Primary Tuberculosis of Cervix Which Simulated Endocervical Polyp: A Case Study.

Tuberculosis has been described as the second great "Imitator" as it can imitate various other disease processes. The manifestations of genitourinary tuberculosis are protean in nature; still tuberculosis is a health concern in South-East Asia region. Tuberculosis of the cervix is rarely found and accounts for 5-10% among all types of genital tuberculosis. Despite meticulous history and clinical examination does not always lead to suspect this disease, the definitive diagnosis is based on the demonstration of the characteristic lesion on histopathology or on bacterial isolation. We are reporting a case of a 26-years-old woman who presented with secondary amenorrhea and a benign looking endocervical polyp. Diagnosis of cervical tuberculosis could be clinched after tissue biopsy which revealed caseous granuloma on histopathological examination along with other supportive laboratory investigation reports. Patient was subsequently started on antitubercular therapy (ATT) according to directly observed treatment schedule- category I, resulting in resumption of her menses after four months of starting of ATT. An awareness of the atypical clinical manifestations of tuberculosis is important, especially in regions where tuberculosis continues to be a major public health problem, such as Bangladesh. One should have high index of suspicion in order to diagnose tuberculosis of cervix in such cases, especially in high prevalence areas, so that patients can be managed appropriately with antitubercular therapy and complications can be prevented.

The impact of climate variability and change on the energy system: A systematic scoping review.

The energy system is a vital infrastructure which can be vulnerable to climate variability and change (CV&C) impacts. Understanding the impacts can prevent disruption and inform policy decision making. This study applied a scoping review in a systematic manner following the Joanna Briggs Institute guidelines to identify consistent patterns of CV&C impacts on the energy system, map and locate research gaps in the literature. A total of 176 studies were identified as eligible for inclusion in the review. This study found evidence of consistent increase in energy demand for Africa, the Americas and Asian continent. Consistent decrease was found in Northern and Eastern Europe, while increase in residential demand was projected in Oceania. There was evidence of consistent decrease in thermal power plant output globally. Solar photovoltaic showed a robust consistent pattern of increase in the Caribbean and Central America, Northern and Southern Africa and Oceania. As the global climate is changing in a future that is highly uncertain, the energy system should also evolve in order to adapt to the changing climate. Future impact assessment must integrate the impact of CV&C on power demand and supply while consider socioeconomic dynamics, cross-sectoral linkages and back-loops in a complete energy system model.

Correlation between Umbilical Cord Diameter and Cross Sectional Area with Gestational Age and Foetal Anthropometric Parameters.

The objective of the study was to find out correlation between umbilical cord diameter, cross sectional area with gestational age and foetal anthropometric parameters. This cross sectional study was conducted among healthy women between the 24(th) and 40(th) completed weeks of a normal pregnancy in the Department of Radiology & Imaging, Mymensingh Medical College Hospital, Mymensingh during the study period, from July 2009 to June 2011. A total of 230 consecutive normal pregnancy patients were included in the study. The diameter & cross-sectional area of the umbilical cord were measured on a plane adjacent to the junction of the umbilical cord and the fetal abdomen, in cross-section, with maximum magnification of the image. The cord was manually circled, and it's cross sectional areas was automatically calculated by the ultrasonograph. The mean±SD age was 24.3±4.7 years with range from 19 to 36 years. The mean gestational age was 32.1±4.5 weeks and more than a half (56.4%) of the pregnant women were nulliparas. A positive significant (p<0.001) correlation were found between umbilical cord diameter with bi-parietal diameter (r=0.548); head circumference (r=0.411); abdominal circumference (r=0.444); femur length (r=0.366) and gestational age gestation age (r=0.643). Similarly, a significant (p<0.001) positive week correlation were found between umbilical cross sectional area with bi-parietal diameter (r=0.3303); head circumference (r=0.3202); abdominal circumference (r=0.2651); femur length (r=0.3307) and gestation age (r=0.4051). A positive significant better correlation was found with umbilical cord diameter than cross sectional area with foetal anthropometric parameters.

Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma.

While mutations in the KRAS oncogene are among the most prevalent in human cancer, there are few successful treatments to target these tumors. It is also likely that heterogeneity in KRAS-mutant tumor biology significantly contributes to the response to therapy. We hypothesized that the presence of commonly co-occurring mutations in STK11 and TP53 tumor suppressors may represent a significant source of heterogeneity in KRAS-mutant tumors. To address this, we utilized a large cohort of resected tumors from 442 lung adenocarcinoma patients with data including annotation of prevalent driver mutations (KRAS and EGFR) and tumor suppressor mutations (STK11 and TP53), microarray-based gene expression and clinical covariates, including overall survival (OS). Specifically, we determined impact of STK11 and TP53 mutations on a new KRAS mutation-associated gene expression signature as well as previously defined signatures of tumor cell proliferation and immune surveillance responses. Interestingly, STK11, but not TP53 mutations, were associated with highly elevated expression of KRAS mutation-associated genes. Mutations in TP53 and STK11 also impacted tumor biology regardless of KRAS status, with TP53 strongly associated with enhanced proliferation and STK11 with suppression of immune surveillance. These findings illustrate the remarkably distinct ways through which tumor suppressor mutations may contribute to heterogeneity in KRAS-mutant tumor biology. In addition, these studies point to novel associations between gene mutations and immune surveillance that could impact the response to immunotherapy.

Obstetric Outcome in Early and Late Onset Gestational Diabetes Mellitus.

Obstetric outcome in early onset and late onset GDM was compared in a prospective study conducted at the Department of Obstetrics & Gynecology in BIRDEM, Dhaka, Bangladesh. A total 120 pregnant women were recruited purposively for the study in which 60 were early onset GDM and 60 were late onset GDM during study period of January 2008 to December 2009. Patients were followed up in different periods of gestation, during delivery and early postpartum period & findings were compared between two groups. BMI & family history of diabetes were significantly higher in early GDM group (p<0.05). Evidence of increased glycaemia was observed in early GDM group & difference of glycaemic status was statistically significant (p<0.05). Insulin was needed in 85% of early onset GDM and 55% in late onset GDM. There was also significant difference (p<0.05). In this study, 23.3% of early onset GDM group developed pre-eclampsia while in late onset GDM it was 10% and was statistically significant (p<0.05). Regarding intrapartum & postpartum complications - perineal tear, PPH wound infection, puerperal sepsis were more in early onset than late onset GDM group with no significant difference. Regarding foetal outcome, 8.3% early GDM group delivered asphyxiated baby in comparison to 3.3% in late GDM group. Twenty percent (20%) of early onset GDM group had to admit their babies in neonatal unit while in late onset group it was 5%. There was significant difference between two groups (p<0.05). Neonatal hypoglycaemia was also statistically significantly (p<0.05) higher in early GDM group. Neonatal hyper-bilirubinaemia, RDS, perinatal death was more in early onset GDM subjects. Early onset GDM subjects are high risk subgroup & have significant deleterious effect on maternal and perinatal outcome than late GDM groups.

IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer.

Serine/threonine kinase IKBKE is a newly identified oncogene; however, its regulation remains elusive. Here, we provide evidence that IKBKE is a downstream target of signal transducer and activator of transcription 3 (STAT3) and that tobacco components induce IKBKE expression through STAT3. Ectopic expression of constitutively active STAT3 increased IKBKE mRNA and protein levels, whereas inhibition of STAT3 reduced IKBKE expression. Furthermore, expression levels of IKBKE are significantly associated with STAT3 activation and tobacco use history in non-small cell lung cancer (NSCLC) patients examined. In addition, we show induction of IKBKE by two components of cigarette smoke, nicotine and nicotine-derived nitrosamine ketone (NNK). Upon exposure to nicotine or NNK, cells express high levels of IKBKE protein and mRNA, which are largely abrogated by inhibition of STAT3. Characterization of the IKBKE promoter revealed two STAT3-response elements. The IKBKE promoter directly bound to STAT3 and responded to nicotine and NNK stimulation. Notably, enforcing expression of IKBKE induces chemoresistance, whereas knockdown of IKBKE not only sensitizes NSCLC cells to chemotherapy but also abrogates STAT3- and nicotine-induced cell survival. These data indicate for the first time that IKBKE is a direct target of STAT3 and is induced by tobacco carcinogens through STAT3 pathway. In addition, our study also suggests that IKBKE is an important therapeutic target and could have a pivotal role in tobacco-associated lung carcinogenesis.

