Enhancing Variant Calling in Whole-Exome Sequencing Data Using Population-Matched Reference Genomes.

Whole-exome sequencing (WES) data are frequently used for cancer diagnosis and genome-wide association studies (GWAS), based on high-coverage read mapping, informative variant calling, and high-quality reference genomes. The center position of the currently used genome assembly, GRCh38, is now challenged by two newly published telomere-to-telomere (T2T) genomes, T2T-CHM13 and T2T-YAO, and it becomes urgent to have a comparative study to test population specificity using the three reference genomes based on real case WES data. Here we report our analysis along this line for 19 tumor samples collected from Chinese patients. The primary comparison of the exon regions among the three references reveals that the sequences in up to ∼ 1% target regions in T2T-YAO are widely diversified from GRCh38 and may lead to off-target in sequence capture. However, T2T-YAO still outperforms GRCh38 genomes by obtaining 7.41% more mapped reads. Due to more reliable read-mapping and closer phylogenetic relationship with the samples than GRCh38, T2T-YAO reduces half of variant calls of clinical significance which are mostly benign, while maintaining sensitivity in identifying pathogenic variants. T2T-YAO also outperforms T2T-CHM13 in reducing calls of Chinese-specific variants. Our findings highlight the critical need for employing population-specific reference genomes in genomic analysis to ensure accurate variant analysis and the significant benefits of tailoring these approaches to the unique genetic backgrounds of each ethnic group.

MRI grading for informed clinical decision-making in Peutz-Jeghers syndrome patients with cervical lesions.

The preoperative diagnosis and management of Peutz-Jeghers syndrome (PJS) patients with cervical lesions remain problematic. This study analysed the associations between pathological types of cervical lesions in PJS patients and their MRI features. A total of 34 PJS patients were included and two experienced radiologists reviewed the MRIs independently. Based on the pathological diagnosis, the patients were categorized into four groups: normal (n  =  4), lobular endocervical glandular hyperplasia (LEGH, n  =  11), atypical LEGH (aLEGH, n  =  8), and gastric-type endocervical adenocarcinoma (G-EAC, n  =  11). By observing the MRI features, we found statistically significant differences in the extent of lesions (P  = 0 .001), distribution of microcysts (P  = 0 .001), proportion of microcysts (P  <  0.001) and endometrial involvement (P  = 0.019) among the four groups. Notably, solid components and disrupted cervical stromal rings were found only in the aLEGH and G-EAC groups (P  < 0.001).  Consequently, we created a novel grading system based on the aforementioned MRI features to align with the potential malignancy of cervical lesions in PJS patients. This system enables patients to receive timely and appropriate treatment recommendations while facilitating collaboration between radiologists and physicians.

Amino Acid Decorated Phenanthroline Diimide as Sustainable Hydrophilic Am(III) Masking Agent with High Acid Resistance.

Hydrophilic actinide masking agents are believed to be efficient alternatives to circumvent the extensive hazardous organic solvents/diluents typically employed in the liquid-liquid extraction for nuclear waste management. However, the practical application of hydrophilic ligands faces significant challenges in both synthetic/purification procedures and, more importantly, the acid resistance of the ligands themselves. Herein, we have demonstrated the combination of phenanthroline diimide framework with a biomotif of histidine flanking parts could achieve efficient separation of trivalent lanthanides/actinides (also actinides/actinides) under high acidity of over 1 M HNO3. This approach leverages the soft-hard coordination properties of N, O-hybrid ligands, as well as the energetically favored imides for metal coordination and the multiple protonation of histidine. These factors collectively contribute to the synthesis of an easily accessible, highly water-soluble, superior selective, and acid-resistant Am(III) masking agent. Thus, we have shown in this paper, by proper combination of synthetic N, O-hybrid ligand with amino acid, trivalent lanthanide and actinide separation could be efficiently fulfilled in a more sustainable manner.

