SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

Local and Nonlocal Transport Spectroscopy in Planar Josephson Junctions.

We report simultaneously acquired local and nonlocal transport spectroscopy in a phase-biased planar Josephson junction based on an epitaxial InAs-Al hybrid two-dimensional heterostructure. Quantum point contacts at the junction ends allow measurement of the 2×2 matrix of local and nonlocal tunneling conductances as a function of magnetic field along the junction, phase difference across the junction, and carrier density. A closing and reopening of a gap was observed in both the local and nonlocal tunneling spectra as a function of magnetic field. For particular tunings of junction density, gap reopenings were accompanied by zero-bias conductance peaks (ZBCPs) in local conductances. End-to-end correlation of gap reopening was strong, while correlation of local ZBCPs was weak. A model of the device, with disorder treated phenomenologically, shows comparable conductance matrix behavior associated with a topological phase transition. Phase dependence helps distinguish possible origins of the ZBCPs.

Realization of Structural Colors via Capped Cu-based F-P Cavity Structure.

Structural colors with tunable properties have several applications in the beautification of mobile devices, surface decoration, art and color filters. Herein, we propose an asymmetric F-P cavity design to systematically tune structural colors by changing the thickness of the top metal and intermediate insulator. In this study, Cu and Si3N4 were chosen as the top metal and intermediate insulator layers, respectively, various reflection colors being realized on the Cu surface. Various capping layers-that is, SiO2, polymethyl methacrylate (PMMA), and a commercially available clear coat named ProtectaClear-were used to protect the Cu surface from scratching and oxidation. PMMA coatings can protect Cu from corrosive environments without degradation of the color quality. The colors can be tuned by controlling the thickness of either the metal or intermediate insulator layers, and vivid structural colors-including orange, bright orange, red, purple, violet, light blue, green-yellow, and yellow-green-can be printed. The colors obtained can be attributed to thin-film interference.

Response of plantain (Plantago lanceolata L.) supplementation on nutritional, endo-parasitic, and endocrine status in lambs.

The aim of the present study was to assess the effects of plantain herb (Plantago lanceolata L.) supplementation on growth, plasma metabolites, liver enzymatic activity, hormonal status, gastrointestinal parasites, and carcass characteristics of lambs. A total of 24 lambs, aged 6 months weighing 8.0 ± 0.5 kg were randomly allocated to one of two dietary treatments: (1) CL diet-roadside grass and concentrate mixture; (2) PL diet-CL diet + 5% fresh plantain supplementation on a DM basis. The PL diet group exhibited 23% higher (P = 0.01) average daily gain and 15% improved (P = 0.03) feed conversion efficiency. Circulating cholesterol concentrations were suppressed by 9% (P = 0.03), and liver enzyme activity was improved by 5-25% (P < 0.05) in the lamb fed PL diet, compared with CL diet only. The inclusion of plantain in the diet was highly effective at suppressing the parasites, Paramphistomum spp. (P = 0.003) and coccidial parasites (P = 0.04), but not stomach worms. Moreover, plantain supplementation increased growth hormone and insulin concentrations in plasma level, whereas decreased carcass fat by 32.7%. Therefore, supplementation of the lambs' diet with plantain showed some beneficial effects on productivity and parasitic infection, while it led to a leaner carcass.

The potential regulatory role of miR16 to the interplay between interferon and transforming growth factor beta pathways through IRF3 and SMAD7 in hepatitis C virus infected patients.

BACKGROUND: The defensive strategy against hepatitis C virus (HCV) infection depends on two antiviral pathways; interferon (IFN) and transforming growth factor ß (TGFß). We aimed at verifying the relation between TGFß and IFN antiviral pathways in HCV infection through SMAD7 and IRF3, and whether a possible regulatory role for microRNA-16 (miR16) on the interplay between IFN and TGFß signaling pathways exists or not. METHODS: We evaluated miR16, IRF3 and SMAD7 expression by real-time polymerase chain reaction in HCV infected patients and age and gender matched healthy controls. RESULTS: miR16 expression was significantly higher while IRF3 and SMAD7 expression was significantly lower in HCV patients compared with healthy controls. Meanwhile, miR16 was negatively correlated to SMAD7 in HCV patients while IRF3 and SMAD7 were positively correlated. CONCLUSIONS: The interplay between IFN and TGFß pathways through IRF3 and SMAD7 in the context of immunity against HCV infection could be under the control of miR16.

