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The Developmental Therapist (DT) is a unique professional training in occupational therapy, physiotherapy, and speech and language therapy. There is unmet demand for developmental therapists in Bangladesh to manage the increasing number of childhood disabilities. However, no academic institute provides training for Developmental therapists in Bangladesh. This paper explains a three-month structured training program for the exercise of the developmental therapist. After completing this training, the DTs gained some essential skills which help them to assess the functional development of children with neurodevelopmental disabilities, identify their problems and provide appropriate management.

Supplemental Figure 1. IQGAP1 levels correlate with disease progression and a poor prognosis;Supplemental Figure 2. IQGAP1 levels correlate with RAS pathway activation gene sets;Supplemental Figure 3. The impact of IQGAP1 WW peptide on cell cycle is reversible.

S1. Ezrin expression in PDAC CSCs. S2. Effects of Ezrin on self-renewal and migration in PDAC cells. S3. Actin dynamics following Ezrin knock-down and in low-passage PDAC xenografts. S4. Actin dynamics in L3.6pl cells. S5. Treatment of PDAC cells with NSC305787. S6. Effects of Ezrin loss on in vivo tumor initiation.

Cancer stem cell characteristics, especially their self-renewal and clonogenic potentials, play an essential role in malignant progression and response to anticancer therapies. Currently, it remains largely unknown what pathways are involved in the regulation of cancer cell stemness and differentiation. Previously, we found that delta-like 1 homolog (Drosophila) or DLK1, a developmentally regulated gene, plays a critical role in the regulation of differentiation, self-renewal, and tumorigenic growth of neuroblastoma cells. Here, we show that DLK1 specifically interacts with the prohibitin 1 (PHB1) and PHB2, two closely related genes with pleiotropic functions, including regulation of mitochondrial function and gene transcription. DLK1 interacts with the PHB1–PHB2 complex via its cytoplasmic domain and regulates mitochondrial functions, including mitochondrial membrane potential and production of reactive oxygen species. We have further found that PHB1 and especially PHB2 regulate cancer cell self-renewal as well as their clonogenic potential. Hence, the DLK1–PHB interaction constitutes a new signaling pathway that maintains clonogenicity and self-renewal potential of cancer cells.Implications: This study provides a new mechanistic insight into the regulation of the stem cell characteristics of cancer cells. Mol Cancer Res; 12(1); 155–64. ©2013 AACR.

PDF file - 144K, S1. Co-immunoprecipitation of DLK1 and PHB2 in human tumor cells. S2. Differential formation of J-aggregates in BE(2)C and SK-N-ER cells. S3. Knockdown of PHB reduces self-renewal of HepG2 hepatocelluar carcinoma cells. S4. Knockdown of PHB reduces clonogenicity of MCF7 human breast cancer cells. S5. Sphere forming potential (A) and clonogenic potential (B) of BE(2)C cells treated with indicated siRNA oligos. S6. DLK1 cytoplasmic domain does not affect protein levels of PHB1 and PHB2.

Supplemental Table S1. Relative expression of stem cell-related genes using RT2 profile PCR array.

Supplemental information includes Supplemental Figure S1. The characterization of SOX2 as an oncogene in bladder cancer, Supplemental Figure S2. Stem cell-related molecules associated with SOX2 expression, Supplemental Figure S3. CD24+/CD133+ as a potential marker for SOX2-expressing CSCs, Supplemental Figure S4. COX2/PGE2 signaling pathway in regulating SOX2, Supplemental Figure S5. The association of PGE2 expression with apoptosis in YAP1-LV or YAP1-sh cells, Supplemental Figure S6. Correlation among SOX2, YAP1, and COX2 expression in human UCB samples, Supplemental Figure S7. CSC expansion following CDDP treatment suppressed by combination treatment with verteporfin and celecoxib, Supplemental Figure S8. The EGFR-regulated YAP1 expression via PI3K signaling in basal-type UCB, and Supplementary Materials and Methods.

Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth-regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2 signaling induced promoter methylation of let-7, resulting in its downregulation and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by binding its enhancer region. In UCB clinical specimens, positive correlations in the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2 and YAP1 particularly commonly observed. Additional investigations suggested that activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings provide a preclinical rationale to target these pathways concurrently with systemic chemotherapy as a strategy to improve the clinical management of UCB.Significance: These findings offer a preclinical rationale to target the COX2 and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical management of UCB, based on evidence that these two pathways expand cancer stem-like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1); 168–81. ©2017 AACR.

Introduction: Fetal distress is a high risk obstetric situation associated with increased perinatal morbidity and mortality. It is also a major contributor to operative interventions in the majority hospitals of developing countries. The objective of this study was to observe clinically diagnosed fetal distress and early neonatal outcome after delivery. Materials and Methods: This hospital based cross-sectional study was carried out in Department of Obstetrics and Gynecology at Bashundhara Addin Medical College Hospital, Keraniganj during the period of January to December 2019. 212 women in active phase of labor at term pregnancy who met the inclusion and exclusion criteria were enrolled. Fetal distress was diagnosed by abnormal FHR and /or presence of meconium in amniotic fluid after rupture of membrane. Neonatal outcome was assesss by 1st & 5th mins Apgar Scores after delivery, babies requiring immediate resuscitation and admission to neonatal care unit & recorded. Result: Among fetal distress 11.32% babies had Apgar score

