Defect Induced Structural Transition and Lipase Immobilization in Mesoporous Aluminum Metal-Organic Frameworks.

The transition from disorder to order and structural transformation are distinctive metal-organic framework (MOF) features. How to adapt or control both behaviors in MOF has rarely been studied. In this case, we demonstrate that our successful synthesis of [Al(OH)(PDA)]n (AlPDA-53-DEF, AlPDA-53-H, and AlPDA-68) with H2PDA=4,4'-[1,4-phenylenebis(ethyne-2,1-diyl)]-di benzoic acid has shown the intricate world of Aluminum Metal-Organic Frameworks (Al-MOFs). It offers profound insights into defect structures to order and transformations. AlPDA-53-DEF, in particular, revealed a fascinating interplay of various pore sizes within both micro and mesoporous regions, unveiling a unique lattice rearrangement phenomenon upon solvent desorption. Defects and disorders emerged as crucial impacts of transforming AlPDA-53-DEF, with its initially imperfect crystallinity, into the highly crystalline, hierarchically porous AlPDA-53-H.

Machine Learning and Radiomics of Bone Scintigraphy: Their Role in Predicting Recurrence of Localized or Locally Advanced Prostate Cancer.

BACKGROUND: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients' clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. METHODS: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image's region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier's effectiveness, the ROC curve area and confusion matrix were employed. RESULTS: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of <0.001. The other models had accuracy ranges from 0.52 to 0.78 and AUC ranges from 0.67 to 0.84. CONCLUSIONS: The study showed that ML based on clinical features and radiomics features of BS improves the prediction of PCa recurrence after initial treatment. These findings highlight the added value of ML techniques for risk classification in PCa based on clinical features and radiomics features of BS.

Exploring the potential of iron-based metal-organic frameworks as peroxidase nanozymes for glucose detection with various secondary building units.

Finding materials in biosensing that balance enzyme-like reactivity, stability, and affordability is essential for the future. Because of their unique peroxidase properties, including variable pore size, surface area, and Lewis acid active sites, iron-based metal-organic frameworks (MOFs) have evolved as viable possibilities. In this study, we constructed a Fe-MOF and tested its peroxidase-like activity and responsiveness toward H2O2 colorimetric techniques. Using encapsulation, we incorporated glucose oxidase into the ZIF-90 PVP MOF and conducted a sequential reaction with the Fe-MOF to detect glucose. The results showed better peroxidase catalytic activity of the MIL-88B(Fe) (1,4-NDC) MOF and similar secondary building unit (SBU) Fe-MOFs were studied in other peroxidase nanozyme studies. When combined with an enzyme-encapsulating ZIF-90 PVP MOF, they could be sequentially employed for glucose detection purposes. This study highlights the potential of nanozymes as an alternative to natural enzymes, with promising applications in biosensing and beyond.

The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia.

PURPOSE: The maelstrom spermatogenic transposon silencer (MAEL) function in postmeiotic germ cells remains unclear, and its protein localization in human testis and spermatozoa awaits determination. This study aims to clarify the MAEL expression in human spermatogenesis and to explore its role in sperm function. MATERIALS AND METHODS: Twenty-seven asthenozoospermic men, 40 normozoospermic controls, and three obstructive azoospermic men were enrolled. The transcripts of MAEL in the seminiferous epithelium and MAEL downstream targets were identified by bioinformatics analysis. MAEL protein expression in human testis and ejaculated sperms were examined by immunohistochemical and immunogold staining, respectively. The roles of MAEL in mitochondria function were investigated by siRNA knockdown in human H358 cells. The association between MAEL protein levels and clinical sperm features was evaluated. RESULTS: Abundant MAEL was expressed in spermatid and spermatozoa of the human testis. Remarkably, MAEL was located in the mitochondria of ejaculated sperm, and bioinformatics analysis identified GPX4 and UBL4B as MAEL's downstream targets. Knockdown of MAEL sabotaged mitochondria function and reduced adenosine triphosphate (ATP) production in H358 cells. MAEL, GPX4, and UBL4B expression levels were significantly decreased in asthenozoospermic sperms than in controls. The MAEL protein levels were positively correlated with GPX4 and UBL4B in human sperm. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL, GPX4, and UBL4B in ejaculated sperms. CONCLUSIONS: We highlight prominent MAEL expression in the intratesticular spermatid and the mitochondria of ejaculated spermatozoa. MAEL directly binds to GPX4 and UBL4B, and loss of MAEL induces mitochondrial dysfunction. MAEL-mitochondrial function-motility relationship might advance our understanding of the causes of asthenozoospermia.

