Background and Aims: Pelvic organ prolapse (POP) is a common condition affecting women during their midlife, leading to various symptoms and decreased quality of life (QoL). This study aimed to ...assess the association of POP severity with QoL and sexual function in women at their midlife, with the objective of providing valuable insights for comprehensive care and effective management of POP. Method: A cross-sectional study included 130 symptomatic GUP women aged 40-60 years from Sir Salimullah Medical College & Mitford Hospital in Dhaka. Group 1 (85 women) had stage 1 GUP, while the remaining were in group 2. Face-to-face interviews and POP-Q staging were conducted, followed by statistical analysis using Chi-Square, Mann-Whitney U, and Spearman rank correlation tests to examine the association of GUP severity with QoL and sexual function between the groups. Results: The mean age of the participants was 51.24 years (SD=5.5). The majority of the respondents were above 50 years of age (56%), and 65.38% of the study population were in group 2. One-third of the respondents (35.38%) had stage III GUP whereas only 4.62% were in stage IV. The frequency of urinary symptoms was most commonly occurring (70%) where dribbling of urine was least frequent (38%). Sexual and bowel symptoms were correlated with advanced stage of disease where urinary symptoms were not associated with GUP severity. Sexual dysfunction symptoms were positively associated with uterine descent. Regarding quality of life, all nine domains of QoL scores had positive correlation with severity of GUP. Conclusion: This study reveals the correlation between POP and urinary, bowel, and sexual symptoms. Clinicians should assess these symptoms for comprehensive care, and further research is required to determine effective treatment options for women with POP.
Thermotolerance is a phenomenon in which cells become resistant to stress by prior exposure to heat shock, and its development is associated with the induction of heat shock proteins (Hsps), ...including Hsp70. We previously showed that the expression of Hsp70 is regulated by the cytokine signaling transcription factor Stat3, but the role of Stat3 in thermotolerance is not known. In this study, we examined the possible involvement of Stat3 in the acquisition of thermotolerance. We found that severe heat shock-induced morphological changes and decreases in cell viability, which were suppressed by exposure to non-lethal mild heat shock prior to severe heat shock. This thermotolerance development was accompanied by Stat3 phosphorylation and the induction of Hsps such as Hsp105, Hsp70, and Hsp27. Stat3 phosphorylation and Hsp induction were inhibited by AG490, an inhibitor of JAK tyrosine kinase. Consistent with this, we found that mild heat shock-induced thermotolerance was partially suppressed by AG490 or knockdown of Hsp105. We also found that the Stat3 inhibitor Stattic suppresses the acquisition of thermotolerance by inhibiting the mild heat shock-induced Stat3 phosphorylation and Hsp105 expression. These results suggest that the mild heat shock-dependent stimulation of the JAK-Stat signaling pathway contributes to the development of thermotolerance via the induction of Hsps including Hsp105. This signaling pathway may be a useful target for hyperthermia cancer therapy.
Anaplastic lymphoma kinase (ALK), a receptor-type tyrosine kinase, is involved in the pathogenesis of several cancers. ALK has been targeted with small molecule inhibitors for the treatment of ...different cancers, but absolute success remains elusive. In the present study, the effects of ALK inhibitors on M phase progression were evaluated. Crizotinib, ceritinib, and TAE684 suppressed proliferation of neuroblastoma SH-SY5Y cells in a concentration-dependent manner. At approximate IC
concentrations, these inhibitors caused misorientation of spindles, misalignment of chromosomes and reduction in autophosphorylation. Similarly, knockdown of ALK caused M phase delay, which was rescued by re-expression of ALK. Time-lapse imaging revealed that anaphase onset was delayed. The monopolar spindle 1 (MPS1) inhibitor, AZ3146, and MAD2 knockdown led to a release from inhibitor-induced M phase delay, suggesting that spindle assembly checkpoint may be activated in ALK-inhibited cells. H2228 human lung carcinoma cells that express EML4-ALK fusion showed M phase delay in the presence of TAE684 at about IC
concentrations. These results suggest that ALK plays a role in M phase regulation and ALK inhibition may contribute to the suppression of cell proliferation in ALK-expressing cancer cells.
Cell division is the process by which replicated chromosomes are separated into two daughter cells. Although regulation of M phase has been extensively investigated, not all regulating factors have ...been identified. Over the course of our research, small molecules were screened to identify those that regulate M phase. In the present study, the vascular endothelial growth factor receptor (VEGFR) inhibitors A83-01, SU4312, and Ki8751 were examined to determine their effects on M phase. Treatment of HeLa S3 cells with these inhibitors suppressed cell proliferation in a concentration-dependent manner, and also suppressed Akt phosphorylation at Ser473, a marker of Akt activation. Interestingly, cleaved caspase-3 was detected in Adriamycin-treated cells but not in inhibitor-treated cells, suggesting that these inhibitors do not suppress cell proliferation by causing apoptosis. A cell cycle synchronization experiment showed that these inhibitors delayed M phase progression, whereas immunofluorescence staining and time-lapse imaging revealed that the M phase delay was accompanied by misalignment of chromosomes and rotation of the mitotic spindle. Treatment with the Mps1 inhibitor AZ3146 prevented the SU4312-induced M phase delay. In conclusion, the VEGFR inhibitors investigated here suppress cell proliferation by spindle assembly checkpoint-induced M phase delay, via misalignment of chromosomes and rotation of the mitotic spindle.
