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Abstract Reportedly, nausea or vomiting after heavy exercise was associated with post-exercise increased blood calcium (Ca) levels, which was correlated with enhanced bone resorption. We conducted a randomized, double-blind, placebo-controlled trial, enrolling 104 healthy trained male members of the Japan Ground Self-Defense Forces. Risedronate (17.5 mg) or placebo was prescribed 3 and 10 days before heavy exercise lasting approximately 5 h. The primary outcome was the severity of nausea or vomiting assessed by a visual analog scale during or post-exercise. The secondary outcomes included clinical symptoms associated with heat illness, post-exercise serum total Ca (tCa), whole blood ionized Ca (iCa), and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels. The mean age was 26 years. The exercise resulted in a 4.5% weight loss. The two groups were comparable in terms of the symptoms, including primary outcome. However, post-exercise tCa and TRACP-5b were significantly lower with risedronate. A similar result was observed for iCa. The post-exercise urinary Ca/Magnesium ratio and the incidence of hypercalcemia (defined as tCa or iCa levels ≥ each median value of all subjects) were significantly lower with risedronate (78.0% vs. 58.5%). A stronger treatment effect of risedronate on blood Ca levels was observed in participants who lost substantial body weight. Post-exercise hypercalcemia is attributed to enhanced bone resorption but not the cause of nausea.

Abstract Accurate prognostic tools for mortality in patients with healthcare-associated pneumonia (HCAP) are needed to provide appropriate medical care, but the efficacy for mortality prediction of tools like PSI, A-DROP, I-ROAD, and CURB-65, widely used for predicting mortality in community-acquired and hospital-acquired pneumonia cases, remains controversial. In this study, we conducted a systematic review and meta-analysis using PubMed, Cochrane Library (trials), and Ichushi web database (accessed on August 22, 2022). We identified articles evaluating either PSI, A-DROP, I-ROAD, or CURB-65 and the mortality outcome in patients with HCAP, and calculated the pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the summary area under the curves (AUCs) for mortality prediction. Additionally, the differences in predicting prognosis among these four assessment tools were evaluated using overall AUCs pooled from AUC values reported in included studies. Eventually, 21 articles were included and these quality assessments were evaluated by QUADAS-2. Using a cut-off value of moderate in patients with HCAP, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were found to be 0.91–0.97, 0.15–0.44, 1.14–1.66, 0.18–0.33, and 3.86–9.32, respectively. Upon using a cut-off value of severe in those patients, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were 0.63–0.70, 0.54–0.66, 1.50–2.03, 0.47–0.58, and 2.66–4.32, respectively. Overall AUCs were 0.70 (0.68–0.72), 0.70 (0.63–0.76), 0.68 (0.64–0.73), and 0.67 (0.63–0.71), respectively, for PSI, A-DROP, I-ROAD, and CURB-65 (p = 0.66). In conclusion, these severity assessment tools do not have enough ability to predict mortality in HCAP patients. Furthermore, there are no significant differences in predictive performance among these four severity assessment tools.

Abstract Background Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer’s disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD. Methods We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study. J-TRC included 474 non-demented individuals (CDR 0: 331, CDR 0.5: 143). Participants underwent plasma Aβ and p-tau217 assessments, and Aβ-PET imaging. Findings in J-TRC were replicated in the BioFINDER cohort including 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). In both cohorts, plasma Aβ(1-42) (Aβ42) and Aβ(1-40) (Aβ40) were measured using immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), and p-tau217 was measured with an immunoassay on the Meso Scale Discovery platform (Eli Lilly). Results Aβ-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma Aβ42/Aβ40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal Aβ-PET scans, which were improved by combining plasma biomarkers and by including age, sex and APOE genotype in the models. In J-TRC, the highest AUCs were observed for the models combining p-tau217/Aβ42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, Aβ42/Aβ40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/Aβ42 ratio, APOE, age, sex in the CDR 0.5 group (AUC = 0.955), respectively. Each subgroup results were replicated in BioFINDER, where the highest AUCs were seen for models combining p-tau217, Aβ42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/Aβ42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914). Conclusions Combination of plasma Aβ-related biomarkers and p-tau217 exhibits high performance when predicting Aβ-PET positivity. Adding basic clinical information (i.e., age, sex, APOE ε genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of Aβ-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials of preclinical and prodromal AD.