A pH-responsive novel delivery system utilizing carbon quantum dots loaded with PT2385 for targeted inhibition of HIF-2α in the treatment of osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a progressive joint disorder marked by the degradation of cartilage. Elevated concentrations of hypoxia-inducible factor-2α (HIF-2α) are intricately linked to the pathological development of OA. PT2385 has demonstrated effective inhibition of HIF-2α, thereby potentially impeding the initial advancement of OA. Nevertheless, challenges persist, including limited penetration into the deeper layers of cartilage, issues related to charge rejection, and a heightened rate of clearance from the joint. These constraints necessitate further consideration and exploration. METHODS: It has been demonstrated that PT2385 exhibits efficient inhibition of HIF-2α expression, thereby contributing to the delay in the progression of osteoarthritis. The pH-responsive attributes of carbon quantum dots, specifically those employing m-phenylenediamine (m-CQDs) coated with bovine serum albumin (BSA), have been systematically evaluated. In both in vitro settings involving cartilage explants and in vivo experiments, the efficacy of BSA-m-CQDs-PT2385 (BCP) has been confirmed in facilitating the transport of PT2385 to the middle and deep layers of cartilage. Furthermore, the BCP system demonstrates controlled drug release contingent upon alterations in environmental pH. RESULTS: While the use of PT2385 alone provides protective effects on chondrocytes within an inflamed environment, there exists an opportunity for further enhancement in its efficacy when administered via intra-articular injection. The BCP formulation, characterized by appropriate particle size and charge, facilitates seamless penetration into cartilage tissue. Additionally, BCP demonstrates the capability to release drugs in response to changes in environmental pH. In vitro experiments reveal that BCP effectively inhibits Hif-2α expression and catabolic factors in chondrocytes. Notably, cartilage explants and in vivo experiments indicate that BCP surpasses PT2385 alone in inhibiting the expression of HIF-2α and matrix metalloproteinase 13, particularly in the middle and deep layers. CONCLUSIONS: The BCP drug delivery system exhibits selective release of PT2385 in response to pH changes occurring during the progression of osteoarthritis (OA), thereby inhibiting HIF-2α expression deep within the cartilage. The use of BCP significantly augments the capacity of PT2385 to retard both cartilage degeneration and the progression of osteoarthritis. Consequently, BCP as an innovative approach utilizing m-CQDs to deliver PT2385 into articular cartilage, shows potential for treating osteoarthritis.This strategy opens new avenues for osteoarthritis treatment.

Spermidine Improves Freezing Tolerance by Regulating H2O2 in Brassica napus L.

Low temperature is a common abiotic stress that causes significant damage to crop production. Polyamines (PAs) are a class of aliphatic amine compounds that serve as regulatory molecules involved in plant growth, development, and response to abiotic and biotic stresses. In this study, we found that the exogenous application of two concentrations of spermidine (Spd) significantly enhanced the freezing tolerance of three differently matured rapeseed (Brassica napus L.) varieties, as manifested by higher survival rates, lower freezing injury indexes, and reduced H2O2 content. RNA-seq and qRT-PCR analyses showed that Spd enhanced the freezing tolerance of rapeseed by regulating genes related to the PA metabolic pathway and antioxidant mechanism, and generally inhibited the expression of genes related to the JA signaling pathway. This study provides a reference basis for understanding the functionality and molecular mechanisms of polyamines in the response of rapeseed to freezing stress.

A methodology for gene level omics-WAS integration identifies genes influencing traits associated with cardiovascular risks: the Long Life Family Study.

The Long Life Family Study (LLFS) enrolled 4953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8 × 10-7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein-Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genes FCER1A, MS4A2, GATA2, HDC, and HRH4 in atherosclerosis risks. Our findings also suggest that lower expression of ATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest that ENPP3 may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform ( https://nf-co.re/omicsgenetraitassociation ).

Live-attenuated PruΔgra72 strain of Toxoplasma gondii induces strong protective immunity against acute and chronic toxoplasmosis in mice.

BACKGROUND: Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown. METHODS: We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0. RESULTS: We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice. CONCLUSIONS: The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.

Endovascular management of intracranial carotid blowout syndrome in patients with head and neck cancer.

