Multi-omics Analysis Reveals Key Gut Microbiota and Metabolites Closely Associated with Huntington's Disease.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

Incorporating Medicare Advantage Admissions Into the CMS Hospital-Wide Readmission Measure.

Importance: Medicare Advantage (MA) enrollment is rapidly expanding, yet Centers for Medicare & Medicaid Services (CMS) claims-based hospital outcome measures, including readmission rates, have historically included only fee-for-service (FFS) beneficiaries. Objective: To assess the outcomes of incorporating MA data into the CMS claims-based FFS Hospital-Wide All-Cause Unplanned Readmission (HWR) measure. Design, Setting, and Participants: This cohort study assessed differences in 30-day unadjusted readmission rates and demographic and risk adjustment variables for MA vs FFS admissions. Inpatient FFS and MA administrative claims data were extracted from the Integrated Data Repository for all admissions for Medicare beneficiaries from July 1, 2018, to June 30, 2019. Measure reliability and risk-standardized readmission rates were calculated for the FFS and MA cohort vs the FFS-only cohort, overall and within specialty subgroups (cardiorespiratory, cardiovascular, medicine, surgery, neurology), then changes in hospital performance quintiles were assessed after adding MA admissions. Main Outcome and Measure: Risk-standardized readmission rates. Results: The cohort included 11 029 470 admissions (4 077 633 [37.0%] MA; 6 044 060 [54.8%] female; mean [SD] age, 77.7 [8.2] years). Unadjusted readmission rates were slightly higher for MA vs FFS admissions (15.7% vs 15.4%), yet comorbidities were generally lower among MA beneficiaries. Test-retest reliability for the FFS and MA cohort was higher than for the FFS-only cohort (0.78 vs 0.73) and signal-to-noise reliability increased in each specialty subgroup. Mean hospital risk-standardized readmission rates were similar for the FFS and MA cohort and FFS-only cohorts (15.5% vs 15.3%); this trend was consistent across the 5 specialty subgroups. After adding MA admissions to the FFS-only HWR measure, 1489 hospitals (33.1%) had their performance quintile ranking changed. As their proportion of MA admissions increased, more hospitals experienced a change in their performance quintile ranking (147 hospitals [16.3%] in the lowest quintile of percentage MA admissions; 408 [45.3%] in the highest). The combined cohort added 63 hospitals eligible for public reporting and more than 4 million admissions to the measure. Conclusions and Relevance: In this cohort study, adding MA admissions to the HWR measure was associated with improved measure reliability and precision and enabled the inclusion of more hospitals and beneficiaries. After MA admissions were included, 1 in 3 hospitals had their performance quintile changed, with the greatest shifts among hospitals with a high percentage of MA admissions.

The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.

INTRODUCTION: Individuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID. METHODS: The PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders. CONCLUSION: The PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.

Hypertension Trends and Disparities Over 12 Years in a Large Health System: Leveraging the Electronic Health Records.

BACKGROUND: The digital transformation of medical data enables health systems to leverage real-world data from electronic health records to gain actionable insights for improving hypertension care. METHODS AND RESULTS: We performed a serial cross-sectional analysis of outpatients of a large regional health system from 2010 to 2021. Hypertension was defined by systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or recorded treatment with antihypertension medications. We evaluated 4 methods of using blood pressure measurements in the electronic health record to define hypertension. The primary outcomes were age-adjusted prevalence rates and age-adjusted control rates. Hypertension prevalence varied depending on the definition used, ranging from 36.5% to 50.9% initially and increasing over time by ≈5%, regardless of the definition used. Control rates ranged from 61.2% to 71.3% initially, increased during 2018 to 2019, and decreased during 2020 to 2021. The proportion of patients with a hypertension diagnosis ranged from 45.5% to 60.2% initially and improved during the study period. Non-Hispanic Black patients represented 25% of our regional population and consistently had higher prevalence rates, higher mean systolic and diastolic blood pressure, and lower control rates compared with other racial and ethnic groups. CONCLUSIONS: In a large regional health system, we leveraged the electronic health record to provide real-world insights. The findings largely reflected national trends but showed distinctive regional demographics and findings, with prevalence increasing, one-quarter of the patients not controlled, and marked disparities. This approach could be emulated by regional health systems seeking to improve hypertension care.

