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1.
bioRxiv ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39005279

ABSTRACT

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remains less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called 'vanishing microbiomes' potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations. RESULTS: Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the United States within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain source. CONCLUSION: Our findings demonstrate that by controlling for geography, we can isolate an important role for lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes.

2.
Clin Psychol Psychother ; 31(4): e3018, 2024.
Article in English | MEDLINE | ID: mdl-38948943

ABSTRACT

BACKGROUND: In this study, we re-examined data from a previous randomized controlled trial investigating 'technology supported mindfulness' (TSM)-an 8-week treatment intervention for individuals experiencing OCD. The current analysis involves an examination of the longitudinal relationships between rumination, worry and OCD symptom changes during mindfulness treatment, in comparison to a waitlist control. METHODS: Participants experiencing OCD (n = 71) were randomly assigned to 8 weeks of (1) TSM or (2) waitlist control. We tested the extent to which rumination (using the Ruminative Response Scale) and worry (using the Penn State Worry Questionnaire) are associated with OCD symptom changes during the acute phase of treatment, concurrently (i.e., within the same longitudinal model). RESULTS: Generalized linear model (GLM) results indicated a significant time (week 1 vs. week 8) by condition interaction involving decreased rumination in the TSM condition: F(1, 61) = 13.37, p = 0.001, partial η2 = 0.18 and observed power = 0.94. A second GLM demonstrated decreased worry in the TSM condition: F(1, 69) = 37.34, p = 0.001, partial η2 = 0.35 and observed power = 0.83. Longitudinal 'latent difference' structural equation analyses demonstrated a cross-lagged association between worry (but not rumination) and OCD symptom changes. CONCLUSIONS: Individuals in the TSM condition experienced greater reductions in rumination and worry during 8 weeks of TSM treatment compared to the waitlist control, and reduced worry predicted subsequent OCD symptom reduction.


Subject(s)
Mindfulness , Obsessive-Compulsive Disorder , Rumination, Cognitive , Humans , Female , Male , Mindfulness/methods , Obsessive-Compulsive Disorder/therapy , Obsessive-Compulsive Disorder/psychology , Adult , Treatment Outcome , Anxiety/psychology , Anxiety/therapy , Middle Aged , Surveys and Questionnaires
3.
Andrology ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011578

ABSTRACT

BACKGROUND: There are limited data on pelvic pain among transgender men and gender diverse people, and the impact of testosterone on pelvic pain is poorly understood. OBJECTIVE: Characterize the prevalence and correlates of chronic pelvic pain (CPP) among transgender men and gender diverse people and examine the association between testosterone use and CPP. MATERIALS AND METHODS: We used 2020-2022 data from The Population Research in Identity and Disparities for Equality (PRIDE) Study, an online prospective cohort study of sexual and gender minority adults in the United States, to conduct complementary cross-sectional and longitudinal analyses. Our primary outcome was self-reported CPP lasting 3 months or longer measured using the Michigan Body Map. RESULTS: Among 2579 transgender men and gender diverse people assigned female at birth included in our sample, 457 (18%) reported CPP. CPP correlates included: inflammatory bowel disease, irritable bowel syndrome (IBS), kidney stones, pelvic inflammatory disease, polycystic ovary syndrome (PCOS), uterine fibroids, current hormonal intrauterine device use, prior pregnancy, vaginal delivery, hysterectomy, and oophorectomy. Individuals with CPP reported a high prevalence of IBS (37%), PCOS (20%), uterine fibroids (9%), post-traumatic stress disorder (51%), and severe depression and anxiety symptoms (42% and 25%, respectively). Current testosterone use was associated with a 21% lower prevalence of CPP (adjusted prevalence ratio (aPR) 0.79, 95% confidence interval [CI]: 0.65-0.96). In longitudinal analyses (N = 79), 15 (19%) participants reported any CPP after initiating testosterone: eight (56%) of whom reported CPP prior to testosterone initiation, and seven (47%) who reported new-onset CPP. DISCUSSION AND CONCLUSIONS: The relationship between CPP and testosterone is complex. Although testosterone use was associated with a lower prevalence of CPP, some transgender and gender diverse individuals experienced new-onset pelvic pain after testosterone initiation. Given the significant impact that CPP can have on mental health and quality of life, future research must examine the role of testosterone in specific underlying etiologies of CPP and identify potential therapies.