Public health qualitative research has largely failed to achieve full inclusion of people with disabilities and Black people and Latinx/as. Although there is a small, but growing, community of academic researchers from each of these communities, there has been limited involvement of non-academic community members in research. While Community-Based Participatory Research (CBPR) has informed the inclusion of marginalized groups in research for decades, instances of full inclusion of disabled Black people and Latinx/as in public health research have been minimal. One way to ensure the inclusion of Black/Latinx community members with disabilities is to involve them as peer researchers. As part of a qualitative study examining pregnancy experiences of individuals with physical disabilities from Black/Latinx communities, academic researchers trained four peer researchers to conduct interviews and analyze the data. This paper describes our approach, which may serve as a model for training peer researchers in qualitative research methodology for future studies. All peer researchers were women who identified as Black or Latina parents with physical disabilities. This approach was chosen due to the study’s focus on the intersections of disability, race, ethnicity, and pregnancy, and applied a disability justice lens. Although CBPR offers important principles for research existing literature suggests CBPR is not always inclusive and power sharing. Therefore, we developed a research training model which places a unique and timely focus on the intersections of CBPR, racial and disability justice, the importance of building the capacity of Black and Latina disabled peer researchers, and its importance to building community relationships and trust.

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

Sinonasal schwannoma (SNS) is a rare entity with 4% occurring at this location and only 36 cases described in the literature. A 22-year-old woman presented recurrent unilateral epistaxis, hyposmia, unilateral nasal obstruction, and hemicranial headache for a year. The endoscopic examination showed a tissue mass filling the left nasal cavity and nasopharynx. Imaging showed a mass that occupied the left posterior ethmoid cells in the hyposignal T1, hyposignal T2, and gadolinium enhancing. A preoperative biopsy was made and the diagnosis was a schwannoma. The tumor mass was completely removed under general anesthesia. The final histopathological study reconfirmed the diagnosis of schwannoma. Six months after surgery, control endoscopic and imaging showed the absence of tumor recurrence. SNS is a rare entity and its diagnosis is generally based on a histological examination. Therefore, the possibility of schwannoma must be considered in front of a mass of the nasal fossa.

Abstract Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially fatal medical conditions that lack established treatment. Therapeutic plasma exchange (PE) is a potential treatment option; however, its effectiveness is unclear. We aimed to evaluate the effectiveness of PE in patients with SJS/TEN. A retrospective cohort study was conducted using data from the Japanese National Administrative Claims database from 2016 to 2021. The analysis included 256 patients diagnosed with SJS/TEN who were admitted to the intensive care unit, of whom 38 received PE and 218 did not. The outcomes of patients who did and did not receive PE within the first 24 h of admission were compared. The risk ratios and 95% confidence intervals of the PE group compared with those of the no-PE group were as follows: in-hospital mortality, 0.983 (0.870–1.155); 30-day mortality rate, 1.057 (0.954–1.217); 50-day mortality rate, 1.023 (0.916–1.186); and length of hospital stay, 1.163 (0.762–1.365). This study does not provide evidence of a benefit of PE in reducing mortality or length of hospital stay in patients with severe SJS/TEN.

Abstract Background High level of physical fitness is a paramount soccer performance factor. As such, developing key components of physical fitness such as sprinting, jumping, and change of direction (CoD) at an early age empowers both short- and long-term performance success. Although previous research in prepubertal male soccer players has reported physical fitness performance enhancements following plyometric jump training (PJT), the effects on inter-limb asymmetries remain unclear. Objective To assess the effects of PJT on measures of physical fitness and inter-limb asymmetries in prepubertal male soccer players. Methods A total of 27 participants were recruited, and randomly assigned to either a PJT group (n = 13; age = 12.7 ± 0.2 years; maturity offset = -1.6 ± 0.7) or an active control group (CG) (n = 14; age = 11.8 ± 0.4 years; maturity offset = -2.51 ± 0.61). The training intervention lasted eight-week and was conducted during the in-season period, with twice-weekly sessions. Physical fitness tests were conducted before and after the intervention, including the 505 change-of-direction (CoD; [505 CoD test]), countermovement-jump (CMJ) height, standing-long-jump (SLJ) distance, and single-leg hop test for distance with dominant (SHTD-D) and non-dominant legs (SHTD-ND). A jump-based asymmetry score was calculated as the difference between HTD and HTND. Results ANCOVA analysis revealed significant between-group differences in all physical fitness measures at post-test. Specifically, the PJT group showed significant large improvements in CMJ height, SLJ distance, HTD and HTND, and CoD speed (d = 0.84 to 2.00; ∆1.05% to 16.85%). Moreover, the PJT group showed a significant, small reduction in the inter-limb asymmetry score (d = 0.43; ∆-45.21%). In contrast, no significant changes were reported in the CG between pre-and post-tests (d = 0.07 to 0.24; ∆0.21% to 0.98%). Conclusions The incorporation of PJT into the training schedules of prepubertal male soccer players resulted in positive effects on various measures of physical fitness. Furthermore, our findings suggest that PJT can reduce lower-limb asymmetry, which could potentially decrease the risk of lower limb injuries. Trial registration This study does not report results related to healthcare interventions using human participants and therefore it was not prospectively registered.