C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability.

Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFCGlu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFCGlu neurons in LPS-treated WT mice, C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFCGlu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFCGlu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.

Measuring Bacterial Colonization on Arabidopsis thaliana Roots in Hydroponic Condition.

Measuring bacterial colonization on Arabidopsis thaliana root is one of the most frequent experiments in plant-microbe interaction studies. A standardized method for measuring bacterial colonization in the rhizosphere is necessary to improve reproducibility. We first cultured sterile A.thaliana in hydroponic conditions and then inoculated the bacterial cells in the rhizosphere at a final concentration of OD600 of 0.01. At 2 days post-inoculation, the root tissue was harvested and washed three times in sterile water to remove the uncolonized bacterial cells. The roots were then weighed, and the bacterial cells colonized on the root were collected by vortex. The cell suspension was diluted in a gradient with a phosphate-buffered saline (PBS) buffer, followed by plating onto a Luria-Bertani (LB) agar medium. The plates were incubated at 37 °C for 10 h, and then, the single colonies on LB plates were counted and normalized to indicate the bacterial cells colonized on roots. This method is used to detect bacterial colonization in the rhizosphere in mono-interaction conditions, with good reproducibility.

Pre-COVID-19 hospital quality and hospital response to COVID-19: examining associations between risk-adjusted mortality for patients hospitalised with COVID-19 and pre-COVID-19 hospital quality.

OBJECTIVES: The extent to which care quality influenced outcomes for patients hospitalised with COVID-19 is unknown. Our objective was to determine if prepandemic hospital quality is associated with mortality among Medicare patients hospitalised with COVID-19. DESIGN: This is a retrospective observational study. We calculated hospital-level risk-standardised in-hospital and 30-day mortality rates (risk-standardised mortality rates, RSMRs) for patients hospitalised with COVID-19, and correlation coefficients between RSMRs and pre-COVID-19 hospital quality, overall and stratified by hospital characteristics. SETTING: Short-term acute care hospitals and critical access hospitals in the USA. PARTICIPANTS: Hospitalised Medicare beneficiaries (Fee-For-Service and Medicare Advantage) age 65 and older hospitalised with COVID-19, discharged between 1 April 2020 and 30 September 2021. INTERVENTION/EXPOSURE: Pre-COVID-19 hospital quality. OUTCOMES: Risk-standardised COVID-19 in-hospital and 30-day mortality rates (RSMRs). RESULTS: In-hospital (n=4256) RSMRs for Medicare patients hospitalised with COVID-19 (April 2020-September 2021) ranged from 4.5% to 59.9% (median 18.2%; IQR 14.7%-23.7%); 30-day RSMRs ranged from 12.9% to 56.2% (IQR 24.6%-30.6%). COVID-19 RSMRs were negatively correlated with star rating summary scores (in-hospital correlation coefficient -0.41, p<0.0001; 30 days -0.38, p<0.0001). Correlations with in-hospital RSMRs were strongest for patient experience (-0.39, p<0.0001) and timely and effective care (-0.30, p<0.0001) group scores; 30-day RSMRs were strongest for patient experience (-0.34, p<0.0001) and mortality (-0.33, p<0.0001) groups. Patients admitted to 1-star hospitals had higher odds of mortality (in-hospital OR 1.87, 95% CI 1.83 to 1.91; 30-day OR 1.46, 95% CI 1.43 to 1.48) compared with 5-star hospitals. If all hospitals performed like an average 5-star hospital, we estimate 38 000 fewer COVID-19-related deaths would have occurred between April 2020 and September 2021. CONCLUSIONS: Hospitals with better prepandemic quality may have care structures and processes that allowed for better care delivery and outcomes during the COVID-19 pandemic. Understanding the relationship between pre-COVID-19 hospital quality and COVID-19 outcomes will allow policy-makers and hospitals better prepare for future public health emergencies.

Nonpathogenic Pseudomonas syringae derivatives and its metabolites trigger the plant "cry for help" response to assemble disease suppressing and growth promoting rhizomicrobiome.

