Tag: nevin manimala

Rev Esc Enferm USP. 2023 Nov 3;57:e20220475. doi: 10.1590/1980-220X-REEUSP-2022-0475en. eCollection 2023.

ABSTRACT

OBJECTIVE: To compare the social support as perceived by elderly persons in a context of social vulnerability according to family functionality.

METHOD: A cross-sectional study using a quantitative approach, carried out in São Carlos-SP, with 123 elderly people living in a context of high social vulnerability. The sample was divided into two groups: good family functionality and moderate/severe family dysfunction. Data was collected on sociodemographic characteristics, family functionality (Family APGAR) and social support (Medical Outcomes Study Social Support Scale). The Mann-Whitney, Chi-square and Fisher’s exact statistical tests were used.

RESULTS: There was a statistically significant difference between social support and family functionality (p < 0.05). The group with good family functionality obtained higher median social support scores: affective 100.00; material 95.00; information 90.00; emotional 90.00; positive social interaction 85.00; when compared to the group with moderate/severe family dysfunction: affective 86.67; material 87.50; information 70.00; emotional 65.00; positive social interaction 65.00.

CONCLUSION: Elderly persons living in dysfunctional families have less perceived social support when compared to those living in families with good family functionality.

PMID:37947163 | DOI:10.1590/1980-220X-REEUSP-2022-0475en

Cancer. 2023 Nov 10. doi: 10.1002/cncr.35103. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is a rare, incurable disease. MYB is a putative oncogenic driver in ACC that is often overexpressed through an MYB-NFIB rearrangement. The authors hypothesized that AKT inhibition with the allosteric inhibitor MK-2206 could decrease MYB expression and induce tumor regression in patients with incurable ACC (ClinicalTrials.gov identifier NCT01604772).

METHODS: Patients with progressive, incurable ACC were enrolled and received MK-2206 150 mg weekly; escalation to 200 mg was allowed. The primary end point was confirmed response. Secondary end points were progression-free survival, overall survival, and safety. An exploratory analysis evaluating the effect of MK-2206 on MYB expression was conducted in a subset of patients.

RESULTS: Sixteen patients were enrolled, and 14 were evaluable for efficacy. No confirmed responses were observed. Thirteen patients had stable disease, and one had disease progression as their best response. The median progression-free survival was 9.7 months (95% CI, 3.8-11.8 months), and the median overall survival was 18.0 months (95% CI, 11.8-29.9 months). Nine of 16 patients (56%) had at least one grade 3 treatment-related adverse event, and the most common were rash (38%), fatigue (19%), decreased lymphocyte count (13%), and hyperglycemia (13%). Twelve of 14 tumors (86%) had detectable MYB expression by immunohistochemistry, and seven of 14 tumors (50%) had an MYB-NFIB gene rearrangement. Serial biopsies revealed decreased MYB levels with MK-2206 in four of five patients.

CONCLUSIONS: MK-2206 failed to induce clinical responses in patients with incurable ACC. AKT inhibition may diminish MYB protein levels, although the effect was highly variable among patients. Novel approaches to target MYB in ACC are needed.

PMID:37947157 | DOI:10.1002/cncr.35103

J Prosthodont. 2023 Nov 10. doi: 10.1111/jopr.13792. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effects of 1 vs. 2 glaze firings on the color and mechanical properties of an extrinsically characterized lithium disilicate ceramic after thermal-cycling, brushing, or both.

MATERIALS AND METHODS: Eighty specimens were divided into 2 groups: one glaze firing (GL1) and two glaze firings (GL2). Each group was subdivided into 4 groups (n = 10), according to the experimental conditions: thermal-cycling, brushing, thermal-cycling + brushing, and immersion in distilled water (control). Color variation, surface roughness, and Vickers microhardness were analyzed before each designated experiment and after the simulated periods of 2.5, 5, and 10 years. Three-way mixed ANOVA was used for all outcomes, followed by one-way ANOVA, repeated measures one-way ANOVA, Bonferroni post hoc test, and t-test to check for statistical differences (α = .05).

RESULTS: Thermal-cycling generated greater color changes in the GL1 group at 2.5- and 5 years (P<.001; P = .013). Brushing generated color changes in GL1 at 5 years (P = .003) and in GL2 at 10 years (P = .017). Regarding surface roughness, the GL1 group suffered alterations in thermal-cycling + brushing at 5 years. In the control group, the GL1 group exhibited higher roughness values than GL2 (P<.05). Most of the groups experienced an increase in microhardness at 2.5 years (P<.05). In the GL1 group, thermal-cycling increased the microhardness at 5 years (P = .006); at 5 and 10 years, the GL1 group had a higher microhardness than the GL2 in thermal-cycling + brushing (P<.05).

CONCLUSIONS: Ceramics with one glaze firing showed greater color, roughness, and microhardness changes compared to those submitted to two firings. This article is protected by copyright. All rights reserved.

PMID:37947149 | DOI:10.1111/jopr.13792

J Am Heart Assoc. 2023 Nov 10:e030084. doi: 10.1161/JAHA.123.030084. Online ahead of print.

ABSTRACT

Background Sterile inflammation caused by metabolic disorders impairs endothelial function; however, the underlying mechanism by which hyperglycemia induces inflammation remains obscure. Recent studies have suggested that stimulator of interferon genes (STING), a key cytosolic DNA sensor in the innate immune system, contributes to the pathogenesis of inflammatory diseases. This study examines the role of the STING in endothelial dysfunction in streptozotocin-induced diabetic mice. Methods and Results Injection of streptozotocin promoted the expression of STING and DNA damage markers in the aorta of wild-type mice. Streptozotocin elevated blood glucose and lipid levels in both wild-type and STING-deficient mice, which showed no statistical differences. Genetic deletion of STING ameliorated endothelial dysfunction as determined by the vascular relaxation in response to acetylcholine (P<0.001) and increased endothelial nitric oxide synthase phosphorylation in the aorta (P<0.05) in STZ-injected mice. Endothelium-independent vascular response to sodium nitroprusside did not differ. Treatment with a direct STING agonist, cyclic GMP-AMP, or mitochondrial DNA increased inflammatory molecule expression (eg, VCAM1 and IFNB) and decreased endothelial nitric oxide synthase phosphorylation in human umbilical vein endothelial cells, partially through the STING pathway. Cyclic GMP-AMP significantly impaired endothelial function of aortic segments obtained from wild-type mice, which was ameliorated in the presence of C-176, a STING inhibitor, or a neutralizing interferon-β antibody. Furthermore, the administration of C-176 ameliorated endothelial dysfunction in STZ-induced diabetic mice (P<0.01). Conclusions The DNA damage response regulated by STING impairs endothelial function. STING signaling may be a potential therapeutic target of endothelial dysfunction caused by hyperglycemia.

PMID:37947148 | DOI:10.1161/JAHA.123.030084

Ortop Traumatol Rehabil. 2023 Aug 31;25(4):195-206. doi: 10.5604/01.3001.0053.9346.

ABSTRACT

BACKGROUND: Besides arch-supportive insoles, sensorimotor insoles are used for the treatment of flatfoot in children. The aim of this study was to compare the effect of both types of insoles on the arch-supporting muscles and clinical aspects in children with flexible flatfoot.

MATERIAL AND METHODS: 52 children with flexible flatfoot (mean age of 8.22.7 years) were enrolled. Supportive, sensorimotor, and placebo insoles were compared. Muscle activity was detected by surface electromyography during the midstance phase. Valgus index, foot and ankle disability index (FADI) and pain were assessed at enrolment and after 6 and 12 months. Mixed-design ANOVA was used for statistical evaluation.

RESULTS: Supportive and sensorimotor insoles caused significantly lower activity in the tibialis anterior in comparison to placebo insoles regarding the parameter Mean. No significant differences could be detected between both types of therapeutic insoles. Supportive insoles showed a significant decrease regarding the parameter Amplitude of the peroneus longus. Placebo insoles produced an increase in the valgus index, while both therapeutic insoles did not induce any changes. The sensorimotor insoles induced an increase in FADI, while the supportive and placebo insoles had no significant effect on this parameter.

CONCLUSIONS: 1. Supportive and sensorimotor insoles potentially influence muscle activity in the lower leg. 2. Both could influence the longitudinal arch in flat feet. 3. While placebo insoles caused a deterioration of the valgus index, both kinds of therapeutic insoles could possibly prevent the progression of the flatfoot. 4. Clinical studies including more clinical aspects and long-term observations are necessary.

PMID:37947144 | DOI:10.5604/01.3001.0053.9346

J Periodontal Res. 2023 Nov 10. doi: 10.1111/jre.13206. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate, in vivo, the effect of local application of Resolvin E1 (RvE1) on the bone regeneration of critical-size defects (CSDs) in Wistar rats utilizing gene expression and micro-computed tomographic (micro-CT) analysis.

BACKGROUND: The inflammation-resolving actions of RvE1 are well established. The molecular mechanism of its bone-regenerative actions has been of significant interest in recent years; however, there is limited information regarding the same.

