-
JCI Insight Jun 2024Genetic defects affecting steroid biosynthesis cause cortisol deficiency and differences of sex development; among them recessive mutations in the steroidogenic enzymes...
Genetic defects affecting steroid biosynthesis cause cortisol deficiency and differences of sex development; among them recessive mutations in the steroidogenic enzymes CYP11A1 and CYP11B, whose function is supported by reducing equivalents donated by ferredoxin reductase (FDXR) and ferredoxin. So far, mutations in the mitochondrial flavoprotein FDXR have been associated with a progressive neuropathic mitochondriopathy named FDXR-Related Mitochondriopathy (FRM), but cortisol insufficiency has not been documented. However, FRM patients often experience worsening or demise following stress associated with infections. We investigated two female FRM patients carrying the novel homozygous FDXR mutation p.G437R with ambiguous genitalia at birth and sudden death in the first year of life; they presented with cortisol deficiency and androgen excess compatible with 11-hydroxylase deficiency. In addition, steroidogenic FDXR-variant cell lines reprogrammed from three FRM patients' fibroblasts displayed deficient mineralocorticoid and glucocorticoid production. Finally, Fdxr-mutant mice allelic to the severe p.R386W human variant, showed reduced progesterone and corticosterone production. Therefore, our comprehensive studies show that human FDXR variants may cause compensated, but possibly life-threatening adrenocortical insufficiency in stress by affecting adrenal glucocorticoid and mineralocorticoid synthesis through direct enzyme inhibition, most likely in combination with disturbed mitochondrial redox balance.
PubMed: 38885337
DOI: 10.1172/jci.insight.179071 -
The Lancet. Global Health Jul 2024Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to...
BACKGROUND
Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero.
METHODS
In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex.
FINDINGS
The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings.
INTERPRETATION
We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted.
FUNDING
National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center.
TRANSLATION
For the Spanish translation of the abstract see Supplementary Materials section.
Topics: Humans; Nicaragua; Zika Virus Infection; Female; Prospective Studies; Child, Preschool; Pregnancy; Male; Prenatal Exposure Delayed Effects; Infant; Pregnancy Complications, Infectious; Child Development; Zika Virus; Adult; Neurodevelopmental Disorders
PubMed: 38876760
DOI: 10.1016/S2214-109X(24)00176-1 -
Scientific Reports Jun 2024High systolic blood pressure (HSBP) is associated with several metabolic and non-metabolic disorders. This research aimed to document the deaths and disability-adjusted...
High systolic blood pressure (HSBP) is associated with several metabolic and non-metabolic disorders. This research aimed to document the deaths and disability-adjusted life-years (DALYs) attributable to HSBP in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex, underlying cause and socio-demographic index (SDI). We used the methodological framework and data drawn from the Global Burden of Disease study 2019 to identify the burden of diseases attributable to HSBP, from 1990 to 2019, in the MENA region. The estimates reported were presented as counts, population-attributable fractions, and age-standardised rates (per 100,000), along with 95% uncertainty intervals. In 2019, 803.6 thousand (687.1 to 923.8) deaths were attributed to HSBP in MENA, which accounted for 25.9% (22.9-28.6%) of all deaths. The number of regional DALYs caused by HSBP in 2019 was 19.0 million (16.3-21.9 million), which accounted for 11.6% (10.1-13.3%) of all DALYs, and was 23.4% (15.9-31.5%) lower than in 1990. The highest age-standardised DALY rate for 2019 was observed in Afghanistan, with the lowest in Kuwait. Additionally, the DALY rate in MENA rose with age for both sexs. Furthermore, a negative linear relationship was found between SDI and the age-standardised DALY rates. The region has a substantial HSBP-related burden. Policymakers and healthcare professionals should prioritize interventions that effectively promote the early detection of HSBP, access to quality healthcare, and lifestyle modifications to mitigate the HSBP burden in the MENA countries.
Topics: Humans; Africa, Northern; Middle East; Male; Female; Middle Aged; Adult; Aged; Hypertension; Global Burden of Disease; Disability-Adjusted Life Years; Young Adult; Cost of Illness; Adolescent; Aged, 80 and over; Blood Pressure
PubMed: 38871791
DOI: 10.1038/s41598-024-64563-x -
BMC Urology Jun 2024Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause...
BACKGROUND
Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China.
METHODS
We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E, were quantified using the enzyme-linked immunosorbent assay (ELISA).
RESULTS
The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p < 0.001). In comparison, the deletion rate of the AZFc region was significantly higher in patients with oligozoospermia (3.08% vs. 6.30%, p < 0.001). Additionally, the AZFb + c subregion association deletion was observed in the highest proportion among all patients (0.89%, 8/897), followed by AZFa + b + c deletion (0.56%, 5/897), and exclusively occurred in patients with azoospermia. Hormone analysis revealed FSH (21.63 ± 2.01 U/L vs. 10.15 ± 0.96 U/L, p = 0.001), LH (8.96 ± 0.90 U/L vs. 4.58 ± 0.42 U/L, p < 0.001) and PRL (263.45 ± 21.84 mIU/L vs. 170.76 ± 17.10 mIU/L, p = 0.002) were significantly increased in azoospermia patients with microdeletions. Still, P and E levels were not significantly different between the two groups.
