A Comprehensive Approach to Parkinson's Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects.

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by a slow progression and varied symptoms. It is the second most common neurodegenerative disease, affecting over six million people in the world. Its multifactorial etiology includes environmental, genomic, and epigenetic factors. Clinical symptoms consist of non-motor and motor symptoms, with motor symptoms being the classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, and surgical interventions. Traditional pharmacological treatment consists of administering drugs (MAOIs, DA, and levodopa), while emerging evidence explores the potential of antidiabetic agents for neuroprotection and gene therapy for attenuating parkinsonian symptoms. Non-pharmacological treatments, such as exercise, a calcium-rich diet, and adequate vitamin D supplementation, aim to slow disease progression and prevent complications. For those patients who have medically induced side effects and/or refractory symptoms, surgery is a therapeutic option. Deep brain stimulation is the primary surgical option, associated with motor symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump succeeded in reducing "off" time, where non-motor and motor symptoms occur, and increasing "on" time. This article aims to address the general aspects of PD and to provide a comparative comprehensive review of the conventional and the latest therapeutic advancements and emerging treatments for PD. Nevertheless, further studies are required to optimize treatment and provide suitable alternatives.

Effects of the Irrigation Needle Design on Root Canal Disinfection and Cleaning.

INTRODUCTION: This ex vivo study evaluated the disinfecting and cleaning effects of root canal preparation using sodium hypochlorite irrigation with 3 different needle designs. METHODS: Mesial roots from extracted mandibular molars with Vertucci class II configuration were anatomically matched based on micro-computed tomography (micro-CT) analyses and distributed into 3 groups (n = 18/group). The canals were contaminated with a mixed bacterial culture for 30 days and then subjected to preparation using 2.5% sodium hypochlorite irrigation with open-ended flat needle (3 mm short of the working length - WL), closed-ended side-vented irrigation needle (1 mm short of the WL), or a closed-ended plastic needle with 2 lateral outlets (TruNatomy) (1 mm short of the WL). Bacteriological samples were taken from the canals before (S1) and after preparation (S2). After another micro-CT scan, the roots were sectioned and samples were also taken from the apical canal segment (S3). Bacterial reduction was assessed by quantitative real-time polymerase chain reaction. The amount of accumulated hard tissue debris was evaluated by micro-CT. RESULTS: A substantial reduction in bacterial counts was observed in all 3 groups when comparing S1 with S2 (99.95%, 98.93%, and 98.90% in the open-ended, closed-ended, and TruNatomy needle groups, respectively) (P < .01). No significant differences were observed between groups for bacterial reduction in the full and apical canal (P > .05). There were no intergroup differences in the amount of accumulated hard tissue debris either (P > .05). The open-ended needle group showed significantly more specimens with quantitative real-time polymerase chain reaction negative results for bacteria in S3 than TruNatomy (P < .05). CONCLUSION: When used up to an appropriate insertion depth, the 3 needle types result in similar antibacterial and cleaning performance, provided variables such as needle size and irrigant type, volume and flow rate are controlled. Exclusive analysis of the apical segment, including the isthmus, revealed that the open-ended needle yielded more cases negative for bacteria.

Endometriosis: A Comprehensive Analysis of the Pathophysiology, Treatment, and Nutritional Aspects, and Its Repercussions on the Quality of Life of Patients.

Endometriosis is a chronic proinflammatory pathology characterized by the growth of tissue similar to the endometrium outside the uterus, affecting approximately 5 to 15% of women worldwide. Suffering from endometriosis entails a complex pathophysiological process, significantly impacting the quality of life and reproductive function of affected women; therefore, it must be addressed in a personalized and comprehensive manner, as its management requires a multidisciplinary approach. This article aims to conduct a comprehensive literature review of endometriosis, not only as a pathophysiological condition but also as a significant factor impacting the social, nutritional, and mental well-being of those who experience it. Emphasis is placed on the importance of understanding and assessing the impact of the pathology to provide a better and more comprehensive approach, integrating various alternatives and strategic treatments for the factors involved in its development. The aim is to provide a complete overview of endometriosis, from its pathophysiology to its impact on the quality of life of patients, as well as a review of current treatment options, both pharmacological and alternative, in order to broaden the perspective on the pathology to improve the care of patients with this disease.