Background: The rate of mortality is increasing in diabetic patients due to diabetes-associated complications. The common complications include neuropathy, nephropathy, retinopathy, foot ulcer, slow wound healing, kidney dysfunction, amputation, dysfunction of organs, frequent infections, sepsis, skin diseases, hearing impairment, cardiovascular disorders, etc. These complications can be diagnosed following some common symptoms such as increased thirst, frequent urination, extreme hunger, unexplained weight loss, fatigue, irritability, blurred vision, slow-healing sores, etc. This survey was designed to study the prevalence of various complications in a group of diabetic patients so that effective treatment options could be developed against the most prevalent complications. Methods: This cross-sectional study was conducted in 2019 in a tertiary care hospital of Karachi after the approval of the ethical committee of the hospital as well as in the University of Karachi. To perform this study, a questionnaire was designed comprised of different questions related to diabetic complications. The consent form was attached to each questionnaire in which the patient agreed to participate voluntarily in this survey. The diabetic patients who visited the General Physician OPD were the subjects of this survey. All designed questions included in the questionnaire were asked either directly from the patients or their attendants. Results: A total of 160 diabetic subjects were part of the study range between the ages of 11 to 90 years. Out of 160 patients, 52 were males, and 108 were females. Among all subjects, 124 (78 %) patients were type 2 while 57 (36 %) were type 1 diabetic patients. 117 (73 %) showed confusion of mind, 104 (65 %) complained of blood pressure, 105 (66 %) had hypertension, 106 (66 %) had eye damage (retinopathy), 96 (60 %) were facing trouble focusing vision, and 70 (44 %) were experiencing seizures, 63 (39 %) patients had laser treatment, 68 (43 %) showed wounds on foot and slow wounds healing, 49 (31 %) were having kidney damage (nephropathy), 79 (49 %) had pain in legs or knee, 35 (22 %) and 26 (16 %) complained of heart problems and liver damage respectively. Some patients were found to deal with more hunger, i.e., 99 (62 %) patients, 118 (74 %) were experiencing frequent urine desire, 138 (86 %) showed fatigue, 123 (77 %) complained of thirst, 35 (22 %) had nausea, 30 (19 %) had a frequent cold, 36 (23 %) had skin problems, 17 (11 %) patients showed frequent vomiting, 19 (12 %), 13 (8 %) and 16 (10 %) were experiencing acne formation, stroke and nerve damage (neuropathy) respectively. Conclusion: All age groups showed diabetes-associated complications and different abnormal body conditions. However, the age groups ranging from thirty to eighty years showed more complications. The most prevalent complications reported were retinopathy, nephropathy, diabetic wounds on the foot, slow wound healing, seizures, hypertension, neuropathy, skin infections, cardiovascular disorders, liver damage, and stroke in both types of diabetic patients. Our survey may aid in pointing out the most prevalent diabetic complications prevailing in our population so that effective treatment options could be developed to reduce these life-threatening complications.

[Image: see text] RNA polymerase I (Pol I) transcribes ribosomal DNA (rDNA) into the 47S ribosomal RNA (rRNA) precursor. Further processing produces the 28S, 5.8S, and 18S rRNAs that are assembled into mature ribosomes. Many cancers exhibit higher Pol I transcriptional activity, reflecting a need for increased ribosome biogenesis and protein synthesis and making the inhibition of this process an attractive therapeutic strategy. Lead molecule BMH-21 (1) has been established as a Pol I inhibitor by affecting the destruction of RPA194, the Pol I large catalytic subunit. A previous structure–activity relationship (SAR) study uncovered key pharmacophores, but activity was constrained within a tight chemical space. This work details further SAR efforts that have yielded new scaffolds and improved off-target activity while retaining the desired RPA194 degradation potency. Pharmacokinetic profiling was obtained and provides a starting point for further optimization. New compounds present additional opportunities for the development of Pol I inhibitory cancer therapies.

Background: In Bangladesh there is a scarcity of data on the degree of knowledge amongadolescents about reproductive health. Objective: To assess the awareness about reproductivehealth issues among adolescent girls in a rural area of Bangladesh. Materials and method: Thisdescriptive type of cross sectional study was conducted among 148 adolescent girls who wereselected purposively at PurbaChandara village of Kaliakairthana of Shafipurupazilla of Gazipurdistrict in Bangladesh. A pre-tested semi structured questionnaire was used to collect data byface to face interview. Results: Most of the respondents (76.35%) were within the age group of15-19 years. The average age of their menarche was 14 years. Majority of the respondents 136(91.89%) had history of menstruation and 97 (65.54%) mentioned the duration of menstrualcycle > 7 days. Regarding the hygienic practice during menstruation, majority of them (68.24%)were unhygienic. About knowledge on age at marriage, 131 (88.51%) reportedly mentionedcorrect answer that marriage age is 18 years or more for girls. Regarding the knowledge onfamily planning and family planning methods, most of them (41.89%) had no knowledge.About the infection of reproductive tract, 87 (58.78%) had no knowledge and about half of therespondents (92; 56.79%) had no knowledge about symptoms of STDs. Conclusion: it is ourresponsibility to improve the condition of adolescent girls by giving clear and correct knowledgeon reproductive health which will help them to maintain a good and sound reproductive healthin future. Bangladesh Journal of Medical Science Vol.19(3) 2020 p.567-574