Plants are capable of assembling beneficial rhizomicrobiomes through a "cry for help" mechanism upon pathogen infestation; however, it remains unknown whether we can use nonpathogenic strains to induce plants to assemble a rhizomicrobiome against pathogen invasion. Here, we used a series of derivatives of Pseudomonas syringae pv. tomato DC3000 to elicit different levels of the immune response to Arabidopsis and revealed that two nonpathogenic DC3000 derivatives induced the beneficial soil-borne legacy, demonstrating a similar "cry for help" triggering effect as the wild-type DC3000. In addition, an increase in the abundance of Devosia in the rhizosphere induced by the decreased root exudation of myristic acid was confirmed to be responsible for growth promotion and disease suppression of the soil-borne legacy. Furthermore, the "cry for help" response could be induced by heat-killed DC3000 and flg22 and blocked by an effector triggered immunity (ETI) -eliciting derivative of DC3000. In conclusion, we demonstrate the potential of nonpathogenic bacteria and bacterial elicitors to promote the generation of disease-suppressive soils.

Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism.

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid ß-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and ß-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy.

Distinct Circuits From the Central Lateral Amygdala to the Ventral Part of the Bed Nucleus of Stria Terminalis Regulate Different Fear Memory.

BACKGROUND: The ability to differentiate stimuli that predict fear is critical for survival; however, the underlying molecular and circuit mechanisms remain poorly understood. METHODS: We combined transgenic mice, in vivo transsynaptic circuit-dissecting anatomical approaches, optogenetics, pharmacological methods, and electrophysiological recording to investigate the involvement of specific extended amygdala circuits in different fear memory. RESULTS: We identified the projections from central lateral amygdala (CeL) protein kinase C δ (PKCδ)-positive neurons and somatostatin (SST)-positive neurons to GABAergic (gamma-aminobutyric acidergic) and glutamatergic neurons in the ventral part of the bed nucleus of stria terminalis (vBNST). Prolonged optogenetic activation or inhibition of the PKCδCeL-vBNST pathway specifically reduced context fear memory, whereas the SSTCeL-vBNST pathway mainly reduced tone fear memory. Intriguingly, optogenetic manipulation of vBNST neurons that received the projection from PKCδCeL neurons exerted bidirectional regulation of context fear, whereas manipulation of vBNST neurons that received the projection from SSTCeL neurons could bidirectionally regulate both context and tone fear memory. We subsequently demonstrated the presence of δ and κ opioid receptor protein expression within the CeL-vBNST circuits, potentially accounting for the discrepancy between prolonged activation of GABAergic circuits and inhibition of downstream vBNST neurons. Finally, administration of an opioid receptor antagonist cocktail on the PKCδCeL-vBNST or SSTCeL-vBNST pathway successfully restored context or tone fear memory reduction induced by prolonged activation of the circuits. CONCLUSIONS: Together, these findings establish a functional role for distinct CeL-vBNST circuits in the differential regulation and appropriate maintenance of fear.

Root colonization by beneficial rhizobacteria.

Rhizosphere microbes play critical roles for plant's growth and health. Among them, the beneficial rhizobacteria have the potential to be developed as the biofertilizer or bioinoculants for sustaining the agricultural development. The efficient rhizosphere colonization of these rhizobacteria is a prerequisite for exerting their plant beneficial functions, but the colonizing process and underlying mechanisms have not been thoroughly reviewed, especially for the nonsymbiotic beneficial rhizobacteria. This review systematically analyzed the root colonizing process of the nonsymbiotic rhizobacteria and compared it with that of the symbiotic and pathogenic bacteria. This review also highlighted the approaches to improve the root colonization efficiency and proposed to study the rhizobacterial colonization from a holistic perspective of the rhizosphere microbiome under more natural conditions.

[Correlation between Peripheral Blood PLR with Treg, Th17 in Newly Diagnosed Multiple Myeloma and Its Influence on Prognosis].

