Objective To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro. Design Laboratory study. Setting University hospitals. ...Patients(s) Not applicable. Interventions(s) Not applicable. Main Outcome Measure(s) HuLM cells were treated with 1,25-dihydroxyvitamin D3 (vitamin D), and cell proliferation was assayed by the methylthiazolyl tetrazolium technique. proliferating cell nuclear antigen (PCNA), BCL-2, BCL-w, cyclin-dependent kinase (CDK) 1, and catechol- O -methyltransferase ( COMT ) protein levels were analyzed by Western blotting. COMT mRNA and enzyme activity were assayed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and high-performance liquid chromatography analysis, respectively. The role of COMT was evaluated in stable HuLM cells by silencing COMT expression. Result(s) Vitamin D inhibited the growth of HuLM cells by 47 ± 0.03% at 1 μM and by 38 ± 0.02% at 0.1 μM compared with control cells at 120 hours of treatment. Vitamin D inhibited extracellular signal–regulated kinase activation and down-regulated the expression of BCL-2, BCL-w, CDK1, and PCNA. Western blot, RT-PCR, and enzyme assay of COMT demonstrated inhibitory effects of vitamin D on COMT expression and enzyme activity. Silencing endogenous COMT expression abolished vitamin D–mediated inhibition of HuLM cell proliferation. Conclusion(s) Vitamin D inhibits growth of HuLM cells through the down-regulation of PCNA, CDK1, and BCL-2 and suppresses COMT expression and activity in HuLM cells. Thus, hypovitaminosis D appears to be a risk factor for uterine fibroids.
BACKGROUND:Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study ...evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults.
METHODS:Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 (APOE ε4) status, and regional tissue volume. Models were repeated testing PWV×APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation.
RESULTS:Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=−0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=−1.16; P=0.047), lower temporal lobe CBF (β=−1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=−0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=−1.20; P=0.02).
CONCLUSIONS:Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer’s disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.
Smokers have lower risk of obesity, which some consider a "beneficial" side effect of smoking. However, some studies suggest that smoking is simultaneously associated with higher central adiposity ...and, more specifically, ectopic adipose deposition. Little is known about the association of smoking with intermuscular adipose tissue (IMAT), an ectopic adipose depot associated with cardiovascular disease (CVD) risk and a key determinant of muscle quality and function. We tested the hypothesis that smokers have higher abdominal IMAT and lower lean muscle quality than never smokers. We measured abdominal muscle total, lean, and adipose volumes (in cubic centimeters) and attenuation (in Hounsfield units HU) along with subcutaneous (SAT) and visceral adipose tissue (VAT) volumes using computed tomography (CT) in 3,020 middle-aged Coronary Artery Risk Development in Young Adults (CARDIA) participants (age 42-58, 56.3% women, 52.6% white race) at the year 25 (Y25) visit. The longitudinal CARDIA study was initiated in 1985 with the recruitment of young adult participants (aged 18-30 years) equally balanced by female and male sex and black and white race at 4 field centers located in Birmingham, AL, Chicago, IL, Minneapolis, MN, and Oakland, CA. Multivariable linear models included potential confounders such as physical activity and dietary habits along with traditional CVD risk factors. Current smokers had lower BMI than never smokers. Nevertheless, in the fully adjusted multivariable model with potential confounders, including BMI and CVD risk factors, adjusted mean (95% CI) IMAT volume was 2.66 (2.55-2.76) cm.sup.3 in current smokers (n = 524), 2.36 (2.29-2.43) cm.sup.3 in former smokers (n = 944), and 2.23 (2.18-2.29) cm.sup.3 in never smokers (n = 1,552) (p = 0.007 for comparison of former versus never smoker, and p < 0.001 for comparison of current smoker versus never and former smoker). Moreover, compared to participants who never smoked throughout life (41.6 41.3-41.9 HU), current smokers (40.4 39.9-40.9 HU) and former smokers (40.8 40.5-41.2 HU) had lower lean muscle attenuation suggesting lower muscle quality in the fully adjusted model (p < 0.001 for comparison of never smokers with either of the other two strata). Among participants who had ever smoked, pack-years of smoking exposure were directly associated with IMAT volume (beta 95% CI: 0.017 0.010-0.025) (p < 0.001). Despite having less SAT, current smokers also had higher VAT/SAT ratio than never smokers. These findings must be viewed with caution as residual confounding and/or reverse causation may contribute to these associations. We found that, compared to those who never smoked, current and former smokers had abdominal muscle composition that was higher in adipose tissue volume, a finding consistent with higher CVD risk and age-related physical deconditioning. These findings challenge the belief that smoking-associated weight loss or maintenance confers a health benefit.