Miracle-dz/UniFAR-FTUs huggingface dataset:
Extrahepatic manifestations of HCV: the role of direct acting antivirals

ABSTRACT Introduction: Hepatitis C virus (HCV) represents a major health concern, as nearly 3 million people become newly infected by this pathogen annually. The majority of infected individuals fail to clear the virus, and chronicity is established. Chronic HCV patients are at high risk for liver disease, ranging from mild fibrosis to cirrhosis and severe hepatocellular carcinoma. Over the last few years, the development of multiple direct acting antivirals (DAA) have revolutionized the HCV infection treatment, demonstrating cure rates higher than 90%, and showing less side effects than previous interferon-based regimens. Areas covered: Besides liver, HCV infection affects a variety of organs, therefore inducing diverse extrahepatic manifestations. This review covers clinical, experimental, and epidemiological publications regarding systemic manifestations of HCV, as well as recent studies focused on the effect of DAA in such conditions. Expert commentary: Though further research is needed; available data suggest that HCV eradication is often associated with the improvement of extrahepatic symptoms. Therefore, the emergence of DAA would offer the opportunity to treat both HCV infection and its systemic manifestations, requiring shorter treatment duration and driving minor adverse effects.
Effects of exercise accumulation on plasma lipid and lipoprotein concentrations

The purpose of this study was to compare the effects of a single session of exercise versus accumulated sessions of exercise on plasma lipid and lipoprotein concentrations. Twelve young (22.5±2.5 years, mean±SEM), overweight (body mass index=29.7±3.9 kg.m-2), sedentary participants performed, in random order, a single exercise session (treadmill exercise at 60% maximal oxygen consumption for 90 minutes), accumulated exercise sessions (the same protocol as above for three consecutive days), and a control session (no exercise for six consecutive days). Blood samples taken immediately before each exercise/control session, and at 24, 48 and 72 after exercise were analyzed for high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. Data were analyzed using a repeated measures ANOVA, based upon a priori analyses (i.e., pre versus post-exercise time points) both within and across protocols. Significant interactions and main effects were analyzed using post-hoc paired samples T-tests. Statistical significance was set at the 0.05 level. The three exercise session protocol produced significant elevations in HDL-C concentrations 24 and 48 hours post-exercise, compared to the control. Additionally, there was a significant time by trial interaction for HDL-C, with concentrations elevated at 48 hours post-exercise for the three exercise session protocol compared to the single session. A significant percentage change reduction in TG concentration was observed after the three exercise session protocol compared to the ontrol. These results suggest that, in young, overweight, sedentary individuals, accumulating three consecutive 90-minute sessions of exercise is more effective in improving plasma HDL-C and TG concentrations when compared to a single session of exercise. In summary, these results support the additive benefits of exercise and justifies future exercise training studies aimed at determining the exact manner in which to accumulate exercise sessions (e.g., every day, every other day, etc.) in an effort to most effectively improve an individual’s lipid and lipoprotein profile.
Diagnostic challenges of kidney diseases in HIV-infected patients

ABSTRACT Introduction: Chronic kidney disease (CKD) is a prevalent comorbidity in persons living with HIV infection (PLWH) associated with an increase in cardiovascular morbidity and all-cause mortality. Furthermore, early diagnosis of CKD is difficult in PLWH. Areas covered: We reviewed the main diagnostic tools for CKD in PLWH, and discussed their strengths and limits. We performed a literature search on PubMed to identify reviews and clinical trials dealing with attractive kidney biomarkers of CKD in PLWH, with the following key words: ‘HIV AND kidney’, ‘HIV AND Kidney biomarkers’, ‘CKD AND Kidney biomarkers’. Expert commentary: Currently, CKD diagnosis is based on the estimation of Glomerular Filtration Rate (GFR), and measurement of proteinuria by urine protein/creatinine ratio (uPCR). These parameters are independent and complementary predictors of outcomes. GFR estimates are lacking in accuracy in PLWH. The best GFR estimate is CKD-EPI study equation. Moreover, low-grade proteinuria is associated with an increased risk of kidney disease progression in PLWH, and guidelines derived from the general population may lack sensitivity. Different biomarkers of kidney diseases like N-acetyl beta glucosaminidase (NAG), Kidney Injury Molecule-1 (KIM-1), and Alpha-1-microglobulin may predict kidney disease progression and mortality in PLWH. Others may help clinicians detect antiretroviral-induced tubulopathy, or predict cardiovascular events. More studies are needed to validate the routine use of these types of biomarkers.
Combination therapy for extensively-drug resistant gram-negative bacteria

