Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Development and validation of a predictive tool for adverse drug reactions in neonates under intensive care.

AIMS: Neonates hospitalized in neonatal intensive care units (NICUs) commonly experience adverse drug reactions (ADRs). Thus, we aimed to develop and validate a tool for predicting ADRs in neonates hospitalized in NICUs. METHODS: A nested case-control study in an open cohort with neonates admitted to the NICU of a maternity hospital in Natal, Brazil was conducted from January 2019 to January 2022 [Correction added on 4 December 2023, after first online publication: 2023 has been changed to 2019 in the preceding sentence.]. Neonates with ADR were randomly paired with 2 controls. For the development of the tool, a multivariate logistic regression was applied on 2/3 of the sample (cases with respective controls). The model's fit was evaluated using the Hosmer-Lemeshow test for calibration and the Brier score for performance assessment. Validation of the tool was performed by determining the area under the receiver operating characteristic curve with bootstrap adjusted c-statistics. RESULTS: In all, 450 neonates (150 cases and 300 controls) were included in the study. We identified 5 independent risk factors for ADR, 4 related to the neonate (current mechanical ventilation, heart rate ≥178 beats/min, intravenous medications, ≥5 prescription medications) and 1 to the mother (gestational hypertension). The tool had a classification cut-off point of ≥15, and its total score ranged from 0 to 34. In validation, the tool had an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI] 0.66-0.81) with sensitivity of 52.02% (95% CI 47.40-56.64) and specificity of 81.35% (95% CI 77.75-84.95). CONCLUSION: The tool demonstrated adequate discriminative ability and utilized 5 commonly monitored variables in the NICU.

Gut-related molecules as potential biomarkers in patients with decompensated cirrhosis.

INTRODUCTION AND OBJECTIVES: Microbial translocation contributes to cirrhosis progression and complications. This study aims to investigate whether molecules related to intestinal permeability or microbial translocation can serve as prognostic biomarkers in patients with decompensated cirrhosis. MATERIALS AND METHODS: We prospectively evaluated hospitalized patients with decompensated cirrhosis for liver function, complications during hospitalization, in-hospital mortality, composite outcomes of in-hospital mortality and complications, 12-month mortality, and survival rates. Blood samples were collected upon admission, and 1,3 beta-d-glucan, zonulin, calprotectin, and lipopolysaccharide-binding protein were measured using commercial kits. RESULTS: Ninety-one patients with decompensated cirrhosis were enrolled. The mean age was 58 ±â€¯12 years; 57% were male. The three main cirrhosis etiologies were hepatitis C (35%), alcohol (25%), and non-alcoholic steatohepatitis (17%). In terms of liver function, 52% were Child C, and 68% had model for end-stage liver disease ≥15. The in-hospital and one-year mortality rates were 31% and 57%, respectively. Child-Pugh, 1,3 beta-glucan, and model for end-stage liver disease were positively correlated; zonulin was associated with complications during hospitalization (acute kidney injury) and composite outcomes, and calprotectin was associated with all outcomes except 12-month mortality. CONCLUSIONS: Serum calprotectin and zonulin levels emerge as noninvasive prognostic biomarkers for potentially unfavorable outcomes in patients with decompensated cirrhosis.

Genome-wide analyses reveal drivers of penguin diversification.

Penguins are the only extant family of flightless diving birds. They currently comprise at least 18 species, distributed from polar to tropical environments in the Southern Hemisphere. The history of their diversification and adaptation to these diverse environments remains controversial. We used 22 new genomes from 18 penguin species to reconstruct the order, timing, and location of their diversification, to track changes in their thermal niches through time, and to test for associated adaptation across the genome. Our results indicate that the penguin crown-group originated during the Miocene in New Zealand and Australia, not in Antarctica as previously thought, and that Aptenodytes is the sister group to all other extant penguin species. We show that lineage diversification in penguins was largely driven by changing climatic conditions and by the opening of the Drake Passage and associated intensification of the Antarctic Circumpolar Current (ACC). Penguin species have introgressed throughout much of their evolutionary history, following the direction of the ACC, which might have promoted dispersal and admixture. Changes in thermal niches were accompanied by adaptations in genes that govern thermoregulation and oxygen metabolism. Estimates of ancestral effective population sizes (Ne ) confirm that penguins are sensitive to climate shifts, as represented by three different demographic trajectories in deeper time, the most common (in 11 of 18 penguin species) being an increased Ne between 40 and 70 kya, followed by a precipitous decline during the Last Glacial Maximum. The latter effect is most likely a consequence of the overall decline in marine productivity following the last glaciation.

