Profound sexual dysfunction among patients with hidradenitis suppurativa : a sross-sectional study

Introduction: Sexual health, a critical aspect of overall well-being, is often compromised in individuals with chronic disorders. Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that mainly affects intertriginous areas, potentially impacting sexual health as a result of its specific symptoms and psychosocial burden. Methods: This cross-sectional study utilized data from the EpiCAi project, focusing on 199 patients with HS. Participants completed digital questionnaires assessing sexual health via sexspecific instruments: the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men, alongside different psychosocial scales. The disease severity was assessed using the Hurley stage and the Lesion Identification Scheme for Acne Inversa (LISAI). Results: The majority of the participants reported impaired sexual health, with significant clinical sexual dysfunctions noted in 71.8% of women (FSFI score < 26) and erectile dysfunction in 63.8% of men. Sexual dysfunction was associated with several factors, including age, and marital status. Psychosocial factors, notably depression and quality of life, showed strong correlations with sexual health outcomes. Notably, women over 40 and those treated with biologics reported more severe dysfunction, while among men, employment status significantly influenced sexual health. Conclusions: HS profoundly affects the sexual health of both male and female patients, with significant impacts on their quality of life and psychological well-being. The findings underscore the necessity for healthcare providers to address sexual health proactively in the management of HS, considering both physical symptoms and psychosocial impacts. This holistic approach is essential for improving patient outcomes and overall quality of life

Real-world effectiveness and safety of the LAight-therapy in patients with hidradenitis suppurativa

Hidradenitis suppurativa (HS)/Acne inversa (Ai) is a chronic debilitating disease with limited therapy options. The device-based LAight therapy was approved in Europe in 2017. The aim of this study was to evaluate the effect of real-world care with at least one treatment with LAight therapy on disease activity and burden in 3,437 patients. Patients were included in the analysis if they had a diagnosis of HS and received at least one treatment. The endpoints Hidradenitis Suppurativa Severity Score System (IHS4), pain on the numeric rating scale (pain-NRS) and Dermatology Life Quality Index (DLQI) were analyzed using a linear mixed model for repeated measures (MMRM) over 26 weeks of care with LAight therapy. Furthermore, responder rates were calculated for all endpoints, and the therapy's safety profile and patient satisfaction were thoroughly examined. A significant decrease in IHS4, pain-NRS, and DLQI was achieved during 26 weeks of care with LAight. The BMI at baseline had a significant negative effect on therapy response for pain-NRS and DLQI. This study confirms that LAight therapy leads to satisfactory disease control in all stages of severity and is a valuable addition to the therapeutic repertoire of HS

Real-World-Effektivität und Sicherheit der LAight-Therapie bei Patienten mit Hidradenitis suppurativa

Hintergrund und Ziele: Hidradenitis suppurativa (HS)/Acne inversa (Ai) ist eine chronische, stark beeinträchtigende Erkrankung mit begrenzten Therapiemög- lichkeiten. Die gerätebasierte LAight-Therapie wurde 2017 in Europa zugelassen. Ziel dieser Studie war es, die Auswirkungen einer Real-World-Versorgung mit der LAight-Therapie auf die Krankheitsaktivität und -belastung von 3437 Patienten zu analysieren. Patienten und Methodik: In die Analyse wurden alle Patienten aufgenom- men, die eine HS-Diagnose und mindestens eine LAight-Behandlung erhalten hatten. Die Endpunkte Hidradenitis Suppurativa Severity Score System (IHS4), Schmerz auf der numerischen Ratingskala (pain-NRS) und der Dermatologische- Lebensqualitäts-Index (DLQI) wurden mit Hilfe eines linearen gemischten Modells für wiederholte Messungen (MMRM) über 26 Wochen Versorgung mit der LAight-Therapie analysiert. Darüber hinaus wurden die Responderraten für alle Endpunkte berechnet und das Sicherheitsprofil der Therapie sowie die Patienten- zufriedenheit eingehend untersucht. Ergebnisse: Während der 26-wöchigen Versorgung mit LAight wurde ein signifi- kanter Rückgang des IHS4, Schmerz-NRS und DLQI erreicht. Der BMI hatbei The- rapiestart hatte einen signifikant negativen Einfluss auf das Therapieansprechen hinsichtlich Schmerz-NRS und DLQI. Schlussfolgerungen: Diese Studie bestätigt, dass die LAight-Therapie zu einer überzeugenden Krankheitskontrolle in allen Schweregraden führt und eine wertvolle Ergänzung des therapeutischen Repertoires bei HS darstellt

Noncommutative solitons on Kahler manifolds

We construct a new class of scalar noncommutative multi-solitons on an arbitrary Kahler manifold by using Berezin's geometric approach to quantization and its generalization to deformation quantization. We analyze the stability condition which arises from the leading 1/hbar correction to the soliton energy and for homogeneous Kahler manifolds obtain that the stable solitons are given in terms of generalized coherent states. We apply this general formalism to a number of examples, which include the sphere, hyperbolic plane, torus and general symmetric bounded domains. As a general feature we notice that on homogeneous manifolds of positive curvature, solitons tend to attract each other, while if the curvature is negative they will repel each other. Applications of these results are discussed.Comment: 26 pages, 3 figures, harvmac; references adde

Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction

BACKGROUND: Hepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro. METHODS: RNA interference was performed by transfecting siRNA to specifically knock down Mcl-1 expression in HCC cells. Mcl-1 expression was measured by quantitative real-time PCR and Western blot. Induction of apoptosis and caspase activity after treatment with chemotherapeutic drugs and different targeted therapies were measured by flow cytometry and fluorometric analysis, respectively. RESULTS: Here we demonstrate that Mcl-1 expressing HCC cell lines show low sensitivity towards treatment with a panel of chemotherapeutic drugs. However, treatment with the anthracycline derivative epirubicin resulted in comparatively high apoptosis rates in HCC cells. Inhibition of the kinase PI3K significantly increased apoptosis induction by chemotherapy. RNA interference efficiently downregulated Mcl-1 expression in HCC cells. Mcl-1 downregulation sensitized HCC cells to different chemotherapeutic agents. Sensitization was accompanied by profound activation of caspase-3 and -9. In addition, Mcl-1 downregulation also increased apoptosis rates after treatment with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and VEGF/PDGF kinase inhibitors. TRAIL-induced apoptosis did not markedly respond to Mcl-1 knockdown. Additionally, knockdown of Mcl-1 efficiently enhanced apoptosis sensitivity towards combined treatment modalities: Mcl-1 knockdown significantly augmented apoptosis sensitivity of HCC cells towards chemotherapy combined with PI3K inhibition. CONCLUSION: Our data suggest that specific downregulation of Mcl-1 by RNA interference is a promising approach to sensitize HCC cells towards chemotherapy and molecularly targeted therapies

An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation

BAG1 Over-expression in Brain Protects Against Stroke

The co-chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over-expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate-induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild-type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti-apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small-molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases