The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin

<p>Abstract</p> <p>Background</p> <p>Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients.</p> <p>Methods</p> <p>Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort.</p> <p>Results</p> <p>The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype.</p> <p>Conclusions</p> <p>IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV.</p

Associations of Lifestyle Factors, Disease History and Awareness with Health-Related Quality of Life in a Thai Population

10.1371/journal.pone.0049921PLoS ONE711

Riparian buffers can help mitigate biodiversity declines in oil palm agriculture

Agricultural expansion is a primary driver of biodiversity decline in forested regions of the tropics. Consequently, it is important to understand the conservation value of remnant forests in production landscapes. In a tropical landscape dominated by oil palm (Elaeis guineensis), we characterized faunal communities across eight taxa occurring within riparian forest buffers, which are legally protected alongside rivers, and compared them to nearby recovering logged forest. Buffer width was the main predictor of species richness and abundance, with widths of 40–100 m on each side of the river supporting broadly equivalent levels of biodiversity as compared to logged forest. However, width responses varied markedly among taxa, and buffers often lacked forest-dependent species. Much wider buffers than are currently mandated are needed to safeguard most species. The largest biodiversity gains are achieved by increasing relatively narrow buffers. To provide optimal conservation outcomes in tropical production landscapes, we encourage policy makers to prescribe width requirements for key taxa and different landscape contexts

New records of Odonata from the Crocker Range National Park, Sabah, Malaysia

We report here the results from two field trips to collect Odonata in the Crocker Range National Park in western Sabah, Borneo, Malaysia. Thirtysix species were collected. Telosticta fugispinosa had not been described at the time of collection, nor had the two Devadatta species. There was no published record of Protosticta species cf kinabaluensis before the 2012 expedition, nor of Drepanosticta species cf crenitis

Predictors of health-related quality of life in patients with chronic liver disease

Background: Patient-reported outcomes such as HRQL have become increasingly important for patients with chronic liver disease (CLD). Aim: To explore the relative impact of different types of liver disease on HRQL as well as predictors of HRQL domains in CLD. Design: Our HRQL databases with Short-Form 36 data (SF-36) as well as clinico-demographic data were used. Scores for each of SF-36 scales (PF - physical functioning, RP - role functioning, BP - bodily pain, GH - general health, VT \u2013 vitality, SF - social functioning, RE - role emotional and MH - mental health, MCS- mental component score, PCS- physical component score) were compared between different types of CLD as well as other variables. SF-36 scales were compared using Wilcoxon tests. Spearman\u2019s rank coefficient was used as a measure of age-HRQL correlations. For all tests and correlation estimations, p-values not exceeding 0.05 after Benjamini-Hochberg correction were considered to be statistically significant. Results: Complete data was available for 1103 CLD patients. Demographic and clinical data included: age 53.7\ub111.8 years, 39% female, 792 (65%) with cirrhosis [357 (45%) Child\u2019s A, 274 (35%) Child\u2019s B and 161 (20%) Child\u2019s C)]. Analysis revealed that age correlated significantly (p&lt;0.05) with worsening HRQL on every scale of the SF-36. Female patients had more HRQL impairments in PF, RP, BP, GH, VT and MH scales of SF-36 (&#916; scale score: 6.6-10.7, p&lt;0.05). Furthermore, cirrhotic patients had more impairment of HRQL in every scale of SF-36 (&#916; scale score: 6.6-43.0, p&lt;0.05). NAFLD patients had more impairment of HRQL. Conclusions: Analysis of this large cohort with CLD suggests a number of important clinico-demographic factors are associated with HRQL impairment. This data contributes to the full understanding of the total impact of CLD on patients and society

Post-Acute SARS-CoV-2 Symptoms are Fewer, Less Intense Over Time in People Treated with Mono-Clonal Antibodies for Acute Infection