4.
ACS Nano ; 18(28): 18683-18692, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38973716

ABSTRACT

The interaction of liquid water with hydrophobic surfaces is ubiquitous in life and technology. Yet, the molecular structure of interfacial liquid water on these surfaces is not known. By using a 3D atomic force microscope, we characterize with angstrom resolution the structure of interfacial liquid water on hydrophobic and hydrophilic silica surfaces. The combination of 3D AFM images and molecular dynamics simulations reveals that next to a hydrophobic silica surface, there is a 1.2 nm region characterized by a very low density of water. In contrast, the 3D AFM images obtained of a hydrophilic silica surface reveal the presence of hydration layers next to the surface. The gap observed on hydrophobic silica surfaces is filled with two-to-three layers of straight-chain alkanes. We developed a 2D Ising model that explains the formation of a continuous hydrocarbon layer on hydrophobic silica surfaces.

5.
Am J Primatol ; : e23657, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967215

ABSTRACT

Primates exhibit diverse social systems that are intricately linked to their biology, behavior, and evolution, all of which influence the acquisition and maintenance of their gut microbiomes (GMs). However, most studies of wild primate populations focus on taxa with relatively large group sizes, and few consider pair-living species. To address this gap, we investigate how a primate's social system interacts with key environmental, social, and genetic variables to shape the GM in pair-living, red-bellied lemurs (Eulemur rubriventer). Previous research on this species suggests that social interactions within groups influence interindividual microbiome similarity; however, the impacts of other nonsocial variables and their relative contributions to gut microbial variation remain unclear. We sequenced the 16S ribosomal RNA hypervariable V4-V5 region to characterize the GM from 26 genotyped individuals across 11 social groups residing in Ranomafana National Park, Madagascar. We estimated the degree to which sex, social group identity, genetic relatedness, dietary diversity, and home range proximity were associated with variation in the gut microbial communities residing in red-bellied lemurs. All variables except sex played a significant role in predicting GM composition. Our model had high levels of variance inflation, inhibiting our ability to determine which variables were most predictive of gut microbial composition. This inflation is likely due to red-bellied lemurs' pair-living, pair-bonded social system that leads to covariation among environmental, social, and genetic variables. Our findings highlight some of the factors that predict GM composition in a tightly bonded, pair-living species and identify variables that require further study. We propose that future primate microbiome studies should simultaneously consider environmental, social, and genetic factors to improve our understanding of the relationships among sociality, the microbiome, and primate ecology and evolution.

6.
FASEB J ; 38(13): e23775, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38967223

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol. The same expression pattern was evidenced in both mouse models. Parp14-deficiency caused increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss, and immune cell infiltration in DSS-exposed mice. The absence of Parp14 did not affect the mouse colon bacterial microbiota. Also, the colon leukocyte populations of Parp14-deficient mice were normal. In contrast, bulk tissue RNA-Seq demonstrated that the colon transcriptomes of Parp14-deficient mice were dominated by abnormalities in inflammation and infection responses both prior and after the DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation.


Subject(s)
Colitis , Dextran Sulfate , Mice, Inbred C57BL , Poly(ADP-ribose) Polymerases , Animals , Mice , Colitis/genetics , Colitis/chemically induced , Colitis/pathology , Poly(ADP-ribose) Polymerases/metabolism , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/deficiency , Humans , Dextran Sulfate/toxicity , Mice, Knockout , Colon/pathology , Colon/metabolism , Male , Disease Models, Animal , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/metabolism , Female , Gastrointestinal Microbiome
7.
Mol Microbiol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960396

ABSTRACT

Bacteria have a remarkable ability to sense environmental stresses and to respond to these stressors by adapting their metabolism and physiology. In recent publications, investigators have suggested that multiple stresses that cause cell death share the mechanistic feature of stimulating the formation of reactive oxygen species (ROS). A central piece of evidence cited in these claims is the ability of exogenous antioxidant compounds to mitigate stress-related cell death. The validity of attributing a positive effect of exogenous antioxidants to ROS-mediated stress is challenged by an important study by Korshunov and Imlay in this issue of Molecular Microbiology. This study reports biochemical data that convincingly show that some commonly used antioxidants quench oxidants orders of magnitude too slowly to have a significant effect on the concentration of ROS in the cell. Under conditions where antioxidants minimize cell death, they also slow growth. Significantly, slowing cell growth by other means has the same restorative effect as adding an antioxidant. Based on the solid biochemical and genetic data, Korshunov and Imlay make the case for discarding the use of antioxidants to diagnose conditions that generate increased internal ROS production.

