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Objective: To understand epidemiology of the neonatal and infant deaths in predominant areas of two tribal districts of Gujarat. Methods: A secondary analysis of pregnancy and mortality surveillance data was done to understand the causes and determinants of infant deaths in predominant tribal areas of two districts of Gujarat, India from 2015 to 2018. All pregnancies, their outcomes, and infant deaths were prospectively registered. A verbal autopsy tool was used to understand the cause of death. Result: A total of 25,130 live births were recorded; 20,994 (83.5%) deliveries occurred at the hospital. Total 1,309 infant deaths (IMR - 52.08/1,000 live births) and 879 neonatal deaths (NMR - 34.97/1,000 live births) occurred during the program duration. The odds of infant deaths was high among male child aOR - 1.5 (CI:1.3–1.7, p < 0.001), born to illiterate/primary educated mother aOR - 1.2 (1.03–1.4, 0.013), born at home or on the way aOR - 1.4 (1.1–1.8, 0.003), born with low birth weight (< 2.5 kg), aOR - 3.7 (3.2–4.3, < 0.001), born preterm (< 37 wk) aOR - 1.9 (1.7–2.2, < 0.001), and born twins aOR - 1.5 (1–2.1, 0.037) in comparison to female child, born to secondary/or above educated mother, born in hospital, born normal weight (>= 2.5 kg), born full-term (>= 37 wk), and born single, respectively. The asphyxia/respiratory distress syndrome (RDS) 282 (56%), sepsis/pneumonia and asphyxia/RDS 188 (63%), and sepsis/pneumonia 281 (65%) were leading cause of death among 0–3 d, 4–28 d, and 29–365 d infant deaths. Conclusion: There is a need to improve quality of intrapartum and postpartum care. Additionally, sepsis detection among infants and referral by community health workers also need to be improved to reduce infant mortality due to sepsis. [ABSTRACT FROM AUTHOR]

It is pertinent to have a Tuning Fork Hearing Test that stand-alone can detect severities (Mild, Moderate, Severe and Profound) and the types of hearing losses (Conductive, Sensorineural, and Mixed). A novel 3-Step Tuning Fork Hearing Test (3-STFHT) was attempted for the first time that could detect both the types and the severities of hearing losses. The study was aimed to describe the method of the 3-STFHT and evaluate its clinical utility and reliability. Research Design: Hospital-based observational study of a diagnostic tool. Settings: Otorhinolaryngology Department of a tertiary care medical college hospital. Subjects: 108 adult patients (216 ears) who required hearing evaluation. Main Outcome measures: Sensitivity and specificity of novel 3-STFHT were assessed by comparing its results with the reports of pure tone audiometry in detecting the type and severity of hearing loss. The new 3-STFHT was found very effective (100% sensitivity and specificity) in detecting conductive and profound sensorineural hearing losses. The sensitivity in detecting sensorineural hearing loss was found 97%-100%. The sensitivity was observed relatively low (92%) at detecting mixed hearing loss. The overall sensitivity and specificity of the 3-STFHT in detecting the types of hearing losses was found 97% and 86% respectively. The novel 3-STFHT, which is simple and convenient, was found very effective in detecting the types and severity of hearing losses. The 3-STFHT can be an important tool in otorhinolaryngology practice and in primary care setting for detecting and screening the types and severities of hearing losses. [ABSTRACT FROM AUTHOR]

Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today's pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis. [ABSTRACT FROM AUTHOR]

Covid-19-associated neurological manifestations are being reported with increased frequency throughout the world. In a study from China, symptoms referable to peripheral nervous system (PNS) were described in approximately 9% of hospitalized Covid-19 patients. Common PNS symptoms reported in the study were loss of taste/smell and muscle pains. With this communication, we expand the spectrum of PNS manifestations of Covid-19 infection by reporting an association of steroid responsive diffuse anterior horn cell disease with Covid-19 infection from a tertiary care centre in India. Neurological manifestations of Covid-19 are diverse, and our case which to best of my knowledge is the first case in literature to report an occurrence of steroid responsive diffuse anterior horn cell disease associated with Covid-19 infection, adds to the ever-increasing spectrum of neurological manifestations associated with this pandemic causing virus. Good response to steroid in our case serves to provide an insight into the possible pathogenesis of this manifestation and also paves the way for future therapeutic decisions related to this association. [ABSTRACT FROM AUTHOR]