Cardiac and Liver Fibrosis Assessed by Multiparametric MRI in Patients with Fontan Circulation.

The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

Is Steatotic Liver Disease Related to Poor Outcome in COVID-19-Hospitalized Patients?

Background: Steatotic liver disease (SLD) has been linked to more exacerbated inflammatory responses in various scenarios. The relationship between SLD and COVID-19 prognosis remains unclear. Our aim was to investigate the impact of SLD on the outcome of COVID-19. Methods: Patients hospitalized with confirmed COVID-19 and who underwent laboratory tests and chest CT scans were included. SLD was assessed by measuring the attenuation coefficient on CT scans. The relationship between SLD, the severity of COVID-19 clinical presentation and in-hospital mortality were assessed. Results: A total of 610 patients were included (mean age 62 ± 16 years, 64% male). The prevalence of SLD was 30%, and the overall in-hospital mortality rate was 19%. Patients with SLD were younger (58 ± 13 vs. 64 ± 16 years, p < 0.001) and had a higher BMI (32 ± 5 vs. 28 ± 4 kg/m2, p = 0.014). Admission AST values were higher in patients with SLD (82 ± 339 vs. 50 ± 37, p = 0.02), while D-dimer (1112 ± 2147 vs. 1959 ± 8509, p = 0.07), C-reactive protein (12 ± 9 vs. 11 ± 8, p = 0.27), ALT (67 ± 163 vs. 47 ± 90, p = 0.11), ALP (83 ± 52 vs. 102 ± 125, p = 0.27), and GGT (123 ± 125 vs. 104 ± 146, p = 0.61) did not significantly differ compared to patients without SLD. No difference was observed regarding lung parenchyma involvement >50% (20% vs. 17%, p = 0.25), hospital length of stay (14 ± 19 vs. 16 ± 23 days, p = 0.20), hemodialysis support (14% vs. 16%, p = 0.57), use of mechanical ventilation (20% vs. 20%, p = 0.96), and in-hospital mortality (17% vs. 20%, p = 0.40) when comparing patients with and without SLD. Conclusions: SLD showed no significant association with morbidity and mortality in patients with COVID-19.

Multiparametric magnetic resonance imaging of the liver and spleen in Gaucher disease.

PURPOSE: To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). METHODS: We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0 T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann-Whitney, Kruskal-Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. RESULTS: Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). CONCLUSION: The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity.

How Cardiac Fibrosis Assessed via T1 Mapping Is Associated with Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Although cardiovascular and NAFLD risk factors overlap, an independent association between these conditions may exist. Hepatic and cardiac fibrosis are important markers of mortality, but the correlation between these markers in patients with NAFLD has not been well studied. Our main objective was to determine the degree of myocardial fibrosis in patients with NAFLD and its correlation with the severity of liver fibrosis. (2) Methods: In this cross-sectional study, patients with NAFLD were allocated to two groups according to the stage of liver fibrosis assessed using MRI: no or mild fibrosis (F0-F1) and significant fibrosis (F2-F4). Framingham risk scores were calculated to evaluate cardiovascular risk factors, and patients underwent multiparametric cardiac and abdominal MRIs. (3) Results: The sample comprised 44 patients (28 with no or mild liver fibrosis and 16 with significant liver fibrosis). The mean age was 57.9 ± 12 years, and 41% were men. Most patients had high cardiac risk factors and carotid disease. Relative to patients with no or mild liver fibrosis, those with significant fibrosis had a higher median calcium score (p = 0.05) and increased myocardial extracellular volume (ECV; p = 0.02). Liver fibrosis correlated with cardiac fibrosis, represented by the ECV (r = 0.49, p < 0.001). The myocardial ECV differentiated patients with and without significant liver fibrosis (AUC = 0.78). (4) Conclusion: This study showed that diffuse myocardial fibrosis is associated with liver fibrosis in patients with NAFLD.

Factors Associated with Disagreement of Fibrosis Stages between 2D-Shear Wave Elastography and Transient Elastography in Chronic Hepatitis B.

