Search

The research aims to elaborate on the management of talent and interest development in students at Islamic High School (Madrasah Aliyah Negeri, MAN) 1 Tidore and identify the supporting and inhibiting factors in the management of developing interests and talents in students at MAN 1 Tidore. The results showed that talent and interest development management was managed by the deputy head of student affairs, extracurricular coaches, student organization coaches, and students council (OSIS). Management stages include planning, implementation, and evaluation stages. This research contributes to the management studies on developing students' talents and interests in Islamic schools integrated into the school system and elaborates on the supporting and inhibiting factors. The supporting factors for the implementation of the management of the development of student's talents and interests include the solid cooperation and performance of all madrasah parties, the effective and efficient use of funds through BOS funds, adequate facilities and infrastructure, and the figure factor of the principal of MAN 1 Tidore. The inhibiting factors include spreading Covid-19 and natural/weather factors, irregular (routine) extracurricular activities, and the absence of counselor teachers.

Background: There is increasing interest in enhancing the response of the PARP inhibitor olaparib, which is currently approved for pancreatic ductal adenocarcinoma (PDAC) patients with defects in DNA damage repair associated with germline BRCA1/2 mutations. Moreover, agents that can mimic these defects in the absence of germline BRCA1/2 mutations are an area of active research in hopes of increasing the number of patients eligible for treatment with PARP inhibitors. The extent to which regorafenib, an FDA-approved tyrosine kinase inhibitor, can be used to enhance the efficacy of PARP inhibitors in PDAC cells without known BRCA1/2 mutations remains to be investigated., Methods: Comet assay, cell cycle analysis, western blotting, and immunofluorescent detection of H2AX S139 were used to evaluate the extent to which regorafenib induces DNA damage in PDAC cell lines. The effects of regorafenib, either alone or in combination with PARPi inhibitors, on PDAC cell death were assessed by Annexin V/PI co-staining assay in cell lines and by immunohistochemistry staining for cleaved caspase-3 in mouse tumors and in ex vivo slice cultures of human PDAC tumors. Flow cytometry-based analysis was used to evaluate the ability of regorafenib to reprogram PDAC tumor microenvironment., Results: We now show that regorafenib, a tyrosine-kinase inhibitor with efficacy in several gastrointestinal malignancies, can enhance the response of olaparib in pancreatic cancer. While regorafenib induces DNA damage and limits the ability of PDAC cells to resolve the damage, regorafenib by itself does not induce apoptosis. However, regorafenib in combination with olaparib further induces DNA damage in vitro, in tumor-bearing mice, and in ex vivo slice cultures of human PDAC tumors, resulting in increased apoptosis compared to olaparib alone. Notably, we show that the efficacy of the combination treatment is not dependent on cytolytic T cells., Conclusions: Together, these findings demonstrate that regorafenib can attenuate DNA damage response and potentiate the efficacy of PARP inhibitors in PDAC tumors., Competing Interests: Declarations. Ethics approval and consent to participate: For human studies, pancreatic tissue was obtained from patients with PDAC undergoing resection on a protocol approved by the Institutional Review Board of Northwestern University. Informed consent was obtained from patients before resection. All resected specimens were deidentified. All experiments on human specimens were performed in accordance with relevant guidelines and regulations. All mouse studies were conducted under protocols approved by the Institutional Animal Care and Use Committee (IACUC) Office at Northwestern University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of FIO. In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with six to eight cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a proinflammatory immune profile similar to human PDAC tumors after neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining trametinib and anti-PD-1 antibodies in patients with PDAC after neoadjuvant or short-term FOLFIRINOX treatment to achieve effective antitumor responses., (©2024 American Association for Cancer Research.)