Selection-driven adaptation to the extreme Antarctic environment in the Emperor penguin.

The eco-evolutionary history of penguins is characterised by shifting from temperate to cold environments. Breeding in Antarctica, the Emperor penguin appears as an extreme outcome of this process, with unique features related to insulation, heat production and energy management. However, whether this species actually diverged from a less cold-adapted ancestor, more ecologically similar to its sister species, the King penguin, is still an open question. As the Antarctic colonisation likely resulted in vast changes in selective pressure experienced by the Emperor penguin, the relative quantification of the genomic signatures of selection, unique to each sister species, could answer this question. Applying phylogeny-based selection tests on 7651 orthologous genes, we identified a more pervasive selection shift in the Emperor penguin than in the King penguin, supporting the hypothesis that its extreme cold adaptation is a derived state. Furthermore, among candidate genes under selection, four (TRPM8, LEPR, CRB1, and SFI1) were identified before in other cold-adapted homeotherms, like the woolly Mammoth, while other 161 genes can be assigned to biological functions relevant to cold adaptation identified in previous studies. Location and structural effects of TRPM8 substitutions in Emperor and King penguin lineages support their functional role with putative divergent effects on thermal adaptation. We conclude that extreme cold adaptation in the Emperor penguin largely involved unique genetic options which, however, affect metabolic and physiological traits common to other cold-adapted homeotherms.

CLIF-C AD Score Predicts Development of Acute Decompensations and Survival in Hospitalized Cirrhotic Patients.

BACKGROUND AND AIMS: Patients with decompensated cirrhosis are at increased risk of mortality, even in absence of ACLF. The CLIF-C AD score (CLIF-C ADs) was proposed as a prognostic score but lacks sufficient validation. Our aim was to describe clinical characteristics and hospital evolution according to score groups and evaluate prognostic capability of CLIF-C ADs alone or in combination with other scores. METHODS: Two hundred and sixty-six patients (55 ± 14 years, ascites in 63%, MELD 14 ± 5) were included, and classified as high, intermediate and low CLIF-C ADs in 13, 60 and 27% of cases. Development of new complications of cirrhosis during hospitalization and survival at 3 months were evaluated. RESULTS: Patients with high CLIF-C ADs had more severe systemic inflammation parameters and higher frequency of organ dysfunction. CLIF-C ADs ≥ 60, when compared to intermediate and low groups, was associated with higher incidence of complications of cirrhosis (90% vs 70% and 49%, p < 0.001) and lower survival (93%, 80% and 50%, p < 0.0001). In multivariate analysis, CLIF-C ADs, ascites and MELD were predictors of survival [(AUROC 0.76 (95% CI 0.69-0.83)]. Absence of ascites or MELD < 14 identified patients with intermediate CLIF-C ADs and good survival (89 and 84%, respectively). CONCLUSION: CLIF-C ADs predicts survival in cirrhotic patients with AD. High CLIF-C ADs is associated with higher frequency of organ dysfunction, increased risk of new complications of cirrhosis and high short-term mortality. On the contrary, individuals with low CLIF-C ADs, as well as those with intermediate score without ascites or with low MELD have excellent prognoses.

Somatic Copy Number Alterations and Associated Genes in Clear-Cell Renal-Cell Carcinoma in Brazilian Patients.

