Vaginal microbiomes show ethnic evolutionary dynamics and positive selection of Lactobacillus adhesins driven by a long-term niche-specific process.

The vaginal microbiome's composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

The utility of intraoperative endoscopy to assist novice surgeons in the detection of gastric stenosis during laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a commonly performed bariatric surgery. Gastric stenosis and leaks are 2 major complications associated with LSG and revision surgery might be needed. Herein, we report our experience of intraoperative endoscopy (IOE) to evaluate stenosis and leaks during LSG. METHODS: LSG was performed by three surgeons. Patients who underwent LSG and IOE between January 2016 and March 2020 were enrolled and assigned to two groups: group 1 (1st-30th LSG case for each surgeon) and group 2 (> 30th LSG for each surgeon). Patients' anthropometric and biochemical data pre- and post-LSG, as well as IOE findings and follow-up esophagogastroduodenoscopy records were reviewed. RESULTS: In total, 352 patients were enrolled including 90 patients in group 1 and 262 patients in group 2. Three out of 352 patients (0.9%) were found to have stenosis by IOE, which was related to tightly gastropexy stitch or reinforcement stitch, all of which were in group 1. Stenosis was resolved after removal of the stitch during LSG. The incidence of gastric stenosis detected by IOE was 3.3% (3/90) and 0% (0/262) in group 1 and group 2, respectively (P = 0.003). No leakage was found in this study and no patient developed clinical or endoscopic stenosis after LSG. CONCLUSIONS: The existing evidence showed that IOE can help detect gastric stenosis during LSG, especially for novice surgeons, and the stenosis could be resolved during operation.

Nonlinear compression toward high-energy single-cycle pulses by cascaded focus and compression.

The advancement of contemporary ultrafast science requires reliable sources to provide high-energy few-cycle light pulses. Through experiments and simulations, we demonstrate an arrangement of pulse postcompression, referred to as cascaded focus and compression (CASCADE), for generating millijoule-level, single-cycle pulses in a compact fashion. CASCADE is realized by a series of foci in matter, whereas pulse compression is provided immediately after each focus to maintain a high efficiency of spectral broadening. By implementing four stages of CASCADE in argon cells, we achieve 50-fold compression of millijoule-level pulses at 1030 nanometers from 157 to 3.1 femtoseconds, with an output pulse energy of 0.98 millijoules and a transmission efficiency of 73%. When driving high harmonic generation, these single-cycle pulses enable the creation of a carrier-envelope phase-dependent extreme ultraviolet continuum with energies extending up to 180 electron volts, providing isolated attosecond pulses at the output.

Statins Are Associated With Increased Insulin Resistance and Secretion.

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.

Prevention of Severe Intestinal Barrier Dysfunction Through a Single-Species Probiotics is Associated With the Activation of Microbiome-Mediated Glutamate-Glutamine Biosynthesis.

INTRODUCTION: Intra-abdominal hypertension (IAH), the leading complication in the intensive care unit, significantly disturbs the gut microbial composition by decreasing the relative abundance of Lactobacillus and increasing the relative abundance of opportunistic infectious bacteria. METHODS: To evaluate the preventative effect of Lactobacillus-based probiotics on IAH-induced intestinal barrier damages, a single-species probiotics (L92) and a multispecies probiotics (VSL#3) were introduced orally to Sprague-Dawley rats for 7 days before inducing IAH. The intestinal histology and permeability to macromolecules (fluoresceine isothiocyanate, FITC-dextran, N = 8 for each group), the parameters of immunomodulatory and oxidative responses [monocyte chemotactic protein 1 (MCP-1), interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interleukin-10 (IL-10), malonaldehyde, glutathione peroxidase (GSH- Px), catalase (CAT), and superoxide dismutase; N = 4 for each group], and the microbiome profiling (N = 4 for each group) were analyzed. RESULTS: Seven-day pretreatments of L92 significantly alleviated the IAH-induced increase in intestinal permeability to FITC-dextran and histological damage (P  < 0.0001), accompanied with the suppression of inflammatory and oxidative activation. The increase of MCP-1 and IL-1ß was significantly inhibited (P  < 0.05); the anti-inflammatory cytokines, IL-4, and IL-10 were maintained at high levels; and the suppression of CAT (P  <  0.05) was significantly reversed when pretreated with L92. On the contrary, no significant protective effects were observed in the VSL#3-pretreated group. Among the 84 identified species, 260 MetaCyc pathways, and 217 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the protective effects of L92 were correlated with an increased relative abundance of Bacteroides finegoldii, Odoribacter splanchnicus, and the global activation of amino acid biosynthesis pathways, especially the glutamate-glutamine biosynthesis pathway. CONCLUSIONS: Seven-day pretreatment with a single-species probiotics can prevent IAH-induced severe intestinal barrier dysfunction, potentially through microbial modulation.

Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer.

BACKGROUND: Expression of Oct4 maintains cancer stem cell (CSC)-like properties in lung cancer cells and is correlated with poor prognosis of lung adenocarcinoma. M2-type tumor-associated macrophages (TAMs) promote cancer cell migration and metastasis. Tumor microenvironments promote monocyte differentiation into M2 TAMs via a complex cytokine-based connection. We explored the role of Oct4 in cytokine secretion in lung cancer and its impact on M2 TAM polarization. METHODS: Monocytes co-cultured with the conditioned medium from Oct4-overexpressing lung cancer cells were used to investigate M2 TAM differentiation. The inflammatory factors in the conditioned medium of Oct4-overexpressing A549 cells were examined using human inflammation antibody arrays. The correlations of Oct4, macrophage colony-stimulating factor (M-CSF), and M2 TAMs were validated in lung cancer cells, syngeneic mouse lung tumor models, and clinical samples of non-small cell lung cancer (NSCLC). RESULTS: Oct4-overexpressing A549 cells expressed elevated levels of M-CSF, which contributed to increased M2 macrophages and enhanced tumor migration. Overexpression of Oct4 enhanced tumor growth and reduced the survival of lung tumor-bearing mice, which was correlated with increased number of M2 macrophages in lung cancer. Notably, NSCLC patients with high expression levels of Oct4, M-CSF, and M2 TAMs had the poorest recurrence-free survival. A positive correlation between Oct4, M-CSF, and M2 TAMs was observed in the tumor tissue of NSCLC patient. Treatment with all-trans retinoic acid exerted anti-tumor effects and reduced M2 TAMs in tumor-bearing mice. CONCLUSIONS: Our results indicate that Oct4 expressed by lung cancer cells promotes M2 macrophage polarization through upregulation of M-CSF secretion, leading to cancer growth and metastasis. Our findings also implicate that the Oct4/M-CSF axis in M2 macrophage polarization may be potential therapeutic targets for lung cancer.

Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Nerve growth factor induced farnesoid X receptor upregulation modulates autophagy flux and protects hepatocytes in cholestatic livers.

Upregulation of nerve growth factor (NGF) in parenchymal hepatocytes has been shown to exert hepatoprotective function during cholestatic liver injury. However, the modulatory role of NGF in regulation of liver autophagy remains unclear. This study aimed to scrutinize the regulatory role of NGF in hepatic expression of farnesoid X receptor (FXR), a bile acid (BA)-activated nuclear receptor, and to determine its cytoprotective effect on BA-induced autophagy and cytotoxicity. Livers of human hepatolithiasis and bile duct ligation (BDL)-induced mouse cholestasis were used for histopathological and molecular detection. The regulatory roles of NGF in autophagy flux and FXR expression, as well as its hepatoprotection against BA cytotoxicity were examined in cultured hepatocytes. FXR downregulation in human hepatolithiasis livers showed positive correlation with hepatic NGF levels. NGF administration upregulated hepatic FXR levels, while neutralization of NGF decreased FXR expression in BDL-induced cholestatic mouse livers. In vitro studies demonstrated that NGF upregulated FXR expression, increased cellular LC3 levels, and exerted hepatoprotective effect in cultured primary rat hepatocytes. Conversely, autophagy inhibition abrogated NGF-driven cytoprotection under BA exposure, suggesting involvement of NGF-modulated auophagy flux. Although FXR agonistic GW4064 stimulation did not affect auophagic LC3 levels, FXR activity inhibition significantly potentiated BA-induced cytotoxicity and increased cellular p62/SQSTM1 and Rab7 protein in SK-Hep1 hepatocytes. Moreover, FXR gene silencing abolished the protective effect of NGF under BA exposure. These findings support that NGF modulates autophagy flux via FXR upregulation and protects hepatocytes against BA-induced cytotoxicity. NGF/FXR axis is a novel therapeutic target for treatment of cholestatic liver diseases.

