The epidemiology and impact of persistent Campylobacter infections on childhood growth among children 0-24 months of age in resource-limited settings.

Background: Campylobacter is the leading cause of bacterial gastroenteritis worldwide. It is generally associated with an acute gastrointestinal infection causing a self-limiting diarrheal episode. However, there is evidence that persistent/recurrent carriage of Campylobacter also occurs. In hyperendemic settings the epidemiology and consequences of persistent Campylobacter enteric infections is poorly studied. Methods: Risk factors for and growth consequences of persistent Campylobacter infections detected by polymerase chain reaction (qPCR) were evaluated with data from the MAL-ED birth cohort study in children 0-24 months of age between November 2009 and February 2012. A persistent Campylobacter infection was defined as three or more consecutive Campylobacter positive monthly stools. Findings: Across all study sites, 45.5% (781/1715) of children experienced at least one persistent Campylobacter episode. The average cumulative duration of days in which children with persistent Campylobacter were positive for Campylobacter spp. was 150 days (inter-quartile range: 28-236 days). Children who experienced a persistent Campylobacter episode had an attained 24-month length-for-age (LAZ) score that was 0.23 (95% (CI): -0.31, -0.15) less than children without a persistent Campylobacter episode. Among children who had at least one episode of Campylobacter over a 3-month or 9-month window, persistent episodes were not significantly associated with poorer 3-month weight gain (-28.7 g, 95% CI: -63.4 g, 6.0 g) but were associated with poorer 9-month linear growth (-0.134 cm 95% CI: -0.246, -0.022) compared to children with an episode that resolved within 31 days. Interpretation: Persistent/recurrent Campylobacter infection is common among children and has a measurable negative impact on linear growth in early childhood. Funding: Funding for this study was provided by the Bill and Melinda Gates Foundation (OPP1066146 and OPP1152146), the National Institutes of Health United States (R01AI158576 and R21AI163801 to MNK and CTP; K43TW012298 to FS; K01AI168493 to JMC; GOL was supported by K01AI145080. This research was also supported in part by USDA-ARS CRIS project 2030-42000-055-00D. The funders had no role in study design, study implementation, data analysis, or interpretation of the results.

Cognitive behavioral stress management effectively facilitates neurologic recovery, alleviates mental distress, and elevates health status in acute ischemic stroke patients.

Cognitive behavioral stress management (CBSM) relieves physical and psychological burdens in patients with some central nervous system diseases, while its utility in acute ischemic stroke (AIS) patients is unclear. This study aimed to explore the effect of CBSM on neurologic recovery and psychosomatic health in AIS patients. Totally, 176 naive AIS patients were randomized into routine care (RC) group (n=88) and CBSM group (n=88) to receive a 3-month corresponding intervention. Modified Rankin scale (mRS) scores at the first month after discharge (M1) (P=0.008) and the third month after discharge (M3) (P=0.016) were lower in the CBSM group than in the RC group. The proportion of AIS patients with mRS score >2 at M3 was reduced in CBSM group vs RC group (P=0.045). Hospital anxiety depression scale (HADS)-anxiety score at M3 (P=0.016), HADS-depression score at M3 (P=0.005), and depression rate at M3 (P=0.021) were decreased in the CBSM group vs the RC group. EuroQol-5 dimension scores at M1 (P=0.024) and M3 (P=0.012) were decreased, while EuroQol-visual analogue scale score at M3 (P=0.026) was increased in the CBSM group vs the RC group. By subgroup analyses, CBSM had favorable outcomes in AIS patients with age ≤65 years. CBSM was beneficial to neurologic recovery and distress relief in AIS patients with an education level of middle school or above, and to health status in those with an education level of primary school or uneducated. In conclusion, CBSM benefitted neurologic recovery and psychosomatic health in AIS patients with minor neurological deficits, however, further studies should verify these results with a larger sample size and longer follow-up.

Molecular characterization of Chinese patients with small bowel adenocarcinoma.

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

Novel rpsK / rpsD primer-probe assay improves detection of Campylobacter jejuni and Campylobacter coli in human stool.