BACKGROUND: Carotid blowout syndrome is a serious complication of head and neck cancer (HNC) that may involve the intracranial or extracranial internal carotid artery (ICA). Although parent artery occlusion (PAO) is the major endovascular treatment for intracranial carotid blowout syndrome (iCBS), the efficacy of using a balloon-expandable coronary stent-graft (BES) remains unclear. METHODS: This was a quasi-randomized trial, prospective study that included patients with iCBS treated by BES or PAO between 2018 and 2024. Patients were allocated to either group based on the last digit of their chart number; even numbers went to the BES group and odd numbers to the PAO group. The inclusion criteria of iCBS included the pathological process of CBS involving petrous and/or cavernous ICA detected by both imaging and clinical features. The primary outcome was defined as rebleeding events after intervention. The secondary outcome was defined as neurological complication after intervention. RESULTS: Fifty-nine patients with 61 iCBS lesions were enrolled. Thirty-three iCBS lesions were treated with BES and 28 underwent PAO. The results for the BES group versus the PAO group, respectively, were: rebleeding events, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); neurological complication, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); median hemostatic time (months), 10.0 vs 11.5 (p=0.22); and median survival time (months), 10.0 vs 11.5 (p=0.39). CONCLUSIONS: No significant difference in rebleeding risk or neurological complication was observed between the BES and PAO groups. Our study confirmed the safety and effectiveness of applying BES for iCBS in HNC patients.

Corrigendum to "Enhancing physical and cognitive function in older adults through walking & resistance exercise: Korean national aging project randomized controlled study" [J Exercise Sci Fitness 22 (4) (October 2024) 383-389].

[This corrects the article DOI: 10.1016/j.jesf.2024.07.002.].

Puerarin Alleviates Blood Pressure via Inhibition of ROS/TLR4/NLRP3 Inflammasome Signaling Pathway in the Hypothalamic Paraventricular Nucleus of Salt-Induced Prehypertensive Rats.

BACKGROUND: Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. PURPOSE: The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. METHODS: Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. RESULTS: We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. CONCLUSION: We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.

Enhancing physical and cognitive function in older adults through walking & resistance exercise: Korean national aging project randomized controlled study.

Background: The rapid aging of Korea's population underscores the urgent need for effective programs to enhance the well-being and longevity of the elderly. This study presents preliminary results from the Korean project, examining the impact of cost-effective and accessible exercise programs on functional performance of older people and to determine the long-term maintenance of intervention. Methods: We randomized 90 older adults aged ≥65 years to the walking group (WG), resistance + walking (RWG), or active control (CG) group. We designed a 12-week main intervention (supervised resistance training 2 d/week and individual walking exercise) and a 12-week follow-up through self-directed exercise (same protocol but unsupervised). The participants' mini mental state examination, color-word Stroop test and 5-time sit to stand, timed up & go, handgrip strength, and knee extensor strength tests were assessed at pre, post, as well as follow-up. Results: For the RWG group, significant improvements were found in timed up & go (P < 0.001), and 5-time sit to stand (P < 0.001) compared to CG, with benefits maintained at follow-up. Both RWG and WG showed significant enhancements in knee extensor power (RWG: P < 0.0001; WG: P < 0.001) and flexor power (RWG: P < 0.01; WG: P = 0.018) compared to CG. Although cognitive performance did not show significant group-by-time interactions, RWG exhibited improvements in the Stroop Color and Color-Word tests at follow-up compared to baseline. Conclusion: A resistance training program combined with walking effectively enhanced functional performance in older adults, providing lasting benefits over 12 weeks on physical functions, such as strength and endurance. However, it showed limited benefits on cognitive performance.

Development of emulsion-filled calcium alginate gels for thermoresponsive release of flavor in plant-based meat analogs.

