Investigating the Evidence of Behavioral, Cognitive, and Psychiatric Endophenotypes in Autism: A Systematic Review

Substantial evidence indicates that parents of autistic individuals often display milder forms of autistic traits referred to as the broader autism phenotype (BAP). To determine if discrete endophenotypes of autism can be identified, we reviewed the literature to assess the evidence of behavioral, cognitive, and psychiatric profiles of the BAP. A systematic review was conducted using EMBASE, MEDLINE, PsycINFO, PsycEXTRA, and Global Health. Sixty papers met our inclusion criteria and results are discussed according to the proportion of studies that yield significant deficits per domain. The behavioral, cognitive, and psychiatric endophenotypes in parents of autistic probands are still not clarified; however, evidence suggests mild social/communication deficits, rigid/aloof personality traits, and pragmatic language difficulties as the most useful sociobehavioral candidate endophenotype traits. The existence of deficits in the cognitive domain does suggest familial vulnerability for autism. Furthermore, increased depressed mood and anxiety can also be useful markers; however, findings should be interpreted with caution because of the small number of studies in such heterogeneously broad domains and several methodological limitations

Biomarkers of systemic inflammation and growth in early infancy are associated with stunting in young Tanzanian children

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone–insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores < −2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72; p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93; p for trend = 0.019); a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12; p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.This research was funded by the National Institutes of Health (R01 HD048969, 2P30 DK040561, K24 DK104676-Dr. Duggan) and the Bill and Melinda Gates Foundation (OPP1066203-Dr. Duggan). (R01 HD048969 - National Institutes of Health; 2P30 DK040561 - National Institutes of Health; K24 DK104676 - National Institutes of Health; OPP1066203 - Bill and Melinda Gates Foundation)Accepted manuscrip

Synthesizing Diabetic Foot Ulcer Images with Diffusion Model

Diabetic Foot Ulcer (DFU) is a serious skin wound requiring specialized care. However, real DFU datasets are limited, hindering clinical training and research activities. In recent years, generative adversarial networks and diffusion models have emerged as powerful tools for generating synthetic images with remarkable realism and diversity in many applications. This paper explores the potential of diffusion models for synthesizing DFU images and evaluates their authenticity through expert clinician assessments. Additionally, evaluation metrics such as Frechet Inception Distance (FID) and Kernel Inception Distance (KID) are examined to assess the quality of the synthetic DFU images. A dataset of 2,000 DFU images is used for training the diffusion model, and the synthetic images are generated by applying diffusion processes. The results indicate that the diffusion model successfully synthesizes visually indistinguishable DFU images. 70% of the time, clinicians marked synthetic DFU images as real DFUs. However, clinicians demonstrate higher unanimous confidence in rating real images than synthetic ones. The study also reveals that FID and KID metrics do not significantly align with clinicians' assessments, suggesting alternative evaluation approaches are needed. The findings highlight the potential of diffusion models for generating synthetic DFU images and their impact on medical training programs and research in wound detection and classification.Comment: 8 pages, 3 figures, 6th Workshop on AI for Aging, Rehabilitation and Intelligent Assisted Living at European Conference on Machine Learning, Italy, 202

Latent tuberculosis among pregnant mothers in a resource poor setting in Northern Tanzania: a cross-sectional study

Untreated latent TB infection (LTBI) is a significant risk factor for active pulmonary tuberculosis, hence predisposing to adverse pregnancy outcomes and mother to child transmission. The prevalence of latent tuberculosis in pregnancy and its association, if any, with various socio-demographic, obstetric and clinical characteristics was evaluated. Northern Tanzania was chosen as the study site. In a cross-sectional study, a total of 286 pregnant women from 12 weeks gestational age to term were assessed. Screening was undertaken using an algorithm involving tuberculin skin testing, symptom screening in the form of a questionnaire, sputum testing for acid fast bacilli followed by shielded chest X-rays if indicated. HIV serology was also performed on consenting participants.\ud Prevalence of latent infection ranged between 26.2% and 37.4% while HIV sero prevalence was 4.5%. After multivariate logistic analysis it was found that age, parity, body mass index, gestational age, and HIV sero status did not have any significant association with tuberculin skin test results. However certain ethnic groups were found to be less vulnerable to LTBI as compared to others (Chi square = 10.55, p = 0.03). All sputum smears for acid fast bacilli were negative. The prevalence of latent tuberculosis in pregnant women was found to be relatively high compared to that of the general population. In endemic areas, socio-demographic parameters alone are rarely adequate in identifying women susceptible to TB infection; therefore targeted screening should be conducted for all pregnant women at high risk for activation (especially HIV positive women). As opposed to the current policy of passive case detection, there appears to be an imminent need to move towards active screening. Ethnicity may provide important clues into genetic and cultural differences which predispose to latent tuberculosis, and is worth exploring further

Sex Differences in The effects of Maternal Vitamin Supplements on Mortality and Morbidity among Children Born to HIV-Infected women in Tanzania.