A bioinspired copper-based coordination polymer for the detection of pheochromocytoma biomarkers.

Oxidase-mimicking (catechol oxidase/laccase) nanozymes provide outstanding specificity in the detection of epinephrine (Epi) for the assessment of pheochromocytoma; however, epinephrine (Epi) and norepinephrine (NE) co-existing in the same systems will reduce the selectivity of the biosensor. In the current study, we synthesized copper-based coordination polymer (Cu-CP) nanozymes capable of accelerating the oxidation of Epi with high specificity. Furthermore, the Cu-CP is able to detect Epi over a wide linear range of 0.5-100 µM with a low detection limit of 0.36 µM while providing excellent stability and recyclability. Furthermore, we employed colorimetric and fluorescence signals for sequential detection of the coexistence of Epi and NE for use in tracking the treatment outcomes of patients with pheochromocytoma. Experiments using artificial urine further confirmed the efficacy of the proposed system.

Clinical Outcomes of Metastatic Breast Cancer in Patients Having Imaging Liver Pseudocirrhosis with or without Evident Varices.

BACKGROUND: Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis-related portal hypertension (pHTN). This study defined evident pHTN by the presence of esophageal or gastric varices and compared patients' outcomes of metastatic breast cancer with imaging-diagnosed pseudocirrhosis with or without varices. METHODS: The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Survival outcomes were compared based on endoscopic evidence of esophageal or gastric varices. RESULTS: Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Eighty-one (76%) had initial metastases in both hepatic lobes, and 32 (30%) had esophageal or gastric varices. The median overall survival (OS) was 5 and 13 months in patients with and without varices (P = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative subtype was 16, 9, and 2 months, respectively (P = .001). Patients with varices usually had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with varices had OS exceeding 1 year. In multivariate analysis, evident varices (P = .007) and triple-negative subtype (P = .013) were associated with poor OS. CONCLUSIONS: Patients with pseudocirrhosis and evident varices had a significantly shorter median OS, and were usually associated with clinical cirrhosis-related complications. To maximize OS, early identification and meticulous supportive care are warranted.

Statins were not associated with hepatocellular carcinoma after controlling for time-varying confounders in patients with diabetes.

BACKGROUND AND OBJECTIVES: We examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods. METHODS: This retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure. RESULTS: Over a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI: 0.79-0.97) after adjusting for baseline covariates and 0.97 (95% CI: 0.87-1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI: 0.94-1.31) using the MSM approach. CONCLUSION: Statin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.

iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2.

The folding capacity of membrane and secretory proteins in the endoplasmic reticulum (ER) can be challenged by physiological and pathological perturbations, causing ER stress. If unresolved, this leads to cell death. We report a role for iRhom pseudoproteases in controlling apoptosis due to persistent ER stress. Loss of iRhoms causes cells to be resistant to ER stress-induced apoptosis. iRhom1 and iRhom2 interact with IP3 receptors, critical mediators of intracellular Ca2+ signalling, and regulate ER stress-induced transport of Ca2+ into mitochondria, a primary trigger of mitochondrial membrane depolarisation and cell death. iRhoms also bind to the anti-apoptotic regulator BCL-2, attenuating the inhibitory interaction between BCL-2 and IP3 receptors, which promotes ER Ca2+ release. The discovery of the participation of iRhoms in the control of ER stress-induced cell death further extends their potential pathological significance to include diseases dependent on protein misfolding and aggregation.

A novel 3D histotypic cartilage construct engineered by supercritical carbon dioxide decellularized porcine nasal cartilage graft and chondrocytes exhibited chondrogenic capability in vitro.