Monitoring the health and production of household Jinding ducks on Hatia Island of Bangladesh.

Duck rearing is an important component of sustainable living in poor rural communities, especially as a source of subsistence. A study was conducted on 118 households (N = 1,373 Jinding ducks, Anas platyrhynchus) from December 2002 to February 2004 on Hatia Island in Bangladesh with the aim of identifying the factors that limit the health and production of Jinding ducks. Overall duck mortality was 29.3%, with disease (19.7%) being a more significant factor than predation (9.6%; p = 0.001). Duck mortality also varied significantly among study zones (p < 0.001). Common diseases were duck plague (21.1%) and duck cholera (32.1%). Helminth infection was prevalent, with endemic trematode (Prosthogonimus spp., Trichobilharzia spp., Echinostoma spp.) and nematode (Cyathostoma bronchialis, Amidostomum anseris, Heterakis gallinarum, Capillaria spp., and Echinuria spp.) infections and epidemic cestode infections due to Hymenolepsis setigera. The median egg production rate per duck per household was 93 for a 6-month laying period. The odds of diminished egg production (average ≤ 93 eggs per duck per household for a 6-month laying period) was 25.4 times higher in ducks that were kept in traditional duck houses (p < 0.001) and 14.2 times higher in ducks that experienced delays in the onset of sexual maturity (days 191 and 280; p < 0.001). Ducks that were provided snails for a shorter period of time over the laying period were 18.2 times more likely to produce fewer eggs than their longer fed peers (p = 0.002). In conclusion, duck mortalities due to diseases and predation and parasitic infections appear to be common constraints on household duck production on Hatia Island. Additionally, improving duck housing and providing longer nutritional supplementation with snails increased the production capabilities of household-raised Jinding ducks on Hatia Island.

Factors limiting traditional household duck production in Bangladesh.

A cross sectional survey of duck production was carried out in 2002 on 771 traditional, semiscavenging household duck farms on the coastal Island of Hatia. We determined the socioeconomic characteristics of duck farmers and their management systems, identified the factors associated with egg production, and measured the level of selected duck diseases and current preventive strategies. Household family size varied from 1 to 14 individuals and women were the main caretakers of ducks. Around 34% of keepers were illiterate. Most duck products (eggs and meat; 85%) were sold at the local market. Duck houses were poorly ventilated and a variety of bedding materials were used. Feed was available in nearby scavenging areas; however, additional feed was frequently supplied by farmers. Almost all farmers (96%) ranked the rainy season as the best time for rearing ducks due to greater feed availability. The annual egg production was 79 eggs per layer with a weight of 48 g and a hatchability rate of 87%. Egg production varied by zone (p < 0.05). The odds of suboptimal egg production was 0.5 times lower in educated farmers (p = 0.001). The odds of suboptimal egg production was 2.5 times more likely in ducks that attained sexual maturity at >22 weeks (p<0.001). Most farmers ranked duck plague as the most important disease, followed by duck cholera, botulism, and duck viral hepatitis. Preventive vaccination was sporadic and used by few farmers (28%). There are significant opportunities for improved duck production on the Island of Hatia and in Bangladesh generally.

Ochratoxin A blood concentration in healthy subjects and bladder cancer cases from Pakistan.

