Risk Factors of Congenital Heart Defects among Bangladeshi Population.

Etiology of congenital heart defects are complex and possibly lie within the interaction of environmental exposures and inherited factors. Exploration of the contribution of environmental risk factors that are potentially modifiable impeded the prevention of CHDs. This study was conducted to evaluate the environmental risk factors of CHD. It was a case control study, conducted from July 2018 to June 2019 in Paediatric Cardiology department of Dhaka Shishu (Children) Hospital, Bangladesh. Parents of the children with CHDs visiting the out-patient department were considered as case. Control was taken from parents of the children not having congenital heart disease. Data were collected by face-to-face interview using a structured questionnaire containing all the variables of interest and analyzed by using SPSS version 21.0. Majority of the respondents were from rural area (86.9% and 80.0% in case and control group respectively) and CHD was found significantly higher in rural population (p<0.05). Consanguinity was present in 8.9% in case group and CHD was found significantly higher among children born to consanguineous parents (p<0.05). Most of the mother (65.4%) had completed primary level of education however 11.9% mother was illiterate in case group. CHD was found significantly higher among illiterate mothers (p<0.05). Most of the respondents belonged to lower and lower-middle class family (83.1% and 75.7% in case and control group respectively) and CHD was found significantly higher among them (p<0.05). Mothers exposed to passive smoking and in stress during pregnancy period, CHD was significantly higher (p<0.05). No significant association was found between maternal drug use and infection during pregnancy period with CHD (p<0.05). Maternal illiteracy, residing in rural areas, low and lower- middle class socioeconomic status, consanguineous marriage, exposed to passive smoking and stress during pregnancy period have been significantly associated with CHDs.

Micafungin: A promising inhibitor of UBE2M in cancer cell growth suppression.

Neddylation is a protein modification process similar to ubiquitination, carried out through a series of activating (E1), conjugating (E2), and ligating (E3) enzymes. This process has been found to be overactive in various cancers, leading to increased oncogenic activities. Ubiquitin-conjugating enzyme 2 M (UBE2M) is one of two neddylation enzymes that play a vital role in this pathway. Studies have shown that targeting UBE2M in cancer treatment is crucial, as it regulates many molecular mechanisms like DNA damage, apoptosis, and cell proliferation. However, developing small molecule inhibitors against UBE2M remains challenging due to the lack of suitable druggable pockets. We have discovered that Micafungin, an antifungal agent that inhibits the production of 1,3-ß-D-glucan in fungal cell walls, acts as a neddylation inhibitor that targets UBE2M. Biochemical studies reveal that Micafungin obstructs neddylation and stabilizes UBE2M. In cellular experiments, the drug was found to interact with UBE2M, prevent neddylation, accumulate cullin ring ligases (CRLs) substrates, reduce cell survival and migration, and induce DNA damage in gastric cancer cells. This research uncovers a new anti-cancer mechanism for Micafungin, paving the way for the development of a novel class of neddylation inhibitors that target UBE2M.

LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy.

Dysregulation of various cells in the tumor microenvironment (TME) causes immunosuppressive functions and aggressive tumor growth. In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. Lysine-specific demethylase 1 (LSD1) is a protein that modifies histone and non-histone proteins and is known to influence a wide variety of physiological processes. The dysfunction of LSD1 contributes to poor prognosis, poor patient survival, drug resistance, immunosuppression, etc., making it a potential epigenetic target for cancer therapy. This review examines how LSD1 modulates different cell behavior in TME and emphasizes the potential use of LSD1 inhibitors in combination with ICB therapy for future cancer research studies.

New insights into the non-enzymatic function of HDAC6.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins. As a result, aggresomes are formed and protein degradation is facilitated by the autophagy-lysosome pathway. This HDAC6-dependent microtubule transport can be used by cells to assemble and activate inflammasomes, which play a critical role in immune regulation. Even viruses can benefit from the carrier of HDAC6 to assist in uncoating their surfaces during their infection cycle. However, HDAC6 is also capable of blocking virus invasion and replication in a non-enzymatic manner. Given these non-enzymatic functions, HDAC6 is closely associated with various diseases, including neurodegeneration, inflammasome-associated diseases, cancer, and viral infections. Small molecule inhibitors targeting the ubiquitin binding pocket of HDAC6 have been investigated. In this review, we focus on mechanisms in non-enzymatic functions of HDAC6 and discuss the rationality and prospects of therapeutic strategies by intervening the activation of HDAC6 ZnF-UBP in concrete diseases.