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Edentulism affects the chewing ability of a person and can engender nutritional deficiencies which can affect the overall quality of life and depression. Aim: Our aim was to evaluate the ...association between perceived chewing ability, oral health-related quality of life (OHRQoL) and depressive symptoms among completely edentulous patients with and without dentures. Settings and Design: Institutional study and cross-sectional design. Methods: A cross-sectional study among 207 completely edentulous persons was conducted in South India. The subjects completed a self-administered questionnaire on demographics, Beck's depression inventory, oral health impact profile-edentulous (OHIP-EDENT), age when edentate, chewing ability, and denture satisfaction. Further, denture status was clinically evaluated. Statistical Analysis: Data were summarised and analysed using the Chi-square test and multivariate logistic regression. P < 0.05 was considered significant. Results: Persons not using complete dentures (odds ratio OR =3.5, P < 0.05), who reported impaired chewing ability (OR = 4.6, P < 0.05), those who became edentate before 55 years (OR = 4.6, P < 0.05) and with poor denture status (OR = 6.2, P < 0.05) were more likely to report depressive symptoms. Lesser impact in relation to OHRQoL was found to be protective against depression among completely edentulous (OR = 0.24, P < 0.05). Conclusion: Depressive symptoms were associated with impaired chewing ability, higher impacts on OHIP-EDENT, and edentulous persons not using complete dentures. High priority must be given to enhance awareness towards oral rehabilitation among completely edentulous to reduce the chance of depression occurring due to impaired chewing ability and poor OHRQoL.
Objective To identify and characterize myometrial/fibroid stem cells by specific stem cell markers in human myometrium, and to better understand the stem cell contribution in the development of ...uterine fibroids. Design Prospective, experimental human and animal study. Setting University research laboratory. Patient(s)/Animal(s) Women undergoing hysterectomy for treatment of symptomatic uterine fibroids and female NOD/SCID/IL-2Rγnull mice. Intervention(s) Identification and isolation of stem cells from human fibroids and adjacent myometrium tissues using Stro-1/CD44–specific surface markers. Main Outcome Measure(s) Flow cytometry, semiquantitative polymerase chain reaction, clonogenicity assays, cell culture, molecular analysis, immunocyto-histochemistry, in vitro differentiation, and xenotransplantation assays. Result(s) Using Stro-1/CD44 surface markers, we were able to isolate stem cells from adjacent myometrium and human fibroid tissues. The undifferentiated status of isolated cells was confirmed by the expression of ABCG2 transporter, as well as additional stem cell markers OCT4 , NANOG , and GDB3 , and the low expression of steroid receptors ER α and PR-A/PR-B . Mesodermal cell origin was established by the presence of typical mesenchymal markers (CD90, CD105, and CD73) and absence of hematopoietic stem cell markers (CD34, CD45), and confirmed by the ability of these cells to differentiate in vitro into adipocytes, osteocytes, and chondrocytes. Finally, their functional capability to form fibroid-like lesions was established in a xenotransplantation mouse model. The injected cells labeled with superparamagnetic iron oxide were tracked by both magnetic resonance imaging and fluorescence imaging, thus demonstrating the regenerative potential of putative fibroid stem cells in vivo. Conclusion(s) We have demonstrated that Stro-1/CD44 can be used as specific surface markers to enrich a subpopulation of myometrial/fibroids cells, exhibiting key features of stem/progenitor cells. These findings offer a useful tool to better understand the initiation of uterine fibroids, and may lead to the establishment of effective therapeutic options.
Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons ...with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART.
A total of 92 PWH with well-controlled viremia underwent computed tomography imaging and abdominal SAT biopsy for gene expression analysis. SAT gene expression was measured using a NanoString panel of 255 immune-related genes. Associations between gene expression and computed tomography measurements of the volume and attenuation (radiodensity) of metabolically relevant ectopic fat depots were assessed using multivariable linear regression and network analysis.