The innate immune response following infection with entero-invasive bacterial species is triggered upon release of cyclic di-guanylate monophosphate (c-di-GMP) into the host cell cytosol. Bacterial c-di-GMP activates the intracellular Sensor Stimulator of Interferon Genes (STING), encoded by Tmem173 in mice. Here we identify Interferon Regulatory Factor (IRF) 1 as a critical effector of STING-mediated microbial DNA sensing that is responsible for TH17 cell generation in the mucosal immune system. We find that STING activation induces IRF1-dependent transcriptional programs in dendritic cells (DCs) that define T cell fate determination, including induction of Gasdermin D, IL-1 family member cytokines, and enzymes for eicosanoid synthesis. Our results show that IRF1-dependent transcriptional programs in DCs are a prerequisite for antigen-specific TH17 subspecification in response to microbial c-di-GMP and Salmonella typhimurium infection. Our identification of a STING-IRF1 signaling axis for adaptive host defense control will aid further understanding of infectious disease mechanisms. Sung-Moo Park et al. identify the transcription factor IRF1 as a critical component of the STING signaling complex following microbial c-di nucleotides stimulation and Salmonella infection. They find that activation of IRF1 by STING is required for antigen-specific T cell specification and subsequent host defense response. [ABSTRACT FROM AUTHOR]

Background: Paraneoplastic Cerebellar degeneration (PCD) is one of the classical paraneoplastic syndromes (PNS) which is characterised by subacute onset, progressive cerebellar ataxia and is usually associated with small cell lung carcinoma, adeno carcinoma of breast and ovary followed by Hodgkin's lymphoma. Objective: We herein report a case of subacute onset, progressive cerebellar ataxia in a 37-year-old female, who on evaluation was found to have non-Hodgkin's lymphoma and experienced good clinical response to treatment. Discussion: As compared to solid tumours, chances of association of PNS with Lymphomas is quite low and there are only few case reports in the literature showing association of PCD with non-Hodgkin's lymphoma. As PCD is one of the classical PNS, it is very important to identify subtle cerebellar manifestations in an otherwise apparently normal individual, as early diagnosis and aggressive treatment can immensely improve the mortality and morbidity associated with this syndrome. Conclusion: This case signifies the importance of suspecting PNS as an important differential diagnosis in a young patient presenting with subacute onset progressive cerebellar ataxia and evaluating her extensively for malignancy in spite of no paraneoplastic antibody been detected as early diagnosis and treatment can lead to gratifying response. We do agree that 2 weeks follow up is a short time interval to determine whether the response was sustained or not, for which a long term follow up is required. [ABSTRACT FROM AUTHOR]

Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL ( p = 0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels ( p = 0.2). To investigate the mechanism for the variability in the change in PCSK9 levels, lymphoblastoid cell lines were incubated with both sirolimus and everolimus, resulting in a 2-3 fold increase in PCSK9 expression and protein levels in mTOR inhibitor sensitive but not in mTOR inhibitor resistant cell lines. This first in human study demonstrates that sirolimus therapy is associated with elevation in PCSK9 levels which is not associated with sirolimus-induced hypercholesterolemia. [ABSTRACT FROM AUTHOR]

In this work, an example of analytical method quality by design (AQbD) principles applied to an in-line NIR method to monitor blend potency and uniformity in the manufacturing of an oral solid dosage product is presented. An integrated process analytical technology (PAT) method was developed following the AQbD workflow, including risk assessment, design of experiments (DoE), method control strategy, and method maintenance. Several aspects particular to partial least square (PLS) chemometric method development and validation (such as the combined use of DoE, optimization, and multivariate data analysis) are addressed. Results from the risk assessment showed that the active pharmaceutical ingredient (API) particle size was the most significant risk factor due to the presence of aggregates. This risk was reduced by introducing changes in the API crystallization procedure and by including a wide range of calibration blends within the expected range of particle size. Other potential risks related to the instrumentation, the API and excipient properties, and the environment were further studied and minimized. System suitability tests based on Mahalanobis distance and discriminant analysis (DA) techniques were developed to ensure the quality of the spectral data before blend potency calculation. The use of AQbD provided a robust and rugged method that has the potential to be used as part of the product real-time release (RTR) control strategy. [ABSTRACT FROM AUTHOR]