Somatic copy number aberrations (CNAs) have been associated with clear-cell renal carcinoma (ccRCC) pathogenesis and are a potential source of new diagnostic, prognostic and therapeutic biomarkers. Recurrent CNAs include loss of chromosome arms 3p, 14q, 9p, and gains of 5q and 8q. Some of these regional CNAs are suspected of altering gene expression and could influence clinical outcomes. Despite many studies of CNAs in RCC, there are currently no descriptions of genomic copy number alterations in a Brazilian ccRCC cohort. This study was designed to evaluate the chromosomal profile of CNAs in Brazilian ccRCC tumors and explore clinical associations. A total of 92 ccRCC Brazilian patients that underwent nephrectomy at Barretos Cancer Hospital were analyzed for CNAs by array comparative genomic hybridization. Most patients in the cohort had early-stage localized disease. The most significant alterations were loss of 3p (87.3%), 14q (35.8%), 6q (29.3%), 9p (28.6%) and 10q (25.0%), and gains of 5q (59.7%), 7p (29.3%) and 16q (20.6%). Bioinformatics analysis revealed 19 genes mapping to CNA significant regions, including SETD2, BAP1, FLT4, PTEN, FGFR4 and NSD1. Moreover, gain of 5q34-q35.3 (FLT4 and NSD1) and loss of 6q23.2-q23.3 (MYB) and 9p21.3 (MLLT3) had gene expression levels that correlated with TCGA data and was also associated with advanced disease features, such as larger tumors, Fuhrman 3, metastasis at diagnosis and death. The loss of region 14q22.1 which encompasses the NIN gene was associated with poor overall survival. Overall, this study provides the first CNA landscape of Brazilian patients and pinpoints genomic regions and specific genes worthy of more detailed investigations. Our results highlight important genes that are associated with copy number changes involving large chromosomal regions that are potentially related to ccRCC tumorigenesis and disease biology for future clinical investigations.

Effectiveness of direct-acting agents for chronic hepatitis C treatment in South America: A systematic review and meta-analysis.

The effectiveness of direct-acting agents (DAAs) for hepatitis C treatment in limited-resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12-week sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention-to-treat (ITT) and per-protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random-effects model (DerSimonian-Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co-infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7393 individuals from five countries [Brazil (n = 11), Argentina (n = 4), Chile (n = 1), Colombia (n = 1) and Peru (n = 1)] and two South-American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2-94.7] and 95.5% [94.3-96.6] by ITT (11 studies; n = 4,153; I2  = 84.2%) and per-protocol analysis (15 studies; n = 4,833; I2  = 64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co-infection [4 studies; RR = 1.03 (0.99-1.07)] and those naive compared with treatment experimented-individuals [9 studies; RR = 1.01 (1.00-1.03)], but significantly higher in patients without cirrhosis compared with those with cirrhosis [11 studies; RR = 1.04 (1.02-1.05), P < .001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited-resource settings to decrease the burden of liver disease in HCV-infected patients. PROSPERO[CRD 42019134603].

Games Applied to Children with Motor Impairment using the Myo Wearable Device.

The characteristic of immersion, involvement and motivation have made serious games an important tool to be used in the medical field. However, there are people that, having some sort of physical disability, are not able to, or do not feel motivated to play. This work presents a strategy to support human- computer interactions for children with a disability in their upper limbs through a wearable device, with the objective of improving access to digital games for the target audience. For the development of this work, the wearable device Myo was used to control a puzzle game as a means of providing the interaction between the individual and the game. In this context, the game is controlled with the movement of the user's upper limb that presents the disability, through the Myo device. For the validation of this research, the game developed was made available for individuals presenting a disability in the upper limbs, from an age range between five and fifteen years old, of the Association of Assistance to the Disabled Child (AACD). Soon, it was noticed that the participants of the research soon could play while utilizing the deficient limb with Myo's support and felt more motivated to play. On the long run, it is expected to contribute to the motivation of patients through technological innovation, so that the process of body consciousness is made more interactive.

Congenital Syphilis as a Measure of Maternal and Child Healthcare, Brazil.