8.
Sci Rep ; 14(1): 15943, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987614

ABSTRACT

Despite their frequent use across many clinical settings, general anesthetics are medications with lethal side effects and no reversal agents. A fluorinated analogue of propofol has previously been shown to antagonize propofol anesthesia in tadpoles and zebrafish, but little further investigation of this class of molecules as anesthetic antagonists has been conducted. A 13-member library of alkyl-fluorobenzene derivatives was tested in an established behavioral model of anesthesia in zebrafish at 5 days post fertilization. These compounds were examined for their ability to antagonize propofol and two volatile anesthetics, as well as their interaction with the anesthetic-binding model protein apoferritin. Two compounds provided significant antagonism of propofol, and when combined, were synergistic, suggesting more than one antagonist sensitive target site. These compounds did not antagonize the volatile anesthetics, indicating some selectivity amongst general anesthetics. For the compounds with the most antagonistic potency, similarities in structure and binding to apoferritin may be suggestive of competitive antagonism; however, this was not supported by a Schild analysis. This is consistent with multiple targets contributing to general anesthesia, but whether these are physiologic antagonists or are antagonists at only some subset of the many anesthetic potential targets remains unclear, and will require additional investigation.


Subject(s)
Propofol , Zebrafish , Propofol/pharmacology , Propofol/chemistry , Animals , Fluorobenzenes/pharmacology , Fluorobenzenes/chemistry , Apoferritins/chemistry , Anesthesia
9.
Pharmacol Res Perspect ; 12(4): e1234, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38961539

ABSTRACT

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium-induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200-fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo-oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation.


Subject(s)
Colitis , Dextran Sulfate , Estradiol , Estrogen Receptor alpha , Ovariectomy , Animals , Female , Estrogen Receptor alpha/metabolism , Colitis/chemically induced , Colitis/metabolism , Colitis/drug therapy , Mice , Estradiol/pharmacology , Estradiol/blood , Mice, Inbred C57BL , Estrogens/pharmacology , Cyclooxygenase 2/metabolism , Disease Models, Animal , Interleukin-17/metabolism , Colon/pathology , Colon/drug effects , Colon/metabolism , Interleukin-6/metabolism , Interleukin-1beta/metabolism
10.
HIV Res Clin Pract ; 25(1): 2363129, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38907537

ABSTRACT

BACKGROUND: COVID-19 profoundly and uniquely impacted people with HIV. People with HIV experienced significant psychosocial and socioeconomic impacts, yet a limited amount of research has explored potential differences across gender and racial/ethnic groups of people with HIV. OBJECTIVE: The objective of this study was to examine psychosocial and socioeconomic stressors related to the COVID-19 pandemic among a diverse sample of people with HIV in South Florida and to determine if the types of stressors varied across gender and racial/ethnic groups. METHODS: We analyzed data from a cross-sectional survey with Miami-Dade County, Ryan White Program recipients. Outcomes included mental health, socioeconomic, drug/alcohol, and care responsibility/social support changes. Weighted descriptive analyses provided an overview of stressors by gender and racial/ethnic group and logistic regressions estimated associations between demographics and stressors. RESULTS: Among 291 participants, 39% were Non-Hispanic Black, 18% were Haitian, and 43% were Hispanic. Adjusting for age, sex, language, and foreign-born status, Hispanics were more likely to report several worsened mental health (i.e. increased loneliness, anxiety) and socioeconomic stressors (i.e. decreased income). Spanish speakers were more likely to report not getting the social support they needed. Women were more likely to report spending more time caring for children. CONCLUSIONS: Findings highlight ways in which cultural and gender expectations impacted experiences across people with HIV and suggest strategies to inform interventions and resources during lingering and future public health emergencies. Results suggest that public health emergencies have different impacts on different communities. Without acknowledging and responding to differences, we risk losing strides towards progress in health equity.


