Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome

The insulin/insulin-like growth factor-1 (IGF-1) pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR) gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS) exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulates IIS. The reduction of IIS in Laron subjects unmasks the potential role of persistent hyperactive IIS mediated by Western diet in the development of diseases of civilization and offers a rational perspective for dietary adjustments with less insulinotropic diets like the Paleolithic diet

Inositoylated Platelet-Activating Factor (Ino-C2-PAF) Modulates Dynamic Lymphocyte–Endothelial Cell Interactions and Alleviates Psoriasis-Like Skin Inflammation in Two Complementary Mouse Models

Psoriasis, a tumor necrosis factor alpha (TNFα)-governed inflammatory disorder with prominent dysregulation of cutaneous vascular functions, has evolved into a model disorder for studying anti-inflammatory therapies. We present experimental in vitro and in vivo data on 1-O-octadecyl-2-O-(2-(myo-inositolyl)-ethyl)-sn-glycero-3-(R/S)-phosphatidyl-choline (Ino-C2-PAF), the lead compound of a class of synthetic glycosylated phospholipids, in anti-inflammatory therapy. Ino-C2-PAF strongly induced apoptosis only in TNFα-stimulated, but not in untreated human vascular endothelial cells. Moreover, TNFα-induced endothelial adhesion molecules that mediated the rolling and firm adhesion of leukocytes (vascular cell adhesion protein-1 (VCAM-1), E-selectin, and ICAM-1) were selectively downregulated by Ino-C2-PAF. Similarly, expression of L-selectin, VCAM-1 receptor α4β1 integrin, and lymphocyte function-associated antigen-1 on human peripheral blood mononuclear cells was reduced without induction of apoptosis. Functionally, these changes were accompanied by significant impairment of rolling and adhesion of human peripheral blood lymphocytes on TNFα-activated endothelial cells in a dynamic flow chamber system. When the therapeutic potential of Ino-C2-PAF was assessed in two complementary mouse models of psoriasis, K5.hTGFβ1 transgenic and JunB/c-Jun-deficient mice, Ino-C2-PAF led to significant alleviation of the clinical symptoms and normalized the pathological cutaneous changes including vascularization. There were no overt adverse effects. These findings suggested that Ino-C2-PAF is a potential candidate in the therapy of inflammatory skin diseases that include abnormal vascular functions

Novel insights into pivotal risk factors for rectal carriage of extended-spectrum-beta-lactamase-producing enterobacterales within the general population in Lower Saxony, Germany

AIMS: To estimate the prevalence of extended-spectrum-β-lactamase (ESBL)-producing enterobacterales (ESBL-E) carriage in the general population of Lower Saxony, Germany, and to identify risk factors for being colonised. METHODS AND RESULTS: Participants were recruited through local press and information events. Detection of ESBL-E by culture was conducted using ESBL-selective chromagar plates containing third generation cephalosporins. Identification of pathogens was performed using Matrix Assisted Laser Desorption Ionization Time-of-Flight-Technology on Vitek mass spectrometry. Antibiotic susceptibility testing was conducted by microdilution (Vitek II) and an ESBL confirmation assay was carried out using a combination disk test. Of 527 randomly collected stool samples from healthy volunteers, 5.5% were tested positive for ESBL-E. Post-stratification for age and gender yielded a similar population estimate (5.9%). People traveling abroad and taking antibiotics had the greatest rectal ESBL-E carriage. CONCLUSIONS: Potential risk factors (e.g., working in healthcare facilities, recent inpatient stay) did not attribute to rectal ESBL-E carriage as other factors (e.g., traveling, taking antibiotics). Rectal ESBL-E carriage within the general population seems to be high. SIGNIFICANCE AND IMPACT OF STUDY: The known risk factors for carriage with MDRO might not be fully applicable to ESBL-E and require further examination in order to develop effective strategies for the prevention of ESBL-E dissemination within the general population

Effectiveness of Manual Therapy, Customised Foot Orthoses and Combined Therapy in the Management of Plantar Fasciitis—A RCT

Background: Plantar fasciitis (PF) is one of the most common causes of plantar heel pain. Objective: To evaluate the effectiveness of three different treatment approaches in the management of PF. Methods: Sixty-three patients (44 female, 19 men; 48.4 ± 9.8 years) were randomly assigned into a manual therapy (MT), customised foot orthosis (FO) and a combined therapy (combined) group. The primary outcomes of pain and function were evaluated using the American Orthopaedic Foot and Ankle Society-Ankle Hindfoot Scale (AOFAS-AHS) and the patient reported outcome measure (PROM) Foot Pain and Function Scale (FPFS). Data were evaluated at baseline (T0) and at follow-up sessions after 1 month, 2 months and 3 months (T1–T3). Results: All three treatments showed statistically significant (p < 0.01) improvements in both scales from T0 to T1. However, the MT group showed greater improvements than both other groups (p < 0.01). Conclusion: Manual therapy, customised foot orthoses and combined treatments of PF all reduced pain and function, with the greatest benefits shown by isolated manual therapy

