Influenza B Virus Triggering Macrophage Activation Syndrome in an Infant.

Macrophage activation syndrome (MAS) is a potentially fatal complication caused by excessive activation and expansion of macrophages and T lymphocytes. It can be triggered by various infections and is characterized by the development of cytopenias, hyperferritinemia, liver dysfunction, and coagulopathy. We report a 10-month-old female infant with fever, convulsions, and hepatosplenomegaly. Laboratory data of bicytopenia, low erythrocyte sedimentation rate, and elevated liver enzymes suggested MAS. This was supported by the presence of hyperferritinemia with hypertriglyceridemia. MAS was triggered by influenza B virus. She responded to treatment with immunoglobulin and steroid.

New role of lupeol in reticence of angiogenesis, the cellular parameter of neoplastic progression in tumorigenesis models through altered gene expression.

There is a major unmet medical need for effective and well tolerated treatment options for cancer. The search now seeks to identify active biomolecules with multiple targets. Lupeol, an important dietary triterpenoid known as anticarcinogen by inducing apoptosis. But it is still more to reveal the potency of lupeol in the inhibition of neovascularization in cancer context. The study aimed to explore the efficacy of the lupeol in targeting angiogenesis. In this study, the inhibition of neovessel formation was assessed by preliminary antiangiogenesis assays like chorio allontoic membrane (CAM) and rat corneal micro pocket models. Further, validated for the micro vessel density (MVD) in histological sections of peritoneum, solid tumor and xenograft tumor by immunostaining with anti CD31 antibody. Antitumor potency was verified in ascites carcinoma, solid lymphoma and human nueroblastoma xenograft in CAM. Altered angiogenic gene expression by RT-PCR, ELISA and gelatin zymography. Lupeol significantly inhibits the neovessel formation in CAM and in the rat cornea. The similar effect was ascertained in mice and human xenograft tumor models with the regressed growth. Eventually reflecting on the differential transcription of angiogenic genes like MMP-2 & 9, HIF-1α, VEGFa and Flt-1 was noteworthy. It is now evident from our studies that, a new avenue of dietary triterpenoid lupeol by targeting angiogenesis, potentially inferring the multimode action in cancer prevention.

An efficient cardio vascular disease prediction using multi-scale weighted feature fusion-based convolutional neural network with residual gated recurrent unit.

The cardiovascular disease (CVD) is the dangerous disease in the world. Most of the people around the world are affected by this dangerous CVD. In under-developed countries, the prediction of CVD remains the toughest job and it takes more time and cost. Diagnosing this illness is an intricate task that has to be performed precisely to save the life span of the human. In this research, an advanced deep model-based CVD prediction and risk analysis framework is proposed to minimize the death rate of humans all around the world. The data required for the prediction of CVD is collected from online data sources. Then, the input data is preprocessed using data cleaning, data scaling, and Nan and null value removal techniques. From the preprocessed data, three sets of features are extracted. The three sets of features include deep features, Principal Component Analysis (PCA), and Support Vector Machine (SVM)-based features. A Multi-scale Weighted Feature Fusion-based Deep Structure Network (MWFF-DSN) is developed to predict CVD. This structure is composed of a Multi-scale weighted Feature fusion-based Convolutional Neural Network (CNN) with a Residual Gated Recurrent Unit (GRU). The retrieved features are given as input to MWFF-DSN, and for optimizing weights, a Modernized Plum Tree Algorithm (MPTA) is developed. From the overall analysis, the developed model has attained an accuracy of 96% and it achieves a specificity of 95.95%. The developed model takes minimum time for the CVD and it gives highly accurate detection results.

Synechococcus elongatus PCC 7942 is more tolerant to chromate as compared to Synechocystis sp. PCC 6803.