Correction to: Bariatric Surgery Did Not Increase the Risk of Gallstone Disease in Obese Patients: a Comprehensive Cohort Study.

In the section "Method" the first sentence should read as follows: This retrospective study was fully evaluated and approved by the Institutional Review Board of Buddhist Dalin Tzu Chi Hospital (approval B10603004) and was conducted in accordance with the principles of the Helsinki Declaration.

Bariatric Surgery Did Not Increase the Risk of Gallstone Disease in Obese Patients: a Comprehensive Cohort Study.

PURPOSE: The aim of this study was to evaluate the influence of bariatric surgery on gallstone disease in obese patients. MATERIALS AND METHODS: This large cohort retrospective study was conducted based on the Taiwan National Health Insurance Research Database. All patients 18-55 years of age with a diagnosis code for obesity (ICD-9-CM codes 278.00-278.02 or 278.1) between 2003 and 2010 were included. Patients with a history of gallstone disease and hepatic malignancies were excluded. The patients were divided into non-surgical and bariatric surgery groups. Obesity surgery was defined by ICD-9-OP codes. We also enrolled healthy civilians as the general population. The primary end point was defined as re-hospitalization with a diagnosis of gallstone disease after the index hospitalization. All patients were followed until the end of 2013, a biliary complication occurred, or death. RESULTS: Two thousand three hundred seventeen patients in the bariatric surgery group, 2331 patients in the non-surgical group, and 8162 patients in the general population were included. Compared to the non-surgery group (2.79%), bariatric surgery (2.89%) did not elevate the risk of subsequent biliary events (HR = 1.075, p = 0.679). Compared to the general population (1.15%), bariatric surgery group had a significantly higher risk (HR = 4.996, p < 0.001). In the bariatric surgery group, female gender (HR = 1.774, p = 0.032) and a restrictive procedure (HR = 1.624, p = 0.048) were risk factors for gallstone disease. CONCLUSION: The risk for gallstone disease did not increase after bariatric surgery, although the risk was still higher than the general population. The benefit of concomitant cholecystectomy during bariatric surgery should be carefully evaluated.

A Higher Preoperative Glycemic Profile Is Associated with Rapid Gastric Emptying After Sleeve Gastrectomy for Obese Subjects.

BACKGROUND: Recent reports have shown that sleeve gastrectomy (SG) accelerates gastric emptying (GE), but the etiology remains unclear. This study aimed to investigate the factors affecting GE before and after SG. METHODS: We enrolled 35 normal weight healthy subjects and 23 obese patients receiving SG. The normal individuals and obese patients before and 3 months after SG received oatmeal-based scintigraphy to measure GE. Gastrointestinal symptoms and circulating levels of peptide YY (PYY) were also measured. RESULTS: There were no differences in the GE parameters, including simple half-time at 3 h and percentage of gastric retention at 0.5, 1, 2, and 3 h between healthy controls and pre-SG obese subjects. SG led to accelerated GE, more gastrointestinal symptoms, and increased fasting PYY levels postoperatively. Based on our previously established normal GE values, 18 (78.3%) obese patients with rapid postoperative GE had higher levels of preoperative fasting glucose and glycated hemoglobin, and homeostasis model assessment of the insulin resistance index than those with normal postoperative GE. Twelve (52.2%) obese patients had preoperative diabetes mellitus (DM), and only four (17.4%) remained diabetic after SG. The post-SG gastric retention at 0.5 and 1 h was lower in patients with preoperative DM than in those without preoperative DM. Neither severity of gastrointestinal symptoms nor fasting PYY levels were associated with postoperative GE alterations. CONCLUSION: Most of the obese patients had accelerated GE after SG. A higher preoperative glycemic profile was associated with rapid post-SG GE.

Traversal of the Blood-Brain Barrier by Cleavable l-Lysine Conjugates of Apigenin.

Apigenin, a flavone abundant in parsley and celery, is known to act on several CNS receptors, but its very poor water solubility (<0.001 mg/mL) impedes its absorption in vivo and prevents clinical use. Herein, apigenin was directly conjugated with glycine, l-phenylalanine, and l-lysine to give the corresponding carbamate derivatives, all of which were much more soluble than apigenin itself (0.017, 0.018, and 0.13 mg/mL, respectively). The Lys-apigenin carbamate 10 had a temporary sedative effect on the mice within 5 min of intraperitoneal administration (single dose of 0.4 mg/g) and could be detected in the mice brain tissues at a concentration of 0.82 µg/g of intact Lys-apigenin carbamate 10 and 0.42 ug/g of apigenin at 1.5 h. This study accomplished the delivery of apigenin across the BBB in a manner that might be applicable to other congeners, which should inform the future development of BBB-crossing flavonoids.

