Depression partially mediated the relationship between basic psychological needs and quality of life among people living with HIV.

Few studies have examined the relationship between basic psychological needs (BPN), depression and quality of life (QOL) in people living with HIV (PLWH). This cross-sectional study (N = 65; 37% females, 37% Caucasian, mean age = 55 ± 6 years, mean CD4 count = 668 ± 368 cells/mm3, average duration of HIV = 18 ± 4 years) found that BPN frustration was related with lower QOL. The strength of this relationship was reduced after controlling for depression. This suggests that depression partially mediated the relationship between BPN and QOL. BPN and depression may be specific targets for psychosocial interventions aimed at improving QOL in PLWH to promote successful aging.

Pathogenesis of the Novel Autoimmune-Associated Long-QT Syndrome.

BACKGROUND: Emerging clinical evidence demonstrates high prevalence of QTc prolongation and complex ventricular arrhythmias in patients with anti-Ro antibody (anti-Ro Ab)-positive autoimmune diseases. We tested the hypothesis that anti-Ro Abs target the HERG (human ether-a-go-go-related gene) K(+) channel, which conducts the rapidly activating delayed K(+) current, IKr, thereby causing delayed repolarization seen as QT interval prolongation on the ECG. METHODS AND RESULTS: Anti-Ro Ab-positive sera, purified IgG, and affinity-purified anti-52kDa Ro Abs from patients with autoimmune diseases and QTc prolongation were tested on IKr using HEK293 cells expressing HERG channel and native cardiac myocytes. Electrophysiological and biochemical data demonstrate that anti-Ro Abs inhibit IKr to prolong action potential duration by directly binding to the HERG channel protein. The 52-kDa Ro antigen-immunized guinea pigs showed QTc prolongation on ECG after developing high titers of anti-Ro Abs, which inhibited native IKr and cross-reacted with guinea pig ERG channel. CONCLUSIONS: The data establish that anti-Ro Abs from patients with autoimmune diseases inhibit IKr by cross-reacting with the HERG channel likely at the pore region where homology between anti-52-kDa Ro antigen and HERG channel is present. The animal model of autoimmune-associated QTc prolongation is the first to provide strong evidence for a pathogenic role of anti-Ro Abs in the development of QTc prolongation. It is proposed that adult patients with anti-Ro Abs may benefit from routine ECG screening and that those with QTc prolongation should receive counseling about drugs that may increase the risk for life-threatening arrhythmias.

Determinants of physical and global functioning in adult HIV-positive heterosexual men.

Little is known about the psychosocial factors that might impact the functioning ability of heterosexual men living with HIV. We examined positive and negative coping, social support, and HIV stigma as predictors of physical and global functioning in a cross-sectional sample of 317 HIV-infected adult heterosexual male patients recruited from clinical and social service agencies in New York City. Study participants were primarily minority and low income. Sixty-four percent were African-American, 55% were single, and 90% were 40 years of age or older. The majority had long-term HIV (LTHIV), with an average duration of 15 years since diagnosis. After controlling for participant characteristics, structural equation modeling analyses revealed that positive coping and social support had a significant positive direct effect on global functioning, while stigma had a significant negative direct effect on global functioning. The physical functioning model revealed that negative coping and HIV stigma had significant negative direct effects, whereas social support had a significant positive indirect effect. Age and duration of HIV diagnosis were not associated with physical and global functioning. In conclusion, we found that heterosexual men living with LTHIV who have ineffective coping, less social support, and greater stigma have reduced functioning ability. Study findings have implications for developing interventions aimed at increasing and retaining functioning ability with the end goal of improving successful aging in this population.

Weight loss, exercise, or both and physical function in obese older adults.

BACKGROUND: Obesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial. METHODS: In this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weight-management (diet) group, an exercise group, or a weight-management-plus-exercise (diet-exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life. RESULTS: A total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet-exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet-exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet-exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet-exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet-exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries. CONCLUSIONS: These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00146107.).

A novel mutation (g.106737G>T) in zone of polarizing activity regulatory sequence (ZRS) causes variable limb phenotypes in Werner mesomelia.

