Search Results (38)

(1) Background: Arterial stiffness, often measured by carotid–femoral pulse wave velocity (cf-PWV), is crucial in cardiovascular disease. Dapagliflozin has shown rapid effects on arterial stiffness, but there is limited evidence of empagliflozin’s acute effects, especially in type 2 diabetes (T2D) patients. This study evaluated the acute effects of empagliflozin and dapagliflozin on arterial stiffness and blood pressure (BP). (2) Methods: A one-week double-blind randomized trial involved 30 T2D patients on stable metformin therapy. Participants received empagliflozin (25 mg/day), dapagliflozin (10 mg/day), or a placebo. Arterial stiffness was assessed via cf-PWV, and BP was measured with an automated sphygmomanometer. (3) Results: Both SGLT2 inhibitors significantly reduced cf-PWV compared to the placebo after one week (p < 0.05), with dapagliflozin showing a more pronounced effect. No significant differences were observed in BP changes. (4) Conclusion: Short-term treatment with SGLT2 inhibitors acutely reduces arterial stiffness in T2D patients, with empagliflozin demonstrating a stronger effect, supporting the potential vascular benefits of SGLT2 inhibitors beyond glucose control. Full article

In dementia care, access to effective psychosocial interventions is often addressed by evidence-based guidelines for care providers. However, it is unclear if current guidelines consider personal characteristics that may impact intervention effectiveness. This study investigates if, and within what framing, dementia care guidelines in Europe address what is effective and for whom. A review of 47 guidelines from 12 European countries was conducted. Content analysis focused on (i) if guidelines recommended specific psychosocial interventions, and how guidelines referred to (ii) social health, (iii) the intersection of social positioning, and (iv) inequities in care or outcomes. Thirty-five guidelines (74%) recommended specific psychosocial interventions. Around half referenced aspects of social health and of intersectionality. Thirteen guidelines (28%) referenced inequities. Social health was not explicitly recognised as a mechanism of psychosocial interventions. Only age and comorbidity were consistently considered to impact interventions’ effectiveness. Inequities were acknowledged to arise from within-country regional variations and individual economic status, but were not linked to (intersectional) individual societal positions such as sex and/or gender, sexuality, and/or religion. The results between European countries were heterogeneous. Current guidelines offer little insight into what works for whom. Policymakers and guideline developers should work with researchers, generating and translating evidence into policy. Full article

Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN−, and 30 healthy controls. Direct measurement of the active enzyme forms of thrombin and APC in the circulation was achieved by using oligonucleotide-based enzyme capture assays (OECA). Additionally, activation markers of coagulation and fibrinolysis were measured. Plasma levels of free thrombin and APC were higher in the MPN+ than in the MPN− cohort, with 0.49 vs. <0.46 pmol/L (p = 0.0057), respectively, 1.23 vs. 0.58 pmol/L (p = 0.0122), and in healthy controls (vs. <0.46 pmol/L, p = 0.0012; vs. 0.54 pmol/L, p = 0.0035). The indirect activation markers prothrombin fragment 1+2, thrombin-antithrombin complex, and D-dimer did not differ between groups. Receiver operating characteristic analysis suggested that SVT patients with MPN can be better distinguished by APC than by conventional indirect thrombin markers. A potential application of these biomarkers to guide anticoagulant therapy and to investigate the role of the PC pathway in MPN-associated hypercoagulability should be further studied. Full article

Understanding document layouts is vital for enhancing document exploration and information retrieval for sighted individuals. However, for blind and visually impaired people, it becomes challenging to have access to layout information using typical assistive technologies such as screen readers. In this paper, we examine the potential benefits of presenting documents on two-dimensional (2D) refreshable tactile displays. These displays enable the tactile perception of 2D data, offering the advantage of dynamic and interactive functionality. Despite their potential, the development of user interfaces (UIs) for such displays has not advanced significantly. Thus, we propose a design of an intelligent tactile user interface (TUI), incorporating touch and audio feedback to represent documents in a tactile format. Our exploratory study for evaluating this approach revealed satisfaction from participants with the experience of directly viewing documents in their true form, rather than relying on screen-reading interpretations. Additionally, participants offered recommendations for incorporating additional features and refining the approach in future iterations. To facilitate further research and development, we have made our dataset and models publicly available. Full article

Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, p < 2 × 10⁻⁶) and non-COVID sepsis (up to 4.7-fold, p < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, p = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, p = 2 × 10⁻⁴) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364–0.661) and non-COVID sepsis patients (r = 0.535–0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (p = 0.036), 6-fold (p = 3 × 10⁻⁷) and 3-fold (p = 8 × 10⁻⁴) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis. Full article

Aim: To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus. Design: A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria. Methods: Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan). Results: The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88). Conclusion: After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect. Full article

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea, consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three-inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module also includes calibration instruments and electronics for power, readout, and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and ten prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, which total 828 as of October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. The validation of a pre-production series has been completed, and a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure safe operation at the bottom of the Mediterranean Sea throughout the observatory’s lifespan. Full article

Fibromyalgia syndrome (FMS) is a common chronic pain disorder and often occurs as a concomitant disease in rheumatological diseases. Managing FMS takes a complex approach and often involves various non-pharmacological therapies. Fasting interventions have not been in the focus of research until recently, but preliminary data have shown effects on short- and medium-term pain as well as on physical and psychosomatic outcomes in different chronic pain disorders. This single-arm observational study investigated the effects of prolonged fasting (3–12 days, <600 kcal/d) embedded in a multimodal treatment setting on inpatients with FMS. Patients who were treated at the Department of Internal Medicine and Nature-Based Therapies of the Immanuel Hospital Berlin, Germany, between 02/2018 and 12/2020 answered questionnaires at hospital admission (V0) and discharge (V1), and then again three (V2), six (V3), and 12 (V4) months later. Selected routine blood and anthropometric parameters were also assessed during the inpatient stay. A total of 176 patients with FMS were included in the study. The Fibromyalgia Impact Questionnaire (FIQ) total score dropped by 13.7 ± 13.9 (p < 0.001) by V1, suggesting an improvement in subjective disease impact. Pain (NRS: reduction by 1.1 ± 2.5 in V1, p < 0.001) and quality of life (WHO-5: +4.9 ± 12.3 in V1, p < 0.001) improved, with a sustainable effect across follow-up visits. In contrast, mindfulness (MAAS: +0.3 ± 0.7 in V1, p < 0.001), anxiety (HADS-A: reduction by 2.9 ± 3.5 in V1, p < 0.0001), and depression (HADS-D: reduction by 2.7 ± 3.0 in V1, p < 0.0001) improved during inpatient treatment, without longer-lasting effects thereafter. During the study period, no serious adverse events were reported. The results suggest that patients with FMS can profit from a prolonged therapeutic fasting intervention integrated into a complex multimodal inpatient treatment in terms of quality of life, pain, and disease-specific functional parameters. ClinicalTrials.gov Identifier: NCT03785197. Full article

For decades, there has been ongoing discussion about whether centralized or decentralized wastewater management systems are better. Decision-makers need to define the best option but do not always have the necessary tools to develop, compare, and identify the most appropriate solution. To address this, studies have been conducted on a settlement level. In this study, the main focus was to develop and optimize wastewater management scenarios for a region containing rural areas, where data scarcity was an issue, by extracting scenario-relevant information from the region using a satellite image and its calibration using locally available data. We selected a study region in India containing 184 villages with a total population of around 210,000 and covering an area of around 400 km². The study considered three different scenarios for the study area: centralized, decentralized, and an optimized scenario, which consists of a hybrid system involving partly decentralized and partly semi-centralized (clustered) infrastructure. The study developed a systematic approach for defining an optimized cluster of villages by considering the cost trade-off between the wastewater treatment plant (WWTP) capacity and sewer network layout. The results showed that the clustered and decentralized scenarios were nearly equal in terms of cost (around EUR 118 million), while the centralized scenario showed a relatively high cost of EUR 168 million. Potential applications and further development of the method were also considered. The proposed methodology may aid global wastewater management by estimating and optimizing infrastructure costs needed to fulfill Sustainable Development Goal 6 (SDG#6) in rural regions. Full article

Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis. Full article

Few studies are available describing animal shelters in Portugal. The aim was to characterize prophylactic measures and disease occurrence in shelters with a questionnaire. The response rates of 67 shelters (42 municipal shelters, 25 associations) were compared by the Fisher’s exact test. More veterinarians answered for municipal shelters (98%) than for associations (40%; p < 0.001). Over 80% of the respondents indicated using individual medical records and routine prophylaxis. Excessive length of stay for dogs was reported by 54% of associations and 33% of municipal shelters. Management tools should be promoted to improve the situation. Puppy vaccinations were similar and a final vaccination at 16 weeks was indicated by >33% of shelters. Annual revaccination of dogs was reported more frequently by associations (88%) than municipal shelters (55%; p = 0.02). The three most reported diseases were parvovirus and mange in dogs, upper respiratory disease and panleukopenia in cats, and dermatophytosis in both species. Similar response rates for diagnostic options were obtained by both shelter types, except for distemper. Testing for feline retroviruses was indicated by most shelters (>69%), but only a few (<24%) confirmed positive test results. Clinical diagnoses should be complemented by testing. Additional information on disease occurrence should be obtained by objective monitoring. Full article

A new network of over 72 organizations from 12 countries was activated during a convening at ARTIS in Amsterdam on 26–27 September 2022. Representatives are aligned with the transdisciplinary field and social movement of Planetary Health, which analyzes and addresses the impacts of human disruptions to natural systems on human health and all life on Earth. The new European Planetary Health Hub consists of organizations from various sectors, including universities, healthcare, youth, business, and civil society. The Convening, co-organized by the Planetary Health Alliance (PHA), the European Environment and Sustainable Development Advisory Councils Network (EEAC), and Natura Artis Magistra (ARTIS), aimed to develop Planetary Health Working Groups for Education, Policy Engagement, Research, and Movement Building. The Convening resulted in an outline for each of the Working Group’s aims, visions, missions, priorities, and activities, and set the framework for sustaining their activities in the future through the establishment of the European Planetary Health Hub Secretariat in the Netherlands. The Hub members shared lessons learned, built relationships, and developed artwork-inspired perspectives on Planetary Health. In conclusion, the Convening led to the establishment of a strong European foundation to contribute to the transformations needed for sustainable, just, and equitable societies that flourish within the limits of our ecosystems. Full article

Preliminary clinical data suggest that pain reduction through fasting may be effective for different diagnoses. This uncontrolled observational clinical study examined the effects of prolonged modified fasting on pain and functional parameters in hip and knee osteoarthritis. Patients admitted to the inpatient department of Internal Medicine and Nature-based Therapies of the Immanuel Hospital Berlin between February 2018 and December 2020 answered questionnaires at the beginning and end of inpatient treatment, as well as at 3, 6, and 12 months after discharge. Additionally, selected blood and anthropometric parameters, as well as subjective pain ratings, were routinely assessed during the inpatient stay. Fasting was the only common intervention for all patients, being performed as part of a multimodal integrative treatment program, with a daily caloric intake of <600 kcal for 7.7 ± 1.7 days. N = 125 consecutive patients were included. The results revealed an amelioration of overall symptomatology (WOMAC Index score: −14.8 ± 13.31; p < 0.001; d = 0.78) and pain alleviation (NRS Pain: −2.7 ± 1.98, p < 0.001, d = 1.48). Pain medication was reduced, stopped, or replaced by herbal remedies in 36% of patients. Improvements were also observed in secondary outcome parameters, including increased quality of life (WHO-5: +4.5 ± 4.94, p < 0.001, d = 0.94), reduced anxiety (HADS-A: −2.1 ± 2.91, p < 0001, d = 0.55) and depression (HADS-D: −2.3 ± 3.01, p < 0.001, d = 0.65), and decreases in body weight (−3.6 kg ± 1.65, p < 0.001, d = 0.21) and blood pressure (systolic: −6.2 ± 15.93, p < 0.001, d = 0.43; diastolic: −3.7 ± 10.55, p < 0.001, d = 0.43). The results suggest that patients with osteoarthritis of the lower extremities may benefit from prolonged fasting as part of a multimodal integrative treatment to improve quality of life, pain, and disease-specific functional parameters. Confirmatory randomized controlled trials are warranted to further investigate these hypotheses. Full article