Thoracolumbar junction fractures (TLJFs) attract controversy for several parameters, including surgery versus conservative treatment, fusion versus stabilization, open versus percutaneous surgery, ...construct length, and downstream metalwork extraction.
The aim of this pilot study was to assess the effectiveness of surgical treatment in patients with burst (AO Classification Type A4) TLJFs using patient-reported outcome measures (PROMs) and evaluate and compare different PROMs in this clinical scenario.
Patient records of consecutive patients who underwent posterior stabilization surgery for TLJFs were retrospectively reviewed. Data were collected on demographics, medical and social history, neurological examination, and postoperative complications. Telephone interviews and a combined PROM methodology (Numerical Rating Scale NRS, EuroQol EQ-5D-5L, and Oswestry Disability Index ODI) were utilized to assess the effectiveness of intervention. Descriptive statistics were used to analyze exposure variables and outcome measures. Spearman's rank correlation was used for the outcome measures.
Thirteen patients were included. The mean age was 42 ± 16 years; the male: female ratio was 8:5; the mean follow-up was 18.9 ± 6.4 months. The mean NRS score was 3.3 ± 2.5, in line with a median score of 2 (2) on EQ-5D-5L pain/discomfort scale. Statistically significant correlations were found between several PROMs: pain-EQ-5D-5L and NRS (rs = 0.8, P = 0.002), pain-EQ-5D-5L and ODI (rs = 0.8, P = 0.001), usual anxiety/depression-EQ-5D-5L, and ODI (rs = 0.7, P = 0.008).
A combined PROM methodology showed supportive evidence for safety and efficacy in the surgical stabilization of burst TLJFs. This alleviated significant pain and prevented neurological deficit and major disability. The preliminary widespread correlation between these PROMs supports further larger studies of their combined use in clinical practice, to measure the outcomes of spine trauma patients.
Plastic pollution has emerged as a major global concern due to its enduring nature and limited recycling options. In response to this critical challenge, this paper presents a novel approach ...utilizing a Detection-Based Reward System (DBRS) alongside an innovative business model to promote effective plastic waste management, reduce plastic waste accumulation in the nature, and uphold environmental cleanliness. Leveraging the YOLOv5 algorithm for its exceptional accuracy, speed, and open-source availability, plastic bottle detection becomes a pivotal aspect of this system. Users seamlessly enroll in the system, triggering an automated detection process that computes reward points corresponding to their deposited plastic bottles. These reward points are meticulously stored within a centralized database. Beyond its operational facets, this comprehensive system encompasses a robust business model, strategically poised to capture widespread engagement with waste disposal practices, thereby contributing to the realization of Sustainable Development Goals (SDGs) geared towards fostering a healthier environment. Notably, the DBRS attains cutting-edge performance in plastic bottle detection, boasting an impressive mean Average Precision (mAP) of 0.973, underscoring its efficacy in tackling plastic pollution.
The segmented body plan of vertebrates is established during somitogenesis, a well-studied process in model organisms; however, the details of this process in humans remain largely unknown owing to ...ethical and technical limitations. Despite recent advances with pluripotent stem cell-based approaches
, models that robustly recapitulate human somitogenesis in both space and time remain scarce. Here we introduce a pluripotent stem cell-derived mesoderm-based 3D model of human segmentation and somitogenesis-which we termed 'axioloid'-that captures accurately the oscillatory dynamics of the segmentation clock and the morphological and molecular characteristics of sequential somite formation in vitro. Axioloids show proper rostrocaudal patterning of forming segments and robust anterior-posterior FGF-WNT signalling gradients and retinoic acid signalling components. We identify an unexpected critical role of retinoic acid signalling in the stabilization of forming segments, indicating distinct, but also synergistic effects of retinoic acid and extracellular matrix on the formation and epithelialization of somites. Comparative analysis demonstrates marked similarities of axioloids to the human embryo, further validated by the presence of a Hox code in axioloids. Finally, we demonstrate the utility of axioloids for studying the pathogenesis of human congenital spine diseases using induced pluripotent stem cells with mutations in HES7 and MESP2. Our results indicate that axioloids represent a promising platform for the study of axial development and disease in humans.
In this study, the pharmacological and toxicological effects along with possible side effects of the classical ayurvedic formulation "Lauhasava" (LSV), which is used in anemia, were evaluated. During ...this study, various experiments on body growth rate, organ-body weight ratio, tissue hydration indices and body fat ratio were performed to evaluate its efficacy and toxicity. In the body weight study, the LSV treated rats, irrespective of sexes, showed significantly lower body weights than the control group rats. LSV treated mice of both sexes gained less weight than their control counterparts. The study involving comparison of the relative weights of the major organs of rats and mice revealed some significant results. The percentage of lung to the body weight is significantly increased in both sexes of rats. Liver weight in LSV treated rats of both sexes were observed to be increased. The percentage of kidney weight was increased in both sexes of rats, the result being significant in the case of female rats. The thymus weight was found significantly decreased in both sexes of rats. Significant increase in the weight of rats' ovaries was observed. In the tissue hydration index experiment, only the increase in the female kidney was significant. No significant result was found in the fat content of the whole mice and eviscerated mice.
The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that ...include hematological malignancies in Bangladesh.
This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the "French American British" classification system.
A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n=3468) and 30.8% females (n=1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin's lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over.
For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country.
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