Subject(s)
COVID-19 , HIV Infections , Poverty , Adult , Female , Humans , Male , Middle Aged , Black or African American/statistics & numerical data , Black or African American/psychology , COVID-19/psychology , COVID-19/epidemiology , Cross-Sectional Studies , Ethnicity/psychology , Ethnicity/statistics & numerical data , Florida/epidemiology , Haiti/ethnology , Hispanic or Latino/statistics & numerical data , Hispanic or Latino/psychology , HIV Infections/psychology , HIV Infections/ethnology , HIV Infections/epidemiology , Mental Health/statistics & numerical data , Pandemics , Poverty/psychology , Poverty/statistics & numerical data , Sex Factors , Social Support , Socioeconomic Factors , Stress, Psychological/psychology , Stress, Psychological/ethnology
11.
Article in English | MEDLINE | ID: mdl-38912736

ABSTRACT

Islet ß-cell dysfunction is an underlying factor for type I diabetes (T1D) development. Insulin sensing and secretion is tightly regulated in ß-cells at multiple subcellular levels. The epithelial intermediate filament protein keratin (K) 8 is the main ß-cell keratin, constituting the filament network with K18. To identify the cell-autonomous functions of K8 in ß-cells, mice with targeted deletion of ß-cell K8 (K8flox/flox; Ins-Cre) were analyzed for islet morphology, ultrastructure and integrity, as well as blood glucose regulation and streptozotocin (STZ)-induced diabetes development. Glucose transporter 2 (GLUT2) localization was studied in ß-cells in vivo and in MIN6 cells with intact or disrupted K8/K18 filaments. Loss of ß-cell K8 leads to a major reduction in K18. Islets without ß-cell K8 are more fragile and these ß-cells display disjointed plasma membrane organization with less membranous E-cadherin and smaller mitochondria, with diffuse cristae. Lack of ß-cell K8 also leads to a reduced glucose stimulated insulin secretion response in vivo, despite undisturbed systemic blood glucose regulation. K8flox/flox; Ins-Cre mice have a decreased sensitivity to STZ compared to K8 wild-type mice, which is in line with decreased membranous GLUT2 expression observed in vivo, as GLUT2 is required for STZ uptake in ß-cells. In vitro, MIN6 cell plasma membrane GLUT2 is rescued in cells overexpressing K8/K18 filaments, but mistargeted in cells with disrupted K8/K18 filaments. ß-cell K8 is required for islet and ß-cell structural integrity, normal mitochondrial morphology and GLUT2 plasma membrane targeting, and has implications on STZ sensitivity as well as systemic insulin responses.

12.
Nat Commun ; 15(1): 5492, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38944653

ABSTRACT

One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.


Subject(s)
Biomarkers , HIV Infections , Humans , HIV Infections/drug therapy , HIV Infections/mortality , HIV Infections/immunology , Biomarkers/blood , Africa South of the Sahara/epidemiology , Male , Female , Adult , Adolescent , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Viral Load , Young Adult , Anti-HIV Agents/therapeutic use , Child
13.
BMC Health Serv Res ; 24(1): 693, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822370

ABSTRACT

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.


Subject(s)
Universal Health Insurance , Uterine Cervical Neoplasms , Humans , Colombia/epidemiology , Uterine Cervical Neoplasms/mortality , Female , Middle Aged , Adult , Insurance, Health/statistics & numerical data
14.
Ann Work Expo Health ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843454

ABSTRACT

Take-home exposures occur when workers accidentally bring workplace contaminants home. Regular job responsibilities may expose construction workers to lead, which extends to their households via the take-home pathway. The present study aimed to develop and evaluate 2 educational sessions addressing take-home lead exposure tailored to construction workers and their families. Educational materials on take-home lead exposure and prevention strategies were designed following guidance from US government institutions and experts on construction work, lead exposure, and educational interventions. The educational materials were pilot-tested with construction workers and their family members during in-person or online sessions in English or Spanish. Changes in knowledge of take-home lead exposure were assessed through pre- and post-testing and open-ended feedback was collected from both participants and session facilitators. The study sample comprised 44 participants, including 33 workers and 11 family members. Among all participants, 81% were male, 46% were Hispanic or Latino, and the average age was 29 years. Post-test scores (µ = 93%, SD = 10%) were higher than pre-test scores (µ = 82%, SD = 19%), and younger participants (<30 years) were more likely to have a lower pre-test score compared to older participants (≥30 years). Overall, feedback from participants and facilitators was positive, indicating appropriate duration, appealing visuals, and ease of engagement through the training activities. Effective public health education for lead-exposed construction workers and their families is needed to reduce lead exposure disparities, especially among children of workers. Interventions must recognize that take-home exposures are not isolated to occupational or home environments.

