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.

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.

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.

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.

Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial.

BACKGROUND: Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions. METHODS/DESIGN: The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling. DISCUSSION: This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017.

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.

A Rare Case of Congenital Tibiofemoral Fusion with Bilateral Proximal Femoral Focal Deficiency: A Case Report.

CASE: We report a unique combination of neonatal bilateral proximal femoral focal deficiency with a congenital tibiofemoral fusion of the right leg. CONCLUSION: To the best of our knowledge, the combination of proximal femoral focal deficiency and the congenital absence of the knee joint in a child has not previously been reported.

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.

Activity engagement and physical function in old age sample.

OBJECTIVES: To describe the patterns of engagement in mental, physical, and social activity (MA, PA, and SA) and to examine the relationship between combined activity engagement and physical function among community-dwelling older adults. DESIGN: Cross-sectional correlational study. SETTING: Multiple communities. PARTICIPANTS: A total of 466 individuals aged 55 years or older. MEASUREMENTS: Physical function was assessed using grip strength and gait speed. Engagement in PA, MA and SA was obtained from self-report questionnaires. RESULTS: We identified four classes ("Active PA and MA", "Active MA", "Active PA", and "Inactive") that significantly differed in the frequency of engagement in MA and PA using latent class analysis. SA didn't differ across classes. Controlling for age, the "Active PA and MA", "Active MA", "Active PA" groups displayed similar grip strength that was superior to the "Inactive" group. "Active PA and MA" group had best gait speed relative to other groups, especially "Active MA" and "Inactive" group, while the "Active PA", "Active MA", and "Inactive" group were similar in gait speed. CONCLUSION: Combined physical and mental activity engagement was associated with better physical function, especially in gait speed. Future interventional research should investigate the combination of both physical and cognitive training to prevent decline of physical function in older adults.

Tyrosine Kinase Inhibitors in Ph+ Chronic Myeloid Leukemia Therapy: a Review.

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCRABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCRABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCRABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKIinsensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either preexisting or induced due to therapy is still a challenge for the clinician. A proposed invitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

Tibial hypoplasia with a bifid tibia: an unclassified tibial hemimelia.

Tibial hemimelia is a rare congenital limb deficiency which is characterised by a hypoplastic/aplastic tibia. It actually represents a spectrum of anomalies, ranging from mild hypoplasia of the tibia to total absence of the tibia. Several classifications based on radiological description exist in the literature. The tibial hemimelia is usually described with preaxial mirror polydactyly, split hand/foot syndrome-ectrodactyly, polydactyly-triphalangeal thumb syndrome (Werner syndrome) and micromelia-trigonal brachycephaly syndrome. We describe a child with unclassified tibial hemimelia. The child had right incomplete tibial hemimelia with bifid tibia, left complete tibial hemimelia, bilateral split hands and left split foot. This is the first report of the bifid tibia in the literature.

Enhancing physical function in HIV-infected older adults: A randomized controlled clinical trial.

OBJECTIVE: HIV-infected older adults (HOA) are at risk of functional decline. Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority. We conducted a randomized, controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory (SDT) improves physical function, autonomous motivation, depression and the quality of life (QOL) in HOA. METHOD: In total, 67 community-dwelling HOA with mild-to-moderate functional limitations were randomized to 1 of 2 groups: a physical activity counseling group or the usual care control group. We used SDT to guide the development of the experimental intervention. Outcome measures that were collected at baseline and final study visits included a battery of physical function tests, levels of physical activity, autonomous motivation, depression, and QOL. RESULTS: The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups. Overall physical performance, gait speed, measures of endurance and strength, and levels of physical activity improved in the treatment group compared to the control group (p < .05). Measures of autonomous regulation such as identified regulation, and measures of depression and QOL improved significantly in the treatment group compared with the control group (p < .05). Across the groups, improvement in intrinsic regulation and QOL correlated with an improvement in physical function (p < .05). CONCLUSION: Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function, autonomous motivation, depression, and QOL in HOA with functional limitations. (PsycINFO Database Record

Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia.

BACKGROUND: The aim of the study was to find a role of Curcumin from natural source to overcome drug resistance as well as to reduce cytotoxicity profile of the drug in Acute Myeloid Leukemia patients. MATERIAL AND METHODS: Primary leukemic cells were obtained from AML patient's bone marrow. These cells were then exposed to different concentration of cytarabine and curcumin to find out IC50 values and also its effect on MDR genes like MDR1, BCRP, LRP and FLT3 by RT-PCR method. RESULT & CONCLUSION: Our results suggested that curcumin down regulates MDR genes. Gene expression was decreased by 35.75, 31.30, 27.97 % for MDR1, LRP, BCRP respectively. In FLT3, it was 65.86 % for wild type and 31.79 % for FLT3-ITD. In addition to this, curcumin has also shown anti-proliferative effect as well as synergistic effect in combination with Cytarabine on primary leukemic cells. Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC50 value decreases when treated in combination.

Spectrum of urorectal septum malformation sequence.

Urorectal septum malformation sequence (URSMS) is a rare spectrum of malformations involving various organ systems. Here, we present eight cases of URSMS, noted in autopsy, with different degrees of complexity, seven being the complete type and one being the partial type. All cases had gastrointestinal tract malformation in the form of the imperforate anus and indeterminate genitalia. Other gastrointestinal tract anomalies were anal agenesis in two cases, anorectal agenesis in two cases, and malformed lower intestinal tract in four cases. The associated renal abnormality was noted in five cases, which were unilateral renal agenesis, dysplastic kidney, hydronephrosis, horseshoe kidney, and unilateral hypoplastic ectopic kidney. External genital malformation, present in both male and female fetuses, included a knob-like structure at perineum in female fetuses, genital fold hypoplasia and penile aplasia or hypoplasia in male fetuses. Skeletal abnormalities included two cases of sacral agenesis and one case of lumbosacral dysraphism. Other anomalies included a case with alobar holoprosencephaly, truncus arteriosus with hypoplastic lungs in one case, and three cases with abdominal wall defects. It is our attempt to delineate a spectrum of abnormalities associated with URSMS.