Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM.

Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort study.

Seroprevalence of SARS-CoV-2 IgG among health care workers (HCWs) is crucial to inform infection control programs. Conflicting reports have emerged on the longevity of SARS-CoV-2 IgG. Our objective is to describe the prevalence of SARS-CoV-2 IgG in HCWs and perform 8 months longitudinal follow-up (FU) to assess the duration of detectable IgG. In addition, we aim to explore the risk factors associated with positive SARS-CoV-2 IgG. The study was conducted at a large COVID-19 public hospital in Riyadh, Saudi Arabia. All HCWs were recruited by social media platform. The SARS-CoV-2 IgG assay against SARS-CoV-2 nucleocapsid antigen was used. Multivariable logistic regression was used to examine association between IgG seropositive status and clinical and epidemiological factors. A total of 2528 (33% of the 7737 eligible HCWs) participated in the survey and 2523 underwent baseline serological testing in June 2020. The largest occupation groups sampled were nurses [n = 1351(18%)], physicians [n = 456 (6%)], administrators [n = 277 (3.6%)], allied HCWs [n = 205(3%)], pharmacists [n = 95(1.2%)], respiratory therapists [n = 40(0.5%)], infection control staff [n = 21(0.27%], and others [n = 83 (1%)]. The total cohort median age was 36 (31-43) years and 66.3% were females. 273 were IgG seropositive at baseline with a seroprevalence of 10.8% 95% CI (9.6%-12.1%). 165/185 and 44/112 were persistently IgG positive, at 2-3 months and 6 months FU respectively. The median (25th- 75th percentile) IgG level at the 3 different time points was 5.86 (3.57-7.04), 3.91 (2.46-5.38), 2.52 (1.80-3.99) respectively. Respiratory therapists OR 2.38, (P = 0.035), and those with hypertension OR = 1.86, (P = 0.009) were more likely to be seropositive. A high proportion of seropositive staff had prior symptoms 214/273(78%), prior anosmia was associated with the presence of antibodies, with an odds ratio of 9.25 (P<0.001), as well as fever and cough. Being a non-smoker, non-Saudi, and previously diagnosed with COVID-19 infection by PCR were statistically significantly different by seroprevalence status. We found that the seroprevalence of IgG against SARS-CoV-2 nucleocapsid antigen was 10.8% in HCWs at the peak of the pandemic in Saudi Arabia. We also observed a decreasing temporal trend of IgG seropositivity over 8 months follow up period.

Frequency of emotional disturbances among hostelites and day scholars medical students.

OBJECTIVE: This study was aimed to determine and compare the frequency of the emotional disturbances, anxiety and depression among the medical students on Hospital Anxiety Depression scale (HAD) score among the hostelites and day scholars. METHODS: This cross sectional study was conducted at a private medical college in Faisalabad, Pakistan, from March 2019 to April 2019, comprising of 105 male and female students. Validated Hospital Anxiety depression scale (HAD-A and HAD-D) was used to collect data from 1st year and 2nd year MBBS students in order to evaluate anxiety and depression among them. Data was analyzed on SPSS 21. Pearson's Chi-square was applied to compare the percentages of anxious and depressed subjects among the studied group. Independent sample t-test was applied for comparison of mean HAD scores between hostelites and day scholars. P value ≤ 0.05 was taken as significant. RESULTS: There were 105 students in the study with a mean age of 19.4±0.68 years. Overall, 82.7% students had anxiety, and 52.1% suffered from depression. Average HAD -A and HAD- D scores were 11.2±3.41 and 7.2±3.37 respectively. Greater number of hostelites was suffering from emotional disturbances as compared to day scholars. HAD -A scores was significantly higher in hostelites than day scholars with P value 0.003*(11.85±3.42 Vs 10.92 ±2.56). HAD- D scores were also higher in hostilities but difference was insignificant. (7.57±3.42 Vs 6.85 ±1.58). CONCLUSIONS: Emotional disturbance including anxiety and depression are found to be highly prevalent among medical students of a private medical college in Faisalabad. Hostelites are more prone to anxiety and depression than day scholars.

Association of apoptotic marker cytokeratin18 with blood pressure in nonalcoholic fatty liver disease patients.

OBJECTIVE: Non Alcoholic fatty liver disease (NAFLD) associated with hypertension (HTN) is an emerging health issue globally. It is associated with increased levels of apoptotic marker CK18. Main objective of this study was to explore association of cytokeratin18 (CK18) with hypertension (HTN) in NAFLD patients. METHODS: Descriptive cross sectional study was conducted in Mayo hospital Lahore. Hundred NAFLD subjects were enrolled from OPD of radiology department after approval from ethical review committee. Anthropometric measurements were taken and blood pressure (BP) was measured by mercury sphygmomanometer. Blood samples were drawn from each patient for CK18 levels with ELISA. Data was analyzed by SPSS 20. Continuous variables were presented as mean± SD. Association between CK18 and HTN were analyzed by regression analysis and results were presented as beta coefficient. P <0.05 was taken as significant. RESULTS: Mean age of studied subjects was 43.8±5.34 with height (m), weight (kg) and BMI 1.59±0.063 m, 78.2±11.17 kg, 30.5±4.07kg/m2 respectively. Systolic and diastolic blood pressures were 106±12.8, 72± 12.8mmHg. CK 18 was not significantly associated with systolic (P value 0.55) and diastolic BP (P value 0.37) most probably due to small size of study. CONCLUSIONS: Most of the NAFLD patients were hypertensive and have raised CK18 levels than normotensive subjects. So, raised levels of CK18 in NAFLD subjects might be helpful in early screening of HTN. However, significant association was not observed probably due to small sample size.

Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle.

In vivo reprogramming is a promising approach for tissue regeneration in response to injury. Several examples of in vivo reprogramming have been reported in a variety of lineages, but some including skeletal muscle have so far proven refractory. Here, we show that acute and chronic injury enables transcription-factor-mediated reprogramming in skeletal muscle. Lineage tracing indicates that this response frequently originates from Pax7+ muscle stem cells. Injury is associated with accumulation of senescent cells, and advanced aging or local irradiation further enhanced in vivo reprogramming, while selective elimination of senescent cells reduced reprogramming efficiency. The effect of senescence appears to be, at least in part, due to the release of interleukin 6 (IL-6), suggesting a potential link with the senescence-associated secretory phenotype. Collectively, our findings highlight a beneficial paracrine effect of injury-induced senescence on cellular plasticity, which will be important for devising strategies for reprogramming-based tissue repair.