Churg-Strauss syndrome (CSS) also called allergic granulomatosis and angiitis is a multisystem disorder. Churg-Strauss syndrome is defined as an eosinophil-rich, granulomatous inflammation involving the respiratory tract, along with necrotizing vasculitis affecting small- to medium-sized vessels, and is associated with asthma and eosinophilia. Renal involvement in CSS varies from 26 to 88 % but is usually of mild to moderate stage, and advanced renal failure is uncommon. We encountered an unusual case of 27-year-old man with asthma and primary focal segmental glomerulosclerosis diagnosed as CSS showing myeloperoxidase anti-neutrophil cytoplasmic antibody-associated acute kidney injury with crescentic glomerulonephritis. Patient responded to steroid and cyclophosphamide. Over a follow-up of 2 months, he has no hematuria/eosinophilia and serum creatinine of 2.3 mg/dL has decreased to 1.7 mg/dL. [ABSTRACT FROM AUTHOR]

A 42-year-old renal transplant recipient was admitted with fever, anorexia, malaise, nonproductive cough, and dyspnea of 1-week duration. Multiple cultures of blood, sputum, and urine were negative. The possibility of bronchiolitis obliterans with organizing pneumonia (BOOP) was considered when pulmonary infiltrate did not respond to conventional antibiotic therapy. High-resolution computed tomography of the chest revealed patchy air-space consolidation and ground-glass opacities, predominantly located in the periphery of the lungs. Cultures and stains of bronchoalveolar lavage specimen and bronchoscopic biopsy of lung tissue were negative for organisms such as Pneumocystis (carinii) jiroveci, bacteria, Mycobacterium tuberculosis, cytomegalovirus, fungi, and atypical germs, and showed evidence of BOOP. The patient recovered completely after treatment with steroids. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. Herein, we report a case of spontaneous resolution of AKI due to collapsing glomerulopathy (CG) and hemolytic-uremic syndrome (HUS) associated with P. falciparum malaria. Our case report highlights the fact that early intervention on the triggering cause of CG without a long course of steroids may obtain a remission of this severe subset of CG and may obtain a remission of HUS without therapeutic plasmapheresis The etiologic treatment of CG and HUS may avoid progression to end-stage renal disease. [ABSTRACT FROM AUTHOR]

Down syndrome is one of the most common genetic causes of learning disabilities in children. Although the incidence of renal and urological involvement in Down syndrome is not very common, monitoring of patients with Down syndrome for renal diseases should be done regularly as patient's age into the second and third decades. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Down syndrome patients are apparently not suited for peritoneal dialysis because of lacking cooperation. This procedure can be prone to failure, mainly because of an increased risk of peritonitis. Handling such patients especially those on peritoneal dialysis is challenging. Here we report a case of Down syndrome with end-stage renal disease treated with hemodialysis for 6 months. To the best of our knowledge and current literature review this is the first case report of a patient with Down syndrome undergoing hemodialysis. [ABSTRACT FROM AUTHOR]

Background: Economic constraints in operating an effective maintenance dialysis program leaves renal transplantation as the only viable option for end-stage renal disease patients in India. Kidney paired donation (KPD) is a rapidly growing modality for facilitating living donor (LD) transplantation for patients who are incompatible with their healthy, willing LD. Materials and methods: The aim of our study was to report a single-center feasibilities and outcomes of KPD transplantation between 2000 and 2012. We performed KPD transplants in 70 recipients to avoid blood group incompatibility ( n = 56) or to avoid a positive crossmatch ( n = 14). Results: Over a mean follow-up of 2.72 ± 2.96 years, one-, five- and ten-year patient survival were 94.6, 81, 81 %, and death-censored graft survival was 96.4, 90.2, 90.2 %, respectively. Ten percent of patients were lost, mainly due to infections ( n = 4). There was 14.2 % biopsy-proven acute rejection, and 5.7 % interstitial fibrosis with tubular atrophy eventually leading to graft loss. Conclusion: The incidences of acute rejection, patient/graft survival rates were acceptable in our KPD program and, therefore, we believe it should be encouraged. These findings are valuable for encouraging participation of KPD pairs and transplant centers in national KPD program. It should be promoted in centers with low-deceased donor transplantation. Our study findings are relevant in the context of Indian government amending the Transplantation of Human Organs Act to encourage national KPD program. To our knowledge, it is largest single-center report from India. [ABSTRACT FROM AUTHOR]

