Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

A hybrid piezoelectric and triboelectric nanogenerator with lead-free BZT-BCT/PDMS composite and PVA film for scavenging mechanical energy.

A hybrid piezo/triboelectric nanogenerator (H/P-TENG) is designed for mechanical energy harvesting using polymer ceramic composite films; polydimethylsiloxane/Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (PDMS/BZT-BCT) and polyvinyl alcohol (PVA). A lead-free BZT-BCT piezoelectric ceramic was prepared via solid-state method and blended into PDMS to form a series of polymer-ceramic composite films, ranging from 5% to 30% by weight. The films were forward/reverse poled with corona poling and their electrical properties were compared to non-poled samples. The H/P-TENG constructed with forward-poled 15 wt% BZT-BCT in PDMS achieved the highest open-circuit voltage, V oc of 127 V, short-circuit current density, J sc of 67 mA m-2, short-circuit charge density, Q sc of 118 µC m-2, and peak power density of 7.5 W m-2, an increase of 190% over pristine PDMS-based TENG. It was discovered that incorporating BZT-BCT into the PDMS matrix improved the triboelectric properties of PDMS. The overlapping electron cloud (OEC) model was used to explain the enhancement and the effect of poling direction of the PDMS/BZT-BCT composite used in H/P-TENG, providing fundamental knowledge of the influence of piezoelectric polarisation on contact electrification.

What is the real morbidity after emergency colectomy for Crohn's disease? A propensity score matched study.

BACKGROUND: In the inflammatory bowel disease literature, emergency surgery for Crohn's disease (CD) is associated with worse postoperative outcomes as compared to elective surgery. Previous studies have compared heterogeneous groups only. We hypothesized that this association would be lost after matched analysis. We aimed to compare matched CD patients undergoing elective vs emergency surgery. METHODS: The National Surgical Quality Improvement database (01/2005-12/2019) was utilized to identify adult CD surgical patients. Univariate and conditional logistic regression models were used to analyze unmatched and matched cohorts. Propensity-score matching was performed to match emergency to non-emergency patients 1:1. Our primary outcome was a composite of any complication. Our secondary endpoints were hospital readmission, unplanned reoperation and 30-day morbidity and mortality. RESULTS: In the unmatched analyses (n = 12,181/95.28% elective and n = 603/4.72% emergency) of Crohn's patients undergoing colectomy, 20% of elective and 42% of emergency patients experienced a complication (p < 0.001). Over 20 outcomes measured including length of stay (LOS), readmission, infections and respiratory, cardiovascular and renal complications, were worse in the emergency cohort. In the matched analyses (n = 400 emergency/400 elective patients) only the categories of any complication (OR 1.44, 1.06-1.96 95% CI, p = 0.02), any surgical site infection (SSI, OR 1.53, 1.07-2.19 95% CI, p = 0.02), superficial SSI (OR 2.25, 1.14-4.44 95% CI, p = 0.02), organ space SSI (1.58 OR 1.04-2.4 95% CI, p = 0.03), unplanned intubation (OR 5.0, 1.45-17.27 95% CI, p = 0.01), ventilation > 48 h (OR 9.0, 1.4-38.79 95% CI, p = 0.003) and septic shock (OR 4.5, 1.86-10.9 95% CI, p < 0.001) were higher in the emergency cohort. CONCLUSIONS: Matching CD patients resulted in a loss of the observed increase in cardiovascular and renal complications, reoperation and LOS following emergency surgery; however, SSIs and respiratory complications remained increased despite matching.

Randomized clinical trial of the effect of intraoperative humidified carbon dioxide insufflation in open laparotomy for colorectal resection.

