Autophagy genes' expression is upregulated in visceral fat in human obesity, associating with obesity-related cardio-metabolic risk. E2F1 (E2F transcription factor 1) was shown in cancer cells to transcriptionally regulate autophagy. We hypothesize that E2F1 regulates adipocyte autophagy in obesity, associating with endocrine/metabolic dysfunction, thereby, representing non-cell-cycle function of this transcription factor. E2F1 protein (N=69) and mRNA (N=437) were elevated in visceral fat of obese humans, correlating with increased expression of ATG5 (autophagy-related 5), MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β), but not with proliferation/cell-cycle markers. Elevated E2F1 mainly characterized the adipocyte fraction, whereas MKI67 (marker of proliferation Ki-67) was elevated in the stromal-vascular fraction of adipose tissue. In human visceral fat explants, chromatin-immunoprecipitation revealed body mass index (BMI)-correlated increase in E2F1 binding to the promoter of MAP1LC3B, but not to the classical cell cycle E2F1 target, CCND1 (cyclin D1). Clinically, omental fat E2F1 expression correlated with insulin resistance, circulating free-fatty-acids (FFA), and with decreased circulating ADIPOQ/adiponectin, associations attenuated by adjustment for autophagy genes. Overexpression of E2F1 in HEK293 cells enhanced promoter activity of several autophagy genes and autophagic flux, and sensitized to further activation of autophagy by TNF. Conversely, mouse embryonic fibroblast (MEF)-derived adipocytes from e2f1 knockout mice (e2f1−/−) exhibited lower autophagy gene expression and flux, were more insulin sensitive, and secreted more ADIPOQ. Furthermore, e2f1−/− MEF-derived adipocytes, and autophagy-deficient (by Atg7 siRNA) adipocytes were resistant to cytokines-induced decrease in ADIPOQ secretion. Jointly, upregulated E2F1 sensitizes adipose tissue autophagy to inflammatory stimuli, linking visceral obesity to adipose and systemic metabolic-endocrine dysfunction.

Repeated blood pressure (BP) measurements allow better control of hypertension. Current measurements rely on cuff-based devices. The aim of the present study was to compare BP measurements using a novel cuff-less photoplethysmography-based device to a standard sphygmomanometer device. Males and females were recruited from within the general population who arrived at a public BP screening station. One to two measurements were taken from each using a sphygmomanometer-based and the photoplethysmography-based devices. Devices were considered equal if the mean difference between paired measurements was below 5 mmHg and the Standard Deviation (SD) was no greater than 8 mmHg. Agreement and reliability analyses were also performed. 1057 subjects were included in the study analysis. There were no adverse events during the study. The mean (± SD) difference between paired measurements for all subjects was -0.1 ± 3.6 mmHg for the systolic and 0.0 ± 3.5 mmHg for the diastolic readings. We found 96.31% agreement in identifying hypertension and an Interclass Correlation Coefficient of 0.99 and 0.97 for systolic and diastolic measurements, respectively. The photoplethysmography-based device was found similar to the gold-standard sphygmomanometer-based device with high agreement and reliability levels. The device might enable a reliable, more convenient method for repeated BP monitoring.

Background Clinical trial guidelines for assessing the safety of vaccines, are primarily based on self-reported questionnaires. Despite the tremendous technological advances in recent years, objective, continuous assessment of physiological measures post-vaccination is rarely performed. Methods We conducted a prospective observational study during the mass vaccination campaign in Israel. 160 participants >18 years who were not previously found to be COVID-19 positive and who received the BNT162b2 COVID-19 (Pfizer BioNTech) vaccine were equipped with an FDA-approved chest-patch sensor and a dedicated mobile application. The chest-patch sensor continuously monitored 13 different cardiovascular, and hemodynamic vitals: heart rate, blood oxygen saturation, respiratory rate, systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, heart rate variability, stroke volume, cardiac output, cardiac index, systemic vascular resistance and skin temperature. The mobile application collected daily self-reported questionnaires on local and systemic reactions. Results We identify continuous and significant changes following vaccine administration in nearly all vitals. Markedly, these changes are observed even in presumably asymptomatic participants who did not report any local or systemic reaction. Changes in vitals are more apparent at night, in younger participants, and in participants following the second vaccine dose. Conclusion the considerably higher sensitivity of wearable sensors can revolutionize clinical trials by enabling earlier identification of abnormal reactions with fewer subjects.