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration.

Nerve growth factor upregulates sirtuin 1 expression in cholestasis: a potential therapeutic target.

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal-regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.

Transcriptome analysis reveals a positive role for nerve growth factor in retinol metabolism in primary rat hepatocytes.

Up-regulation of nerve growth factor (NGF) in parenchymal hepatocytes with cholestatic injury has been previously demonstrated to exert hepatoprotective effects in an autocrine manner; however, the overall impact of NGF up-regulation remains elusive. This study aimed to profile the effects of exogenous NGF on cultured primary rat hepatocytes using transcriptome analysis. Total RNA was isolated from hepatocytes with and without 24 h of NGF exposure, and subjected to RNA enrichment by PCR and RNA sequencing procedures. Comparison of transcriptome profiles between control and NGF-stimulated hepatocytes demonstrated that NGF significantly up-regulated 10 genes and down-regulated 23 genes in hepatocytes. Subsequent KEGG pathway enrichment analysis indicated that NGF significantly affected the retinol metabolism pathway via increased retinol dehydrogenase 16 (RDH16) expression. In a mouse model of bile duct ligation-induced cholestatic liver injury, NGF supplementation significantly enhanced RDH16 expression, whereas administration of anti-NGF neutralizing antibodies prominently decreased RDH16 expression in cholestatic livers, supporting the positive role of NGF in the regulation of RDH16 in diseased livers. In vitro study further demonstrated that NGF triggered de novo synthesis of RDH16 in primary rat hepatocytes, mainly through an NF-κB signaling pathway. In conclusion, this study demonstrates the up-regulation of RDH16 by NGF in cultured rat hepatocytes and mouse cholestatic livers, and provides novel insights on the mechanistic role of NGF in the retinol metabolism of livers.

Lipopolysaccharides induce Smad2 phosphorylation through PI3K/Akt and MAPK cascades in HSC-T6 hepatic stellate cells.

AIMS: Endotoxemia and its pro-fibrogenic signaling play a significant role in the development of hepatic fibrosis. This study investigated whether lipopolysaccharide (LPS) directly activate cultured HSC-T6 hepatic stellate cells (HSCs) through triggering Smad-dependent pro-fibrogenic signaling pathway. MAIN METHODS: Direct cell counting and assays for cell proliferation and migration were used to measure the effects of LPS on HSC behaviors. Quantitative PCR, Western blot, and gelatin zymography were used to quantify the molecular effects of LPS on expression of HSC activation markers and signaling activity. KEY FINDINGS: Long-term exposure to LPS exhibited moderately stimulatory effect on HSC cell growth. A wound-healing cell migration assay showed that LPS suppressed HSC-T6 cell migration. qPCR and Western blotting detection indicated that LPS treatment induced upregulation of type I and IV collagens, α-smooth muscle actin (α-SMA), and matrix metalloproteinase-9 (MMP-9). Gelatin zymography confirmed that LPS elevated MMP-9, but not MMP-2 gelatinolytic activity. Moreover, LPS immediately stimulated Akt, EKR1/2, JNK, p38 MAPK, and Smad2 hyperphosphorylation, supporting that LPS directly triggers pro-fibrogenic Smad signaling cascade without TGF-ß1 stimulation. Kinase blockade experiments demonstrated the involvement of PI3K/Akt, JNK, p38 MAPK, but not ERK1/2 signaling activation in the LPS-elicited Smad2 phosphorylation as well as the overexpression of type I collagen and α-SMA in HSC-T6 cells. SIGNIFICANCE: These findings demonstrate that LPS exerts pro-fibrogenic effect through activation and transformation of HSCs. The tissue-remodeling effect of LPS may be attributable to its ability to activate non-canonical Smad pathway through PI3K/Akt and MAPK signaling cascades.

Gastrectomy is Associated with an Increased Risk of Pyogenic Liver Abscess: A 13-Year Nationwide Cohort Study.