Background: Periodontal diseases are inflammatory reactions that affect the supporting tissues of the teeth, which consist of Gingiva, periodontal ligament, root cementum and alveolar bone. The third generation of cephalosporins - cefixime (CEF), which is an antibiotic with wide spectrum of effect on Gram-positive and Gramnegative bacteria, was used in cases of oral infections. Objective: The aim of the study to evaluate the efficacy of non-surgical therapy and combination of amoxicillin and metronidazole compared with cefixime. Methods: The clinical study was conducted at the Department of Periodontology, Clinic for Dentistry of the Khulna Medical College. In order to assess the condition of periodontium, we used the level of gingival inflammation which is expressed through gingival index (GI) according to Loe and Silness, bleeding on probe (BOP), according to M?hlemann and Son, probing depth (PD) and clinical attachment level (CAL). Results: In control group, mean gingival index, bleeding on probing and probing pocket depth were statistically significantly (p

The experimental study on the dynamic behavior of helium atmospheric pressure plasma jet exposed on the surface of different conductivity is reported in this article. Electrical, optical, and gas dynamics characteristics are monitored using a high voltage probe, current probe, and imaging technique. The turbulence-free plasma jet length is estimated from the image of the plasma jet and correlated with the length estimated through the Electrohydrodynamic number (Ehd number). It has been shown that plasma species strongly modify the gas dynamics on the contact surface. The irradiation area on agar gel, metal, and Teflon is observed and the different flow regimes (free jet, stagnant region, and accelerating region) are identified. The irradiation area is significantly broadened for the polymer-like substrate and intensity is higher close to the stagnant region. The excited nitrogen and OH intensity is higher than the other observed chemical species on the target surface. The turbulence is higher near the outer radius of the irradiated surface, and it increases with operating voltage. The chemistry of the water changes with the presence of the metal probe inside the water.

Background The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration ClinicalTrials.gov Identifier: NCT01088815.

Publisher Copyright: © 2022 The Authors RNA Polymerase I (Pol I) synthesizes rRNA, which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing Pol I inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degradation of the largest subunit of Pol I, RPA194. To identify the E3 ligase(s) involved, we conducted a cell-based RNAi screen for ubiquitin pathway genes. We establish Skp–Cullin–F-box protein complex F-box protein FBXL14 as an E3 ligase for RPA194. We show that FBXL14 binds to RPA194 and mediates RPA194 ubiquitination and degradation in cancer cells treated with BMH-21. Mutation analysis in yeast identified lysines 1150, 1153, and 1156 on Rpa190 relevant for the protein degradation. These results reveal the regulated turnover of Pol I, showing that the stability of the catalytic subunit is controlled by the F-box protein FBXL14 in response to transcription stress.

Vitriolage is an extreme form of violence in Bangladesh. The alarming increase in its frequency is a cause of concern. Violence against woman within South Asia includes rape and sexual abuse, trafficking, prostitution, domestic violence, dowry related deaths and psychological abuse. The reported case is of a 25 years old lady affected by acid burn in her face and adjoining part of the head during night while she was sleeping. On medicolegal point of view, the injury was homicidal in nature to run away without having a motive to kill the person. We should create public consciousness against this sort of brutal act. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.336-338

Background: Among term infants, hypoxic-ischemic encephalopathy due to acute perinatal asphyxia remains an important cause of neurodevelopmental deficits in childhood. Treatment is currently limited to supportive intensive care, without any specific brain-oriented therapy. Objective: To determine whether the risk of death or moderate/severe neurodevelopmental impairment in term infants with hypoxic-ischemic encephalopathy increases with relatively high skin or rectal temperature between 12 and 72 hours of birth. Materials and Methods: This was a prospective observational study. Asphyxiated newborns who came within 12 hours of birth were enrolled in this study. Both axillary and rectal temperature were recorded 6 hourly for 72 hours and each infant`s temperature for each site were rank ordered. Then mean of all axillary and rectal temperatures of each neonate was calculated. Outcomes were related to temperatures in logistic regression analyses for the elevated/relatively high temperatures and normal/low temperatures group, with adjustment of the level of encephalopathy and gender. Results: The mean axillary temperature was 36.07 ± 6.10C and in 25.71%, 11.92% and 6.32% cases axillary temperatures were >370C, >37.50C and >380C respectively. The mean rectal temperature was 36.8 ± 60C, and in 43.53%, 30.02% and 19.97% cases rectal temperatures were >370C, >37.50C and >380C respectively. Mean ambient temperature was 26.170C. There was significant correlation between axillary and rectal temperatures (r=0.889). For elevated temperature, the odds of death or moderate to severe impairment increased 8.9-fold (CI 0.906–88.18) and the odds of death alone increased 4.6-fold (CI 0.373–56.83). The odds of impairment increased 1.84-fold (CI 0.45– 7.50). Conclusion: Relatively high temperature during usual care after hypoxic-ischemia in term neonates was associated with adverse neurodevelopmental outcomes. J Enam Med Col 2019; 9(3): 160-165

Self-renewal maintains the long-term clonogenic growth that is required for cancer relapse and progression, but the cellular processes regulating this property are not fully understood. In many diseases, self-renewal is enhanced in cancer stem cells (CSC), and in pancreatic ductal adenocarcinoma (PDAC), CSCs are characterized by the surface expression of CD44. In addition to cell adhesion, CD44 impacts cell shape and morphology by modulating the actin cytoskeleton via Ezrin, a member of the Ezrin/Radixin/Moesin (ERM) family of linker proteins. We examined the expression of Ezrin in PDAC cells and found higher levels of both total and activated Ezrin in CSCs compared with bulk tumor cells. We also found that the knockdown of Ezrin in PDAC cells decreased clonogenic growth, self-renewal, cell migration, and CSC frequency in vitro as well as tumor initiation in vivo. These effects were associated with cytoskeletal changes that are similar to those occurring during the differentiation of normal stem cells, and the inhibition of actin remodeling reversed the impact of Ezrin loss. Finally, targeting Ezrin using a small-molecule inhibitor limited the self-renewal of clinically derived low-passage PDAC xenografts. Our findings demonstrate that Ezrin modulates CSCs properties and may represent a novel target for the treatment of PDAC. Implications: Our findings demonstrate that Ezrin modulates CSCs' properties and may represent a novel target for the treatment of PDAC.