Werner mesomelia is characterized by a sequence variation in the specific region (position 404) of the enhancer ZRS of SHH. The phenotype comprises variable mesomelia, abnormalities of the thumb and great toe and supernumerary digits. We describe extensive variation in limb phenotype in a large family and report on a novel sequence variation NG_009240.1: g.106737G>T (traditional nomenclature: ZRS404G>T) in the ZRS within the LMBR1 gene. The newly recognized clinical features in this family include small thenar eminence, sandal gap, broad first metatarsals, mesoaxial polydactyly, and postaxial polydactyly. We provide information on 12 affected family members. We review the literature on how a sequence variation in ZRS may cause such diverse phenotypes.

Adrenal insufficiency in hemodialysis patients-An under-recognized problem: A case series.

Adrenal insufficiency is an uncommon disorder and presents with non-specific symptoms. Identifying adrenal insufficiency in patients with chronic kidney disease requiring dialysis is increasingly difficult as there is a significant overlap of the signs and symptoms of adrenal insufficiency with those seen in chronic kidney failure. We highlight this diagnostic uncertainty in a case series of three patients with chronic kidney disease requiring hemodialysis as renal replacement therapy from a single center identified as hypoadrenal. Steroid replacement improved symptoms and hemodynamic parameters. Increased vigilance for adrenal insufficiency in dialysis patients is necessary. It is likely under recognized in hemodialysis patients given their multi-morbidity.

Dopamine-Functionalized, Red Carbon Quantum Dots for In Vivo Bioimaging, Cancer Therapeutics, and Neuronal Differentiation.

One of the crucial requirements of quantum dots for biological applications is their surface modification for very specific and enhanced biological recognition and uptake. Toward this end, we present the green synthesis of bright, red-emitting carbon quantum dots derived from mango leaf extract (mQDs). These mQDs are conjugated electrostatically with dopamine to form mQDs-dopamine (mQDs:DOPA) bioconjugates. Bright-red fluorescence of mQDs was used for bioimaging and uptake in cancerous and noncancerous cell lines, tissues, and in vivo models like zebrafish. mQDs exhibited the highest uptake in brain tissue compared to the heart, kidney, and liver. mQD:DOPA conjugates killed breast cancer cells and increased uptake in epithelial RPE-1 cells and zebrafish. Additionally, mQDs:DOPA promoted neuronal differentiation of SH-SY5Y cells to differentiated neurons. Both mQDs and mQDs:DOPA exhibited the potential for higher collective cell migrations, implicating their future potential as next-generation tools for advanced biological and biomedical applications.

The role of muscle in bone repair: the cells, signals, and tissue responses to injury.

Bone repair is a complicated process that includes many types of cells, signaling molecules, and growth factors. Fracture healing involves a temporally and spatially regulated biologic process that involves recruitment of stem cells to the injury site, tissue specific differentiation, angiogenesis, and remodeling. In light of its proximity to bone and abundant vascularity, muscle is an important potential source of cells and signals for bone healing. More complete understanding of the role of muscle in bone formation and repair will provide new therapeutic approaches to enhance fracture healing. Recent studies establish that muscle-derived stem cells are able to differentiate into cartilage and bone and can directly participate in fracture healing. The role of muscle-derived stem cells is particularly important in fractures associated with more severe injury to the periosteum. Sarcopenia is a serious consequence of aging, and studies show a strong association between bone mass and lean muscle mass. Muscle anabolic agents may improve function and reduce the incidence of fracture with aging.

Effect of highly active antiretroviral therapy (HAART) and menopause on risk of progression of cervical dysplasia in human immune-deficiency virus- (HIV-) infected women.

BACKGROUND: More HIV-infected women are reaching older age and menopause, but there is limited information on cervical squamous intraepithelial lesions (SILs) on these women. METHODS: To assess the effect of HAART and menopause on SILs in HIV-infected women, we reviewed the results of Papanicolaou (Pap) tests obtained between 1991 and 2011 on 245 women. Progression to SILs was determined by comparing Pap test results. The association of HAART and transition to menopause on SILs was assessed using survival analysis. RESULTS: Women receiving HAART had a 52% reduced risk in the progression to SILs compared to women receiving any other antiretroviral regimen or no regimen (CI: 0.33-0.70, P = 0.0001). A greater increase of CD4(+) cell counts was associated with a greater reduction on the risk of progression to SILs. Menopausal women had a 70% higher risk of progression to SILs than premenopausal women (CI: 1.11-2.62, P < 0.0001), adjusting for HIV medications, CD4(+) count, duration of HIV infection, moderation effect of menopause by age, prior IV drug use, and smoking. CONCLUSION: HAART had a positive long-term effect on the progression to SILs. However, being younger and menopausal increases the risk of progression.

