Impact of physical distance and psychological distress on job turnover intention among front-line health workers during COVID-19 pandemic

COVID-19 pandemic compels strict isolation to avoid the spread of Coronavirus. Physical distance with COVID-19 patients is undeniable for font-line health workers. This physical proximity of doctors and nurses at hospital affects their mental health and generating psychological distress. They sacrifice their social life and keeping themselves isolated due to their regular contact with COVID-19 patients. This causes high rate of depression, anxiety and stress. Therefore, this study aims to identify the effect of physical distancing and psychological distress on job turnover intention among the front line health workers. This study is applying Protection Motivation Theory (PMT) to understand this relationship. Data has been collected between March and April 2021 through structured questionnaire from doctors, nurses and hospital staffs who are managing COVID-19 patients at hospitals. This research has discovered that as front-line health workers' fear of COVID-19 grows, so does their relational anxiety, as well as their organizational and technical turnover intentions. Therefore, there is a need of psychological assistance and increasing capacity building for the front-line workers. This study includes only two variables to understand job turnover intention. For more insights and understanding of the experience in the light of COVID-19, further study can be done by including other factors like institutional support, policy implementation and social dilemma

HIV-1 Promotes Renal Tubular Epithelial Cell Protein Synthesis: Role of mTOR Pathway

Tubular cell HIV-infection has been reported to manifest in the form of cellular hypertrophy and apoptosis. In the present study, we evaluated the role of mammalian target of rapamycin (mTOR) pathway in the HIV induction of tubular cell protein synthesis. Mouse proximal tubular epithelial cells (MPTECs) were transduced with either gag/pol-deleted NL4-3 (HIV/MPTEC) or empty vector (Vector/MPTEC). HIV/MPTEC showed enhanced DNA synthesis when compared with Vector/MPTECs by BRDU labeling studies. HIV/MPTECs also showed enhanced production of β-laminin and fibronection in addition to increased protein content per cell. In in vivo studies, renal cortical sections from HIV transgenic mice and HIVAN patients showed enhanced tubular cell phosphorylation of mTOR. Analysis of mTOR revealed increased expression of phospho (p)-mTOR in HIV/MPTECs when compared to vector/MPTECs. Further downstream analysis of mTOR pathway revealed enhanced phosphorylation of p70S6 kinase and associated diminished phosphorylation of eEF2 (eukaryotic translation elongation factor 2) in HIV/MPTECs; moreover, HIV/MPTECs displayed enhanced phosphorylation of eIF4B (eukaryotic translation initiation factor 4B) and 4EBP-1 (eukaryotic 4E binding protein). To confirm our hypothesis, we evaluated the effect of rapamycin on HIV-induced tubular cell downstream signaling. Rapamycin not only attenuated phosphorylation of p70S6 kinase and associated down stream signaling in HIV/MPTECs but also inhibited HIV-1 induced tubular cell protein synthesis. These findings suggest that mTOR pathway is activated in HIV-induced enhanced tubular cell protein synthesis and contributes to tubular cell hypertrophy

Diagnosis of breast lesions on frozen section and its cyto-histopathological correlation

Aim: To compare the finding of frozen section with findings of FNAC and histopathology & study the sensitivity, specificity and predictive value of frozen section biopsy. Methods: A hospital based cross sectional study was done to compare the finding of frozen section with findings of FNAC and histopathology. This research included total 70 female patients of age group 11-80 years clinically presenting with palpable breast lesions referred to the Department of Pathology, for FNAC, frozen section and histopathological evaluation and a prospective study was conducted. FNAC procedure was performed according to the standard protocol. Only diagnosed cases were included in the study. Cases did not undergo surgery were excluded from the study. Results: Following FNAC, out of the total 70 cases, 35 (50%) patients had benign breast lesions while 35 (50%) patients had malignant breast lesions. Following Frozen Section, out of the total 70 cases, 33 cases (47.1%) were benign lesions and 37 cases (52.9%) were malignant. According to The histopathological diagnosis of breast lesions noted that 32 (45.7%) patients had benign breast lesions while 38 (54.3%) patients had malignant breast lesions. Frozen section findings correlated with the histopathological findings in 69 of 70 cases (98.6%), which included 32 of 32 (100%) of the benign lesions and 37 of 38 (97.4%) of the malignant lesions. 1 case of malignant lesion was wrongly diagnosed as benign on frozen section findings. The correlation of frozen section and histopathological findings was found to be statistically significant as per Chi-Square test (p<0.05). FNAC findings correlated with the histopathological findings in 65 of 70 cases (92.9%), which included 31 of 32 (96.9%) of the benign lesions and 34 of 38 (89.5%) of the malignant lesions. 1 case was wrongly diagnosed as malignant on FNAC findings while 4 cases were wrongly diagnosed as benign. The correlation of FNAC and histopathological findings was found to be statistically significant as per Chi-Square test (p<0.05). The Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Frozen section were 97.37%, 100%, 100% and 96.97% respectively. Accuracy of Frozen section was 98.57%. It was observed that frozen section was more accurate than FNAC with higher sensitivity (97.37% vs. 89.47%), specificity (100% vs. 96.88%), PPV (100% vs. 97.14%), NPV (96.97% vs. 88.57%) and accuracy (98.57% vs. 92.86%). Conclusion: Despite increasing popularity and undisputed utility of FNAC, there are cases where frozen section still stands out as the method of choice for rapid diagnosis mainly for determining the resection margins of the lesion and the extent of metastasis in case of malignant lesion to ensure no residual tumour mass thus helping in further treatment and follow-up of patients. Final histopathological study is required to accurately arrive at a definitive diagnosis along with IHC marker study which is considered as a gold standard for patient care