Curriculum vitae of HDAC6 in solid tumors.

Histone deacetylase 6 (HDAC6) is the only member of the HDAC family that resides primarily in the cytoplasm with two catalytic domains and a ubiquitin-binding domain. HDAC6 is highly expressed in various solid tumors and participates in a wide range of biological activities, including hormone receptors, the p53 signaling pathway, and the kinase cascade signaling pathway due to its unique structural foundation and abundant substrate types. Additionally, HDAC6 can function as an oncogenic factor in solid tumors, boosting tumor cell proliferation, invasion and metastasis, drug resistance, stemness, and lowering tumor cell immunogenicity, so assisting in carcinogenesis. Pan-HDAC inhibitors for cancer prevention are associated with potential cardiotoxicity in clinical investigations. It's interesting that HDAC6 silencing didn't cause any significant harm to normal cells. Currently, the use of HDAC6 specific inhibitors, individually or in combination, is among the most promising therapies in solid tumors. This review's objective is to give a general overview of the structure, biological functions, and mechanism of HDAC6 in solid tumor cells and in the immunological milieu and discuss the preclinical and clinical trials of selective HDAC6 inhibitors. These endeavors highlight that targeting HDAC6 could effectively kill tumor cells and enhance patients' immunity during solid tumor therapy.

Evaluation of feed utilization, immune response and disease resistance in striped catfish, Pangasianodon hypophthalmus (Sauvage 1878) fed with a novel Aeromonas hydrophila biofilm vaccine.

Striped catfish, Pangasianodon hypophthalmus was immunized with Biofilm (BF) and Free cell (FC) of Aeromonas hydrophila vaccine at 1010 CFU g-1 for 20 days and monitored for growth parameters, immune responses and disease resistance up to 60 day post vaccination (dpv). Pangasius catfish in the BF vaccinated group had considerably higher growth and feed utilization than the FC vaccinated and unvaccinated groups (p < 0.05). Biofilm vaccinated group showed a significant increase (p < 0.05) in the mean weight gain (46.91 ± 0.59) than the FC (35.94 ± 0.21) and unvaccinated group (34.92 ± 0.35). The vaccinated fishes were challenged with A. hydrophila at 107 CFU/ml. Significant higher relative percentage survival (RPS) was recorded with BF (84.21 ± 1.49%) compared to that with FC (33.33 ± 1.21%). Polyclonal antibody-based ELISA was used to quantify the antibody titre. BF vaccinated group showed significantly higher antibody titer compared to other treatments (p < 0.05). Moreover, higher haematological parameters recorded in the present study were differentially stimulated by the oral administration of A. hydrophila biofilm vaccine. The mean total protein, albumin, and globulin levels of the BF vaccine groups were significantly higher (p < 0.05) than the mean total protein, albumin, and globulin contents of the unvaccinated group. Furthermore, biochemical stress parameters (SGPT, SGOT) in the vaccinated groups showed an incremental trend in the early days of the experimental period. However, the values were significantly lower (p < 0.05) in the biofilm group on 20 dpv onwards indicating improved health condition. Vaccinated BF fishes showed gut associated lymphoid tissues (GALT) within the laminar propria of mid gut. But in FC group fishes showed less aggregation of lymphoid cells. The unvaccinated control fish had no lymphoid cell aggregation in their intestines. The findings of the current research suggested that biofilm vaccine has the capability to be one of the potential oral vaccines in striped catfish against A. hydrophila infection.

Comparative Study between Acacia Nilotica versus Povidone Iodine in Topical Treatment of Omphalocele Major.

