DNAJC9 prevents CENP-A mislocalization and chromosomal instability by maintaining the fidelity of histone supply chains.

The centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined. Here, we performed a genome-wide RNAi screen for regulators of CENP-A localization which identified DNAJC9, a J-domain protein implicated in histone H3-H4 protein folding, as a factor restricting CENP-A mislocalization. Cells lacking DNAJC9 exhibit mislocalization of CENP-A throughout the genome, and CIN phenotypes. Global interactome analysis showed that DNAJC9 depletion promotes the interaction of CENP-A with the DNA-replication-associated histone chaperone MCM2. CENP-A mislocalization upon DNAJC9 depletion was dependent on MCM2, defining MCM2 as a driver of CENP-A deposition at ectopic sites when H3-H4 supply chains are disrupted. Cells depleted for histone H3.3, also exhibit CENP-A mislocalization. In summary, we have defined novel factors that prevent mislocalization of CENP-A, and demonstrated that the integrity of H3-H4 supply chains regulated by histone chaperones such as DNAJC9 restrict CENP-A mislocalization and CIN.

The histone H3/H4 chaperone CHAF1B prevents the mislocalization of CENP-A for chromosomal stability.

Restricting the localization of the evolutionarily conserved centromeric histone H3 variant CENP-A to centromeres prevents chromosomal instability (CIN). The mislocalization of CENP-A to non-centromeric regions contributes to CIN in yeasts, flies and human cells. Even though overexpression and mislocalization of CENP-A have been reported in cancers, the mechanisms responsible for its mislocalization remain poorly understood. Here, we used an imaging-based high-throughput RNAi screen to identify factors that prevent mislocalization of overexpressed YFP-tagged CENP-A (YFP-CENP-A) in HeLa cells. Among the top five candidates in the screen - the depletion of which showed increased nuclear YFP-CENP-A fluorescence - were the histone chaperones CHAF1B (or p60) and CHAF1A (or p150). Follow-up validation and characterization experiments showed that CHAF1B-depleted cells exhibited CENP-A mislocalization, CIN phenotypes and increased enrichment of CENP-A in chromatin fractions. The depletion of DAXX, a histone H3.3 chaperone, suppressed CENP-A mislocalization and CIN in CHAF1B-depleted cells. We propose that in CHAF1B-depleted cells, DAXX promotes mislocalization of the overexpressed CENP-A to non-centromeric regions, resulting in CIN. In summary, we identified regulators of CENP-A localization and defined a role for CHAF1B in preventing DAXX-dependent CENP-A mislocalization and CIN.

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a rare, cholestatic liver disease with no currently approved therapies. Obeticholic acid (OCA) is a potent farnesoid X receptor (FXR) agonist approved for the treatment of primary biliary cholangitis. We investigated the efficacy and safety of OCA in patients with PSC. METHODS: AESOP was a phase II, randomized, double-blind, placebo-controlled, dose-finding study. Eligible patients were 18 to 75 years of age with a diagnosis of PSC and serum alkaline phosphatase (ALP) ≥2× the upper limit of normal (ULN) and total bilirubin <2.5× ULN. Patients were randomized 1:1:1 to receive placebo, OCA 1.5-3.0 mg, or OCA 5-10 mg once daily for a 24-week, double-blind phase followed by a 2-year, long-term safety extension (LTSE). Primary endpoints were change in ALP from baseline to week 24, and safety. RESULTS: The intent-to-treat population comprised 76 patients randomized to placebo (n = 25), OCA 1.5-3.0 mg (n = 25), and OCA 5-10 mg (n = 26). At week 24, serum ALP was significantly reduced with OCA 5-10 mg vs. placebo (least-square [LS] mean difference = -83.4 [SE = 40.3] U/L; 95% CI -164.28 to -2.57; p = 0.043). Serum ALP was not significantly reduced with OCA 1.5-3.0 mg vs. placebo at week 24 (LS mean [SE] difference = -78.29 [41.81] U/L; 95% CI -162.08 to 5.50; p = 0.067). Total bilirubin remained comparable to baseline in all groups. The most common treatment-emergent adverse event was dose-related pruritus (placebo 46%; OCA 1.5-3.0 mg 60%; OCA 5-10 mg 67%). Reductions in ALP were maintained during the LTSE, and no new safety signals emerged. CONCLUSIONS: Treatment with OCA 5-10 mg reduced serum ALP in patients with PSC. Mild to moderate dose-related pruritus was the most common adverse event. REGISTRATION: ClinicalTrials.gov: NCT02177136; EudraCT: 2014-002205-38. LAY SUMMARY: Primary sclerosing cholangitis (PSC) is a long-term disease that damages the bile ducts in the liver over time. In the AESOP clinical study in patients with PSC, obeticholic acid reduced serum alkaline phosphatase (a potential marker of disease severity) during an initial 24-week treatment period. The result was sustained during the 2-year, long-term extension of the study. The most common side effect of obeticholic acid in the study was itchy skin, which is consistent with earlier clinical studies.

