Clinical presentation of ulcerative colitis among Bangladeshi population twenty years experience from a tertiary care hospital in Bangladesh

Background: The prevalence of Ulcerative colitis has been increasingly reported from Western countries as well as other Asian countries. Our personal experience shows that Ulcerative colitis is not uncommon in our country and is being diagnosed more commonly. So, there is need to study the disease pattern in our country. Objective: To find out the clinical presentation, among Bangladeshi population. Methods: A hospital (Department of Gastroenterology, Bang­abandhu Sheikh Mujib Medical University) based study registering previously diagnosed and newly diagnosed cases of Ulcerative colitis, was carried out from January 1990 to June 2010. Data that were obtained are: age and sex of the patients, clinical presentations like bloody diarrhoea, per rectal bleeding, diarrhoea without per rectal bleeding, urgency, tenesmus, abdominal pain, fever, anorexia, weakness, weight loss. Data regarding physical findings and extra intestinal manifestations were also recorded. Results: Out of 164 patients 65.24% (107) were male and 34.76% (57) were female. The male- female ratio was 1.88 : 1. Mean age of male patients was 36.14(±11.66) years and mean age for female patients was 33.15(±11.12) years. Maximum number of male patients were in 21-40 years age group (65.42%, 70). Maximum number of female patients were in 21-30 years age group (42.10%, 24). Maximum number of both male and female patients were in 21-30 years age group (35.97%, 59). Clinical features of 164 patients showed that 87.28% (143) had bloody diarrhoea, 20.12% (33) had per-rectal bleeding, 4.26% (7) had diarrhoea without per rectal bleeding, 1.21% (2) had urgency, 5.48% (9) had tenesmus, 33.53% (55) had abdominal pain, 17.66% (29) had fever, 18.29% (30) had anorexia, weakness and 17.68% (29) had weight loss at their initial presentation. Physical examination of 164 patients revealed that 81(49.39%) patients had normal findings, 7 (4.27%) patients had oedema and 83 (50.61%) patients had anaemia. Extra intestinal features were absent in 143 (87.20%) patients out of 164 patients. The rest 21 (12.80%) patients had joint involvement and 2 ( 1.21 % ) patients had ocular involvement. There was no patient with skin involvement. Conclusion: The clinical presentation of Ulcerative colitis in our country is mostly similar compared to other Asian' and Western countries except higher male-female ratio, presence of oedema and wide variability of extra intestinal involve­ment. These differences are probably due to social and cultural reasons, poor nutritional status, incomplete workup or records and influence of various enviornmental factors. To validate these results further prospective studies are needed

Science in the wilderness: the predicament of scientific research in India’s wildlife reserves

Ecology and allied scientific disciplines aim to understand patterns and processes pertaining to wild species, their ecosystems and their relationships with humans. India’s wildlife reserves are important ‘living laboratories’ for these disciplines. Today, there is a disturbing trend across India where scientists are increasingly denied access to wildlife reserves for scientific research or are seriously impeded, without scope for redress. Although official wildlife management rhetoric emphasizes the need for scientific research, in reality, it is viewed as undesirable and permitted, if at all, as a concession, subject to the discretion of individual forest officials. With no enabling legislative or policy framework to promote and apply science in our wildlife reserves, we are concerned that the future of many scientific disciplines in India is being jeopardized. Here, we provide an analysis of this issue and outline steps needed to promote scientific research in our natural areas

Identification and Characterization of Inhibitors of Human Apurinic/apyrimidinic Endonuclease APE1

APE1 is the major nuclease for excising abasic (AP) sites and particular 3′-obstructive termini from DNA, and is an integral participant in the base excision repair (BER) pathway. BER capacity plays a prominent role in dictating responsiveness to agents that generate oxidative or alkylation DNA damage, as well as certain chain-terminating nucleoside analogs and 5-fluorouracil. We describe within the development of a robust, 1536-well automated screening assay that employs a deoxyoligonucleotide substrate operating in the red-shifted fluorescence spectral region to identify APE1 endonuclease inhibitors. This AP site incision assay was used in a titration-based high-throughput screen of the Library of Pharmacologically Active Compounds (LOPAC1280), a collection of well-characterized, drug-like molecules representing all major target classes. Prioritized hits were authenticated and characterized via two high-throughput screening assays – a Thiazole Orange fluorophore-DNA displacement test and an E. coli endonuclease IV counterscreen – and a conventional, gel-based radiotracer incision assay. The top, validated compounds, i.e. 6-hydroxy-DL-DOPA, Reactive Blue 2 and myricetin, were shown to inhibit AP site cleavage activity of whole cell protein extracts from HEK 293T and HeLa cell lines, and to enhance the cytotoxic and genotoxic potency of the alkylating agent methylmethane sulfonate. The studies herein report on the identification of novel, small molecule APE1-targeted bioactive inhibitor probes, which represent initial chemotypes towards the development of potential pharmaceuticals

Evolution of microscopic heterogeneity and dynamics in choline chloride-based deep eutectic solvents

Deep eutectic solvents (DESs) are an emerging class of non-aqueous solvents that are potentially scalable, easy to prepare and functionalize for many applications ranging from biomass processing to energy storage technologies. Predictive understanding of the fundamental correlations between local structure and macroscopic properties is needed to exploit the large design space and tunability of DESs for specific applications. Here, we employ a range of computational and experimental techniques that span length-scales from molecular to macroscopic and timescales from picoseconds to seconds to study the evolution of structure and dynamics in model DESs, namely Glyceline and Ethaline, starting from the parent compounds. We show that systematic addition of choline chloride leads to microscopic heterogeneities that alter the primary structural relaxation in glycerol and ethyleneglycol and result in new dynamic modes that are strongly correlated to the macroscopic properties of the DES formed

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets

Measuring local depletion of terrestrial game vertebrates by central-place hunters in rural Amazonia

The degree to which terrestrial vertebrate populations are depleted in tropical forests occupied by human communities has been the subject of an intense polarising debate that has important conservation implications. Conservation ecologists and practitioners are divided over the extent to which community-based subsistence offtake is compatible with ecologically functional populations of tropical forest game species. To quantify depletion envelopes of forest vertebrates around human communities, we deployed a total of 383 camera trap stations and 78 quantitative interviews to survey the peri-community areas controlled by 60 semi-subsistence communities over a combined area of over 3.2 million hectares in the Médio Juruá and Uatumã regions of Central-Western Brazilian Amazonia. Our results largely conform with prior evidence that hunting large-bodied vertebrates reduces wildlife populations near settlements, such that they are only found at a distance to settlements where they are hunted less frequently. Camera trap data suggest that a select few harvest-sensitive species, including lowland tapir, are either repelled or depleted by human communities. Nocturnal and cathemeral species were detected relatively more frequently in disturbed areas close to communities, but individual species did not necessarily shift their activity patterns. Group biomass of all species was depressed in the wider neighbourhood of urban areas rather than communities. Interview data suggest that species traits, especially group size and body mass, mediate these relationships. Large-bodied, large-group-living species are detected farther from communities as reported by experienced informants. Long-established communities in our study regions have not “emptied” the surrounding forest. Low human population density and low hunting offtake due to abundant sources of alternative aquatic protein, suggest that these communities represent a best-case scenario for sustainable hunting of wildlife for food, thereby providing a conservative assessment of game depletion. Given this ‘best-case’ camera trap and interview-based evidence for hunting depletion, regions with higher human population densities, external trade in wildlife and limited access to alternative protein will likely exhibit more severe depletion

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe