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Aplastic anaemia is characterised by cytopenias and hypocellular bone marrow without any evidence of marrow fibrosis or marrow infiltration. There is no specific cytogenetic abnormality associated with aplastic anaemia. Most common abnormalities are trisomies of chromosome 6, 8 and loss of 7. A 17-year-old female, presented with generalised weakness, exertional breathlessness and menorrhagia for last six months. She also gave a history of 12 units Packed Red Blood Cells (PRBC) transfusion, at the rate of 2-3 units per month in the last five months. Routine haematology showed severe pancytopenia with reticulocytopenia. Bone marrow evaluation revealed hypoplastic marrow with 15% bone marrow cellularity suggesting aplastic anaemia. Karyotyping using Giemsa (GTG) banding of unstimulated culture showed a very unique constitutional Robertsonian Translocation (RT) karyotype 45+XX, der(13;14)(q10;q10). Patient responded partially to treatment with cyclosporine and anabolic steroids. The final diagnosis was severe aplastic anaemia associated with constitutional RT t(13;14) karyotype. Although cytogenetic abnormalities are neither common nor specific in aplastic anaemia, some of them can have diagnostic and therapeutic implications

Carvedilol (CVD) is an antihypertensive agent with a short half-life, pH-dependent solubility, and narrow absorption window. The purpose of this research was to prepare a floating-drug delivery-system of carvedilol to increase its half-life. The present study investigates the preparation of carvedilol-floating microspheres, evaluates the floating-drug delivery-system (FDDS) (by scanning electron microscope), it’s in vitro stability, and in vivo profile. Floating microspheres were prepared by solvent-evaporation (oil-in-water emulsion) technique using hydroxypropyl methylcellulose (HPMC) and ethyl cellulose (EC) as the rate controlling polymers. The surface morphology of the prepared microspheres w:as char:acterized by scanning electron microscopy. In this study, the particle size analysis, drug entrapment efficiency, surface morphology, buoyancy percentage, and release studies were performed. The microspheres were found to be spherical and porous. The results showed that the mean/mean (SD) values of tapped density, Carr's compressibility index, angle of repose, percentage yield, in vitro buoyancy, %entrapment efficiency of CVD-loaded floating microspheres were 0.42 (0.012), 12.5 (1.895), 23.5 (1.856), 80.2 %, 79.0 %, and 85.81(1.40), respectively. The developed floating-microsphere of CVD released the drug for 24 h and based on in vivo studies, the drug-loaded floating microspheres help in maintaining the mean (SD) systolic blood pressure within the range of 120 (0.32) to 120 (1.02) mmHg and diastolic pressure within 91 (0.71) to 92 (0.79) mmHg. Thus, floating microsphere of CVD offers a suitable and practical approach for prolonged release of the drug over an extended period, and thus improves the oral bioavailability and efficacy of the drug as well as the patient’s compliance.

Objective: NOV/CCN3 is an adipocytokine recently linked to obesity, insulin resistance, and cardiometabolic dysfunction. NOV is manufactured and secreted from adipose tissue, with blood levels highly correlated with BMI. NOV levels are increased in obesity and a myriad of inflammatory diseases. Elevated NOV levels cause oxidative stress by increasing free radicals, decreasing antioxidants, and decreasing heme oxygenase (HO-1) levels, resulting in decreased vascular function. Silencing NOV in NOV knockout mice improved insulin sensitivity. We wanted to study how suppressing NOV expression in an obese animal model affected pathways and processes related to obesity, inflammation, and cardiometabolic function. This is the first study to investigate the interaction of adipose tissue-specific NOV/CCN3 and cardiometabolic function. Methods: We constructed a lentivirus containing the adiponectin-promoter-driven shNOV to examine the effect of NOV inhibition (shNOV) in adipose tissue on the heart of mice fed a high-fat diet. Mice were randomly divided into three groups (five per group): (1) lean (normal diet), (2) high-fat diet (HFD)+ sham virus, and (3) HFD + shNOV lentivirus. Blood pressure, tissue inflammation, and oxygen consumption were measured. Metabolic and mitochondrial markers were studied in fat and heart tissues. Results: Mice fed an HFD developed adipocyte hypertrophy, fibrosis, inflammation, and decreased mitochondrial respiration. Inhibiting NOV expression in the adipose tissue of obese mice by shNOV increased mitochondrial markers for biogenesis (PGC-1α, the nuclear co-activator of HO-1) and functional integrity (FIS1) and insulin signaling (AKT). The upregulation of metabolic and mitochondrial markers was also evident in the hearts of the shNOV mice with the activation of mitophagy. Using RNA arrays, we identified a subgroup of genes that highly correlated with increased adipocyte mitochondrial autophagy in shNOV-treated mice. A heat map analysis in obese mice confirmed that the suppression of NOV overrides the genetic susceptibility of adiposity and the associated detrimental metabolic changes and correlates with the restoration of anti-inflammatory, thermogenic, and mitochondrial genes. Conclusion: Our novel findings demonstrate that inhibiting NOV expression improves adipose tissue function in a positive way in cardiometabolic function by inducing mitophagy and improving mitochondrial function by the upregulation of PGC-1α, the insulin sensitivity signaling protein. Inhibiting NOV expression increases PGC-1, a key component of cardiac bioenergetics, as well as key signaling components of metabolic change, resulting in improved glucose tolerance, improved mitochondrial function, and decreased inflammation. These metabolic changes resulted in increased oxygen consumption, decreased adipocyte size, and improved cardiac metabolism and vascular function at the structural level. The crosstalk of the adipose tissue-specific deletion of NOV/CCN3 improved cardiovascular function, representing a novel therapeutic strategy for obesity-related cardiometabolic dysfunction.