ABSTRACT Introduction: The ongoing crisis and emergence of extensively-drug resistant (XDR) gram-negative pathogens in the nosocomial setting is worrisome. The limited armamentarium in combination with the increasing resistance rates of last resort antibiotics has led clinicians to re-exploit existing antibiotic classes. Areas covered: Current state of evidence concerning the administration of monotherapy versus combination therapy for the treatment of XDR gram-negative microorganism as well as salvage treatment are presented. Herein, the current knowledge concerning in vitro studies, animal models and clinical studies are discussed in detail. Expert commentary: The efficacy of combination therapy in carbapenemase-producing K. pneumoniae is associated with reduced mortality in patients with septic shock and rapidly fatal underlying diseases. There is moderate evidence in support of the use of monotherapy for treating carbapenemase-producing Acinetobacter baumannii infections, however for septic shock patients, cancer patients and infections with an isolate with MIC in the upper limit of susceptibility combination therapy could be recommended. There are currently minimal and of low quality clinical evidence suggesting that combination treatment has no therapeutic advantage over monotherapy for XDR Pseudomonas aeruginosa infections. The in vivo validity of novel compounds and necessity for combination therapy is to be evaluated in future studies particularly for XDR infections.
Community-acquired bacterial pneumonia in adult HIV-infected patients

ABSTRACT Introduction: Despite active antiretroviral therapy (ART), community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients and incurs high health costs. Areas covered: This article reviews the most recent publications on bacterial CAP in the HIV-infected population, focusing on epidemiology, prognostic factors, microbial etiology, therapy, and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline, and references from relevant articles. Expert commentary: HIV-infected patients are more susceptible to bacterial CAP. Although ART improves their immune response and has reduced CAP incidence, these patients continue to present increased risk of pneumonia in part because they show altered immunity and because immune activation persists. The risk of CAP in HIV-infected patients and the probability of polymicrobial or atypical infections are inversely associated with the CD4 cell count. Mortality in HIV-infected patients with CAP ranges from 6% to 15% but in well-controlled HIV-infected patients on ART the mortality is low and similar to that seen in HIV-negative individuals. Vaccination and smoking cessation are the two most important preventive strategies for bacterial CAP in well-controlled HIV-infected patients on ART.
Reduced Bone Mineral Density in Children With Screening-detected Celiac Disease

Objectives: The aim of the study was to assess whether bone mass and metabolism are impaired in genetically at-risk children with screening-detected celiac disease. Methods: Included were 71 children with screening-detected celiac disease diagnosed at 10.0 ± 0.7 (mean ± standard deviation) years and 142 matched controls and 30 children with screening-detected celiac disease diagnosed at 3.3 ± 0.4 years of age presently on a gluten-free diet for 6.9 ± 1.1 years and 60 matched controls. All participants were assessed for bone mineral density (BMD) of total body and spine by dual x-ray absorptiometry, serum 25(OH) vitamin D3, parathyroid hormone (PTH), interleukin (IL)-1&bgr;, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, interferon gamma, and tumor necrosis factor alpha. Results: At diagnosis, screening-detected celiac disease children as compared to controls had a mean −0.03 g/cm2 reduced BMD of both total body and spine (P = 0.009 and P = 0.005, respectively), a mean −11.4 nmol/L lower level of 25(OH) vitamin D3 (P < 0.001), and a mean +1.0 pmol/L higher PTH level (P < 0.001). Systemic levels of the cytokines IL-1&bgr;, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were all increased in screening-detected celiac disease as compared to controls (P < 0.001). No difference in BMD, 25(OH) vitamin D3, PTH, and cytokine levels were detected in children on a gluten-free diet compared with controls. Conclusions: Children with screening-detected celiac disease have reduced BMD, lower levels of vitamin D3, higher levels of PTH, and signs of systemic inflammation compared with controls. These differences were not found in celiac disease children on a gluten-free diet, indicating that children with screening-detected celiac disease benefit from an early diagnosis and treatment.
Using proteomics to explore the effects of radiation on the heart - impacts for medicine

The heart was long considered as a radiation-resistant organ that showed no obvious signs of damage at doses below 30 Gy. This view started to change slowly in the beginning of this century when data from big clinical studies with radiotherapy patients showed long-term adverse effects on the heart at much lower thorax doses than previously expected. Especially striking was the observation that patients with leftsided breast cancer had significantly higher risk of cardiac complications later in life than right-sided breast cancer patients [1]. Data accruing from recent epidemiological studies with nuclear workers have pushed the radiation dose limit even lower showing significant ischemic heart disease risk under the dose of 1 Gy [2]. Nowadays, it is known that radiation exposure is able to cause pericarditis, myocardial fibrosis, myocardial infarction, conduction defects, and valvular insufficiency. The fact that these different radiation-induced heart diseases remained undetected so long can partly be explained by the decadelong latent time, especially at low radiation doses. In addition, the biological experiments measuring functional parameters or structural changes of the heart could not detect any significant alteration after exposure to low or moderate radiation doses. First after the development of modern omics techniques the door was opened for experiments providing a deep insight into molecular alterations that could explain the etiology of radiation-induced heart disease.
Functional organization of the human posterior cingulate cortex, revealed by multiple connectivity‐based parcellation methods

