The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries.

The contribution of psychological disorders to the burden of skin disease has been poorly explored, and this is a large-scale study to ascertain the association between depression, anxiety, and suicidal ideation with various dermatological diagnoses. This international multicenter observational cross-sectional study was conducted in 13 European countries. In each dermatology clinic, 250 consecutive adult out-patients were recruited to complete a questionnaire, reporting socio-demographic information, negative life events, and suicidal ideation; depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. A clinical examination was performed. A control group was recruited among hospital employees. There were 4,994 participants--3,635 patients and 1,359 controls. Clinical depression was present in 10.1% patients (controls 4.3%, odds ratio (OR) 2.40 (1.67-3.47)). Clinical anxiety was present in 17.2% (controls 11.1%, OR 2.18 (1.68-2.82)). Suicidal ideation was reported by 12.7% of all patients (controls 8.3%, OR 1.94 (1.33-2.82)). For individual diagnoses, only patients with psoriasis had significant association with suicidal ideation. The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers. These results identify a major additional burden of skin disease and have important clinical implications.Peer reviewedFinal Published versio

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as standalone or in combination with targeted drugs.Peer reviewe

The association between diabetes and cognitive changes during aging

Abstract Background/Objectives: Worldwide, we are observing a rising prevalence of dementia and mild cognitive impairments that often co-occur with the heightened incidence of non-communicable diseases in the elderly. It is suggested that type 2 diabetes and defects in glucose metabolism might predispose to poorer cognitive performances and more rapid decline in old age. Methods: To address existing knowledge gaps in this area, we systematically reviewed the literature to identify whether patients with type 2 diabetes (T2DM) and pre-diabetes are at a higher risk of poorer cognitive performance, and whether the risk (if any) might affect specific cognitive abilities. We concentrated the review on elderly individuals (65 years or older) at intake. In total, 3251 original articles were retrieved, of which 17 met our inclusion and quality control criteria, which comprised 12 structured questions used to define the articles. Results: 11 of 17 studies found a statistically significant decline in cognition among individuals who had T2DM or pre-diabetes compared to their non-diabetic counterparts. The association between diabetes and cognitive decline was not always clear, and the extent of the cognitive tests used seemed to have the greatest effect on the results. Conclusion: Focusing on a population age 65 years and over, we found insufficient evidence to support an association between pre-diabetes stages and mild cognitive impairment. However, there is consistent evidence to support diabetes as an independent risk factor for low cognitive ability in the elderly. Finally, we found insufficient evidence to support effect of T2DM on distinct cognitive ability due to the scarcity of comparable findings

Long-term dysglycemia as a risk factor for faster cognitive decline during aging:a 12-year follow-up study

Abstract Aims: This longitudinal study evaluated associations between glucose metabolism and cognitive performance during a 12-year follow-up. Methods: We included 714 subjects, which were followed from the age 55 to 70 years. Using oral glucose tolerance tests the population was classified as normoglycemic (NGT) and based on WHO diagnostic criteria for diabetes and prediabetes. Cognitive performance was assessed with a verbal fluency (category) test and wordlist learning tests of CERAD-nb, a verbal fluency (letter) test, and trail-making tests A and B. Results: Compared to the normal group subjects with long-lasting prediabetes showed significantly greater decline (4.6 versus 2.9 words) on the verbal fluency (category) test (p = 0.041); subjects with long-lasting type 2 diabetes showed significantly greater decline (13 versus 6 s) on the trail making A test (p = 0.021) and on the wordlist learning test (3.3 versus 1.7 words) (p = 0.013); and a combined group of subjects with prediabetes or incident type 2 diabetes showed significantly greater cognitive decline (3.8 versus 2.9 words) in the verbal fluency (category) test (p = 0.039). Conclusion: Prediabetes was associated with cognitive decline during aging. This finding should be incorporated into prevention strategies, because both type 2 diabetes and dementia are increasing world-wide

Waist circumference and waist-to-height ratio are associated with periodontal pocketing:results of the Health 2000 Survey

Abstract Background: Body mass index (BMI) has been found to associate with different parameters of chronic periodontal disease in previous studies. It is reasonable to expect that central adiposity measures, such as waist circumference and waist-to-height ratio, which indirectly takes into account visceral fat, are more accurate measures of obesity-related oral health risks than BMI. The aim of this study was to examine whether central obesity is associated with periodontal pocketing, an indication of infectious chronic periodontal disease. Methods: The study was based on a subpopulation from the national Health 2000 Survey in Finland. It included dentate, non-diabetic, never-smoking subjects aged 30–49 (n = 1287). The outcome variable was the number of teeth with deepened periodontal pockets (4 mm or more) and the number of teeth with deep periodontal pockets (6 mm or more). Central obesity was measured by means of waist circumference (WC) and waist-to-height ratio (WHtR). Poisson regression models were used to estimate prevalence rate ratios (PRR) and their 95% confidence intervals. Results: Our main finding was that both WC and WHtR were associated with the number of teeth with deeper (4 mm or more) periodontal pockets; the PRR for the fifth quintile in WC was 1.5, CI: 1.2–1.9 and in WHtR 1.4, CI: 1.1–1.7, when compared to the lowest quintile. Corresponding figures for deep (6 mm or more) periodontal pockets were 2.3, CI: 0.9–6.1 for WC and 1.9, CI: 0.8–4.4 for WHtR. There were no essential differences in the strengths of the associations between WC and WHtR and the number of teeth with deepened periodontal pockets. Conclusion: Both central adipose measures—WC and WHtR—seem to be associated with periodontal pocketing in non-diabetic, never-smoking subjects aged 30–49 years old

Laboratory and field evaluation of the Aerosol Dynamics Inc. concentrator (ADIc) for aerosol mass spectrometry

An air-to-air ultrafine particle concentrator (Aerosol Dynamics Inc. concentrator; ADIc) has been designed to enhance online chemical characterization of ambient aerosols using aerosol mass spectrometry. The ADIc employs a three-stage, moderated water-based condensation growth tube coupled to an aerodynamic focusing nozzle to concentrate fine particles into a portion of the flow. The system can be configured to sample between 1.0 and 1.7 L min−1, with an output concentrated flow between 0.08 and 0.12 L min−1, resulting in a theoretical concentration factor (sample flow / output flow) ranging from 8 to 21. Laboratory tests with monodisperse particles show that the ADIc is effective for particles as small as 10 nm. Laboratory experiments conducted with the Aerosol Mass Spectrometer (AMS) showed no shift in the particle size with the ADIc, as measured by the AMS particle time-of-flight operation. The ADIc-AMS system was operated unattended over a 1-month period near Boston, Massachusetts. Comparison to a parallel AMS without the concentrator showed concentration factors of 9.7±0.15 and 9.1±0.1 for sulfate and nitrate, respectively, when operated with a theoretical concentration factor of 10.5±0.3. The concentration factor of organics was lower, possibly due to the presence of large particles from nearby road-paving operations and a difference in aerodynamic lens cutoff between the two AMS instruments. Another field deployment was carried out in Helsinki, Finland. Two ∼10 d measurement periods showed good correlation for the concentrations of organics, sulfate, nitrate and ammonium measured with an Aerosol Chemical Speciation Monitor (ACSM) with the ADIc and a parallel AMS without the concentrator. Additional experiments with an AMS alternating between the ADIc and a bypass line demonstrated that the concentrator did not significantly change the size distribution or the chemistry of the ambient aerosol particles