BACKGROUND: Animal studies have shown that peritoneal injury can be minimized by insufflating the abdominal cavity with warm humidified carbon dioxide gas. METHODS: A single-blind RCT was performed at a tertiary colorectal unit. Inclusion criteria were patient aged 18 years and over undergoing open elective surgery. The intervention group received warmed (37°C), humidified (98 per cent relative humidity) carbon dioxide (WHCO2  group). Multiple markers of peritoneal inflammation and oxidative damage were used to compare groups, including cytokines and chemokines, apoptosis, the 3-chlorotyrosine/native tyrosine ratio, and light microscopy on peritoneal biopsies at the start (T0 ) and end (Tend ) of the operation. Postoperative clinical outcomes were compared between the groups. RESULTS: Of 40 patients enrolled, 20 in the WHCO2 group and 19 in the control group were available for analysis. A significant log(Tend /T0 ) difference between control and WHCO2 groups was documented for interleukin (IL) 2 (5·3 versus 2·8 respectively; P = 0·028) and IL-4 (3·5 versus 2·0; P = 0·041), whereas apoptosis assays documented no significant change in caspase activity, and similar apoptosis rates were documented along the peritoneal edge in both groups. The 3-chlorotyrosine/tyrosine ratio had increased at Tend by 1·1-fold in the WHCO2 group and by 3·1-fold in the control group. Under light microscopy, peritoneum was visible in 11 of 19 samples from the control group and in 19 of 20 samples from the WHCO2 group (P = 0·006). The only difference in clinical outcomes between intervention and control groups was the number of days to passage of flatus (2·5 versus 5·0 days respectively; P = 0·008). CONCLUSION: The use of warmed, humidified carbon dioxide appears to reduce some markers related to peritoneal oxidative damage during laparotomy. No difference was observed in clinical outcomes, but the study was underpowered for analysis of surgical results. Registration number: NCT02975947 ( www.ClinicalTrials.gov/).

ANTECEDENTES: Los estudios en animales han demostrado que la lesión peritoneal se puede minimizar insuflando gas de dióxido de carbono caliente y humidificado (warm, humidified carbon dioxide gas,WHCO2(g) ) en la cavidad abdominal. El objetivo de este ensayo fue investigar los marcadores de inflamación peritoneal y de daño oxidativo en pacientes sometidos a cirugía colorrectal y abdominal tratados dióxido de carbono calentado humidificado en comparación con controles. El objetivo secundario fue evaluar los resultados clínicos perioperatorios. MÉTODOS: Se llevó a cabo un ensayo aleatorizado, controlado y simple ciego en una unidad colorrectal terciaria. Se incluyeron pacientes de > 18 años de edad sometidos operaciones electivas por vía abierta. El grupo de intervención recibió CO2(g) calentado (37°C) y humidificado (98% humedad relativa). Para la comparación de los grupos, se determinaron múltiples marcadores de inflamación peritoneal y daño oxidativo, incluyendo citocinas y quimiocinas, apoptosis (actividad Caspasas -3 y -7 y DeadEndTM TUNEl sistema fluorométrico), la tasa 3-clorotirosina/tirosina nativa (HPLC-MS) y microscopía electrónica de biopsias peritoneales al inicio (T0 ) y al término (Tfinal ) de la operación. Los resultados clínicos postoperatorios se compararon entre los grupos. RESULTADOS: De los 40 pacientes incluidos en el estudio, se dispuso de datos para el análisis en 20 pacientes asignados al grupo de CO2 y en 19 asignados al grupo control. Se observó una diferencia significativa Log(Tend/T0) entre los grupos respecto a IL-2 (grupo control: 5,34, grupo CO2: 2,78, P = 0,028) y IL-4 (grupo control: 3,53, grupo CO2: 2,00, P = 0,04), en tanto que los análisis relativos a la apoptosis no pusieron de manifiesto cambios significativos en la actividad de la caspasa, y se observaron tasas de apoptosis similares a lo largo del borde peritoneal en ambos grupos. La tasa 3-clorotirosina/tirosina nativa aumentó en 1,05 veces en el grupo del CO2 y en 3,1 veces en el grupo control. Por microscopía óptica el peritoneo era visible en el 57,9% de los sujetos del grupo control y en el 95% de los que recibieron tratamiento con WHCO2(g) (P = 0,006). La única diferencia en los resultados clínicos entre los grupos de intervención y control fue el número de días para el paso de gases (2,5 en el grupo de CO2 versus 5,0 días en el grupo control, P = 0,008). CONCLUSIÓN: El uso de WHCO2(g) parece disminuir algunos de los marcadores relacionados con el daño peritoneal por estrés oxidativo durante la laparotomía. Aunque no se observaron diferencias en los resultados clínicos, el estudio no tenía la suficiente potencia para analizar los resultados quirúrgicos.

Embolization of percutaneous transhepatic portal venous access tract with N-butyl cyanoacrylate.