Campylobacter causes bacterial enteritis, dysentery, and growth faltering in children in low- and middle-income countries (LMICs). Campylobacter spp. are fastidious organisms, and their detection often relies on culture independent diagnostic technologies, especially in LMICs. Campylobacter jejuni and Campylobacter coli are most often the infectious agents and in high income settings together account for 95% of Campylobacter infections. Several other Campylobacter species have been detected in LMIC children at an increased prevalence relative to high income settings. After doing extensive whole genome sequencing of isolates of C. jejuni and C. coli in Peru, we observed heterogeneity in the binding sites for the main species-specific PCR assay (cadF) and designed an alternative rpsKD-based qPCR assay to detect both C. jejuni and C. coli. The rpsKD-based qPCR assay identified 23% more C.jejuni/ C.coli samples than the cadF assay among 47 Campylobacter genus positive cadF negative samples verified to have C. jejuni and or C. coli with shotgun metagenomics. This assay can be expected to be useful in diagnostic studies of enteric infectious diseases and be useful in revising the attribution estimates of Campylobacter in LMICs.

Real-world evaluation of first-line treatment of extensive-stage small-cell lung cancer with atezolizumab plus platinum/etoposide: a focus on patients with brain metastasis.

PURPOSE: A previous real-world study conducted in China confirmed that first-line atezolizumab, in combination with etoposide/platinum (EP), leads to significantly longer progression-free survival (PFS) compared to EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC). The present study aimed to provide updated survival outcome data and evaluate the clinical efficacy of atezolizumab plus chemotherapy in ES-SCLC patients with brain metastasis (BM). METHODS: This retrospective study included 225 patients with ES-SCLC who were treated with EP alone (EP group) or a combination of EP + atezolizumab (atezolizumab group). Survival outcomes for the total study sample and patients in the BM subgroup were estimated using the Kaplan-Meier method. RESULTS: The atezolizumab group continued to demonstrate significantly longer PFS than the EP group (hazard ratio [HR], 0.68). The median overall survival (OS) was 26.2 months in the atezolizumab group vs. 14.8 months in the EP group (HR, 0.63). Additionally, among the BM patients in our study, the median PFS was found to be longer in the atezolizumab group (7.0 months) than in the EP group (4.1 months) (HR, 0.46). The OS of the BM patients did not differ significantly between the two treatment groups. CONCLUSIONS: The addition of atezolizumab to EP as a first-line treatment for ES-SCLC was found to improve survival outcomes. This treatment combination may also prolong PFS in patients with BM, regardless of the administration of cranial irradiation. However, among the BM patients in our study, there was no significant difference in OS between the two treatment groups.

Cognitive behavioral stress management effectively facilitates neurologic recovery, alleviates mental distress, and elevates health status in acute ischemic stroke patients

Cognitive behavioral stress management (CBSM) relieves physical and psychological burdens in patients with some central nervous system diseases, while its utility in acute ischemic stroke (AIS) patients is unclear. This study aimed to explore the effect of CBSM on neurologic recovery and psychosomatic health in AIS patients. Totally, 176 naive AIS patients were randomized into routine care (RC) group (n=88) and CBSM group (n=88) to receive a 3-month corresponding intervention. Modified Rankin scale (mRS) scores at the first month after discharge (M1) (P=0.008) and the third month after discharge (M3) (P=0.016) were lower in the CBSM group than in the RC group. The proportion of AIS patients with mRS score >2 at M3 was reduced in CBSM group vs RC group (P=0.045). Hospital anxiety depression scale (HADS)-anxiety score at M3 (P=0.016), HADS-depression score at M3 (P=0.005), and depression rate at M3 (P=0.021) were decreased in the CBSM group vs the RC group. EuroQol-5 dimension scores at M1 (P=0.024) and M3 (P=0.012) were decreased, while EuroQol-visual analogue scale score at M3 (P=0.026) was increased in the CBSM group vs the RC group. By subgroup analyses, CBSM had favorable outcomes in AIS patients with age ≤65 years. CBSM was beneficial to neurologic recovery and distress relief in AIS patients with an education level of middle school or above, and to health status in those with an education level of primary school or uneducated. In conclusion, CBSM benefitted neurologic recovery and psychosomatic health in AIS patients with minor neurological deficits, however, further studies should verify these results with a larger sample size and longer follow-up.

DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors.

OBJECTIVE: Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors. METHODS: To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR. RESULTS: The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo. CONCLUSION: In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.

Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study.

BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Frequently mutated genes in predicting the relapse of stage I lung adenocarcinoma.

PURPOSE: Approximately, 45-65% stage I non-small cell lung cancer (NSCLC) patients with surgical resection relapse within 5 years. Therefore, it is urgent to identify the predictors involved in the relapse of stage I NSCLC. METHODS/PATIENTS: Targeted sequencing was used to examine the mutation of tumor tissues and matched adjacent normal tissues from 35 patients with stage I lung adenocarcinoma (LUAD). Then, tissue microarrays containing tumor tissues from 149 stage I LUAD patients were used to assess protein expression of frequently mutated genes by immunohistochemistry. COX regression model was used to evaluate the impacts of frequently mutated genes and their protein expression on relapse-free survival (RFS) in stage I LUAD. RESULTS AND CONCLUSIONS: Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15-1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54-6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance.

Fast screening of enteropathogens in marine water samples.

This study aimed to fast screen the microbiological contamination of recreational waters using a TaqMan Array Card (TAC), a multiplexed platform designed for the simultaneous detection of 35 enteropathogens. Surface and deep marine water samples were concentrated by skimmed milk flocculation and processed for nucleic acid extraction protocol using QIAamp Fast DNA Stool Mini Kit. Twelve microorganisms and parasites, including bacteria (n = 6), protozoa (4), and viruses (2), were detected in 85.7% (24/28) of samples. Campylobacter (82.1%), Cryptosporidium (39.3%), and adenovirus (14.3%) were the most detected pathogens. Neither fungi nor helminths were detected. A spatial pollution profile of microbiological contamination was observed in the area. Methodologies for simultaneous detection of multiple pathogens, such as TAC, can assist decision-makers by providing a quick assessment of the microbiological water quality in areas used for recreational purposes, which in many cases are in accordance with the bacteriological indicators.

Effect of football on rehabilitation of ankle injury patients / Efeito do futebol na reabilitação de pacientes com lesão no tornozelo / Efecto del fútbol en la rehabilitación de pacientes con lesiones de tobillo

