Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with Krtcap3 (preprint)

We previously identified Keratinocyte-associated protein 3, Krtcap3, as an obesity-related gene in female rats where a whole-body Krtcap3 knock-out (KO) led to increased adiposity compared to wild-type (WT) controls when fed a high-fat diet (HFD). We sought to replicate this work to better understand the function of Krtcap3 but were unable to reproduce the adiposity phenotype. In the current work, WT female rats ate more compared to WT in the prior study, with corresponding increases in body weight and fat mass, while there were no changes in these measures in KO females between the studies. The prior study was conducted before the COVID-19 pandemic, while the current study started after initial lock-down orders and was completed during the pandemic with a generally less stressful environment. We hypothesize that the environmental changes impacted stress levels and may explain the failure to replicate our results. Analysis of corticosterone (CORT) at euthanasia showed a significant study by genotype interaction where WT had significantly higher CORT relative to KO in Study 1, with no differences in Study 2. These data suggest that decreasing Krtcap3 expression may alter the environmental stress response to influence adiposity. We also found that KO rats in both studies, but not WT, experienced a dramatic increase in CORT after their cage mate was removed, suggesting a separate connection to social behavioral stress. Future work is necessary to confirm and elucidate the finer mechanisms of these relationships, but these data indicate the possibility of Krtcap3 as a novel stress gene.

Results of the national biomonitoring program show persistent iodine deficiency in Israel.

BACKGROUND: Adequate iodine intake is essential for human health, for normal thyroid function, and for attainment of full intellectual potential in children. In light of Israel's lack of a mandatory salt fortification policy, heavy reliance on desalination and low iodine intake from dairy products and seafood, there is concern in Israel that the population is iodine deficient. Indeed, the first Israeli National Iodine Survey in 2016 found a median urinary iodine concentration (UIC) of 83 µg/L among school age children, falling below the WHO's adequacy range of 100-299 µg/L for children. METHODS: In the framework of the National Human Biomonitoring Program in Israel, spot urine samples and questionnaire data were collected from 166 healthy children aged 4-12 years in 2020-2021. Urinary iodine concentrations were measured at the Ministry of Health National Biomonitoring Laboratory, using mass spectrometry. An international comparison of median urinary iodine concentrations (UIC) was performed taking into consideration the levels of desalinated water per capita, and fortification policies. RESULTS: The overall median (interquartile range [IQR]) UIC was 80.1 µg/L (44.7-130.8 µg/L) indicating that the population's iodine status has not improved in the five years that have passed since inadequacy was first identified. When comparing 13 countries with population size above 150,000, whose desalinated water per capita was at least 1 m3, Israel and Lebanon were the only countries with median UIC below the WHO adequacy range. CONCLUSIONS: There is an urgent need for mandatory salt fortification in Israel. Based on our international comparison, we conclude that the potential impact of desalination on iodine intake can be compensated for using the implementation of salt fortification policy. This study highlights the critical need for public health surveillance of nutritional and environmental exposures using human biomonitoring, with emphasis on vulnerable populations such as pregnant women and children.

Child food insecurity in the wake of the COVID-19 pandemic: urgent need for policy evaluation and reform in Israel's school feeding programs.

Even in high-income countries like Israel, children have been particularly vulnerable to the surge in food insecurity driven by quarantines, unemployment, and economic hardships of the COVID-19 pandemic. Under normal circumstances, School Feeding Programs (SFPs) can help to ensure child food security. In the wake of the pandemic, policy makers worldwide have been challenged to adapt national SFPs to provide nutritional support to children (and indirectly to their families) during extended school closures. Most national SFPs implemented contingency plans to ensure continued nutritional support for children. In Israel, where SFPs were largely suspended during long periods of mandated school closing, there was a loss of 30-50% of feeding days for the ~ 454,000 children enrolled in the program. The lack of emergency contingency planning and failure to maintain Israeli SFPs during school closures reveals longstanding structural policy flaws that hindered coordination between relevant ministries and authorities and impeded the mobilization of funds and existing programs to meet the emergent need. The school feeding law does not identify child food security as an explicit aim, there are no benchmarks for monitoring and evaluating the program to ensure that the food aid reaches the children most in need, even routinely, and the Ministry of Education had no obligation to maintain the program and to marshal data on the participants that could be acted upon in the emergency. Moreover, because Israeli SFPs are "selective", in other words, implemented according to community risk (low-income, high poverty rate) and geographical factors, attendant stigma and financial burdens can make participation in the program less attractive to families and communities that need them the most. We argue that Israel should make urgent, long-term improvements to the SFPs as follows: First, eliminating childhood food insecurity should be made an explicit goal of legislation in the broader context of national social, health, and nutritional goals, and this includes ensuring SFPs are maintained during emergencies. Second, the government should assume responsibility for the routine assessment and data collection on food insecurity among Israeli children. Third, SFPs should be subjected to rigorous independent program evaluation. Finally, a "universal" SFP providing nutritious diets would likely improve the health of all Israeli children, across all socioeconomic backgrounds. These steps to guarantee that Israeli children have food to realize their full physical and cognitive potential would emphasize Israel's firm commitment to support multiple dimensions of health, educational achievement, and societal values, to combat the complex and long-term consequences of the pandemic, and to prepare for the next one.

CSO (Canadian Society of Otolaryngology - Head & Neck Surgery) position paper on return to Otolaryngology - Head & Neck Surgery Clinic Practice during the COVID-19 pandemic in Canada.