Greater SAT volume was associated with higher visceral and pericardial adipose tissue volume, but lower skeletal muscle attenuation. Lower SAT attenuation, a measure of lipid content, was associated with lower visceral adipose tissue attenuation. Hierarchical clustering identified a subset of macrophage-related genes in SAT, including CCL2, CCL22, CCL13, CCR1, CD86, CD163, IL-6, IL-10, MRC1, and TREM2, which were associated with an increased lipid deposition in multiple ectopic depots.
Altered expression of macrophage-related genes in SAT is associated with differences in ectopic fat depot morphometrics among PWH on long-term ART, including in the pericardial and visceral compartments. These findings provide basis for future studies to assess host, virus, and treatment factors shaping the SAT immune environment and its effects on morphometric changes and metabolic comorbidities in PWH.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with prominent impairments in sociocommunicative abilities, which have been linked to anomalous brain network organization. Despite ...ample evidence of atypical long-distance connectivity, the literature on local connectivity remains small and divergent. We used resting-state functional MRI regional homogeneity (ReHo) as a local connectivity measure in comparative analyses across several well-matched low-motion subsamples from the Autism Brain Imaging Data Exchange and in-house data, with a grand total of 147 ASD and 184 typically developing (TD) participants, ages 7–18 years. We tested for group differences in each subsample, with additional focus on the difference between eyes-open and eyes-closed resting states. Despite selection of highest quality data and tight demographic and motion matching between groups and across samples, few effects in exactly identical loci (voxels) were found across samples. However, there was gross consistency across all eyes-open samples of local overconnectivity (ASD > TD) in posterior, visual regions. There was also gross consistency of local underconnectivity (ASD < TD) in cingulate gyrus, although exact loci varied between mid/posterior and anterior sections. While all eyes-open datasets showed the described gross similarities, the pattern of group differences for participants scanned with eyes closed was different, with local overconnectivity in ASD in posterior cingulate gyrus, but underconnectivity in some visual regions. Our findings suggest that fMRI local connectivity measures may be relatively susceptible to site and cohort variability and that some previous inconsistencies in the ASD ReHo literature may be reconciled by more careful consideration of eye status.
The restoration of normal function and esthetics is often challenging in the prosthetic rehabilitation of patients with hemimandibulectomy defects due to unstable occlusion and mandibular deviation. ...The extensive period of time for completion of healing of the reconstructed mandible through reconstructive plastic surgery and/or implant-assisted prosthesis may compromise the masticatory function by causing delay in the fabrication of definitive prosthesis. This case report describes a novel technique for the construction of customized attachment-retained mandibular guiding flange prosthesis for immediate rectification of the frontal plane rotation occurring after hemimandibulectomy.
Self-generation of material compared to passive learning results in mproved memory performance; this may be related to recruitment of a fronto-temporal encoding network. Using a verbal ...paired-associate learning fMRI task, we examined the effects of sex, age, and handedness on the neural correlates of self-generation.
Data from 174 healthy English-speaking participants (78M, 56 atypically handed; ages 19-76) were preprocessed using AFNI and FSL. Independent component analysis was conducted using GIFT (Group ICA fMRI Toolbox). Forty-one independent components were temporally sorted by task time series. Retaining correlations (
> 0.25) resulted in three task-positive ("generate") and three task-negative ("read") components. Using participants' back-projected components, we evaluated the effects of sex, handedness, and aging on activation lateralization and localization in task-relevant networks with two-sample
-tests. Further, we examined the linear relationship between sex and neuroimaging data with multiple regression, covarying for scanner, age, and handedness.
Task-positive components identified using ICA revealed a fronto-parietal network involved with self-generation, while task-negative components reflecting passive reading showed temporo-occipital involvement. Compared to older adults, younger adults exhibited greater task-positive involvement of the left inferior frontal gyrus and insula, whereas older adults exhibited reduced prefrontal lateralization. Greater involvement of the left angular gyrus in task-positive encoding networks among right-handed individuals suggests the reliance on left dominant semantic processing areas may be modulated by handedness. Sex effects on task-related encoding networks while controlling for age and handedness suggest increased right hemisphere recruitment among males compared to females, specifically in the paracentral lobe during self-generation and the suparmarginal gyrus during passive reading.
Identified neuroimaging differences suggest that sex, age, and handedness are factors in the differential recruitment of encoding network regions for both passive and active learning.
Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to ...other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease.
We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort.
We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.
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