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    Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm: A Meta-Analysis.

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    IMPORTANCE International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. OBJECTIVE To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. DATA SOURCES Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. STUDY SELECTION The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. DATA EXTRACTION AND SYNTHESIS Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. MAIN OUTCOMES AND MEASURES The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. RESULTS A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. CONCLUSIONS AND RELEVANCE In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome

    Motives for desiring children among individuals of different sexual-romantic orientations: a cross-sectional study.

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    PURPOSE Little is known about the reasoning behind the desire to have children in non-heterosexual individuals. This study compares the motives of different sexual-romantic orientations and their preferred ways of fulfilling this desire. METHODS This was a monocentric cross-sectional study. Subjects were recruited via social media, personal contacts and queer organisations in Switzerland. An anonymous questionnaire comprised general questions about the participant's background, a validated survey about the desire to have children and additional non-validated questions addressing the impact of sexual-romantic orientation on the desire to have children. The inclusion criteria were adults without children and a completed questionnaire. RESULTS Of 837 participants, 642 were included in the study. Four groups of sexual-romantic orientations consisted of more than 35 participants: bisexual-biromantic (n = 38), heterosexual-heteroromantic (n = 230), homosexual-homoromantic (n = 159) and pansexual-panromantic (n = 55). Subgroups with a positive wish for a child rated all motives in the same order and with minimal numeric difference. The most important aspect seemed to be emotional involvement. Non-heterosexual-heteroromantic showed concerns about adverse reactions regarding their wish for a child. All orientations hoped for a biological child. CONCLUSION Our findings about bi-, hetero-, homo- and pansexual people and their motives for a desire to have children agree with the existing literature about hetero, homo and bisexual. The impact of the fear of adverse reaction and discrimination has been discussed before and is supported by our data. We suggest better support before and during the realization of the wish for a child as well as support for non-traditional aspiring parents

    Antimicrobial activity, surface properties, and cytotoxicity of microencapsulated phytochemicals incorporated into three-dimensionally printable dental polymers.

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    OBJECTIVES This study aimed to investigate the antimicrobial properties of three dimensionally-printed dental polymers (3DPs) incorporated with microencapsulated phytochemicals (MPs) and to assess their surface characteristics and cytotoxicity. METHODS MPs derived from phytoncide oil and their specific chemical components were introduced into suspensions of three microbial species: Streptococcus gordonii, Streptococcus oralis, and Candida albicans. Optical density was measured to determine the microbial growth in the presence of MPs for testing their antimicrobial activity. MPs at 5% (w/w) were mixed with dental polymers and dispersants to 3DP discs. These microbial species were then seeded onto the discs and incubated for 24 h. The antibacterial and antifungal activities of MP-containing 3DPs were evaluated by counting the colony-forming units (n=3). The biofilm formation on the 3DP was assessed by crystal violet staining assay (n=3). Microbial viability was determined using a live-dead staining and CLSM observation (n=3). Surface roughness and water contact angle were assessed (n=10). Cytotoxicity of MP-containing 3DPs for human gingival fibroblast was evaluated by MTT assay. RESULTS MPs, particularly (-)-α-pinene, suppressed the growth of all tested microbial species. MP-containing 3DPs significantly reduced the colony count (P≤0.001) and biofilm formation (P≤0.009), of all tested microbial species. Both surface roughness (P<0.001) and water contact angle (P<0.001) increased. The cytotoxicity remained unchanged after incorporating MPs to the 3DPs (P=0.310). CONCLUSIONS MPs effectively controlled the microbial growth on 3DPs as evidenced by the colony count, biofilm formation, and cell viability. Although MPs modified the surface characteristics, they did not influence the cytotoxicity of 3DPs. CLINICAL SIGNIFICANCE Integration of MPs into 3DPs could produce dental prostheses or appliances with antimicrobial properties. This approach not only provides a proactive solution to reduce the risk of oral biofilm-related infection but also ensures the safety and biocompatibility of the material, thereby improving dental care

    Does tissue fixation change the mechanical properties of dry ovine bone extracellular matrix?

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    Tissue fixation is a prevalent method for bone conservation. Bone biopsies are typically fixed in formalin, dehydrated in ethanol, and infiltrated with polymethyl methacrylate (PMMA) Since some experiments can only be performed on fixed bone samples, it is essential to understand how fixation affects the measured material properties. The aim of this study was to quantify the influence of tissue fixation on the mechanical properties of cortical ovine bone at the extracellular matrix (ECM) level with state-of-the-art micromechanical techniques. A small section from the middle of the diaphysis of two ovine tibias (3.5 and 5.5 years old) was cut in the middle and polished on each side, resulting in a pair of mirrored surfaces. For each pair, one specimen underwent a fixation protocol involving immersion in formalin, dehydration with ethanol, and infiltration with PMMA. The other specimen (mirrored) was air-dried. Six osteons were selected in both pairs, which could be identified in both specimens. The influence of fixation on the mechanical properties was first analyzed using micropillar compression tests and nanoindentation in dry condition. Additionally, changes in the degree of mineralization were evaluated with Raman spectroscopy in both fixed and native bone ECM. Finally, micro tensile experiments were conducted in the 3.5-year fixed ovine bone ECM and compared to reported properties of unfixed dry ovine bone ECM. Interestingly, we found that tissue fixation does not alter the mechanical properties of ovine cortical bone ECM compared to experiments in dry state. However, animal age increases the degree of mineralization (p = 0.0159) and compressive yield stress (p = 0.041). Tissue fixation appears therefore as a valid conservation technique for investigating the mechanical properties of dehydrated bone ECM

    Point-of-Care Diagnostics for Infection and Antimicrobial Resistance in Sub-Saharan Africa - A Narrative Review.