Syphilis is a sexually transmitted infection that has direct adverse effects on maternal and infant health through vertical Treponema pallidum transmission during early pregnancy. We evaluated congenital syphilis as a predictor of the quality of basic maternal and child healthcare in Brazil during 2010-2015. We investigated case rates and correlations with epidemiologic and socioeconomic indicators. We observed rising congenital syphilis incidence rates and increasing syphilis-associated perinatal and infant mortality rates in all regions. Case rates were highest in the Northeast, Southeast, and South, and congenital syphilis infant mortality rates were highest in the Northeast and Southeast. We observed correlations between congenital syphilis rates and infant death, spontaneous abortion (miscarriage), and stillbirth rates. We also noted correlations between rates of stillbirth caused by syphilis and inadequate prenatal care. Our study suggests gaps in basic healthcare for pregnant women and indicates the urgent need for measures to increase early diagnosis and appropriate treatment.

Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response.

BACKGROUND AND AIM: Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS: This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS: Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION: DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.

Prevalence and profile of adverse drug reactions in high-risk pregnancy: a cohort study.

BACKGROUND: Commonly used drugs in pregnant women include antihypertensives, hypoglycemic agents, analgesics, antimicrobials, antiemetics and antispasmodics but the use of medicines during pregnancy, especially in high-risk pregnancy, may be associated with high risk of adverse drug reactions (ADR). The objective of this study was to determine the risk of an adverse drug reaction in hospitalized high-risk pregnant women and the factors associated with their occurrence. METHODS: The study received IRB approval and all patients gave written informed consent. Observational cohort study conducted from September 2015 to November 2016 in 1070 pregnant women consecutively admitted to the high risk sector of the University Maternity Januário Cicco in Brazil. ADR were detected through daily active search. Risk factors for the occurrence of ADR were determined using multivariate logistic regression. RESULTS: The mean age of the study population was 26.2 ± 7.2 years and gestational age was 31.2 ± 7.2 weeks. The average number of previous pregnancies was 2.4 ± 1.8 and 46.4% reported cases of previous abortion/miscarriage. ADR were observed in 10.7% of women. The main medicines involved, with the incidence rate of ADR per 100 prescriptions of the drug (IR), were parenteral scopolamine (IR 14.9%), methyldopa (IR 15.9%), insulin (IR 8.46%), oral scopolamine (IR 3.58%), captopril (IR 2.38%) and ceftriaxone (IR 18.4%). Multivariate analysis showed that only gestational age in weeks (odds-ratio 0.97, 95% confidence interval 0.95-0.98) was related to the occurrence of adverse reactions. CONCLUSION: Lower gestational age is a risk factor for high-risk pregnant women, increasing the likelihood of adverse reactions, with parenteral medications being those that have the highest potential risk of harm.

Mapping Study on the Use of Digital Games for Persons with Disabilities in Upper Members.

Digital games are no longer seen as a form of entertainment detrimental to health. They have become an important tool to improve the treatment of patients, ranging from those who are experiencing a serious illness, such as cancer, to those requiring milder procedures such as physiotherapy. However, there are people who are physically disabled and have difficulty playing digital games. In this line of reasoning, this work presents a systematic review on the use of digital games for people with physical disabilities in the upper limbs. The sources of research were the following indexed databases: IEEE Xplore, Portal of Periodicals of the Coordination of Improvement of Personnel of Higher Level (CAPES), PubMed, Scielo, Science Direct, Scopus and Web of Science. It should be noted that the application of Systematic Mapping in the elaboration of a bibliographical review allowed to identify the main gaps for the development of new research, and to redirect to the main publications related to the study. Finally, the results shows that it is an area that is constantly expanding.

Treatment of slaughterhouse wastewater by acid precipitation (H2SO4, HCl and HNO3) and oxidation (Ca(ClO)2, H2O2 and CaO2).