ABSTRACT Introduction: Brief introduction: Ankle tendon and ligament sports injuries are common in football players. Objective: To continue to improve special strength training related to the characteristics of football after rehabilitation of injured ankle tendons and ligaments. Methods: Two master football sportsmen were rehabilitated by multi-point equal-length, short-arc and long-arc equal-speed training combined with balance ability exercises. Results: There were two long muscle L be maintain muscle tone plantar flexors force four times of 96 n/m, n/m 121, 140 n/m, 145 n/m than back flexors force of 63 n/m, 52 n/m, 60 n/m, 74 n/m tall. Plantar flexor fatigue was 57%, 30%, 29%, 12%, 28%, 18%, 20%, 21%. Conclusions: With the passing of time, the relative peak moment value of the right ankle plantar flexor muscle group of the two patients kept rising, the dorsiflexor muscle was basically flat, and the work fatigue index decreased step by step, indicating that the right ankle muscle strength level was significantly improved, the anti-fatigue ability was improved, and the rehabilitation treatment had a good effect. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: Introdução breve: Lesões esportivas nos tendões e ligamentos do tornozelo são comuns em jogadores de futebol. Objetivo: Atingir melhora no treinamento de força especial relacionado com as lesões características do futebol depois de reabilitação de tendões e ligamentos do tornozelo. Métodos: Dois futebolistas de primeira linha foram reabilitados por treinamento multipontos de comprimento igual, arco curto e arco longo em velocidade igual, combinado com exercícios de habilidade de equilíbrio. Resultados: Havia dois músculos longos L para manter o tônus muscular, força dos flexores plantares antes e depois de quatro vezes de 96 n/m, 121 n/m, 140 n/m, 145 n/m e força dos flexores dorsais de 63 n/m, 52 n/m, 60 n/m, 74 n/m de altura. A fadiga do flexor plantar foi de 57%, 30%, 29%, 12%, 28%, 18%, 20%, 21%. Conclusões: Com o passar do tempo, o valor do momento de pico relativo do grupo de músculos flexores plantares do tornozelo direito dos dois pacientes continuou aumentando; o músculo flexor do dorso estava basicamente plano e o índice de fadiga no trabalho diminuiu gradativamente, indicando que o nível de força muscular do tornozelo direito melhorou significativamente, assim como a capacidade antifadiga e, portanto, que o tratamento de reabilitação teve efeito positivo. Nível de Evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: Breve introducción: Las lesiones deportivas en los tendones y ligamentos del tobillo son comunes en los jugadores de fútbol. Objetivo: Lograr una mejora en el entrenamiento de fuerza especial relacionado con las lesiones características del fútbol tras la rehabilitación de los tendones y ligamentos del tobillo. Métodos: Dos jugadores de fútbol de alto nivel fueron rehabilitados mediante un entrenamiento multipunto de igual longitud, arco corto y arco largo a igual velocidad, combinado con ejercicios de habilidad de equilibrio. Resultados: Hubo dos músculos L largos para mantener el tono muscular, fuerza de los flexores plantares antes y después de cuatro veces de 96 n/m, 121 n/m, 140 n/m, 145 n/m y fuerza de los flexor dorsales de 63 n/m, 52 n/m, 60 n/m, 74 n/m de altura. La fatiga de los flexores plantares fue del 57%, 30%, 29%, 12%, 28%, 18%, 20%, 21%. Conclusiones: Con el paso del tiempo, el valor del momento máximo relativo del grupo de músculos flexores plantares del tobillo derecho de los dos pacientes continuó aumentando; el músculo flexor dorsal estaba básicamente plano y el índice de fatiga de trabajo disminuyó gradualmente, lo que indica que el nivel de fuerza muscular del tobillo derecho mejoró significativamente, al igual que la capacidad antifatiga, y, por tanto, que el tratamiento de rehabilitación tuvo un efecto positivo. Nivel de Evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

The characteristic of otoacoustic emissions in full-term neonates according to ABO blood groups / Característica das emissões otoacústicas em neonatos a termo segundo grupos sanguíneos do sistema ABO

Abstract Introduction: Previous research has suggested that individuals with different blood groups show varied incidences of noise-induced hearing loss. The reduced otoacoustic emissions amplitudes indicate the higher possibilities of outer hair cell damage for noise exposure. Objective: The objective is to analyze the characteristics of otoacoustic emissions, including the occurrence of spontaneous otoacoustic emission and the amplitudes of distortion product otoacoustic emission at certain frequencies in full term neonates with different ABO blood groups. Methods: A total of 80 selected full-term female neonates who passed the initial newborn hearing screen were enrolled into the study, with equal number of participants in four ABO blood groups (Blood Group A, Blood Group B, Blood Group AB, Blood Group O). Measurements of spontaneous otoacoustic emission and distortion product otoacoustic emission were performed in both ears for all participants. Results: (1) The blood group O participants showed significantly fewer spontaneous otoacoustic emission occurrences than the other three blood groups (A = 70%, B = 80%, AB = 67%, O = 25%, p < 0.05). (2) The blood group O participants showed lower DPOAE amplitudes at 1257 Hz (M = 4.55 dB, SD = 8.36), 1587 Hz (M = 11.60 dB, SD = 6.57), 3174 Hz (M = 7.25 dB, SD = 5.99), 5042 Hz (M = 13.60, SD = 6.70) than participants with the other three blood groups in left ears (p < 0.05). In right ears, the blood group O participants showed reduced amplitudes at 1257 Hz (M = 6.55 dB, SD = 8.36), 1587 Hz (M = 13.60 dB, SD = 6.57), 3174 Hz (M = 7.65 dB, SD = 6.43), 5042 Hz (M = 13.65 dB, SD = 6.50) than participants from non-O blood groups (p < 0.05). Conclusion: Female individuals with blood group O have lower otoacoustic emissions values than individuals with the other three blood groups. We need to further investigate the possible relationships between ABO blood group and cochlear function, including the potential influences of noise damage on cochlear outer hair cells.