Risk of cutaneous squamous cell carcinoma due to occupational exposure to solar ultraviolet radiation: Protocol for a systematic review and meta-analysis

: Solar ultraviolet radiation (UVR) is the most significant occupational carcinogenic exposure in terms of the number of workers exposed (i.e., outdoor workers). Consequently, solar UVR-induced skin cancers are among the most common forms of occupational malignancies that are potentially expected globally. This systematic review is registered in PROSPERO (CRD42021295221) and aims to assess the risk of cutaneous squamous cell carcinoma (cSCC) associated to occupational solar UVR exposure. Systematic searches will be performed in three electronic literature databases (PubMed/Medline, EMBASE, and Scopus). Further references will be retrieved by a manual search (e.g., in grey literature databases, internet search engines, and organizational websites). We will include cohort studies and case-control studies. Risk of Bias assessment will be conducted separately for case-control and cohort studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used for the certainty of assessment. In case quantitative pooling is not feasible, a narrative synthesis of results will be performed

Digitally measuring solar ultraviolet radiation in outdoor workers: A study protocol for establishing the use of electronic personal dosimeters in Portugal

IntroductionThe rising incidence of skin cancer over the years has made it a significant public and occupational health issue. However, skin cancer is highly preventable, mainly through reduced exposure to solar ultraviolet radiation (UVR), which can be achieved by a variety of individual and collective protective measures and interventions. The relative risk associated with different patterns of exposure to solar UVR differs for the subtypes of keratinocyte cancers (KC). Specifically, whether the exposure is intermittent or continuous, and occurs in an occupational or leisure/recreational setting. The main aim of the study using this protocol is to contribute to raising public and policy awareness on solar UVR-inflicted occupational skin cancers in Lisbon. This will be achieved by performing direct measurements of the solar UVR dose received by outdoor workers using a digital platform. Results will likely contribute to further understanding the risk estimates for keratinocyte cancer estimations in this population.MethodsA prospective observational study will be conducted in Lisbon, Portugal. Personal electronic dosimeters (GENESIS-UV system) integrated with a digital platform will be used to assess occupational solar UVR doses of gardeners, masons, and gravediggers of the municipality of Lisbon. Two hundred and ten outdoor workers will be selected to wear the dosimeter for 1 month each, between April and October during their daily working hours. A digital web-based platform that offers private access to information through dashboard visualization will provide information for the outdoor workers and facilitate communication with the participants.DiscussionThe expected results of the overall proposal comprise the occupational solar UVR doses, expressed in standard erythemal dose (SEDs) per day of outdoor work for 7 months. Study data will provide outdoor workers with information on their personal solar UVR exposure during their working hours and an estimate of their risk of developing skin cancer. It is expected that the occupational solar UVR doses of the outdoor workers in Portugal will be above the threshold of 1 to 1.33 SED/day, due to the latitude of Lisbon and the nature of the occupations. The results prospectively should flow into the design of adequate prevention campaigns for skin cancer in outdoor workers

A study protocol for establishing the use of electronic personal dosimeters in Portugal

Funding: This research is funded by Fundação para a Ciência e Tecnologia 2022.01888.PTDC.Introduction: The rising incidence of skin cancer over the years has made it a significant public and occupational health issue. However, skin cancer is highly preventable, mainly through reduced exposure to solar ultraviolet radiation (UVR), which can be achieved by a variety of individual and collective protective measures and interventions. The relative risk associated with different patterns of exposure to solar UVR differs for the subtypes of keratinocyte cancers (KC). Specifically, whether the exposure is intermittent or continuous, and occurs in an occupational or leisure/recreational setting. The main aim of the study using this protocol is to contribute to raising public and policy awareness on solar UVR-inflicted occupational skin cancers in Lisbon. This will be achieved by performing direct measurements of the solar UVR dose received by outdoor workers using a digital platform. Results will likely contribute to further understanding the risk estimates for keratinocyte cancer estimations in this population. Methods: A prospective observational study will be conducted in Lisbon, Portugal. Personal electronic dosimeters (GENESIS-UV system) integrated with a digital platform will be used to assess occupational solar UVR doses of gardeners, masons, and gravediggers of the municipality of Lisbon. Two hundred and ten outdoor workers will be selected to wear the dosimeter for 1 month each, between April and October during their daily working hours. A digital web-based platform that offers private access to information through dashboard visualization will provide information for the outdoor workers and facilitate communication with the participants. Discussion: The expected results of the overall proposal comprise the occupational solar UVR doses, expressed in standard erythemal dose (SEDs) per day of outdoor work for 7 months. Study data will provide outdoor workers with information on their personal solar UVR exposure during their working hours and an estimate of their risk of developing skin cancer. It is expected that the occupational solar UVR doses of the outdoor workers in Portugal will be above the threshold of 1 to 1.33 SED/day, due to the latitude of Lisbon and the nature of the occupations. The results prospectively should flow into the design of adequate prevention campaigns for skin cancer in outdoor workers.publishersversionpublishe

German S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" – long version of the update 2023

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC