Prediction of visceral leishmaniasis incidence using the Seasonal Autoregressive Integrated Moving Average model (SARIMA) in the state of Maranhão, Brazil / Previsão da incidência da leishmaniose visceral usando o modelo de média móvel integrado autorregressivo sazonal (SARIMA) no Maranhão, Brasil

Abstract Visceral leishmaniasis (VL) is an infectious disease predominant in countries located in the tropics. The prediction of occurrence of infectious diseases through epidemiologic modeling has revealed to be an important tool in the understanding of its occurrence dynamic. The objective of this study was to develop a forecasting model for the incidence of VL in Maranhão using the Seasonal Autoregressive Integrated Moving Average model (SARIMA). We collected monthly data regarding VL cases from the National Disease Notification System (SINAN) corresponding to the period between 2001 and 2018. The Box-Jenkins method was applied in order to adjust a SARIMA prediction model for VL general incidence and by sex (male or female) for the period between January 2019 and December 2013. For 216 months of this time series, 10,431 cases of VL were notified in Maranhão, with an average of 579 cases per year. With regard to age range, there was a higher incidence among the pediatric public (0 to 14 years of age). There was a predominance in male cases, 6437 (61.71%). The Box-Pierce test figures for overall, male and female genders supported by the results of the Ljung-Box test suggest that the autocorrelations of residual values act as white noise. Regarding monthly occurrences in general and by gender, the SARIMA models (2,0,0) (2,0,0), (0,1,1) (0,1,1) and (0,1,1) (2, 0, 0) were the ones that mostly adjusted to the data respectively. The model SARIMA has proven to be an adequate tool for predicting and analyzing the trends in VL incidence in Maranhão. The time variation determination and its prediction are decisive in providing guidance in health measure intervention.

Resumo A leishmaniose visceral (LV) é uma doença de natureza infecciosa, predominante em países de zonas tropicais. A predição de ocorrência de doenças infecciosas através da modelagem epidemiológica tem se revelado uma importante ferramenta no entendimento de sua dinâmica de ocorrência. O objetivo deste estudo foi desenvolver um modelo de previsão da incidência da LV no Maranhão usando o modelo de Média Móvel Integrada Autocorrelacionada Sazonal (SARIMA). Foram coletados os dados mensais de casos de LV através do Sistema de Informação de Agravos de Notificação (SINAN) correspondentes ao período de 2001 a 2018. O método de Box-Jenkins foi aplicado para ajustar um modelo de predição SARIMA para incidência geral e por sexo (masculino e feminino) de LV para o período de janeiro de 2019 a dezembro de 2023. Durante o período de 216 meses dessa série temporal, foram registrados 10.431 casos de LV no Maranhão, com uma média de 579 casos por ano. Em relação à faixa etária, houve maior registro no público pediátrico (0 a 14 anos). Houve predominância do sexo masculino, com 6437 casos (61,71%). Os valores do teste de Box-Pierce para incidência geral, sexo masculino e feminino reforçados pelos resultados do teste Ljung-Box sugerem que as autocorrelações de resíduos apresentam um comportamento de ruído branco. Para incidência mensal geral e por sexo masculino e feminino, os modelos SARIMA (2,0,0) (2,0,0), (0,1,1) (0,1,1) e (0,1,1) (2, 0, 0) foram os que mais se ajustaram aos dados, respectivamente. O modelo SARIMA se mostrou uma ferramenta adequada de previsão e análise da tendência de incidência da LV no Maranhão. A determinação da variação temporal e sua predição são determinantes no norteamento de medidas de intervenção em saúde.

Minimum acceptable diet and its associated factors among children aged 6-23 months in Lalibela, northeast Ethiopia: a community-based cross-sectional study.