Diagnosis of breast lesions on frozen section and its cyto-histopathological correlation

Aim: To compare the finding of frozen section with findings of FNAC and histopathology & study the sensitivity, specificity and predictive value of frozen section biopsy. Methods: A hospital based cross sectional study was done to compare the finding of frozen section with findings of FNAC and histopathology. This research included total 70 female patients of age group 11-80 years clinically presenting with palpable breast lesions referred to the Department of Pathology, for FNAC, frozen section and histopathological evaluation and a prospective study was conducted. FNAC procedure was performed according to the standard protocol. Only diagnosed cases were included in the study. Cases did not undergo surgery were excluded from the study. Results: Following FNAC, out of the total 70 cases, 35 (50%) patients had benign breast lesions while 35 (50%) patients had malignant breast lesions. Following Frozen Section, out of the total 70 cases, 33 cases (47.1%) were benign lesions and 37 cases (52.9%) were malignant. According to The histopathological diagnosis of breast lesions noted that 32 (45.7%) patients had benign breast lesions while 38 (54.3%) patients had malignant breast lesions. Frozen section findings correlated with the histopathological findings in 69 of 70 cases (98.6%), which included 32 of 32 (100%) of the benign lesions and 37 of 38 (97.4%) of the malignant lesions. 1 case of malignant lesion was wrongly diagnosed as benign on frozen section findings. The correlation of frozen section and histopathological findings was found to be statistically significant as per Chi-Square test (p<0.05). FNAC findings correlated with the histopathological findings in 65 of 70 cases (92.9%), which included 31 of 32 (96.9%) of the benign lesions and 34 of 38 (89.5%) of the malignant lesions. 1 case was wrongly diagnosed as malignant on FNAC findings while 4 cases were wrongly diagnosed as benign. The correlation of FNAC and histopathological findings was found to be statistically significant as per Chi-Square test (p<0.05). The Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Frozen section were 97.37%, 100%, 100% and 96.97% respectively. Accuracy of Frozen section was 98.57%. It was observed that frozen section was more accurate than FNAC with higher sensitivity (97.37% vs. 89.47%), specificity (100% vs. 96.88%), PPV (100% vs. 97.14%), NPV (96.97% vs. 88.57%) and accuracy (98.57% vs. 92.86%). Conclusion: Despite increasing popularity and undisputed utility of FNAC, there are cases where frozen section still stands out as the method of choice for rapid diagnosis mainly for determining the resection margins of the lesion and the extent of metastasis in case of malignant lesion to ensure no residual tumour mass thus helping in further treatment and follow-up of patients. Final histopathological study is required to accurately arrive at a definitive diagnosis along with IHC marker study which is considered as a gold standard for patient care

Newborn weight change and predictors of underweight in the neonatal period in Guinea-Bissau, Nepal, Pakistan and Uganda

In low- and middle-income countries (LMIC), growth impairment is common; however, the trajectory of growth over the course of the first month has not been well characterised. To describe newborn growth trajectory and predictors of growth impairment, we assessed growth frequently over the first 30 days among infants born ≥2000 g in Guinea-Bissau, Nepal, Pakistan and Uganda. In this cohort of 741 infants, the mean birth weight was 3036 ± 424 g. For 721 (98%) infants, weight loss occurred for a median of 2 days (interquartile range, 1-4) following birth until weight nadir was reached 5.9 ± 4.3% below birth weight. At 30 days of age, the mean weight was 3934 ± 592 g. The prevalence of being underweight at 30 days ranged from 5% in Uganda to 31% in Pakistan. Of those underweight at 30 days of age, 56 (59%) had not been low birth weight (LBW), and 48 (50%) had reached weight nadir subsequent to 4 days of age. Male sex (relative risk [RR] 2.73 [1.58, 3.57]), LBW (RR 6.41 [4.67, 8.81]), maternal primiparity (1.74 [1.20, 2.51]) and reaching weight nadir subsequent to 4 days of age (RR 5.03 [3.46, 7.31]) were highly predictive of being underweight at 30 days of age. In this LMIC cohort, country of birth, male sex, LBW and maternal primiparity increased the risk of impaired growth, as did the modifiable factor of delayed initiation of growth. Interventions tailored to infants with modifiable risk factors could reduce the burden of growth impairment in LMIC