Resumo Introdução: Pesquisas anteriores sugeriram que indivíduos de diferentes grupos sanguíneos apresentam incidências distintas de perda auditiva induzida por ruído. As amplitudes reduzidas das emissões otoacústicas indicaram maiores ou menores possibilidades de danos às células ciliadas por exposição a ruídos. Objetivo: Analisar as características das emissões otoacústicas, inclusive a ocorrência de emissões otoacústicas espontâneas e as amplitudes de emissões otoacústicas por produto de distorção em determinadas frequências em neonatos a termo de diferentes grupos sanguíneos do sistema ABO. Método: Foram incluídos 80 neonatos a termo selecionados na triagem auditiva neonatal inicial para participar do estudo, com número igual de participantes de grupos sanguíneos do sistema ABO (grupo sanguíneo A, grupo sanguíneo B, grupo sanguíneo AB e grupo sanguíneo O). As emissões otoacústicas espontâneas e emissões otoacústicas por produto de distorção foram medidas em ambas as orelhas de todos os participantes. Resultados: (1) Os participantes do grupo sanguíneo O apresentaram ocorrências de emissões otoacústicas espontâneas significantemente menores do que os dos outros três grupos sanguíneos (A = 70%, B = 80%, AB = 67%, O = 25%, p < 0,05). (2) Os participantes do grupo sanguíneo O apresentaram amplitudes de emissões otoacústicas por produto de distorção mais baixas a 1257 Hz (M = 4,55 dB, DP = 8,36), 1587 Hz (M = 11,60 dB, DP = 6,57), 3174 Hz (M = 7,25 dB, DP = 5,99), 5042 Hz (M = 13,0, DP = 6,70) do que os participantes dos outros três grupos sanguíneos nas orelhas esquerdas (p < 0,05). Nas orelhas direitas, os participantes do grupo sanguíneo O apresentaram amplitudes reduzidas em 1257 Hz (M = 6,55 dB, DP = 8,36), 1587 Hz (M = 13,60 dB, DP = 6,57), 3174 Hz (M = 7,65 dB, DP = 6,43), 5042 Hz (M = 13,65 dB, DP = 6,50) em comparação aos participantes de grupos sanguíneos não O (p < 0,05). Conclusão: Os indivíduos do sexo feminino do grupo sanguíneo O apresentaram valores menores de emissões otoacústicas do que os indivíduos dos outros três grupos sanguíneos. É necessário continuar a investigar as possíveis relações entre o grupo sanguíneo ABO e a função coclear, inclusive as possíveis influências do dano por ruídos às células ciliadas externas da cóclea.

Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.

Efficacy of vitamin D supplement in children with nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The number of children with nonalcoholic fatty liver disease (NAFLD) is proliferating. However, currently, there are no drugs approved for the management of NAFLD. There have been some studies on vitamin D and NAFLD in children. However, the effectiveness of vitamin D in children with NAFLD has not been systematically evaluated. The objective of this systematic review will be to evaluate the effectiveness of vitamin D in children with NAFLD. METHODS: We will search through PubMed, Google Scholar, Cochrane Library, Web of Science, and the ClinicalTrials.gov website without restriction on publishing status. To supplement our search strategy, we will scan the reference lists of the identified studies for detailed evaluation for additional possible eligible studies, and we will also search conference proceedings related to this topic. All databases were searched from inception to present. Any clinical randomized controlled trials related to vitamin D supplement for treating NAFLD (simple steatosis/NAFL and NASH) in children will be included. NAFLD had to be diagnosed by liver histology, imaging (ultrasound, computer tomography, magnetic resonance imaging). The primary outcomes will be changes in liver fibrosis and liver enzymes. The variations in serum vitamin D level, BMI, insulin levels, lipid profiles, liver fat content will also be assessed. All statistical analyses will be carried out using RevMan, version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. RESULTS: This study will provide a comprehensive high-quality synthesis to evaluate the effectiveness of vitamin D supplementation in children with NAFLD. CONCLUSION: This systematic review and meta-analysis will provide evidence to judge whether vitamin D supplementation is an effective intervention for children with NAFLD. REGISTRATION NUMBER: INPLASY202050049.