OBJECTIVE: To investigate the correlation of peripheral blood platelet/lymphocyte ratio (PLR) with Treg and Th17 and its influence on prognosis in newly diagnosed multiple myeloma (MM). METHODS: One hundred thirty-five newly diagnosed multiple myeloma patients admitted to the Department of Hematology of Zhengzhou People's Hospital from June 2015 to October 2022 were selected as MM group. Clinical data included sex, age, immune typing, ISS stage, blood calcium (Ca), albumin (ALB), hemoglobin (Hb), PLR, LDH, ß2 microglobulin (ß2-MG), Treg and Th17 levels. Sixty healthy volunteers who underwent physical examination in our hospital during the same period were selected as the control group. PLR, Treg and Th17 levels in MM group and control group were compared. Pearson was used to analyze the correlation between PLR and Treg, Th17. The relationship between MM patients with different PLR and clinical features and prognosis was analyzed. RESULTS: The PLR and Th17 of MM patients were significantly higher than that of control group, and Treg was significantly lower than that of control group (P<0.05). In MM patients, PLR was negatively correlated with Treg (r=-0.616), and PLR was positively correlated with Th17 (r=0.555). Using mean PLR=132.72 as the boundary, 135 MM patients were divided into high PLR group (n=54) and low PLR group (n=81). In MM patients with high PLR, ISS stage, ALB and Treg were significantly higher than those in low PLR group, while Th17 was significantly lower than those in low PLR group (P<0.05). By univariate and COX regression analysis, PLR was an independent prognostic risk factor for newly diagnosed MM patients (P<0.05). MM patients with high PLR had better PFS and OS, and the difference was statistically significant compared with MM patients with low PLR (P<0.05). 65 patients admitted from June 2015 to December 2018 were used as the training set, and 70 patients admitted from January 2019 to October 2022 were used as the validation set. The OS of MM patients with different PLR were compared respectively. The results showed that the conclusions of the training set and the validation set were consistent. PLR with high expression had higher OS (P<0.01). CONCLUSION: PLR is correlated with Treg and Th17 in newly diagnosed MM patients, and high PLR has better prognosis. PLR can be used to evaluate the prognosis of MM patients.

Effects of exogenous melatonin on growth and physiological characteristics of Agropyron mongolicum seedlings under drought stress.

To clarify the alleviation effect of exogenous melatonin (MT) on Agropyron mongolicum under drought stress, we examined the response of A. mongolicum 'Yanchi' seedlings to simulated drought stress with polyethylene glycol 6000 (PEG-6000), by investigating the effects of exogenous addition of different concentrations (0, 1, 10, 50, 100, 150 and 200 mg·L-1) of MT on seedlings growth and physiological characteristics under drought stress. The results showed that drought stress significantly inhibited the growth of A. mongolicum seedlings, and that exogenous addition of different concentrations of MT could alleviate the growth inhibition caused by drought stress, with the strongest mitigation effect observed at MT concentration of 100 mg·L-1. Compared with the drought stress treatment alone, exogenous addition of 100 mg·L-1 MT under drought stress increased plant height, aboveground dry weight, and leaf relative water content by 58.2%, 121.2% and 48.1%. The contents of chlorophyll a, chlorophyll b, carotenoids increased by 48.7%, 80.8% and 38.3%, superoxide dismutase, peroxidase and root activity increased by 12.6%, 33.9% and 39.1%, and the contents of ascorbic acid and glutathione increased by 19.5% and 18.3%, respectively. The contents of proline, soluble sugar and soluble protein were increased by 16.2%, 32.6% and 14.3%, while that of malondialdehyde, hydrogen peroxide and superoxide anion radical were decreased by 45.8%, 65.8% and 30.8%, respectively. In summary, exogenous addition of 100 mg·L-1 MT could improve drought tolerance of A. mongolicum seedlings by promoting growth, enhancing antioxidant capacity, increasing the content of osmoregulation substances, inhibiting the excessive production of reactive oxygen, and reducing membrane peroxide level.

Malignant proliferative ependymoma of the neck with lymph node metastasis: A case report.