We examined whether there are sex differences in the effect of vitamin supplements on birth outcomes, mortality and morbidity by 2 years of age among children born to HIV-infected women in Tanzania. A randomised placebo-controlled trial was conducted among 959 mother-infant pairs. HIV-infected pregnant women were randomly assigned to receive a daily oral dose of one of four regimens: multivitamins (vitamins B-complex, C and E), vitamin A plus beta-carotene, multivitamins including vitamin A plus beta-carotene or placebo. Supplements were administered during pregnancy and continued after delivery. The beneficial effect of multivitamins on decreasing the risk of low birth weight was stronger among girls (relative risks (RR) = 0.39, 95 % CI 0.22, 0.67) than among boys (RR = 0.81, 95 % CI 0.44, 1.49; P for interaction = 0.08). Maternal multivitamin supplements resulted in 32 % reduction in mortality among girls (RR = 0.68, 95 % CI 0.47, 0.97), whereas no effect was found among boys (RR = 1.20, 95 % CI 0.80, 1.78; P for interaction = 0.04). Multivitamins had beneficial effects on the overall risks of diarrhoea that did not differ by sex. Vitamin A plus beta-carotene alone increased the risk of HIV transmission, but had no effects on mortality, and we found no sex differences in these effects. Sex differential effects of multivitamins on mortality may be due to sex-related differences in the immunological or genetic factors. More research is warranted to examine the effect of vitamins by sex and better understand biological mechanisms mediating such effects

Multivitamin Supplementation Improves Haematologic Status in Children Born to HIV-positive women in Tanzania.

Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality. To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding. A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations <11 g/dL and severe anaemia <8.5 g/dL. Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79-0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56-0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79-1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV. Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy

Primary HIV-1 Infection Among Infants in sub-Saharan Africa: HPTN 024.

Our objectives were to assess clinical signs and diagnoses associated with primary HIV-1 infection among infants. We analyzed data from a clinical trial (HIV Prevention Trials Network Protocol 024) in sub-Saharan Africa. Study visits were conducted at birth, at 4-6 weeks, and at 3, 6, 9, and 12 months. The study population comprised live born, singleton, first-born infants of HIV-1-infected women with negative HIV-1 RNA assays who were still breastfeeding at 4-6 weeks. Of 1317 HIV-1-exposed infants, 84 became HIV-1 infected after 4-6 weeks and 1233 remained uninfected. There were 102 primary and 5650 nonprimary infection visits. The most common signs were cough and diarrhea, and the most common diagnoses were malaria and pneumonia. Primary infection was associated with significantly increased odds of diarrhea [odds ratio (OR) = 2.4], pneumonia (OR = 3.5), otitis media (OR = 3.1), and oral thrush (OR = 2.9). For the clinical signs and diagnoses evaluated, sensitivity was low (1%-16.7%) and specificity was high (88.2%-99%). Positive predictive values ranged from 0.1%-1.4%. Negative predictive values ranged from 28.0%-51.1%. Certain clinical signs and diagnoses, although more common during primary HIV-1 infection, had low sensitivity and high specificity. Efforts to expand access to laboratory assays for the diagnosis of primary HIV-1 infection among infants of HIV-1-infected women should be emphasized

Cryptosporidium, Enterocytozoon, and Cyclospora Infections in Pediatric and Adult Patients with Diarrhea in Tanzania.

Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously

Bacteraemia, Malaria, and Case Fatality Among Children Hospitalized With Fever in Dar es Salaam, Tanzania

Background Febrile illness is the commonest cause of hospitalization in children <5 years in sub-Saharan Africa, and bacterial blood stream-infections and malaria are major causes of death. Methods From March 2017 to July 2018, we enrolled 2226 children aged 0-5 years hospitalized due to fever in four major public hospitals of Dar es Salaam namely; Amana, Temeke and Mwananyamala Regional Hospitals and Muhimbili National Hospital. We recorded social demographic and clinical data, performed blood-culture and HIV-antibody testing. We used qPCR to quantify Plasmodium falciparum parasitaemia and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) to identify bacterial isolates. Disk diffusion method was used for antimicrobial susceptibility testing. Results Nineteen percent of the children (426/2226) had pathogens detected from blood. Eleven percent (236/2226) of the children had bacteraemia/fungaemia and 10% (204/2063) had P. falciparum malaria. Ten children had concomitant malaria and bacteraemia. Gram-negative bacteria (64%) were more frequent than Gram-positive (32%) and fungi (4%). Over fifty percent of Gram-negative bacteria were extended-spectrum beta-lactamase (ESBL) producers and multidrug resistant. Methicillin resistant Staphylococcus aureus (MRSA) was found in 11/42 (26.2%). The most severe form of clinical malaria was associated with high parasitaemia (>four million genomes/µL) of P. falciparaum in plasma. Overall, in-hospital death was 4% (89/2146) and it was higher in children with bacteraemia (8%, 18/227) than malaria (2%, 4/194, P=0.007). Risk factors for death were bacteraemia (p=0.03), unconsciousness at admission (p<0.001) and admission at a tertiary hospital (p=0.003). Conclusions Compared to previous studies in this region, our study showed a reduction in malaria prevalence, a decrease in in-hospital mortality and an increase in antimicrobial resistance (AMR) including ESBLs and multidrug resistance. An increase of AMR highlights the importance of continued strengthening of diagnostic capability and antimicrobial stewardship programs. We also found malaria and bacteraemia contributed equally in causing febrile illness but bacteraemia caused higher in-hospital death. The most severe form of clinical malaria was associated with P. falciparum parasitaemia