Augmentative and reconstructive rhinoplasty surgical procedures use autologous tissue grafts or synthetic grafts to repair the nasal defect and aesthetic reconstruction. Donor site trauma and morbidity are common in autologous grafts. The desperate need for the production of grafted 3D cartilage tissues as rhinoplasty grafts without the adverse effect is the need of the hour. In the present study, we developed a bioactive 3D histotypic construct engineered with the various ratio of adipose-derived stem cells (ADSC) and chondrocytes together with decellularized porcine nasal cartilage graft (dPNCG). We decellularized porcine nasal cartilage using supercritical carbon dioxide (SCCO2) extraction technology. dPNCG was characterized by H&E, DAPI, alcian blue staining, scanning electron microscopy and residual DNA content, which demonstrated complete decellularization. 3D histotypic constructs were engineered using dPNCG, rat ADSC and chondrocytes with different percentage of cells and cultured for 21 days. dPNCG together with 100% chondrocytes produced a solid mass of 3D histotypic cartilage with significant production of glycosaminoglycans. H&E and alcian blue staining showed an intact mass, with cartilage granules bound to one another by extracellular matrix and proteoglycan, to form a 3D structure. Besides, the expression of chondrogenic markers, type II collagen, aggrecan and SOX-9 were elevated indicating chondrocytes cultured on dPNCG substrate facilitates the synthesis of type II collagen along with extracellular matrix to produce 3D histotypic cartilage. To conclude, dPNCG is an excellent substrate scaffold that might offer a suitable environment for chondrocytes to produce 3D histotypic cartilage. This engineered 3D construct might serve as a promising future candidate for cartilage tissue engineering in rhinoplasty.

Comparison of clinicopathological features and treatment outcomes in aggressive primary intestinal B- and T/NK-cell lymphomas.

BACKGROUND: Primary intestinal lymphomas (PILs) are rare, and this study compared the clinical outcomes of aggressive primary intestinal B-cell lymphomas (aB-PILs) and T/natural killer-cell lymphomas (T/NK-PILs). METHODS: The clinical information of patients diagnosed with aggressive PILs at our institution between 1995 and 2015 were retrospectively investigated. Pathological subtypes were confirmed according to the 2016 revision of the World Health Organization classification. The correlation between clinicopathological features and overall survival (OS) was determined using univariate and multivariate analyses. RESULTS: Cases of T/NK-PILs had higher initial bowel perforation incidence (67% vs. 7%, P < 0.001) and lower complete response rate to first-line chemotherapy regimens (22% vs. 69%, P = 0.009) than aB-PILs. Patients with aB-PILs had a better 5-year event-free survival rate (55.8% vs. 13.9%, P = 0.026) and a 5-year OS rate (74.3% vs. 29.6%, P = 0.036) than those with T/NK-cell lymphomas. Multivariate analysis identified that female gender and stage III/IV were unfavorable prognostic factors. Among the 54 patients with diffuse large B-cell lymphoma (DLBCL), those with International Prognostic Index (IPI) scores of 0-2 had a better 5-year OS rate than those with scores of 3-5 (84.2% vs. 46.8%, P = 0.002). IPI scores of 3-5 (P = 0.026) and tumors located in the large intestine (P = 0.015) were poor prognostic factors based on the multivariate analysis. CONCLUSION: The prognosis of T/NK-PILs was less favorable than that of aB-PILs. Female gender, stage III/IV disease, DLBCL with IPI scores of 3-5, or tumors in the large intestine were poor prognostic factors.

Role of novel protein kinase C in neuroendocrine-immune regulatory network in haemocytes of Litopenaeus vannamei: An in vitro approach.