Purpose: To study the frequency of hypernatremia in hospitalized cancer patients and its impact on clinical outcomes and healthcare cost. Methods: Cross-sectional analysis of data obtained from patients admitted to the University of Texas M. D. Anderson Cancer Center over a 3-month period in 2006. The clinical outcomes and hospital costs were compared among hypernatremics, eunatremics, and hyponatremics (serum sodium values include >147, 135-147, and <135 mEq/L, respectively). Results: Of 3,446 patients with at least one serum sodium value, 51.4 % were eunatremic, 46.0 % hyponatremic, and 2.6 % hypernatremic with most of the hypernatremia (90 %) acquired during hospital stay. The multivariate hazard ratio (HR) for mortality in hypernatremic was 5-fold higher than eunatremic (HR for 90 days-5.09 (95 % CI, 3.32-7.81); p < 0·01) and over 2-fold higher than hyponatremic (HR for 90 days-2.79 (95 % CI, 1.91-4.11), p < 0.01). The length of hospital stay in hypernatremic was 2-fold higher than in hyponatremic and 4-fold higher than in eunatremic (e.g., 27 ± 22 days in hypernatremic vs. 6 ± 5 days in eunatremic; mean ± SD, p < 0.01). The hospital bill was higher for hypernatremic compared with the rest of the groups (46 % over eunatremic and 37 % over hyponatremic, p < 0.01 for both). Conclusions: Although hypernatremia was far less frequent than hyponatremia in the hospitalized cancer patients, most hypernatremia were acquired in the hospital and had substantially higher mortality, hospital stay, and hospital bills than eunatremic or even hyponatremic patients. Studies are warranted to determine whether avoidance of hypernatremia or its prompt and sustained correction improves clinical outcomes. [ABSTRACT FROM AUTHOR]

Nocardiosis is a rare opportunistic infection, especially seen in immunocompromised patients, including renal allograft recipients. Primary pulmonary infection is the most common clinical pattern and can easily result in disseminated Nocardia infection if treatment therapy is not adequate at the beginning. We report a case of pulmonary nocardiosis associated with cytomegalovirus retinitis in a renal transplant recipient, followed by chronic allograft dysfunction. Our patient was a 50-year-old male renal allograft recipient, with diabetes mellitus and hypertension, who was diagnosed with pneumonia and cytomegalovirus retinitis. High-resolution computed tomography scan of the thorax and bronchoscopy revealed nocardial pneumonia. The patient responded well to ceftriaxone and was later switched to oral minocycline. To our knowledge, this is the first report of a successful treatment of co-infection with Nocardia pneumonia and cytomegalovirus retinitis in a renal transplant patient, with early diagnosis and prompt treatment. [ABSTRACT FROM AUTHOR]

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive condition characterized by retinitis pigmentosa, postaxial polydactyly, central obesity, and renal involvement. Renal failure is the commonest cause of death. We report a case of BBS with chronic kidney disease (CKD) at younger age (17 year) from India. This diagnosis should be considered in patients with renal disease and the characteristic phenotype of retinitis pigmentosa, postaxial polydactyly and central obesity. These patients should undergo regular monitoring of renal function test to early diagnosis and treatment of CKD to prevent morbidity and mortality. Renal transplantation is a viable option of renal replacement therapy in these patients. These findings are valuable for comparing phenotype of BBS patients with CKD from various national and international centers. [ABSTRACT FROM AUTHOR]

Plasmodium vivax infection is increasingly a major public health burden and the second most frequent human malaria. Higher levels of clinical severity and chloroquine resistance are major factors responsible for such increases. Malarial glomerular injury is uncommon and mainly observed in Plasmodium malariae-infected patients. Occasionally, transient immune complex-mediated glomerulonephritis is associated with Plasmodium falciparum infection. Coexistent crescentic glomerulonephritis and vivax malaria have not previously been reported. We report a fatal case of P. vivax malaria, who presented with acute renal failure. P. vivax monoinfection status was diagnosed with peripheral blood smear and rapid antigen test. Further evaluation for renal failure related to systemic illness and immunological markers were inconclusive. He was treated with antimalarial drugs, hemodialysis, and supportive therapy. Renal biopsy performed for nonrecovering renal failure reveled crescentic glomerulonephritis. This case highlights the need to thoroughly search for malaria-associated crescentic glomerulonephritis using renal biopsy after nonrecovering renal failure. [ABSTRACT FROM AUTHOR]

Plasmodium vivax is causing increasingly more cases of severe malaria worldwide. There is an urgent need to reexamine the clinical spectrum and burden of P. vivax so that adequate control measures can be implemented against this emerging but neglected disease. Herein, we report a case of renal acute cortical necrosis and acute kidney injury (AKI) associated with P. vivax monoinfection. Her initial serum creatinine was 7.3 mg/dL on admission. Modification of Diet in Renal Disease (MDRD) Study glomerular filtration rate (GFR) value was 7 mL/min/1.73 m (normal kidney function-GFR above 90 mL/min/1.73 m and no proteinuria). On follow-up, 5 months later, her SCr. was 2.43 mg/dl with no proteinuria. MDRD GFR value was 24 mL/min/1.73 m suggesting severe chronic kidney disease (CKD; GFR less than 60 or kidney damage for at least 3 months), stage 4. Our case report highlights the fact that P. vivax malaria is benign by name but not always by nature. AKI associated with P. vivax malaria can lead to CKD. Further studies are needed to determine why P. vivax infections are becoming more severe. [ABSTRACT FROM AUTHOR]

Severe and complicated malaria is usually caused by Plasmodium falciparum malaria (PF ) but it has been increasingly observed that Plasmodium vivax malaria (PV), which was otherwise considered to be benign malaria, with a low case-fatality ratio, can also occasionally result in severe disease as with PF malaria. There is an urgent need to re-examine the clinical spectrum and burden of PV so that adequate control measures can be implemented against this emerging but neglected disease. We report a case of severe PV malaria with multi-organ dysfunction. Patients exhibited acute kidney injury, severe anemia/thrombocytopenia, jaundice, hypoglycemia, hyponatremia, and pulmonary edema. Peripheral blood microscopy by trained and expert pathologist and rapid diagnostic test showed the presence of PV and absence of PF. The patient recovered completely with anti-malarial drugs, supportive measures, and hemodialysis.Recent microrheologic research that analyzed malaria severity in PV clearly demonstrated enhanced aggregation, erythrocyte clumping, and reduced deformability affecting microcirculation. Our case report highlights the fact that PV malaria is benign by name but not always by nature. PV can lead to unusual and potentially life-threatening complications. Further large-scale multi-centric studies are needed to define this less known entity. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (DM) is the commonest cause of end-stage renal disease (ESRD) worldwide. Renal transplantation (RTx) is the best therapeutic modality for such patients. First-degree relatives of patients with type 2 DM have high risk of diabetes/pre-diabetes. Parents are often too old to be suitable donors, and siblings/children/spouse are either not suitable/acceptable or do not come forward for organ donation. This leaves deceased donation (DD) as only suitable donors. Data scarcity on DDRTx outcome in diabetic nephropathy (DN) prompted us to review our experience. This retrospective single-center 10-year study was undertaken to evaluate patient/graft survival, graft function, rejection episodes, and mortality in these patients. Materials and methods: Between January 2001 and March 2011, thirty-five DN-ESRD patients underwent DDRTx in our center following cardiac fitness assessment of recipients. All patients received single-dose rabbit-anti-thymocyte globulin for induction and steroids, calcineurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression. Mean recipient age was 49.66 ± 6.76 years, and 25 were men. Mean donor age was 50 ± 16.45 years, 23 were men. Results: Over a mean follow-up of 2.28 ± 2.59 years, patient and graft survival rates were 68.5% and 88.5%, respectively, with mean SCr of 1.9 ± 0.62 mg/dl. Delayed graft function was observed in 34.3% patients, and 25.7% had biopsy-proven acute rejection; 31.5% patients died, mainly because of infections (22.8%), coronary artery disease (2.86%), and cerebrovascular events (5.7%). Conclusion: DDRTx in patients with DN has acceptable graft function and patient/graft survival over 10-year follow-up in our center and, therefore, we believe it should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (DM) is the commonest cause of end-stage renal disease (ESRD) worldwide. Data scarcity on renal transplantation (RTx) outcome in diabetic nephropathy (DN) prompted us to review our experience. This retrospective single-center, 5-year study was undertaken to evaluate patient and graft survival and function, evaluated by serum creatinine (SCr), rejection episodes, and mortality in patients. Patients and methods: One hundred type 2 DM-ESRD patients underwent RTx [80 living-related (LRD), 20 deceased