BACKGROUND: Malignant proliferating trichilemmal tumor (MPTT) is an infrequent malignant neoplasm originating from cutaneous appendages, with only a handful of documented cases. This report delineates a unique instance of MPTT situated in the neck, accompanied by lymph node metastasis. A comprehensive exposition of its clinical trajectory and imaging manifestation is presented, aiming to enhance comprehension and management of this atypical ailment. CASE SUMMARY: Patient concerns: A 79-year-old male presented with a longstanding right neck mass persisting for over six decades, exhibiting recent enlargement over the past year. Diagnoses: Enhanced magnetic resonance imaging of the neck unveiled an elliptical mass on the right neck side, characterized by an ill-defined border and a heterogeneous signal pattern. The mass exhibited subdued signal intensity on T1-weighted imaging (T1WI) and a heterogeneous high signal on T2-weighted imaging (T2WI), interspersed with a lengthy T1 and T2 cystic signal motif. Close anatomical association with the submandibular gland joint was noted, and intravenous gadolinium diethylene triamine pentaacetic acid administration facilitated conspicuous enhancement. Substantial enhancement of the solid segment prompted an initial preoperative diagnosis of malignant nerve sheath tumor. However, post-surgery histopathological and immunohistochemical analysis conclusively confirmed the diagnosis as malignant hyperplastic external hair root sheath tumor. Intervention: Complete excision of the tumor was successfully executed. Outcomes: The patient experienced a favorable postoperative recovery. CONCLUSION: Malignant proliferative trichilemmal tumor external hair root sheath tumor is a cystic-solid lesion, appearing as low signal on T1WI images or high signal on T2WI with enhancement of the solid component. Suspicions of malignancy are heightened when the tumor border is indistinct, tissue planes are breached, or when linear or patchy high signals are observed in the subcutaneous tissue on T1 liver acquisition with volume acceleration enhanced images along with intermediate signal on T2WI and restricted diffusion on diffusion-weighted imaging images. Strong consideration for malignancy should arise if there are signs of compromised adjacent tissue relationships or direct invasion evident on imaging. We have incorporated the above-mentioned content into the entire manuscript.

Value of faecal exfoliated cells in colorectal tumour screening using SDC2 methylation test.

BACKGROUND: This study aimed to evaluate the diagnostic value of a non-invasive methylation gene test in clinical colorectal tumour screening. METHOD: The quantitative methylation-specific PCR technique was used to detect faecal methylated syndecan-2 (mSDC2) in patients who received the screening of colorectal cancer (CRC).To evaluate the positive predictive value (PPV) of mSDC2 in patients with colorectal cancer, advanced adenoma (AA), and colorectal tumor (CRN) in risk factor stratification. RESULTS: The PPV of CRC, CRC + AA and CRN in male patients were 28.03%, 43.55% and 56.24%, respectively, which were higher than female patients. The positive detection rate of mSDC2 and the PPV of CRC gradually increased with age; The PPV in patients aged over 80 years was up to 78.05%, which was more significant than in younger patients with CRC. The PPV of CRC, AA and CRN were 37.10%, 11.80% and 63.37%, respectively. mSDC2 has a high detection rate of 85-100% in AA with intramucosal carcinoma alone or in combination with severe atypical hyperplasia or villous adenoma. CONCLUSION: The mSDC2 test has a higher PPV in patients with colorectal cancer and colorectal adenoma (AD), especially in high-risk groups over 50 years of age, and may help in the early diagnosis of colorectal tumours in the future.

Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022.

Background: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. Results: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). Conclusions: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. Trial registration: NCT04610515.

Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms.

Background: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection. Methods: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms. Results: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months. Conclusions: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.

An Antenna-Abundant Glutathione S-Transferase BdGSTd8 Participates in Detoxification of Two Organophosphorus Insecticides in Bactrocera dorsalis (Hendel).

The oriental fruit fly, Bactrocera dorsalis, is a damaging insect pest for many vegetable and fruit crops that has evolved severe chemical insecticide resistance, including organophosphorus, neonicotinoid, pyrethroid, and macrolides. Hence, it is important to elucidate its detoxification mechanism to improve its management and mitigate resource destruction. Glutathione S-transferase (GST) is a critical secondary phase enzyme that plays multiple detoxification functions against xenobiotics. In this study, we identified several BdGSTs by characterizing their potential relationships with five insecticides using inducible and tissue-specific expression pattern analyses. We found that an antenna-abundant BdGSTd8 responded to four different classes of insecticides. Subsequently, our immunohistochemical and immunogold staining analysis further confirmed that BdGSTd8 was primarily located in the antenna. Our investigations also confirmed that BdGSTd8 possesses the capability to enhance cell viability by directly interacting with malathion and chlorpyrifos, which clarified the function of antenna-abundant GST in B. dorsalis. Altogether, these findings enrich our understanding of GST molecular characteristics in B. dorsalis and provide new insights into the detoxification of superfluous xenobiotics in the insect antenna.

Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.