Shrimp lack adaptive immune systems and mainly rely on the cellular and humoral defences, involving the haemocytes (functionally analogous to vertebrate leukocytes) in non-self matter recognition, elimination, and in downstream coagulation. Furthermore, the linkage between stress-induced catecholamine (CA), a class of biogenic amines (BAs), releasing and immunological responses has been detected in shrimp. Varied isotypes of protein kinase C (PKC) regulate multiple cellular processes following their specific location and distribution within the cells, and a novel PKC identified in Litopenaeus vannamei (termed as LvnPKC) is proposed to mediate signaling transduction of immunocompetence and BA biosynthesis. In the present study, we analyzed the effects of the LvnPKC-silenced haemocytes by co-incubating with its dsRNA on the immune responses specific to prophenoloxidase (proPO) and antioxidant systems as well as phagocytic activity. In addition, the capability of haemocytes to produce BAs was assessed. The results revealed that LvnPKC-silenced haemocytes can induce interference in phenoloxidase and superoxide dismutase activities, respiratory bursts, and phagocytic activity; meanwhile, the disturbed gene expressions of proPO activating enzyme, proPOII, lipopolysaccharide- and ß-1,3-glucan-binding protein, and cytosolic manganese superoxide dismutase were detected. The same deviated pattern was observed in tyrosine, dopamine, and norepinephrine levels, and in dopamine ß-hydroxylase (DBH) activity and gene expressions of tyrosine hydroxylase, DOPA decarboxylase, and DBH involving in BA biosynthesis. Taken together, these results suggest that the immunocompetence and BA biosynthesis of haemocytes can be mediated via LvPKC signaling transduction, which proved the presence of a neuroendocrine-immune regulatory network in haemocytes.

Length of stay in relation to the risk of inpatient and post-discharge suicides: A national health insurance claim data study.

BACKGROUND: This study aimed to compare the predictors of suicides among psychiatric inpatients and recently discharged patients and to examine the association between the length of stay and suicides. METHODS: Data from psychiatric inpatients were extracted from the National Health Insurance databank and merged with information from the Cause of Death data using unique identification numbers. Poisson regression analyses were used to estimate the incidence rate ratio for inpatient and post-discharge suicides, which included the variables of sex, age, psychiatric diagnosis, and number of admissions in the preceding year. The associations between length of stay and inpatient and post-discharge suicide were examined using multivariate Poisson regression analyses that were adjusted for these variables. RESULTS: A diagnosis of affective disorders and a higher number of previous admissions increased both inpatient and post-discharge suicides. Patients older than 15-24 years had a significantly lower inpatient suicide risk but were more likely to die by suicide post-discharge. The risk of suicide both during the inpatient stay and post-discharge statistically significantly decreased when the length of stay was longer. LIMITATIONS: As there were variations in societal, environmental, and facility-level factors that might have influenced the association between length of stay and suicide, the generalization of our findings to different settings may be impeded. CONCLUSIONS: This study provides additional evidence that hospitalization helps to reduce the suicide risk. It suggests that medical professionals should be alert to inpatient suicide and that they should determine the optimal length of stay considering post-discharge suicide.

Comparative efficacy and safety of new surgical treatments for benign prostatic hyperplasia: systematic review and network meta-analysis.

OBJECTIVE: To assess the efficacy and safety of different endoscopic surgical treatments for benign prostatic hyperplasia. DESIGN: Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES: A comprehensive search of PubMed, Embase, and Cochrane databases from inception to 31 March 2019. STUDY SELECTION: Randomised controlled trials comparing vapourisation, resection, and enucleation of the prostate using monopolar, bipolar, or various laser systems (holmium, thulium, potassium titanyl phosphate, or diode) as surgical treatments for benign prostatic hyperplasia. The primary outcomes were the maximal flow rate (Qmax) and international prostate symptoms score (IPSS) at 12 months after surgical treatment. Secondary outcomes were Qmax and IPSS values at 6, 24, and 36 months after surgical treatment; perioperative parameters; and surgical complications. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the study data and performed quality assessments using the Cochrane Risk of Bias Tool. The effect sizes were summarised using weighted mean differences for continuous outcomes and odds ratios for binary outcomes. Frequentist approach to the network meta-analysis was used to estimate comparative effects and safety. Ranking probabilities of each treatment were also calculated. RESULTS: 109 trials with a total of 13 676 participants were identified. Nine surgical treatments were evaluated. Enucleation achieved better Qmax and IPSS values than resection and vapourisation methods at six and 12 months after surgical treatment, and the difference maintained up to 24 and 36 months after surgical treatment. For Qmax at 12 months after surgical treatment, the best three methods compared with monopolar transurethral resection of the prostate (TURP) were bipolar enucleation (mean difference 2.42 mL/s (95% confidence interval 1.11 to 3.73)), diode laser enucleation (1.86 (-0.17 to 3.88)), and holmium laser enucleation (1.07 (0.07 to 2.08)). The worst performing method was diode laser vapourisation (-1.90 (-5.07 to 1.27)). The results of IPSS at 12 months after treatment were similar to Qmax at 12 months after treatment. The best three methods, versus monopolar TURP, were diode laser enucleation (mean difference -1.00 (-2.41 to 0.40)), bipolar enucleation (0.87 (-1.80 to 0.07)), and holmium laser enucleation (-0.84 (-1.51 to 0.58)). The worst performing method was diode laser vapourisation (1.30 (-1.16 to 3.76)). Eight new methods were better at controlling bleeding than monopolar TURP, resulting in a shorter catheterisation duration, reduced postoperative haemoglobin declination, fewer clot retention events, and lower blood transfusion rate. However, short term transient urinary incontinence might still be a concern for enucleation methods, compared with resection methods (odds ratio 1.92, 1.39 to 2.65). No substantial inconsistency between direct and indirect evidence was detected in primary or secondary outcomes. CONCLUSION: Eight new endoscopic surgical methods for benign prostatic hyperplasia appeared to be superior in safety compared with monopolar TURP. Among these new treatments, enucleation methods showed better Qmax and IPSS values than vapourisation and resection methods. STUDY REGISTRATION: CRD42018099583.