Using fungi in decomposition is an important indicator of success in biogas production from oil palm empty fruit bunches (EFB). This study isolated fungi from EFB to be used in the biogas production process. The results identified the fungus as Aspergillus niger based on macroscopic, microscopic, and molecular analysis. Adding the substrate (S) to Palm Oil Mill Effluent (POME) increased CH4 concentration from 6 % to 60 %. POME-S10 produced 80 % more biogas compared to POME-S0. POME 0-S100 had the highest CH4 to CO2 ratio in biogas (±260 %), compared to POME-S0 (±20 %), POME-S4 (±25 %), POME-S7 (±21 %), and POME-S10 (±100 %).

Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection.

Hidup seorang biarawan katolik tidak lepas dari kitab suci. Maka seorang biarawan katolik dalam formasi di bidang intelektual dan pastoral mendapat pembekalan keterampilan mengenai kitab suci. Biara Bruder Keluarga Kudus Nazaret Liliba Kupang melaksanakan pelatihan keterampilan membaca dan mendalami kitab suci khususnya mengenai Surat Paulus sebagai bagian dari formasi tersebut. Dengan itu diharapkan agar para bruder biarawan ini dapat meningkatkan pemahaman dan keterampilan membaca Surat Paulus sehingga bermanfaaat bagi spiritualitas pribadi maupun bagi kepentingan pelayanan pastoral melalui katekese. Metode pembelajaran ini ditempuh dengan cara ceramah, diskusi, latihan teknik mendalami teks, hingga latihan menyusun renungan biblis. Hasil yang dicapai adalah adanya pemahaman dan keterampilan mendalami Surat Paulus, serta menyusun renungan biblis yang bermanfaat dalam pelayanan pastoral. Kata kunci: Kitab suci, Surat-surat Paulus, mendalami teks, renungan biblis

In response to global clean energy demands, this study develops mixed matrix membranes (MMMs) for gas separation in renewable energy applications. MMMs are produced through phase inversion by employing polysulfone and bimetallic-ZIF (Ni–Co-ZIF-67). Bimetallic-ZIF, formed in-situ by Co and Ni metals in water solvent with triethylamine, enhances gas selectivity. MMMs with 4 wt% bimetallic-ZIF, Co: Ni ratio of 9:1 (4Ni10Z67), exhibit remarkable selectivity: CO2/CH4 (21.19), H2/N2 (1.47), H2/CH4 (44.82), and N2/CH4 (30.40). Strong interactions between bimetallic-ZIF and CO2, facilitated by molecular sieving and Ni–Co sites, contribute to these results.

This paper discusses the concept and model to develop a prototype extracellular vesicle bulk-isolation device (EBID). It proposes an engineering design and potential ways to mitigate limitations in the currently available extracellular vesicle (EV) isolation techniques. A more convenient isolation technique is developed and presented to ensure production-scale isolation and purification of the specific size of EV (approximately 0.1 to 0.34 µm) from a large quantity of cell-culture media or biological fluid sources. A more appropriate design concept was established based on the chitosan-assisted precipitation of EV techniques and the membrane filtration technology-based prototype. After that, a novel theoretical model for bulk isolation of EVs was developed and presented using pressure-driven circulation and particulate flow in the EBID loop, where the EV production results from the biofluid flowing through the EBID membrane filter module (MFM). Governing equations are coupled with Darcy's law to investigate the biofluid flow behavior in the EBID MFM, therefore simulating the isolation process of EVs from their biofluids. The flow characteristics of the EV isolation process within the EBID MFM are theoretically simulated and discussed for improved isolation yield with a high degree of quality and purity.

Summary: Background: Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD. Methods: 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and symptomatic AD). Tau burden and tau spatial spread were calculated for all participants. Findings: We found both tau metrics significantly elevated across increasing disease stages (p

Introduction Advanced adrenocortical carcinoma has a poor prognosis and is treated with chemotherapy that includes mitotane with etoposide, doxorubicin, and cisplatin as first‐line therapy. However, second‐line therapy has not been determined yet. Pembrolizumab has been approved for high microsatellite instability for which standard treatments have failed. Case presentation Here, we present a patient with advanced adrenocortical carcinoma treated with complete surgical resection. 21 months later, he had local and metastatic recurrences. After four cycles of first‐line therapy, we switched to pembrolizumab because microsatellite instability‐high was detected in his tumor. He has received mitotane and pembrolizumab for 15 months, and this has exerted a radiographical response without severe adverse events. Conclusion We presented a patient with microsatellite instability‐high advanced adrenocortical carcinoma treated with pembrolizumab and mitotane.