Based on cytoarchitecture, the posterior cingulate cortex (PCC) is thought to be comprised of two distinct functional subregions: the dorsal and ventral PCC (dPCC and vPCC). However, functional subregions do not completely match anatomical boundaries in the human brain. To understand the relationship between the functional organization of regions and anatomical features, it is necessary to apply parcellation algorithms based on functional properties. We therefore defined functionally informed subregions in the human PCC by parcellation of regions with similar patterns of functional connectivity in the resting brain. We used various patterns of functional connectivity, namely local, whole‐brain and diffuse functional connections of the PCC, and various clustering methods, namely hierarchical, spectral, and k‐means clustering to investigate the subregions of the PCC. Overall, the approximate anatomical boundaries and predicted functional regions were highly overlapped to each other. Using hierarchical clustering, the PCC could be clearly separated into two anatomical subregions, namely the dPCC and vPCC, and further divided into four subregions segregated by local functional connectivity patterns. We show that the PCC could be separated into two (dPCC and vPCC) or four subregions based on local functional connections and hierarchical clustering, and that subregions of PCC display differential global functional connectivity, particularly along the dorsal‐ventral axis. These results suggest that differences in functional connectivity between dPCC and vPCC may be due to differences in local connectivity between these functionally hierarchical subregions of the PCC. Hum Brain Mapp 38:2808–2818, 2017. © 2017 Wiley Periodicals, Inc.
Efficacy and Safety of Adalimumab in Pediatric Ulcerative Colitis: A Real-life Experience from the SIGENP-IBD Registry

Objectives: The aim of this study was to evaluate the effectiveness and safety of adalimumab (ADA) in children with ulcerative colitis (UC) previously treated with infliximab (IFX). Methods: Retrospective study including children with UC from a national registry who received ADA therapy. The primary endpoint was the rate of corticosteroid-free remission at week 52. Secondary outcomes were the rate of sustained clinical remission, primary nonresponse, and loss of response at weeks 12, 30, and 52 and rate of mucosal healing and side effects at week 52. Results: Thirty-two children received ADA (median age 10 ± 4 years). Median disease duration before ADA therapy was 27 months. All patients received previous IFX (43% intolerant, 50% nonresponders [37.5% primary, 42.5% secondary nonresponders], 6.7% positive anti-IFX antibodies). Fifty-two weeks after ADA initiation, 13 patients (41%) were in corticosteroid-free remission. Mucosal healing occurred in 9 patients (28%) at 52 weeks. The cumulative probability of a clinical relapse-free course was 69%, 59%, and 53% at 12, 30, and 52 weeks, respectively. Ten patients (31%) had a primary failure and 5 (15%) a loss of response to ADA. No significant differences in efficacy were reported between not-responders and intolerant to IFX (P = 1.0). Overall, 19 patient (59%) maintained ADA during 52-week follow-up. Seven patients (22%) experienced an adverse event, no serious side effects were observed and none resulted in ADA discontinuation. Conclusions: Based on our data, ADA seems to be effective in children with UC, allowing to recover a significant percentage of patients intolerant or not-responding to IFX. The safety profile was good.
Auditive identification of signal-processed environmental sounds: Monitoring the environment

The goal of the present study was to compare six transposing signal-processing algorithms based on different principles (Fourier-based and modulation based), and to choose the algorithm that best enables identification of environmental sounds, i.e. improves the ability to monitor events in the surroundings. Ten children (12–15 years) and 10 adults (21–33 years) with normal hearing listened to 45 representative environmental (events) sounds processed using the six algorithms, and identified them in three different listening experiments involving an increasing degree of experience. The sounds were selected based on their importance for normal hearing and deaf-blind subjects. Results showed that the algorithm based on transposition of 1/3 octaves (fixed frequencies) with large bandwidth was better (p<0.015) than algorithms based on modulation. There was also a significant effect of experience (p<0.001). Adults were significantly (p<0.05) better than children for two algorithms. No clear gender difference was observed. It is concluded that the algorithm based on transposition with large bandwidth and fixed frequencies is the most promising for development of hearing aids to monitor environmental sounds.
Discrimination of envelope statistics reveals evidence of sub-clinical hearing damage in a noise-exposed population with ‘normal’ hearing thresholds