Immune response to temperature stress in three bivalve species: Pacific oyster Crassostrea gigas, Mediterranean mussel Mytilus galloprovincialis and mud cockle Katelysia rhytiphora.

Summer mortality of some bivalve species is often associated with the change of environmental temperature. This study compares the response of immunological parameters to temperature change in three marine bivalves: Pacific oyster Crassostrea gigas, Mediterranean mussel Mytilus galloprovincialis and mud cockle Katelysia rhytiphora. Each species was exposed to three temperatures, 15 °C, 20 °C and 25 °C for 14 days. The total haemocyte count (THC), phagocytosis, reactive oxygen species (ROS) and the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were used as indicators to measure the response of each species to different temperatures. The highest temperature (25 °C) significantly increased the THC and phagocysis of haemocytes in all species. The SOD and CAT activities in the haemocytes of M. galloprovincialis and K. rhytiphora rapidly increased with temperature elevation, concomitantly with the increase of ROS ions. In contrast, the increases of ROS and SOD in C. gigas only occurred from 20 °C to 25 °C, suggesting that this intertidal species is more adaptive to different temperature levels. This study indicates that the activities of antioxidant enzymes can reflect the immune response of marine bivalves to thermal stress. Intertidal species such as Pacific oysters have a greater tolerance to thermal stress than subtidal species (e.g. Mediterranean mussel) and demersal species buried in sand (e.g. cockle).

Dog Sperm Cryopreservation in Glucose-Fructose or Sucrose Supplemented Glycerol-Free Tris: Effect of Post-Thaw Incubation Time on Gene Expression Related to Apoptosis and Motility.

　　OBJECTIVE: The study evaluated the effects of glucose-fructose or sucrose supplementation in glycerol-free Tris (GFT) solution on motility, viability, the level of reactive oxygen species (ROS), as well as the level of apoptosis (BAX and BCL2) and motility (SMCP)-related gene expression of dog spermatozoa. MATERIALS AND METHODS: Spermatozoa (5×107 sperm/ml) were cryopreserved in GFT containing 86 mM glucose and 86 mM fructose (GF-GFT) or 100 mM sucrose (S-GFT). Progressive motility, viability, ROS (H2O2) level and mRNA gene expression of spermatozoa were evaluated 0 h, 3 h or 6 h post-thaw at 24°C. RESULTS: The motility of spermatozoa cryopreserved in GF-GFT was increased throughout the post-thaw incubation time. The motility of spermatozoa cryopreserved in S-GFT was increased at 3 h of post-thaw incubation. The sperm ROS level in the GF-GFT group was inconsistent during the post-thaw incubation time; however, the ROS level in the S-GFT group was gradually increased with progression of the post-thaw incubation period. The post-thaw incubation had no substantial effect on the mRNA expression of the BAX, BCL2, and SMCP genes of spermatozoa in both the GF-GFT and S-GFT groups. CONCLUSION: The supplementation of glucose and fructose improves progressive sperm motility during 6 h of post-thaw incubation while maintaining similar sperm viability. The addition of GF to GFT for cryopreservation and post-thaw incubation would yield more functional spermatozoa for future assisted reproduction practices.

A pilot randomised trial of community-based care following discharge from hospital with a recent spinal cord injury in Bangladesh.