RNA polymerase I inhibitors represent a new class of cancer therapeutics with potential application in many cancer types. By curbing the transcription of ribosomal RNAs they block the rate-limiting step in ribosome biogenesis and protein synthesis. We have recently identified specific and selective first-in-class inhibitors of Pol I. This class of Pol I inhibitors, represented by small-molecule BMH-21, blocks transcription initiation and elongation and causes the destruction of the enzyme catalytic subunit. BMH-21 activity is genetically dependent on Pol I in cancer cells and in yeast confirming the targeting specificity. Our earlier mechanistic and efficacy studies with BMH-21 have demonstrated the utility of the approach in targeting colon and prostate cancers and melanoma. The goal of this study was to pinpoint cancer types with specific sensitivity to these inhibitors and to identify markers of this sensitivity. To do so, we undertook unbiased large-scale cancer cell line screens with our Pol I inhibitors and conducted correlative analyses using open source DepMap and Achilles databases to identify cancer types and features that sensitize cancer cells to these inhibitors. The most sensitive lineages were colorectal, endometrial, esophageal, leukemia, myeloma, and ovarian. Comparison of the cancer cell line responses to the Achilles gene essentiality database showed high correlation to genetic knock-out of three Pol I subunits. This unbiased finding strongly supports identification of Pol I as the target. Further, we identified two ribosomal proteins, RPL22 and RPL22L1 as the top genetic and expression markers denoting sensitivity, and MDM4, a p53 transcriptional repressor, as the top protein marker. Together, these three markers conform to a new p53 regulatory pathway. These findings were validated using genetic and mechanistic analyses. We show that Pol I inhibition alters the MDM4 splicing and decreases the expression of MDM4 isoform that represses p53, and that this activity is dependent on the RPL22/RPL22L1 proteins. Notably, perturbation of the biomarkers is strongly associated with mismatch repair defective (MMRd) cancers. We show the efficacy of the Pol I inhibitors in xenograft and patient-derived MMRd models. Our data suggest that RPL22mutation could serve as tumor-agnostic biomarker for targeting cancers with the Pol I inhibitors. Furthermore, this work identifies a new Pol I transcription-dependent ribosomal protein-governed pathway that converges on the regulation of p53. Citation Format: Wenjun Fan, Hester Liu, Asma Begum, Stephanie Pitts, Brittany Ford, Tony Dorado, Pablo de Leon, Rajeshkumar NV, James C. Barrow, Marikki Laiho. Therapeutic inhibition of RNA polymerase I reveals vulnerability of mismatch repair defective cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2644.

Nuclear energy renders itself as one of the sustainable energy sources for power production available now. But the major nuclear accident that occurred in the nuclear industry has shown that the generation of nuclear energy has an inherent risk for the environment and the eco-system. Therefore, members of the public - the principal stakeholders - shall be provided with significant opportunities for their engagement in every phase of construction of the Nuclear Power Plant (NPP). National and regional level public support is very important for the implementation of the first-ever NPP of Bangladesh, the Rooppur NPP (24°4′0″N 89°2′50″E) as well as for the future power plant of the country. This paper analyses public awareness and stakeholder involvement systems in the nuclear energy establishment process in Bangladesh. According to the best international practices settled by the IAEA and national authorities like the Rosatom, this paper recommends certain solutions to the improvement of the public outreach mechanism for the construction of NPP in Bangladesh.

The ongoing health crisis has impacted businesses worldwide, drastically reducing production, consumption and distribution of goods and services, leading to an economic downturn. An increasing unemployment rate has led to a surge in the sense of job insecurity among employees. Lack of job security has a direct impact on an employee’s health and work–life balance. This article focusses on the relationship between and impact of job insecurity on work–life balance, that is, to understand the impact of perceived job insecurity on working hours, employee’s health and reduced family time. Using a self-completed questionnaire, data was collected from 413 employees from different sectors like construction, banks, hospitals, hotels, schools, FMCG, telecommunication, etc., in India, which assisted in testing five hypotheses. The study found a positive relationship between job insecurity and health issues and work–life conflict. Additionally, job insecurity was negatively linked with job performance. Regression analysis showed mediating effects of work demand, work time, family time and family demand on the relationship of job insecurity with health issues, job performance and work–life conflict. However, the article also discusses various effective mechanisms to reduce job insecurity and ways to curb its negative impacts on various organizational and personal outcomes.