Development of IglC and GroEL recombinant vaccines for francisellosis in Nile tilapia, Oreochromis niloticus.

Warm-water piscine francisellosis is a granulomatous bacterial disease caused by Francisella orientalis (Fo). The disease has been detected in a wide range of fish species globally, causing mortalities as high as 90% and significant economic losses. Currently there are no commercially available vaccines and few treatment options exist. In the current study, two novel recombinant vaccines were prepared using diatom-expressed IglC or bacterial-expressed GroEL proteins. The vaccine antigens were emulsified with either nanoparticles or a commercially available oil-based adjuvant. Nile tilapia, Oreochromis niloticus, fingerlings were immunized intracoelomically with the recombinant IglC or GroEL vaccines, diatoms alone or phosphate buffer saline. Approximately 840-degree days post-vaccination, fish were challenged via immersion with 106 CFU/mL of wild-type Fo. Twenty-one days post challenge (dpc), the highest relative percent survival was recorded in the IglC-Montanide group (75%), compared to 53%, 50%, 22%, 19% and 16% in the IglC-nanoparticles, GroEL-Montanide, GroEL-nanoparticles, diatoms-Montanide and diatoms-nanoparticles groups, respectively. Protection correlated with significantly higher specific antibody responses in the IglC-Montanide group. Moreover, a significantly lower bacterial load was detected in spleen samples from the IglC-Montanide survivor tilapia compared to the other experimental groups. This is the first report of recombinant vaccines against piscine francisellosis in tilapia. The Fo vaccines described in our study may facilitate development of a safe, cost-effective and highly protective vaccine against francisellosis in farmed tilapia.

Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years' experience at Patan Hospital, Nepal.

The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty-nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3-140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource-poor settings.

The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal.

Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty-five patients (11 female 34 male) were studied; 18 different BCR-ABL1 mutations were seen in 33 patients. P-loop mutation, Kinase domain and A-loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for BCR-ABL1 mutations, 4 were lost to follow-up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in BCR-ABL1 may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.

Development of a silicon limitation inducible expression system for recombinant protein production in the centric diatoms Thalassiosira pseudonana and Cyclotella cryptica.

BACKGROUND: An inducible promoter for recombinant protein expression provides substantial benefits because under induction conditions cellular energy and metabolic capability can be directed into protein synthesis. The most widely used inducible promoter for diatoms is for nitrate reductase, however, nitrogen metabolism is tied into diverse aspects of cellular function, and the induction response is not necessarily robust. Silicon limitation offers a means to eliminate energy and metabolic flux into cell division processes, with little other detrimental effect on cellular function, and a protein expression system that works under those conditions could be advantageous. RESULTS: In this study, we evaluate a number of promoters for recombinant protein expression induced by silicon limitation and repressed by the presence of silicon in the diatoms Thalassiosira pseudonana and Cyclotella cryptica. In addition to silicon limitation, we describe additional strategies to elevate recombinant protein expression level, including inclusion of the 5' fragment of the coding region of the native gene and reducing carbon flow into ancillary processes of pigment synthesis and formation of photosynthetic storage products. We achieved yields of eGFP to 1.8% of total soluble protein in C. cryptica, which is about 3.6-fold higher than that obtained with chloroplast expression and ninefold higher than nuclear expression in another well-established algal system. CONCLUSIONS: Our studies demonstrate that the combination of inducible promoter and other strategies can result in robust expression of recombinant protein in a nuclear-based expression system in diatoms under silicon limited conditions, separating the protein expression regime from growth processes and improving overall recombinant protein yields.