Biallelic mutations in Protein O-mannosyltransferase 1 (POMT1) are among the most common causes of a severe group of congenital muscular dystrophies (CMDs) known as dystroglycanopathies. POMT1 is a glycosyltransferase responsible for the attachment of a functional glycan mediating interactions between the transmembrane glycoprotein dystroglycan and its binding partners in the extracellular matrix (ECM). Disruptions in these cell-ECM interactions lead to multiple developmental defects causing brain and eye malformations in addition to CMD. Removing Pomt1 in the mouse leads to early embryonic death due to the essential role of dystroglycan during placental formation in rodents. Here, we characterized and validated a model of pomt1 loss of function in the zebrafish showing that developmental defects found in individuals affected by dystroglycanopathies can be recapitulated in the fish. We also discovered that pomt1 mRNA provided by the mother in the oocyte supports dystroglycan glycosylation during the first few weeks of development. Muscle disease, retinal synapse formation deficits, and axon guidance defects can only be uncovered during the first week post fertilization by generating knock-out embryos from knock-out mothers. Conversely, maternal pomt1 from heterozygous mothers was sufficient to sustain muscle, eye, and brain development only leading to loss of photoreceptor synapses at 30 days post fertilization. Our findings show that it is important to define the contribution of maternal mRNA while developing zebrafish models of dystroglycanopathies and that offspring generated from heterozygous and knock-out mothers can be used to differentiate the role of dystroglycan glycosylation in tissue formation and maintenance., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa . Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

This scoping review summarises the findings of research conducted on cancer screening in Bangladesh, including the prevalence, awareness, barriers, and evaluation of screening programmes, by performing a comprehensive search of electronic databases and gray literature. 25 studies that met inclusion criteria were included in the final analysis. Most of the studies were about screening for cervical cancer, were quantitative, were cross-sectional, and were conducted in hospital settings. The main challenges to screening uptake were shyness, fear, a lack of knowledge, and an inadequate understanding of the concept of screening. Visual inspection with acetic acid (VIA) was found to be a simple and cost-efficient way to detect early-stage cervical cancer. However, breast self-examination (BSE) was reported to be insufficient. Education was found to have a positive impact on cancer screening knowledge and practice, but more needs to be done to improve screening rates, such as the utilisation of media, particularly in rural areas. The results of this scoping review highlight Bangladesh's low cancer screening prevalence and uptake and suggest that targeted awareness campaigns and enhanced access to screening services are required to increase cancer screening uptake and reduce the cancer burden in Bangladesh.

Background and aim Antenatal care (ANC) is universally acknowledged as an essential intervention for enhancing the well-being of both mothers and children. The World Health Organization advises a minimum of four ANC visits. The objective of this study is to assess the effectiveness of adequate ANC in mitigating adverse perinatal outcomes. Methods This cross-sectional study was done at the Department of Obstetrics and Gynecology, Delta Medical College & Hospital, Bangladesh, from March 2023 to August 2023. A total of 226 mothers who gave birth at the hospital during this period were enrolled in the study. Results More than 87% of the participants received adequate (≥4 visits) antenatal care from a registered physician. More than 84% of the mothers gave birth via cesarean section. Among the mothers who received inadequate ANC, the proportion of adverse perinatal outcomes was higher (69.0%) than that of those who received adequate ANC (32.0%). A significant association (p<0.05) was noted between inadequate antenatal care and adverse perinatal outcomes. Pregnant women receiving adequate antenatal checkups were 79% less likely to experience adverse perinatal outcomes compared to those receiving inadequate ANC. Conclusion Adequate ANC is a very efficient and economical strategy for mitigating adverse perinatal outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mina et al.)

Background: Patient adherence is important for maximizing patient outcomes. The purpose of this randomized controlled trial was to determine patient adherence and confidence in home therapy exercises of the hand and wrist at multiple time points when distributed by either paper handout or video., Methods: Patients were prospectively enrolled and randomized in orthopedic clinics to either the handout or video exercise group. Exclusion criteria included patients less than 18 years old. Questionnaires were electronically distributed each week for 4 weeks following enrollment. Questionnaires assessed the frequency of exercise performance, percentage of exercises utilized, and confidence in performing the exercises correctly. The handout and video groups were compared via 2-sample t tests for continuous data and χ 2 tests for categorical data., Results: Of the 89 patients enrolled, 71 patients responded to the initial follow-up survey (80% of randomized patients), and 54 of these patients (76%) completed all surveys at each time point. The handout group (37 patients) and the video group (34 patients) had no differences in response rate or demographics. There were no differences in frequency, exercise utilization rate, or confidence in performing exercises between groups at week 1. However, the video group reported higher exercise utilization and confidence than the handout group at subsequent time points., Conclusions: Video-format distribution of home therapy exercises is superior to that of paper handout distribution for the distal upper extremity rehabilitation. Patients in the video group utilized more exercises and had higher confidence in completing them correctly following initiation of the exercise program.