OBJECTIVE: To evaluate the safety and feasibility of N-butyl cyanoacrylate (N-BCA) embolization of percutaneous transhepatic portal venous access tract and to establish an appropriate technique. METHODS: 40 consecutive patients underwent percutaneous transhepatic portal venous intervention for various reasons. Embolization of percutaneous transhepatic portal venous access tract was performed after the procedure in all of the patients using N-BCA and Lipiodol® (Lipiodol Ultra Fluide; Laboratoire Guerbet, Aulnay-sous-Bois, France) mixture. Immediate ultrasonography and fluoroscopy were performed to evaluate perihepatic haematoma formation and unintended embolization of more than one segmental portal vein. Follow-up CT was performed, and haemoglobin and haematocrit levels were checked to evaluate the presence of bleeding. RESULTS: Immediate haemostasis was achieved in all of the patients, without development of perihepatic haematoma or unintended embolization of more than one segmental portal vein. Complete embolization of percutaneous access tract was confirmed in 39 out of 40 patients by CT. Seven patients showed decreased haemoglobin and haematocrit levels. Other complications included mild pain at the site of embolization and mild fever, which resolved after conservative management. 16 patients died during the follow-up period owing to progression of the underlying disease. CONCLUSION: Embolization of percutaneous transhepatic portal vein access tract with N-BCA is feasible and technically safe. With the appropriate technique, N-BCA can be safely used as an alternate embolic material since it is easy to use and inexpensive compared with other embolic materials. ADVANCES IN KNOWLEDGE: This is the first study to investigate the efficacy of N-BCA for percutaneous transhepatic portal venous access tract embolization.

Association of a microRNA-323b polymorphism with the persistence of hepatitis B virus infection by the enhancement of viral replication.

Recent studies have shown that some mammalian microRNAs (miRNAs) play a role in antiviral defence. However, little is known about the role of miRNA-323b in hepatitis B virus (HBV)-host interaction. We explored whether single nucleotide polymorphism (SNP) of miRNA-323b affects HBV replication in a Korean HBV cohort. Genotyping was performed in a total of 1439 subjects composed of 404 spontaneously recovered (SR) subjects as normal controls and 1035 chronic carriers (CC) of HBV who were further classified into 313 patients with chronic hepatitis, 305 patients with liver cirrhosis and 417 patients with hepatocellular carcinoma. To confirm the effect of SNP of miRNA-323b on HBV replication in vitro, HepAD38 cells were transfected with miRNA-323b wild type or miRNA-323b SNP plasmid vectors, and HBV replication was induced for 5 days. HBV DNA was isolated and quantified using real-time PCR. The polymorphism rs56103835C>T in the pre-miRNA region of miRNA-323b revealed significant minor allele frequency (0.273). rs56103835C>T SNP showed significantly affect persistence of HBV in CC group compared with SR group (OR = 1.29, P = 0.009 in a codominant model; OR = 1.29, P = 0.03 in a dominant model; and OR = 1.78, P = 0.03 in a recessive model). In vitro, the total intracellular HBV DNA content was significantly reduced by miRNA-323b wild-type plasmid vector transfection (P = 0.014). The polymorphism of miRNA-323b was significantly associated with persistence of HBV by the enhancement of HBV replication (P = 0.021). Our findings provide a novel perspective on the role SNP of miRNAs in host-virus interactions in HBV infection.

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients.

OBJECTIVES: The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin. METHODS: A total of 76 patients admitted between January 2005 and February 2011 were included in the study. Serum vancomycin trough concentration data were collected from the microbiology records. The clinical response was evaluated on the basis of clinical notes and culture test results. RESULTS: A total of 262 appropriate trough concentration data were included, with a median of 3 trough concentrations per patient. Fifty-four patients responded to vancomycin therapy. The initial trough concentration did not differ between responders and non-responders (p=0.135) but the corrected trough concentration was higher among responders than among non-responders (11.64±1.50 mg/l and 9.25±1.59 mg/l, respectively; p=0.036). The average total daily dose of vancomycin was significantly higher among the responders (p=0.008). CONCLUSION: In this critically ill population, a vancomycin dose of 15 mg/kg/day was found sufficient to produce optimal trough concentrations to eradicate the MRSA infection. This study demonstrated the significant relationship between response to treatment of MRSA infection and serum vancomycin trough concentrations.

International retrieval of adults on extracorporeal membrane oxygenation support.