Liver transplantation for fulminant genotype 2a/c hepatitis C virus marked by a rapid recurrence followed by cure.

Although chronic hepatitis C is still the leading indication for liver transplantation (LT) in the United States and Europe, acute liver failure caused by hepatitis C is distinctly uncommon and transplantation for fulminant hepatitis C virus (HCV) has not been documented in the United States. We present a case report of fulminant hepatic failure caused by genotype 2a/c HCV not only treated with LT but also complicated by severe, rapid recurrence of HCV within 6 days of transplantation. The risk factor for the initial infection was likely sexual, and there were no explanations for acute hepatitis post-transplant other than recurrent hepatitis C. Treatment with all-oral direct antiviral agents was swiftly initiated during the index hospitalization, leading to resolution of the acute hepatitis and resulting in sustained virologic response. It can only be speculated whether this was an infection with the JFH-1 strain or another similarly virulent genotype 2a/c HCV infection.

Evidence for a regulatory role of diatom silicon transporters in cellular silicon responses.

The utilization of silicon by diatoms has both global and small-scale implications, from oceanic primary productivity to nanotechnological applications of their silica cell walls. The sensing and transport of silicic acid are key aspects of understanding diatom silicon utilization. At low silicic acid concentrations (<30 µM), transport mainly occurs through silicic acid transport proteins (SITs), and at higher concentrations it occurs through diffusion. Previous analyses of the SITs were done either in heterologous systems or without a distinction between individual SITs. In the present study, we examined individual SITs in Thalassiosira pseudonana in terms of transcript and protein abundance in response to different silicic acid regimes and examined knockdown lines to evaluate the role of the SITs in transport, silica incorporation, and lipid accumulation resulting from silicon starvation. SIT1 and SIT2 were localized in the plasma membrane, and protein levels were generally inversely correlated with cellular silicon needs, with a distinct response being found when the two SITs were compared. We developed highly effective approaches for RNA interference and antisense knockdowns, the first such approaches developed for a centric diatom. SIT knockdown differentially affected the uptake of silicon and the incorporation of silicic acid and resulted in the induction of lipid accumulation under silicon starvation conditions far earlier than in the wild-type cells, suggesting that the cells were artificially sensing silicon limitation. The data suggest that the transport role of the SITs is relatively minor under conditions with sufficient silicic acid. Their primary role is to sense silicic acid levels to evaluate whether the cell can proceed with its cell wall formation and division processes.

Metabolic engineering of lipid catabolism increases microalgal lipid accumulation without compromising growth.

Biologically derived fuels are viable alternatives to traditional fossil fuels, and microalgae are a particularly promising source, but improvements are required throughout the production process to increase productivity and reduce cost. Metabolic engineering to increase yields of biofuel-relevant lipids in these organisms without compromising growth is an important aspect of advancing economic feasibility. We report that the targeted knockdown of a multifunctional lipase/phospholipase/acyltransferase increased lipid yields without affecting growth in the diatom Thalassiosira pseudonana. Antisense-expressing knockdown strains 1A6 and 1B1 exhibited wild-type-like growth and increased lipid content under both continuous light and alternating light/dark conditions. Strains 1A6 and 1B1, respectively, contained 2.4- and 3.3-fold higher lipid content than wild-type during exponential growth, and 4.1- and 3.2-fold higher lipid content than wild-type after 40 h of silicon starvation. Analyses of fatty acids, lipid classes, and membrane stability in the transgenic strains suggest a role for this enzyme in membrane lipid turnover and lipid homeostasis. These results demonstrate that targeted metabolic manipulations can be used to increase lipid accumulation in eukaryotic microalgae without compromising growth.

