The Malaysian construction industry is stigma-laden 'dangerous, dirty and difficult' (3 D) with a high number of blue-collar foreign workers. Poor safety performance is undermining the public ...perception. The purpose of this study is to examine the current level of safety awareness in construction, to determine the significant factors affecting safety performance and to evaluate the potential measures for improving the construction workers' safety awareness. A total of 27 reasons were first identified through a comprehensive literature review. A questionnaire survey then employed to evaluate the perceptions of construction personnel on the factors that affect safety performance and potential measures to improve safety awareness, in which the understanding on the hierarchy of controls is still lacking. The primary safety issues are: personal protective equipment (PPE), working environment, working attitude, communication and maintenance of equipment. Then, an exploratory factor analysis revealed eight underlying factors. The most effective preventive measure are: install fall protection system, effective communication and regular safety inspection. Finally, the relationships between the factors and preventive measures were identified using correlation tests. This paper provides more profound insights into the underlying factors affecting safety performance in construction and recommends feasible measures to raise safety awareness among the construction personnel.
Ovarian cancer is one of the most lethal types of female malignancy. Although most patients are initially responsive to platinum-based chemotherapy, almost all develop recurrent chemoresistant tumors ...and succumb to their diseases. Elucidating the pathogenesis underlying drug resistance is fundamental to the development of new therapeutics, leading to improved clinical outcomes in these patients.
We compared the proteomes of paired primary and recurrent post-chemotherapy ovarian high-grade serous carcinomas from nine ovarian cancer patients using CIEF/Nano-RPLC coupled with ESI-Tandem MS. As compared to their primary tumors, more than half of the recurrent tumors expressed higher levels of several proteins including CP, FN1, SYK, CD97, AIF1, WNK1, SERPINA3, APOD, URP2, STAT5B and RELA (NF-kappaB p65), which were also validated by quantitative RT-PCR. Based on shRNA screening for the upregulated genes in in vitro carboplatin-resistant cells, we found that simultaneous knockdown of RELA and STAT5B was most effective in sensitizing tumor cells for carboplatin treatment. Similarly, the NF-kappaB inhibitor, BMS-345541, and the STAT5 inhibitor, Dasatinib, significantly enhanced cell sensitivity to carboplatin. Moreover, both RELA and STAT5 are known to bind to the promoter region of Bcl-X, regulating its promoter activity. In this regard, augmented Bcl-xL expression was detected in carboplatin-resistant cells. Combined ectopic expression of RELA and STAT5B enhanced Bcl-xL promoter activity while treatment with BMS-345541 and Dasatinib decreased it. Chromatin immunoprecipitation of the Bcl-X promoter region using a STAT5 antibody showed induction of RELA and STAT5 DNA-binding segments both in naïve cells treated with a high concentration of carboplatin as well as in carboplatin-resistant cells.
Proteomic analysis identified RELA and STAT5 as two major proteins associated with carboplatin resistance in ovarian tumors. Our results further showed that NF-kappaB and STAT5 inhibitor could sensitize carboplatin-resistant cells and suggest that such inhibitors can be used to benefit patients with carboplatin-resistant recurrent ovarian cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nonketotic hyperglycinemia (NKH) is a relatively well‐characterized inborn error of metabolism that results in a combination of lethargy, hypotonia, seizures, developmental arrest, and, in severe ...cases, death early in life. Three genes encoding components of the glycine cleavage enzyme system—GLDC, AMT, and GCSH—are independently associated with NKH. We report on a patient with severe NKH in whom the homozygous pathogenic variant in AMT (NM_000481.3):c.602_603del (p.Lys201Thrfs*75) and the homozygous likely pathogenic variant in GLDC(NM_000170.2):c.2852C>A (p.Ser951Tyr) were both identified. Our patient demonstrates a novel combination of two homozygous disease‐causing variants impacting the glycine cleavage pathway at two different components, and elicits management‐ and genetic counseling‐related challenges for the family.
Pathogenic heterozygous variants in DHX16 have been recently identified in association with a variety of clinical features, including neuromuscular disease, sensorineural hearing loss, ocular ...anomalies, and other phenotypes. All DHX16 disease‐causing variants previously reported in affected individuals are missense in nature, nearly all of which were found to be de novo. Here we report on a patient with neuromuscular disease, hearing loss, retinal degeneration, and previously unreported phenotypic features including mitochondrial deficiency and primary ovarian insufficiency, in whom a novel de novo likely pathogenic variant in DHX16 NM_003587.4:c.2033A > G (p.Glu678Gly) was identified. Furthermore, we conducted an in‐depth literature review of DHX16's role in disease and utilized high‐performing in silico prediction algorithms to compare and contrast the predicted effects of all reported disease‐associated DHX16 variants on protein structure and function.