CONCLUSIONS
The incidence of AZF microdeletion can reach 7.13% in infertile men in Hainan province, and the deletion of the AZFc subregion is the highest. Although the Y chromosome microdeletion rate is distinct in different regions or populations, the regions mentioned above of the Y chromosome may serve an indispensable role in regulating spermatogenesis. The analysis of Y chromosome microdeletion plays a crucial role in the clinical assessment and diagnosis of male infertility.
Topics: Humans; Male; Chromosomes, Human, Y; Infertility, Male; Chromosome Deletion; China; Sex Chromosome Aberrations; Adult; Sex Chromosome Disorders of Sex Development; Reproductive Techniques, Assisted; Luteinizing Hormone; Follicle Stimulating Hormone; Azoospermia; Prolactin; Oligospermia; Testosterone; Estradiol; Semen Analysis
PubMed: 38867229
DOI: 10.1186/s12894-024-01503-x -
PloS One 2024Sexual behavior (SB) is a well-documented pathway to HIV acquisition in emerging adults and remains common amongst African emerging adults. Previous research in...
BACKGROUND
Sexual behavior (SB) is a well-documented pathway to HIV acquisition in emerging adults and remains common amongst African emerging adults. Previous research in high-income countries indicates a correlation between disordered eating behavior (DEB) and engaging in sexual behaviors. We aimed to describe the relationship between DEB and SB amongst emerging adults attending a tertiary educational institution at the Kenyan Coast.
METHODS
We applied a cross-sectional design nested in a young adults' cohort study. Eligibility included sexually active emerging adults aged 18-24 years. Three DEBs (emotional, restrained and external eating) were assessed using the Dutch Eating Behavior Questionnaire and analysed using exploratory factor analysis. Seven SB indicators were assessed: non-condom use, casual sex, multiple sex partners, transactional sex, group sex, age-disparate relationship and anal sex, and grouped into low vs. high SB using latent class analysis. Logistic regression was used to assess the association between DEB and SB.
RESULTS
Of 273 eligible participants (female, n = 110 [40.3%]), the mean of emotional, restrained and external eating was 1.9 [0.6], 2.0 [0.6] and 3.0 [0.5] respectively. Overall, 57 (20.9%) were grouped into the latent high SB class. Emotional (Adjusted odds ratio, AOR [95% confidence interval, CI]: 1.0 [0.9-1.0], p = 0.398), restrained (AOR, 1.0 [CI: 0.9-1.1], p = 0.301) and External (AOR, 1.0 [CI: 0.8-1.2], p = 0.523) eating were not independently associated with latent high SB.
CONCLUSION
There was no significant association between DEB and SB in this study sample. In low- and middle-income countries like Kenya, interventions targeted at DEB among emerging adults towards controlling SB are unnecessary.
Topics: Humans; Female; Kenya; Male; Young Adult; Sexual Behavior; Adolescent; Feeding and Eating Disorders; Cross-Sectional Studies; Adult; Surveys and Questionnaires; Sexual Partners; Feeding Behavior
PubMed: 38861516
DOI: 10.1371/journal.pone.0301436 -
Frontiers in Endocrinology 2024
Topics: Turner Syndrome; Humans; Female; Adult; Young Adult; Transition to Adult Care; Adolescent
PubMed: 38859906
DOI: 10.3389/fendo.2024.1431972 -
MedRxiv : the Preprint Server For... May 2024Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the...
BACKGROUND
Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI.
METHODS
We examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally in pre-and-early adolescence, can predict future SUI. In an independent sub-sample, we also tested whether these patterns are associated with key environmental factors, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the Adolescent Brain Cognitive Development (ABCD) Study. SUI was defined as first-time use of at least one full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group ( = 228) of participants without SUI who were matched with the SUI group ( = 233) on age, sex, race/ethnicity, and parental income and education.
RESULTS
Multivariate analysis showed that whole-brain rsFC prior to SUI during 9-10 and 11-12 years of age successfully differentiated the prospective SUI and control groups. This rsFC signature was expressed more at older ages in both groups, suggesting a pattern of accelerated maturation in the SUI group in the years prior to SUI. In an independent sub-sample ( = 2,854) and adjusted for family socioeconomic factors, expression of this rsFC pattern was associated with higher pollution, but not neighborhood disadvantage.
CONCLUSION
Brain functional connectivity patterns in early adolescence that are linked to accelerated maturation and environmental exposures can predict future SUI in youth.
PubMed: 38853927
DOI: 10.1101/2024.05.29.24308134 -
European Journal of Medical Genetics Jun 202421-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the CYP21A2 gene. On the other hand,...