Risk prediction for 30-day mortality among patients with Clostridium difficile infections: a retrospective cohort study.

Background: Current guidelines have unsatisfied performance in predicting severe outcomes after Clostridium difficile infection (CDI). Our objectives were to develop a risk prediction model for 30-day mortality and to examine its performance among inpatients with CDI. Methods: This retrospective cohort study was conducted at China Medical University Hospital, a 2111-bed tertiary medical center in central Taiwan. We included adult inpatients who had a first positive C. difficile culture or toxin assay and had diarrhea as the study population. The main exposure of interest was the biochemical profiles of white blood cell count, serum creatinine (SCr), estimated glomerular filtration rate, blood urea nitrogen (BUN), serum albumin, and glucose. The primary outcome was the 30-day all-cause mortality and the secondary outcome was the length of stay in the intensive care units (ICU) following CDI. A multivariable Cox model and a logistic regression model were developed using clinically relevant and statistically significant variables for 30-day mortality and for length of ICU stay, respectively. A risk scoring system was established by standardizing the coefficients. We compared the performance of our models and the guidelines. Results: Of 401 patients, 23.4% died within 30 days. In the multivariable model, malignancy (hazard ratio [HR] = 1.95), ≥ 1.5-fold rise in SCr (HR = 2.27), BUN-to-SCr ratio > 20 (HR = 2.04), and increased glucose (≥ 193 vs < 142 mg/dL, HR = 2.18) were significant predictors of 30-day mortality. For patients who survived the first 30 days of CDI, BUN-to-SCr ratio > 20 (Odds ratio [OR] = 4.01) was the only significant predictor for prolonged (> 9 days) length of ICU stay following CDI. The Harrell's c statistic of our Cox model for 30-day mortality (0.727) was significantly superior to those of SHEA-IDSA 2010 (0.645), SHEA-IDSA 2018 (0.591), and ECSMID (0.650). Similarly, the conventional c statistic of our logistic regression model for prolonged ICU stay (0.737) was significantly superior to that of the guidelines (SHEA-IDSA 2010, c = 0.600; SHEA-IDSA 2018, c = 0.634; ESCMID, c = 0.645). Our risk prediction scoring system for 30-day mortality correctly reclassified 20.7, 32.1, and 47.9% of patients, respectively. Conclusions: Our model that included novel biomarkers of BUN-to-SCr ratio and glucose have a higher predictive performance of 30-day mortality and prolonged ICU stay following CDI than do the guidelines.

Dichotomy of the function of DDR1 in cells and disease progression.