The first 2 years of life are a critical window of opportunity for ensuring optimal child growth and development. In Ethiopia, the magnitude of the minimum acceptable diet ranges from 7 to 74⋅6 %. The evidence revealed the variation and unrelated data on the prevalence of minimum acceptable diet. Therefore, the present study aimed to assess the minimum acceptable diet and its associated factors among children aged 6-23 months in Lalibela town administration, northeast Ethiopia. A community-based cross-sectional study was conducted in Lalibela town administration, northeast Ethiopia among 387 mothers/caregivers with children aged 6-23 months from May 1 to 30, 2022. The data were entered by Epidata version 3.1 and analysed by SPSS version 25.0. A multivariable binary logistic regression model was fitted to identify factors associated with minimum acceptable diet. The degrees of association were assessed using an adjusted odds ratio with a 95 % confidence interval and P-value of 0⋅05. The magnitude of minimum acceptable diet in the study area was 16⋅7 % (95 % confidence interval: 12⋅8-20⋅6 %). Sex of child, getting infant and young child feeding counselling at antenatal care, infant feeding practice-related knowledge and childhood illness are the variables that were found to be an independent predictor of minimum acceptable diet. Health facilities should strengthen infant feeding counselling starting from antenatal care visits during pregnancy for the recommended minimum acceptable diet is crucial.

Epidemiological and Spatiotemporal Descriptive Analysis of Patients with Nonsyndromic Cleft Lip and/or Palate: A 12-Year Retrospective Study in Southern Iran.

Objectives: The current study is aimed at evaluating epidemiological characteristics and spatiotemporal distribution of cleft lip and/or palate (CL/P) in the south of Iran. Methods: Data were extracted from the 1840 medical records of patients who were referred to the Cleft Lip and Palate Center of Shiraz University of Medical Sciences, from January 1, 2011, to September 1, 2022. The collected variables included demographic data (gender, birth date and season, place, birth order, and weight), cleft types and the subtypes, parental information (health status, education level, marital status, and age during the pregnancy), and other basic parameters. The chi-square test at a significance level of 0.05 was used to analyze collected data. The geographic information system (GIS) analysis was also used for analyzing the spatial distribution of CL/P patients. Results: Based on our inclusion criteria, 1281 nonsyndromic patients were included in this study. The most common type was cleft lip and palate (CLP) with 48.32%, whereas cleft palate (CP) and cleft lip (CL) accounted for 40.75% and 10.93% of the patients, respectively. There was a progressive increase in the frequency of all types of clefts, and most of them were male (P ≤ 0.001). The urban population outnumbered the rural ones in all provinces. Parents were mostly healthy (>80%) with low educational status (47.5%). Most born CL/P patients were from consanguineous marriages (58.9%), especially between first-degree relatives. A majority of CL/P patients (73.1%) were born in the first two gestations with a birth weight of 2500-4000 g (77.4%). Most infants with CL/P (84.3%) were born from mothers who had at least one of the predisposing factors. Conclusion: In this study, the frequency of cleft types and subtypes was similar to the existing literature. However, high rate of consanguineous marriage, especially between first-degree relatives, was the most notable feature of this population.

Hypochondriacal fear of breast cancer - a failure of the dual maternal functions: "mother-of-the-infant" and "censorship of the lover".

Fain's theoretical conceptualisation of the 'Censorship of the Lover' (1971) offers a framework to investigate the unrepresented traumatic aspects of the hypochondriacal fear of breast cancer. The failure of the maternal role to function as both the mother-of-the-infant and the lover-of-the-father creates considerable deficits in the primal psychosomatic tie. The authors aim to draw attention on to the importance of the mother-of-the-infant facet of the dual maternal function. The threatening repetitive scenario experienced by the hypochondriacal patient is considered as a form of pathological autoerotism, indicating an insufficient construction of psychic bisexuality, and, subsequently, of sexual identity. The hypochondriacal fear of breast cancer constitutes a positive hallucination whereas the denial of the healthy breast represents a negative hallucination (Green, 1993). The topos of the body onto which the fear of death is projected implies the existence of underlying associations related to the subject's history. The complexities surrounding such acute hypochondriacal anxieties are demonstrated in the analysis of a female patient, during which the analytic dyad was called upon to disclose and construct different levels of meaning in order to enhance the capacity for mentalization.