INTRODUCTION AND OBJECTIVES: The agreement of elastography techniques in chronic Hepatitis B (CHB) needs evaluation. We aimed to evaluate, in CHB, the agreement between transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE), analyzing the factors related to the disagreement of measures. MATERIALS AND METHODS: CHB patients underwent liver stiffness measures with both TE and 2D-SWE on the same day. For concordance analysis, we defined liver fibrosis as F0/1 vs. F ≥ 2, F0/1-F2 vs. F ≥ 3 and F0/1-F2-F3 vs. F4 for both methods. Logistic regression analysis was used to identify the variables independently associated with the disagreement between methods. RESULTS: A total of 150 patients were enrolled. Liver fibrosis categorization according to TE was: F0-F1 = 73 (50.4%), F ≥ 2 = 40 (27.6%), F ≥ 3 = 21 (14.5%) and F4 = 11 (7.6%), and according to 2D-SWE was: F0/F1 = 113 (77.9%), F ≥ 2 = 32 (22.1%), F≥ 3 = 25 (17.2%) and F4 = 11 (7.6%). It was observed that 20.0% of the sample had steatosis (CAP≥ 275 dB/m). TE and SD-SWE estimated equal fibrosis stages in 79.3% of cases. Spearman's correlation coefficient was 0.71 (p < 0.01). Kappa values for F ≥ 2, F ≥ 3 and F = 4 were: 0.78, p < 0.001; 0.73, p < 0.001; and 0.64, p < 0.001, respectively. Diabetes mellitus (DM) (OR 5.04; 95%CI: 1.89-13.3; p < 0.001) and antiviral treatment (OR 6.79; 95%CI: 2.33-19.83; p < 0.001) were independently associated with discordance between both methods. CONCLUSIONS: In CHB, there is strong correlation and good agreement between TE and 2D-SWE in identifying fibrosis stages. Diabetes mellitus and antiviral therapy may impact the agreement of stiffness measures obtained with these elastographic methods.

Influence of brushing motions on the shaping of oval canals by rotary and reciprocating instruments.

OBJECTIVE: The effects of brushing on shaping with three different instruments were assessed in oval canals. DESIGN: Mandibular incisors were assigned to 6 groups (n = 12/group) according to the system, each one with or without brushing: Reciproc Blue, VDW.Rotate, and Race EVO. Micro-computed tomography was performed before and after preparation. RESULTS: Brushing strokes caused no increase in canal volume, surface area, and structure model index independently of the system (p > 0.05), except for RaCe EVO in the full canal surface area (p < 0.05). Brushing did not increase the prepared areas (p > 0.05), except for Reciproc in the apical canal (p < 0.05). Reciproc with no brushing exhibited less pericervical dentin than with brushing (p < 0.05), while RaCe EVO with brushing resulted in less remaining dentin (p < 0.05). CONCLUSIONS: The brushing motion had no effects on the overall shaping performance of the 3 instruments tested. An exception was the increase in prepared surface area in the apical canal segment when the Reciproc instrument was used with brushing strokes.

Immunization with Neural-Derived Peptides in Neurodegenerative Diseases: A Narrative Review.

Neurodegenerative diseases (NDDs) are a major health problem worldwide. Statistics suggest that in America in 2030 there will be more than 12 million people suffering from a neurodegenerative pathology. Furthermore, the increase in life expectancy enhances the importance of finding new and better therapies for these pathologies. NDDs could be classified into chronic or acute, depending on the time required for the development of clinical symptoms and brain degeneration. Nevertheless, both chronic and acute stages share a common immune and inflammatory pathway in their pathophysiology. Immunization with neural-derived peptides (INDP) is a novel therapy that has been studied during the last decade. By inoculating neural-derived peptides obtained from the central nervous system (CNS), this therapy aims to boost protective autoimmunity, an autoreactive response that leads to a protective phenotype that produces a healing environment and neuroregeneration instead of causing damage. INDP has shown promising findings in studies performed either in vitro, in vivo or even in some pre-clinical trials of different NDDs, standing as a potentially beneficial therapy. In this review, we will describe some of the studies in which the effect of INDP strategies have been explored in different (chronic and acute) neurodegenerative diseases.

Impact of multidrug resistance on the management of bacterial infections in cirrhosis.