Tissue-Derived Primary Cell Type Dictates the Endocytic Uptake Route of Carbon Quantum Dots and In Vivo Uptake.

Carbon quantum dots (CQDs) require systemic biological delivery to advance their applications in drug delivery, biosensing, and bioimaging. We describe the endocytic pathways of green-emitting fluorescent carbon quantum dots (GCQDs) with sizes varying from 3 to 5 nm in mouse tissue-derived primary cells, tissues, and zebrafish embryos. The GCQDs demonstrated cellular internalization into mouse kidney and liver primary cells via a clathrin-mediated pathway. Using imaging, we were able to identify and reinforce the animal's body features in terms of different tissues exhibiting differential affinity for these CQDs, which will be extremely beneficial in the development of next-generation bioimaging and therapeutic scaffolds based on carbon-based quantum dots.

Impact of the Covid-19 Pandemic on the Prevalence of MTP Cases and Their Clinicodemographic Profile in India: A Retrospective Multicentric Study.

Background: During the Covid-19 pandemic, reproductive health of women was disproportionately affected due to difficult access to safe abortion and contraceptive services. This study aims to assess the impact of the Covid-19 pandemic on the prevalence of MTP cases and to find out the clinicodemographic profiles of women undergoing MTP during three Covid-waves in different hospitals-Government and private sectors in India. Methods: This retrospective multicentric cohort study was conducted during three Covid-19 pandemic waves. The records were retrieved from the centers' medical record section and the MTP register from the Department of Obstetrics and Gynaecology. Results: On an average, 1.1 women/day underwent MTP during covid waves compared to 1.9 women/day during the pre-covid 2019. The first Covid wave's average MTP/day was very low (0.71) compared to the third (2.88) and second wave (1.12), respectively. These differences were statistically significant (p<0.0001). The most common indication for MTP was contraceptive failure 245(50.9%), followed by eugenic/congenital anomalies 88(18.9%). A total of 244 cases (50.6%) reported for MTP ≤ seven weeks and 114(23.6%) presented between 7 and 12 weeks. More than half (54%) of the women underwent surgical methods for abortion as the unavailability of medical abortion (MA) drugs. IUCD and sterilization were severely affected during the first and second Covid waves. Conclusion: Safe abortions are essential services for reproductive-age women. With the uncertainty of future Covid-like an emergency, we should strengthen our telemedicine network so that women can reach out early and MMA can be initiated to reduce the number of surgical abortions and unwanted pregnancies.

Cognitive and neural correlates of aerobic fitness in obese older adults.

UNLABELLED: BacKGROUND/STUDY CONTEXT: Aerobic fitness is associated with preserved cognition and brain volume in older adulthood. The current study investigated whether the benefits of aerobic fitness extend to obese older adults, a segment of the population that is rapidly growing and who exhibit compromised cognition and brain structure relative to their nonobese counterparts. METHODS: Measures of obesity, aerobic fitness, cognition (processing speed, executive function, spatial ability, memory), and regional brain volumes (prefrontal gray, prefrontal white, hippocampus) were obtained from 19 obese older adults aged 65 to 75. Hierarchical linear regression analyses were conducted to examine the proportion of unique variance in cognitive and volumetric measures accounted for by aerobic fitness after controlling for covariates (age, gender, and waist circumference). RESULTS: Aerobic fitness accounted for a significant amount of unique variance in processing speed (adjusted R (2) = .44), executive function (adjusted R (2) = .34), and hippocampal volume (adjusted R (2) = .27). CONCLUSION: This novel pattern of results suggests that obesity does not preclude the benefits of fitness for cognition and brain volume in older adults. Fitness appears to be a beneficial factor for maintenance of processing speed, executive function, and hippocampal volume, which are vulnerable to age- and/or obesity-related decline.

