

The aim of this review is to provide evidence-based recommendations on the secondary prevention of atherothrombotic ischemic stroke. Antiplatelets are the major therapy for the secondary stroke prevention. The most commonly used antiplatelets agents are aspirin, clopidogrel and extended-release dipyridamol. A lot of progress had been made in last years regarding aspirin resistance and genotyping of clopidogrel metabolism. According to the results of the accomplished studies it is difficult to broadly recommend one antithrombotic agent in favor of the other. Instead, a review of the currently published data suggests the importance of focusing on the individualizing approach in antiplatelet therapy.

Se presenta el caso de un paciente de sexo femenino, de 72 años de edad, que fue inicialmente intervenida con un diagnóstico de apendicitis aguda y en quien se encontró durante la exploración una masa infiltran te del ciego. Estudios complementarios no fueron conclusivos para descartar malignidad y se decidió practicar una hemicolectomía derecha en un segundo acto operatorio. La patología demostró una úlcera benigna del ciego. Dicha patología es rara y su etiología es aún desconocida. Las úlceras inespecíficas del colon se localizan más frecuentemente en el ciego (44-55%). Esta entidad es más frecuente en varones (2:1). El diagnóstico diferencial debe establecerse con una neoplasia (CA, linfoma), una enfermedad inflamatoria intestinal (Enf. de Crohn, TBC, ameboma) o una apendicitis aguda. Se aceptan como posibles etiologías las infecciosas, mecánicas, vasculares o químicas. Aunque el colon por enema, la colonoscopia y la tomografía axial computarizada del abdomen pueden sugerir el diagnóstico, si persiste la duda de una enfermedad neoplásica, la resección quirúrgica está indicada.

Detecting life has driven research and exploration for centuries, but recent attempts to compile and generate a framework that summarizes life features, aimed to develop strategies for life detection missions beyond planet Earth, have disregarded a key life feature: behavior. Yet, some behaviors such as biomineralization or motility have occasionally been proposed as biosignatures to detect life. Here, we capitalize on a specific taxis' motility behavior, magnetotaxis, to experimentally provide insights in support of behavior as an unambiguous, sensitive biosignature, and magnetic forces as a prescreening option. Using a magnetotactic bacterial species, Magnetospirillum magneticum, we conducted a lab sensitivity experiment comparing PCR with the hanging drop behavioral assay, using a dilution series. The hanging drop behavioral assay visually shows the motility of MTB toward magnetic poles. Our findings reveal that the behavioral assay exhibits higher sensitivity in the detection of M. magneticum when compared to the established PCR protocol. While both methods present similar detection sensitivities at high concentrations, at ≥ 10 -7 fold dilutions, the behavioral method proved more sensitive. The behavioral method can detect bacteria even when samples are diluted at 10 -9 . Comparable results were obtained with environmental samples from the Hula Valley. We propose behavioral cues as valuable biosignatures in the ongoing efforts of life detection in unexplored aquatic habitats on Earth and to stimulate and support discussions about how to detect extant life beyond Earth. Generic and robust behavioral assays can represent a methodological revolution., (© 2024. The Author(s).)

The Rel proteins of the NF-κB complex comprise one of the most investigated transcription factor families, forming a variety of hetero- or homodimers. Nevertheless, very little is known about the fundamental kinetics of NF-κB complex assembly, or the inter-conversion potential of dimerised Rel subunits. Here, we examined an unexplored aspect of NF-κB dynamics, focusing on the dissociation and reassociation of the canonical p50 and p65 Rel subunits and their ability to form new hetero- or homodimers. We employed a soluble expression system to enable the facile production of NF-κB Rel subunits, and verified these proteins display canonical NF-κB nucleic acid binding properties. Using a combination of biophysical techniques, we demonstrated that, at physiological temperatures, homodimeric Rel complexes routinely exchange subunits with a half-life of less than 10 min. In contrast, we found a dramatic preference for the formation of the p50/p65 heterodimer, which demonstrated a kinetic stability of at least an order of magnitude greater than either homodimer. These results suggest that specific DNA targets of either the p50 or p65 homodimers can only be targeted when these subunits are expressed exclusively, or with the intervention of additional post-translational modifications. Together, this work implies a new model of how cells can modulate NF-κB activity by fine-tuning the relative proportions of the p50 and p65 proteins, as well as their time of expression. This work thus provides a new quantitative interpretation of Rel dimer distribution in the cell, particularly for those who are developing mathematical models of NF-κB activity., (© 2021 The Protein Society.)