Background: Oral health is associated to general health and one of the most common chronic diseases is diabetes mellitus. Diabetes can have difficult effects on oral health. Several studies have shown that some oral disease like gingivitis, periodontitis, and periapical lesion can be complicated by the severity of diabetes. Objective: To compare the healing after tooth extraction in diabetic versus non-diabetic patients. Methodology: This prospective clinical trial consists of one hundred patients that were recruited in to two groups having 50 known diabetic (type 1 and type 2) and 50 non-diabetic. All Patients above ten years and both genders were included in this study through consecutive sampling. Patients with any other systemic illness and those on anticoagulants and steroids were excluded from the study. Tooth extraction was carried out for all patients under aseptic conditions, and these patients were recalled after one week for a clinical and radiological examination after tooth extraction assesses its healing status. Results: Majority (40.0%) patients were hypertension in diabetic group and 31(62.0%) in non diabetic group. Mean negative attitude score was found 17.4?3.3 in diabetic group and 15.6?3.1 in non diabetic group. Twenty two (44.0%) patients were abnormal healing in diabetic group and 4(8.0%) in non diabetic group. The difference was statistically significant (p

The 2017 political violence against the Rohingya people in the state of Rakhine resulted in a large influx of displaced populations into Bangladesh. Given harsh conditions and experiences in Myanmar, and the harrowing journey to the border, raised levels of child neurodevelopmental disorders (NDDs) and mental health problems were expected.A team of child development professionals, physicians, psychologists, and developmental therapists screened 622 children in clinics within the refugee camps using the Developmental Screening Questionnaire (DSQ; 0-2 years), and the Ten Questions Plus (TQP) for NDDs, and Strengths and Difficulties Questionnaire (SDQ; 2-16 years) for mental health problems. Any child positive on the DSQ or the TQP was assessed for NDDs.Only 4.8% children aged 0-2 years and 7.3% children aged2-16 years screened positive for NDDs, comparable with a local Bangladesh population. However, 52% of children were in the abnormal range for emotional symptoms on the SDQ, and 25% abnormal for peer problems. Significant risk factors were being parentless and having lost one or more family members in the recent crisis.This screening study provides objective evidence of the urgent need for psychosocial support of Rohingya children within camps, with special attention to those without parents, including monitoring of their well-being and counselling of families and other care providers.

Background: Burns are a global public health problem.Objectives: To find out the status of burn victims along with the causes and consequences of fatal burn injuries.Material and method: The data is collected from the autopsy reports of Dhaka Medical College in 2012. The purpose of this study was to record and evaluate the causes and magnitude of the fatal burn injuries.Results: In 2012, among total 2527 deaths reported at Dhaka Medical College, 158 (6.25%) cases were due to burn. The victims within 21 to 40 years were more vulnerable in comparison to other age groups. Female were more vulnerable than male (55.69% vs. 44.31%). Accidental burn was the commonest cause (55%).Conclusion: Thermal burns and related injuries are major cause of death and disability all over the world as well as Bangladesh. Detail study regarding flame burn is required to be carried out in this country.Delta Med Col J. Jan 2018 6(2): 82-85

Chronic arsenic exposure is associated with the development of urothelial carcinoma of the bladder (UCB). To elucidate the contribution of arsenic exposure to urothelial cancer stem cell (CSC) generation, we established an in vitro stepwise malignant model transformed by chronically exposing human urothelial cells to arsenic. Using this model, we found that chronic arsenic exposure endows urothelial cells with malignant stemness properties including increased expression of stemness-related factors such as SOX2, sphere formation, self-renewal, invasion and chemoresistance. SOX2 was gradually and irreversibly overexpressed in line with acquired sphere-forming and self-renewal abilities. Following gene set enrichment analyses of arsenic-exposed and arsenic-unexposed cells, we found COX2 as an enriched gene for oncogenic signature. Mechanistically, arsenic-induced COX2/PGE2 increases SOX2 expression that eventually promotes malignant stem cell generation and repopulation. In urine samples from 90 subjects exposed to arsenic and 91 control subjects, we found a significant linear correlation between SOX2 and COX2 expression and the potential of SOX2 and COX2 expression as urinary markers to detect subjects exposed to arsenic. Furthermore, the combination marker yielded a high sensitivity for UCB detection in a separate cohort. Finally, our in vitro model exhibits basal-type molecular features and dual inhibition of EGFR and COX2 attenuated stem cell enrichment more efficiently than an EGFR inhibitor alone. In conclusion, the COX2/PGE2-SOX2 axis promotes arsenic-induced malignant stem cell transformation. In addition, our findings indicate the possible use of SOX2 and COX2 expression as urinary markers for the risk stratification and detection of UCB.

Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here, we report that the proinflammatory COX2/PGE2 pathway and the YAP1 growth-regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSCs. Mechanistically, COX2/PGE2 signaling induced promoter methylation of let-7, resulting in its downregulation and subsequent SOX2 upregulation. YAP1 induced SOX2 expression more directly by binding its enhancer region. In UCB clinical specimens, positive correlations in the expression of SOX2, COX2, and YAP1 were observed, with coexpression of COX2 and YAP1 particularly commonly observed. Additional investigations suggested that activation of the COX2/PGE2 and YAP1 pathways also promoted acquired resistance to EGFR inhibitors in basal-type UCB. In a mouse xenograft model of UCB, dual inhibition of COX2 and YAP1 elicited a long-lasting therapeutic response by limiting CSC expansion after chemotherapy and EGFR inhibition. Our findings provide a preclinical rationale to target these pathways concurrently with systemic chemotherapy as a strategy to improve the clinical management of UCB. Significance: These findings offer a preclinical rationale to target the COX2 and YAP1 pathways concurrently with systemic chemotherapy to improve the clinical management of UCB, based on evidence that these two pathways expand cancer stem-like cell populations that mediate resistance to chemotherapy. Cancer Res; 78(1); 168–81. ©2017 AACR.