Two unicellular cyanobacteria Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 showed contrasting responses to chromate stress with EC50 of 12 ± 2 and 150 ± 15 µM potassium dichromate respectively. There was no depletion of chromate in growth medium in both the cases. Using labeled chromate, very low accumulation (<1 nmol/10(8) cells) was observed in Synechocystis after incubation for 24 h in light. No accumulation of chromate could be observed in Synechococcus under these conditions. Chromate oxyanion is known to enter the cells using sulfate uptake channels. Therefore, inhibition of sulfate uptake caused by chromate was monitored using (35)S labeled sulfate. IC50 values of chromate for (35)sulfate uptake were higher in Synechococcus as compared to Synechocystis. The results suggested that the sulfate transporters in Synechococcus have lower affinity to chromate than those from Synechocystis possibly due to differences in affinity of sulfate receptors for chromate. Bioinformatic analyses revealed presence of sulfate and chromate transporters with considerable similarity; however, minor differences in these may play a role in their differential response to chromate. In both cases the IC50 values decreased when sulfate concentration was reduced in the medium indicating competitive inhibition of sulfate uptake by chromate. Interestingly, Synechococcus showed stimulation of growth at concentrations of chromate less than 100 µM, which affected its cell size without disturbing the ultrastructure and thylakoid organization. In Synechocystis, growth with 12 µM potassium dichromate damaged the ultrastructure and thylakoid organization with slight elongation of the cells. The results suggested that Synechococcus possesses efficient strategies to prevent entry and to remove chromate from the cell as compared to Synechocystis. This is the first time a differential response of Synechococcus 7942 and Synechocystis 6803 to chromate is reported. The contrasting characteristics observed in the two cyanobacteria will be useful in understanding the basis of resistance or susceptibility to chromate.

Histone octamer trans-transfer: a signature mechanism of ATP-dependent chromatin remodelling unravelled in wheat nuclear extract.

BACKGROUND AND SCOPE: In eukaryotes, chromatin remodelling complexes are shown to be responsible for nucleosome mobility, leading to increased accessibility of DNA for DNA binding proteins. Although the existence of such complexes in plants has been surmised mainly at the genetic level from bioinformatics studies and analysis of mutants, the biochemical existence of such complexes has remained unexplored. METHODS: Histone H1-depleted donor chromatin was prepared by micrococcal nuclease digestion of wheat nuclei and fractionation by exclusion chromatography. Nuclear extract was partially purified by cellulose phosphate ion exchange chromatography. Histone octamer trans-transfer activity was analysed using the synthetic nucleosome positioning sequence in the absence and presence of ATP and its analogues. ATPase activity was measured as (32)Pi released using liquid scintillation counting. KEY RESULTS: ATP-dependent histone octamer trans-transfer activity, partially purified from wheat nuclei using cellulose phosphate, showed ATP-dependent octamer displacement in trans from the H1-depleted native donor chromatin of wheat to the labelled synthetic nucleosome positioning sequence. It also showed nucleosome-dependent ATPase activity. Substitution of ATP by ATP analogues, namely ATPγS, AMP-PNP and ADP abolished the octamer trans-transfer, indicating the requirement of ATP hydrolysis for this activity. CONCLUSIONS: ATP-dependent histone octamer transfer in trans is a recognized activity of chromatin remodelling complexes required for chromatin structure dynamics in non-plant species. Our results suggested that wheat nuclei also possess a typical chromatin remodelling activity, similar to that in other eukaryotes. This is the first report on chromatin remodelling activity in vitro from plants.

Adjuvant therapy with methylene blue in the treatment of right ventricular failure after pulmonary embolectomy.

Severe pulmonary embolism often leads to right ventricular failure after surgical embolectomy secondary to ischaemia reperfusion injury and acute lung injury (ALI). Acute right ventricular dysfunction is traditionally treated with inotropes and vasopressors to maintain cardiac output and coronary perfusion as well as selective pulmonary vasodilators to provide right ventricular afterload reduction. We report the first case of utilisation of methylene (MB) in a patient with acute right ventricular failure and vasoplegic shock after surgical pulmonary embolectomy.

