Effect of Body Mass Index on work related musculoskeletal discomfort and occupational stress of computer workers in a developed ergonomic setup

<p>Abstract</p> <p>Background</p> <p>Work urgency, accuracy and demands compel the computer professionals to spend longer hours before computers without giving importance to their health, especially body weight. Increase of body weight leads to improper Body Mass Index (BMI) may aggravate work related musculoskeletal discomfort and occupational-psychosocial stress. The objective of the study was to find out the effect of BMI on work related musculoskeletal discomforts and occupational stress of computer workers in a developed ergonomic setup.</p> <p>Methods</p> <p>A descriptive inferential study has been taken to analyze the effect of BMI on work related musculoskeletal discomfort and occupational-psychosocial stress. A total of 100 computer workers, aged 25-35 years randomly selected on convenience from software and BPO companies in Bangalore city, India for the participation in this study. BMI was calculated by taking the ratio of the subject's height (in meter) and weight (in kilogram). Work related musculoskeletal discomfort and occupational stress of the subjects was assessed by Cornell University's musculoskeletal discomfort questionnaire (CMDQ) and occupational stress index (OSI) respectively as well as a relationship was checked with their BMI.</p> <p>Results</p> <p>A significant association (p < 0.001) was seen among high BMI subjects with their increase scores of musculoskeletal discomfort and occupational stress.</p> <p>Conclusion</p> <p>From this study, it has been concluded that, there is a significant effect of BMI in increasing of work related musculoskeletal discomfort and occupational-psychosocial stress among computer workers in a developed ergonomic setup.</p

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mutant p53 Gain of Oncogenic Function : In Vivo Evidence, Mechanism of Action and Its Clinical Implications

p53 is an indispensible tumor suppressor and exerts this function by transactivating numerous downstream target genes that play vital roles in controlling cell proliferation, apoptosis, senescence, and DNA repair. Mutations in the p53 gene, which are frequently seen in human tumors, impair its tumor suppressor function. Several of these tumor-derived p53 mutants can confer further aggressive oncogenic properties such as exacerbated malignant transformation and metastatic phenotype when overexpressed in p53-null cells. This oncogene-like behavior of mutant p53 is referred to as gain of function. The exact mechanism underlying gain-of-function phenotypes, however, remains enigmatic. Recently, we have generated mice with a point mutation (p53R172H) in their endogenous p53 loci as a model for the human Li-Fraumeni syndrome. The mutant p53R172H knock-in mice spontaneously develop tumors with high frequency of metastasis, contrary to that observed in mice with p53 deletion, indicating gain of function by the mutant p53R172H. In addition, our results show that other p53 family members, p63 and p73, are involved in the gain-of-function phenotypes. We further demonstrate that mutant p53R172H is inherently unstable and its stabilization is required for its gain-of-function phenotypes. This review focuses on recent reports regarding the potential molecular pathways for mutant p53 gain of oncogenic function and discusses its clinical implications.環境ストレスは細胞の恒常性に重要な役割を果たす遺伝子の突然変異を誘発する．中でも癌遺伝子や腫瘍抑制遺伝子に生じる変異は発癌の発端になりうる．腫瘍抑制遺伝子の一つであるTp53遺伝子産物p53は，細胞増殖，細胞死，細胞老化，DNA修復などに関与する遺伝子群を転写制御することによりその機能を果たしている．しかし，p53の遺伝子上に生じた突然変異により，その転写活性化能は失われる．Tp53遺伝子の突然変異がヒトの腫瘍の約50％で認められることは，いかにp53 がヒトの腫瘍抑制に重要な働きをしているかを示唆している．腫瘍由来の変異p53 の中には，p53 の欠損した培養細胞株に導入された際に，腫瘍の悪性度を高めるものがあることが知られている．このような癌遺伝子的な機能を有するp53 の変異を機能獲得型変異と呼ぶ．しかしながら，変異p53 の機能獲得のメカニズムは未だ不明である．最近我々は，遺伝子組換え技術を用いて，ヒトの遺伝性腫瘍症候群の１つであり，70％以上の症例でp53 に異常の認められるリー・フラウメニ症候群のマウスモデルを作出した．これは，マウスのp53 の遺伝子内にアルギニンからヒスチジンへの点突然変異を導入したもので，Tp53 遺伝子欠損マウスとは異なるものである．Tp53 遺伝子欠損マウスは転移性の腫瘍を発生しないことが知られているが，点突然変異を導入したマウスは高頻度に転移性腫瘍を発生する．このマウスに認められた腫瘍の転移は，p53 の機能獲得変異によって誘発されたものである．我々はまた，p53 のホモログであるp63とp73 がp53 の機能獲得変異に関与することを示した．さらに我々は，変異p53 が元来不安定な蛋白質であるが，野生型のp53 と同様に種々のストレスにより安定化し，それが転移性腫瘍を誘発することを示した．化学療法や放射線療法は現行の腫瘍の治療に頻繁に用いられているが，これらの治療法は，変異p53 を安定化し，より悪性度の高い腫瘍を誘発する可能性がある．それゆえ，治療前に個々の腫瘍内でのTp53 の突然変異の有無を調べることは重要な意義があると思われる．近年，変異p53 の高次構造を変化させ，野生型p53の機能を回復させる薬剤が報告されてきている．これらの薬剤は，現行の腫瘍の治療法に大きく貢献することが期待される

