Clinical characteristics of enteric fever and performance of TUBEX TF IgM test in Indonesian hospitals.

BACKGROUND: Accurate diagnosis of enteric fever is challenging, particularly in low- and middle-income countries, due to the overlap of clinical and laboratory features with other pathogens. To better understand the difficulties in enteric fever diagnosis, we evaluated the characteristics of patients clinically diagnosed with enteric fever and the real-world performance of TUBEX TF, one of the most used tests in Indonesia. METHODOLOGY/PRINCIPAL FINDINGS: Patients were recruited through the AFIRE (Etiology of Acute Febrile Illness Requiring Hospitalization) study at eight Indonesian hospitals. Blood culture was performed for all patients, and TUBEX TF was performed for suspected enteric cases. Salmonella PCR and ELISA tests were performed at a reference lab. Sensitivity and specificity of TUBEX TF and IgM and IgG anti-S. Typhi ELISA were determined. Of 301 patients clinically diagnosed with enteric fever, 50 (16.6%) were confirmed by blood culture and/or PCR. Confirmed cases were mostly school-aged children presenting with fever, anorexia, dizziness and/or abdominal pain with normal leukocyte count or leukopenia. TUBEX TF demonstrated a sensitivity of 97.6% to 70.7% and specificity of 38.3% to 67.2% at cutoffs of 4 and 6, respectively. Acute IgG demonstrated the best sensitivity and specificity, at 90.7% and 82.7%, respectively, and the best ROC characteristics. CONCLUSIONS/SIGNIFICANCE: A substantial proportion of enteric fever was misdiagnosed at all study hospitals, likely due to the overlap of clinical characteristics and lab parameters with those of other common pathogens. The TUBEX TF rapid serological assay demonstrated suboptimal performance in our setting and tended to over-diagnose enteric fever. The role of IgG from acute specimens for identification of enteric fever cases merits additional consideration.

[Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma: analysis of 653 cases].

OBJECTIVE: To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma. METHODS: We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, n=111), chemotherapy (CT group, n=108) and clinical observation (CO group, n=434). RESULTS: In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group (P < 0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group (P < 0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age (P < 0.05; HR=0.631, 95% CI: 0.401-0.993), solid nodules (P < 0.01; HR=7.620, 95% CI: 3.037-19.121), micropapillary or solid component (P < 0.05; HR= 1.776, 95% CI: 1.010-3.122), lymphovascular invasion (P < 0.05; HR=2.981, 95% CI: 1.198-7.419), and adjuvant therapy (P < 0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% vs 9.0%). CONCLUSION: Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Flp-recombinase mouse line for genetic manipulation of ipRGCs.

Light has myriad impacts on behavior, health, and physiology. These signals originate in the retina and are relayed to the brain by more than 40 types of retinal ganglion cells (RGCs). Despite a growing appreciation for the diversity of RGCs, how these diverse channels of light information are ultimately integrated by the ~50 retinorecipient brain targets to drive these light-evoked effects is a major open question. This gap in understanding primarily stems from a lack of genetic tools that specifically label, manipulate, or ablate specific RGC types. Here, we report the generation and characterization of a new mouse line (Opn4FlpO), in which FlpO is expressed from the Opn4 locus, to manipulate the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells. We find that the Opn4FlpO line, when crossed to multiple reporters, drives expression that is confined to ipRGCs and primarily labels the M1-M3 subtypes. Labeled cells in this mouse line show the expected intrinsic, melanopsin-based light response and morphological features consistent with the M1-M3 subtypes. In alignment with the morphological and physiological findings, we see strong innervation of non-image forming brain targets by ipRGC axons, and weaker innervation of image forming targets in Opn4FlpO mice labeled using AAV-based and FlpO-reporter lines. Consistent with the FlpO insertion disrupting the endogenous Opn4 transcript, we find that Opn4FlpO/FlpO mice show deficits in the pupillary light reflex, demonstrating their utility for behavioral research in future experiments. Overall, the Opn4FlpO mouse line drives Flp-recombinase expression that is confined to ipRGCs and most effectively drives recombination in M1-M3 ipRGCs. This mouse line will be of broad use to those interested in manipulating ipRGCs through a Flp-based recombinase for intersectional studies or in combination with other, non-Opn4 Cre driver lines.