Well established and common practice in conservative management of omphalocele major is escharotics therapy with different topical agents. Among them mercurochrome, alcohol, silver salts, povidone iodine, acacia nilotca paste are commonly used. It is a comparative study between application of acacia nilotica paste and povidone iodine solution as a primary non surgical treatment of omphalocele major regarding efficacy and safety of these two topical agents. A double blind randomized controlled study was conducted at the department of Paediatric Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2016 to June 2019. In this study 20 cases of omphalocele major and randomly divided into two equal groups. Group A and Group B treated with acacia nilotica paste and povidone iodine solution respectively. Gastroschisis, ruptured-omphalocele major or omphalocele minor excluded in this study. The size of the fascial defect in cm, time required for full oral feeding tolerance and duration of hospital stay were evaluating parameters. Patients with Group A tolerated full oral feeding earlier, shorter total hospital stay duration and low mortality rate than those from Group B. Application of acacia nilotica is a safe and effective treatment of omphalocele major regarding rapid full oral feeding tolerance, shorter hospital stay and low mortality rate.

Improving the electrostatic design of the Jefferson Lab 300 kV DC photogun.

The 300 kV DC high voltage photogun at Jefferson Lab was redesigned to deliver electron beams with a much higher bunch charge and improved beam properties. The original design provided only a modest longitudinal electric field (Ez) at the photocathode, which limited the achievable extracted bunch charge. To reach the bunch charge goal of approximately few nC with 75 ps full-width at half-maximum Gaussian laser pulse width, the existing DC high voltage photogun electrodes and anode-cathode gap were modified to increase Ez at the photocathode. In addition, the anode aperture was spatially shifted with respect to the beamline longitudinal axis to minimize the beam deflection introduced by the non-symmetric nature of the inverted insulator photogun design. We present the electrostatic design of the original photogun and the modified photogun and beam dynamics simulations that predict vastly improved performance. We also quantify the impact of the photocathode recess on beam quality, where recess describes the actual location of the photocathode inside the photogun cathode electrode relative to the intended location. A photocathode unintentionally recessed/misplaced by sub-millimeter distance can significantly impact the downstream beam size.

Clinical Outcome on Comminuted Femoral Shaft Fractures in Adults Treated by Minimally Invasive Plate Osteosynthesis (MIPO) with Locking Plate.

Intramedullary nailing is a pillar in the treatment of femoral shaft fractures. But it is not possible in all cases especially in comminuted fractures. This study has been designed to explain the importance of Minimally Invasive Plate Osteosynthesis (MIPO) with the locking plate in the treatment of comminuted Femoral Shaft Fracture. Twenty (20) such patients were treated by MIPO and analysis has been done in this study to get fruitful result and to find out the effectiveness of this procedure who were admitted at Mymensingh Medical College Hospital, Mymensingh, a tertiary level hospital of Bangladesh from February 2018 to January 2019. Mean age of the patients were 49.20±14.41 years. Based on AO classification, there were 4, 8 and 8 patients belong to type A, B and C respectively. The union period for all the patients was in between 12 to 14 weeks. The mean union period was 12.90±1.997 weeks. Mean follow up period was 19.70±2.77 weeks. Mean full weight bearing period was 16.50±1.10 weeks. In Thoresen scoring system excellent result was 9(45%), good result was 10(20%) and fair result was 01(5%). Mal-alignment happened in two cases. However, delayed union and broken screws were found in two cases each of which was treated accordingly. Comminuted Femoral shaft fracture with MIPO procedure is more effective treatment than intramedullary nailing. Furthermore, mal-alignment is the basic complexity that must be taken away intraoperatively.

Clinical Presentation, Management and In-Hospital Outcome of COVID-19 among Non-Healthcare Personnel and Healthcare Personnel in a Tertiary Cardiac Care Hospital.

The huge numbers of non-healthcare personnel (non-HCP) who get infected by corona virus disease 2019 (COVID-19) not only paralyze health care systems but also put health care personnel (HCP) at potential risk globally. Objective of the study was to compare the Healthcare personnel (HCP) and non-HCP COVID-19 cases. This prospective observational study was carried out in National Heart Foundation Hospital and Research Institute of Bangladesh from March 08, 2020 to July 20, 2020. During this study period all admitted non-HCP who subsequently was diagnosed as COVID-19 positive by rRT-PCR and HCP of this hospital, who experienced fever or respiratory symptoms or came in close contact with COVID-19 patients at home or their workplace and become COVID-19 positive, were included. Out of 320 infected patients, 181(56.6%) patients were non-HCP and 139(43.4%) were HCP. Non-HCP were older than HCP (Mean age: 52.95±13.82 years vs. 34.08±11.11 years; p=0.001). Non-HCP were predominantly male and HCP were predominantly female (73.5% vs. 41% & 26.5% vs. 59%; p=0.001). Non-HCP had more risk factors and co-morbidities than HCP (p=0.001). Typical symptoms of COVID-19 such as fever and cough were prevalent in HCP. More aggressive treatment was required for non-HCP. Non-HCP had more severe disease and higher case fatality rate (9.4% vs. 0.7%; p=0.001) than HCP. Disease severity (OR 0.03, 95% CI 0.01-0.15) and DM (OR 0.09, 95% CI 0.01-0.94) were the independent predictor of mortality. Non-HCP was older in age, predominantly male and had more co-morbidities than HCP. Typical symptoms of COVID-19 were prevalent in HCP. Non-HCP had more severe disease and higher case fatality rate than HCP.

Targeting neddylation E2s: a novel therapeutic strategy in cancer.

Ubiquitin-conjugating enzyme E2 M (UBE2M) and ubiquitin-conjugating enzyme E2 F (UBE2F) are the two NEDD8-conjugating enzymes of the neddylation pathway that take part in posttranslational modification and change the activity of target proteins. The activity of E2 enzymes requires both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of neural precursor cell-expressed developmentally downregulated 8 (NEDD8). By recruiting E3 ligases and targeting cullin and non-cullin substrates, UBE2M and UBE2F play diverse biological roles. Currently, there are several inhibitors that target the UBE2M-defective in cullin neddylation protein 1 (DCN1) interaction to treat cancer. As described above, this review provides insights into the mechanism of UBE2M and UBE2F and emphasizes these two E2 enzymes as appealing therapeutic targets for the treatment of cancers.

Risk Factors of Malnutrition in Under-5 Children of Slum Area in Dhaka City.

Malnutrition is a serious public health problem that has been linked to increase risk of morbidity and mortality in slums of Dhaka city and where the prevalence of malnutrition is very high. This study was conducted to evaluate the risk factors of malnutrition among under-5 children of selective slum area in Dhaka City. This cross sectional study was conducted from January 2016 to December 2019, among 500 under-5 children selected by random sampling technique from Agargaon and Beribadh slums of Dhaka city. Anthropometric measurements were taken using standard methods those were weight, height, MUAC and age. A questionnaire was ready for data collection containing episode of diseases, breast feeding status, complementary feeding, family size, family income, maternal education status, housing, source of drinking water etc in under-5 children. Data were analyzed by using SPSS version 21.0. Among 500 children from slums area, malnutrition was present in 220(44%) cases. Out of them 115(23%) children were wasted, 205(41%) children were stunted and 175(35%) children were underweight. Malnutrition was found significantly high among non-breast feed babies, who breast feed only for 6 months, in whom colostrum was not given and also when complimentary feeding was not given properly (p<0.05). Malnourished children were found significantly higher among illiterate mothers and those who used Kancha house (p<0.05). Wasting, stunting and underweight were more with increasing family size. There were a decreased number of malnutrition cases when family income rises. Diarrhoea and ARI was significantly associated with malnutrition (p<0.05). Large number of children in slum areas of Dhaka city was suffering from malnutrition. Malnutrition was significantly higher among children who did not get colostrum; non-breast fed and got improper complimentary feeding. Maternal illiteracy, living in Kancha house, large family size, family income and associated disease condition were also contributed to malnutrition.

Supplementation of nano-selenium in fish diet: Impact on selenium assimilation and immune-regulated selenoproteome expression in monosex Nile tilapia (Oreochromis niloticus).