Hepatic autophagy fluctuates during the development of non-alcoholic fatty liver disease.

INTRODUCTION AND OBJECTIVES: Autophagy has emerged as a critical regulatory pathway in non-alcoholic fatty liver disease (NAFLD). However, the variability of hepatic autophagy during NAFLD development remains controversial. This study aimed to elucidate the dynamics of hepatic autophagy and its underlying mechanism during NAFLD development both in vivo and in vitro. MATERIALS AND METHODS: Autophagy markers were evaluated in the livers of mice fed a high fat diet or a methionine-choline-deficient diet and in HepG2 cells treated with palmitic acid (PA) by western blotting. Intrahepatic and intracellular triacylglycerol levels were assessed using biochemical quantification and lipid staining. Autophagic flux was monitored using an LC3 turnover assay and tandem mRFP-GFP-LC3 fluorescence analysis. RESULTS: Hepatic autophagy was enhanced in early stages but blocked at later stages of NAFLD development both in vivo and in vitro. Analysis of autophagic flux revealed that both autophagic synthesis and degradation were initially activated and progressively inhibited afterwards. The activation of mammalian target of rapamycin complex 1 (mTORC1), a central regulator of autophagy, was found to be negatively correlated with autophagic synthesis; moreover, pharmacological inhibition of mTORC1 by rapamycin alleviated hepatic steatosis through recovery of autophagic flux in hepatocytes with prolonged PA treatment. CONCLUSIONS: Hepatic autophagy fluctuates during the development of NAFLD in which mTORC1 signalling plays a critical regulatory role, suggesting a therapeutic potential of autophagy modulation by targeting the mTORC1 signalling pathway in NAFLD.

The characteristic of otoacoustic emissions in full-term neonates according to ABO blood groups.

INTRODUCTION: Previous research has suggested that individuals with different blood groups show varied incidences of noise-induced hearing loss. The reduced otoacoustic emissions amplitudes indicate the higher possibilities of outer hair cell damage for noise exposure. OBJECTIVE: The objective is to analyze the characteristics of otoacoustic emissions, including the occurrence of spontaneous otoacoustic emission and the amplitudes of distortion product otoacoustic emission at certain frequencies in full term neonates with different ABO blood groups. METHODS: A total of 80 selected full-term female neonates who passed the initial newborn hearing screen were enrolled into the study, with equal number of participants in four ABO blood groups (Blood Group A, Blood Group B, Blood Group AB, Blood Group O). Measurements of spontaneous otoacoustic emission and distortion product otoacoustic emission were performed in both ears for all participants. RESULTS: (1) The blood group O participants showed significantly fewer spontaneous otoacoustic emission occurrences than the other three blood groups (A=70%, B=80%, AB=67%, O=25%, p< 0.05). (2) The blood group O participants showed lower DPOAE amplitudes at 1257 Hz (M = 4.55 dB, SD = 8.36), 1587 Hz (M = 11.60 dB, SD = 6.57), 3174 Hz (M = 7.25 dB, SD = 5.99), 5042 Hz (M = 13.60, SD = 6.70) than participants with the other three blood groups in left ears (p < 0.05). In right ears, the blood group O participants showed reduced amplitudes at 1257Hz (M=6.55dB, SD=8.36), 1587Hz (M=13.60dB, SD=6.57), 3174Hz (M=7.65dB, SD=6.43), 5042Hz (M=13.65dB, SD=6.50) than participants from non-O blood groups (p<0.05). CONCLUSION: Female individuals with blood group O have lower otoacoustic emissions values than individuals with the other three blood groups. We need to further investigate the possible relationships between ABO blood group and cochlear function, including the potential influences of noise damage on cochlear outer hair cells.

Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells.

BACKGROUND: Berberine (BBR), a compound extracted from a variety of medicinal herbs, has been shown multiple pharmacological effects against cancer cells of different origins. Cisplatin (DDP) is known as an effective chemotherapeutic agent against cancer by inducing DNA damage and cell apoptosis. However, the effect of the combined used of BBR and DDP on cell necroptosis in ovarian cancer has not been reported. METHODS: OVCAR3 and three patient-derived primary ovarian cancer cell lines (POCCLs) were chosen as the experimental objects. To determine the potential anti-cancer activity of BBR and DDP in combination, we firstly treated OVCAR3 and POCCLs cells with BBR and/or DDP. The cell viability of OVCAR3 and POCCLs with treatment of BBR or DDP for different hours was measured by CCK-8 assay. Flow cytometry was used to analyze cell cycle distribution and changes in apoptotic cells after treatment with BBR and/or DDP. The morphological changes of OVCAR3 cells were observed by using Transmission electron microscopy (TEM) analysis. Proliferation, apoptosis and necroptosis related markers of OVCAR3 and POCCLs with treatment of BBR or DDP were measured by RT-qPCR, western blotting and immunofluorescence assay. RESULTS: Our results demonstrated that BBR significantly inhibited the proliferation of OVCAR3 and primary ovarian cancer cells in a dose- and time-dependent manner. The combination treatment of BBR and DDP had a prominent inhibitory effect on cancer cell growth and induced G0/G1 cell cycle arrest. TEM revealed that the majority of cells after BBR or DDP treatment had an increasing tendency of typical apoptotic and necrotic cell death morphology. Besides, BBR and DDP inhibited the expression of PCNA and Ki67 and enhanced the expression and activation of Caspase-3, Caspase-8, RIPK3 and MLKL. CONCLUSION: This study proposed that the combination therapy of BBR and DDP markedly enhanced more ovarian cancer cell death by inducing apoptosis and necroptosis, which may improve the anticancer effect of chemotherapy drugs. The apoptosis involved the caspase-dependent pathway, while the necroptosis involved the activation of the RIPK3-MLKL pathway. We hope our findings might provide a new insight for the potential of BBR as a therapeutic agent in the treatment of ovarian cancer.

Hydrogen sulfide protects H9c2 cardiomyoblasts against H2O2-induced apoptosis.

Reactive oxygen species (ROS) are highly reactive chemical species that may cause irreversible tissue damage, and play a critical role in cardiovascular diseases. Hydrogen sulfide (H2S) is a gasotransmitter that acts as a ROS scavenger with cardio-protective effects. In this study, we investigated the cytoprotective effect of H2S against H2O2-induced apoptosis in cardiomyocytes. H9c2 rat cardiomyoblasts were treated with H2S (100 µM) 24 h before challenging with H2O2 (100 µM). Apoptosis was then assessed by annexin V and PI, and mitochondrial membrane potential was measured using a fluorescent probe, JC-1. Our results revealed that H2S improved cell viability, reduced the apoptotic rate, and preserved mitochondrial membrane potential. An increased Bcl-2 to Bax ratio was also seen in myocytes treated with H2S after H2O2-induced stress. Our findings indicated a therapeutic potential for H2S in preventing myocyte death following ischemia/reperfusion.

Huntsmen of the Caribbean: Multiple tests of the GAARlandia hypothesis.