Platelet enhancement by Carica papaya L. leaf fractions in cyclophosphamide induced thrombocytopenic rats is due to elevated expression of CD110 receptor on megakaryocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya leaf juice/decoction has been in use in folk medicine in Srilanka, Malaysia and in few parts of India for enhancing the platelet counts in dengue. In Siddha medicine, a traditional form of medicine in India, papaya leaf juice has been used for increasing the platelet counts. Papaya leaf has been reported to enhance blood volume in ancient Ayurveda books in India. Carica papaya leaf is well known for its platelet enhancement activity. Although many preclinical and clinical studies have demonstrated the ability of papaya leaf juice for platelet enhancement, but the underlying mechanisms are still unclear. AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp). MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting. RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/µL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/µL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats. CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.

Modulation of photosynthesis in Synechocystis and Synechococcus grown with chromium (VI).

Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 exhibit dissimilar tolerance to Cr(VI) with a tenfold difference in their EC50 value for Cr(VI). This contrasting tolerance was attributed to the difference in the ability to transport Cr(VI) and to detoxify ROS. The present study used biochemical assays and chlorophyll fluorescence to investigate the effect of growth with Cr(VI) on photosynthesis in the two cyanobacteria. In absence of Cr(VI), all the measured parameters viz., rates of CO2 fixation, PSII and PSI activities were higher in Synechocystis in comparison to Synechococcus, suggesting intrinsic differences in their photosynthesis. Growth in the presence of Cr(VI) reduced the pigment content and photosystems' activities in both cyanobacteria. It was further observed that photosynthetic functions were more adversely affected in Synechocystis in comparison to Synechococcus, in spite of exposure to tenfold lower Cr(VI) concentration. The effective quantumyield of PSII and PSI obtained by chlorophyll fluorescence measurements increased in the presence of Cr(VI) in Synechococcus whereas it decreased in Synechocystis. However, the overall CO2 fixation remained unchanged. These results indicated that, in addition to the intrinsic difference in photosynthetic rates, the two cyanobacteria exhibit differential modulation of photosynthetic machinery upon Cr(VI) exposure and Synechococcus could adapt better it's photosystems to counter the oxidative stress.

Villous adenoma: a rare tumor of vaginal vault.

Villous adenomas are extremely rare tumors in the vagina and are indistinguishable from their colonic counterparts. These are considered as enteric type neoplasms of lower female genital tract arising from cloacal remnants. The significance of this lesion lies in the fact that it has to be distinguished from metastatic adenocarcinoma from other sites. We present a case of villous adenoma of vaginal vault, a rare site of presentation in a 30-year-old female.

Depression and Anxiety Disorders among Schoolgoing Adolescents in an Urban Area of South India.

CONTEXT: Adolescence is a period of turmoil, leading to several mental health challenges including anxiety and/or depression. AIMS: To study the prevalence of depression and anxiety among higher school going adolescents and their sociodemographic correlates. SETTINGS AND DESIGN: This cross-sectional study included 201 schoolgoing adolescents. SUBJECTS AND METHODS: Depression and anxiety were measured using Beck Depression Inventory and Screen for Child Anxiety Related Disorders. STATISTICAL ANALYSIS USED: Chi-square test and binary logistic Regression with Hosmer-Lemeshow goodness-of-fit model. RESULTS: Overall, 82 (40.8%) showed depression (from mild mood disturbance to severe and extreme depression). Among females, it was 49.3% (vs. 35.9% among males, odds ratio [OR] 2.00; 95% confidence interval [CI]: 1.02-03.97, P = 0.046). Overall, 110 (54.7%) participants had one or the other type of anxiety. Depression among the participants having one or other type of anxiety was 60% (vs. 17.6% without anxiety, OR 7.34; 95% CI: 3.68-14.64, P < 0.0001). CONCLUSIONS: Depression and anxiety were high among the study participants. Co-existing anxiety and female gender are significantly associated with depression among them. Increasing age, socioeconomic factors, and parental education are other factors influencing depression and anxiety but were statistically not significant.

Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study.

OBJECTIVE: As evidence-based guidance to aid clinicians with mechanical ventilation mode selection is scant, we sought to characterize the epidemiology thereof within a university healthcare system and hypothesized that nonconforming approaches could be readily identified. We conducted an exploratory retrospective observational database study of routinely recorded mechanical ventilation parameters between January 1, 2010 and December 31, 2016 from 12 intensive care units. Mode epoch count proportions were examined using Chi squared and Fisher exact tests as appropriate on an inter-unit basis with outlier detection for two test cases via post hoc pairwise analyses of a binomial regression model. RESULTS: Final analysis included 559,734 mode epoch values. Significant heterogeneity was demonstrated between individual units (P < 0.05 for all comparisons). One unit demonstrated heightened utilization of high-frequency oscillatory ventilation, and three units demonstrated frequent synchronized intermittent mandatory ventilation utilization. Assist control ventilation was the most commonly recorded mode (51%), followed by adaptive support ventilation (23.1%). Volume-controlled modes were about twice as common as pressure-controlled modes (64.4% versus 35.6%). Our methodology provides a means by which to characterize the epidemiology of mechanical ventilation approaches and identify nonconforming practices. The observed variability warrants further clinical study about contributors and the impact on relevant outcomes.

In vivo growth inhibitory and anti-angiogenic effects of synthetic novel dienone cyclopropoxy curcumin analogs on mouse Ehrlich ascites tumor.

In the present study, four novel dienone cyclopropoxy curcumin analogs 1a-4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a-4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a-4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance.

Effects of anxiety on TNF-alpha levels during psychological stress.

OBJECTIVES: Psychological stress can influence the immune system, which may result in stress-related illnesses. In this study, we investigated the effect of psychological stress and the coping skill on plasma cytokine levels. MATERIALS AND METHODS: One hundred eighty-three students, at different stages of an academic year, participated in this study. Plasma tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-2 soluble receptor alpha, and IL-4 were measured and examined in relation to the measures of anxiety [State Anxiety Inventory (SAI)] and Bell Adjustment Inventory (BAI) score. RESULTS: SAI scores were significantly higher in both midterm students (MTS) and examination-taking students (ETS), compared with the freshly admitted students (FAS). In addition, TNF-alpha levels were significantly different between the high- and the low-anxiety groups of ETS but not in MTS or FAS. The correlation between SAI scores and the BAI emotional scores was highest in the ETS group. CONCLUSIONS: TNF-alpha level was significantly lower in the ETS group with high anxiety scores, and it is situation specific.

Mechanical ventilation for cardiac support.

Postoperative lung injury is a common, although decreasing, complication of cardiac surgery. This article discusses various means to prevent and minimize postoperative lung injury. These include lung-protective strategies, pharmacologic strategies, and mechanical ventilation.

Modularity: a new perspective in biology.

Several decades of research in biochemistry and molecular biology have been devoted for studies on isolated enzymes and proteins. Recent high throughput technologies in genomics and proteomics have resulted in avalanche of information about several genes, proteins and enzymes in variety of living systems. Though these efforts have greatly contributed to the detailed understanding of a large number of individual genes and proteins, this explosion of information has simultaneously brought out the limitations of reductionism in understanding complex biological processes. The genes or gene products do not function in isolation in vivo. A delicate and dynamic molecular architecture is required for precision of the chemical reactions associated with "life". In future, a paradigm shift is, therefore, envisaged, in biology leading to exploration of molecular organizations in physical and genomic context, a subtle transition from conventional molecular biology to modular biology. A module can be defined as an organization of macromolecules performing a synchronous function in a given metabolic pathway. In modular biology, the biological processes of interest are explored as complex systems of functionally interacting macromolecules. The present article describes the perceptions of the concept of modularity, in terms of associations among genes and proteins, presenting a link between reductionist approach and system biology.

Efficacy of transcutaneous electrical nerve stimulation in the treatment of chronic pelvic pain.