Selenium (Se), a fundamental element of nutrigenomic science in fish nutrition, was used to investigate its impact on selenoproteome expression and Se regulation in tilapia. Different concentrations (T1 - 0, T2 - 0.5, T3 - 1.0 and T4 - 2.0 mg/kg of feed) of dietary nano-Se were incorporated in the diets of monosex Nile tilapia. A total of 180 tilapia fingerlings with initial weight (15.73 ± 0.05 g) were stocked in 150 L capacity FRP tanks categorized into four diet groups with triplicate each for a feeding trial of 90 days. At the end of first, second and third months of the feeding trial, gill, liver, kidney and muscle tissues were harvested to evaluate the effect on the kinetics of Se bioaccumulation and assimilation as well as immune-regulated selenoprotein transcripts (GPx2, SelJ, SelL, SelK, SelS, SelW and Sepp1a) and their synthesis factors (SPS1 and Scly). The findings depicted that significantly (p < 0.05) higher weight gain was found in the diet supplemented with 1.0 mg/kg of nano-Se. The theory of second-order polynomial regression supported the same. The liver showed significantly (p < 0.05) higher Se accumulation and concentration factor among the harvested tissues in a different timeline. All the selected immune-regulated selenoproteins and synthesis factors in different fish tissues showed significantly (p < 0.05) up-regulation in the diet supplemented with 1.0 mg/kg of nano-Se for the second month. Therefore, the present findings suggested that the supplementation of nano-Se could be more effective for improved growth, better selenium regulation and expression of immune-regulated selenoproteins in the fish model.

The role of deubiquitinating enzymes in gastric cancer.

The epigenetic regulation of gene expression (via DNA methylation, histone modification and microRNA interference) contributes to a variety of diseases, particularly cancer. Protein deubiquitination serves a key role in the mechanism underlying histone modification, and consequently influences tumor development and progression. Improved characterization of the role of ubiquitinating enzymes has led to the identification of numerous deubiquitinating enzymes (DUBs) with various functions. Gastric cancer (GC) is a highly prevalent cancer type that exhibits a high mortality rate. Latest analysis about cancer patient revealed that GC is sixth deadliest cancer type, which frequently occur in male (7.2%) than female (4.1%). Complex associations between DUBs and GC progression have been revealed in multiple studies; however, the molecular mechanism underpinning the metastasis and recurrence of GC is yet to be elucidated. Generally, DUBs were upregulated in gastric cancer. The relation of DUBs and tumor size, classification and staging was observed in GC. Besides, 5-yar survival rate of patients with GC is effeccted by expression level of DUBs. Among the highly expressed DUBs, specifically six DUBs namely UCHs, USPs, OTUs, MJDs, JAMMs and MCPIPs effect on this survival rate. Consequently, the association between GC and DUBs has received increasing attention in recent years. Therefore, in the present review, literature investigating the association between DUBs and GC pathophysiology was analyzed and critically appraised.

The composition and stability of the faecal microbiota of Merino sheep.

AIMS: To determine the composition and temporal stability of the gut (faecal) microbiota of sheep (Ovis aries). METHODS AND RESULTS: Microbial population dynamics was conducted using ARISA (28 sheep) and 16S rRNA sequencing (11 sheep). Firmicutes and Bacteroidetes were the predominant bacterial phyla, constituting ~80% of the total population. The core faecal bacterial microbiota of sheep consisted of 67 of 136 detected families and 91 of 215 detected species. Predominant microbial taxa included Ruminococcaceae, unassigned families in Bacteroidales and Clostridiales, Verrucomicrobiaceae and Paraprevotellaceae. Diversity indices and core microbiota composition demonstrated the stability of the core microbiota over 2-4 weeks. The core microbiota remained similar over ~5 months. CONCLUSIONS: Temporal stability of the sheep microbiota is high over 2-4 weeks in the absence of experimental variables. The core microbiota of Merino sheep shares taxa found in other breeds of sheep and other ruminants. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerous studies seek to investigate the impact of experimental variables on gut microbiota composition. To do so, knowledge of the innate stability (or instability) of the microbiota over an experimental time course is required, independent of other variables. We have demonstrated high stability of the gut microbiota in sheep over 3-4 weeks, with moderate stability over ~5 months.