The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4+ T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment., Competing Interests: The authors have read the journal’s policy and have the following competing interests: JF was an employee of Microsoft Research Cambridge at the time the study was conducted, but is no longer an employee of the company. EN is an employee of Aleph Labs, but was not employed by the company at the time the study was conducted. GK is an employee of AstraZeneca, but was not employed by the company at the time the study was conducted. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

The identity of a magnetic sensor in animals remains enigmatic. Although the use of the geomagnetic field for orientation and navigation in animals across a broad taxonomic range has been well established over the past five decades, the identity of the magnetic-sensing organ and its structure and/or apparatus within such animals remains elusive-'a sense without a receptor'. Recently, we proposed that symbiotic magnetotactic bacteria (MTB) may serve as the underlying mechanism behind a magnetic sense in animals-'the symbiotic magnetic-sensing hypothesis'. Since we first presented this hypothesis, both criticism and support have been raised accordingly. Here we address the primary criticisms and discuss the plausibility of such a symbiosis, supported by preliminary findings demonstrating the ubiquity of MTB DNA in general, and specifically in animal samples. We also refer to new supporting findings, and discuss host adaptations that could be driven by such a symbiosis. Finally, we suggest the future research directions required to confirm or refute the possibility of symbiotic magnetic-sensing. This article is part of the theme issue 'The role of the microbiome in host evolution'.

Background: Current recommendation for performing the ACTH stimulation test (ACTHST) for diagnosis of hyperadrenocorticism (HAC) advocates the collection of baseline serum cortisol concentration (BC), but no references for interpretation of its results exist., Objective: Evaluate the contribution of BC of the ACTHST to the diagnosis of HAC., Animals: Fifty-four dogs were evaluated for suspected HAC at a referral hospital., Methods: Records of dogs that had been evaluated by ACTHST for suspected HAC were reviewed. Receiver operator characteristics (ROC) analyses were used to assess the performance of BC, post-stimulation serum cortisol concentrations (PC), post-to-baseline cortisol concentration difference (DeltaC) and quotient (RatioC) for the diagnosis of HAC by comparing the area under the ROC curve (AUC) of PC to each of the other tests., Results: The AUC of PC (95% confidence interval [CI]: 0.92; 95% CI, 0.81-0.98) was significantly higher than AUCs of BC (0.70; 95% CI, 0.56-0.82; P = .01) and RatioC (0.55; 95% CI, 0.41-0.69; P < .001), and was not significantly different from AUC of DeltaC (0.86; 95% CI, 0.74-0.94; P = .09). An optimal cutoff value of 683 nmol/L (24.8 μg/dL) for PC yielded a sensitivity of 86% and a specificity of 94%, respectively, and a cutoff value of 718 nmol/L (26.0 μg/dL) yielded a specificity of 100% with of 81% sensitivity for the diagnosis of pituitary-dependent HAC., Conclusion and Clinical Importance: The PC had good discriminatory ability for the diagnosis of HAC. It was comparable to DeltaC, whereas BC and RatioC were ineffective. Current recommendations to collect samples for BC appear redundant., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Cotranslational protein folding can facilitate rapid formation of functional structures. However, it can also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. By analyzing known protein structures, we show that homomeric protein contacts are enriched toward the C termini of polypeptide chains across diverse proteomes. We hypothesize that this is the result of evolutionary constraints for folding to occur before assembly. Using high-throughput imaging of protein homomers in Escherichia coli and engineered protein constructs with N- and C-terminal oligomerization domains, we show that, indeed, proteins with C-terminal homomeric interface residues consistently assemble more efficiently than those with N-terminal interface residues. Using in vivo, in vitro and in silico experiments, we identify features that govern successful assembly of homomers, which have implications for protein design and expression optimization.