Discoidin domain receptors DDR1 and DDR2 are collagen receptor tyrosine kinases that have many roles in tissue development and disease progression. Under physiological conditions, DDR1 is predominantly expressed in epithelial cells and functions to maintain cell differentiation and tissue homeostasis. A switch in expression from DDR1 to DDR2 occurs during epithelial-to-mesenchymal transition. However, opposite effects of DDR1 are reported to be involved in the progression of cancer and fibrotic diseases. Accumulating evidence suggests that DDR1 is involved in pro-metastasis and pro-survival signals. This review summarizes the roles of DDR1 in epithelial cell differentiation, cell migration, cancer progression and tissues fibrosis and highlights how the dichotomous functions of DDR1 may relevant to different cell types and statues. Elucidation of the underlying mechanism of the dichotomous functions of DDR1 will help to develop DDR1 as a therapeutic target.

Spasmolytic polypeptide-expressing metaplasia associated with higher expressions of miR-21, 155, and 223 can be regressed by Helicobacter pylori eradication in the gastric cancer familial relatives.

BACKGROUND AND AIMS: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a preneoplastic gastric cancer lesion related to epigenetic microRNA (miRNA) expression. This study elucidated whether Helicobacter pylori-infected first-degree relatives of patients with gastric cancer (GCF) are susceptible to have SPEM and correlated with miR-21, 155, and 223 expressions. We also validated whether SPEM and these miRNAs can be regressed after H pylori eradication. METHODS: We prospectively enrolled 148 GCF and 148 nonulcer dyspepsia (NUD) subjects without gastric cancer familial history as controls. Each case had received a panendoscopy to determine H pylori status and gastric histology, including SPEM. The cases with SPEM were followed after H pylori eradication to determine SPEM regression. The total RNA was extracted to analyze tissues miR-21, 155, and 223 before and after eradication. RESULTS: GCF subjects had a higher prevalence of H pylori infection (73% vs 32%) and SPEM (42% vs 14%, P < 0.01) than controls. The tissue miR-21, 155, and 223 in antrum were higher in cases with SPEM than in those without SPEM (P <= 0.05). There was similar SPEM reversibility after H pylori eradication between GCF subjects and controls (72% vs 69%, P = 0.852). In the SPEM regressed cases, tissue miR-21, 155, and 223 decreased after H pylori eradication (P < 0.05). CONCLUSION: The H pylori-infected GCF subjects were prone to have SPEM with higher tissues miR-21, 155, and 223 expressions. H pylori eradication can result in a 70% SPEM regression, accompanied by a decline in miR-21, 155, and 233 expression levels.

H. pylori isolates with amino acid sequence polymorphisms as presence of both HtrA-L171 & CagL-Y58/E59 increase the risk of gastric cancer.

BACKGROUND: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. METHODS: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. RESULTS: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1-6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001). CONCLUSIONS: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.

Sleep Duration and Proteinuria Progression: A Population-Based Cohort Study.

BACKGROUND: Extensive studies have demonstrated that sleep is an important modulator of cardiovascular and metabolic diseases. However, its impact on renal function remains uncertain. METHODS: A total of 26,249 adults aged ≥20 years were recruited through voluntary health examinations in Taiwan. Sleep duration was self-reported by questionnaire. Proteinuria was graded semi-quantitatively by dipstick urine test. The associations of sleep duration with proteinuria and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS: After an average follow-up period of 2.62 years, the crude hazard ratio (HR) for proteinuria progression were 1.92 (95% CI 1.22-3.03), 1.23 (95% CI 1.09-1.39), and 1.18 (95% CI 1.00-1.39) for those with sleep duration < 4, 4-6, and > 8 h compared to those with sleep duration of 6-8 h (the reference group), respectively. The HR remained significant for those with sleep duration < 4 h (adjusted HR 1.65 [95% CI 1.05-2.61]) and 4-6 h (adjusted HR 1.19 [95% CI 1.06-1.35]) after adjustment for age, sex, blood pressure, fasting glucose, body mass index, cholesterols, triglycerides, uric acids, physical activity, smoking, alcohol consumption, income/educational levels, and baseline eGFR. However, eGFR was not significantly different among different sleep duration groups. DISCUSSION: This result indicates short sleep duration is independently associated with the progression of proteinuria.

The impacts of H. pylori virulence factors on the development of gastroduodenal diseases.

Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.

Risk of Infective Endocarditis After Invasive Dental Treatments: Case-Only Study.

BACKGROUND: Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE. METHODS: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT. RESULTS: In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94-1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02-1.26) for 1 to 4 weeks after IDTs. CONCLUSIONS: In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.