15.
Obstet Gynecol ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843528

ABSTRACT

BACKGROUND: Ectopic prostatic tissue in female patients is rare. It is theorized that the presence of prostatic tissue in female patients is likely a Wolffian remnant or transformation of hormonally mediated tissue of the uterus, cervix, Skene's gland, and, rarely, periurethral tissue. Due to the increase in the use of testosterone and gender-affirming therapies, it is important to understand the role of testosterone in mediating the presence of ectopic prostatic tissue. CASE: We present a case of ectopic prostatic tissue in a urethral diverticulum in a female patient with exposure to testosterone hormone therapy and review the literature on this finding. CONCLUSION: Although rare, ectopic prostatic tissue should be considered in the differential diagnosis of anterior vaginal cysts, especially in the setting of testosterone supplementation.

16.
Article in English | MEDLINE | ID: mdl-38860856

ABSTRACT

Keratin intermediate filaments form dynamic filamentous networks, which provide mechanical stability, scaffolding and protection against stress to epithelial cells. Keratins and other intermediate filaments have been increasingly linked to the regulation of mitochondrial function and homeostasis in different tissues and cell types. While deletion of keratin 8 (K8‒/‒) in mouse colon elicits a colitis-like phenotype, epithelial hyperproliferation and blunted mitochondrial ketogenesis, the role for K8 in colonocyte mitochondrial function and energy metabolism is unknown. We used two K8 knockout mouse models and CRISPR/Cas9 K8‒/‒ colorectal adenocarcinoma Caco-2 cells to answer this question. The results show that K8‒/‒ colonocyte mitochondria in vivo are smaller and rounder, and that mitochondrial motility is increased in K8‒/‒ Caco-2 cells. Furthermore, K8-/- Caco-2 cells displayed diminished mitochondrial respiration and decreased mitochondrial membrane potential compared to controls, whereas glycolysis was not affected. The levels of mitochondrial respiratory chain complex proteins and mitochondrial regulatory proteins mitofusin-2 and prohibitin were decreased both in vitro in K8‒/‒ Caco-2 cells and in vivo in K8‒/‒ mouse colonocytes, and re-expression of K8 into K8‒/‒ Caco-2 cells normalizes the mitofusin-2 levels. Mitochondrial Ca2+ is an important regulator of mitochondrial energy metabolism and homeostasis, and Caco-2 cells lacking K8 displayed decreased levels and altered dynamics of mitochondrial matrix and cytoplasmic Ca2+. In summary, these novel findings attribute an important role for colonocyte K8 in stabilizing mitochondrial shape and movement and maintaining mitochondrial respiration and Ca2+ signaling. Further, how these metabolically compromised colonocytes are capable of hyperproliferating presents an intriguing question for future studies.

17.
Cereb Cortex ; 34(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38850213

ABSTRACT

The relative contributions of genetic variation and experience in shaping the morphology of the adolescent brain are not fully understood. Using longitudinal data from 11,665 subjects in the ABCD Study, we fit vertex-wise variance components including family effects, genetic effects, and subject-level effects using a computationally efficient framework. Variance in cortical thickness and surface area is largely attributable to genetic influence, whereas sulcal depth is primarily explained by subject-level effects. Our results identify areas with heterogeneous distributions of heritability estimates that have not been seen in previous work using data from cortical regions. We discuss the biological importance of subject-specific variance and its implications for environmental influences on cortical development and maturation.


Subject(s)
Cerebral Cortex , Magnetic Resonance Imaging , Humans , Cerebral Cortex/growth & development , Cerebral Cortex/anatomy & histology , Cerebral Cortex/diagnostic imaging , Male , Female , Adolescent , Longitudinal Studies , Gene-Environment Interaction , Child , Environment
18.
Bol Med Hosp Infant Mex ; 81(3): 191-194, 2024.
Article in English | MEDLINE | ID: mdl-38941642

ABSTRACT

BACKGROUND: Transverse myelitis (TM) is a demyelinating inflammatory disease that presents with motor, sensory, and autonomic dysfunction, which may be acute or subacute. COVID-19-associated TM has been described in a scarce number of patients. CLINICAL CASE: A 15-year-old previously healthy male patient with respiratory disease before his neurological deterioration presented to the emergency room after developing a complete medullary syndrome located at the cervical-dorsal level, with ascending and symmetric paraparesis that rapidly progressed to paraplegia, with sensory dysfunction from the T3 level, sphincter dysfunction and sudden ventilatory deterioration that required mechanical ventilation. Magnetic resonance imaging was compatible with acute TM. Inflammatory and non-inflammatory etiologies were discarded. In addition, a positive severe acute respiratory syndrome coronavirus 2 test was obtained. Treatment included steroid pulses and plasmapheresis, with an insidious evolution. CONCLUSION: COVID-19 is an infrequent cause of TM and should be suspected when other etiologies have been ruled out.


