Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder.

OBJECTIVE: Body dysmorphic disorder (BDD) is an often-severe condition in which individuals are preoccupied by misperceptions of their appearance as defective or ugly. Only serotonin reuptake inhibitors and cognitive-behavioral therapy have been demonstrated efficacious in randomized controlled trials. Psilocybin is a psychedelic drug with growing evidence for safety and efficacy in treatment of depression. This study aimed to pilot test the feasibility, tolerability, safety, and efficacy of psilocybin treatment of adults with BDD. METHODS: In this open-label trial, 12 adults (8 women, 4 men) with moderate-to-severe non-delusional BDD that had been unresponsive to at least one serotonin reuptake inhibitor trial received a single oral dose of psilocybin 25 mg. There was no control group. Psychological support was provided before, during, and after the dosing session. The primary outcome measure for efficacy was the Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDD-YBOCS) score during 12 weeks of assessments after dosing. RESULTS: All participants completed dosing and all follow-up assessments. BDD-YBOCS scores decreased significantly over 12 weeks of follow-up (p < .001) with a large effect size (partial eta squared = 0.54), and significant changes from baseline were present at week 1 and persisted through week 12. Secondary efficacy measures of BDD symptoms, conviction of belief, negative affect, and disability also improved significantly, and no serious adverse events occurred. At week 12, seven participants (58%) were rated responders, based on ≥30% decrease in BDD-YBOCS. CONCLUSION: This study provides promising preliminary support for psilocybin as a treatment of BDD, warranting future controlled studies.

Relationship Between Moderate-to-Vigorous Physical Activity and Glycemia Among Young Adults with Type 1 Diabetes and Overweight or Obesity: Results from the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) Study.

Aims: Using data from the ACT1ON study, we conducted secondary analyses to assess the relationship between minutes of moderate-to-vigorous physical activity (MVPA) and glycemia in adults with type 1 diabetes (T1D) and overweight or obesity. Materials and Methods: Participants (n = 66) with T1D provided measures of glycemia (hemoglobin A1c [HbA1c], percent of time below range <70 mg/dL, time-in-range [TIR 70-180 mg/dL], and time above range [TAR >180 mg/dL]) and self-reported physical activity (Global Physical Activity Questionnaire [GPAQ] and Previous Day Physical Activity Recalls [PDPAR]) at baseline, 3, 6, and 9 months postintervention. Wearable activity data were available for a subset of participants (n = 27). Associations were estimated using mixed effects regression models adjusted for design, demographic, clinical, and dietary covariates. Results: Among young adults 19-30 years of age with a baseline HbA1c of 7.9% ± 1.4% and body mass index of 30.3 (interquartile range 27.9, 33.8), greater habitual weekly MVPA minutes were associated with higher HbA1c through the GPAQ (P < 0.01) and wearable activity data (P = 0.01). We did not observe a significant association between habitual MVPA and any continuous glucose monitoring metrics. Using PDPAR data, however, we observed that greater daily MVPA minutes were associated with more TAR (P < 0.01) and reduced TIR (P < 0.01) on the day following reported physical activity. Conclusions: Among young adults with T1D and overweight or obesity, increased MVPA was associated with worsened glycemia. As physical activity is vital to cardiovascular health and weight management, additional research is needed to determine how to best support young adults with T1D and overweight or obesity in their efforts to increase physical activity. Clinical Trial Registration number: NCT03651622.

Physical Activity and Glycemia among Young Adults with Type 1 Diabetes and Overweight or Obesity-Results from Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)