ASTRACT: The mycotoxin ochratoxin A (OTA) is a public health issue in many countries. Data on OTA concentrations in foods and in blood are available for several European countries including the Balkan area, as well as for Canada and Japan. Yet, for developing countries such data are scarce. In this study we determined OTA blood levels as biomarker of exposure in bladder cancer patients and in healthy controls from Pakistan. OTA in blood was analyzed after extraction by HPLC with fluorescence detection (limit of detection: <0.03 ng/mL) in 96 patients and in 31 controls. Over 92% of all blood samples (87 patients, 30 controls) contained quantifiable amounts of OTA: The mean OTA concentrations were 0.33 ng/mL (SD 0.42; range: 0.03 to 3.41 ng/mL) in bladder cancer patients, and 0.31 ng/mL (SD 0.29; range: 0.04 to 1.25 ng/mL) in healthy controls. These OTA concentrations are comparable to those reported for the general population in the European Union.

Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment.

NF-kappaB binding sites are present in the promoter regions of many acute phase and inflammatory response genes, suggesting that NF-kappaB plays an important role in the initiation of innate immune responses. However, targeted mutations of the various NF-kappaB family members have yet to identify members responsible for this critical role. RelA-deficient mice die on embryonic day 15 from TNF-alpha-induced liver degeneration. To investigate the importance of RelA in innate immunity, we genetically suppressed this embryonic lethality by breeding the RelA deficiency onto a TNFR type 1 (TNFR1)-deficient background. TNFR1/RelA-deficient mice were born healthy, but were susceptible to bacterial infections and bacteremia and died within a few weeks after birth. Hemopoiesis was intact in TNFR1/RelA-deficient newborns, but neutrophil emigration to alveoli during LPS-induced pneumonia was severely reduced relative to that in wild-type or TNFR1-deficient mice. In contrast, radiation chimeras reconstituted with RelA or TNFR1/RelA-deficient hemopoietic cells were healthy and demonstrated no defect in neutrophil emigration during LPS-induced pneumonia. Analysis of RNA harvested from the lungs of mice 4 h after LPS insufflation revealed that the induction of several genes important for neutrophil recruitment to the lung was significantly reduced in TNFR1/RelA-deficient mice relative to that in wild-type or TNFR1-deficient mice. These results suggest that TNFR1-independent activation of RelA is essential in cells of nonhemopoietic origin during the initiation of an innate immune response.

An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells.

Tissue damage induced by infection or injury can result in necrosis, a mode of cell death characterized by induction of an inflammatory response. In contrast, cells dying by apoptosis do not induce inflammation. However, the reasons for underlying differences between these two modes of cell death in inducing inflammation are not known. Here we show that necrotic cells, but not apoptotic cells, activate NF-kappaB and induce expression of genes involved in inflammatory and tissue-repair responses, including neutrophil-specific chemokine genes KC and macrophage-inflammatory protein-2, in viable fibroblasts and macrophages. Intriguingly, NF-kappaB activation by necrotic cells was dependent on Toll-like receptor 2, a signaling pathway that induces inflammation in response to microbial agents. These results have identified a novel mechanism by which cell necrosis, but not apoptosis, can induce expression of genes involved in inflammation and tissue-repair responses. Furthermore, these results also demonstrate that the NF-kappaB/Toll-like receptor 2 pathway can be activated both by exogenous microbial agents and endogenous inflammatory stimuli.

NF-kappa B RelA (p65) is essential for TNF-alpha-induced fas expression but dispensable for both TCR-induced expression and activation-induced cell death.

The Fas death receptor plays a key role in the killing of target cells by NK cells and CTLs and in activation-induced cell death of mature T lymphocytes. These cytotoxic pathways are dependent on induction of Fas expression by cytokines such as TNF-alpha and IFN-gamma or by signals generated after TCR engagement. Although much of our knowledge of the Fas death pathway has been generated from murine studies, little is known about regulatory mechanisms important for murine Fas expression. To this end, we have molecularly cloned a region of the murine Fas promoter that is responsible for mediating TNF-alpha and PMA/PHA-induced expression. We demonstrate here that induction of Fas expression by both stimuli is critically dependent on two sites that associate with RelA-containing NF-kappaB complexes. To determine whether RelA and/or other NF-kappaB subunits are also important for regulating Fas expression in primary T cells, we used CD4 T cells from RelA(-/-), c-Rel(-/-), and p50(-/-) mice. Although proliferative responses were significantly impaired, expression of Fas and activation-induced cell death was unaffected in T cells obtained from these different mice. Importantly, we show that unlike fibroblasts, which consist primarily of RelA-containing NF-kappaB complexes, T cells have high levels of both RelA and c-Rel complexes, suggesting that Fas expression in T cells may be dependent on redundant functions of these NF-kappaB subunits.

Antimicrobial and phytochemical studies on 45 Indian medicinal plants against multi-drug resistant human pathogens.

Ethanolic extracts of 45 Indian medicinal plants traditionally used in medicine were studied for their antimicrobial activity against certain drug-resistant bacteria and a yeast Candida albicans of clinical origin. Of these, 40 plant extracts showed varied levels of antimicrobial activity against one or more test bacteria. Anticandidal activity was detected in 24 plant extracts. Overall, broad-spectrum antimicrobial activity was observed in 12 plants (L. inermis, Eucalyptus sp., H. antidysentrica, H. indicus, C. equistifolia. T. belerica, T. chebula, E. officinalis, C. sinensis, S. aromaticum and P. granatum). No correlation was observed between susceptibility of test strains with plant extracts and antibiotic resistance behaviour of the microbial strains (Staphylococcus aureus, Salmonella paratyphi, Shigella dysenteriae, Escherichia coli, Bacillus subtilis, Candida albicans). Qualitative phytochemical tests, thin layer chromatography and TLC-bioautography of certain active extracts demonstrated the presence of common phytocompounds in the plant extracts including phenols, tannins and flavonoids as major active constituents.

The Rela(p65) subunit of NF-kappaB is essential for inhibiting double-stranded RNA-induced cytotoxicity.

Double-stranded RNA (dsRNA) molecules generated during virus infection can initiate a host antiviral response to limit further infection. Such a response involves induction of antiviral gene expression by the dsRNA-activated protein kinase (PKR) and the NF-kappaB transcription factor. In addition, dsRNA can also induce apoptosis by an incompletely understood mechanism that may serve to further limit viral replication. Here we demonstrate a novel role for the RelA subunit of NF-kappaB in inhibiting dsRNA-induced cell death. dsRNA treatment resulted in caspase 3 activation and apoptotic morphological transformations in mouse embryonic fibroblasts (MEFs) derived from RelA-/- mice but not from RelA+/+ mice. Such dsRNA-induced killing could be inhibited by expression of either a dominant-negative mutant of PKR or wild-type RelA. Interestingly, caspase 3 activated following dsRNA treatment of RelA-/- MEFs was essential for apoptotic nuclear changes but dispensable for cytotoxicity. A broader specificity caspase inhibitor was also unable to inhibit dsRNA-induced cytotoxicity, suggesting that caspase activation is not essential for the induction of cell death by dsRNA in MEFs. However, combined inhibition of caspase 3 and reactive oxygen species production resulted in complete inhibition of dsRNA-induced cytotoxicity. These results demonstrate an essential role for NF-kappaB in protecting cells from dsRNA-induced apoptosis and suggest that NF-kappaB may inhibit both caspase-dependent and reactive oxygen species-dependent cytotoxic pathways.

Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon.