COVID-19 is a global health emergency. People living with human immunodeficiency virus (PLHIV) have concerns about whether they have a higher risk of getting the infection and suffer worse COVID-19 ...outcomes. Findings from studies on these questions have largely been inconsistent. We aimed to determine the epidemiological characteristics, clinical signs and symptoms, blood parameters, and clinical outcomes among PLHIV who contracted COVID-19. Relevant studies were identified through Medline, Cinahl, and PubMed databases. A random-effects model was used in meta-analyses with a 95% confidence interval. Eighty-two studies were included in the systematic review and sixty-seven studies for the meta-analysis. The pooled incidence proportion of COVID-19 among PLHIV was 0.9% (95% CI 0.6%, 1.1%) based on the data from seven cohort studies. Overall, 28.4% were hospitalised, of whom, 2.5% was severe-critical cases and 3.5% needed intensive care. The overall mortality rate was 5.3%. Hypertension was the most commonly reported comorbidity (24.0%). Fever (71.1%) was the most common symptom. Chest imaging demonstrated a wide range of abnormal findings encompassing common changes such as ground glass opacities and consolidation as well as a spectrum of less common abnormalities. Laboratory testing of inflammation markers showed that C-reactive protein, ferritin, and interleukin-6 were frequently elevated, albeit to different extents. Clinical features as well as the results of chest imaging and laboratory testing were similar in highly active antiretroviral therapy (HAART)-treated and non-treated patients. PLHIV were not found to be at higher risk for adverse outcomes of COVID-19. Hence, in COVID-19 management, it appears that they can be treated the same way as HIV negative individuals. Nevertheless, as the pandemic situation is rapidly evolving, more evidence may be needed to arrive at definitive recommendations.
Background:
Lower extremity amputation (LEA) is defined as the complete loss in the transverse anatomical plane of any part of the lower limb. The objective of this study is to look at the trend and ...mortality trend of LEA performed in diabetes patients from 2008 to 2013.
Methods:
All patients age 15 and above with diabetes mellitus who had undergone LEAs (both major and minor) in Tan Tock Seng Hospital, Singapore from 1 January 2008 to 31 December 2013 were included. The outcomes of interest were deaths from all causes within 30 days and within 1 year.
Results:
Major LEA rate has increased from 11.0 per 100,000 population in 2008 to 13.3 per 100,000 population in 2013. The 30-day mortality rate ranges from 6.0% to 11.1% and the 1-year mortality rate ranges from 24.3% to 30.6%. Minor LEA rate has increased from 10.8 per 100,000 population in 2008 to 13.9 per 100,000 population in 2013. The 30-day mortality rate ranges from 1.5% to 3.7% and the 1-year mortality rate ranges from 9.7% to 18.3%.
Conclusions:
The trends in major and minor LEA are increasing. The 30-day and 1-year mortality for both major and minor LEA are comparable to figures reported worldwide. There is a need to re-look at preventive strategies to reduce LEA in diabetes patients in Singapore.
Myoepithelial tumors (MET) constitute a group of neoplasms with a variety of morphologic, immunophenotypic, and molecular features. Approximately half of MET of soft tissue harbor EWSR1 gene ...rearrangements with a subset showing EWSR1‐POU5F1 fusions and demonstrating distinctive tendency towards aggressive behavior in children. Histologically, EWSR1‐POU5F1‐positive MET typically show clear‐cell morphology with malignant features including marked pleomorphism and atypical mitotic figures. The cytomorphology of these tumors has not been well characterized. Reported here are the cytomorphologic features of two cases of EWSR1‐POUF1‐positive MET with histology correlation.
Because of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination of potential genetic drivers offers the possibility of improving therapeutic approaches ...and discovering novel prognostic indicators.
Using pTN staging, we case-matched 81 patients with resected ≥pT2 bladder cancers for whom perioperative chemotherapy use and disease recurrence status were known. Whole-exome sequencing was conducted in 43 cases to identify recurrent somatic mutations and targeted sequencing of 10 genes selected from the initial screening in an additional 38 cases was completed. Mutational profiles along with clinicopathologic information were correlated with recurrence-free survival (RFS) in the patients.
We identified recurrent novel somatic mutations in the gene UNC5C (9.9%), in addition to TP53 (40.7%), KDM6A (21.0%), and TSC1 (12.3%). Patients who were carriers of somatic mutations in DNA repair genes (one or more of ATM, ERCC2, FANCD2, PALB2, BRCA1, or BRCA2) had a higher overall number of somatic mutations (P = 0.011). Importantly, after a median follow-up of 40.4 months, carriers of somatic mutations (n = 25) in any of these six DNA repair genes had significantly enhanced RFS compared with noncarriers median, 32.4 vs. 14.8 months; hazard ratio of 0.46, 95% confidence interval (CI), 0.22-0.98; P = 0.0435, after adjustment for pathologic pTN staging and independent of adjuvant chemotherapy usage.
Better prognostic outcomes of individuals carrying somatic mutations in DNA repair genes suggest these mutations as favorable prognostic events in muscle-invasive bladder cancer. Additional mechanistic investigation into the previously undiscovered role of UNC5C in bladder cancer is warranted.
Generalized anxiety disorder (GAD) is one of the most common mental disorders in Malaysia. Psychometrically sound measurements are urgently needed to assess anxiety symptoms. The extensively used ...Generalized Anxiety Disorder 7-item (GAD-7) is a promising candidate. However, studies on its factorial validity show mixed findings. While the one-factor solution has been replicated in different cultural contexts, some studies found different factorial structures instead. This study aimed to clarify the factorial validity of the English version of the GAD-7 in the Malaysian context. The responses collected from 1272 emerging to older adults in Malaysia were randomly divided into two halves and submitted to exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) respectively. Four acceptable models were explored in EFA ranging from unidimensional factor with 7 items to 3-factor models with 6 items. The four models revealed in EFA and the other competing models found in past studies were then examined and compared using CFA. The 6-item second-order model with a general factor of anxiety and three first-order factors with two items respectively (i.e., GAD-6) showed a more harmonic result and hence, is preferable. Moreover, the GAD-6 and its three subscales also showed satisfactory internal consistency and construct validity. This study uncovers a new and unique factorial structure of the GAD screening tool that fits in the Malaysian context. The scale may reveal GAD symptomatic dimensions that guide clinical interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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