Solution studies, synthesis and antibacterial activity of Ga(III) complexes with bis-kojate derivatives.

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.

Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

BACKGROUND: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. OBJECTIVES: To determine the potential of retinoids to repair photoaged black skin. METHODS: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. RESULTS: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. CONCLUSIONS: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

Pouring cold water on fake news - a qualitative review of misinformation related to burns first aid.

Health misinformation is pervasive on the internet and social media, and can have wide-ranging and devastating repercussions. Burn injuries are highly prevalent, especially in resource-poor countries with less rigorous health and safety regulations and reduced access to quality healthcare, and especially among the pediatric population who rely on caregivers to tend to their injuries. Correct first aid is crucial to improving burn outcomes and avoiding further complications. The aim of this study was to qualitatively assess the content of misinformation related to burns online. A literature search was conducted on PubMed using search terms 'burns' OR 'burn injury' OR 'burns trauma' OR 'major burns' AND 'first aid' AND 'conspiracy' OR 'disinformation' OR 'misinformation' OR 'fake news'. Combinations of these terms were searched via Google, YouTube, Facebook, Instagram, TikTok and PubMed. Key areas of misinformation included unfounded use of 'natural' remedies, injudicious use of antibiotics, omission of key steps of first aid, and errors in specific details of first aid. Clinicians should be aware of misinformation available online related to first aid for burns, be aware that patients presenting with burns may have caused further injury with insufficient first aid or inappropriate home remedies, and lead public health campaigns to educate on the initial emergency management of burns.

Opportunities for Education in Heart Failure Pharmacotherapy Demonstrated by a Survey of Clinicians.

Aim We conducted a survey of practitioners' knowledge of the clinical application of the major drug classes in HF, with reference to the European Society of Cardiology guidelines. The aim was to identify areas for practice development through education, which may improve HF morbidity and mortality. Methods We distributed a 14 item questionnaire assessing doctors knowledge of indications and contraindications for the major HF drug classes. Results Total number of responses was 127: Intern (N=21), SHO (N=64), Registrar (N=12), SpR (N=14), Consultant (N=4), GP (N=2). Consultants and GPs were excluded from analysis due to underrepresentation. Median years of practice was 4. Indications were correctly identified in a mean of 78% of responses overall. Of participants who felt comfortable with initiation and up-titration of beta blockers (N=84), only 31% (N=26) correctly identified an optimal target heart rate of less than 70 beats per minute. Forty-five percent (N=50) identified serum potassium and creatinine concentrations generally considered safe as contraindications to the initiation of MRA. Twenty-five percent of respondents (N=28) were unaware of a specialist HF service that catered to their institution, and how to refer to it, but 99% (N=110) felt that their practice would benefit from further education on HF pharmacotherapy. Conclusion Results of this survey suggest a need, and indeed a demand, for further education for clinicians in order to reduce mortality, morbidity, and hospital readmission in HF, as well as their attendant costs.

Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality.

BACKGROUND: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multi-professional communication became more difficult, weakening stewardship activities. AIM: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in critical care, and mortality rates, between the first and second waves. METHODS: Prospective audit comparing bacterial co-/secondary infections and their treatment during the first two waves of the pandemic in a single-centre teaching hospital intensive care unit. Data on demographics, daily antibiotic use, clinical outcomes, and culture results in patients diagnosed with COVID-19 infection were collected over 11 months. FINDINGS: From March 9th, 2020 to September 2nd, 2020 (Wave 1), there were 156 patients and between September 3rd, 2020 and February 1st, 2021 (Wave 2) there were 235 patients with COVID-19 infection admitted to intensive care. No significant difference was seen in mortality or positive blood culture rates between the two waves. The proportion of patients receiving antimicrobial therapy (93.0% vs 81.7%; P < 0.01) and the duration of meropenem use (median (interquartile range): 5 (2-7) vs 3 (2-5) days; P = 0.01) was lower in Wave 2. However, the number of patients with respiratory isolates of Pseudomonas aeruginosa (4/156 vs 21/235; P < 0.01) and bacteraemia from a respiratory source (3/156 vs 20/235; P < 0.01) increased in Wave 2, associated with an outbreak of infection. There was no significant difference between waves with respect to isolation of other pathogens. CONCLUSION: Reduced broad-spectrum antimicrobial use in the second wave of COVID-19 compared with the first wave was not associated with significant change in mortality.