Background: Both clinical audits within hospitals, and population-based surveys of childhood disability in Bangladesh, have shown that large numbers of children have speech and language difficulties. This study determined the improvement of language skills of children presenting with difficulties to the Speech, Language and Communication (SLC) clinic of the Child Development Center (CDC) in Dhaka Shishu (Children) Hospital (DSH). Methodology: This is a retrospective study where records of children enrolled from April 2009 to March 2014, who had visited the SLC Clinic at least 3 times over a span of 6 months were analyzed. Preverbal language skills, comprehension, and expressive language levels were measured informally based upon play and interactive sessions and observation of function. Interventions involved training parents on informal intervention techniques following some international standard guidelines. Pre and post-intervention observations on preverbal, comprehensive, and expressive language skills were recorded to determine outcomes. Results: Of the 706 enrolled children 11.0%, 79.2%, 9.5%, .3% were 0-5-9 and 10-16 years old, respectively. 69.5% of children were males. Preverbal skills (attention span, awaiting, eye contact, attention sharing, turn-taking, copying), comprehension, and expressive language status showed significant improvement between the first and last visit (p= 0.000) Conclusions: Interactive play, music, books, etc. are important means of improving communication between parents and children. Professionals working with developmentally delayed children need to be trained to utilize these strategies, with the provision of appropriate facilities within clinical settings. A large majority of children can be assisted to overcome delays and optimize their potential.

Percutaneous Coronary Intervention (PCI) is the most commonly performed invasive therapeutic cardiac procedure and plays an important role in the treatment of ischemic heart disease. Complications of Percutaneous Coronary Intervention (PCI) are relatively infrequent. The most common complications include discomfort and bleeding at the puncture site where the catheter was inserted. Major complications include death, MI, or stroke and other infrequent complications include transient ischemic attacks (minor myocardial injury), vascular complication and contrast induced nephropathy, transient ischemia, or minor myocardial injury (MMI), myocardial necrosis due to compromisation of threatened coronary circulation during balloon inflation. Cardiac Troponin I (cTnI) assays for the assessment of myocardial injury has been demonstrated for the diagnosis of MMI and long term prognosis after PCI.Delta Med Col J. Jul 2017 5(2): 94-98

Background: Hanging is always suicidal unless otherwise proved. It is a form of violent asphyxial death. It produces painless death for the victims so that it is a widely practiced method of suicide. In Bangladesh hanging is one of the commonest methods of suicide. Objective: The objective of this study was to find out socio-demographic characteristics of victims, common ligature materials used by victims and post-mortem findings. Materials and method: A retrospective cross sectional study was done in Dhaka Medical College Mortuary during the period of January 2009 to January 2010. During this period data were collected from 2133 cases of medicolegal autopsies by purposive sampling. Results: A total of 2133 medicolegal autopsies were analyzed of which 78 (3.65%) were deaths due to hanging. Out of these 78 cases maximum 37 (47.44%) deaths due to hanging were in the age group of 21-30 years. Majority of the cases (48; 61.54%) were observed in females. Majority (32; 41.03%) of victims had used Dopatta (orna) as a ligature material. Cyanosis of fingertips and nail beds was the commonest (75; 96.15%) findings in cases of asphyxial death due to hanging. Conclusion: Suicidal hanging is observed in this study mostly within the young age group ranging from 21-30 yrs. So, awareness at the level of family and community should be raised to improve personal and social relation in every sphere. The factors provoking an individual for an attempt to suicide should also be investigated for its prevention. Delta Med Col J. Jul 2017 5(2): 89-93

Tumor suppressor and upstream master kinase Liver kinase B1 (LKB1) plays a significant role in suppressing cancer growth and metastatic progression. We show that low-LKB1 expression significantly correlates with poor survival outcome in breast cancer. In line with this observation, loss-of-LKB1 rendered breast cancer cells highly migratory and invasive, attaining cancer stem cell-like phenotype. Accordingly, LKB1-null breast cancer cells exhibited an increased ability to form mammospheres and elevated expression of pluripotency-factors (Oct4, Nanog and Sox2), properties also observed in spontaneous tumors in Lkb1−/− mice. Conversely, LKB1-overexpression in LKB1-null cells abrogated invasion, migration and mammosphere-formation. Honokiol (HNK), a bioactive molecule from Magnolia grandiflora increased LKB1 expression, inhibited individual cell-motility and abrogated the stem-like phenotype of breast cancer cells by reducing the formation of mammosphere, expression of pluripotency-factors and aldehyde dehydrogenase activity. LKB1, and its substrate, AMP-dependent protein kinase (AMPK) are important for HNK-mediated inhibition of pluripotency factors since LKB1-silencing and AMPK-inhibition abrogated, while LKB1-overexpression and AMPK-activation potentiated HNK’s effects. Mechanistic studies showed that HNK inhibited Stat3-phosphorylation/activation in an LKB1-dependent manner, preventing its recruitment to canonical binding-sites in the promoters of Nanog, Oct4 and Sox2. Thus, inhibition of the coactivation-function of Stat3 resulted in suppression of expression of pluripotency factors. Further, we showed that HNK inhibited breast tumorigenesis in mice in an LKB1-dependent manner. Molecular analyses of HNK-treated xenografts corroborated our in vitro mechanistic findings. Collectively, these results present the first in vitro and in vivo evidence to support crosstalk between LKB1, Stat3 and pluripotency factors in breast cancer and effective anticancer modulation of this axis with HNK treatment.