Noise exposure can affect the functioning of inner hair cells (IHC) within the cochlea, leading to a ‘noisy’ representation of the properties of sounds even when absolute thresholds are normal. This may lead to a reduced ability to discriminate sounds based on their statistical properties, especially for narrowband sounds presented at low levels, since such sounds excite only a small proportion of the IHCs. This idea was tested by requiring subjects to discriminate a Gaussian noise from a ‘low-noise noise’ with minimal envelope fluctuations. The noises were centred at 2, 3, or 4kHz. The stimulus duration required for threshold was measured as a function of sensation level (SL) for two groups of normal-hearing subjects, one rarely exposed to high-noise events (control group, C) and one frequently exposed to high-noise events (experimental group, X). For group X, threshold consistently rose for SLs below about 20dB, while for group C the threshold did not consistently rise at low SLs (although it did for a minority of subjects). The worsening in performance with decreasing level was significantly greater for group X than for group C.
Achilles tendon diagnostic ultrasound examination: A locally designed protocol and audit

Abstract Background Diagnostic ultrasound is regarded as the gold standard for imaging tendinopathies for diagnosis, focusing rehabilitation, and guided intervention. However, there are no published diagnostic ultrasound protocols for the Achilles tendon which represent best practice. In the Felixstowe Community Hospital Physiotherapy Department a protocol for diagnostic ultrasound examination of the Achilles tendon was implemented in January 2013 and acts as a local guideline. Objectives To determine whether a local Achilles tendon image protocol is being adhered to in diagnostic ultrasound examinations of mid-portion Achilles tendinopathy. A pre-determined 75% adherence to the protocol was set as the standard representing best practice in diagnostic ultrasound examination of the Achilles tendon. A target of 100% of diagnostic ultrasound examinations should meet this standard. Methods Data collection of acquired and archived diagnostic ultrasound examinations with a subsequent diagnosis of mid-portion Achilles tendinopathy was included. A proforma was developed to collect data to determine whether diagnostic ultrasound examinations met the protocol standard. Results The sample included all patients from 1 January to 31 May 2013 (n = 30). The study population included 16 females and 14 males with a mean age of 54.2 (SD ± 15.01) years and mostly represented by the age category 36–65 years (76.7%). This audit demonstrated that 73% (22 patients from 30) of diagnostic ultrasound examinations adhered to the standard set. This audit demonstrated inconsistencies in performing components of the diagnostic ultrasound examination procedure including the region of interest power Doppler, contra-lateral grey-scale, contra-lateral power Doppler, split screen images and annotation. Conclusions The audit has highlighted the need to enhance Achilles tendon diagnostic ultrasound examinations; a number of recommendations have been made in improving the service for Achilles tendon examinations. It is envisaged that by adoption of these recommendations the musculo-skeletal service for these patients at the Felixstowe Community Hospital Physiotherapy Department will be enhanced before commencement of the second Clinical Audit Cycle is undertaken.
Percutaneous Liver Biopsy in Hemophiliac Children With Chronic Hepatitis C Virus Infection

Objective: To develop a protocol for safe performance of percutaneous liver biopsies in children with deficiency of factor VIII (n = 12) or IX (n = 2) and chronic hepatitis C virus infection. Patients and Methods: Liver biopsies were performed after administration of factor VIII or IX, before and 24 weeks after cessation of antiviral therapy. To define the optimal means of providing replacement therapy, 10 children were enrolled in a randomized crossover design study of bolus versus continuous factor VIII for performance of the liver biopsy. For the crossover study, all of the patients were given a loading dose of 50 ± 5 IU recombinant factor (rF)VIII/kg; a minimum of factor VIII activity of ≥80% 30 to 60 minutes following factor VIII infusion was required for liver biopsy. For the bolus protocol, rFVIII 25 to 50 IU/kg was given 6, 14, 24, 36, 48, and 60 hours after completion of the loading dose. For the continuous protocol, rFVIII was given 3 to 4 IU/kg per hour for 48 hours, followed by a bolus of 25 IU/kg at 60 hours. In patients with factor IX deficiency, a loading dose of 100 IU/kg was followed by a bolus of 50 IU/kg at 3, 15, 27, and 48 hours after the loading dose. Results: Twenty liver biopsies were performed in children with factor VIII deficiency without major complications. One of the 3 biopsies in the patients with factor IX deficiency was complicated by a hemoperitoneum. Midazolam and fentanyl were used in the first 8 patients. However, postbiopsy pain, presumably secondary to hematoma in 2 patients and hemoperitoneum in 1, prompted us to use ultrasound to locate a suitable biopsy site and to change to propofol; this allowed us to better immobilize the liver, to minimize postbiopsy bleeding. The subsequent 15 biopsies were well tolerated without postbiopsy pain or other complication. Conclusions: Percutaneous liver biopsy in children with factor VIII deficiency can be safely performed using either bolus or continuous infusion of recombinant factor VIII. A brief general anesthetic and ultrasound guidance are recommended.