The ACT1ON pilot study evaluated the feasibility of three dietary strategies to optimize weight and glycemic management among young adults with T1D and overweight or obesity. As a secondary measure, self-reported physical activity (PA) was collected at baseline, 3-, 6-, and 9-months from 68 young adults with T1D (age 25.5 ± 3.1 years, 72.1% female, HbA1c 7.9 ± 1.8%, BMI 30.4 (27.9 - 33.9)) . Using the Global Physical Activity Questionnaire (GPAQ, n=195) and Previous Day Physical Activity Recalls (PDPAR, n=123) , we estimated weekly minutes of moderate-to-vigorous physical activity (MVPA) . Following the COVID-19 outbreak, a subset of participants wore Garmin Vivosmart4® PA trackers for two weeks at each visit (44 measurements from 27 participants) . Mixed effects regression models assessed the relationship between weekly minutes of MVPA and HbA1c using each PA measure. Median weekly minutes of MVPA were 33% lower following the COVID-19 outbreak compared to pre-pandemic PA levels (p=0.02) per the GPAQ, but not PDPAR (-7.7%, p=0.34) . After adjusting for design, demographic, clinical, and dietary variables, a 1 standard deviation increase in weekly minutes of MVPA (GPAQ) was associated with an absolute increase of 0.27% HbA1c (p>0.001) . A small, statistically non-significant association was observed for PDPAR (β=0.13, p=0.19) ;however, we observed a borderline statistically significant association using the PA tracker data (β=0.231, p=0.08) , despite a smaller sample size (n=44) . These results suggest that among young adults with T1D and overweight and obesity, higher levels of PA may lead to challenges in achieving optimal glycemia. Future work is needed to determine how to best support young adults with T1D and overweight and obesity in attaining both their PA and glycemic management goals.

Estimating the social and spatial impacts of Covid mitigation strategies in United Kingdom regions: synthetic data and dashboards

This study advances understanding of the broader social and spatial impacts of COVID-19 restrictive measures, particularly how they may have impacted individuals and households and, in turn, the geographic areas in which these individuals and households are concentrated. Data are combined and linked to a novel individual-level synthetic dataset and an interactive dashboard is developed to assist with the identification and understanding of the social and spatial impacts of restrictions. To illustrate the utility of this approach, the analysis focuses on the impact of three restrictions within a defined spatial area: Yorkshire and Humberside (UK). Results highlight the additive nature of restriction impacts and suggest areas that may have the least future resilience as policy priority areas. This approach is transferable to other regions and the use of the dashboard allows rapid consideration and communication of the social and spatial nature of inequalities to researchers, practitioners and the general public.

Babies born in the 1st 2020 lockdown: Early data from the CORAL study

Background: The CORAL study is a cross-sectional study of the impact of the Coronavirus pandemic on allergic and autoimmune dysregulation of infants born in March, April and May 2020, during Ireland's 1 st COVID-19 pandemic Lockdown. Method: Invitations were sent to families of 3065 term, singleton babies. Exclusion criteria were ante-natal PCR-proven SARSCoV-2 in a parent or co-dwelling person, IV antibiotics in neonatal period, multiple births and major congenital anomalies. At 6 months babies were invited to attend CHI Connolly for point-of-care SARSCoV-2 antibody testing. Results: Of the 3065 letters sent 353 babies were enrolled.53.7% of enrolled infants were male, 78.4% were white-Irish, average birth weight was 3.506kg. 45% were first-born and 95.5% of mothers were educated at 3 rd level or higher. Babies' average number of close contacts other than household members was 2.3 during lockdown and 5.6 afterwards. 42.5% were reported to be currently breast-fed at enrolment. By 6 months, 97% of infants had solid foods introduced but only 24.5% had tried egg and 9.6% had tried peanut. Complete primary immunisation uptake at 6 months was 99%. Lastly, 3 babies out of 200 (1.3%) tested showed presence of IgM & IgG SARSCoV-2 antibodies;2 were PCR negative, the other PCR positive. Conclusion: Initial breastfeeding and immunisation uptake to 6 months are reassuringly high in this self-selected, highly-educated cohort. The rare positive antibody tests suggest recent or current infection, so newborn babies appear to have been protected from SARSCoV-2 exposure during the 1 st COVID Pandemic lockdown.

Endocytosis of abiotic nanomaterials and nanobiovectors: Inhibition of membrane trafficking.