MATERIALS AND METHODS: Thirty Wistar rats with a 5 mm induced critical-size calvarial defect were randomly allocated into four groups: no treatment/negative control (n = 5), treatment using bovine bone grafts/positive control (n = 5), treatment using local delivery of RvE1 (n = 11) and treatment using RvE1 mixed with bovine bone graft (n = 9). After 4 weeks, RNA isolation, complementary DNA synthesis and real-time polymerase chain reaction were used for genetic expression of alkaline phosphatase (ALP), osteocalcin (OCN) and osteopontin (OPN). The rats were sacrificed after 12 weeks and micro-CT imaging was performed to analyse the characteristics of the newly formed bone (NFB). The data were analysed using ANOVA and the least significant difference tests (α ≤ .05).

RESULTS: The RvE1 + bovine graft group had statistically highest mean NFB (20.75 ± 2.67 mm³ ) compared to other groups (p < .001). Similarly, RvE1 + bovine graft group also demonstrated statistically highest mean genetic expression of ALP (31.71 ± 2.97; p = .008) and OPN (34.78 ± 3.62; p < .001) compared to negative control and RvE1 groups.

CONCLUSION: Resolvin E1 with adjunct bovine bone graft demonstrated an enhanced bone regeneration compared to RvE1 or bovine graft alone in the calvarial defect of Wistar rats.

PMID:37947141 | DOI:10.1111/jre.13206

J Ment Health. 2023 Nov 10:1-9. doi: 10.1080/09638237.2023.2278107. Online ahead of print.

ABSTRACT

BACKGROUND: Latent disease classification is currently the accepted approach to mental illness diagnosis. In the United States, this takes the form of the Diagnostic and Statistical Manual of Mental Disorders-5-Text Revision (DSM-5-TR). Latent disease classification has been criticized for reliability and validity problems, particularly regarding diagnostic heterogeneity. No authors have calculated the scope of the heterogeneity problem of the entire DSM-5-TR.

AIMS: We addressed this issue by calculating the unique diagnostic profiles that exist for every DSM-5-TR diagnosis.

METHODS: We did this by applying formulas previously used in smaller heterogeneity analyses to all diagnoses within the DSM-5-TR.

RESULTS: We found that there are 10,130,814 ways to be diagnosed with a mental illness using DSM-5-TR criteria. When specifiers are considered, this number balloons to over 161 septillion unique diagnostic presentations (driven mainly by bipolar II disorder). Additionally, there are 1,951,065 ways to present with psychiatric symptoms, yet not meet diagnostic criteria.

CONCLUSIONS: Latent disease classification leads to considerable heterogeneity in possible presentations. We provide examples of how latent disease classification harms research and treatment programs. We echo recommendations for the dismissal of latent disease classification as a mental illness diagnostic program.

PMID:37947129 | DOI:10.1080/09638237.2023.2278107

J Am Heart Assoc. 2023 Nov 10:e030117. doi: 10.1161/JAHA.123.030117. Online ahead of print.

ABSTRACT

Background Mortality from cardiovascular diseases in Asian populations is considerable. Menopause is a risk-enhancing factor for cardiovascular disease, but it is unclear whether menopause is an independent risk factor for cardiovascular disease and mortality in Asian women. Methods and Results A total of 1 159 405 postmenopausal women, who had participated in the health examinations of the Korean National Health Insurance Service in 2009, were analyzed, and their reproductive histories were taken. A multivariable Cox proportional hazard model assessed the hazard ratios (HRs) of myocardial infarction (MI), ischemic stroke, and all-cause mortality, according to the history of premature menopause and age at menopause. After an average 10-year follow-up, there were 31 606, 45 052, and 77 680 new cases of MI, ischemic stroke, and all-cause mortality, respectively. The women with premature menopause exhibited increased risks of MI (HR, 1.40 [95% CI, 1.31-1.50]), ischemic stroke (HR, 1.24 [95% CI, 1.17-1.31]), and all-cause mortality (HR, 1.19 [95% CI, 1.14-1.24]) when compared with women with menopause aged ≥50 years. The highest risk was evident with menopause between the ages of 30 and 34 years (HR for MI, 1.52 [95% CI, 1.30-1.78]; HR for ischemic stroke, 1.29 [95% CI, 1.12-1.48]; HR for all-cause mortality, 1.33 [95% CI, 1.20-1.47]) when compared with women with menopause aged ≥50 years. Conclusions Earlier age at menopause was associated with increased risks for MI, ischemic stroke, and all-cause mortality. Future guidelines and risk assessment tools should consider menopause as an independent risk factor of cardiovascular disease in Korean women.