Many complexes of Cu, Ag, Au in combination with dianions derived from 2, 5-dihydroxy-1, 4-benzoquinone and 3, 6-dichloro-2, 6-dihydroxy-1, 4-benzoquinones have been synthesized and analysed for their antimicrobial activity. The I.R, 1H and 13CNMR data reveals that 2, 5-dihydroxy-1, 4-benzoquinone, coordinates as an O, O donor of the o-quinone type in cis-Na2[Cu2O5(HBQ)2] 5H2O, cis-(PPh4)2[Cu2O5(HBQ)2], cis-Na2[Ag2O5(HBQ)2]4H2O, trans-AuO2(HBQ).H2O and chloranilate di-anion functions as an O, O ligand in cis-Na2[Cu2O5(DDB)2] 6H2O, cis-(PPh4)2[Cu2O5(DDB)2] 4H2O, cis-Na2[AgO2(DDB)2], cis-(PPh4)2[AgO2(DDB)2] 5H2O, trans-(n-Bu4N)2[AuO2(DDB)2]3H2O. The complexes synthesized showed a good response as antimicrobial agents against the bacterial strains, viz, Bacillus subtilis, Staphylococcus aureus, Xanthomonas malvacearum, E. coli, Rhodococcus sp, Pseudomonas putida.

Recent studies suggest that PGC1-α plays a crucial role in mitochondrial and vascular function, yet the physiological significance of PGC1α and HO expression in adipose tissues in the context of obesity-linked vascular dysfunction remains unclear. We studied three groups of six-week-old C57BL/6J male mice: (1) mice fed a normal chow diet; (2) mice fed a high-fat diet (H.F.D.) for 28 weeks, and (3) mice fed a high-fat diet (H.F.D.) for 28 weeks, treated with adipose-specific overexpression of PGC-1α (transgenic-adipocyte-PGC-1α) at week 20, and continued on H.F.D. for weeks 20–28. R.N.A. arrays examined 88 genes involved in adipocyte proliferation and maturation. Blood pressure, tissue fibrosis, fasting glucose, and oxygen consumption were measured, as well as liver steatosis, and the expression levels of metabolic and mitochondrial markers. Obese mice exhibited a marked reduction of PGC1α and developed adipocyte hypertrophy, fibrosis, hepatic steatosis, and decreased mitochondrial respiration. Mice with adipose-specific overexpression of PGC1-α exhibited improvement in HO-1, mitochondrial biogenesis and respiration, with a decrease in fasting glucose, reduced blood pressure and fibrosis, and increased oxygen consumption. PGC-1α led to the upregulated expression of processes associated with the browning of fat tissue, including UCP1, FGF21, and pAMPK signaling, with a reduction in inflammatory adipokines, NOV/CCN3 expression, and TGFβ. These changes required HO-1 expression. The R.N.A. array analysis identified subgroups of genes positively correlated with contributions to the browning of adipose tissue, all dependent on HO-1. Our observations reveal a positive impact of adipose-PGC1-α on distal organ systems, with beneficial effects on HO-1 levels, reversing obesity-linked cardiometabolic disturbances.

