A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Nasolabial appearance of bilateral cleft lip repair at five years of age. Comparing techniques of modified advancement-rotation (Delaire) with Manchester repair: a retrospective cohort study.

The techniques used to repair bilateral cleft lip have evolved over time, yet little data exist to compare outcomes using the various techniques. The aim of this study was to retrospectively evaluate and compare the aesthetic outcomes of two types of complete bilateral cleft repair: advancement rotation and a historic cohort repaired with the Manchester technique. A total of 32 consecutive patients who had complete repair of bilateral cleft lips were identified retrospectively from our centre using inpatient records. The first 16 (born between 1994 and 2005) underwent the Manchester repair, the second 16 (born between 2006 and 2010) a Delaire modified advancement rotation technique. Standardised photographs were taken at five years post repair and cropped to isolate the nasolabial component. Appearance outcomes were assessed by 20 members of the cleft and plastic surgery team, who were each asked to rate all 32 images using the Asher-McDade five-point scale. A chi squared test was used to determine whether there was a statistically significant difference in cleft scores between the two approaches. There was a mean (SD) of 2.8 (1.02) in the advancement rotation group and a mean (SD) of 3.1 (1.07) in the Manchester group. There was a statistically significant difference in the distribution of scores in the advancement rotation group compared with the Manchester group, with lower scores (better results) in the advancement rotation group (p=0.003). This study demonstrates that the advancement rotation technique for the repair of bilateral cleft lip defects resulted in a superior nasolabial appearance when directly compared with the Manchester repair at 5 years of age.

Personal protective equipment for surgeons during COVID-19 pandemic: systematic review of availability, usage and rationing.

BACKGROUND: Surgeons need guidance regarding appropriate personal protective equipment (PPE) during the COVID-19 pandemic based on scientific evidence rather than availability. The aim of this article is to inform surgeons of appropriate PPE requirements, and to discuss usage, availability, rationing and future solutions. METHODS: A systematic review was undertaken in accordance with PRISMA guidelines using MEDLINE, Embase and WHO COVID-19 databases. Newspaper and internet article sources were identified using Nexis. The search was complemented by bibliographic secondary linkage. The findings were analysed alongside guidelines from the WHO, Public Health England, the Royal College of Surgeons and specialty associations. RESULTS: Of a total 1329 articles identified, 95 studies met the inclusion criteria. Recommendations made by the WHO regarding the use of PPE in the COVID-19 pandemic have evolved alongside emerging evidence. Medical resources including PPE have been rapidly overwhelmed. There has been a global effort to overcome this by combining the most effective use of existing PPE with innovative strategies to produce more. Practical advice on all aspects of PPE is detailed in this systematic review. CONCLUSION: Although there is a need to balance limited supplies with staff and patient safety, this should not leave surgeons treating patients with inadequate PPE.

Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells.

Low and high serum retinol levels are associated with increased fracture risk and poor bone health. We recently showed retinoic acid receptors (RARs) are negative regulators of osteoclastogenesis. Here we show RARs are also negative regulators of osteoblast and adipocyte differentiation. The pan-RAR agonist, all-trans retinoic acid (ATRA), directly inhibited differentiation and mineralisation of early osteoprogenitors and impaired the differentiation of more mature osteoblast populations. In contrast, the pan-RAR antagonist, IRX4310, accelerated differentiation of early osteoprogenitors. These effects predominantly occurred via RARγ and were further enhanced by an RARα agonist or antagonist, respectively. RAR agonists similarly impaired adipogenesis in osteogenic cultures. RAR agonist treatment resulted in significant upregulation of the Wnt antagonist, Sfrp4. This accompanied reduced nuclear and cytosolic ß-catenin protein and reduced expression of the Wnt target gene Axin2, suggesting impaired Wnt/ß-catenin signalling. To determine the effect of RAR inhibition in post-natal mice, IRX4310 was administered to male mice for 10 days and bones were assessed by µCT. No change to trabecular bone volume was observed, however, radial bone growth was impaired. These studies show RARs directly influence osteoblast and adipocyte formation from mesenchymal cells, and inhibition of RAR signalling in vivo impairs radial bone growth in post-natal mice.

Perception of facial profiles: influence of female sex hormones and personality traits.

OBJECTIVES: The observational study investigated whether women's perception of the facial profile is related to changes in sex hormones during the menstrual cycle and under the influence of personality traits. SETTING AND SAMPLE POPULATION: Participants were heterosexual Caucasian normally menstruating women not using oral contraceptives (N = 30, aged 20-44 years). MATERIAL AND METHODS: The profile attractiveness was assessed by grading of thirteen men's and women's Caucasian profile distortions by a visual analogue scale (0 = least to 100 = most attractive) in the non-ovulating phase and ovulating phase of the menstrual cycle. Male profiles were graded twice-in social and emotional contexts. Personality traits were assessed by Big Five Inventory. RESULTS: The most attractive male profiles in both phases and contexts were a straight profile or mild lip retrusion. According to cluster analysis, non-ovulating females distinguish skeletal from dentoalveolar alterations; however, maxillary retrognathism was considered to be closer to an attractive profile, which were resulting from dentoalveolar manipulations only. Ovulating females, when considering emotional relationship, exhibit lowest preference for males with convex profiles and extreme concave profile, while they consider males with slightly prominent chins due to maxillary retrognathism, mandibular prognathism or pronounced lip retrusion closer to the most attractive males. No clear patterns of influence of personality traits were detected. Moderate lip protrusion was the most attractive female profile in ovulating and straight profile in non-ovulating phase. CONCLUSION: The favorable profiles, on average, are the same regardless of the female hormonal status and personality traits.

Restless legs syndrome in patients with systemic sclerosis. Prevalence and possible causes.

This study aims to assess the prevalence and possible causes of restless legs syndrome (RLS) in patients with systemic sclerosis (SSc). The prevalence of RLS was assessed in 27 patients with SSc and 60 healthy controls. We evaluated the impact of age, disease duration, disease form, antibodies, and metoclopramide on the development of RLS in SSc patients. In order to reveal peripheral neuropathy or iron deficiency as possible causes of the syndrome, patients with RLS underwent electromyoneurography (EMNG) and ferritin level testing. RLS was diagnosed in 40.7% of SSc patients (11 out of 27), compared to 4.9% of healthy controls (p< 0.001). Eight out of 18 patients (44.4%) with diffuse SSc and 3 out of 9 patients (33.3%) with limited SSc exhibited RLS (p = 0.28). Mean age and mean disease duration did not differ significantly between patients with or without RLS. RLS was observed in 47.1% of patients with anticentromere antibodies and 30% of patients with anti-topoisomerase I antibodies (p = 0.22). RLS was diagnosed more frequently (p = 0.02) in patients taking metoclopramide (75%) than in patients who were not being treated with this drug (26.3%). EMNG revealed sensitive polyneuropathy in four, and lumbosacral radiculopathy in two out of 11 patients with RLS. Two patients with SSc and RLS had low levels of ferritin. Three patients had normal EMNG findings and ferritin levels. In conclusion, RLS is a common disorder in patients with SSc. Possible causes include sensitive polyneuropathy, lumbosacral radiculopathy, and iron deficiency. A strong relationship was observed between RLS and metoclopramide, which is sometimes used to treat SSc-related gastrointestinal motility disturbances.