BACKGROUND: Chronic pelvic pain is prevalent in 2% of women population globally. The etiology is multifactorial. Even in the absence of pelvic pathology, there is a subgroup of women who do not respond to analgesic and anti-inflammatory therapy. Chronic pelvic pain can be inhibited by direct inhibition of impulses in the preganglionic afferent neuron by closing the hypothetical gate in the dorsal horn of the spinal cord. Transcutaneous electrical nerve stimulation (TENS) is based on the gate control theory of abolishing the painful stimuli by providing simultaneous inputs in larger myelinated nerve fibers. AIMS AND OBJECTIVES: This study was designed to assess the effectiveness and safety of TENS in idiopathic chronic pelvic pain. METHODS: It is a prospective, experimental study to evaluate the effectiveness of TENS versus placebo in reducing pain severity in chronic pelvic pain (G1 = 30, G2 = 32, G3 = 30, and G0 = 30). Patients with chronic pelvic pain due to benign lesions of genital tract, gastrointestinal, and renal disorders were excluded from the study after performing an ultrasound study of abdomen and pelvis. Ten treatment sessions (5 sessions/week) of 30 min were conducted. OBSERVATIONS AND RESULTS: There was a significant improvement in pain scores in TENS group as compared with control group, and two patients were completely pain free following TENS therapy. CONCLUSION: In women patients with idiopathic chronic pelvic pain, TENS can be a useful intervention. TENS units are safe, economical, and easily commercially available.

Role of Serpine Gene Polymorphism in Recurrent Implantation Failure and Preeclampsia.

This is a rare case of serpine gene polymorphism causing thrombophilia and recurrent implantation failure following intrauterine insemination. SERPINE1 gene encodes plasminogen activator inhibitor type 1 and inhibits fibrinolysis, or clot dissolution. The 4G variant results in increased expression of SERPINE1 and consequently higher inhibition of fibrinolysis, thus leading to thrombophilia. The patient had unexplained primary infertility for 9 years. Ovulation induction was done with gonadotropin releasing hormone (GnRH) agonist long protocol. Recombinant follicle stimulating hormone (FSH) with step down protocol was used. Ovulation trigger was given with recombinant human chorionic gonadotrophin (HCG). Ovum pick up was done after 40 h of trigger. A total of 13 eggs were collected. Patient was put on Cabergoline to prevent ovarian hyperstimulation syndrome (OHSS). Four frozen embryos were transferred on day 14 after Laser-assisted hatching. EmbryoGlue was used to prevent implantation failure. Luteal phase support was given. She was put on enoxaparin and pregnancy has now been confirmed. The patient was on strict monitoring as this gene is also associated with preeclampsia during pregnancy.

A tumoural angiogenic gateway blocker, Benzophenone-1B represses the HIF-1α nuclear translocation and its target gene activation against neoplastic progression.

Hypoxia is an important module in all solid tumours to promote angiogenesis, invasion and metastasis. Stabilization and subsequent nuclear localization of HIF-1α subunits result in the activation of tumour promoting target genes such as VEGF, MMPs, Flt-1, Ang-1 etc. which plays a pivotal role in adaptation of tumour cells to hypoxia. Increased HIF-α and its nuclear translocation have been correlated with pronounced angiogenesis, aggressive tumour growth and poor patient prognosis leading to current interest in HIF-1α as an anticancer drug target. Benzophenone-1B ([4-(1H-benzimidazol-2-ylmethoxy)-3,5-dimethylphenyl]-(4-methoxyphenyl) methanone, or BP-1B) is a new antineoplastic agent with potential angiopreventive effects. Current investigation reports the cellular biochemical modulation underlying BP-1B cytotoxic/antiangiogenic effects. Experimental evidences postulate that BP-1B exhibits the tumour specific cytotoxic actions against various cancer types with prolonged action. Moreover BP-1B efficiently counteracts endothelial cell capillary formation in in-vitro, in-vivo non-tumour and tumour angiogenic systems. Molecular signaling studies reveal that BP-1B arrests nuclear translocation of HIF-1α devoid of p42/44 pathway under CoCl2 induced hypoxic conditions in various cancer cells thereby leading to abrogated HIF-1α dependent activation of VEGF-A, Flt-1, MMP-2, MMP -9 and Ang-1 angiogenic factors resulting in retarded cell migration and invasions. The in-vitro results were reproducible in the reliable in-vivo solid tumour model. Taken together, we conclude that BP-1B impairs angiogenesis by blocking nuclear localization of HIF-1α which can be translated into a potent HIF-1α inhibitor.