Background: Violence against women has many forms including physical aggression or threats, sexual abuse, emotional abuse, controlling or domineering, intimidation, stalking, passive/covert abuse, and economic deprivations. Alcohol consumption and mental illness can be co-morbid with abuse and present additional challenges when present alongside patterns of abuse. Objective: The objective of this study was to find out the status of victims of Violence against Women along with the causes and consequences of this heinous crime. Materials and method: A retrospective cross sectional study was done in Dhaka Medical College on the victims who underwent treatment at One Stop Crisis Centre (OCC) and burn unit. The victims were interviewed and the data received were later on analyzed by computer and organized in tables. Total cases of Violence against Women were 1143 during the study period. Due permission was taken from the authority. Results: Among the victims about 63% belonged to 16 to 30 years of age group. Most of the victims (56%) were from low socioeconomic conditions, 60% of them were housewife and most of the victims (71%) were married. Dowry cases and familial conflict (33% and 32% respectively) were the main background behind Violence against Women. Conclusion: At community level, improvement of economic status of women as well as women empowerment is essential. Mass awareness about Violence against Women through mass media is needed to be diffused. Delta Med Col J. Jan 2017 5(1): 25-29

Despite improved outcomes in newly diagnosed multiple myeloma, virtually all patients relapse and ultimately develop drug-resistant disease. Aberrant RAS/MAPK signaling is activated in the majority of relapsed/refractory multiple myeloma patients, but its biological consequences are not fully understood. Self-renewal, as defined by the long-term maintenance of clonogenic growth, is essential for disease relapse, and we examined the role of RAS/MAPK activation on multiple myeloma self-renewal by targeting IQ motif–containing GTPase-activating protein 1 (IQGAP1), an intracellular scaffold protein required for mutant RAS signaling. We found that loss of IQGAP1 expression decreased MAPK signaling, cell-cycle progression, and tumor colony formation. Similarly, a peptide mimicking the WW domain of IQGAP1 that interacts with ERK inhibited the clonogenic growth and self-renewal of multiple myeloma cell lines and primary clinical specimens in vitro as well as tumor-initiating cell frequency in immunodeficient mice. During multiple myeloma progression, self-renewal may be enhanced by aberrant RAS/MAPK signaling and inhibited by targeting IQGAP1. Mol Cancer Ther; 15(11); 2733–9. ©2016 AACR.

Objectives IQ motif containing GTPase-activating protein 1 (IQGAP1) acts as a scaffold for aberrant mitogen-activated protein kinase (MAPK) signaling driven by KRAS mutations in pancreatic ductal adenocarcinoma (PDAC). We determined the role of IQGAP1 in clonogenic growth and metastasis in PDAC. Methods We inhibited IQGAP1 expression using shRNA and assessed clonogenic growth, cell migration, and MAPK signaling in vitro and tumor initiation and metastasis in vivo. The efficacy of a peptide mimicking the IQGAP1 WW domain that binds and inhibits ERK1/2 was determined in vitro and in vivo. Results IQGAP1 loss inhibited clonogenic growth and migration of KRAS-dependent PDAC cells by disrupting MAPK signaling. In mice, IQGAP1 knockdown decreased tumor-initiating cell frequency and metastasis. WW peptide treatment inhibited clonogenic growth and in vivo tumor growth. Conclusions Pancreatic ductal adenocarcinoma clonogenic growth, metastasis, and tumor initiation are dependent on MAPK signaling via IQGAP1. Treatment with a WW peptide disrupts IQGAP1 function and represents a novel targeting strategy for PDAC.

OBJECTIVE To validate a Rapid Neurodevelopmental Assessment (RNDA) tool for use by child health professionals to determine neurodevelopmental impairments (NDIs) in young adolescents aged 10-16 years in Bangladesh. STUDY DESIGN In a convenience sample of community children (n = 47), inter-rater reliability was determined between four testers, and concurrent validity was determined by simultaneous administration of an intelligence quotient (IQ) test (Wechsler Intelligence Scale for Children, Revised) by a child psychologist. RESULTS Inter-rater reliability was excellent between the testers on the 47 children administered the RNDA (kappa = 1.00). Significantly lower IQ scores were obtained in those identified with 'any (>1) NDI' (n = 34) compared with those with no NDI (n = 13) on Verbal IQ (P-value < 0.0001), Performance IQ (P-value < 0.0001) and Full-scale IQ (P-value < 0.0001) scores on the Wechsler Intelligence Scale for Children, Revised. CONCLUSION The RNDA shows promise as a tool for use by child health professionals for identifying NDIs in young adolescents aged 10-16 years. A larger study sample is needed to determine its usefulness for identification of some impairments not found in the study population, i.e. gross motor, fine motor, hearing and seizures.

Escilatopram is an orally administered selective serotonin reuptake inhibitor (SSRI). The ADRs associated with Escilatopram are- abnormal bleeding, Hyponatremia, activation of Mania/Hypomania, Seizures, Interference with Cognitive and Motor Performance. Also it has got serious Drug-Drug Interactions with a variety of drugs. A female patient of age 60 years was brought to casualty with hypertensive urgency. She was put on metoprolol, amlodipine, telmisartan and hydrochlorthiazide combination, escilatopram and clonazepam combination, along with other drugs. On day 2 her lab reports stated dyselectrolytemia and upon analysing the prescription, it was found that there were many drug- drug interactions. By avoiding such combination of drugs and also by choosing an appropriate antidepressant, such adverse effects could have been averted. KEYWORDS: Escilatopram, Hyponatremia, Elderly people, Antidepressants, SSRI.