donor (DD)] at our center following cardiac fitness of recipient. Post-transplant immunosuppression consisted of calcineurin inhibitor-based regimen. The mean donor age in the LRD group was 40.6 years and 52 years in the DD group. Male recipients constituted 95% in the LRD and 65% in the DD group. Results: Over a mean follow-up of 2.47 years, 1- and 5-year patient/graft survival in LRDRTx was 85.1%/95.9% and 82.6%/95.9%, respectively, and mean SCr (in mg/dl) at 1 and 5 years was 1.38 and 1.58 mg/dl, respectively, with 20% of cases developing acute rejection (AR) episodes. Fifteen percent of patients died, mainly due to infections, and 1.3% died of coronary artery disease (CAD). In DDRTx, over a mean follow-up of 3.17 years, 1- and 4-year patient/graft survival was 72%/89.7% and 54%/89.7%, respectively; mean SCr at 1 and 4 years was 1.40 and 1.75 mg/dl, respectively, with 20% of cases developing AR episodes. Totally, 30% of patients were lost, mainly due to infections, and 10% of patients died from cerebrovascular events. Conclusion: In our center, in patients with RTx for type 2 DM diabetic nephropathy, the 4- and 5-year patient and graft survival rates and graft function can be considered acceptable. The results are better in LRDRTx than in DDRTx patients. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated donor hypo-responsiveness in renal allograft recipients to donor adipose tissue-derived mesenchymal stem cell (h-AD-MSC) +hematopoietic stem cell transplantation (HSCT) vs. HSCT alone. Methods: Patients were divided into 2 demographically equal groups ( n = 100) A and B subjected to equal non-myeloablative conditioning of target-specific irradiation, anti-T + B cell antibodies and cyclophosphamide with HSCT. Group A was administered h-AD-MSC additionally. Transplantation was performed following favorable cross-matching. Cyclosporine, 3 mg/kg BW/day + prednisone, 20 mg/day were immunosuppressants for first 3 months, cyclosporine was replaced by azathioprine subsequently and prednisone lowered to 5-10 mg/day. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique at 3/18 months post transplant. Biopsy was performed for graft dysfunction and reported as per Banff criteria,'05. Results: Mean nucleated HSC counts ( n × 10/kgBW) was 7.32 with mean CD34+ yield 0.09% in group A; and 6.98 and 0.40% in group B, respectively; CD45−/90+ was 13.49% in former. Over 18 months post transplant, former had mean serum creatinine (SCr), 1.59 mg%, 12% acute rejection (AR) episodes, 3% patient, 1% patient +graft loss; latter had mean SCr 1.49 mg%, 18% AR episodes, 1% patient, 6% graft and 8% patient +graft losses. PBC was higher (4%) in former than later (1.8%). Conclusion: Combined h-AD-MSC +HSCT under non-myeloablative conditioning was safe, more effective than HSCT alone to achieve donor hypo-responsiveness with adequate stable graft function and reduced rejection episodes. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of various malignancies. The study evaluated a comprehensive profile of MMP-2 and MMP-9 and their inhibitors, tissue inhibitor of metalloproteinases-2 (TIMP-2) and tissue inhibitor of metalloproteinases-1 (TIMP-1), respectively in 50 controls and 75 patients with oral squamous cell carcinoma (OSCC). Blood samples from controls and patients as well as malignant and adjacent normal tissues from the patients were collected. The study examined pro, active and total forms of MMP-2 and MMP-9 using zymography. Enzyme-linked immunoassay (ELISA) and reverse transcription polymerase chain reaction were carried out to evaluate protein levels and mRNA expression; respectively, for the MMPs and TIMPs. Plasma pro, active and total MMP-2, MMP-9 as well as TIMP-1 and TIMP-2 levels were significantly higher in oral cancer patients as compared to the controls. mRNA expression of the MMPs and TIMPs was significantly higher in malignant tissues as compared to adjacent normal tissues. A significant positive correlation was observed between levels of proMMP-9 and active MMP-9 with differentiation, stage and infiltration. ProMMP-2 and active MMP-2 exhibited significant positive correlation with differentiation and lymph node involvement. The multivariate analysis of ELISA results revealed a significant positive correlation between MMP-2, TIMP-1 and TIMP-2 levels with lymph node involvement, stage and differentiation. The receiver operating characteristic curve (ROC) analysis showed that the levels of MMPs and TIMPs have significant discriminatory efficacy to differentiate between controls and patients. The results indicate that MMP-2, MMP-9, TIMP-1 and TIMP-2 have significant clinical usefulness for oral cancer patients. Zymographic analysis is a simple, cost effective, rapid and sensitive alternative assay. [ABSTRACT FROM AUTHOR]