PAPA-like syndrome with heterozygous mutation in the MEFV gene.

A patient presented with a history of recurrent pyoderma gangrenosum, arthritis and extensive acne, prompting a genetic workup for PAPA syndrome. An MEFV mutation was identified and a change in therapeutic strategy from anakinra to colchicine was successful. Click https://www.wileyhealthlearning.com/#/online-courses/b52447c0-1d37-472d-b0c0-7817352d6f68 for the corresponding questions to this CME article.

A qualitative analysis of online misinformation and conspiracy theories in psoriasis.

Psoriasis is a chronic, hereditary disease with a complex immunopathogenesis, rendering it susceptible to misinformation. Misinformation related to psoriasis can have negative effects both on the public perception of psoriasis and on patients' knowledge of psoriasis. To characterize misinformation related to psoriasis available online, we performed a formal literature review via PubMed and a thematic review via Google. Key themes of misinformation included 'victim-blaming' (hygiene), 'vector' (contagion), 'vaccination', 'vilification' of conventional therapy, 'validation' of natural treatment and diet, 'veneration' of cures and 'vocalization' from celebrities. Misinformation related to psoriasis is pervasive on social media and other websites. Dermatologists, as patient advocates, should be aware of the content of misinformation available online and combat misleading health information to optimize health outcomes for patients with psoriasis.

Confidence of Irish dermatologists in caring for patients with skin of colour.

To assess Irish dermatologists' confidence with dermatology in patients with skin of colour (SOC), an online survey was distributed to all members of the Irish Association of Dermatology (IAD) by email. Half (50%) of respondents were 'not confident' or 'not at all confident' in diagnosing skin conditions and one-third (33.9%) were 'not confident' or 'not at all confident' in managing skin conditions in patients with SOC. Irish dermatologists have low confidence with skin pathology in SOC, and specific training could reduce this disparity.

Anakinra for recalcitrant pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is an autoinflammatory neutrophilic dermatosis characterized by rapidly enlarging, painful ulcers. Anakinra is a recombinant interleukin (IL)-1 receptor antagonist that blocks the activity of IL-1α and IL-1ß by competitively inhibiting IL-1 binding to the IL-1 type 1 receptor. We present a series of two patients with recalcitrant PG, who had limited therapeutic options and multiple comorbidities and multiple previous treatment failures, who obtained 100% healing with anakinra. Compared with conventional first-line therapies for PG, the safety profile of anakinra may be preferable for patients with multiple comorbidities. Further research is needed to assess the safety and efficacy of anakinra for PG.

Measurement of the Charge-Averaged Elastic Lepton-Proton Scattering Cross Section by the OLYMPUS Experiment.

We report the first measurement of the average of the electron-proton and positron-proton elastic scattering cross sections. This lepton charge-averaged cross section is insensitive to the leading effects of hard two-photon exchange, giving more robust access to the proton's electromagnetic form factors. The cross section was extracted from data taken by the OLYMPUS experiment at DESY, in which alternating stored electron and positron beams were scattered from a windowless gaseous hydrogen target. Elastic scattering events were identified from the coincident detection of the scattered lepton and recoil proton in a large-acceptance toroidal spectrometer. The luminosity was determined from the rates of Møller, Bhabha, and elastic scattering in forward electromagnetic calorimeters. The data provide some selectivity between existing form factor global fits and will provide valuable constraints to future fits.

Scratching the surface: a review of online misinformation and conspiracy theories in atopic dermatitis.

Misinformation is one of the greatest threats to global health. Atopic dermatitis (AD) is a common skin disorder with a complex multifactorial aetiology, rendering it susceptible to misinformation. Little is known about the content of misinformation regarding AD online. We performed a review of AD-related misinformation available online, via PubMed for scientific papers and Google for nonscientific websites. Key areas of misinformation were identified, including 'simple cures' for AD, diet, chemicals, dust, vaccines, red skin syndrome and alternative therapies. Patients with AD and their families are vulnerable to misinformation given the severe impact of AD on quality of life. Dermatologists must be aware of the false AD-related content being shared online, and be prepared to refute and rebut misinformation by providing appropriate evidence.