Medigene (Germany)

Abstract Voltage-gated (Kv) potassium channels are critical for neuronal physiology, and their dysfunction can lead to serious consequences. For example, mutations in the silent modulatory Kv8.2 subunit are known to cause irreversible inherited blindness ( KCNV2 retinopathy). This is a currently incurable condition that causes lifelong visual loss, reduced visual acuity, photoaversion, night blindness and abnormal colour vision, alongside a distinctive supernormal electrophysiological (ERG) retinal response to light. In this study, we demonstrate that AAV-mediated gene replacement therapy delivering a codon-optimised human KCNV2 gene subretinally into Kv8.2 knock-out mice significantly restores retinal function. Treated mice exhibited improved ERG responses and correct expression of KCNV2 and its encoded Kv8.2 protein in photoreceptors. Recovery of visually guided scotopic and photopic optomotor responses to wildtype levels was achieved at lower vector doses, highlighting dose-dependent efficacy. Furthermore, treatment of human retinal organoids derived from a KCNV2 patient iPSC line resulted in substantial Kv8.2 protein rescue. This work provides the first preclinical proof-of-concept for the safety and therapeutic potential of gene therapy for KCNV2 retinopathy, laying a strong foundation for future clinical trials.

Background: Vitamin D deficiency is a global health concern affecting all age groups, despite the implementation of supplementation strategies. This study aimed to investigate the roles of genetic polymorphisms, epigenetic mechanisms, and microbiota interactions in vitamin D metabolism, as well as their potential contributions to allergies, autoimmune thyroiditis, and autism spectrum disorder.Methods: This retrospective, descriptive study analyzed data from 60 individuals (16 males and 44 females) who underwent nutrigenetic testing between 2022 and 2024 at Epigenetic Coaching, Istanbul, Turkey. Genetic analyses focused on the cytochrome P450 family 2 subfamily R member 1 (CYP2R1) gene, group-specific component (GC) gene, and vitamin D receptor (VDR) polymorphisms. Inclusion criteria included the presence of allergic symptoms, a diagnosis of autism spectrum disorder, or a diagnosis of Hashimoto’s thyroiditis, along with prior genetic testing for the selected variants. Individuals with any known genetic disorder other than the studied variants were excluded.Results: CYP2R1, GC, and VDR polymorphisms associated with vitamin D insufficiency were found at higher frequencies in patients with autism, Hashimoto’s thyroiditis, and allergic conditions. When examining the associations between genetic variants and diseases, VDR FokI, VDR ApaI, and VDR BsmI variants were more frequently observed in patients with Hashimoto’s thyroiditis, while the VDR TaqI variant was more common in individuals with autism. In the allergy group, BsmI, FokI, ApaI, and TaqI variants were identified at higher frequencies.Conclusion: Genetic variants and epigenetic modifications may disrupt vitamin D metabolism and alter gut microbiota diversity, contributing to the development of various diseases. Evaluating vitamin D deficiency together with its genetic, epigenetic, and microbiota determinants is essential for developing effective prevention and treatment strategies. These findings emphasize the necessity of personalized, nutrigenetic-based approaches to optimize vitamin D function and support overall health.

Presentamos datos sobre la distribución de Dinomys branickii-Peters, 1873 (guagua loba) en el departamento del Huila, Colombia; cuya presencia estaba relacionada con comunicaciones personales y/o anecdóticas de las comunidades rurales. Confirmamos la distribución de la guagua loba en el Huila a partir de registro de cámara trampa instalada en el año 2021, en bosque andino húmedo del Parque Natural Regional El Dorado. Registramos tenencia ilegal de la especie en zona rural del municipio de Rivera. Estos registros amplían la distribución de la especie en la región suroccidental del país, incluyendo nuevas localidades para Colombia.

AbstraktEs wird ein probabilistischer Ansatz vorgestellt, um die Kennwerte und die Wahrscheinlichkeitsverteilung der Betondruckfestigkeit basierend auf Messdaten und aus der Planungsphase vorhandenen Informationen zu bestimmen. Der resultierende charakteristische Wert der Betondruckfestigkeit kann für Nachweise mit dem semiprobabilistischen Teilsicherheitskonzept verwendet werden, während die Wahrscheinlichkeitsverteilung für Zuverlässigkeitsanalysen und weitergehende Untersuchungen benutzt werden kann. Der Ansatz ist in einem frei verwendbaren Web‐Tool umgesetzt.

Wprowadzenie: Celem badania było potwierdzenie fizycznych parametrów głosu jako biomarkerów depresji, wytrenowanie na ich bazie AI i ocena jej skuteczności w wykrywaniu zmian stanu psychicznego w podłużnym badaniu klinicznym. Materiał i metody: System MoodMon oparty na AI został wytrenowany przez psychiatrów na fizycznych parametrach głosu 25 pacjentów z depresją nawracającą. Zanonimizowane próbki głosu pobierano podczas codziennych odpowiedzi na neutralne emocjonalnie pytania. Wyniki: Stwierdzono, że 19 fizycznych parametrów głosu okazało się najsilniej skorelowanymi ze zmianami stanu psychicznego. System wykazał wysoką wydajność, z wartościami czułości (TPR, true positive rate ) = 89,1% i swoistości (TNR, true negative rate ) = 98,5%. Wnioski: Dzięki uczeniu maszynowemu potwierdzono, że fizyczne parametry głosu są biomarkerami w depresji. Mogą one służyć do monitorowaniu stanu psychicznego. Ostateczne decyzje terapeutyczne na podstawie kompleksowego badania pacjenta nadal powinien podejmować psychiatra.

BACKGROUND AND OBJECTIVES Geospatial mapping has been a valuable tool in public health interventions, yet its application in resource-limited settings remains challenging. This study aimed to map cases of typhoid fever intestinal perforations in northeastern Ghana and identify potential case clusters, while assessing the feasibility of conducting such analysis in a resource-limited setting. METHODS We conducted a retrospective analysis of 84 cases treated at a regional referral hospital from September 2023 to January 2024, and patient demographics and hometown locations were collected and mapped. When necessary, focused interviews with hospital staff and community members were conducted to approximate village locations. RESULTS Of the 84 cases, 88% (74 cases) were successfully mapped to the town or village level. However, precise neighborhood mapping was not possible due to the lack of standardized addressing systems. No significant disease clusters were identified, likely due to the small sample size and low population density. The study revealed specific challenges in conducting geospatial analysis in this setting, including duplicate village names, reliance on unpaved roads, and scarcity of detailed mapping systems. CONCLUSIONS While geospatial mapping of typhoid fever cases was largely successful at the town/village level, significant challenges remain in conducting precise analyses in resource-limited settings. This study emphasizes the need for improved mapping technologies, standardized addressing systems, and basic infrastructure enhancements to increase the effectiveness of public health interventions in similar settings worldwide.

This paper presents, for the first-time, measurement results of frequency-dependent impedances of ship electrical systems, obtained during three measurement campaigns. The introduction covers shipboard networks, the trend towards DC networks and explains the measurement procedure. The results from an AC secondary ship grid on an AC-ship, a fixed DC system, and a floating DC system installed on a ferry are presented, compared and discussed. The three shipboard power networks all show resonances in various degrees and different characteristic curves of the magnitudes and phase curves of the impedance. The frequency-dependent behaviour of on-board power systems, especially DC systems, has not been scientifically explored before. However, such exploration is crucial for the stable and safe operation of future ships equipped with numerous power electronic systems