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.

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.

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.

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.

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.

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.

Evaluation of Iron Store by Serum Ferritin in Healthy Blood Donors of Bangladesh.

Iron stores in the body exist primarily in the form of ferritin. Small amounts of ferritin secreted into the plasma and plasma ferritin is positively correlated with the size of the total body iron stores. The present study conducted to determine the iron status using the serum ferritin level among healthy Bangladeshi blood donors. The present cross sectional study was conducted in the Department of Transfusion Medicine, Dhaka Medical College, Dhaka, Bangladesh from July 2011 to June 2012. Blood donor signed informed consent and has satisfactory pre-donation health assessment and satisfactory post-donation blood test results were included in the study. Full blood counts were performed within 4 hours of collection using an automated haematology analyzer. Serum ferritin was measured using a validated enzyme immunoassay. Data were analyzed using SPSS version 16 (SPPS Incorporation, Chicago, IL, USA). P value <0.05 was considered as statistically significant. Total 100 blood donors were included in the study, among them 88 were male and 12 were female. Mean±SD of the age of the respondents was 26.8±5.9 years with a range of 19 to 45 years. Mean±SD of heamoglobin level (gm/dl) and total count of Red Blood Cell (million/cmm) were 14.1±1.4 and 5.1±0.4 respectively. Mean±SD of serum ferritin level (ng/ml) was 96.4±69.0ng/ml with a range of 4.1ng/ml to 298.7ng/ml. Among the respondents 9.0% had depleted iron store, 7.0 reduced iron store and 84.0% had normal iron store. Among the respondents 5.0% had iron deficiency anaemia in term of serum ferritin level. Statistically significant difference of serum ferritin level observed between male and female and donors with and without history of previous blood donation. Among the healthy blood donors of Bangladesh abnormal serum ferritin is highly prevalent among blood donors specially among female. Monitoring of iron stores by serum ferritin seems justified in order to identify those with depleted iron stores who will benefit from iron supplementation.

Relationship between Serum Iron Profile and Blood Groups among the Voluntary Blood Donors of Bangladesh.

Blood donation results in a substantial iron loss and subsequent mobilization from body stores. Chronic iron deficiency is a well-recognized complication of regular blood donation. The present study conducted to compare the level of serum ferritin, serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation in different ABO and Rhesus type blood groups among the voluntary blood donors of Bangladesh. The present prospective study included 100 healthy voluntary donors attending at Department of Blood Transfusion, Dhaka Medical College, Dhaka between the periods of July 2013 to Jun 2014. From each donor 10mL venous blood sample was taken and divided into heparinized and non-heparinized tubes for determination of hemoglobin (Hb), hematocrit (Hct), serum iron (SI), total iron binding capacity (TIBC) and serum ferritin by standard laboratory methods. Percentage of transferrin saturation (TS) calculated from serum iron and TIBC. Data were analyzed with SPSS (version 16) software and comparisons between groups were made using student's t-test and one way ANOVA. In the present study mean±SD of age of the respondents was 27.2±6.5 years with a range of 18 to 49 years and 81.0% were male and 19.0% were female. Among the donors 18.0% had blood group A, 35.0% had blood group B, 14.0% had blood group AB and 33.0% had blood group O. Among the donors 91.0% had rhesus positive and 9.0% had rhesus negative. Donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels. Donors with blood group A had highest TIBC level. Donors with blood group B had lowest serum ferritin level. An independent samples 't' test showed statistically significant difference in serum ferritin and percentage transferrin saturation between blood group AB and blood group O and in percentage transferrin saturation between blood group B and blood group O. One way ANOVA showed that there is no significant difference in haemoglobin, serum iron, serum ferritin and percentage transferring saturation in different ABO and Rh blood grouping categories. Blood donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels and donors with blood group A had highest TIBC level. Blood donors with blood group B had lowest serum ferritin level. The understanding of the different blood groups ability to retain iron in their system can give an insight into their ability to handle the disease iron deficiency anaemia.

An in silico model to demonstrate the effects of Maspin on cancer cell dynamics.