INTRODUCCIÓN: La mielitis transversa (MT) es una enfermedad inflamatoria desmielinizante que se presenta con disfunción motora, sensitiva y autonómica, de forma aguda o subaguda. La MT asociada al COVID-19 se ha escrito en un escaso número de pacientes. CASO CLÍNICO: Se presenta el caso de un masculino de 15 años previamente sano, quien cursaba con un cuadro respiratorio y que desarrollo un deterioro neurológico súbito que involucro un síndrome medular completo localizado en el nivel cérvico dorsal, con paraparesia simétrica que progreso a la paraplejia, con disfunción sensitiva desde el nivel medular de T3, disfunción de esfínteres y deterioro ventilatorio que requirió manejo avanzado de la vía aérea. Su resonancia magnética fue compatible con mielitis transversa aguda. Se descartaron causas inflamatorias y no inflamatorias de la patología. Además, se obtuvo un resultado positivo de SARS-COV-2. Se inició tratamiento con pulsos de metilprednisolona y plasmaféresis, con una evolución insidiosa. CONCLUSIÓN: El COVID-19 es una causa infrecuente de MT y debe sospecharse cuando otras causas han sido descartadas.


Subject(s)
COVID-19 , Magnetic Resonance Imaging , Myelitis, Transverse , Humans , Myelitis, Transverse/diagnosis , Myelitis, Transverse/virology , Myelitis, Transverse/therapy , COVID-19/complications , COVID-19/diagnosis , Male , Adolescent , Plasmapheresis/methods , Respiration, Artificial , Paraplegia/etiology , Paraplegia/virology , Paraparesis/etiology
19.
J Clin Sleep Med ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38935051

ABSTRACT

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) therapy has historically had strict eligibility requirements including a body mass index (BMI) < 32 kg/m2. However, recent Food and Drug Administration approval expanded indications to a BMI < 40 kg/m2. There is a wide variability in body fat distribution. This study sought to determine if neck circumference is a better surrogate predictive variable for HGNS outcomes than BMI. METHODS: A retrospective chart review was conducted at a tertiary care center on adults who underwent HGNS implantation by a single surgeon from March 2017 to October 2021. Baseline demographic data including neck circumference, diagnostic sleep studies and post-implantation HGNS titration studies were collected. Linear regression and Spearman's Correlation Coefficient (SCC) analysis were utilized to compare neck circumference (NC), percentage of predicted neck circumference (PPNC) and BMI with the apnea-hypopnea index at effective voltage (AHI-v). RESULTS: This study included 43 patients who were middle aged (61.1 years), predominantly male (76.7%), with severe obstructive sleep apnea (median AHI 35) and mean neck circumference of 15.3 inches. Utilizing the NC and PPNC, positive correlations with AHI-v were observed (p = 0.0033, SCC = .438, and p = 0.0029, SCC = .444). While controlling for BMI, a 1-inch increase in neck circumference was associated with a 35% increase in AHI-v (p = 0.0411). CONCLUSIONS: A larger neck circumference was independently associated with worse HGNS outcomes. Further research is needed to support and confirm these findings, particularly across sexes.

20.
Vet Sci ; 11(6)2024 May 29.
Article in English | MEDLINE | ID: mdl-38921991

ABSTRACT

Cattle ticks are a significant health concern in tropical livestock production due to their hematophagous behavior and potential as vectors for human and animal pathogens. In this study, we investigated the tick population present in dairy cattle production, calves, and grazing areas of livestock systems in the northwestern Colombian Amazon. Identification was based on taxonomic keys and molecular markers. Phylogenetic relationships were established using mitochondrial COX1 and 16S genes. Population structure analysis was performed considering age, racial type (B. indicus vs. B. taurus), and the influence of environmental factors and the geomorphological landscape on tick population dynamics. Our findings revealed the presence of a single tick species, with a unique haplotype identified for each mitochondrial gene assessed. Phylogenetic analysis classified the found species within Clade A of the Rhipicephalus microplus complex. Ticks were more prevalent during periods of low rainfall and high temperature, and B. taurus cows exhibited the highest tick abundance. Thus, these results provide insights into the population characteristics and distribution of the tick species present in dairy cattle production systems in the northwestern part of the Colombian Amazon. This information is fundamental for developing targeted strategies based on seasonal variation and host characteristics to mitigate tick infestation severity in the region.

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