OBJECTIVES: To explore the feasibility of conducting a full trial designed to determine the effectiveness of a model of community-based care for people with spinal cord injury in Bangladesh. STUDY DESIGN: A pilot randomised trial. SETTING: Community, Bangladesh. SUBJECTS: Participants were 30 people with recent spinal cord injury who were wheelchair-dependent and soon to be discharged from hospital. INTERVENTION: Participants randomised to the intervention group received a package of care involving regular telephone contact and three home visits over two years. Participants randomised to the control group received usual care consisting of a telephone call and an optional home visit. MAIN MEASURES: Participants were assessed at baseline and two years after randomization. The primary outcome was mortality and secondary outcomes were measures of complications, depression, participation and quality of life. RESULTS: A total of 24 participants had a complete spinal cord injury and six participants had an incomplete spinal cord injury. Median (interquartile) age and time since injury at baseline were 31 years (24 to 36) and 7 months (4 to 13), respectively. Two participants, one in each group, died. Five participants had pressure ulcers at two years. There were no notable impediments to the conduct of the trial and no significant protocol violations. The phone calls and home visits were delivered according to the protocol 87% and 100% of the time, respectively. Follow-up data were 99% complete. CONCLUSION: This pilot trial demonstrates the feasibility of a full clinical trial of 410 participants, which has recently commenced. SPONSORSHIP: University of Sydney, Australia.

Effect of Monosaccharides in Glycerol-free Tris Extender on Reactive Oxygen Species and Apoptosis in Dog Sperm Cryopreservation.

BACKGROUND OBJECTIVE: The present study investigated the effect of monosaccharides in a glycerol-free tris (GFT) extender on reactive oxygen species (ROS) levels and apoptosis in cryopreserved dog spermatozoa. MATERIALS AND METHODS: The sperm pellets were resuspended (5 × 107 mL-1) with GFT containing 172 mM glucose (G), 86 mM glucose + 86 mM fructose (GF), 86 mM glucose + 86 mM galactose (Gg), 172 mM fructose (F), 172 mM galactose (g) or 86 mM fructose + 86 mM galactose (Fg). The sperm (500 µL) were loaded in 0.5 mL straws and cooled for 50 min at 4 degree C. The straws were then frozen 7 cm from the surface of liquid nitrogen (LN2) for 20 min and were finally plunged into LN2. After freezing-thawing, the sperm motility and viability were evaluated. The ROS level (H2O2) and apoptosis index were assessed by using flow cytometry. RESULTS: GFT supplemented with GF resulted in significantly higher (P < 0.05) progressive sperm motility and viability followed by only G, which had greater ROS reducing capacity. However, sperm cell apoptosis had no significant differences among all the experimental groups. CONCLUSION: Cryopreservation of dog sperm in GFT containing GF yields more motile and viable sperm followed by only G, which has greater ROS reducing efficiency.

Outcome of Upper Gastrointestinal Surgery With or Without Nasogastric Intubation.

Nasogastric intubation is a common procedure with both merits and demerits. Controversies exist about the routine use of nasogastric intubation following upper gastrointestinal surgery. Good numbers of literatures were published in favour of selective nasogastric intubation pointing out some complications of routine use of nasogastric tube. In 1995, Cheatham et al. concluded in a meta-analysis that although patients may develop abdominal distension or vomiting without a nasogastric tube, this is not associated with an increase in complications or length of hospital stay. For every patient requiring insertion of a nasogastric tube in the postoperative period, at least 20 patients will not require nasogastric decompression. In July 2004, Cochrane database of systemic review published the result of their systemic review on the prophylactic decompression after abdominal surgery, that review was revised and updated in 2007. According to this database, routine nasogastric intubation should be abandoned in favour of selective use of nasogastric tube. In our country some surgeons are practicing it routinely and some are not. This observation prompted us to conduct this study in order to see and compare the outcome of upper gastrointestinal surgery with and without nasogastric intubation. This will help us to make decision whether nasogastric intubation will be done routinely or not following upper gastrointestinal surgery.

Clinical Evaluation of Bucco-lingual Crestal Bone Remodeling in Mandibular Posterior Implants placed immediately and Delayed into Extraction Sites.