Ghosts of parasites past influence current non-consumptive effects in Drosophila nigrospiracula.

Parasites can indirectly impact hosts through non-consumptive effects (NCEs) via changes in behaviour, morphology, and/or physiology. These responses can be understood in terms of the ecology of fear (ectoparasites) or the ecology of disgust (endoparasites) framework. We tested the hypothesis that NCEs of parasite exposure (e.g., parasite avoidance and defense) trade off with other important behaviours such as feeding and resting. We predicted that when exposed to parasites (without infection), hosts will increase their defensive behaviors at the expense of feeding. We also posited that history of exposure (without infection), or previous infection would impact the expression of these NCEs. The study system involves a cactophilic fruit fly (Drosophila nigrospiracula) and a naturally occurring parasitic mite (Macrocheles subbadius). First, we assessed how prior mite exposure affected fly behaviour in response to current parasite exposure. Mite presence resulted in increased grooming and movement, but exposure history did not affect these behaviours. However, the interaction between previous and current exposure influenced host feeding and resting behaviours. We found that previously exposed flies increased feeding and decreased resting upon a secondary mite exposure. In a second experiment, we tested the role of infection history on current parasite exposure. Compared with naïve flies, previously infected flies were expected to increase defensive behaviours upon secondary exposure. Flies increased defensive and ambulatory behaviour in the presence of mites, and consequently less time was spent resting but feeding was unaffected. None of the behaviours measured were affected by previous infection status. In general, current parasite exposure resulted in NCEs. Moreover, our results showed that previous exposure (without infection) to parasites may have an even stronger effect upon secondary exposure than infection history. Our study highlights the importance of the ecology of fear and the role that exposure and infection history plays in generating NCEs of parasitism.

Analysis of risk factors affecting the prognosis of patients with sepsis and construction of nomogram prediction model.

OBJECTIVE: This study analyzed the clinical data of 200 sepsis patients, exploring the risk factors that affect patient prognosis and providing the basis for clinically targeted intervention to improve patient prognosis. PATIENTS AND METHODS: 200 septic patients were admitted to Yulin Second Hospital, and they were divided into a survival group of 151 patients and a death group of 49 patients, according to their clinical outcomes on admission. The relevant clinical parameters within 24 h of admission were collected, and the independent risk factors affecting the prognosis of septic patients were analyzed by multivariate Logistic regression. R language 4.21 software was used to construct a nomogram prediction model. The receiver operating characteristic curve was used to evaluate the discrimination of the nomogram model, and decline curve analysis was drawn to evaluate the effectiveness of the model. RESULTS: In the nomogram prediction model, age, the Acute Physiology and Chronic Health Scoring System Domain (APACHE II) score, the Sequential Organ Failure Assessment (SOFA) score, C-reactive protein (CRP), total bilirubin, albumin (Alb), urea nitrogen, creatinine, and lactate (Lac) were independent risk factors for death in septic patients. The area under the receiver operating characteristic (ROC) curve for predicting the prognosis of septic patients was 0.597-1.000, and the calibration curve tends to be the ideal curve. The model had good discrimination and calibration and had high accuracy in evaluating septic patients. The modeling curves in the decline curve analysis (DCA) were all above the two extreme curves, which had good clinical value. CONCLUSIONS: Nine clinical variables have been found to be independent risk factors for death in septic patients. The prediction model established based on this has good accuracy, discrimination, and consistency in predicting the prognosis of sepsis patients.

Managing ischemic and necrotic incarcerated femoral hernia contents and their risk factors.