Modeling of Noisy Spindle Dynamics Reveals Separable Contributions to Achieving Correct Orientation.

The mechanisms by which the mammalian mitotic spindle is guided to a predefined orientation through microtubule-cortex interactions have recently received considerable interest, but there has been no dynamic model that describes spindle movements toward the preferred axis in human cells. Here, we develop a dynamic model based on stochastic activity of cues anisotropically positioned around the cortex of the mitotic cell and we show that the mitotic spindle does not reach equilibrium before chromosome segregation. Our model successfully captures the characteristic experimental behavior of noisy spindle rotation dynamics in human epithelial cells, including a weak underlying bias in the direction of rotation, suppression of motion close to the alignment axis, and the effect of the aspect ratio of the interphase cell shape in defining the final alignment axis. We predict that the force exerted per cue has a value that minimizes the deviation of the spindle from the predefined axis. The model has allowed us to systematically explore the parameter space around experimentally relevant configurations, and predict the mechanistic function of a number of established regulators of spindle orientation, highlighting how physical modeling of a noisy system can lead to functional biological understanding. We provide key insights into measurable parameters in live cells that can help distinguish between mechanisms of microtubule and cortical-cue interactions that jointly control the final orientation of the spindle.

Multivariate analysis of prognostic factors for survival following doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To identify prognostic factors for survival in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (DEBs). MATERIALS AND METHODS: In a retrospective, single-center analysis, tumor- and patient-related factors were recorded for univariate and multivariate analyses via Kaplan-Meier and Cox regression. Infiltrative HCC phenotype and portal vein invasion (PVI) were correlated, and patients with either or both were classified as having radiographically advanced (RAdv) HCC. The primary endpoint was overall survival, which was calculated from the time of first DEB chemoembolization procedure. RESULTS: A total of 168 patients underwent 248 procedures, of which 215 (86.7%) were outpatient procedures. Mean length of stay was 0.33 days, and 25 patients (10.1%) were readmitted within 30 days. A total of 33 patients underwent liver transplantation and were excluded from survival analyses. A total of 130 had cirrhosis; 62, 50, and 18 had Child class A, B, and C disease, respectively. Forty-one patients had infiltrative HCC phenotype, 28 of whom also had PVI. Multivariate analysis of survival in all patients showed α-fetoprotein (AFP), performance status (PS), RAdv HCC, Child classification, albumin level, and ascites to predict survival. In patients without RAdv HCC, AFP, PS, Child classification, albumin level, and International Normalized Ratio were independent predictors. Increased bilirubin level was not an independent risk factor for death. CONCLUSIONS: Independent prognostic factors in patients with HCC undergoing DEB chemoembolization have been identified. Increased bilirubin level was not an independent risk factor. These data can be used in HCC patient selection and counseling for DEB chemoembolization.

Assessment of App Store Description and Privacy Policy to Explore Ethical and Safety Concerns Associated with the Use of Mental Health Apps for Depression.

Background: Mental Health apps (MH apps) could help address the huge unmet mental health care need of developing countries. This study aimed to explore potential ethical, data safety, and privacy issues associated with using MH apps for depression. Methods: A cross-sectional assessment of the top 50 MH apps (by Google Play store search result ordering) for depression available in India was conducted in November 2021. Results: Most apps were listed under the category of health and fitness (54%). The median number of total and dangerous permissions requested at the time of download was nine and three, respectively. Privacy policy in English was available for 76%. The average length of the privacy policy was 2171 words, and the mean Flesch-Kincaid reading grade level was 12 (much higher than the recommended cut-off of eight). Important features relevant to safeguarding consumer confidentiality, including names of third parties with which user data could be shared (42%), explicit consent before sharing data with third parties (16%), and assurance regarding the collection of de-identifiable data (11%), were missing from the majority of privacy policies. Conclusion: There is an urgent need to improve the accessibility and usability of privacy policies by app developers, with the active involvement of other stakeholders.

Mad honey poisoning presenting with syncopal attack: a case report.