The treatment of slaughterhouse wastewater was investigated by both acid precipitations and by oxidation processes. Precipitation tests were developed using three acids (H2SO4, HCl and HNO3) at different operating pH (1-6). A decrease of the precipitation pH led to an increase of the conductivity values of the supernatant. Precipitation processes allowed the removal of chemical oxygen demand (COD) (41-97%), turbidity (56-99%) and total phosphorus (27-56%). Total phenols were removed (15-96%) from pH ≥ 2, depending on the precipitation process. Generally, precipitation processes decreased the hydroxide and bicarbonates species. Additionally, three different oxidation processes were tested at different concentrations (1-15 g L-1): Ca(ClO)2, H2O2 and CaO2. When Ca(ClO)2 and CaO2 were applied, an increase of the supernatant conductivity was achieved. COD removal ≥71% and turbidity elimination in the range of 85-100% were achieved by using oxidation processes. CaO2 was very effective to remove total phosphorus (81-96%). The increase of the oxidant concentration in H2O2 and Ca(ClO)2 oxidation processes led to a decrease in the removal of total phenols and bicarbonates species. Optical density of the microorganism cultures was efficiently eliminated (up to 100%) by oxidation processes. In addition, acid precipitation and oxidation allowed to remove total solids (TS), total volatile solids (TVS), total suspended solids (TSS), ammonia nitrogen, nitrates and biochemical oxygen demand (BOD5). Acid precipitation and oxidation produced sludge rich in organic matter and nutrients (Ca, Mg, P, Cl, Na and K). Despite the high removal efficiencies, a post-treatment following the precipitation and oxidation processes can be required.

Assessment of the risk of QT-interval prolongation associated with potential drug-drug interactions in patients admitted to Intensive Care Units.

OBJECTIVES: To evaluate the relationship between drug interactions and QT-interval prolongation in patients admitted to a general intensive care unit (ICU). METHODS: This study was approved by the Institutional Review Board and written informed consent was obtained from all patients. From May 2015 to July 2016, all patients over 18 years-old admitted to the ICU for more than 24 h and in whom the QT-interval on the ECG could be read were prospectively included in this observational, cross-sectional study. All medications administered in the 24 h prior to admission were recorded and the QT-interval was measured upon ICU admission and corrected with Bazzet's formula (QTc). Drug-drug interactions involving drugs potentially associated with QTc prolongation (DDIQT) were searched and QTc increase associated with pharmacokinetic (PK-DDIQT) and pharmacodynamic (PD-DDIQT) interactions was assessed with multiple regression adjusted by patient varibles. RESULTS: The study population consisted of 283 patients, 54.4% males, mean age 57.6 ±â€¯16.7 years-old. Forty five (15.9%) patients presented 65 DDIQT with predominance of pharmacodynamic (66.1%). The risk of DDIQT prescription increased with lower systolic blood pressure, in hypokalemia, in non-diabetics and with the number of medications. PK-DDIQT alone did not affect the QTc interval (7.75 ms, 95%CI: -22.4 to 37.9 ms, p = 0.61), but PD-DDIQT increased QTc by 28.4 ms (95%CI: 9.67 to 47.4 ms, p = 0.003). Most PD-DDIQT involved metoclopramide with ondansetron or amiodarone, and ondansetron with ciprofloxacin. CONCLUSIONS: In patients exposed to drugs associated with prolonged QTc in the 24 h prior to ICU admission, pharmacodynamic DDIQT are associated with increased risk of QTc prolongation.

Reliability and safety of transnasal compared to conventional endoscopy for detecting oesophageal varices in cirrhotic patients.

BACKGROUND & AIMS: Unsedated transnasal endoscopy may be used for detecting oesophageal varices. However, few studies evaluated feasibility and accuracy of this technique. We aimed to evaluate accuracy, interobserver agreement and safety of the transnasal ultrathin compared to conventional endoscopy in patients with cirrhosis. METHODS: This cross-sectional study included consecutive patients referred for screening or surveillance of oesophageal varices. Patients underwent unsedated transnasal and sedated conventional endoscopies at the same day, which were recorded in a digital video file and randomly analysed by two double-blinded endoscopists. High-risk varices were defined by the presence of large calibre or red wale marks. Accuracy, interobserver agreement and safety of transnasal were compared to conventional endoscopy. RESULTS: One hundred and thirty-three cirrhotic patients (48% male, aged of 60 ± 5, 34% Child-Pugh B/C and 71% of cases for variceal screening) were included in the study. The prevalence of oesophageal varices and high-risk oesophageal varices were 59% (n = 79) and 29% (n = 39) respectively. For the presence of oesophageal varices, transnasal GIE yielded sensitivity of 94% [95% Confidence Interval, CI 88-99], specificity of 89% [81-97] as well as positive and negative predictive value of 93% and 91% respectively. A satisfactory interobserver agreement was observed for the presence of oesophageal varices (κ = 0.89) and high-risk varices (κ = 0.65). No serious adverse events were recorded; transnasal GIE was safe and significantly associated with lower rates of hypoxaemia (P < .0001) and hypotension (P < .0001) compared to conventional endoscopy. CONCLUSIONS: Unsedated transnasal endoscopy was safe and had an excellent accuracy and high interobserver agreement for detecting oesophageal varices and for identifying high-risk varices in cirrhotic patients.