The objective of this cross sectional study was to evaluate the bucco-lingual crestal bone remodeling in mandibular posterior implants placed immediately and delayed into extraction sites and carried out in the department of Prosthodontics of Dhaka Dental College and Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from July 2010 to July 2014. Forty patients were evaluated in this study; of them 25(62.5%) patients were males and 15(37.5%) were females with age range from 24 to 70 years. At first surgery during implant placement the mean distance from buccal bone to lingual bone was 11.11mm for immediate implants and 9.265mm for delayed implants. At second-stage surgery the mean distance from buccal bone to lingual bone was 9.765mm for immediate implants and 6.25mm for delayed implants. The mean±SD change of bone reduction at second surgery was 1.28±0.31 for immediate implants and 3.01±0.33 for delayed implants. Unpaired t test was done for statistical analysis and p value was less than 0.05. So, the changes were statistically significant.

Multimodality Treatment Outcome of Hepatoblastoma in a Resource Limited Country.

Our objective is to review the records of management of hepatoblastoma (HB) at the Paediatric Haematology and Oncology (PHO) department in the Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2004 to December 2012. This is a retrospective study of clinical, radiological and pathological data of hepatoblastoma patients treated at our institution. Thirteen patients were treated for HB between 2004 and 2012. The records of clinical presentations, chemotherapy tolerance and response, surgical procedure undertaken, and complications were analyzed. Median age of the study population was 12 months (3-60 months) and male: female was 3.3:1. Nine patients were treated with neoadjuvant chemotherapy consists of cisplatin and adriamycin. Primary surgery was done in four patients. Extent of hepatic resection in the operated patients varied. Mixed type was the predominant histopathological diagnosis. Adjuvant chemotherapy was well tolerated with no morbidity or mortality. Five-year event-free survival (EFS) and overall survival (OS) of all the 13 patients is 76.9%. All the nine patients who could complete multimodality treatment are alive with no evidence of disease or complications with median follow-up of 63 months (46-122 months). Treatment of HB with multidisciplinary approach was well tolerated. OS and EFS of patients were comparable with published studies.

Diagnostic Importance of Platelet in Patients with Acute Coronary Syndrome Admitted in Mymensingh Medical College Hospital.

This cross sectional descriptive study was carried out in the Department of Cardiology, Mymensingh Medical College Hospital from July 2015 to December 2015, included 50 patients admitted with acute coronary syndrome diagnosed on the basis of history, typical anginal type of chest pain, characteristic electrocardiographic changes and increased cardiac biomarkers. Platelet count (PC), Mean platelet volume (MPV) and platelet distribution width (PDW) were measured using automated hematological analyzer and compared them with 50 age and sex matched healthy controls. All platelet parameter indices - platelet count (PC), mean platelet volume (MPV) & platelet distribution width (PDW) - were significantly raised in patients with ACS. In patients with ACS the mean values of platelet count, MPV & PDW were 352.2×109/L), 13.9fL & 15.6fL, respectively; while in normal healthy control the mean values of these indices were 256.2×109/L), 8.1fL & 10.5fL, respectively. Statistically significant difference in mean values of these indices was found (p value <0.05). Larger platelets are haemostatically more active and are a risk factor for developing coronary thrombosis and subsequent acute coronary events (myocardial infarction and unstable angina). Patients with larger platelets can easily be identified during routine hematological analysis and could possibly benefit from preventive treatment.

New Therapeutic Approach to Treat Allergic Rhinitis & Bronchial Asthma, Considering These Two as One United Airway Disease.

The relationship between allergic rhinitis and asthma is now established, and most of the clinical, epidemiological and biological data recommend integrated management. This review discusses rhinosinusitis as a co-morbid condition, a precipitating or triggering condition, and an epiphenomenon as an integrated part of the disease. A better understanding and a more pragmatic method of diagnosis and management is needed using cost-effective long-term strategies. Allergic Rhinitis, though a non-life threatening disease, its pathogenesis reveals that Bronchial Asthma also develops by the same aetiopathogenesis. The United airway disease hypothesis proposes that the upper & lower airway diseases are both manifestations of a single inflammatory process and studies have already proved it. Allergic Rhinitis when once develops if not treated vigorously, can later turn up to Asthma. As chronic inflammation is the central process which is actually continuously changing pathologically the lower respiratory tract & helping to develop Bronchial Asthma. The conventional therapies for Allergic Rhinitis such as antihistamines & decongestants are only symptom relievers, to stop the ongoing pathogenesis of Bronchial Asthma to develop it, the chronic inflammatory process should have to be stopped. This can be done by corticosteroid nasal sprays. Also Asthma with Rhinitis is better controlled by them. Even Bronchial Asthma treatment should be started with inhaler corticosteroid therapy rather than getting it after intermittent use of only bronchodilators (salbutamol) only.