Background: Cancer remains one of the primary causes of death in Bangladesh. The success of cancer control in rural areas depends on the ability of the health care system and workforce to identify and manage cases properly at early stages. Community Health Workers (CHW) can play a vital role in this process. The present study aims to assess cancer related Knowledge, Attitude, and Practice (KAP) among 2 categories of CHWs - Community Health Care Providers (CHCP) and Health Assistants (HA) in rural Bangladesh., Methods: A descriptive cross-sectional study was conducted using a self-administered questionnaire from July 2019 to June 2020. Multi-stage sampling technique was used to determine the sample. One Upazilla Health Complex (UHC) from each of the eight administrative divisions of Bangladesh were randomly chosen as study sites, from which 325 CHCPs and HAs were in the final sample. Multivariate logistic regression models were developed to determine the association between KAP scores and demographic variables., Results: Our study shows that a modest number of respondents scored above average in the knowledge (54.15%), attitude (58.15%), and practice (65.54%) sections. Majority CHCPs (90.91%) and HAs (96.06%) did not receive govt. training on cancer. Only 20.71% HAs and 25.2% CHCPs knew about the availability of cancer treatment options in Bangladesh. Uncertainty about the availability of relevant treatments or vaccinations at public facilities was also high. Having cancer in the family, income, duration of employment and workplace locations were important predictors of cancer related KAP scores., Conclusion: Healthcare workforce's knowledge gap and unfavorable attitude towards cancer may result in poor delivery of care at the rural level. For many people in rural areas, CHCPs and HAs are the first point of contact with the healthcare system and thus effective cancer control strategies must consider them as key stakeholders. Targeted training programs must be adopted to address the cancer related KAP gaps among CHCPs and HAs.

In the present study, we investigated potential of chitosan-based nanoparticles (CNPs) to deliver loaded therapeutic molecules to pathogen harboring macrophages. We fabricated stable CNPs employing ionic cross-linking method and evaluated their potential to target RAW 264.7 cells. The physicochemical characterization of as-synthesized CNPs was determined using electron microscopy, infrared microscopy and zeta potential measurement. Next, cellular uptake and intracellular localization studies of CNPs were followed in living RAW264.7 cells using confocal microscopy. We found that both Acr-1 loaded (CNP-A) and 4-SO 4 -GalNAc ligand harboring (CNP-L) chitosan nanoparticle experience increased cellular uptake by Mycobacterium smegmatis infected RAW cells. Following cellular digestion in model macrophage cell line (RAW), CNPs provide an increased immune response. Further, 4-SO 4 -GalNAc bearing CNP-L exhibits high binding affinity as well as antibacterial efficacy toward M. smegmatis . The data of the present study suggest that CNP-based nanoparticle offer a promising delivery strategy to target infected macrophages for prevention and eradication of intracellular pathogens such as M. smegmatis .

Mycobacterium tuberculosis (M.tb) contrives intracellular abode as a strategy to combat antibody onslaught. Additionally, to thrive against hostile ambiance inside host macrophages, the pathogen inhibits phago-lysosomal fusion. Finally, to further defy host cell offensives, M.tb opts for dormant phase, where it turns off or slows down most of its metabolic process as an added stratagem. While M.tb restrains most of its metabolic activities during dormancy, surprisingly latency-associated alpha-crystallin protein (Acr-1) is expressed most prominently during this phase. Interestingly, several previous studies described the potential of Acr-1 to induce the robust immuno-prophylactic response in the immunized host. It is intriguing to comprehend the apparent discrepancy that the microbe M.tb overexpresses a protein that has the potential to prime host immune system against the pathogen itself. Keeping this apparent ambiguity into consideration, it is imperative to unravel intricacies involved in the exploitation of Acr-1 by M.tb during its interaction with host immune cells. The present study suggests that Acr-1 exhibits diverse role in the maturation of macrophages (MΦs) and related immunological responses. The early encounter of bone marrow derived immune cells (pre-exposure during differentiation to MΦs) with Acr-1 (AcrMΦpre), results in hampering of their function. The pre-exposure of naïve MΦs with Acr-1 induces the expression of TIM-3 and IL-10. In contrast, exposure of fully differentiated MΦs to Acr-1 results in their down-modulation and induces the phosphorylation of STAT-1 and STAT-4 in host MΦs. Furthermore, Acr-1 mediated activation of MΦs results in the induction of Th1 and Th17 phenotype by activated T lymphocyte., Competing Interests: The authors have declared that no competing interests exist.