Humans are exposed to nanoscopical nanobiovectors (e.g. coronavirus SARS-CoV-2) as well as abiotic metal/carbon-based nanomaterials that enter cells serendipitously or intentionally. Understanding the interactions of cell membranes with these abiotic and biotic nanostructures will facilitate scientists to design better functional nanomaterials for biomedical applications. Such knowledge will also provide important clues for the control of viral infections and the treatment of virus-induced infectious diseases. In the present review, the mechanisms of endocytosis are reviewed in the context of how nanomaterials are uptaken into cells. This is followed by a detailed discussion of the attributes of man-made nanomaterials (e.g. size, shape, surface functional groups and elasticity) that affect endocytosis, as well as the different human cell types that participate in the endocytosis of nanomaterials. Readers are then introduced to the concept of viruses as nature-derived nanoparticles. The mechanisms in which different classes of viruses interact with various cell types to gain entry into the human body are reviewed with examples published over the last five years. These basic tenets will enable the avid reader to design advanced drug delivery and gene transfer nanoplatforms that harness the knowledge acquired from endocytosis to improve their biomedical efficacy. The review winds up with a discussion on the hurdles to be addressed in mimicking the natural mechanisms of endocytosis in nanomaterials design.

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy.

In late 2019, a new member of the Coronaviridae family, officially designated as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.

Evolution of Specimen Self-Collection in the COVID-19 Era: Implications for Population Health Management of Infectious Disease.

Laboratory testing is an important component in the diagnosis of respiratory tract infections such as with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, specimen collection not only risks exposure of health care workers and other patients to infection, but also necessitates use of personal protective equipment that may be in short supply during periods of heightened disease activity. Self-collection of nasal or oropharyngeal swabs offers an alternative to address these drawbacks. Although studies in the past decade have demonstrated the utility of this approach for respiratory infections, it has not been widely adopted in routine clinical practice. The rapid spread of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has focused attention on the need for safe, convenient, timely, and scalable methods for collecting upper respiratory specimens for testing. The goals of this article are to highlight the literature regarding self-collected nasal or oropharyngeal specimens for respiratory pathogen testing; discuss the role of self-collection in helping prevent the spread of the COVID-19 disease from infected patients and facilitating a shift toward "virtual" medicine or telemedicine; and describe the current and future state of self-collection for infectious agents, and the impacts these approaches can have on population health management and disease diagnosis and prevention.

Nanobased Platforms for Diagnosis and Treatment of COVID-19: From Benchtop to Bedside.

Human respiratory viral infections are the leading cause of morbidity and mortality around the world. Among the various respiratory viruses, coronaviruses (e.g., SARS-CoV-2) have created the greatest challenge and most frightening health threat worldwide. Human coronaviruses typically infect the upper respiratory tract, causing illnesses that range from common cold-like symptoms to severe acute respiratory infections. Several promising vaccine formulations have become available since the beginning of 2021. Nevertheless, achievement of herd immunity is still far from being realized. Social distancing remains the only effective measure against SARS-CoV-2 infection. Nanobiotechnology enables the design of nanobiosensors. These nanomedical diagnostic devices have opened new vistas for early detection of viral infections. The present review outlines recent research on the effectiveness of nanoplatforms as diagnostic and antiviral tools against coronaviruses. The biological properties of coronavirus and infected host organs are discussed. The challenges and limitations encountered in combating SARS-CoV-2 are highlighted. Potential nanodevices such as nanosensors, nanobased vaccines, and smart nanomedicines are subsequently presented for combating current and future mutated versions of coronaviruses.

Pityriasis rubra pilaris post-infection due COVID-19: case report.

CASE DESCRIPTION: 32-month-old boy, IgG positive for SARS-CoV-2, presented to the emergency department with dermatologic lesions. CLINICAL FINDINGS: Four days before admission, he presented skin eruptions with redness and pruritus on hands and feet. Generalized papular erythema was evidenced, upper extremities with diffuse erythematosquamous plaques, palmoplantar keratoderma, so he was evaluated by a dermatologist who diagnosed pityriasis rubra pilaris. TREATMENT AND OUTCOME: rehydrating cream, cetirizine 0.5 mg/kg/day every two days, and prednisolone 2 mg/kg/day in the morning. He was discharged after 14 days, the patient presented clinical improvement, but the erythematous lesion persisted on the trunk and extremities. In the evaluation, after three months, the patient did not show the described lesions, evidencing an improvement and clinical resolution of the dermatological problems. CLINICAL RELEVANCE: We report a patient with pityriasis rubra piloris associated with a post-infection by SARS-CoV-2 that had not been described before.