Healing effect of Dillenia indica fruit extracts standardized to betulinic acid on ultraviolet radiation-induced psoriasis-like wounds in rats.

CONTEXT: Dillenia indica Linn. (Dilleniaceae) is traditionally used to treat skin inflammation. OBJECTIVE: This study evaluated the healing effect of Dillenia indica fruit extracts on induced psoriasis-like wounds in Wistar rats. MATERIALS AND METHODS: Extracts were standardized to betulinic acid, including an aqueous ethanolic extract (AEE), ethyl acetate extract (EAE) and petroleum ether extract. Effects against lipid peroxidation were assessed in vitro. Wounds were created at rat tails (n = 12). Topical treatments were applied once daily for 7 days (1 mL of AEE or EAE at 5 or 50 mg/mL). Maximal dose was defined by the extract solubility. A 10-fold lower dose was also tested. Positive and negative controls were treated with clobetasol (0.5 mg/mL) or excipient. Half of each group was euthanized for histology. The remaining animals were observed for 20 days for wound measurements. RESULTS: Yields of AEE and EAE were 4.3 and 0.7%, respectively. Betulinic acid concentrations in AEE and EAE were 4.6 and 107.6 mg/g. Extracts neutralized lipid peroxidation in vitro at 0.02 µg/mL, accelerating healing at 50 mg/mL. Complete healing in mice treated with AEE occurred 16 days after wound induction. This time was 14 and 12 days in mice treated with EAE and clobetasol. Compared to orthokeratosis, parakeratosis was reduced by AEE (25%), EAE (45%) and clobetasol (55%). EAE caused superior protection against biomolecules oxidation of skin compared to AEE. DISCUSSION AND CONCLUSION: EAE exhibited activity closer to that of clobetasol. Betulinic acid may be an active constituent, which should be assessed in future studies.

Interobserver variability in transient elastography analysis of patients with chronic hepatitis C.

BACKGROUND & AIMS: Transient elastography based on liver stiffness measurement is a non-invasive method to assess hepatic fibrosis. However, interobserver variability has led to controversy over its use in fibrosis evaluation. To evaluate the interobserver variation in transient elastography in chronic hepatitis C. METHODS: We performed a cross-sectional study, analysing findings from two experienced operators who each assessed 195 patients by transient elastography on the same day. Liver stiffness measurement used to define fibrosis stages, based on METAVIR score, was: <7.1 as F0F1, 7.1-9.4 as F2, 9.5-12.4, as F3 and >12.4 kPa as F4. We also assessed interobserver variation in identification of potential oesophageal varices screening based on transient elastography. RESULTS: The interobserver intraclass correlation coefficient was 0.940 (95% CI 0.863-0.967) and measurements made by operators correlated [Spearman's ρ = 0.924; P < 0.001]. However, the median liver stiffness measurement assessed by first operators was higher (11.5 vs 9.8 kPa; P < 0.001). The discordance between operators was 35% for at least one stage of fibrosis and 5% for two or more stages. Interobserver reliability values were κ = 0.61 for fibrosis stages F ≥ 2 and κ = 0.80 for cirrhosis. Among the 74 patients determined to have cirrhosis by at least one operator, there was considerable discordance in identification of those with indication for oesophageal varices screening (κ values from 0.13 to 0.61) according to several cut-offs. CONCLUSION: Although a high correlation of liver stiffness measurement between operators, interobserver variability in transient elastography was not negligible. This method should not be used as the only screening tool for oesophageal varices in chronic hepatitis C.