Background: Staphylococcus xylosus is coagulase-negative staphylococci (CNS), found occasionally on the skin of humans but recurrently on other mammals. Recent reports suggest that this commensal bacterium may cause diseases in humans and other animals. In this study, we present the first report of whole genome sequencing of S. xylosus strain DMB3-Bh1, which was isolated from the stool of a mouse., Results: The draft genome of S. xylosus strain DMB3-Bh1 consisted of 2,81,0255 bp with G+C content of 32.7 mol%, 2623 predicted coding sequences (CDSs) and 58 RNAs. The final assembly contained 12 contigs of total size 2,81,0255 bp with N50 contig length of 4,37,962 bp and the largest contig assembled measured 7,61,338 bp. Further, an interspecies comparative genomic analysis through rapid annotation using subsystem technology server was achieved with Staphylococcus aureus RF122 that revealed 36 genes having similarity with S. xylosus DMB3-Bh1. 35 genes encoded for virulence, disease and defense and 1 gene encoded for phages, prophages and transposable elements., Conclusions: These results suggest co linearity in genes between S. xylosus DMB3-Bh1 and S. aureus RF122 that contribute to pathogenicity and might be the result of horizontal gene transfer. The study indicates that S. xylosus DMB3-Bh1 may be a potential emerging pathogen for rodents.

Background: Shigellosis is an acute form of gastroenteritis caused by the bacteria belonging to the genus Shigella. It is the most common cause of morbidity and mortality in children. Shigella belongs to the family Enterobactericeae, which is a Gram-negative and rod shaped bacterium. In the present study, we report the draft genome of Shigella dysenteriae strain SD1D, which was isolated from the stool sample of a healthy individual., Results: Based on 16S rRNA gene sequence and phylogenetic analysis, the strain SD1D was identified as Shigella dysenteriae. The draft genome of SD1D consisted of 45, 93, 159 bp with a G + C content of 50.7%, 4, 960 predicted CDSs, 75 tRNAs and 2 rRNAs. The final assembly contained 146 contigs of total length 45, 93, 159 bp with N50 contig length of 77, 053 bp; the largest contig assembled measured 3, 85, 550 bp., Conclusions: We have for the first time performed the whole genome sequencing of Shigella dysenteriae strain SD1D. The comparative genomic analysis revealed several genes responsible for the pathogenesis, virulence, defense, resistance to antibiotics and toxic compounds, multidrug resistance efflux pumps and other genomic features of the bacterium.

Background: The genus Salmonella is Gram-negative which belongs to the family Enterobacteriaceae. In this study, we have sequenced the whole genome of the strain DMA-1, which was isolated from mouse stool sample and identified as Salmonella enterica subspecies salamae., Results: The strain DMA-1 was closely related at the 16S rRNA gene sequence level with the members of the genus Salmonella: Salmonella enterica subspecies salamae DSM 9220T (100%), followed by Salmonella enterica subspecies diarizonae (99.1%), Salmonella enterica subspecies enterica (99.0%) and Salmonella enterica subspecies indica (98.5%). We obtained the draft genome of S. enterica subspecies salamae strain DMA-1 with a size of 4,826,209 bp and mean G+C content of 52.0 mol%., Conclusions: We for the first time, sequenced the entire genome of the strain DMA-1 which was isolated from the mouse stool sample and identified it as Salmonella enterica, sub species salamae. Further, we subjected the whole genome sequencing data for annotation that revealed several genes responsible for the pathogenesis, virulence, defense, metabolism and other genomic features.