Mutant p53 Gain of Oncogenic Function : In Vivo Evidence, Mechanism of Action and Its Clinical Implications

p53 is an indispensible tumor suppressor and exerts this function by transactivating numerous downstream target genes that play vital roles in controlling cell proliferation, apoptosis, senescence, and DNA repair. Mutations in the p53 gene, which are frequently seen in human tumors, impair its tumor suppressor function. Several of these tumor-derived p53 mutants can confer further aggressive oncogenic properties such as exacerbated malignant transformation and metastatic phenotype when overexpressed in p53-null cells. This oncogene-like behavior of mutant p53 is referred to as gain of function. The exact mechanism underlying gain-of-function phenotypes, however, remains enigmatic. Recently, we have generated mice with a point mutation (p53R172H) in their endogenous p53 loci as a model for the human Li-Fraumeni syndrome. The mutant p53R172H knock-in mice spontaneously develop tumors with high frequency of metastasis, contrary to that observed in mice with p53 deletion, indicating gain of function by the mutant p53R172H. In addition, our results show that other p53 family members, p63 and p73, are involved in the gain-of-function phenotypes. We further demonstrate that mutant p53R172H is inherently unstable and its stabilization is required for its gain-of-function phenotypes. This review focuses on recent reports regarding the potential molecular pathways for mutant p53 gain of oncogenic function and discusses its clinical implications.環境ストレスは細胞の恒常性に重要な役割を果たす遺伝子の突然変異を誘発する．中でも癌遺伝子や腫瘍抑制遺伝子に生じる変異は発癌の発端になりうる．腫瘍抑制遺伝子の一つであるTp53遺伝子産物p53は，細胞増殖，細胞死，細胞老化，DNA修復などに関与する遺伝子群を転写制御することによりその機能を果たしている．しかし，p53の遺伝子上に生じた突然変異により，その転写活性化能は失われる．Tp53遺伝子の突然変異がヒトの腫瘍の約50％で認められることは，いかにp53 がヒトの腫瘍抑制に重要な働きをしているかを示唆している．腫瘍由来の変異p53 の中には，p53 の欠損した培養細胞株に導入された際に，腫瘍の悪性度を高めるものがあることが知られている．このような癌遺伝子的な機能を有するp53 の変異を機能獲得型変異と呼ぶ．しかしながら，変異p53 の機能獲得のメカニズムは未だ不明である．最近我々は，遺伝子組換え技術を用いて，ヒトの遺伝性腫瘍症候群の１つであり，70％以上の症例でp53 に異常の認められるリー・フラウメニ症候群のマウスモデルを作出した．これは，マウスのp53 の遺伝子内にアルギニンからヒスチジンへの点突然変異を導入したもので，Tp53 遺伝子欠損マウスとは異なるものである．Tp53 遺伝子欠損マウスは転移性の腫瘍を発生しないことが知られているが，点突然変異を導入したマウスは高頻度に転移性腫瘍を発生する．このマウスに認められた腫瘍の転移は，p53 の機能獲得変異によって誘発されたものである．我々はまた，p53 のホモログであるp63とp73 がp53 の機能獲得変異に関与することを示した．さらに我々は，変異p53 が元来不安定な蛋白質であるが，野生型のp53 と同様に種々のストレスにより安定化し，それが転移性腫瘍を誘発することを示した．化学療法や放射線療法は現行の腫瘍の治療に頻繁に用いられているが，これらの治療法は，変異p53 を安定化し，より悪性度の高い腫瘍を誘発する可能性がある．それゆえ，治療前に個々の腫瘍内でのTp53 の突然変異の有無を調べることは重要な意義があると思われる．近年，変異p53 の高次構造を変化させ，野生型p53の機能を回復させる薬剤が報告されてきている．これらの薬剤は，現行の腫瘍の治療法に大きく貢献することが期待される