PURPOSE: Incarcerated femoral hernia patients had high risk of hernia contents necrosis. We provide our experience of management ischemia and necrosis of hernia contents in emergency incarcerated femoral hernia patients, and to investigate its risk factors. METHODS: This is a case-control study. Eighty-nine incarcerated femoral patients who underwent emergency surgery from January 2015 to December 2021 were included, and divided into normal group (60 cases) and ischemia/necrosis group (29 cases) according to the intraoperative condition of hernia contents. The surgical methods, intraoperative and postoperative conditions were compared between the two groups. Multivariate logistic regression was used to analyze the risk factors of ischemia and necrosis of hernia contents. RESULTS: Open preperitoneal tension-free repair was the most commonly used surgical methods (68.5%) for incarcerated femoral patients. The utilization rate of laparoscopic repair in the ischemia/necrosis group was lower than that in the normal group (13.8% vs. 20.0%, P = 0.475). The proportion of mesh placement in the normal group was significantly higher than that in the ischemia/necrosis group (98.3% vs 65.5%, P < 0.001). The hernia contents resection rate (55.2% vs 1.7%), operation time (90 vs 40 min), intraoperative bleeding (5 vs 2 ml), ICU admission rate (31.0% vs 1.7%), and hospital stay (7 vs 4 d) were significantly higher in the ischemia/necrosis group than those in normal group. Results of multivariate logistic regression showed that incarceration time more than 9 h (aOR = 19.3, 95%CI: 1.9-192.9) was an independent risk factor for ischemia and necrosis of hernia contents in emergency incarcerated femoral hernia patients. CONCLUSION: Open tension-free repair was the most commonly used surgical methods for emergency incarcerated femoral hernia patients. Ischemia and necrosis of hernia contents will increase bowel resection rate and prolong operation and hospital stay. Long incarceration time is an independent risk factor for ischemia and necrosis of hernia contents.

[Analysis of clinical characteristics of 129 acute and chronic occupational brucellosis in HulunBuir City].

Objective: To analyze the epidemiological characteristics and clinical data of acute and chronic occupational brucellosis patients in order to provide a scientific basis for the prevention and treatment of occupational brucellosis. Methods: In October 2022, a study was conducted on 129 patients diagnosed with occupational brucellosis by HulunBuir Center for Disease Control and Prevention from January 2016 to December 2021. The epidemiological characteristics, clinical features, and laboratory test results of patients in the acute and chronic phases were compared and analyzed using chi-square test and student's t test. Results: The acute phase patients included 38 men and 4 women with an average age of (36.6±8.4) years old; the chronic phase patients included 73 men and 14 women with an average age of (38.4±7.9) years old. There were no significant differences in gender and age between the two groups (P>0.05). The patients had a clear history of occupational exposure, and the proportion of veterinarians in acute stage (21 cases, 50.0%) was significantly higher than that in chronic stage (25 cases, 28.7%), the difference was statistically significant (P<0.05). The symptoms of fever and loss of appetite in acute phase of occupational brucellosis were significantly higher than those in chronic phase, and the symptoms of fatigue and joint muscle pain were significantly lower than those in chronic phase, with statistical significances (P<0.05). The increase of alanine aminotransferase, aspartate aminotransferase, C-reactive protein, erythrocyte sedimentation rate and positive rate of blood culture in acute stage were significantly higher than those in chronic stage, with statistical significances (P<0.05) . Conclusion: Occupational brucellosis patients are predominantly middle-aged men, the acute phase is characterized by fever, loss of appetite, and increased inflammatory indicators and liver enzymes, while the chronic phase is characterized by symptoms such as fatigue and joint muscle pain. Brucellosis related occupational exposure population should seek medical treatment as soon as possible when the above symptoms occur, timely detection and treatment of occupational diseases.

Roles of Baseline Intrinsic Capacity and its Subdomains on the Overall Efficacy of Multidomain Intervention in Promoting Healthy Aging among Community-Dwelling Older Adults: Analysis from a Nationwide Cluster-Randomized Controlled Trial.

BACKGROUND: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty. OBJECTIVE: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults. DESIGN: a cluster-randomized controlled trial. SETTING AND PARTICIPANTS: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan. INTERVENTION: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management. MEASUREMENTS: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months. RESULTS: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001). CONCLUSION AND IMPLICATIONS: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging.

Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions.

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.