The novel Coronavirus (COVID-19) has created a worldwide deadly pandemic that has become a major public health challenge. All semi-urgent and elective medical care has come to a halt to conserve capacity to care for patients during this pandemic. As the numbers of COVID-19 cases decrease across Canada, our healthcare system also began to reopen various facilities and medical offices. The aim for this document is to compile the current evidence and provide expert consensus on the safe return to clinic practice in Otolaryngology - Head & Neck Surgery. These recommendations will also summarize general precaution principles and practical tips for office across Canada to optimize patient and provider safety. Risk assessment and patient selection are crucial to minimizing exposure to COVID-19. Controversial topics such as COVID-19 mode of transmission, duration of exposure, personal protective equipment, and aerosol-generating procedures will be analyzed and discussed. Practical solutions of pre-visit office preparation, front office and examination room set-up, and check out procedures are explored. Specific considerations for audiology, pediatric population, and high risk AGMPs are also addressed. Given that the literature surrounding COVID-19 is rapidly evolving, these guidelines will serve to start our specialty back into practice over the next weeks to months and they may change as we learn more about this disease.

Influence of recent administration and type of oncological treatment (T) in survival of oncological patients (p) with COVID-19: Experience of Vall d'Hebron University Hospital

Background: SARS-CoV-2 outbreak has impacted on the management of oncological p, leading to treatment delays in a considerable number of cases. The aim of this study was to evaluate if oncological T affected negatively COVID-19 outcome. Methods: We retrospectively analyzed clinical data from p with solid tumors under active systemic T (received in the last 6 months) that were diagnosed with SARS-CoV-2 infection (defined as positive PCR) between March and 11th May 2020 in our center. Study endpoint was death due to COVID-19. We divided the patients in two groups;those who had received treatment in the last 4 weeks and those who had not. Descriptive and univariate analysis were performed to detect the effect of T type and other variables on COVID-19 related mortality. Results: A total of 70 p were included with a median follow-up of 28 days (10-47) and active oncological T had been administered in the past 4 weeks to 44 p. Median age was 66 (IQR 56-74), 23 p (52.27%) were female and 41 (93.2%) had a baseline ECOG≤1. The most frequent primary site was lung tumor (12 p [27.3%]), followed by breast (11 p [25%]) and gastrointestinal (5 p [11.4%]). Thirty-one p (70.5%) had metastatic disease and 13 (29.5%) were included in clinical trials. Twenty-four p (54.5%) received chemotherapy (CT), 14 (31.8%) targeted therapies, 9 (20.4%) immunotherapy (IT), 5 (11.4%) radiotherapy and 6 (13.6%) hormonotherapy. A total of 13 p (29.5%) received different combinations of oncological T. Death due to COVID-19 occurred in 5/22 (22.7%) p receiving CT and 6/21 (28.5%) p in the non-CT (p>0.05). Only 1/9 (11.1%) p treated with IT died compared to 11/35 (31.4%) p in the rest of the cohort (p>0.05). Age>71, comorbidities such as chronic obstructive pulmonary disease and ECOG status>2 were associated to a higher mortality. The distribution of these variables between the anticancer T groups was not different. Conclusions: Our results suggest that CT and other anticancer T might not worsen COVID-19 related mortality;nevertheless, the number of patients was small. and decision making has to be individualized. Our findings may warrant further investigation in larger studies. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie;AstraZeneca;Blueprint medicines;Boehringer Ingelheim;Bristol-Myers Squibb;Celgene;Eli Lilly;Guardant Health;Janssen;Medscape;Merck KGaA;Novartis;Pfizer;Roche;Takeda;Touchtime;Research grant/Funding (self), Research grant/Funding (institution): Fundación Merck Salud;Oncology Innovation EMD Serono. J. Carles: Advisory/Consultancy, Speaker Bureau/Expert testimony: Johnson & Johnson;Bayer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Astellas Pharma;Advisory/Consultancy: Pfizer;Sanofi;MSD Oncology;Advisory/Consultancy, Research grant/Funding (self): Roche;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZéneca;Speaker Bureau/Expert testimony: Asofarma;Research grant/Funding (self), Travel/Accommodation/Expenses: BMS;ravel/Accommodation/Expenses: Ipsen;Roche;Research grant/Funding (self): AB Science;Aragon Pharmaceuticals;Pharmaceuticals;INC;Blueprint Medicines Corporation;N Immunotherapeutics INC;Boehringer Ingelheim España, S.A.;Clovis Oncology;Cougar Biotechnology INC;Deciphera Pharmaceuticals LLC;Exelixis INC;F. Hoffmann-La Roche LTD;Genentech INC;Glaxosmithkline;Incyte Corporation;Janssen-Cilag International NV;Karyopharm Therapeutics INC;Laboratoires Leurquin Mediolanum SAS. J. Tabernero: Honoraria (self): Array Biopharma;AstraZeneca;Bayer;BeiGene;Boehringer Ingelheim;Chugai;Genentech;Genmab A/S;Halozyme;Imugene Limited;Inflection Biosciences Limited;Ipsen;Kura Oncology;Lilly;MSD;Merck Serono;Menarini;Merrimack;Merus;Molecular Partners;Novartis;Peptomyc;Pfizer;Pharmacyclics;ProteoDesign SL;Rafael Pharmaceuticals;F. Hoffmann-La Roche Ltd;): Sanofi;eaGen;Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. All other authors have declared no conflicts of interest.