We developed emulsion-filled calcium alginate gels (EF-CAG) as a novel thermoresponsive carrier for plant-based meat analogs (PBMA), designed to mimic the cooking-induced flavor release of real meat. Optimized to maximize flavor release upon heating, EF-CAG demonstrated a thermoresponsive release of 51% with a notable size reduction. Initial release profiles varied between media; a burst release of 43% occurred in water within the first 5 min, while <1% was released in air. EF-CAG consistently increased flavor release in PBMA during cooking, without adversely affecting appearance or flavor stability, maintaining flavor retention at 4 °C for 10 days. The sensory evaluation confirmed that EF-CAG successfully masked the beef flavor before cooking and enhanced its release afterward. Our findings suggest that EF-CAG can be effectively used as a flavoring agent for PBMA, offering similar flavor attributes to real meat during cooking.

Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR-Mutated Lung Cancer Cells Resistant to Osimertinib.

Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R/T790M double mutation and osimertinib-resistance. Liquid chromatography-mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD-9291, Tagrisso), H1975 cells were used to establish the osimertinib-resistant cells, named H1975/TR cells. The expressions of Integrin αV and stemness markers were much higher in H1975/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin αV and ß1 in H1975/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin αV signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin αV-related signaling pathway in EGFR-mutated and osimertinib-resistant lung cancer cells.

Safety of herbal medicine in the postpartum period of a Korean Medicine hospital and postpartum care centre: protocol of a registry study (SAFEHERE-PC).

INTRODUCTION: Herbal medicines (HMs) are commonly used during the postpartum period in South Korea. However, the safety concerns associated with these medicines remain unresolved. This study aims to establish a registry of patients receiving HM treatment during the postpartum period and collect clinical data on treatments and adverse reactions to build evidence evaluating the safety of HM use. METHODS AND ANALYSIS: This study will use a prospective observational registry, including patients admitted to the obstetrics and gynaecology department of the Woosuk University Korean Medicine Hospital's postpartum care centre. A total of 1000 eligible patients visiting the Korean medicine hospital to recover from various postchildbirth symptoms and opting for HM treatment will be enrolled in the registry. For safety assessment, demographic information, medical history, adverse events (AEs) and treatment details, including HM prescription and concomitant medication usage, will be collected throughout the patient's hospitalisation period at the postpartum care centre for analysis. Adverse reactions will be monitored daily during hospitalisation, and collected AEs will be analysed for causality using the WHO Uppsala Monitoring Centre causality assessment and the Naranjo Algorithm Score. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Woosuk University Korean Medicine Medical Center (WSOH IRB H2311-03-01). The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: KCT0009060.

Integrating network pharmacology with pharmacological research to elucidate the mechanism of modified Gegen Qinlian Decoction in treating porcine epidemic diarrhea.

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug's efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-ß, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections.

Multitasking during medication management in a nursing home: A time motion study.

BACKGROUND: Multitasking, defined as performing two or more interventions simultaneously, increases the cognitive burden of clinicians. This may, in turn, lead to higher risk of medication and procedural errors. Time motion study (TMS) data for nurses in nursing homes revealed an extensive amount of multitasking while managing medications. Further investigation of multitasked nursing interventions will provide a foundation for optimizing medication management workflows. OBJECTIVES: Using a continuous observational TMS method, this study aimed to describe pairs of multitasked nursing interventions associated with medication management interventions, including preparing and administering medications, assessing medication effects, instructing on medications, and documenting medication administration. METHODS: An external nurse observer used 57 pre-defined Omaha System nursing interventions embedded within TimeCaT (version 3.9) TMS data recording software to collect observation data in a single nursing home. A total of 120 hours of time-stamped observation data from nine nurses was downloaded from TimeCaT and analyzed using descriptive and inferential statistics. RESULTS: The majority (74%) of medication management interventions were multitasked, resulting in 2,003 pairs of multitasked interventions. Of the 57 Omaha System nursing interventions, 35 were involved in these multitasking pairs. When nurses multitasked, the average duration of medication preparation was longer (non-multitasked: 81 seconds; multitasked: 162 seconds, p<0.05), while the average duration of medication administration record documentation was shorter (non-multitasked: 93 seconds; multitasked: 66 seconds, p<0.05). CONCLUSIONS: The findings reveal the complexity of medication management in nursing homes with numerous and diverse multitasking pairs. Findings provide a platform for in-depth study of medication management multitasking in the clinical context, and inform future efforts to create clinical and informatics solutions to optimize medication management workflow. This method may be also applied to examine medication management and multitasking in other clinical settings.