Patients with cirrhosis have an increased risk of infection and differently from other complications, that over the years are improving in their outcomes, infections in cirrhotic patients are still a major cause of hospitalization and death (up to 50% in-hospital mortality). Infections by multidrug-resistant organisms (MDRO) have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact. About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years. MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution. An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects, such as the type of infection (spontaneous bacterial peritonitis, pneumonia, urinary tract infection and spontaneous bacteremia), bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition (community acquired, healthcare associated or nosocomial). Furthermore, regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology. Antibiotic treatment is the most effective measure to treat infections caused by MDRO. Therefore, optimizing antibiotic prescribing is critical to effectively treat these infections. Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality. On the other hand, the supply of new agents to treat these infections is very limited. Thus, specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.

Incidence and Risk Factors of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Treated with Direct-Acting Antivirals.

BACKGROUND: Conflicting data regarding the incidence of hepatocellular carcinoma (HCC) after cure of HCV infection with direct-acting antivirals (DAAs) remains. We investigated the incidence and risk factors to HCC after treatment with DAAs followed up for five years. METHODS: A total of 1075 HCV patients ≥ 18 years were treated with DAAs from 2015 to 2019 and followed until 2022. Ultrasonography was performed before DAAs and each 6 months thereafter. RESULTS: Of the total, 51/1075 (4.7%) developed HCC in the median of 40 (IQR 25-58) months: 26/51 (51%) male, median age 60 (IQR 54-66) years, alpha-fetoprotein (AFP) 12.2 (IQR 6.1-18.8) ng/mL, 47/51 (92.1%) cirrhotic 78.7%, 8/51 (15.7%) without sustained virological response (SVR). Seventeen percent had non-characterized nodules before DAAs. Cumulative HCC incidence was 5.9% in 5 years. Overall incidence was 1.46/100 patient-years (PY) (95% CI = 1.09-1.91), being 2.31/100 PY (95% CI = 1.70-3.06), 0.45/100 PY (95% CI = 0.09-1.32) and 0.20/100 PY (95% CI 0.01-1.01) in METAVIR F4, F3 and F2, respectively, and the main risks to HCC were non-characterized nodule, cirrhosis, high AFP values and non-SVR. CONCLUSION: HCV cure reduced risk for HCC, but it still occurred particularly in cirrhotic patients. Some risk factors can be identified to predict early HCC diagnosis.

Relative enhancement index can be used to quantify liver function in cirrhotic patients that undergo gadoxetic acid-enhanced MRI.

OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.

Unwrapping broken tails: Biological and environmental correlates of predation pressure in limbless reptiles.

Studying species interactions in nature often requires elaborated logistics and intense fieldwork. The difficulties in such task might hinder our ability to answer questions on how biotic interactions change with the environment. Fortunately, a workaround to this problem lies within scientific collections. For some animals, the inspection of preserved specimens can reveal the scars of past antagonistic encounters, such as predation attempts. A common defensive behaviour that leaves scars on animals is autotomy, the loss of a body appendage to escape predation. By knowing the collection site of preserved specimens, it is possible to assess the influence of organismal biology and the surrounding environment in the occurrence of autotomy. We gathered data on tail loss for 8189 preserved specimens of 33 snake and 11 amphisbaenian species to investigate biological and environmental correlates of autotomy in reptiles. We applied generalized linear mixed effect models to evaluate whether body size, sex, life-stage, habitat use, activity pattern, biome, tropicality, temperature and precipitation affect the probability of tail loss in limbless reptiles. We observed autotomy in 23.6% of examined specimens, with 18.7% of amphisbaenian and 33.4% of snake specimens showing tail loss. The probability of tail loss did not differ between snakes and amphisbaenians, but it was higher among large-sized specimens, particularly in adults and females. Chance of tail loss was higher for diurnal and arboreal species, and among specimens collected in warmer regions, but it was unaffected by biome, precipitation, and tropicality. Autotomy in limbless reptiles was affected by size-dependent factors that interplay with ontogeny and sexual dimorphism, although size-independent effects of life-stage and sex also shaped behavioural responses to predators. The increase in probability of tail loss with verticality and diurnality suggests a risk-balance mechanism between species habitat use and activity pattern. Although autotomy is more likely in warmer regions, it seems unrelated to seasonal differences in snakes and amphisbaenians activity. Our findings reveal several processes related to predator-prey interactions involving limbless reptiles, demonstrating the importance of scientific collections to unveil ecological mechanisms at different spatio-temporal scales.