Mad honey contains grayanotoxin, which is commonly derived from the nectar of a few Rhododendron species. It is commonly used by natives of the Himalayas in the belief of its medicinal use. Case presentation: The authors report a case of 62 years old male with mad honey poisoning who was presented to the emergency department with loss of consciousness and had bradycardia and hypotension on arrival. The patient received intravenous fluids, atropine, and vasopressor support and was closely monitored in the coronary care unit for 48 h. Discussion: Grayanotoxin I and II are believed to be primarily responsible for mad honey intoxication and act by persistent activation of voltage-gated sodium channels. Hypotension, dizziness, nausea, vomiting, and impaired consciousness are the common presentation of mad honey intoxication. Toxic effects are usually mild and close monitoring for 24-48 h is sufficient but life-threatening complications like cardiac asystole, convulsions, and myocardial infarction have also been reported. Conclusion: Most cases of mad honey intoxication only need symptomatic treatment and close observation but the potential for deterioration and life-threatening complications must also be considered.

Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B.

Matrin3 is an RNA-binding protein that regulates diverse RNA-related processes, including mRNA splicing. Although Matrin3 has been intensively studied in neurodegenerative diseases, its function in cancer remains unclear. Here, we report Matrin3-mediated regulation of mitotic spindle dynamics in colorectal cancer (CRC) cells. We comprehensively identified RNAs bound and regulated by Matrin3 in CRC cells and focused on CDC14B, one of the top Matrin3 targets. Matrin3 knockdown results in increased inclusion of an exon containing a premature termination codon in the CDC14B transcript and simultaneous down-regulation of the standard CDC14B transcript. Knockdown of CDC14B phenocopies the defects in mitotic spindle dynamics upon Matrin3 knockdown, and the elongated and misoriented mitotic spindle observed upon Matrin3 knockdown are rescued upon overexpression of CDC14B, suggesting that CDC14B is a key downstream effector of Matrin3. Collectively, these data reveal a role for the Matrin3/CDC14B axis in control of mitotic spindle dynamics.

Whole transcriptome analysis of the silicon response of the diatom Thalassiosira pseudonana.

BACKGROUND: Silicon plays important biological roles, but the mechanisms of cellular responses to silicon are poorly understood. We report the first analysis of cell cycle arrest and recovery from silicon starvation in the diatom Thalassiosira pseudonana using whole genome microarrays. RESULTS: Three known responses to silicon were examined, 1) silicified cell wall synthesis, 2) recovery from silicon starvation, and 3) co-regulation with silicon transporter (SIT) genes. In terms of diatom cell wall formation, thus far only cell surface proteins and proteins tightly associated with silica have been characterized. Our analysis has identified new genes potentially involved in silica formation, and other genes potentially involved in signaling, trafficking, protein degradation, glycosylation and transport, which provides a larger-scale picture of the processes involved. During silicon starvation, an overrepresentation of transcription and translation related genes were up-regulated, indicating that T. pseudonana is poised to rapidly recover from silicon starvation and resume cell cycle progression upon silicon replenishment. This is in contrast to other types of limitation, and provides the first molecular data explaining the well-established environmental response of diatoms to grow as blooms and to out-compete other classes of microalgae for growth. Comparison of our data with a previous diatom cell cycle analysis indicates that assignment of the cell cycle specific stage of particular cyclins and cyclin dependent kinases should be re-evaluated. Finally, genes co-varying in expression with the SITs enabled identification of a new class of diatom-specific proteins containing a unique domain, and a putative silicon efflux protein. CONCLUSIONS: Analysis of the T. pseudonana microarray data has provided a wealth of new genes to investigate previously uncharacterized cellular phenomenon related to silicon metabolism, silicon's interaction with cellular components, and environmental responses to silicon.

Interaction of Phthalates with Lipid Bilayer Membranes.