Effect of mixed protein supplementation on golf performance and muscle function: a randomized, double-blind, placebo-controlled study.

BACKGROUND: As a relatively novel approach to enhancing skeletal muscle health, mixed protein supplementation has shown similar responses to whey protein. However, no previous studies have examined its impact on golf swing performance. This study aimed to examine the effect of mixed protein supplementation on the swing performance and muscle strength of casual golfers. METHODS: Sixty participants with a handicap of less than 20 were recruited and randomly assigned to a double-blind, placebo-controlled study design. The participants were divided into two groups: a mixed protein group (MG, n = 30), and a placebo control group (CG, n = 30). They were instructed to ingest either a supplement containing casein calcium, whey protein, and isolated pea protein, or a placebo, once daily for 8 weeks. Pre- and posttests consisted of anthropometric measurements, muscle strength (isokinetic knee and trunk strength, and handgrip strength), 2-minute push-ups, balance, and golf swing performance using a driver and 7-iron. RESULTS: After the 8-week supplementation period, ANCOVA, using baseline values as covariates, revealed significant differences for driver distance (p = .004) and driver ball speed (p < .001). MG significantly increased driver distance by 5.17 ± 12.8 m (p = .046), driver ball speed by 1.36 ± 2.87 m/s (p = .021). Additionally, significantly improvements were observed in hand grip strength (+2.12 ± 3.47 kg, p = .004), two-minute push-ups (+4.89 ± 8.14 reps, p = .004), and balance score (-0.37 ± 0.69 min, p = .009). No significant differences were observed in body composition parameters (p > .05). CONCLUSION: The intake of a mixed protein containing both animal and plant proteins had positive effects on golf performance and muscle function. Therefore, mixed proteins may represent a safe and effective approach to enhancing skeletal muscle health in golf players.

Efficacy and safety of fospropofol disodium sedation for same-day bidirectional endoscopy in elderly patients: protocol for a prospective, single-center, randomized, double-blind, non-inferiority trial.

Introduction: Fospropofol disodium is a novel prodrug that has improved pharmacokinetic and pharmacodynamic properties when compared with propofol. This trial aims to compare the efficacy and safety of fospropofol versus propofol sedation for same-day bidirectional endoscopy in elderly patients. Methods and analysis: This is a prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial. A total of 256 patients aged 65 years or older, who are scheduled for same-day bidirectional endoscopy under sedation, will be randomly allocated, in a 1:1 ratio, to either fospropofol group or propofol group (n = 128 in each group). All patients will receive analgesic pre-treatment with sufentanil 5 µg. Two minutes later, an initial bolus dose of fospropofol 6.5 mg/kg or 1.5 mg/kg propofol and supplemental doses of fospropofol 1.6 mg/kg or 0.5 mg/kg propofol will be titrated as needed to achieve target sedation levels during the procedures. The primary outcome is the success rate of same-day bidirectional endoscopy. Secondary outcomes include the time to successful induction of sedation, duration, time to being fully alert, time to patient discharge, endoscopist satisfaction, patient satisfaction, and the top-up frequency and dosage of sedative medications. The safety endpoints consist of adverse events concerning cough reflex, gag reflexes, body movement, muscular tremor, and pain on injection. Sedation-related AEs, including episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), and bradycardia, will also be recorded. Data will be analyzed on an intention-to-treat basis. Discussion: We hypothesize that the efficacy and safety of fospropofol sedation for elderly patients undergoing same-visit bidirectional endoscopy will not be inferior to that of propofol. Our findings will potentially provide a new sedation regimen for same-visit bidirectional endoscopy in elderly patients. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02875639.

Excluding confusable diseases in patients with presumptive diagnosis of interstitial cystitis: A large patient cohort study.

OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. CONCLUSION: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.

Correction: Bo et al. Atg5 Regulates Selective Autophagy of the Parental Macronucleus during Tetrahymena Sexual Reproduction. Cells 2021, 10, 3071.

In the original publication [...].