Most cancer treatments efficacy depends on tumor metastasis suppression, where tumor suppressor genes play an important role. Maspin (Mammary Serine Protease Inhibitor), an non-inhibitory serpin has been reported as a potential tumor suppressor to influence cell migration, adhesion, proliferation and apoptosis in in vitro and in vivo experiments in last two decades. Lack of computational investigations hinders its ability to go through clinical trials. Previously, we reported first computational model for maspin effects on tumor growth using artificial neural network and cellular automata paradigm with in vitro data support. This paper extends the previous in silico model by encompassing how maspin influences cell migration and the cell-extracellular matrix interaction in subcellular level. A feedforward neural network was used to define each cell behavior (proliferation, quiescence, apoptosis) which followed a cell-cycle algorithm to show the microenvironment impacts over tumor growth. Furthermore, the model concentrates how the in silico experiments results can further confirm the fact that maspin reduces cell migration using specific in vitro data verification method. The data collected from in vitro and in silico experiments formulates an unsupervised learning problem which can be solved by using different clustering algorithms. A density based clustering technique was developed to measure the similarity between two datasets based on the number of links between instances. Our proposed clustering algorithm first finds the nearest neighbors of each instance, and then redefines the similarity between pairs of instances in terms of how many nearest neighbors share the two instances. The number of links between two instances is defined as the number of common neighbors they have. The results showed significant resemblances with in vitro experimental data. The results also offer a new insight into the dynamics of maspin and establish as a metastasis suppressor gene for further molecular research.

A hybrid computational model for the effects of maspin on cancer cell dynamics.

Cancer metastasis is a complex multistep process which allows cancer cells to establish new tumours in distant organs. The process of metastasis involves cell migration and invasion; it is what makes cancer a fatal disease. The efficiency of most cancer treatments depends on metastasis suppression. Maspin is a type II tumour metastasis suppressor which has multiple cellular effects. It has been described as a key regulatory protein in both the intracellular and extracellular environments. Maspin has been shown to reduce cell migration, invasion, proliferation and angiogenesis, and increase apoptosis and cell-cell adhesion in in vitro and in vivo experiments. The clinical data regarding the predictive effects of maspin expression are variable. To date, the whole cellular mechanisms that maspin uses to influence tumour cell behaviours have not been clearly defined. The diversity of the effects of maspin motivated us to develop an intelligent model to investigate its effects on cellular proliferation and migration. This paper reports a hybrid model of solid tumour growth in order to investigate the impact of maspin on the growth and evolutionary dynamics of the cancer cell. A feed-forward neural network was used to model the behaviours (proliferation, quiescence, apoptosis and/or movement) of each cell, which has been suggested as a suitable model of cell signalling pathways. Results show that maspin reduces migration by 10-40%, confirmed by published in vitro data. The model also shows a reduction in cell proliferation by 20-30% in the presence of maspin. So far, this is the first attempt to model the effect of maspin in a computational model to verify in vitro data. This will provide new insights into the tumour suppressive properties of maspin and inform the development of novel cancer therapies.

Avascular tumour growth dynamics and the constraints of protein binding for drug transportation.

The potential for the use of in-silico models of disease in progression monitoring is becoming increasingly recognised, as well as its contribution to the development of complete curative processes. In this paper we report the development of a hybrid cellular automaton model to mimic the growth of avascular tumours, including the infusion of a bioreductive drug to study the effects of protein binding on drug transportation. The growth model is operated within an extracellular tumour microenvironment. An artificial Neural Network based scheme was implemented that modelled the behaviours of each cell (proliferation, quiescence, apoptosis and/or movement) based on the complex heterogeneous microenvironment; consisting of oxygen, glucose, hydrogen ions, inhibitory factors and growth factors. To validate the growth model results, we conducted experiments with multicellular tumour spheroids. These results showed good agreement with the predicted growth dynamics. The outcome of the avascular tumour growth model suggested that tumour microenvironments have a strong impact on cell behaviour. To address the problem of cellular proteins acting as resistive factors preventing efficient drug penetration, a bioreactive drug (tirapazamine) was added to the system. This allowed us to study the drug penetration through multicellular layers of tissue after its binding to cellular proteins. The results of the in vitro model suggested that the proteins reduce the toxicity of the drug, reducing its efficacy for the most severely hypoxic fractions furthest from a functional blood vessel. Finally this research provides a unique comparison of in vitro tumour growth with an intelligent in silico model to measure bioreductive drug availability inside tumour tissue through a set of experiments.

Effect of aerobic exercise on patients with primary fibromyalgia syndrome.

Sixty eight adult patients of fibromyalgia were included in this prospective study from the Outpatient Department of Physical Medicine and Rehabilitation of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka during the period of January 2003 to June 2003. Study samples were assigned into two treatment groups: Group A (n = 38) with exercise by static bicycle and aerobic walking in addition to tricyclic antidepressant and analgesic and Group B (n = 30) was non exercise group, treated with tricyclic antidepressant and analgesic only. The total duration of treatment was 16 weeks. Pre-treatment (week 0) and post treatment (week 16) evaluation was performed in both groups. Evaluation parameters included pain grade, number of trigger points, occurrence of arousal at night, frequency of micturition and global evaluation by the physician. After 16 weeks, mean improvement of exercise group and non exercise group was 48% and 39% respectively but this difference was not statistically significant. Therefore, from this study it was observed that aerobic exercise showed no significant benefit to fibromyalgia patients.