Molecular epidemiology of Acinetobacter baumannii complex causing invasive infections in Korean children during 2001-2020.

BACKGROUND: Acinetobacter baumannii (AB) has emerged as one of the most problematic pathogens affecting critically ill patients. This study aimed to investigate the longitudinal epidemiology of AB causing invasive diseases in children. METHODS: Acinetobacter spp. cultured from sterile body fluids and identified as Acinetobacter calcoaceticus-baumannii (ACB) complexes by automated systems from children aged below 19 years old were prospectively collected during 2001-2020. The discriminative partial sequence of rpoB gene was sequenced to identify the species, and sequence types (STs) were determined. Temporal changes in antimicrobial susceptibilities and STs were analyzed. RESULTS: In total, 108 non-duplicate ACB isolates were obtained from patients with invasive infections. The median age was 1.4 (interquartile range, 0.1-7.9) years, and 60.2% (n = 65) were male. Acinetobacter baumannii comprised 55.6% (n = 60) of the isolates, and the 30-day mortality was higher in patients with isolated AB than in those with non-baumannii Acinetobacter spp. (46.7% vs. 8.3%, P < 0.001). After 2010, complete genotype replacement was observed from non-CC92 genotypes to only CC92 genotypes. Carbapenem resistance rates were highest in AB CC92 (94.2%), followed by AB non-CC92 (12.5%) and non-baumannii Acinetobacter spp. (2.1%). During 2014-2017, which included clustered cases of invasive ST395, colistin resistance increased to 62.5% (n = 10/16), showing a mortality rate of 88% during this period. CONCLUSION: Complete genotype replacement of non-CC92 with CC92 genotypes was observed. AB CC92 was extensively drug-resistant, and pandrug resistance was observed depending on the ST, warranting careful monitoring.

The Multilayered Atrium: An Unusual Case of a Life-Threatening Cor Triatriatum With Persistent Levotrial Cardinal Vein in a 2-Month-Old Infant.

Cor triatriatum sinister (CTS) is a rare congenital cardiac malformation. In CTS, a fibromuscular membrane subdivides the left atrium into 2 chambers. The communication between the 2 chambers is through 1 or more orifices in the dividing membrane. We present an interesting case of a 2-month-old infant with obstructed CTS membrane who first presented on account of poor feeding and failure to thrive. Echocardiography showed a persistent levoatrial cardinal vein (LACV) connecting the left atrium and the innominate vein. This allowed the proximal left atrial chamber to decompress its blood volume into the innominate vein and subsequently the superior vena cava. There was minimal prograde blood flow across the Cor triatriatum membrane, so the majority of pulmonary venous blood ultimately returned to the heart by way of the decompressing vertical vein into the systemic venous circulation. Surgical repair was performed with an uneventful postoperative course. The specific anatomical variant of Cor triatriatum found in our subject has rarely been reported.

Neonatal health care costs of very preterm babies in England: a retrospective analysis of a national birth cohort.

OBJECTIVES: Babies born between 27+0 and 31+6 weeks of gestation represent the largest group of very preterm babies requiring National Health Service (NHS) care; however, up-to-date, cost figures for the UK are not currently available. This study estimates neonatal costs to hospital discharge for this group of very preterm babies in England. DESIGN: Retrospective analysis of resource use data recorded within the National Neonatal Research Database. SETTING: Neonatal units in England. PATIENTS: Babies born between 27+0 and 31+6 weeks of gestation in England and discharged from a neonatal unit between 2014 and 2018. MAIN OUTCOME MEASURES: Days receiving different levels of neonatal care were costed, along with other specialised clinical activities. Mean resource use and costs per baby are presented by gestational age at birth, along with total costs for the cohort. RESULTS: Based on data for 28 154 very preterm babies, the annual total costs of neonatal care were estimated to be £262 million, with 96% of costs attributable to routine daily care provided by units. The mean (SD) total cost per baby of this routine care varied by gestational age at birth; £75 594 (£34 874) at 27 weeks as compared with £27 401 (£14 947) at 31 weeks. CONCLUSIONS: Neonatal healthcare costs for very preterm babies vary substantially by gestational age at birth. The findings presented here are a useful resource to stakeholders including NHS managers, clinicians, researchers and policymakers.