Testing the missing at random assumption in generalized linear models in the presence of instrumental variables.

Practical problems with missing data are common, and many methods have been developed concerning the validity and/or efficiency of statistical procedures. On a central focus, there have been longstanding interests on the mechanism governing data missingness, and correctly deciding the appropriate mechanism is crucially relevant for conducting proper practical investigations. In this paper, we present a new hypothesis testing approach for deciding between the conventional notions of missing at random and missing not at random in generalized linear models in the presence of instrumental variables. The foundational idea is to develop appropriate discrepancy measures between estimators whose properties significantly differ only when missing at random does not hold. We show that our testing approach achieves an objective data-oriented choice between missing at random or not. We demonstrate the feasibility, validity, and efficacy of the new test by theoretical analysis, simulation studies, and a real data analysis.

[The ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion].

Objective: The present retrospective study aimed to analyses the ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion. Methods: A total of 37 advanced aged patients diagnosed with atrial fibrillation(>65 years)who underwent left atrial appendage occlusion (LAAO) in Xuanwu Hospital of Capital Medical University from March 2021 to March 2022 were enrolled in this study. All patients received supplemental oxygen by a new nasopharyngeal airway to ensure intraoperative ventilation. The primary outcome was the occurrence of hypoxemia. The secondary outcomes included the incidence of hypotension after anesthesia, the incidence of body movement during surgery, significant fluctuations of the vital signs such as mean arterial pressure (MAP), heart rate (HR), saturation of pulse oxygen (SpO2) and respiratory rate (RR) at different time points (T1: pre-operation; T2: at the time of placing nasopharyngeal airway; T3: at the time of placing transesophageal echocardiography(TEE); T4: at the time of TEE intraoperative exploration; T5: end of the surgery; T6: at the time of patient woke up), and the incidence of postoperative adverse events. Results: There were 24 males and 13 females with a mean age of (73.8±7.7) years. The incidence of hypoxemia was 16.2% (6/37), which could return to normal after simple treatment. The incidence of hypotension was 27.0% (10/37), occurred after anesthesia induction mainly.32.4% (12/37) of the patients experienced movements, but no adverse events led to surgical termination. MAP at different time points was significantly different (P=0.001), but other vital signs of HR, SpO2 and RR were not significantly different(all P>0.05), without serious hemodynamic fluctuations. The incidence of postoperative adverse cardiovascular events was 10.8% (4/37), and delirium was 2.7% (1/37). All patients successfully completed the surgery and were safely discharged from the hospital. Conclusion: The new nasopharyngeal airway can meet the requirements of airway management during left atrial appendage occlusion under intravenous anesthesia without serious adverse events.

Predictive value of hematological parameters in cirrhotic patients with open umbilical hernia repair.

PURPOSE: Patients with liver cirrhosis sometimes suffer from high recurrence rates and postoperative complications. We previously reported that platelet-related hematological parameters are associated with the outcomes after incisional herniorrhaphy, and aim to evaluate the predictive value of these criteria in cirrhotic patients undergoing open umbilical herniorrhaphy. METHODS: This is a retrospective study. The data of 95 cirrhotic patients undergoing open umbilical herniorrhaphy were analyzed. Patients were grouped based on the recurrence and defined hematological values. Platelet-multiple-lymphocyte index (PLM), neutrophil-leukocyte ratio, lymphocyte-monocyte ratio, platelet-neutrophil ratio, systemic immune-inflammation index, and aspartate aminotransferase-leukocyte ratio values were calculated based on preoperative blood analyses. The outcomes were obtained from hospital records and follow-up calls to patients. RESULTS: Using cutoff values acquired by the Youden Index, we found a PLM value < 27.9, and the history of inguinal herniorrhaphy were revealed to be statistically significant in the recurrence based on univariant and multivariant analyses (p < 0.05). We further divided patients into two groups based on the cutoff value of PLM and found that a PLM value < 27.9 was significantly associated with the recurrence of incisional hernias (p = 0.018) and the occurrence of postoperative foreign sensation (p = 0.044), and tended to result in other postoperative complications such as cardiopathy, respiratory infection, hypoproteinemia, and hepatic diseases (p = 0.089). CONCLUSION: The preoperative hematological values, especially PLM, may indicate the outcomes in cirrhotic patients after open umbilical herniorrhaphy. Accurate identification of risks may alert the intraoperative and postoperative care for patients.

HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity.

Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T cell response may require a vaccination strategy that drives further TCR clonal selection.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

Comparative Analysis of Intrinsic Capacity Impairments, Determinants, and Clinical Consequences in Older Community-Dwellers in Japan and Taiwan: Longitudinal Studies Showing Shared Traits and Distinct Presentations.

OBJECTIVES: Despite the recognized impact of intrinsic capacity (IC) impairment on healthy aging, international comparisons in different sociocultural contexts are scarce. This study aimed to compare IC impairment among community-dwelling older adults in Japan and Taiwan to explore the context of healthy aging in different countries. DESIGN: Comparative observational study. SETTING: National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan and Longitudinal Aging Study of Taipei (LAST) in Taiwan. PARTICIPANTS: 794 individuals (age range, 60.0-86.5 years) from NILS-LSA and 1,358 (60.0-96.7 years) from LAST. MEASUREMENTS: IC impairment was evaluated across the domains of locomotion, cognition, vitality, sensory capacity, and psychological well-being. Participants were categorized as having impaired IC or healthy. We investigated associations between IC impairment, falls, and all-cause mortality. RESULTS: IC impairment was present in 54.9% and 37.3% of participants in the NILS-LSA and LAST cohorts, respectively. Male NILS-LSA participants with impaired IC (odds ratio [OR]:1.50, 95% confidence interval [CI]:1.03-2.20), with hearing loss (OR:1.98, 95% CI:1.00-3.90) were more likely to fall. In LAST, impaired locomotion (OR:2.14, 95% CI:1.46-3.14) increased the risk of falls. Men with impaired IC (hazard ratio [HR]; 2.14, 95% CI:1.10-4.15) and visual impairment (HR:2.21, 95% CI:1.15-4.25) and women with impaired psychological well-being (HR:4.94, 95% CI:1.28-18.97) in the NILS-LSA cohort had greater risk for all-cause mortality; however, this was not shown for LAST participants. CONCLUSION: The prevalence and distribution of IC impairment and associated biomarkers differed significantly between participants in Japan and Taiwan. However, the associations with adverse outcomes remained similar, emphasizing the need for tailored interventions for healthy aging.

Gelanxinning capsule improves coronary microvascular dysfunction by inhibiting inflammation and restoring endothelial function.

OBJECTIVE: Gelanxinning capsule (GXSC) is a Chinese medicine to cure coronary artery disease (CAD) and a compound of Pueraria lobata, hawthorn extract, and gypenosides. However, whether GXSC could improve coronary microvascular dysfunction (CMD) is unknown. We aimed to demonstrate the therapeutic effect of GXSC on CMD and its underlying mechanisms in CAD patients. PATIENTS AND METHODS: This was a single-center, randomized control trial. A total of 78 patients diagnosed by selective coronary angiography (CAG) participated in this study. Patients' demographics, medical history, medications, and results of laboratory testing were collected. The index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were obtained by CAG and single-photon emission computed tomography (SPECT) separately. Fasting blood samples were obtained on the morning following the admission day. Concentrations of several molecules of inflammation, endothelial function, and coronary microvascular function were measured by ELISA. Patients were followed-up two months after discharge and fasting blood samples were also acquired. RESULTS: All patients were randomly divided into 2 groups: GXSC, 38 (48.7%), and control, 40 (51.3%). The intergroup comparison revealed no significant differences with respect to all baseline variables. As for inflammation biomarkers, proinflammatory NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin (IL)-1 were significantly decreased in GXSC compared with the control group (0.71±0.08 vs. 1.04±0.07, p<0.01 and 7.16±0.59 vs. 10.93±1.04, p<0.01). Anti-inflammatory adropin was increased in the GXSC group (7.75±0.59 vs. 5.71±0.68, p=0.03). As for indexes of endothelial function, the concentrations of syndecan (SDC) 1, SDC4 and heparan sulphates (HS) were significantly downregulated in 2 months GXSC treatment (3.31±0.28 vs. 4.85±0.43, p<0.01, 3.79±0.56 vs. 5.69±0.68, p=0.03 and 21.31±2.79 vs. 35.18±4.11 p<0.01). In addition, the level of SIRTUIN 1 (SIRT1), which is a vascular protective protein, was upregulated in GXSC group (5.63±0.30 vs. 4.22±0.37, p<0.01). As for molecules of coronary microvascular function, endocan, soluble urokinase plasminogen activator receptor (suPAR), and growth differentiation factor (GDF)-15 were significantly decreased consistently in GXSC compared with the control group (0.09±0.01 vs. 0.19±0.03, p<0.01, 4.44±0.40 vs. 5.73±0.40, p=0.03 and 2.08±0.17 vs. 2.69±0.18, p=0.02). CONCLUSIONS: In conclusion, GXSC could improve CMD by inhibiting inflammation and restoring endothelial function. GXSC might be an effective drug in CAD patients without obstructive epicardial coronary arteries but suffering from angina.