Phthalates are esters of phthalic acid, widely used as additives in the manufacture of plastics. They are not covalently linked to polymer chains and can easily leach out, disperse in the environment, and get into contact with living organisms. Several short chain phthalates are classified as endocrine disruptors or hormonal active agents, and have also been reported to promote various kinds of cancer. However, the biological effects of longer chain analogues are less well known. Moreover, little is known on the permeation of phthalates and their metabolites through biological membranes and on their effects on the physical properties of membranes. Here we explore the interaction of a group of phthalates and their main metabolites with model biological membranes. We focus on three industrially relevant phthalates, with acyl chains of different sizes, and their monoester metabolites. We use molecular dynamics simulations to predict the distribution in model membranes, as well as permeabilities and effects on the structural, dynamic, and elastic properties of the membranes. We find that alterations of membrane properties are significant and only weakly affected by the size of acyl chains, suggesting that modifications of molecular size may not be sufficient to reduce the impact of this class of molecules on the environment and health.

Intravenous Ringers lactate versus normal saline for predominantly mild acute pancreatitis in a Nepalese Tertiary Hospital.

BACKGROUND: Acute pancreatitis (AP) is a common presentation in patients admitted with acute abdomen. Whether Ringers lactate (RL) or Normal Saline (NS) as a resuscitation fluid is better still remains unclear. The aim of this study is to compare the efficacy of RL and NS in terms of control of systemic inflammation by measuring indirect markers specifically Systemic Inflammation Response Syndrome (SIRS) scores and C- Reactive Protein (CRP) level. METHODS: This was an open label randomized trial conducted in a tertiary level hospital of Nepal. Ethical approval was obtained prior to the study. Patients with acute pancreatitis were randomized to either RL or NS group for the fluid resuscitation. The fluid was given as per the study protocol for three days for hydration. Baseline SIRS and CRP were recorded on admission and subsequently as defined. All the data were analyzed using SPSS ver 20.0 software. RESULTS: Total 51 patients were enrolled, 26 in RL and 25 in NS group. The commonest etiology of AP was alcohol (84.31%). SIRS was present in 46.2% and 64.0% of patients in RL and NS group respectively (p = 0.20) on admission. At least one SIRS criteria was still present in 44.0% of patients in the NS group compared to only 15.4% in the RL group after 24 hours (p = 0.025). The baseline CRP were comparable in both the groups. However after 72 hours, the increment of CRP was more in the NS group compared to the RL group; median value of 14.2 mg/dl (12.15, 16.45) and 22.2 mg/dl (18.20, 30.60) in RL and NS group respectively (p<0.001). CONCLUSIONS: Ringers lactate was associated with a reduction in systemic inflammation compared to normal saline in patients with acute pancreatitis. Incidence of SIRS at 72 hours and occurrence of local complications were however similar in both the groups.

Pregnancy with heart disease in South Asia: A systematic review and meta-analysis of prevalence and outcome.

Background: The prevalence and paradigm of antenatal heart disease are contrasting between high-income, industrialized, and low- and middle-income countries. In this systematic review, we report the prevalence of heart disease and its spectrum in pregnant women of South Asia. Methods: We searched through different electronic databases (PubMed, Google-scholar, Embase, Cochrane Library) to locate relevant articles. Studies with sufficient data that met our inclusion criteria were included. Two reviewers independently screened the articles. Discrepancies were resolved by other reviewers. Subsequently, data extraction was done using a standardized form and quality assessment of studies using the Joanna Briggs Institute tool. Meta-analysis was done using R software. Results: After various stages of screening 25 studies were included in the final quantitative synthesis. The pooled prevalence of heart disease among pregnant women was 1.46% (95% CI 0.99-2.01). Among those with heart disease, 70.25% (95% CI 64.87-75.38) had Rheumatic heart disease and 18.10% (95% CI 14.39-22.12) had congenital heart disease. The pooled prevalence of preterm labor and delivery among pregnant women with heart disease was 17.63% (95% CI 12.18-23.80). Similarly, the pooled maternal and fetal mortality rates were 26.14 (95% CI 12.47-43.55) and 50.48 (95% CI 29.59-75.83) per 1000 pregnant women with heart disease respectively. Conclusion: As pregnancy, itself is a prolonged state of physiologic stress, heart disease further adds to the risk both for the mother and fetus. Having such a high prevalence, efforts must be made to detect and closely monitor the condition antenatally, and decisions should be made according to the clinical conditions of the patient.