21-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the CYP21A2 gene. On the other hand, mutations within the CYP17A1 gene lead to 17α-hydroxylase/17,20-lyase enzyme deficiencies. The scarcity of 17-OH deficiency is noteworthy, accounting for less than 1% of all congenital adrenal hyperplasia cases. The male patient, born from a first-degree cousin marriage, exhibited several symptoms, including left undescended testis, micropenis, penile chord, left sensorineural hearing loss, and gynecomastia. He reported micropenis as a concern at the age of 13.5 years. His hormone profile revealed high levels of serum 17-hydroxyprogesterone, progesterone, and pregnenolone. In this case with a 46 XY karyotype, suspicions arose regarding Cytochrome P450 oxidoreductase deficiency due to ambiguous genitalia and an atypical hormone profile. Analysis unveiled two distinct homozygous and pathogenic variants in the CYP21A2 and CYP17A1 genes. Notably, mineralocorticoid precursors escalated, while cortisol and sex steroid precursors decreased during the high (250 mcg) dose ACTH stimulation test. The mutation c.1169C > G (p.Thr390Arg) in CYP17A1, which is the second documented case in literature, stands out due to its unique set of accompanying features. Mutations occurring in CYP21A2 and CYP17A1 result in complete or partial enzyme deficiencies, and the detection of homozygous mutations in two different enzyme systems within the steroidogenic pathway is noteworthy.
Topics: Humans; Adrenal Hyperplasia, Congenital; Male; Steroid 17-alpha-Hydroxylase; Steroid 21-Hydroxylase; Adolescent; Mutation
PubMed: 38852772
DOI: 10.1016/j.ejmg.2024.104952 -
BMJ Paediatrics Open Jun 2024To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function. (Observational Study)
Observational Study
OBJECTIVES
To assess sex-specific differences in the association between pre-transfusion haemoglobin values and early neurodevelopmental function.
DESIGN
Observational follow-up of infants with birth weights <1000 g and gestational ages 22-28 weeks who were enrolled in the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial at 19 U.S. sites, 2012-2017.
MAIN OUTCOME MEASURES
Pretransfusion haemoglobin values were obtained longitudinally through 36 weeks' postmenstrual age. The infant's mean pretransfusion haemoglobin was used as a marker of degree of anaemia (n=1655 measures). Measures of brain function were obtained at 22-26 months' corrected age using the Bayley Scales of Infant & Toddler Development, third edition (BSID-III) (n=1290 BSID-III scores). Sex-specific estimates for the linear relation between pretransfusion haemoglobin and BSID-III scores were obtained from repeated-measures regression analysis, adjusted for gestational age, birth weight, study site, clinical characteristics, and demographic covariates.
RESULTS
The relation of pretransfusion haemoglobin with 24-month BSID-III scores showed significant, independent interactions with both (1) sex (p=0.046) and (2) retinopathy of prematurity (ROP; p=0.004). In 614 males, BSID-III scores were higher by 1.07 points per g/dL (95% CI 1.58 to 4.33; p=0.008), not differing significantly among the three subscales (cognitive, language and motor; p=0.94). In 247 infants with ROP, BSID-III scores were higher by 2.95 points per g/dL (95% CI 0.28 to 1.87; p<0.0001), uniformly across subscales (p=0.73). These associations were non-significant in 676 females (p=0.96) and 1043 infants without ROP (p=0.81).
CONCLUSIONS
This study demonstrates sex-specific associations between mean pretransfusion haemoglobin (a marker of the severity of anaemia throughout the neonatal intensive care unit [NICU] hospitalisation) and early neurodevelopmental function at 22-26 months' corrected age.
Topics: Humans; Female; Male; Hemoglobins; Infant, Newborn; Infant, Premature; Cognition; Sex Factors; Infant; Gestational Age; Child Development; Follow-Up Studies; Child, Preschool; Anemia
PubMed: 38851221
DOI: 10.1136/bmjpo-2024-002541 -
BMC Public Health Jun 2024Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such...
BACKGROUND
Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such associations remains unclear.
METHODS
Cigarette exposure, trouble sleeping, and depression were assessed by standard questionnaires, and the levels of cotinine and sex steroid hormones were determined among 9900 adults from the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression, logistic regression, and mediation models were conducted to evaluate the associations between smoking, sex steroid hormones, trouble sleeping, and depression.
RESULTS
With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293) as well as testosterone level (β = 0.083, 95% CI: 0.028, 0.140). Pack-years of smoking and cigarettes per day were positively associated with the prevalence of trouble sleeping and depression as well as testosterone level (P <0.05). The restricted cubic spline model showed linear relationships of cotinine with trouble sleeping, depression, and testosterone. The positive associations of cigarettes per day with trouble sleeping and depression were greater in females than that in males (P <0.05). However, the potential role of sex hormones was not observed in the association of cotinine with trouble sleeping or depression (P >0.05).
CONCLUSION
Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms, and ceasing smoking may reduce the risk of such complications.
Topics: Humans; Male; Female; Cross-Sectional Studies; Adult; Nutrition Surveys; Depression; Middle Aged; United States; Cotinine; Sleep Wake Disorders; Smoking; Prevalence; Gonadal Steroid Hormones; Young Adult; Testosterone; Aged
PubMed: 38849814
DOI: 10.1186/s12889-024-19045-0