The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset.

Evidence has accumulated that gut microbiota and its metabolites, in particular the short-chain fatty acid propionate, are significant contributors to the pathogenesis of a variety of diseases. However, little is known regarding its impact on pediatric bronchial asthma, one of the most common allergic diseases in childhood. This study aimed to elucidate whether, and if so how, intestinal propionate during lactation is involved in the development of bronchial asthma. We found that propionate intake through breast milk during the lactation period resulted in a significant reduction of airway inflammation in the offspring in a murine house dust mite-induced asthma model. Moreover, GPR41 was the propionate receptor involved in suppressing this asthmatic phenotype, likely through the upregulation of Toll-like receptors. In translational studies in a human birth cohort, we found that fecal propionate was decreased one month after birth in the group that later developed bronchial asthma. These findings indicate an important role for propionate in regulating immune function to prevent the pathogenesis of bronchial asthma in childhood.

Rapid quantitative analysis of calcium in infant formula powder assisted by long short-term memory with variable importance using laser-induced breakdown spectroscopy.

Calcium is the main mineral responsible for healthy bone growth in infants. Laser-induced breakdown spectroscopy (LIBS) was combined with a variable importance-based long short-term memory (VI-LSTM) for the quantitative analysis of calcium in infant formula powder. First, the full spectra were used to establish PLS (partial least squares) and LSTM models. The R2 and root-mean-square error (RMSE) of the test set (R P2 and R M S E P) were 0.1460 and 0.0093 in the PLS method, respectively, and 0.1454 and 0.0091 in the LSTM model, respectively. To improve the quantitative performance, variable selection based on variable importance was introduced to evaluate the contribution of input variables. The variable importance-based PLS (VI-PLS) model had R P2 and R M S E P of 0.1454 and 0.0091, respectively, whereas the VI-LSTM model had R P2 and R M S E P of 0.9845 and 0.0037, respectively. Compared with the LSTM model, the number of input variables in the VI-LSTM model was reduced to 276, R P2 was improved by 114.63%, and R M S E P was reduced by 46.38%. The mean relative error of the VI-LSTM model was 3.33%. We confirm the predictive ability of the VI-LSTM model for the calcium element in infant formula powder. Thus, combining VI-LSTM modeling and LIBS has great potential for the quantitative elemental analysis of dairy products.

Skin and Soft Tissue Infections in Young Infants.

INTRODUCTION: The management of young infants with skin and soft tissue infection is not well-defined. METHODS: We performed a survey study of pediatric hospital medicine, emergency medicine, urgent care, and primary care physicians to assess the management of young infants with skin and soft tissue infection. The survey included 4 unique scenarios of a well-appearing infant with uncomplicated cellulitis of the calf with the combination of age ≤ 28 days vs 29-60 days and the presence vs absence of fever. RESULTS: Of 229 surveys distributed, 91 were completed (40%). Hospital admission was chosen more often for younger infants (≤ 28 days) versus older infants regardless of fever status (45% vs 10% afebrile, 97% vs 38% febrile, both P < 0.001). Younger infants were more likely to get blood, urine, and cerebrospinal fluid studies (P < 0.01). Clindamycin was chosen in 23% of admitted younger infants compared to 41% of older infants (P < 0.05). CONCLUSIONS: Frontline pediatricians appear relatively comfortable with outpatient management of cellulitis in young infants and rarely pursued meningitis evaluation in any afebrile infants or older febrile infants.

[On the reasons for ankyloglossia relapse. Part 1. Frenotomy in newborns]. / O prichinakh povtornoi plastiki uzdechki yazyka. Chast' 1. Frenulotomiya v grudnom vozraste.