The origin of the Caribbean biota remains debated, but amassing evidence suggests important roles of both dispersal and vicariance events in the colonization the archipelago. The most prominent vicariance hypothesis is colonization over the GAARlandia land bridge that putatively connected the Greater Antilles to South America around 33 mya. This hypothesis has received support from studies of individual lineages, but its main prediction-the simultaneous colonization of multiple lineages during that time window-requires further unambiguous corroboration. Here, we examine the phylogenetic structure of huntsman spiders (Sparassidae) of the Caribbean. Huntsman spiders are appropriate models for this question, as they are expected to be dispersal limited as substrate and foliage dwelling spiders that rarely balloon, yet are found on some volcanic islands, and thus at least some overwater dispersal must have occurred. We focus on the Caribbean endemic Neostasina, but also include Caribbean Olios, for a deeper biogeographical understanding. We use two mitochondrial and four nuclear markers to reconstruct dated phylogenetic trees and to test taxonomic and biogeographic hypotheses. Our analyses strongly support the monophyly of Neostasina and the polyphyly of Olios, with a new clade endemic to the Caribbean. Both Neostasina and Caribbean Olios occur on the Greater and Lesser Antilles and independently colonized the Caribbean around 36-28 mya. Hypothesis testing in BioGeoBEARS suggests a role of the GAARlandia landbridge in the colonization of both clades. The 'Olios-like' clade, in contrast, is restricted to the southern Lesser Antilles and shows a biogeographic history consistent with colonization from S. America, probably within the last 10 my. Thus, many spider lineages on the Greater Antilles seem to have colonized the Caribbean during a relatively short time span approximately coinciding with the proposed timing of GAARlandia. The synchronous colonization of multiple lineages suggests a temporary land connection. However, the main problem in concluding synchronous events across lineages in this study, as in most others, is the ambiguity in chronogram analyses meaning that many different patterns can be 'consistent' with GAARlandia, thus potentially providing a false positive result. Broad comparative biogeographical studies such as the CarBio project will offer the best opportunity to multiply test shared biogeographic patterns among independent lineages. The current paper contributes evidence from multiple lineages that will contribute to this synthesis.

Huntsmen of the Caribbean: multiple tests of the GAARlandia hypothesis

The origin of the Caribbean biota remains debated, but amassing evidence suggests important roles of both dispersal and vicariance events in the colonization the archipelago. The most prominent vicariance hypothesis is colonization over the GAARlandia land bridge that putatively connected the Greater Antilles to South America around 33?mya. This hypothesis has received support from studies of individual lineages, but its main prediction—the simultaneous colonization of multiple lineages during that time window—requires further unambiguous corroboration. Here, we examine the phylogenetic structure of huntsman spiders (Sparassidae) of the Caribbean. Huntsman spiders are appropriate models for this question, as they are expected to be dispersal limited as substrate and foliage dwelling spiders that rarely balloon, yet are found on some volcanic islands, and thus at least some overwater dispersal must have occurred. We focus on the Caribbean endemic Neostasina, but also include Caribbean Olios, for a deeper biogeographical understanding. We use two mitochondrial and four nuclear markers to reconstruct dated phylogenetic trees and to test taxonomic and biogeographic hypotheses. Our analyses strongly support the monophyly of Neostasina and the polyphyly of Olios, with a new clade endemic to the Caribbean. Both Neostasina and Caribbean Olios occur on the Greater and Lesser Antilles and independently colonized the Caribbean around 36–28?mya. Hypothesis testing in BioGeoBEARS suggests a role of the GAARlandia landbridge in the colonization of both clades. The ‘Olios-like’ clade, in contrast, is restricted to the southern Lesser Antilles and shows a biogeographic history consistent with colonization from S. America, probably within the last 10 my. Thus, many spider lineages on the Greater Antilles seem to have colonized the Caribbean during a relatively short time span approximately coinciding with the proposed timing of GAARlandia. The synchronous colonization of multiple lineages suggests a temporary land connection. However, the main problem in concluding synchronous events across lineages in this study, as in most others, is the ambiguity in chronogram analyses meaning that many different patterns can be ‘consistent’ with GAARlandia, thus potentially providing a false positive result. Broad comparative biogeographical studies such as the CarBio project will offer the best opportunity to multiply test shared biogeographic patterns among independent lineages. The current paper contributes evidence from multiple lineages that will contribute to this synthesis.