Sirtuins, NAD + dependent proteins belonging to class III histone deacetylases, are involved in regulating numerous cellular processes including cellular stress, insulin resistance, inflammation, mitochondrial biogenesis, chromatin silencing, cell cycle regulation, transcription, and apoptosis. Of the seven mammalian sirtuins present in humans, Sirt6 is an essential nuclear sirtuin. Until recently, Sirt6 was thought to regulate chromatin silencing, but new research indicates its role in aging, diabetes, cardiovascular disease, lipid metabolism, neurodegenerative diseases, and cancer. Various murine models demonstrate that Sirt6 activation is beneficial in alleviating many disease conditions and increasing lifespan, showing that Sirt6 is a critical therapeutic target in the treatment of various disease conditions in humans. Sirt6 also regulates the pathogenesis of multiple diseases by acting on histone proteins and non-histone proteins. Endogenous and non-endogenous modulators regulate both activation and inhibition of Sirt6. Few Sirt6 specific non-endogenous modulators have been identified. Hence the identification of Sirt6 specific modulators may have potential therapeutic roles in the diseases described above. In this review, we describe the development of Sirt6, the role it plays in the human condition, the functional role and therapeutic importance in disease processes, and specific modulators and molecular mechanism of Sirt6 in the regulation of metabolic homeostasis, cardiovascular disease, aging, and neurodegenerative disease.

There are substantial shortcomings in the drugs currently available for treatment of type 2 diabetes mellitus. The global diabetic crisis has not abated despite the introduction of new types of drugs and targets. Persistent unaddressed patient needs remain a significant factor in the quest for new leads in routine studies. Drug discovery methods in this area have followed developments in the market, contributing to a recent rise in the number of molecules. Nevertheless, troubling developments and fresh challenges are still evident. Recently, metformin, the most widely used first-line drug for diabetes, was found to contain a carcinogenic contaminant known as N-nitroso dimethylamine (NDMA). Therefore, purity and toxicity are also a big challenge for drug discovery and development. Moreover, newer drug classes against SGLT-2 illustrate both progress and difficulties. The same was true previously in the case of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Furthermore, researchers must study the importance of mechanistic characteristics of novel compounds, as well as exposure-related hazardous aspects of current and newly identified protein targets, in order to identify new pharmacological molecules with improved selectivity and specificity.

Abstract Background Growing concerns about the value and effectiveness of short-term volunteer trips intending to improve health in underserved Global South communities has driven the development of guidelines by multiple organizations and individuals. These are intended to mitigate potential harms and maximize benefits associated with such efforts. Method This paper analyzes 27 guidelines derived from a scoping review of the literature available in early 2017, describing their authorship, intended audiences, the aspects of short term medical missions (STMMs) they address, and their attention to guideline implementation. It further considers how these guidelines relate to the desires of host communities, as seen in studies of host country staff who work with volunteers. Results Existing guidelines are almost entirely written by and addressed to educators and practitioners in the Global North. There is broad consensus on key principles for responsible, effective, and ethical programs--need for host partners, proper preparation and supervision of visitors, needs assessment and evaluation, sustainability, and adherence to pertinent legal and ethical standards. Host country staff studies suggest agreement with the main elements of this guideline consensus, but they add the importance of mutual learning and respect for hosts. Conclusions Guidelines must be informed by research and policy directives from host countries that is now mostly absent. Also, a comprehensive strategy to support adherence to best practice guidelines is needed, given limited regulation and enforcement capacity in host country contexts and strong incentives for involved stakeholders to undertake or host STMMs that do not respect key principles.

