It Remains Unknown Whether Filaggrin Gene Mutations Evolved to Increase Cutaneous Synthesis of Vitamin D

About 8-10% of normal Northern Europeans are heterozygous carriers of common FLG mutations, while only 1-4% of southern Europeans display these mutations, and only very rarely are mutations detected in African populations. Although mutations are found in Asians, they are different from those encountered in Northern Europeans. Importantly, FLG mutation carriers have 10% increased serum vitamin D concentrations compared to controls. Based on these observations, we have proposed that this latitude-dependent gradient of FLG mutations across Europe, Asia and Africa could have provided an evolutionary advantage for heterozygous FLG mutation carriers, residing at northern latitudes, depletion of the FLG downstream product, trans-urocanic acid, would facilitate the intracutaneous synthesis of vitamin D3 by allowing increased transcutaneous absorption of UVB photons. Such loss-of-function FLG mutations would have provided an evolutionary advantage for modern humans, living in the far North of Europe, where little UV-B penetrates the atomosphere. In a recent article, it was concluded not only that the UVB-Vitamin D3 hypothesis is invalid, but also that FLG genetic variations, including loss-of-function variants, provide little or no impact on the fitness of modern humans. While we welcome studies that reassess our hypothesis, their conclusions are not valid for reasons explained in this letter

Skin disorders in Parkinson's disease:potential biomarkers and risk factors

Astrid-Helene Ravn, Jacob P Thyssen, Alexander Egeberg Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Abstract: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by a symptom triad comprising resting tremor, rigidity, and akinesia. In addition, non-motor symptoms of PD are well recognized and often precede the overt motor manifestations. Cutaneous manifestations as markers of PD have long been discussed, and cumulative evidence shows an increased prevalence of certain dermatological disorders in PD. Seborrheic dermatitis is considered to occur as a premotor feature of PD referable to dysregulation of the autonomic nervous system. Also, an increased risk of melanoma has been observed in PD. Light hair color is a known risk factor for melanoma, and interestingly the risk of PD is found to be significantly higher in individuals with light hair color and particularly with red hair. Furthermore, several studies have reported a high prevalence of PD in patients with bullous pemphigoid. Moreover, a 2-fold increase in risk of new-onset PD has been observed in patients with rosacea. Besides the association between PD and various dermatological disorders, the skin may be useful in the diagnosis of PD. Early PD pathology is found not only in the brain but also in extra-neuronal tissues. Thus, the protein α-synuclein, which is genetically associated with PD, is present not only in the CNS but also in the skin. Hence, higher values of α-synuclein have been observed in the skin of patients with PD. Furthermore, an increased risk of PD has been found in the Cys/Cys genotype, which is associated with red hair color. In this review, we summarize the current evidence of the association between PD and dermatological disorders, the cutaneous adverse effects of neurological medications, and describe the potential of skin protein expression and biomarkers in identification of risk and diagnosis of PD. Keywords: Parkinson’s disease, melanoma, rosacea, seborrheic dermatitis, bullous pemphigoi

The attitudes and perceptions of sworn Victoria Police personnel in relation to the implementation and ongoing enforcement of the Victoria Police cannabis cautioning program

The research examines the attitudes and perceptions of Victoria Police personnel in relation to the Victoria Police Cannabis Cautioning Program (CCP). The CCP (1998) was introduced as a means of reducing the harms associated with cannabis consumption and to divert first-time minor offenders away from the criminal justice system. The program was designed to give offenders a second chance by allowing them to avoid the stigma associated with a court appearance. The thesis examines the implementation of the CCP and the impact it has had on drug law enforcement within Victoria. This is explored through the examination of police interactions with minor cannabis offenders. The research further examines police perceptions in relation to the CCP, the move away from strict prosecution of minor cannabis offenders and its effect on police exercising their discretionary powers. The research considers the impact of police training, force instruction and offender attitude on the police decision-making process. Also examined is police acceptance of the CCP concept and how they perceive its acceptance within the community. Police experiences of the CCP and ultimately their perceptions of the program are discussed through the use of an interpretivist framework. Symbolic interaction and the development of a shared “meaning system” can possibly explain how police view the CCP and its impact on drug law enforcement and the criminal justice system as a whole. The research uses qualitative techniques. Qualitative data include semi-structured face-to-face and telephone interviews with sworn Victoria Police personnel from uniform, Criminal Investigations Unit (CIU) and prosecutions departments. Police accepted the concept of the CCP and were willing to give offenders a second chance, however they also wanted offenders to be compelled to attend drug education sessions. Offender attitude towards police and drug use as a whole ultimately determined whether police would issue an offender with a caution. The research shows that although police would like to see some changes to the program, there was a general acceptance of its aims and objectives. Acceptance of the CCP was, however, not solely based on these aims and objectives. The research shows that police used the CCP because it saved them time in the processing of offenders, preparing briefs of evidence and appearing at court to give evidence. This was considered in the first instance. The CCP as a harm minimisation strategy was only considered in the second instance and therefore illustrates a need for additional police training. A number of other suggestions for further police and policy development are posed

Eimeria Curvata N. Sp.(apicomplexa: Eimeriidae) In Columbina Talpacoti And Scardafella Squammata (aves: Columbidae) From Brazil.

Eimeria curvata is a new coccidian described in the doves Columbina talpacoti and Scardafella squammata from western of the State of São Paulo, Brazil. The oocysts are ovoid to ellipsoid, 18.3 (17-19) microm x 15.5 (15-17) microm, with a shape index of 1.2 (1.1-1.3). The wall is colorless, smooth and double-layered. A polar granule is present, but there is no micropyle or oocyst residuum. The sporocysts are elongate, 12.3 (11.5-13) microm x 5.8 (5.5-6) microm with a curved anterior portion and a smooth, thin, single-layered wall. The Stieda body is protuberant and nipple-like; there is no substieda body. The sporozoites lie head-to-tail in the sporocyst and contain a large refractile body at the extremities. The sporocyst residuum contains small granules uniformly distributed in the middle of the sporocyst. The prevalence of E. curvata n. sp. was 17.4% and 12.8% in C. talpacoti and S. squammata, respectively.9553-

A detailed look at the European Medicines Agency's recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis

Background Oral Janus kinase inhibitors (JAKi) have been approved for the treatment of several chronic inflammatory conditions, including rheumatoid arthritis (RA) and atopic dermatitis (AD). Prompted by new evidence, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recently reassessed the benefit–risk balance of oral JAKi. The PRAC recommended that oral JAKi should be used only if no suitable alternatives are available in patients ≥65 years of age, or who have a history of atherosclerotic cardiovascular (CV) disease, other CV risk factors (e.g. history of long-term smoking) or have malignancy risk factors, and used with caution in patients at risk of pulmonary embolism or deep vein thrombosis. The European Commission's final decision was issued in March 2023. Objectives Our goal was to highlight the PRAC recommendations, especially in the context of oral JAKi use in AD. Methods Authors summarized the PRAC recommendations, the new clinical evidence on oral JAKi safety and key differences between patients with RA and AD. Results Risk of developing adverse events of special interest (e.g. cardiovascular events, malignancy) is higher in patients with RA than in patients with AD, because of the higher prevalence of the underlying risk factors. Conclusions The benefit–risk profile of JAKi approved for AD remains favourable, including use as first-line systemic therapy for patients with AD <65 years of age and without CV or malignancy risk factors