Upper GIT Endoscopic Evaluation and Psychological State Assessment of Patients with Globus Sensation.

Globus sensation is a subjective feeling of a lump or foreign body in the throat without interfering swallowing of food. It is a persistent and distressing sensation in throat. It affects about 6% of population. But cause of globus is still unknown. Exact aetiology of globus is considered to be multifactorial. Some other studies also show association between globus and psychological distress including anxiety and depression. As there is no established pharmacological treatment, adequate investigations with negative result could reassure patients and improve their symptoms. In this prospective study consecutive patients with globus symptoms examined by upper GIT endoscopy with attention to larynx, epiglottis, base of tongue, both pyriform fossa and hypo-pharynx using Olympus forward viewing video Gastroscope (GIF Q-150 & GIF Q-170) to exclude organic lesion and was conducted in the department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU) and North East Medical College, Sylhet from 1st July 2014 to 31 December 2016. Their psychological status and epidemiological information including personal and family history were noted in a pre-designed data sheet. Total 104 patients were examined, among them definite anxiety was found in 36(34.95%) and borderline feature of anxiety was found in 19(18.44%) and 48(46.60%) were free of anxiety. Incidence of anxiety was significantly higher among females and was more prevalent among housewife, married people and people from rural community. In this series, 13(12.5%) patients had definite depression and 29(27.9%) patients had borderline depression, while 61(59.2%) patients had no feature of depression. Incidence of depression was significantly higher among females, housewife and married people. Organic lesion is rare in patients with globus symptoms. Globus sensation is more common among females. Psychological factors like anxiety and depression are frequently associated with globus sensation.

The association between Facebook addiction and depression: A pilot survey study among Bangladeshi students.

Social media addiction has become an area of increasing research interest over the past few years. However, there has been no previous research on social media addiction in Bangladesh. The present pilot study is the first ever in Bangladesh to examine the relationship between one specific form of social media addiction (i.e., 'Facebook addiction') and its associated predictors. This present study comprised 300 students from the University of Dhaka (Bangladesh) who participated in a survey that included questions relating to socio-demographics, health and behavioral measures, and the Bergen Facebook Addiction Scale (BFAS), and the nine-item Patient Health Questionnaire (PHQ9). The prevalence of FA was 39.7% (cutoff score was ≥18 on the BFAS). Using a regression analysis, the risk of being addicted to Facebook was predicted by being single, having less involvement in physical activities, sleep disturbance (more or less than 6 to 7 h of sleep), time spent on Facebook (≥5 h per day), and depression symptoms. Based on the sample in the present study, the risk of Facebook addiction (as assessed using the BFAS) appears to be a significant issue among Bangladeshi students, and depression to be one of the main comorbid factors.

Use of an Individual-based Model to Control Transmission Pathways of Mycobacterium avium Subsp. paratuberculosis Infection in Cattle Herds.

Johne's disease (JD) is a chronic enteric disease in cattle caused by Mycobacterium avian subsp. paratuberculosis (MAP). Eradicating JD is a difficult task due to the long incubation period of MAP, inefficient diagnostic tests, and delayed clinical signs. Effective control strategies can help farmers to reduce prevalence, but those most acceptable to farmers combine specific information about lactation performance and testing results, which existing models do not provide. This paper presents an individual-based model of MAP infection dynamics and assesses the relative performance of the applied alternative control strategies. The base dairy herd model included the daily life events of a dairy cow and reflects several current dairy management processes. We then integrated MAP infection dynamics into the model. The model adopted four different test-based control strategies based on risk-based culling decisions and three hygiene scenarios. The model tracked the source of each infection and quantified the efficacy of each control strategy in reducing the risks of different transmission routes. The results suggest that risk-based culling can reduce prevalence compared with no control, but cannot eliminate the infection. Overall, this work provides not only a valuable tool to investigate MAP transmission dynamics but also offers adaptability to model similar infectious diseases.