Background: Every year, world wide, 200 million women become pregnant. The development of urban areas allowed women to receive more care and treatment. However, in rural areas such measures are not available to every woman. Data on delivery practice of rural woman may help the social and public health planners and decision makers to minimize and prevent maternal mortality and morbidity ensuring safe motherhood. Objective: The aim of the study was to observe the delivery practice of rural women of Bangladesh. Materials and method: A cross-sectional study was conducted and data were collected from Dhamrai upazila, Dhaka, Bangladesh in April 2008. Total 159 women of reproductive age group at least having one child were selected purposively to elicit information on various demographic, socioeconomic, cultural and selected programmatic variables including maternal health care and delivery practices. Results: Among the respondents about 55% were literate. Majority (80%) of the respondents delivered at home and most of the them (71%) felt that home delivery was comfortable where as about 29% of the respondents were compelled to deliver at home due to family decision and financial constraint. Among the deliveries about 82% occurred normally and 18.2% were by cesarean section. A considerable percentage of deliveries (49%) were attended by traditional birth attendants. Blade was used for cutting umbilical cord in majority of the cases (74%) who delivered at home. Most of the respondents (90%) took ante natal check up and about 74% were vaccinated by tetanus toxoid. Conclusion: The results of the study suggest that a lot of work is still to do for the policy makers and health planners to target, plan, develop and deliver maternal health services to the rural women of Bangladesh. DOI: http://dx.doi.org/10.3329/dmcj.v1i2.15917 Delta Med Col J. Jul 2013;1(2):42-45

OBJECTIVE: Validate a tool to determine neurodevelopmental impairments (NDIs) in >2- to 5-year-old children in a country with limited child development expertise. METHODS: Rapid Neurodevelopmental Assessment (RNDA) is a tool designed to detect functional status and NDIs across multiple neurodevelopmental domains. Validity was determined in 77 children enrolled by door-to-door sampling in Dhaka and who were administered the RNDA by 1 of 6 testers (4 developmental therapists, 2 special education teachers) and simultaneously administered a test of adaptive behavior (AB; Independent Behavior Assessment Scale) and intelligence quotient (IQ) tests (Bayley Scales of Infant Development II, Stanford Binet Intelligence Scale, Wechsler Preschool and Primary Scales of Intelligence) by psychologists. RESULTS: Interrater reliability ranged from good to excellent. There were significant differences in AB in mean percentile scores on the Independent Behavior Assessment Scale for motor (P = .0001), socialization (P = .001), communication (P = .001), and full-scale (P = .001) scores in children with ≥1 NDI (“any NDI”) versus no NDI. Significant differences in those with versus those without “any NDI” were found on IQ scores. Sensitivity and specificity for “significant difficulties” (defined as AB z-scores < −2 SDs and/or IQ CONCLUSIONS: The RNDA validity results are promising for use by child care professionals in field and clinical settings, but the tool needs further replication and refinement for assessment of specific impairments of vision, hearing, and seizures.

Background Home-based screening to identify young children at risk for neurodevelopmental impairments (NDIs) is needed to guide the targeting of child neurodevelopmental intervention services in Bangladesh. This study aimed to validate such a tool for children under age 2 years. Methods A Developmental Screening Questionnaire was administered to mothers of children aged 0–

The stem cell-like characteristics of tumor cells are not only essential for tumor development and malignant progression, but also significantly contribute to therapy resistance. However, it remains poorly understood how cancer cell differentiation or stemness is regulated in vivo. We investigated the role of the stem cell gene DLK1, or delta-like 1 homolog (Drosophila), in the regulation of cancer cell differentiation in vivo using neuroblastoma (NB) xenografts as a model. We found that loss-of-function mutants of DLK1 significantly enhanced NB cell differentiation in vivo likely by increasing the basal phosphorylation of MEK and ERK kinases, a mechanism that has been shown to facilitate neuronal differentiation. We also found that DLK1(+) cells are preferentially located in hypoxic regions. These results clearly demonstrate that DLK1 plays an important role in the maintenance of undifferentiated, stem cell-like phenotypes of NB cells in vivo.

Stabbing is the most common method of homicide in developing countries like Bangladesh, due to poverty, over population, joblessness, political unrest, etc. The reported case is of a 27 years old man stabbed on the front of the left thigh, a relatively unusual site by a sharp pointed knife by some snatchers while sitting on a rickshaw. On medicolegal point of view the injury was homicidal in nature to run away without having a motive to kill the person. The site was easily approachable for the snatchers. We need to create awareness among general population about the circumstances and probable mishaps that can happen unexpectedly. DOI: http://dx.doi.org/10.3329/dmcj.v2i1.17795 Delta Med Col J. Jan 2014; 2(1): 36-38

OBJECTIVE: To develop a simple tool for assessing the severity of disability resulting from Japanese encephalitis and whether, as a result, a child is likely to be dependent. METHODS: A new outcome score based on a 15-item questionnaire was developed after a literature review, examination of current assessment tools, discussion with experts and a pilot study. The score was used to evaluate 100 children in Malaysia (56 Japanese encephalitis patients, 2 patients with encephalitis of unknown etiology and 42 controls) and 95 in India (36 Japanese encephalitis patients, 41 patients with encephalitis of unknown etiology and 18 controls). Inter- and intra-observer variability in the outcome score was determined and the score was compared with full clinical assessment. FINDINGS: There was good inter-observer agreement on using the new score to identify likely dependency (K = 0.942 for Malaysian children; K = 0.786 for Indian children) and good intra-observer agreement (K = 1.000 and 0.902, respectively). In addition, agreement between the new score and clinical assessment was also good (K = 0.906 and 0.762, respectively). The sensitivity and specificity of the new score for identifying children likely to be dependent were 100% and 98.4% in Malaysia and 100% and 93.8% in India. Positive and negative predictive values were 84.2% and 100% in Malaysia and 65.6% and 100% in India. CONCLUSION: The new tool for assessing disability in children after Japanese encephalitis was simple to use and scores correlated well with clinical assessment.