The alpha/beta interferon (IFN-alpha/beta) system represents one of the first lines of defense against virus infections. As a result, most viruses encode IFN antagonistic factors which enhance viral replication in their hosts. We have previously shown that a recombinant influenza A virus lacking the NS1 gene (delNS1) only replicates efficiently in IFN-alpha/beta-deficient systems. Consistent with this observation, we found that infection of tissue culture cells with delNS1 virus, but not with wild-type influenza A virus, induced high levels of mRNA synthesis from IFN-alpha/beta genes, including IFN-beta. It is known that transactivation of the IFN-beta promoter depends on NF-kappaB and several other transcription factors. Interestingly, cells infected with delNS1 virus showed high levels of NF-kappaB activation compared with those infected with wild-type virus. Expression of dominant-negative inhibitors of the NF-kappaB pathway during delNS1 virus infection prevented the transactivation of the IFN-beta promoter, demonstrating a functional link between NF-kappaB activation and IFN-alpha/beta synthesis in delNS1 virus-infected cells. Moreover, expression of the NS1 protein prevented virus- and/or double-stranded RNA (dsRNA)-mediated activation of the NF-kappaB pathway and of IFN-beta synthesis. This inhibitory property of the NS1 protein of influenza A virus was dependent on its ability to bind dsRNA, supporting a model in which binding of NS1 to dsRNA generated during influenza virus infection prevents the activation of the IFN system. NS1-mediated inhibition of the NF-kappaB pathway may thus play a key role in the pathogenesis of influenza A virus.

Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase inhibitors: novel mechanism for killing virus-infected cells.

Induction of apoptotic cell death generally requires the participation of cysteine proteases belonging to the caspase family. However, and similar to most cell types, mouse fibroblasts are normally resistant to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis. Surprisingly, TNF-alpha treatment of vaccinia virus-infected mouse fibroblasts resulted in necrotic-like cell death, which was significantly reduced in cells infected with a vaccinia virus mutant lacking the caspase inhibitor B13R. Furthermore, TNF-alpha also induced necrotic-like cell death of fibroblasts in the presence of peptidyl caspase inhibitors. In both cases, necrosis was accompanied by generation of superoxide species. Caspase inhibitors also sensitized fibroblasts to killing by double-stranded RNA and gamma interferon. In all cases, cell death was efficiently blocked by antioxidants or mitochondrial respiratory chain inhibitors. These results define a new mitochondrion-dependent mechanism which may be important in the killing of cells infected with viruses encoding caspase inhibitors.

A mechanism of suppression of TGF-beta/SMAD signaling by NF-kappa B/RelA.

A number of pathogenic and proinflammatory stimuli, and the transforming growth factor-beta (TGF-beta) exert opposing activities in cellular and immune responses. Here we show that the RelA subunit of nuclear factor kappaB (NF-kappaB/RelA) is necessary for the inhibition of TGF-beta-induced phosphorylation, nuclear translocation, and DNA binding of SMAD signaling complexes by tumor necrosis factor-alpha (TNF-alpha). The antagonism is mediated through up-regulation of Smad7 synthesis and induction of stable associations between ligand-activated TGF-beta receptors and inhibitory Smad7. Down-regulation of endogenous Smad7 by expression of antisense mRNA releases TGF-beta/SMAD-induced transcriptional responses from suppression by cytokine-activated NF-kappaB/RelA. Following stimulation with bacterial lipopolysaccharide (LPS), or the proinflammatory cytokines TNF-alpha and interleukin-1beta (IL-1beta, NF-kappaB/RelA induces Smad7 synthesis through activation of Smad7 gene transcription. These results suggest a mechanism of suppression of TGF-beta/SMAD signaling by opposing stimuli mediated through the activation of inhibitory Smad7 by NF-kappaB/RelA.

An investigation into the behaviour of the electrolytes in presence of ionic urfactants.

The effect of various concentrations of Sodium Chloride and Lithium Sulphate in presence of Carbonate-bicarbonate buffer at pH 9.20 on the base-catalyzed hydrolysis of procaine was investigated. The whole study was done in the presence of different concentration of cetyltrimethyl ammonium bromide (CTAB) and Sodium dodecyl Sulphate (SDS) at 60 degrees C. Addition of different electrolytes suppressed the maxima in the Surfactant Effect Ratio (SER). The presence of these additives increase the inhibitory effect with a corresponding in their concentrations SDS/SO4, appeared to be most effective inhibitory amongst SDS/Li2SO4, SDS/NaCl, CTAB/Li2SO4, and CTAB/NaCl systems.