Background: As many as 40% of the shoulder injuries involve acromioclavicular (AC) joint. AC joint injuries have been classified by Rockwood into six types. Treatment of Type 3 AC joint injuries has been controversial. We present a series of 15 cases of Rockwood Type 3 AC joint injuries treated surgically with a method that addresses both superior- inferior as well as anteroposterior AC joint instability. Materials and Methods: Fifteen cases of Rockwood Type 3 AC joint injuries presented to us between November 2011 and November 2015. There were 11 male and four female patients. All patients were treated surgically with the reconstruction of AC and coracoclavicular (CC) ligaments using autogenous semitendinosus graft. The patients were evaluated pre operatively and postoperatively by radiological and functional (using American Shoulder and Elbow Surgeons [ASES] and Constant-Murley scores) methods. Results: X-rays done immediate postoperatively and at 6 weeks, 6 months, and 12 months postoperatively showed good maintenance of the reduction of the AC joint. The ASES score improved from a preoperative score of 41 to a postoperative score of 81 and 95 at 6 and 12 months, respectively. Constant-Murley score improved from a preoperative score of 42 to a post operative score of 79 and 93 at 6 and 12 months, respectively. Conclusion: Surgical management of Rockwood Type 3 AC joint injuries by AC and CC ligament reconstructions using autogenous semitendinosus graft leads to good functional results.

Context: Currently, family medicine is not taught as a part of the undergraduate medical curriculum in India. In this context, the perceptions and attitudes of Indian medical students regarding family medicine as a career choice were studied. Aims: This study aims to study the perceptions and attitudes prevalent among Indian medical students regarding family medicine as a career choice and discuss its future implications. Settings and Design: Cross-sectional survey study design. Methods and Material: We conducted a cross-sectional survey of undergraduate medical (MBBS) students attending the 2016 medical student conference DEMEDCON at Sri Devaraj Urs Medical College in Kolar, Karnataka, India. Besides demographics, the survey included questions pertaining to awareness, exposure, and interest in family medicine in India. We also asked an open-ended question regarding the respondent's perception of the future of family medicine in India. Statistical Analysis: Simple statistics such as mean and frequency (%) were calculated. Given the small sample size, no formal tests for statistical significance were performed. Results: Responses were collected from 45 students between the ages of 18–24 from 6 medical colleges across Karnataka and Puducherry. The majority (64%) of respondents were in their 3rd or 4th year of medical college. 98% of respondents expressed a desire to learn more about family medicine as a specialty, and 82% expressed a need to introduce it as a subject in medical college. However, only 58% were aware of the Medical Council of India accredited status of family medicine in India. Conclusions: There exists a significant lack of awareness and inadequate exposure among Indian medical students toward family medicine. Nonetheless, there is widespread optimism and a desire to learn more about the subject. Increased awareness and avenues for exposure to family medicine in the formal undergraduate medical curriculum is the need of the hour.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'X: standing up for diversity, equity and inclusion', authors address the following themes: 'The power of diversity-why inclusivity is essential to equity in healthcare', 'Medical education for whom?', 'Growing a diverse and inclusive workforce', 'Therapeutic judo-an inclusive approach to patient care', 'Global family medicine-seeing the world "upside down"', 'The inverse care law', 'Social determinants of health as a lens for care', 'Why family physicians should care about human rights' and 'Toward health equity-the opportunome'. May the essays that follow inspire readers to promote change.

Background and Objectives. Chronic myeloid leukemia (CML) is characterized by hyperproliferation of myeloid precursors, increased fibrosis, and neoangiogenesis in the bone marrow. Imatinib inhibits BCR-ABL tyrosine kinase produced due to reciprocal translocation t(9;22) in neoplastic CML cells. It reduces hyperproliferation of myeloid precursors and has been found to affect bone marrow fibrosis and angiogenesis. This study was done to assess the effect of imatinib on bone marrow morphology and angiogenesis in CML. Methods. 31 newly diagnosed CML patients were evaluated before and after 3 months of imatinib therapy. A marrow morphological response (MMR) score was used to assess marrow cytological and histological features including grade of fibrosis. Mean microvessel density (MVD) was also assessed. Hematological parameters and BCR-ABL transcript levels were assessed in the peripheral blood. Results. 86.21% of patients showed decrease in marrow cellularity with normalization of M:E ratio. 72.42% of patients had decrease in grade of fibrosis and 17.24% showed no change while 10.34% of patients showed progression of fibrosis grade. Patients with MMR score ≥ 2 (n=4) and those with progression of fibrosis grade (n=3) showed suboptimal molecular response (BCR-ABL transcripts > 10%). Pretherapy mean MVD of patients (14.69 ± 5.28) was higher than that of controls (6.32 ± 1.64). A significant reduction of 66.51% was observed in posttherapy mean MVD (4.98 ± 2.77) of CML patients (p