The article presents modern data on the structure of the lingual frenulum in newborns and factors associated with restricted tongue mobility besides the length of the mucosal part of the frenulum. The diversity of these factors dictates to limit the indications for frenectomy in newborns to cases with breastfeeding negative events evaluated and documented by a pediatrician. The assessment protocol should include weight gain but also child and mother position, duration, and comfort of the breastfeeding sessions, as well as breast condition in mother. The cases of long-term complications of frenotomy performed in newborns are described, as well as a case illustrating indications for frenotomy associated with chronic injury (Riga-Fede disease).

Standardizing Child Passenger Safety Screening in the Emergency Department: A Quality Improvement Study.

BACKGROUND: Motor vehicle collisions remain a leading cause of death and injury in children in the United States. Our Level I trauma center found that 53% of children ages 1-19 years are improperly restrained or unrestrained. Our center employs a Pediatric Injury Prevention Coalition with nationally certified child passenger safety technicians who are active in the community yet remain underutilized in the clinical setting. OBJECTIVE: The purpose of the quality improvement project was to standardize child passenger safety screening in the emergency department to increase referrals to a Pediatric Injury Prevention Coalition. METHODS: This quality improvement project utilized a pre-/postdesign of data collected before and after implementing the child passenger safety bundle. Using the Plan-Do-Study-Act model, organizational change processes were identified, and quality improvement interventions implemented from March to May 2022. RESULTS: The total number of families referred was 199, representing 230 children, which was 3.8% of the eligible population. A significant relationship was found between child passenger safety screening and referral to the Pediatric Injury Prevention Coalition in 2019 and 2021, χ2 (1, n = 230) = 239.98, p < .001, and χ2 (1, n = 230) = 240.78, p < .001, respectively. Forty-one percent of the referred families established contact with the Pediatric Injury Prevention Coalition. CONCLUSION: Standardizing child passenger safety screening in the emergency department increased referrals to a Pediatric Injury Prevention Coalition and resulted in improved child safety seat distribution and child passenger safety education.

Changes in the intestinal microbiota of children with hand, foot, and mouth disease under 3 years old.

This study aimed to clarify the characteristics of intestinal microbiota in children with hand, foot, and mouth disease (HFMD) under 3 years old. Fresh feces were collected from 54 children with HFMD and 30 healthy children. All of them were <3 years old. Sequencing of the 16S rDNA amplicons was performed. Between the 2 groups, the richness, diversity, and structure of the intestinal microbiota were analyzed by α-diversity and ß-diversity. Linear discriminant analysis and LEfSe analyses were used to compare different bacterial classifications. The sex and age of the children in the 2 groups were not statistically significant (P = .92 and P = .98, respectively). Compared to healthy children, the Shannon index, Ace index, and Chao index were lower in children with HFMD (P = .027, P = .012, and P = .012, respectively). Based on the weighted or unweighted UniFrac distance analysis, the structure of the intestinal microbiota in HFMD was also significantly changed (P = .002 and P < .001, respectively). Linear discriminant analysis and LEfSe analysis showed that the changes of key bacteria were manifested as a decrease in Prevotella and Clostridium_XIVa (P < .001 and P < .001, respectively), while Escherichia and Bifidobacterium increased (P = .025 and P = .001, respectively). Children with HFMD under 3 years of age have intestinal microbiota disorder and show a decrease in diversity and richness. The decrease in the abundance of Prevotella and Clostridium, which can produce short-chain fatty acids, is also one of the characteristics of the change. These results can offer a theoretical foundation for the pathogenesis and microecological treatment of HFMD in infants.

Indirect Estimation of the Pediatric Reference Intervals for Thyroid Function Tests in Public Health Laboratory.

