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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 -
JAMA Network Open Jun 2024Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial...
IMPORTANCE
Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.
OBJECTIVE
To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection.
EXPOSURE
Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires.
MAIN OUTCOMES AND MEASURES
Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days.
RESULTS
Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections.
CONCLUSIONS AND RELEVANCE
In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.
Topics: Humans; COVID-19; Female; Male; Middle Aged; SARS-CoV-2; Prospective Studies; Aged; Adult; Post-Acute COVID-19 Syndrome; Pandemics; United States
PubMed: 38884994
DOI: 10.1001/jamanetworkopen.2024.17440 -
Open Research Europe 2024The prevalence of hormone-related health issues caused by exposure to endocrine disrupting chemicals (EDCs) is a significant, and increasing, societal challenge....
The prevalence of hormone-related health issues caused by exposure to endocrine disrupting chemicals (EDCs) is a significant, and increasing, societal challenge. Declining fertility rates together with rising incidence rates of reproductive disorders and other endocrine-related diseases underscores the urgency in taking more action. Addressing the growing threat of EDCs in our environment demands robust and reliable test methods to assess a broad variety of endpoints relevant for endocrine disruption. EDCs also require effective regulatory frameworks, especially as the current move towards greater reliance on non-animal methods in chemical testing puts to test the current paradigm for EDC identification, which requires that an adverse effect is observed in an intact organism. Although great advances have been made in the field of predictive toxicology, disruption to the endocrine system and subsequent adverse health effects may prove particularly difficult to predict without traditional animal models. The MERLON project seeks to expedite progress by integrating multispecies molecular research, new approach methodologies (NAMs), human clinical epidemiology, and systems biology to furnish mechanistic insights and explore ways forward for NAM-based identification of EDCs. The focus is on sexual development and function, from foetal sex differentiation of the reproductive system through mini-puberty and puberty to sexual maturity. The project aims are geared towards closing existing knowledge gaps in understanding the effects of EDCs on human health to ultimately support effective regulation of EDCs in the European Union and beyond.
PubMed: 38883262
DOI: 10.12688/openreseurope.17319.1 -
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 -
The American Journal of Case Reports Jun 2024BACKGROUND Laparoscopic-perineal neovagina construction by sigmoid colpoplasty is a popular therapeutic approach for patients with Mayer-Rokitansky-Kuster-Hauser (MRKH)...
BACKGROUND Laparoscopic-perineal neovagina construction by sigmoid colpoplasty is a popular therapeutic approach for patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. The conventional approach requires an auxiliary abdominal incision to exteriorize the descending colon to fix the anvil for end-to-end colorectal anastomosis. We modified the natural orifice specimen extraction surgery (NOSES) approach by exteriorizing the descending colon through the artificial neovaginal tunnel to replace the anvil extracorporeally, without requiring an auxiliary abdominal incision. It was a more minimally invasive technique. CASE REPORT We performed this modified laparoscopic-perineal sigmoid colpoplasty in a 26-year-old woman with MRKH syndrome. We cut off a segment of the sigmoid colon with a vascular pedicle to make a new vagina out of it, the same as in the traditional laparoscopic-perineal sigmoid colpoplasty. What is new about this technique is that it has no need for abdominal incision and is more minimally invasive. The operating time was 315 min. No postoperative complications occurred. The postoperative hospital stay was 4 days. The modified laparoscopic-perineal approach, free from an auxiliary abdominal incision, demonstrated advantages, including a shorter hospital stay, expedited recovery, and comparable anatomical outcomes, when compared with the traditional approach. This innovation improves the surgical experience for patients with MRKH syndrome, addressing the physical and psychological aspects of their condition. CONCLUSIONS This refined laparoscopic-perineal neovagina construction by sigmoid colpoplasty represents a feasible and minimally invasive technique. It is an attractive option for MRKH syndrome patients in need of vaginal reconstruction, offering a streamlined procedure with reduced postoperative recovery time and enhanced patient outcomes.
Topics: Humans; Female; Adult; Laparoscopy; Colon, Sigmoid; Vagina; 46, XX Disorders of Sex Development; Mullerian Ducts; Perineum; Congenital Abnormalities; Plastic Surgery Procedures
PubMed: 38867420
DOI: 10.12659/AJCR.943305 -
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