Lamellar Fluctuations Melt Ferroelectricity.

We consider a standard Ginzburg-Landau model of a ferroelectric whose electrical polarization is coupled to gradients of elastic strain. At the harmonic level, such flexoelectric interaction is known to hybridize acoustic and optic phonon modes and lead to phases with modulated lattice structures that precede the state with spontaneously broken inversion symmetry. Here, we use the self-consistent phonon approximation to calculate the effects of thermal and quantum polarization fluctuations on the bare hybridized modes to show that such long-range modulated order is unstable at all temperatures. We discuss the implications for the nearly ferroelectric SrTiO_{3} and KTaO_{3}, and we propose that these systems are melted versions of an underlying modulated state that is dominated by nonzero momentum thermal fluctuations except at the very lowest temperatures.

[A study on the mediation effect of insulin use on diabetic retinopathy in a community population].

Objective: To explore the risk factors for diabetic retinopathy (DR) in patients with diabetes and the mediating effect of insulin use on the relationship between glycated hemoglobin (HbA1c) and DR. Methods: Cross-sectional study. Random cluster sampling was conducted using a random number table method. A total of 84 sampling points (including 2 pilot points) were selected from the registered population of patients with type 2 diabetes aged 50 years and above at the Disease Prevention and Control Center in Funing County, Jiangsu Province. Questionnaires and biochemical tests were performed to obtain information on the general characteristics of the participants, medical history, insulin use, and glycated hemoglobin (HbA1c) levels. Ocular examinations, including anterior segment and fundus examinations, were conducted. The participants were divided into two groups, DR (diabetic retinopathy) and non-DR, based on the presence or absence of retinal hemorrhages, hard exudates, cotton wool spots, neovascularization, preretinal or vitreous hemorrhage. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors for DR. The Karlson-Holm-Breen analysis method was used for mediation effect analysis. Results: A total of 2 067 diabetic patients were enrolled, of whom 1 965 completed the survey and 1 802 were included in the statistical analysis, resulting in a response rate of 87.2%. Among them, 660 patients were diagnosed with DR, with a detection rate of 36.63%. The results of multivariate analysis showed that diabetes duration (OR=1.166, 95%CI: 1.138-1.196), family history of diabetes (OR=1.325, 95%CI: 1.001-1.755), insulin therapy (OR=1.995, 95%CI: 1.434-2.777), HbA1c level (OR=1.513, 95%CI: 1.189-1.925), and alcohol consumption (OR=0.712, 95%CI: 0.514-0.985) were independent risk factors for DR. The mediating effect of insulin use accounted for 13.67% of the total effect of HbA1c on DR (P<0.001). Conclusions: The risk factors for DR in patients with diabetes include a history of insulin therapy, longer duration of diabetes, family history of diabetes, alcohol consumption, and high HbA1c levels. Insulin use increases the impact of HbA1c on DR and has a partial mediating effect on DR.