BACKGROUND: Reference intervals (RI) are an essential section of the information that medical laboratories present to clinicians to facilitate the management process of the patient. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) are the most valuable and cost-effective parameters of thyroid functions. According to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), Clinical and Laboratory Standards Institute (CLSI), and American Thyroid Association (ATA), every laboratory should determine own RI on own population and method. In this study we aim to evaluate the pediatric reference intervals in a public health laboratory. METHODS: The results of TSH, fT4, and fT3 from pediatric patients (aged: 0 - 18 years) were included in our study. These results were stored in our laboratory information system. TSH, fT4, and fT3 are measured in Abbott Architect i2000 (Abbott Diagnostics, Abbott Park, IL, USA) chemiluminescent microparticle immunoassay analyzer. RI study was conducted according to CLSI EP28-A3 guidelines. Results were evaluated with MedCalc ver. 19.2.1 (MedCalc Software Ltd., Ostend, Belgium), and Minitab 19.2 (Minitab Statistical Software, AppOnFly Inc., San Fransisco, CA, USA). RESULTS: The final study included 483 samples. Study sample consisted of 288 girls and 195 boys. Our reference intervals for TSH, fT4 and fT3 were found as 0.74 - 4.11 mIU/L, 0.80 - 1.42 ng/dL, and 2.40 - 4.38 pg/mL, respectively. Reference intervals were compatible with expected values in the insert sheets, except for fT3. CONCLUSIONS: Laboratories should implement their reference intervals based on CLSI C28-A3 guidelines.

Determinants of breastfeeding attitudes of mothers in Jordan: A cross-sectional study.

Breastfeeding provides the optimal nutrition for an infant. However, breastfeeding practice is on decline globally. Attitude toward breastfeeding may determine the practice. This study aimed to examine postnatal mothers' attitude to breastfeeding and its determinants. A cross-sectional study was conducted, and data on attitude were collected using the Iowa Infant Feeding Attitude Scale (IIFAS). A convenience sample of 301 postnatal women were recruited from a major referral hospital in Jordan. Data on sociodemographic characteristics, pregnancy and delivery outcomes were collected. SPSS was used to analyze the data and identify the determinants of attitudes to breastfeeding. The mean total attitude score for participants was 65.0 ±7.15, which is close to the upper limit of the neutral attitude range. Factors associated with attitude that is positive to breastfeeding were high income (p = 0.048), pregnancy complications (p = 0.049), delivery complications (p = 0.008), prematurity (p = 0.042), intention to breastfeed (p = 0.002) and willingness to breastfeed (p = 0.005). With binary logistic regression modelling, determinants of attitude positive to breastfeeding were highest income level and willingness to breastfeed exclusively (OR = 14.77, 95%CI = 2.25-99.64 and OR = 3.41, 95%CI = 1.35-8.63 respectively). We conclude that mothers in Jordan have neutral attitude to breastfeeding. Breastfeeding promotion programs and initiatives should target low-income mothers and the general population. Policymakers and health care professionals can use the results of this study to encourage breastfeeding and improve breastfeeding rate in Jordan.

Subciliary Rotating Sutures Combined With Modified Hotz Procedure for Correction of Congenital Lower Eyelid Entropion.

PURPOSE: Standard techniques for the treatment of congenital lower eyelid entropion may not yield suitable outcomes or may result in overcorrection if disinsertion of the lower eyelid retractors is not the primary cause. Herein, we propose and evaluate a technique using subciliary rotating sutures combined with a modified Hotz procedure for repair of lower eyelid congenital entropion that addresses these concerns. METHODS: A retrospective chart review was conducted of all patients who underwent lower eyelid congenital entropion repair by a single surgeon using subciliary rotating sutures combined with a modified Hotz procedure between 2016 and 2020. Study variables included patient demographics, follow-up period, postoperative complications, operative success, and recurrence. RESULTS: Twelve patients (19 eyelids) met the study inclusion criteria. The mean patient age was 7.1 ± 6.1 years (range, 0.2-22 years). Nine of the patients were female (75%) and 3 were male (25%). The distribution of eyelids was 8 right (42%) and 11 left (58%). The mean follow-up time was 19.5 ± 15 (range 2.5-45) months. There were two eyelids (11%) that had entropion recurrence after initial repair in patients with concomitant compound disease processes. Repeated repair resulted in success with no recurrence at last follow-up. Overall, the described entropion repair technique was successful and without recurrence in 17 eyelids (89%). There were no cases of ectropion, lid retraction, or other complications. CONCLUSIONS: Subciliary rotating sutures combined with a modified Hotz procedure are effective for correction of congenital lower eyelid entropion. As the technique does not manipulate the posterior layer of the lower eyelid retractors, it may be useful for when retractor reinsertion does not yield adequate improvement and may also reduce the risk of eyelid retraction and overcorrection in particular cases.