A systematic review of maternal diabetes and congenital skeletal malformation.

The magnitude of association of skeletal anomalies with maternal diabetes is not known. The systemic review was done to detect the frequency of congenital skeletal malformations with diabetes mellitus in pregnancy in the literature evidence of the past 50 years. Literature on maternal diabetes and skeletal malformation was searched by two independent authors by following PRISMA guidelines. Strict inclusion and exclusion criteria were followed. After quality assessment, 21 original articles were included. The frequency of congenital malformation, skeletal malformation was extracted from the included studies. 11,574 congenital anomalies were detected diabetic mothers. 1182 skeletal anomalies were noted in 20,11 552 diabetic mothers. The skeletal malformation was noted in 20.4% of total anomalies. The most common skeletal malformation was the defect of the spine (39.9%). The limb deficiency was found in 32.8% of the infants of diabetic mothers. The skeletal malformations were higher, that is, 24.6% in pre-gestational diabetes. The incidence of skeletal malformation from the evidence was 1.5% (range: 0.03-4.27%) in maternal diabetes. Pre-gestation diabetes is more frequently associated with skeletal malformations, which is 1.9% (range: 0.07-5.89%). The association of congenital malformations and skeletal malformations in diabetic pregnancy is significant and hence, effective management of diabetes in childbearing age is essential to reduce this incidence and related long-term morbidity.

Pregnancy associated plasma protein A: An indicator of adverse obstetric outcomes in a South India population.

OBJECTIVE: First trimester aneuploidy screening (FTAS) has become an integral part of antenatal care in most of centers in India. The serum markers used for FTAS are pregnancy-associated plasma protein A (PAPP-A) and beta human chorionic gonadotropin. In the present study, we aimed to assess the role of PAPP-A in specific adverse fetal maternal events. To analyze pregnancy outcomes with low maternal PAPP-A (≤5th percentile) at the FTAS screening test in southern India, and them compared with a control group of >5th percentile value. MATERIALS AND METHODS: A total of 1800 consecutive pregnancies in the first trimester were followed up with PAPP-A levels. The study group consisted 108 subjects, which was compared with a matched control group of 288 subjects. The outcomes considered were spontaneous abortions, fetal anomalies, preterm delivery (PTD), hypertension in pregnancy, intrauterine growth restriction, gestational diabetes, mode of delivery, and birthweight. RESULTS: For our grouped data, the 5th percentile value for PAPP-A was 0.49 multiple of medians, (incidence-6%). The incidence of fetal major anomalies was higher in the study group [odds ratio (OR): 1.87]. The incidence of minor anomalies, gestational diabetes, and hypertensive disorders was higher in the study group but not statistically significant. The total rate of PTDs (OR:2.1), small-for-gestation-age fetuses (OR:2.3), and low birthweight babies (OR- 2.12) was significantly higher in the study group. We found positive likelihood ratio of 1.4 for PTD, 2 for <5th percentile birthweight, and 1.7 for <10th centile birthweight. CONCLUSION: Low PAPP-A pregnancies are at risk of various obstetric complications. Hence, such a pregnancy should have closer surveillance. Further research work on intervention strategy is needed.

Healthy Aging: American Geriatrics Society White Paper Executive Summary.

In July 2015, the Journal of the American Geriatrics Society published a manuscript titled, "Failing to Focus on Healthy Aging: A Frailty of Our Discipline?" In response, the American Geriatrics Society (AGS) Clinical Practice and Models of Care Committee and Public Education Committee developed a white paper calling on the AGS and its members to play a more active role in promoting healthy aging. The executive summary presented here summarizes the recommendations from that white paper. The full version is published online at GeriatricsCareOnline.org. Life expectancy has increased dramatically over the last century. Longer life provides opportunity for personal fulfillment and contributions to community but is often associated with illness, discomfort, disability, and dependency at the end of life. Geriatrics has focused on optimizing function and quality of life as we age and reducing morbidity and frailty, but there is evidence of earlier onset of chronic disease that is likely to affect the health of future generations of older adults. The AGS is committed to promoting the health, independence, and engagement of all older adults as they age. Geriatrics as an interprofessional specialty is well positioned to promote healthy aging. We draw from decades of accumulated knowledge, skills, and experience in areas that are central to geriatric medicine, including expertise in complexity and the biopsychosocial model; attention to function and quality of life; the ability to provide culturally competent, person-centered care; the ability to assess people's preferences and values; and understanding the importance of systems in optimizing outcomes. J Am Geriatr Soc 67:17-20, 2019.