Quality of Life in Children with Asthma in Bangladesh.

Asthma is a public health problem that adversely affects different aspects of quality of life. Childhood asthma is common in Bangladesh affecting their lifestyle. The objective of the study was to assess health-related quality of life in children with bronchial asthma. A descriptive, cross-sectional study was carried out from January 2014 to December 2014 at the Outpatient Department of National Asthma Centre, Mohakhali, Dhaka among hundred sixty-two purposively selected children of both sexes with bronchial asthma aged from 7 to 17 years. Data were collected through interview with children or their parents using an interviewer-administered questionnaire based on Pediatric Asthma Quality of Life Questionnaire (PAQLQ). Data were analyzed by computer software SPSS version 16.0. The mean age was 12.5 years with a standard deviation (SD) of 2.9 years. Overwhelming majority 157(96.9%) of children were literate, while only 5(3.1%) children were illiterate. Eighty (49.4%) children were male, while 82(50.6%) female. As many as 148(91.4%) children were students, while 10(6.2%) children were engaged in some type of job and 4(2.5%) children had no occupation. Parents of 145(89.5%) children were currently married, while 10(6.2%) children had single parent and 7(4.3%) children's parents were divorced or separated. Quality of life in children with asthma decreases with age as the disease intensity increases with age. Female asthmatic children had lower overall score of Quality of life (p=0.017), as well as lower activity domain score (p<0.001). Emotional domain score was found lower in children with single parent (p=0.021) and low monthly family income (p<0.001). Furthermore, children with lower monthly family income and working children had lower Quality of life score in all domains.

Psychiatric Disorders in Drop out from Educational Attainment Attending Mental Health Facilities: A Descriptive Cross Sectional Study.

Studies of the impact of mental disorders on educational attainment are rare. Mental disorders, those beginning in childhood or adolescence may increase the risk of early drop out from education. The latter has been shown to have adverse life-course consequences on individuals such as greater demand on social welfare entitlements. A descriptive cross sectional study was carried out at the department of Psychiatry, Comilla Medical College, Comilla, Bangladesh. All cases were selected from patients attending at Comilla Medical College Hospital and Private Mental Health Facilities in Comilla City from March 2015 to February 2016. We found out the psychiatric disorders and socio-demographic status of patients with educational drop out over the early life course. A total of 50 dropout patients aged 10 to 30 years who fullfiled the enrolment criteria included in the study. Sociodemographic questionnaires, diagnostic information (DSM-5 and ICD-10) as well as an account of a various level of education were used as research instruments. The Frequency tables, summary tables and appropriate graphs were prepared to describe the population characteristics and study finding. The most of the psychiatric morbidity presents in male (62%) and age group of 18-24 years (54%). In this study, anxiety disorders was 8%, behaviour/ impulse control disorders was 8%, mood disorders was 16%, substance use disorders was 24%, schizophrenia spectrum disorders was 12% and composite psychiatric disorders was 32%. Among drop out patient's non- completion of primary education was 14%, non-completion of secondary education was 20%, non- completion of higher secondary education was 24%, not entry to tertiary education was 12% and non-completion of tertiary education was 30%. Among behaviour/impulse control disorders non-completion of primary education was 6%, substance use disorders non-completion of higher secondary education was 10%, mood disorder both non-completion of higher secondary education and non-completion of tertiary education were 6%. Among composite psychiatric disorders non-completion of secondary education, non-completion of higher secondary education and non-completion of tertiary education were 8%, 6% and 12% respectively. Onset of mental disorders and subsequent drop out from education was found in this study. Further multi-centered prospective and population-based studies should be designed to find out the exact situation.

Childhood Wilson Disease: Bangladesh Perspective.

Wilson's disease (WD) is an autosomal recessive disorder affecting copper metabolism causing copper induced damage to various organs. In children liver is commonly involved. Central nervous system, eyes, RBC, kidneys, brain and bones may also be affected. Aim of the study is to evaluate clinical & laboratory profile of Wilson's disease in children. This cross sectional descriptive study was conducted at the department of Paediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2011 to December, 2013. One hundred consecutive children of WD between 3 to 18 years of age were evaluated for clinical & biochemical profile. Mean age of studied children was 8.5±1.5 years. Male female ratio was 2:1. Ninety one percent patients were Muslim and nine percent Hindu. Consanguinity of marriage was found in 30% cases. Seven parents were first degree cousin. Family history of chronic liver disease was present in 15% of patients. Most (53%) cases of the hepatic WD presented between 5 to 10 years of age and most of the neurologic WD manifested in 10-15 years age group. Among 100 patients of WD, 69 children presented only with hepatic manifestations, 6 only with neurological manifestations, 14 with both hepatic & neurological manifestation, 10 children was asymptomatic and 1 patient presented with psychiatric features. WD presented as chronic liver disease (CLD) in 42%, CLD with portal hypertension in 34%, acute hepatitis in 20% and fulminant hepatic failure in 4% cases. Stigmata of chronic liver disease were found in 18% patients. Commonest stigmata was thenar and hypothenar wasting (n=8). Keiser- Fleischser ring (K-F ring) was found in 76% of the total patients. K-F ring was present in 84% ( 58 out of 69) of the hepatic only Wilsonian patients and in 90% (18 out of 20) of all neurologic Wilsonian patients. Asymptomatic and psychiatric patient had no K-F ring. About 26% of the WD patients had Coombs negative hemolytic anemia in PBF. Most of the WD patients had altered liver function. Elevated serum transaminase was found in 85% of all cases, prolonged prothrombin time in 59% cases & low serum albumin in 53% cases. Seventy three percent patients had low serum ceruloplasmin, basal urinary copper of >100µgm/day was found in 81% cases and urinary copper following penicillamine challenge of >1200µgm/day was found in 92% cases. In 28 cases with hepatic presentation esophageal varices were identified by upper gastrointestinal endoscopy. WD patient with hepatic presentations were given zinc sulphate along with penicillamine. All patients with neurological manifestation as well as asymptomatic cases were maintained on zinc therapy. WD is a treatable metabolic cause of liver disease. Majority of studied WD children presented with hepatic manifestation of which 76% presented with CLD. Any child presented with jaundice after the age of 3 years should be investigated for WD.

Outcome of Pregnancy Related Acute Kidney Injury Observed in a Tertiary Care Hospital.

This prospective case control study was carried out in Mymensingh Medical College Hospital (MMCH) from April 2011 to March 2012. The main objective of the study was to determine the short term maternal outcome of pregnancy related Acute Kidney Injury and to identify aetiological factors and to observe clinical features of pregnancy related Acute Kidney Injury. Total 60 pregnant women with AKI were included in the study as sample and equal (60) number of pregnant women with normal renal function was taken as control. Mean ages (±SD) of study and control group were observed 31.6±6.9 years and 25.5±4.7 years respectively. It was observed that most patients were from rural area with low income group. Most women were multiparous and presented in third trimester and postpartum period. Majority of the study subjects did not receive antenatal care at any stage of pregnancy. Fifty (86.7%) of the study subjects were oligo-anuric, forty-nine (81.7%) were edematous and fifty one (85%) were anaemic. Twenty-five (41.7%) patients presented with abnormal vaginal bleeding. Sepsis (including septic abortion and puerperal sepsis) was responsible for of Pregnancy Related AKI (PR-AKI) in more than two fifths of cases. Haemorrhage (APH & PPH combined) was the next common cause of Pregnancy Related AKI (PR-AKI). Toxemia of Pregnancy was responsible in one fourth of cases. Dialysis (HD & IPD combined) was required for two fifths of the patients. Rest patients were treated conservatively with antibiotics, blood transfusion, maintenance of fluid and electrolytes balance etc. Maternal outcome of Pregnancy related acute kidney injury was considered for the period of patient's hospital staying. 56.6% patients recovered completely, 15.0% patients recovered partially, 6.7% did not recover at the time of hospital discharge; while 21.7% died. So it can be concluded that, pregnancy related acute kidney injury is a critical condition, associated with worse prognosis.

Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models.

BACKGROUND: Glioblastomas (GBMs) are highly malignant brain tumours with a poor prognosis, and current cytotoxic regimens provide only a limited survival benefit. The PI3K/Akt/mTOR pathway has been an attractive target for therapy due to its high activation in GBMs as well as other cancers. The dual pan-PI3K/mTOR kinase inhibitor dactolisib (NVP-BEZ235) is an anti-neoplastic compound currently under investigation. However, little is known about its efficacy in human GBMs. We aimed at evaluating the efficacy of dactolisib in human glioblastoma cells, as well as in murine models carrying human GBM xenografts. METHODS: To assess the effect of dactolisib in vitro, MTS assay, manual cell count, BrdU incorporation and Annexin V staining experiments were used to observe growth and apoptosis. Furthermore, Akt phosphorylation (S473), a downstream target of PI3K, was explored by western blotting. Animal studies utilizing orthotopic xenograft models of glioblastoma were performed in nude rats and NOD/SCID mice to monitor survival benefit or inhibition of tumor growth. RESULTS: We found that dactolisib in vitro shows excellent dose dependent anti-growth properties and increase in apoptosis. Moreover, dose dependent inhibition of Akt phosphorylation (S473), a downstream effect of PI3K, was observed by western blotting. However, in two independent animal studies utilizing nude rats and NOD/SCID mice in orthotopic xenograft models of glioblastoma, we observed no survival benefit or inhibition of tumour growth. Severe side effects were observed, such as elevated levels of blood glucose and the liver enzyme alanine transaminase (ALT), in addition to diarrhoea, hair loss (alopecia), skin rash and accumulation of saliva in the oral cavity. CONCLUSION: Taken together, our results suggest that despite the anti-neoplastic efficacy of dactolisib in glioma treatment in vitro, its utility in vivo is questionable due to toxicity.

Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats.

Glioblastomas (GBMs) are aggressive brain tumours with a dismal prognosis, despite combined surgery, radio- and chemotherapy. Close to 90 % of all GBMs harbour a deregulated PI3K pathway, which is essential in regulating central cellular functions such as proliferation, cell growth, motility and survival. Thus, PI3K represents a potential target for molecular therapy in GBM. We investigated the anti-tumour efficacy of the PI3K inhibitor buparlisib (NVP-BKM120) in GBM cell lines in vitro and in vivo, when treatment was initiated after MRI-confirmed tumour engraftment. We found that buparlisib inhibited glioma cell proliferation in a dose dependent manner, demonstrated by MTS assay, manual cell count and BrdU incorporation. A dose dependent increase in apoptosis was observed through flow cytometric analysis. Furthermore, by immunocytochemistry and western blot, we found a dose dependent inhibition of Akt phosphorylation. Moreover, buparlisib prolonged survival of nude rats harboring human GBM xenografts in three independent studies and reduced the tumours' volumetric increase, as determined by MRI. In addition, histological analyses of xenograft rat brains showed necrotic areas and change in tumour cell nuclei in buparlisib-treated animals. The rats receiving buparlisib maintained their weight, activity level and food- and water intake. In conclusion, buparlisib effectively inhibits glioma cell proliferation in vitro and growth of human GBM xenografts in nude rats. Moreover, the compound is well tolerated when administered at doses providing anti-tumour efficacy. Thus, buparlisib may have a future role in glioma therapy, and further studies are warranted to validate this compound for human use.