A retrieval service was established in New South Wales to provide mobile extracorporeal membrane oxygenation support to patients with severe, acute cardiac or respiratory failure. This service has also retrieved four adult patients from Nouméa, New Caledonia to Sydney on extracorporeal membrane oxygenation support, which are the first international retrievals of this type from Australia. We discuss our experience with these patients, three of whom survived to hospital discharge. However, one patient referred from New Caledonia died before extracorporeal membrane oxygenation could be established.

Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis B.

BACKGROUND: Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan. AIM: To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB). METHODS: One hundred and ninety-nine patients were enrolled. Only procedures yielding > or =10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens <15 mm were considered ineligible. RESULTS: The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.'s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0-2 vs. F3-4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005-1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213-0.949 respectively) with Marcellin et al.'s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131-0.685) with Chan's cutoffs. CONCLUSIONS: Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0-2) was the only factor to predict significant discordance between LB and LSM.

Low efficacy of entecavir therapy in adefovir-refractory hepatitis B patients with prior lamivudine resistance.

We determined the virologic response, incidence of entecavir resistance, and evolution of lamivudine and adefovir-resistant mutants during entecavir (ETV) therapy in adefovir-refractory patients with prior lamivudine resistance. Forty adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance who had received entecavir for > or = 6 months were included and monitored for virologic response and entecavir resistance. Ten per cent of patients achieved HBV DNA < 50 copies/mL by PCR after 24 weeks of ETV therapy, and an initial virologic response was observed in 12 of 40 patients (30%). Higher pretreatment ALT (P = 0.039) and the presence of the rtL180M mutation (P = 0.038) were associated with an initial virologic response. During a mean follow-up of 11.4 months, four patients (10%) experienced virologic breakthrough, while ETV-resistant mutants were detected in six patients (15%). YMDD and adefovir-resistant mutants were detected in 57 and 35% of patients at baseline, respectively. At 48 weeks of therapy, 96 and 4% of patients had YMDD and adefovir-resistant mutants, respectively. These data suggest an early development of ETV resistance and low antiviral response during ETV therapy in adefovir-refractory patients with prior lamivudine resistance.

Late onset Rasmussen's encephalitis with triple pathology.

Rasmussen's encephalitis is a devastating illness characterized by intractable focal seizures due to chronic localised encephalitis. We report on a rare variant of delayed onset Rasmussen's encephalitis with triple pathology. A 27-year-old male, who was initially diagnosed with seizures when he was 16 years old, presented with focal seizures that became refractory to multiple anticonvulsants. Multiple investigations, including subdural electrode monitoring, revealed foci of onset in the right frontotemporal region. The patient underwent right front-temporal lobectomy. Post-operatively, the seizures became more severe and he developed new epilepsia partialis continua. Treatment with intravenous immunoglobulin was unsuccessful. He subsequently underwent a right hemispherectomy that rendered him seizure free. The three pathologies identified were old ischemic changes, type II cortical dysplasia and stage II Rasmussen's encephalitis.

Knowledge, attitude and vaccination status of varicella among students of Universiti Kebangsaan Malaysia (UKM).

UNLABELLED: Varicella is a highly infectious disease that can lead to severe complications such as pneumonia, encephalitis and death. Vaccination is the best method to prevent the disease. The objective of this study was to assess the level of knowledge, attitude and vaccination status of varicella among UKM students. A cross sectional study involving pre-tested questionnaires was undertaken between February and April, 2005. Questionnaires were distributed and filled by the first and second year students from four faculties in UKM (n = 879). The faculties included were divided into two categories: medical fields and non-medical fields. The results showed that the overall level of knowledge on varicella among respondents was intermediate. The score of knowledge was significantly higher among medical students (t = 10.9, p < 0.05) compared to non-medical students. The varicella vaccination coverage was low among UKM students (19.3%). The vaccination status was significantly higher among medical students compared to non-medical students (chi2 = 8.6, p < 0.05). Vaccination status of varicella among respondents had no association with the level of knowledge (chi2 = 2.42, p > 0.05). IN CONCLUSION: the awareness and vaccination status of varicella among UKM students were low. More varicella awareness programs should be held on universities' campuses to educate students on methods of prevention of this serious disease.

Knowledge, attitude and vaccination status of varicella among students of Universiti Kebangsaan Malaysia (UKM).