Effect of weight loss and exercise therapy on bone metabolism and mass in obese older adults: a one-year randomized controlled trial.

BACKGROUND: Although weight loss and exercise ameliorates frailty and improves cardiac risk factors in obese older adults, the long-term effect of lifestyle intervention on bone metabolism and mass is unknown. OBJECTIVE: The objective was to evaluate the effects of diet-induced weight loss in conjunction with exercise on bone metabolism and mass in obese older adults. DESIGN AND SETTING: We conducted a one-year randomized, controlled clinical trial in a university-based research center. PARTICIPANTS: Twenty-seven frail, obese (body mass index = 39 +/- 5 kg/m(2)), older (age 70 +/- 5 yr) adults participated in the study. INTERVENTION: Participants were randomly assigned to diet and exercise (treatment group; n = 17) or no therapy (control group; n = 10). OUTCOME MEASURES: Body weight decreased in the treatment group but not in the control group (-10 +/- 2 vs. +1 +/- 1%, P < 0.001). Compared with the control group, the treatment group had greater changes in bone mass, bone markers, and hormones, including 1) bone mineral density (BMD) in total hip (0.1 +/- 2.1 vs. -2.4 +/- 2.5%), trochanter (0.2 +/- 3.3 vs. -3.3 +/- 3.1%), and intertrochanter (0.3 +/- 2.7 vs. -2.7 +/- .3.0%); 2) C-terminal telopeptide (12 +/- 35 vs. 101 +/- 79%) and osteocalcin (-5 +/- 15 vs. 66 +/- 61%); and 3) leptin (2 +/- 12 vs. -30 +/- 25%) and estradiol (0.1 +/- 14% vs. -14 +/- 21%) (all P < 0.05). Changes in weight (r = 0.55), bone markers (r = -0.54), and leptin (r = 0.61) correlated with changes in hip BMD (all P < 0.05). CONCLUSION: Weight loss, even when combined with exercise, decreases hip BMD in obese older adults. It is not known whether the beneficial effects of weight loss and exercise on physical function lower the overall risk of falls and fractures, despite the decline in hip BMD.

Prenatal diagnosis and management of fetal intra-abdominal umbilical vein varix.

Fetal intra-abdominal umbilical vein varix (FIUVV) is a rare pathology and suggests an enlargement of the umbilical vein. Prenatal diagnosis is done through meticulous ultrasound imaging. Management variables are the diameter of varix, presence or absence of turbulent flow, and fetal anomalies. Color and power Doppler ultrasound helps in diagnosis and follow-up and has a critical role in decision-making for intervention. Clinical guidelines for management are not clear. The adverse fetal outcome is usually associated with multiple malformations, turbulent flow, and thrombotic varix. This case study presents the prenatal diagnosis, obstetric management, and neonatal development of a fetus, diagnosed with FIUVV along with a brief review of the literature.

Significant Role of Segmental Duplications and SIDD Sites in Chromosomal Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic Analysis.

Recurrent non-random chromosomal translocations are hallmark characteristics of leukemogenesis, and however, molecular mechanisms underlying these rearrangements are less explored. The fundamental question is, why and how chromosomes break and reunite so precisely in the genome. Meticulous understanding of mechanism leading to chromosomal rearrangement can be achieved by characterizing breakpoints. To address this hypothesis, a novel multi-parametric computational approach for characterization of major leukemic translocations within and around breakpoint region was performed. To best of our knowledge, this bioinformatic analysis is unique in finding the presence of segmental duplications (SDs) flanking breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were analyzed for stress-induced duplex destabilization (SIDD) sites along with other complex genomic architecture and physicochemical properties. Our study distinctly emphasizes on the probable correlative role of SDs, SIDD sites and various genomic features in the occurrence of breakpoints. Further, it also highlights potential features which may be playing a crucial role in causing double-strand breaks, leading to translocation.