Modulation of renin angiotensin system predominantly alters sclerotic phenotype of glomeruli in HIVAN

HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role of the RAS we have used a genetically engineered mouse model of HIVAN (Tg26) with two and four copies of angiotensinogen (Agt) gene (Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6 glomeruli exhibited sclerosed phenotype, whereas 1 out of 25 glomeruli displayed collapsed phenotype; on the other hand, in Tg26/Agt4, 1 out of 3 glomeruli exhibited sclerotic phenotype and only 1 out of 7 glomeruli showed collapsed phenotype. To inhibit the effect of RAS, Tg26/Agt2 were administered captopril, aliskiren, aliskiren plus captopril or aliskiren plus telmisartan by miniosmotic pumps for 4 weeks. In all experimental groups there was a significant reduction in percentage of sclerosed glomeruli and only minimal reduction in collapsed glomeruli compared to normal saline receiving Tg26/Agt2. These findings suggest that the manifestation of the sclerosed phenotype in HIVAN is predominantly dependent on activation of the RAS

Effect of rapamycin on HIV-induced tubular cell protein synthesis.

<p>Growth arrested vector/MPTECs, and HIV/MPTECs with or without rapamycin (100 nM) were incubated in media for 48 hours. Subsequently, number of cells were counted and total proteins were measured quantitatively. Protein content per cell was calculated (n = 3). P<0.05 compared to vector and HIV + R.</p

Rapamycin inhibits HIV-induced tubular cell phosphorylation of mTOR and 70S6K.

<p>A. MPTECs were transduced either empty vector (Vector), NL4-3 (HIV) and incubated in media containing either buffer or rapamycin (100 nM) for 72 hours. Subsequently, proteins were extracted, Western blots were prepared and probed for phospho-mTOR. The blots were stripped and reprobed for total mTOR. Representative gels (in duplicate) showing tubular cell phospho-mTOR in control (vector), HIV infected (HIV) and rapamycin-treated/HIV-infected (HIV + R) cells are shown (upper lane). The lower lane shows tubular cell expression of mTOR under similar conditions. Cumulative data of four sets of experiments in the form of a bar diagram are displayed in the lower panel. P<0.01 compared to vector and HIV + R. B. Proteins from the MPTECs treated under similar condition were probed for phospho-70S6K. The blots were stripped and reprobed for actin. Representative gels (in duplicate) showing tubular cell phospho-70S6K in control (vector), HIV infected (HIV) and rapamycin-treated/HIV-infected (HIV + R) cells are shown (upper lane). The lower lane shows tubular cell expression of actin under similar conditions. Cumulative data of four sets of experiments in the form of a bar diagram are displayed in the lower panel. *P<0.01 compared to vector and HIV + R.</p

HIV enhances tubular cell UBF phosphorylation, DNA synthesis and intracellular protein content.

<p>A. Vector/MPTECs and HIV/MPTECs were incubated in media for 72 hours. Subsequently, proteins were extracted and probed for phospho-UBF and total UBF. Representative gels (in duplicate) are shown displaying tubular cell expression of phospho-UBF and toral UBF. The upper lane shows the effect of HIV on tubular cell expression of phospho-UBF. The lower lane shows lane total tubular cell UBF expression under similar conditions. B. Vector/MPTECs (control) and HIV/MPTECs were incubated 96 well plates and pulsed with BRDU and incubated for 72 hours. BRDU incorporation in MPTECs was assayed by ELISA. Cumulative data of three sets of experiments is show in the form a bar diagrams C. Vector/MPTECs and HIV/MPTECs were growth arrested and then incubated in media containing 1% serum for 72 hours. At the end of the incubation period, cells were harvested, total number of cells were counted and proteins were extracted. Protein content per cell was calculated. Cumulative data are displayed as bar graphs.</p

HIV induces phosphorylation p70S6K and downstream signaling in Tubular cells.

<p>MPTECs were tranduced either with empty vector or NL4-3 and then incubated in media for 72 hours. Subsequently, proteins were extracted from vector/MPTECs and HIV/MPTECs, Western blots were prepared and probed for phospho-70S6K, phospho-eIF4B, and phospho-4EBP1. Immunoblots were stripped and reprobed for actin (n = 4). A. Representative gels (in duplicate) showing tubular cell expression of phospho-70S6K under control (vector) and HIV infection states (upper lane). The lower lane shows tubular cell expression of actin under similar conditions. A bar diagram shows cumulative data of four sets of experiments in the right panel. B. Representative gels (in duplicate) showing tubular cell expression of phospho-eIF4B under control (vector) and HIV infection states (upper lane). The lower lane shows tubular cell expression of actin under similar conditions. A bar diagram showing cumulative data of four sets of experiments is in the right panel. C. Representative gels (in duplicate) showing tubular cell expression of phospho-EBP1 under control (vector) and HIV infection states (upper lane). The lower lane shows tubular cell expression of actin under similar conditions. A bar diagram showing cumulative data of 4 sets of experiments is shown in the right panel.</p