Methadone alters transcriptional programs associated with synapse formation in human cortical organoids.

Opioid use disorder (OUD) among pregnant women has become an epidemic in the United States. Pharmacological interventions for maternal OUD most commonly involve methadone, a synthetic opioid analgesic that attenuates withdrawal symptoms and behaviors linked with drug addiction. However, evidence of methadone's ability to readily accumulate in neural tissue, and cause long-term neurocognitive sequelae, has led to concerns regarding its effect on prenatal brain development. We utilized human cortical organoid (hCO) technology to probe how this drug impacts the earliest mechanisms of cortico-genesis. Bulk mRNA sequencing of 2-month-old hCOs chronically treated with a clinically relevant dose of 1 µM methadone for 50 days revealed a robust transcriptional response to methadone associated with functional components of the synapse, the underlying extracellular matrix (ECM), and cilia. Co-expression network and predictive protein-protein interaction analyses demonstrated that these changes occurred in concert, centered around a regulatory axis of growth factors, developmental signaling pathways, and matricellular proteins (MCPs). TGFß1 was identified as an upstream regulator of this network and appeared as part of a highly interconnected cluster of MCPs, of which thrombospondin 1 (TSP1) was most prominently downregulated and exhibited dose-dependent reductions in protein levels. These results demonstrate that methadone exposure during early cortical development alters transcriptional programs associated with synaptogenesis, and that these changes arise by functionally modulating extra-synaptic molecular mechanisms in the ECM and cilia. Our findings provide novel insight into the molecular underpinnings of methadone's putative effect on cognitive and behavioral development and a basis for improving interventions for maternal opioid addiction.

A systematic review and meta-analysis: the therapeutic and preventive effect of Lactobacillus reuteri DSM 17,938 addition in children with diarrhea.

OBJECTIVE: To summarize the effect of adding Lactobacillus reuteri in the treatment plan for diarrheal disease in children, and analyze the potential of probiotics in preventing the occurrence of diarrheal disease. METHODS: Search for randomized controlled trials of Lactobacillus reuteri for the treatment and prevention of diarrhea in the Pubmed, Web of science, Medline, and Cochrane databases. Data such as the number of diarrhea patients, time, length of stay, clinical symptoms and effect of diarrhea prevention were extracted for meta-analysis. Relative risk and confidence interval (RR and 95% CI) were used as outcome indicators. RESULTS: 963 participants in the 9 RCTs came from multiple countries/regions. Compared with placebo/no intervention, the number of diarrhea patients in the Lactobacillus reuteri group was significantly reduced on the day 1 (RR = 0.87, 95%CI: 0.78-0.97) and day 2 (RR = 0.61, 95%CI: 0.44-0.83). Cumulative statistics analysis showed that the effect was stable and significant starting on the 4th day after treatment. A few studies have shown that Lactobacillus reuteri can reduce the time of diarrhea, the number of days with watery stools, and days of hospital stay. However, it has no effect on the occurrence of nosocomial diarrhea (RR = 1.11, 95%CI: 0.68-1.83), rotavirus diarrhea (RR = 1.46, 95%CI: 0.78-2.72), antibiotic-related diarrhea (RR = 1.76, 95%CI: 0.77-4.05), and diarrhea (RR = 1.35, 95%CI: 0.95-1.92). CONCLUSION: Addition of Lactobacillus reuteri in the treatment plan has a significant effect on reducing the number of diarrhea and reducing the symptoms of diarrhea, but has no obvious effect on the prevention of diarrhea. Combining probiotics and improving the ability of probiotics to respond is the focus of attention.