PMID:37947103 | DOI:10.1161/JAHA.123.030117

J Am Heart Assoc. 2023 Nov 10:e030211. doi: 10.1161/JAHA.123.030211. Online ahead of print.

ABSTRACT

Background Patients with rheumatoid arthritis (RA) have a 2- to 10-fold increased risk of cardiovascular disease (CVD), but the biological mechanisms and existence of causality underlying such associations remain to be investigated. We aimed to investigate the genetic associations and underlying mechanisms between RA and CVD by leveraging large-scale genomic data and genetic cross-trait analytic approaches. Methods and Results Within UK Biobank data, we examined the genetic correlation, shared genetics, and potential causality between RA (N_cases=6754, N_controls=452 384) and cardiovascular diseases (CVD, N_cases=44 238, N_controls=414 900) using linkage disequilibrium score regression, cross-trait meta-analysis, and Mendelian randomization. We observed significant genetic correlations of RA with myocardial infarction (r_g:0.40 [95% CI, 0.24-0.56), angina (r_g:0.42 [95% CI, 0.28-0.56]), coronary heart diseases (r_g:0.41 [95% CI, 0.27-0.55]), and CVD (r_g:0.43 [95% CI, 0.29-0.57]) after correcting for multiple testing (P<0.05/5). When stratified by frequent use of analgesics, we found increased genetic correlation between RA and CVD among participants without aspirin usage (r_g:0.54 [95% CI, 0.30-0.78] for angina; P_value=6.69×10^-6) and among participants with paracetamol usage (r_g:0.75 [95% CI, 0.20-1.29] for myocardial infarction; P_value=8.90×10^-3), whereas others remained similar. Cross-trait meta-analysis identified 9 independent shared loci between RA and CVD, including PTPN22 at chr1p13.2, BCL2L11 at chr2q13, and CCR3 at chr3p21.31 (P_{single trait}<1×10^-3 and P_meta<5×10^-8), highlighting potential shared pathogenesis including accelerating atherosclerosis, upregulating oxidative stress, and vascular permeability. Finally, Mendelian randomization estimates showed limited evidence of causality between RA and CVD. Conclusions Our results supported shared genetic pathogenesis rather than causality in explaining the observed association between RA and CVD. The identified shared genetic factors provided insights into potential novel therapeutic target for RA-CVD comorbidities.

PMID:37947095 | DOI:10.1161/JAHA.123.030211

Circulation. 2023 Nov 10. doi: 10.1161/CIRCULATIONAHA.123.067626. Online ahead of print.

ABSTRACT

Background: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the AHA Predicting Risk of CVD EVENTs (PREVENT) equations among US adults aged 30-79 years without known CVD. Methods: The derivation sample included individual-level participant data from 25 datasets (N=3,281,919) between 1992-2017. The primary outcome was CVD (atherosclerotic CVD [ASCVD] and heart failure [HF]). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, anti-hypertensive or statin use, diabetes) and estimated glomerular filtration rate [eGFR]. Models were sex-specific, race-free, developed on the age-scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each dataset and meta-analyzed. Discrimination was assessed using Harrell’s C-statistic. Calibration was calculated as the slope of the observed vs. predicted risk by decile. Additional equations to predict each CVD subtype (ASCVD, HF) and include optional predictors (urine albumin-to-creatinine ratio [UACR], hemoglobin A1c [HbA1c]), and social deprivation index [SDI]) were also developed. External validation was performed in 3,330,085 participants from 21 additional datasets. Results: Among 6,612,004 adults included, mean (SD) age was 53 (12) years and 56% were female. Over a mean (SD) follow-up of 4.8 (3.1) years, there were 211,515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval [IQI]: 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (IQI 0.81 -1.16) and 0.94 (0.81-1.13) among females and males, respectively. Similar estimates for discrimination and calibration were observed for ASCVD- and HF-specific models. The improvement in discrimination was small but statistically significant when UACR, HbA1c, and SDI were added together to the base model to total CVD (ΔC-statistic [IQI] 0.004 [0.004, 0.005] and 0.005 [0.004, 0.007] among females and males, respectively). Calibration improved significantly when UACR was added to the base model among those with marked albuminuria (>300mg/g) (1.05 [0.84-1.20] vs. 1.39 [1.14-1.65], p=0.01). Conclusions: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults using routinely available clinical variables.

PMID:37947085 | DOI:10.1161/CIRCULATIONAHA.123.067626