Jillian Kallman Price,1 Lynn H Gerber,1,2 Maria Stepanova,1– 3 Leyla de Avila,1 Ali A Weinstein,4 Huong Pham,1 Fatema Nader,1 Mariam Afendy,1 Kathy Terra,3 Patrick Austin,1 Wisna’odom Keo,1 Andrei Racila,1 James Michael Estep,1 Suzannah Gerber,1 Manisha Verma,1 Pegah Golabi,1 Brian P Lam,1– 3 Zobair Younossi1– 3 1Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; 2Inova Medicine, Inova Health System, Falls Church, VA, USA; 3Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA; 4Department of Global and Community Health, George Mason University, Fairfax, VA, USACorrespondence: Jillian Kallman Price, Research Investigator, Outcomes Research, Beatty Liver and Obesity Research Program, Center for Integrated Research, Department of Medicine, Inova Health System, Claude Moore Health Education and Research Building, Inova Fairfax Medical Campus, 3300 Gallows Road, Falls Church, VA, 22042, USA, Tel +1-703-776-3032, Fax +1-703- 776-4386, Email [email protected]: Many with post-acute SARS-CoV-2 (PASC) have persistent symptoms impacting physical and cognitive function, decreased health and health-related life quality. Monoclonal antibody (mAb) treatment was available to acutely infected patients which might improve these outcomes.Purpose: To compare patient perception of PASC symptoms for those receiving bamlanivimab or casirivimab and imdevimab (mAbs) to those not receiving this treatment (non-mAbs). To compare changes between these groups in symptoms, function and quality of life over a 6-month follow-up.Patients and Methods: Consented adults > 28 days post-infection with positive SARS-CoV-2 qPCR or antigen test and SARS-CoV-2 infection between March of 2020 and July of 2022 were enrolled. This prospective, repeated measure observational study reports baseline through 6-month follow-up. Extensive sociodemographic data, detailed medical history, COVID-19 symptom history, and standardized measures of well-being, depression, anxiety, stigma, cognition, symptom assessment, distress, and health status were collected.Results: 323 participants [101 mAb, 221 non-mAb, 52.7± 15.5 years, 47.7% male, body mass index (BMI) 31.4± 8.4] were analyzed. Fewer symptoms at baseline were reported in mAb versus non-mAb participants (1.06± 1.31 vs 1.78± 2.15, respectively p=0.0177) 6 months: (0.911± 1.276 mAb vs.1.75± 2.22 non-mAb, p=0.0427). Both groups showed significant within-group decreases in symptom number (52 to 21 mAb, 126 to 63 non-mAb) and symptom burden (p=0.0088 mAb, p< 0.00001 non-mAb). mAb patients had significantly shorter infection-to-baseline interval (days) (120.4± 55.3 mAb vs 194.0± 89.3 non-mAb, p< 0.00001); less frequent history of myocardial infarction (0.0 vs 3.9%, p=0.0464); headache (2.0% vs.11.8%, p=0.0046), rash (3.1% vs 9.9%, p=0.0377), and miscellaneous muscle complaints (2.0% vs 12.3%, p=0.0035), plus significantly better 6-month mood. (2.2% vs 13.2%, p=0.0390).Conclusion: mAb treated participants had reduced symptom burden and consistently reported fewer symptoms than non-mAb at all time points despite less time since acute illness. Both groups reported a statistically significant decrease in symptoms by 6-month visit with no statistically significant differences between them at follow-up.Keywords: monoclonal antibodies, patient-reported outcomes, symptom burden, recovery, COVID-1

Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients With Nonalcoholic and Alcohol-Related Fatty Liver Disease

Background &amp;amp; Aims: Non-alcoholic and alcohol-related fatty liver disease are overlapping diseases in which metabolic syndrome and alcohol consumption each contribute to progressive liver disease. We aimed to assess the effects of alcohol consumption and metabolic syndrome on mortality in individuals with fatty liver. Methods: We searched the National Health and Nutrition and Examination Survey III for adults (20–74 years old) with hepatic steatosis, detected by ultrasound, for whom mortality and follow-up data were available. We collected data from the alcohol use questionnaire (self-reported number of days a participant drank alcohol; the number of drinks [10 g alcohol] per day on a drinking day; the number of days the participant had 5 or more drinks) and calculated the average amount of alcohol consumption in drinks/day for each participant during the year preceding enrollment. Excessive alcohol consumption for men was &amp;gt;3 drinks/day and for women was &amp;gt;1.5 drinks/day. We also collected clinical data, and mortality data were obtained from the National Death Index. Demographic and clinical parameters were compared among consumption groups using the χ2 test for independence or survey regression models. We used Cox proportional hazard models to identify independent predictors of all-cause and cause-specific mortality. Results: The study cohort included 4264 individuals with hepatic steatosis (mean age, 45.9 years; 51% male; 76% white; 46% with metabolic syndrome; 6.2% with excessive alcohol use). There was no significant difference in mean age between individuals with vs without excessive alcohol consumption (P=.65). However, overall mortality was significantly higher among participants with excessive alcohol consumption (32.2%) vs participants with non-excessive alcohol use (22.2%) after mean 20 years of follow up (P=.003), as well as after 5 years of follow up. In multivariate analysis, the presence of metabolic syndrome (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.12–1.83) and excessive alcohol consumption (aHR, 1.79; 95% CI, 1.21–2.66) were independently associated with an increased risk of death in individuals with hepatic steatosis; any lower average amount of alcohol consumption was not associated with mortality (all P&amp;gt;.60). In a subgroup analysis, the association of excessive alcohol use with mortality was significant in individuals with metabolic syndrome (aHR, 2.46; 95% CI, 1.40–4.32) but not without it (P=.74). Conclusion: In review of data from the National Health and Nutrition and Examination Survey III, we associated alcohol consumption with increased mortality in participants with fatty liver and metabolic syndrome. These findings indicate an overlap between non-alcoholic and alcohol-related fatty liver disease. © 2019 AGA Institut

Riparian buffers can help mitigate biodiversity declines in oil palm agriculture

Agricultural expansion drives biodiversity decline in forested tropical regions. Consequently, it is important to understand the conservation value of remnant forest in production landscapes. In a tropical landscape dominated by oil palm we characterized faunal communities across eight taxa occurring within riparian forest buffers, which are legally protected alongside rivers, and compared them to nearby recovering logged forest. Buffer width was the main predictor of species richness and abundance, with widths of 40-100 m on each side of the river supporting broadly equivalent levels of biodiversity to logged forest. However, width responses varied markedly among taxa, and buffers often lacked forest-dependent species. Much wider buffers than are currently mandated are needed to safeguard most species. The largest biodiversity gains are achieved by increasing relatively narrow buffers. To provide optimal conservation outcomes in tropical production landscapes we encourage policymakers to prescribe width requirements for key taxa and different landscape contexts.Newton-Ungku Omar Fund (grants 216433953, 537134717) – delivered by the British Council and funded by the UK Department for Business, Energy and Industrial Strategy and the Malaysian Industry-Government Group for High Technology – as well as the UK Natural Environment Research Council (NE/K016407/1, NE/K016261/1; https://lombok.nerc-hmtf.info/). MJS was supported by a Research Leadership Award from the Leverhulme Trust