UNLABELLED: Varicella is a highly infectious disease that can lead to severe complications such as pneumonia, encephalitis and death. Vaccination is the best method to prevent the disease. The objective of this study was to assess the level of knowledge, attitude and vaccination status of varicella among UKM students. A cross sectional study involving pre-tested questionnaires was undertaken between February and April, 2005. Questionnaires were distributed and filled by the first and second year students from four faculties in UKM (n=879). The faculties included were divided into two categories: medical fields and non-medical fields. The results showed that the overall level of knowledge on varicella among respondents was intermediate. The score of knowledge was significantly higher among medical students (t = 10.9, p < 0.05) compared to non-medical students. The varicella vaccination coverage was low among UKM students (19.3%). The vaccination status was significantly higher among medical students compared to non-medical students (chi2 = 8.6, p < 0.05). Vaccination status of varicella among respondents had no association with the level of knowledge (chi2 = 2.42, p > 0.05). IN CONCLUSION: the awareness and vaccination status of varicella among UKM students were low. More varicella awareness programs should be held on universities' campuses to educate students on methods of prevention of this serious disease.

Genetic association between functional haplotype of collagen type III alpha 1 and chronic hepatitis B and cirrhosis in Koreans.

Collagen type III alpha 1 (COL3A1) is one of the extracelluar matrix (ECM) proteins. The expression of COL3A1 is closely related to chronic liver diseases. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of COL3A1 confer genetic susceptibility to patients with hepatitis B virus-infected liver diseases including chronic hepatitis B (CH), liver cirrhosis (CIR), and hepatocellular carcinoma (HCC). A total of 399 Korean (KOR) people, 111 patients with CH, 95 patients with CIR, 86 patients with HCC, and 107 spontaneously recovery, were genotyped for 16 SNPs of the COL3A1 gene. The 'A' allele of rs3106796 was highly associated with the CH [odds ratio (OR) = 1.62, P = 0.01], CIR (OR = 1.67, P = 0.01), and HCC (OR = 1.59, P = 0.03). There were six polymorphic SNPs that could be divided into two linkage disequilibrium (LD) blocks. The haplotype pattern of the KOR control seems to be similar to the patterns displayed in the Japanese, Chinese, and Caucasian populations sampled in the International HapMap project. Haplotype 3 (A-G-A) of the LD block 2 was significantly associated with CH (OR = 2.23, P = 0.02), CIR (OR = 2.24, P = 0.03), and HCC (OR = 2.27, P = 0.03). Moreover, diplotype analysis showed that they had increased relative risk for CH and CIR in the two diplotypes, dt3 (A-G-A/G-G-A; OR = 4.05, P = 0.01) and dt6 (A-A-A/A-G-A; OR = 7.42, P = 0.01 and OR = 5.84, P = 0.05) against dt1 (G-G-A/G-G-A), the most common diplotype in both KOR groups. In vitro reporter gene assays showed that the constructs containing the 'G' allele of rs3106796 appear to exert lower transcriptional activity of COL3A1 than the 'A' allele, depending on the promoter types.

Evaluations of inhibitory effect on the motor cortex by cutaneous pain via application of capsaicin.

To evaluation the effect of experimental tonic cutaneous pain on motor cortex excitability by means of transcranial magnetic stimulation (TMS). Thirty healthy adults (male: 12, female: 18) were tested with TMS. Cutaneous pain was induced by topical application of capsaicin cream (0.025%) on the skin overlying the flexor carpi radialis of dominant limb. And the cream had been under an occlusive dressing for 40 minutes until we removed it. Magnetic stimulation was performed to the contralateral cortex with a circular coil at 80% intensity of maximum stimulator output. MEPs were recorded at flexor carpi radialis (FCR), extensor carpi radialis (ECR) and opponens pollicis (OP) with constant isometric contraction of 10%, 30% maximal voluntary contraction (MVC). Main outcome measures the intensity of pain by visual analog scale (VAS). The latency, amplitude and silent period of motor evoked potentials (MEPs). Values at baseline and 20, 40, 60, 80 minutes from applying capsaicin were compared. VAS score reached the peak value at 40 minutes. Amplitudes of MEPs at FCR progressively decreased up to 40 minutes than returned to nearly baseline value at 80 minutes. The decrease in MEP amplitude at FCR was accompanied by the increase in VAS score significantly and sustained for 20 min after washing out capsaicin cream. At ECR & OP, we could not demonstrate any changes in amplitude with time. Silent period at FCR only was significantly prolonged with the increase in VAS score. The present findings support that noxious cutaneous stimulation inhibit motor cortex excitability by so-called cortico-cortical circuits.