Whether patients who have undergone gastrectomy are at a high risk of developing pyogenic liver abscess (PLA) remains debatable. From the inpatient claims records of Taiwan's National Health Insurance Research Database, we identified 33 834 patients with a history of 2000-2010 and135 336 controls without a history of gastrectomy. The 2cohorts were matched by age, sex, and admission year and followed-up until the end of 2011 for estimating the risk of PLA. Overall, the incidence of PLA was 3.5-fold higher in the gastrectomy cohort than in the control cohort (21.6 vs 5.76 per 10 000 person-y). The adjusted hazard ratio (aHR) for the gastrectomy cohort obtained using the multivariate Cox proportional hazards regression model was 3.08 (95% confidence interval [CI] = 2.60-3.64). An elevated post gastrectomy PLA risk was observed in both men and women. Age-specific data revealed that the aHR for the gastrectomy cohort, compared with the control cohort, was the highest in patients younger than 50 years (aHR = 5.16, 95% CI = 2.96-9.01). An addition analysis showed that the gastrectomy cohort exhibited an elevated PLA risk regardless of whether the patients underwent total or partial gastrectomy. Patients with a history of gastrectomy exhibit a high risk of PLA.

Increased Risk of Pyogenic Liver Abscess Among Patients With Colonic Diverticular Diseases: A Nationwide Cohort Study.

Whether patients with diverticular diseases exhibit a higher risk of developing pyogenic liver abscess (PLA) remains inconclusive.From the inpatient claims in Taiwan's National Health Insurance Research Database, we identified 54,147 patients diagnosed with diverticulosis in the 1998 to 2010 period and 216,588 controls without the disorder. The 2 cohorts were matched by age, sex, and admission year, and were followed up until the end of 2010 to estimate the risk of PLA.Overall, the incidence of PLA was 2.44-fold higher in the diverticular-disease group than in the controls (11.5 vs 4.65 per 10,000 person-year). The adjusted hazard ratio (aHR) of PLA was 2.11 (95% confidence interval [CI], 1.81-2.44) for the diverticular-disease group, according to a multivariate Cox proportional hazards regression model. The age-specific data showed that the aHR for the diverticular-disease group, compared with the controls, was the highest inpatients younger than 50 years old (aHR, 4.03; 95% CI, 2.77-5.85). Further analysis showed that the diverticular-disease group exhibited an elevated risk of PLA regardless of whether patients had diverticulitis.The patients with diverticular diseases exhibited a higher risk of PLA.

Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats.

It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg(-1) d(-1)) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg(-1) d(-1)) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max), using the elastance-resistance model. Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in E max associated with the increased Q max in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased E max, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Q max, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal resistance, possibly through its ability to reduce the aforementioned myocardial depressant substances. However, since our results were obtained in anesthetized open-chest rats, extrapolation to what may occur in conscious intact animals should be done with caution.

Dopamine impairs functional integrity of rat hepatocytes through nuclear factor kappa B activity modulation: An in vivo, ex vivo, and in vitro study.

Dopamine (DA) is commonly used to maintain the hemodynamic stability of brain-dead donors despite its controversial effects on organ functions. This study aimed at examining the hemodynamic effect of DA in a rat brain-dead model in vivo, alteration of hepatocyte integrity in liver grafts after ex vivo preservation, and changes in cultured clone-9 hepatocytes including cellular viability, cell cycle, apoptotic regulators, and lipopolysaccharide (LPS)-stimulated nuclear factor kappa B (NF-κB) signaling machinery. Although in vivo findings demonstrated enhanced portal venous blood flow and hepatic microcirculatory perfusion after DA infusion, no apparent advantage was noted in preserving hepatocyte integrity ex vivo. In vitro, prolonged exposure to high-dose DA reduced proliferation and induced G1 growth arrest of clone-9 hepatocytes with concomitant decreases in B cell lymphoma 2 (BCL2)/B cell lymphoma 2-associated X protein (BAX) and heat shock protein 70/BAX protein ratios and intracellular NF-κB p65. Moreover, DA pretreatment suppressed LPS-elicited inhibitor of κBα phosphorylation and subsequent NF-κB nuclear translocation, suggesting that DA may down-regulate NF-κB signaling, thereby reducing expression of antiapoptotic regulators, such as BCL2. In conclusion, despite augmentation of hepatic perfusion, DA infusion failed to preserve hepatocyte integrity both in vivo and ex vivo. In vitro findings demonstrated that high-dose DA may hamper the function of NF-κB signaling machinery and eventually undermine functional integrity of hepatocytes in liver grafts.