Time trends and geographic distribution of hepatocellular carcinoma in Brazil: An ecological study.

The incidence of hepatocellular carcinoma (HCC) is increasing globally, and HCC is the fourth leading cause of cancer-related death. This ecological study aimed to investigate the time trends and geographic distribution of HCC in Brazil. Data from the Brazilian Health Public System were retrospectively collected from January 2005 to December 2018. Hospitalization and intrahospital lethality rates for HCC were stratified by age and sex. Hospitalization rates and associated lethality per 100,000 inhabitants in each municipality were included in a worksheet to build maps displaying the estimates and the geographic distribution of HCC. From 2005 to 2018, a total of 75,466 admissions for HCC were registered and the mean hospitalizations increased from 2.1 to 5.8/100,000 inhabitants (176%). The greatest increase occurred among patients older than 50, particularly in males above 70 years old. Prevalence rates increased throughout the country, with the highest levels detected in the South and Southeast. However, the increase was proportionally higher in the Northeast (377%), especially in municipalities not integrated into metropolitan regions. The HCC lethality rate remained relatively stable in both sexes, ranging from 21% to 25% (19%), but it was higher among older patients. The length of hospital stay did not differ between survivors and nonsurvivors throughout the study period. HCC hospitalizations are rising, particularly above 50 years of age and in rural areas, not paralleled by lethality rates. This suggests ongoing changes in environmental and socioeconomic factors in Brazil.

Two new surprising species of leaf-litter toad of the Rhinella margaritifera species group (Anura: Bufonidae) from the Peruvian Amazon, LoretoPeru.

We describe two new species of Rhinella (Anura: Bufonidae) from the department of Loreto, Peru. We integrate morphological and phylogenetic analyses to provide evidence of new species. R. angeli sp. nov. is diagnosable from all congeners by its pronounced fleshy proboscis and R. unapensis sp. nov. by the small size (mean snout-vent length=37.7 4.1 mm) of adult males, snout pointed in dorsal view, nearly acute in lateral view, and small bony protrusion at the angle of jaws among other characters. The two species are allopatric, where the first species is known to be associated inhabits upland (=terra firme) forests, while the second white sand forests (=varillales) around Iquitos city. The two new species represent the 20th and 21st species of the Rhinella margaritifera species group.

Results of interferon-free treatment for HCV-infected patients with decompensated cirrhosis from a Brazilian real-life cohort.

Real-life data on the HCV treatment with direct-acting agents in patients with decompensated cirrhosis are scarce. Study to investigate the effectiveness and safety of sofosbuvir-containing regimens in a prospective cohort of patients with HCV decompensated cirrhosis. A total of 150 patients were enrolled (64% male, 84% genotype 1 with a mean age of 61 ± 9 years). The median MELD was 12, and 79% were Child-PughB. Most patients were treated with sofosbuvir and daclatasvir (98%) with ribavirin in 27%. The overall intention to treat SVR12 was 91% (137/150). The most frequent adverse event was anemia (17%), 73% associated with ribavirin. Twenty-one (14%) patients experienced renal dysfunction, 81% AKI I, and 1 discontinued treatment. Thirty-five (23%) patients presented at least 1 infectious episode, mainly respiratory tract infection (29%). Thirty-three patients (22%) had at least 1 episode of cirrhosis decompensation throughout treatment, particularly worsening of previous ascites in 19%. Nine patients died, and among those, 7 patients died from sepsis. The probability of decompensation in 28, 90 and 180 days was 4%, 19% and 25%. During treatment, infection (OR 2.24; 95 CI 1.09-4.61; P = .03) was a predictor of cirrhosis decompensation, and baseline MELD and CHILD ≥ B8 were both associated with infection. In decompensated cirrhosis, the overall virological response was high with mild adverse events. However, this population had a high frequency of liver-associated decompensation and infections.

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study.

INTRODUCTION: The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. PATIENTS AND METHODS: This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. RESULTS: One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001). CONCLUSIONS: Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.