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    INTRODUCTION Sub-Saharan African (SSA) countries are severely impacted by antimicrobial resistance (AMR). Due to gaps in access to diagnostics in SSA the true extent of AMR remains unknown. This diagnostic gap affects patient management and leads to significant antimicrobial overuse. This review explores how point-of-care (POC) testing for pathogen identification and AMR may be used to close the diagnostic gap in SSA countries. METHODS A narrative review exploring current clinical practice and novel developments in the field of point-of-care (POC) testing for infectious diseases and AMR. FINDINGS POC assays for identification of various pathogens have been successfully rolled out in SSA countries. While implementation studies have mostly highlighted impressive test performance of POC assays, there is limited data on effect of implementation on clinical outcomes and cost-effectiveness. We did not encounter local studies of host-directed POC assays relevant to AMR. Novel POC assays using real-time PCR, isothermal amplification, microfluidics and other technologies are in various stages of development. DISCUSSION Available literature shows that POC testing for AMR applications is implementable in SSA and holds the potential to reduce the diagnostic gap. Implementation will require effective regulatory pathways, incorporation of POC testing in clinical and laboratory guidelines, and adequate value capture in existing health financing models

    Reduced anterior callosal white matter in risk for psychosis associated with processing speed as a fundamental cognitive impairment

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    Background Previous research in psychotic disorders discovered associations between reduced integrity of white matter (WM) in the corpus callosum (CC) and impaired cognitive functions, suggesting processing speed as a central construct. However, it is still largely unexplored to what extent disruption in callosal WM is related to cognitive deficits during the risk stage prior to psychosis. Methods To address this gap, we measured the WM integrity in CC by fractional anisotropy (FA) and assessed cognition in 60 clinical-high risk for psychosis (CHR) patients during adolescence/young adulthood and 38 healthy control (HC) subjects. We employed tract based spatial statistics to examine group differences and associations between CC-FA and processing speed, executive function, and spatial working memory. Results We revealed deficits in processing speed, executive function, and spatial working memory of CHR patients, and reductions in FA of the genu and the body of the CC (p < 0.05, corrected for multiple comparisons) compared to HC. A mediation analysis using the combined sample (CHR + HC) showed that processing speed mediates the associations between the impaired CC structure and executive function and spatial working memory, respectively. Exploratory analyses between CC-FA and the cognitive domains located associations of processing speed in the genu and the body of CC with distinct spatial distributions of executive function and spatial working memory. Conclusion We suggest processing speed as a subordinate cognitive factor contributing to the associations between callosal WM, executive function and working memory. These results extend findings in psychotic disorders to the prior risk stage

    Taken along the Edge of Empires: ‘The Eagle of the Ninth’ by Rosemary Sutcliff

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    S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

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    The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups

    Pseudomonas aeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group.

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    SCOPE Pseudomonas aeruginosa, a ubiquitous opportunistic pathogen considered one of the paradigms of antimicrobial resistance, is among the main causes of hospital-acquired and chronic infections associated with significant morbidity and mortality. This growing threat results from the extraordinary capacity of P. aeruginosa to develop antimicrobial resistance through chromosomal mutations, the increasing prevalence of transferable resistance determinants (such as the carbapenemases and the extended spectrum β-lactamases), and the global expansion of epidemic lineages. The general objective of this initiative is to provide a comprehensive update of P. aeruginosa resistance mechanisms, especially for the extensively drug-resistant (XDR)/difficult to treat resistance (DTR) international high-risk epidemic lineages, and how the recently approved β-lactams and β-lactam/β-lactamase inhibitor combinations may affect resistance mechanisms and the definition of susceptibility profiles. METHODS To address this challenge, the European Study Group for Antimicrobial Resistance Surveillance (ESGARS) from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) launched the "Improving Surveillance of Antibiotic-Resistant Pseudomonas aeruginosa in Europe" (ISARPAE) initiative in 2022, supported by the Joint programming initiative on antimicrobial resistance (JPIAMR) network call and included a panel of over 40 researchers from 18 European Countries. Thus, an ESGARS-ISARPAE position paper was designed and the final version agreed after four rounds of revision and discussion by all panel members. QUESTIONS ADDRESSED IN THE POSITION PAPER To provide an update on (i) the emerging resistance mechanisms to classical and novel antipseudomonal agents, with a particular focus on β-lactams, (ii) the susceptibility profiles associated with the most relevant β-lactam resistance mechanisms, (iii) the impact of the novel agents and resistance mechanisms on the definitions of resistance profiles and (iv) the globally expanding XDR/DTR high-risk lineages and their association with transferable resistance mechanisms. IMPLICATION The evidence presented herein can be used for coordinated epidemiological surveillance and decision-making at the European and global level

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