Sprycel® (dasatinib) film-coated tablet is a new medicinal product that was recently launched for the treatment of chronic myelogenous leukemia. Due to the early success of dasatinib in phase I clinical trials, development activities were accelerated significantly to enable wide distribution of this drug to patients. As a BCS class II compound, dissolution was considered a critical quality attribute of dasatinib film-coated tablets and a discriminating dissolution method was required to support tablets intended for Phase II clinical trials and commercial use. A systematic experimental approach was established to rapidly screen media pH, solubility enhancers, and concentration in order to overcome the challenges of a tight timeline and limited study materials. The final validated method utilizes 1,000 mL of pH 4.0 acetate buffer with 1% Triton X-100 with a USP Apparatus II (paddle) rotating at 60 rpm and a HPLC sample analysis. [ABSTRACT FROM AUTHOR]

Increased sialylation of cell surface glycoconjugates is among the key molecular changes associated with malignant transformation and cancer progression. We investigated significance of linkage-specific sialylation changes in oral carcinogenesis. Tissue and serum levels of total sialic acid (TSA), linkage-specific sialyltransferases (ST) and sialoproteins were analyzed from patients with oral precancerous conditions (OPC) and oral cancer as well as the post-treatment follow-up blood samples of oral cancer patients. TSA levels were measured using a spectrophotometric method. The linkage-specific lectins, Sambusus nigra (SNA) and Maackia amurensis (MAM) detects α2-6- and α2-3-linked sialic acid, respectively, were used to analyze ST activity and sialoproteins. Malignant tissues showed significantly higher levels of TSA, reactivity of SNA and MAM, and α2,3-ST activity compared to the adjacent normal tissues. α2,6-ST was also higher in malignant tissues. Similarly, the marker levels were higher in precancerous tissues than their adjacent normal tissues. Serum levels of TSA, TSA/ total proteins, α2-6-sialoproteins and α2,6-ST were markedly increased in untreated oral cancer patients compared to the controls and OPC as well as responder (CR) patients. Serum levels of the markers were higher or comparable between untreated oral cancer patients and non-responders (NR). Serum levels of α2-3-sialylation were elevated in non-responders compared with the responders. Further, the observed sialylation changes in tissue and serum were found to be associated with various clinicopathological features and disease progression. Thus, the data suggest potential utility of sialylation markers in early detection, prognostication and treatment monitoring of oral cancer. [ABSTRACT FROM AUTHOR]

In vitro studies have established that free fatty acids (FFAs) are important regulators of hepatic glucose metabolism. FFAs can increase hepatic glucose release by increasing the amount and activity of glucose-6-phosphatase and multiple gluconeogenic enzymes. Elevated FFAs can also potentially decrease hepatic glucose uptake by decreasing hepatic glucokinase activity. In vivo studies in both animals and humans have shown a close correlation between changes in plasma FFAs and endogenous glucose production (EGP). Intervention studies have established that changes in plasma FFAs are accompanied by changes in the relative contribution of gluconeogenesis and glycogenolysis to EGP. The effects of a change in FFAs on EGP itself are more evident when compensatory changes in insulin secretion are prevented or when insulin secretion is impaired (eg, diabetes mellitus). The effects of elevated FFAs on splanchnic glucose uptake are less clear, in that they appear to have no effect in nondiabetic humans and may impair uptake in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s10072-021-05161-x [ABSTRACT FROM AUTHOR]

Integrated interventions for child survival as carried out in community health project of SEWA-Rural, a voluntary organisation working in tribal area of Gujarat, were discussed. They were introduced in phased manner over a period of ten years. It throws considerable light on field problems and how they can be overcome. The interventions mainly related to development of local manpower, appropriate technology like delivery pack and pictorial cards, functional referral support and linkages with other agencies, particularly with government. The latter is quite unprecedented in which the state government handed over entire PHC to a voluntary organisation. Utilisation of majority of Maternal & Child Health services has reached up to the target to be achieved by 2000 A.D. There is near-eradications of measles mortality, newborn tetanus and dramatic fall in the prevalence of vitamin A deficiency, complication of childhood tuberculosis and dehydration death. The childhood & infant mortalities have reduced to less than half, but after an initial fall there was very little further improvement in perinatal and neonatal mortality. There is an immediate need to strengthen the existing facilities of neonatal and perinatal care at all level. Those who conduct most of the deliveries in rural area, i.e. TBA's and nurses at home and in health center required appropriate training to improve their skill and knowledge. There is a need to design safe, simple, cheap but efficient technology to diagnose and manage low birth weight babies and birth asphyxia at community level. [ABSTRACT FROM AUTHOR]

Neutropenic entrocolitis (NE) is a life threatening complication of acute leukemia. The case presented here is of a 12 year old boy with acute myeloid leukemia, who developed neutropenic enterocolitis after induction with BFM-93 protocol. Patient underwent exploratory laparotomy during grade 4 neutropenia after failure on conservative line of management of NE. Patient withstood the procedure with supportive care and recovered. This case is reported because NE is a rare but potentially fatal complication and there are no clear guidelines for surgical intervention. [ABSTRACT FROM AUTHOR]

Plasmodium vivax is causing increasingly more cases of severe malaria worldwide. We reported a case of postrenal transplantation acute kidney injury (AKI) associated with P. vivax, a neglected human malaria parasite. The diagnosis of P. vivax monoinfection was confirmed by direct visualization of the parasite in blood smear and rapid diagnostic test. On admission, serum creatinine (SCr.) increased from 1.45 to 3.7 mg/dl. The other etiologies of fever and AKI were ruled out. He responded to prompt therapy with antimalarial drugs. There was no change in tacrolimus trough level before and after antimalarial drugs. Two weeks after discharge, his SCr. was 1.43 mg/dl. Our patient lived in an endemic malarial area and the transplant took place in December 2010. The patient subsequently presented with clinical malaria in June 2012, so we thought that posttransplantation transmission by the mosquito was a possibility and very less likely that other dormant form of the parasite had been the source of the clinical infection. P. vivax can lead to as AKI in renal transplant recipient. P. vivax should be considered in the differential diagnosis of fever in transplant recipients who had received organs or blood products from malaria-endemic area to facilitate a prompt diagnosis and adequate treatment. [ABSTRACT FROM AUTHOR]

A case of primary intranasal meningioma located in right nasal cavity and eroding right ethmoid, medial wall and floor of right orbit and medial wall of right antrum is presented with a brief review of relevant literature. To our knowledge, it forms 34th case of its kind, in the series of primary meningioma of the nasal cavity and paranasal sinuses' and is amongst the very few to have occured in a child of just eight years. Both primary tumor and its recurrence are successfully removed by lateral rhinotomy. [ABSTRACT FROM AUTHOR]

During infection, transcription factor interferon regulatory factor 5 (IRF5) is essential for the control of host defense. Here we show that the microtubule-associated guanine nucleotide exchange factor (GEF)-H1, is required for the phosphorylation of IRF5 by microbial muramyl-dipeptides (MDP), the minimal structural motif of peptidoglycan of both Gram-positive and Gram-negative bacteria. Specifically, GEF-H1 functions in a microtubule based recognition system for microbial peptidoglycans that mediates the activation of IKKε which we identify as a new upstream IKKα/β and IRF5 kinase. The deletion of GEF-H1 or dominant-negative variants of GEF-H1 prevent activation of IKKε and phosphorylation of IRF5. The GEF-H1-IKKε-IRF5 signaling axis functions independent of NOD-like receptors and is critically required for the recognition of intracellular peptidoglycans and host defenses against Listeria monocytogenes. The transcription factor IRF5 is essential for immune defense against pathogens. Here, the authors show that the microtubule-associated factor GEF-H1 plays a critical role in host defense against Listeria monocytogenes in macrophages via activation of the IRF5 kinase IKKε. [ABSTRACT FROM AUTHOR]