A comparison of weekly versus 3-weekly cisplatin during adjuvant radiotherapy for high-risk head and neck cancer

SummaryObjectivesTo compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC).Materials and methodsConsecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin.ResultsOf 270 high risk patients, 60 received 3-weekly 100mg/m2 and 48 received weekly 50mg/m2 cisplatin during adjuvant radiotherapy (60–66Gy in 30–33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m2 (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m2 (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m2 was given to 67.7% of patients in the 3-weekly cohort and 85.2% (P=0.039) in the weekly cohort. The rate of feeding tube dependency 6months after treatment, osteoradionecrosis, neutropenic fever, and persistent renal function decline were not statistically different.ConclusionsAbout one half of high-risk HNSCC patients are not eligible for cisplatin during postoperative radiotherapy. Patients treated with weekly 50mg/m2 cisplatin received a higher cumulative dose with comparable toxicity as patients who received 3-weekly 100mg/m2 cisplatin. Efficacy and applicability to the frequently used weekly 40mg/m2 schedule remains to be evaluated

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Comparison of depressive symptoms among healthcare workers in high-risk versus low-risk areas during the first month of the COVID-19 pandemic in China

IntroductionThe psychological health of healthcare workers (HCWs) has become a significant concern, particularly during the initial stage of a pandemic. This study compared the depressive symptoms among HCWs in high-risk areas (HRAs) and low-risk areas (LRAs) with matching demographics.MethodsA cross-sectional study was employed to compare the depressive symptoms (Patient Health Questionnaire score ≥ 10), workplace environment characteristics, the Health Belief Model (HBM) and socio-demographics of the HCWs working in HRAs and LRAs in several accessible regions (mainly Hubei Province and Guangdong–Hong Kong–Macao Greater–Bay–Area) in China. Eight hundred eighty-five HCWs were recruited for unmatched analysis between March 6 and April 2, 2020. After matching with occupation and years of service using a 1:2 ratio, 146 HCWs in HRAs and 290 HCWs in LRAs were selected for matched analysis. Subgroup analyzes were performed using two individual logistic regressions to delineate the associated factors in LRAs and HRAs, respectively.ResultsHCWs in LRAs (Prevalence = 23.7%) had 1.96 times higher odds of depressive symptoms than those in HRAs (Prevalence = 15.1%) after adjusting for occupation and years of service (p < 0.001). Significant differences in workplace environment characteristics (p < 0.001) and the 5-dimension of the HBM of HCWs (p < 0.001 to p = 0.025) were found between HRAs and LRAs.Logistic regression showed that workers with years of service between 10 and 20  years (OR:6.27), ever had contact with COVID-19 patients (OR:14.33) and had higher scores of “perceived barrier” of HBM (OR:4.48) predicted depressive symptoms in HRAs while working in pneumology departments and infectious disease units (OR:0.06), and high “self-efficacy” in the HBM (OR:0.13) was a protective factor against depressive symptoms.Contrarily, in LRAs, those HCWs who worked in ICUs (OR:2.59), had higher scores of “perceived susceptibility toward the COVID-19 outbreak” (OR:1.41), “perceived severity of the pandemic” (OR:1.25), and “perceived barriers of wearing masks” (OR:1.43) in the HBM predicted depressive symptoms. High “cues to action” (OR:0.79), and better “knowledge” (OR:0.79) in the HBM were protective factors against depressive symptoms.ConclusionThe risk of depressive symptoms of HCWS was double in LRAs than in HRAs in the first month of the COVID-19 pandemic. Furthermore, salient predictors for depressive symptoms among HCWs in HRAs and LRAs were very different

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy