Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review.

BACKGROUND AND AIMS: The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS: A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS: Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION: Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.

Communication strategies for adults in palliative care: the speech-language therapists' perspective.

BACKGROUND: Communication disorders are a challenge that many patients in palliative care (PC) may encounter. This intervention area is emerging for the speech-language therapist (SLT), the professional who works in preventing, assessing, diagnosing, and treating human communication disorders. This study aims to identify and classify the communication strategies considered most important by SLTs for use in PC and evaluate whether there are any differences in perception regarding the importance of strategies between SLTs with and without PC experience. METHODS: This cross-sectional quantitative study was conducted using a survey, which employed a well-structured, self-completion questionnaire previously validated by a panel of experts with over six years of PC experience. RESULTS: The strategies rated as most important within each group were the following: (i) adjust the patient's position and minimise environmental noise; (ii) establish eye contact and adjust the pace of speech; (iii) adjust the language level and raise one topic at a time; (iv) use images of the patient's interests and their personal objects; (v) use orality and multimodal form; (vi) use simplified language and structured pauses; and (vii) use tables with images and books with pictures. CONCLUSIONS: Verbal and non-verbal strategies were rated as highly important. There was no evidence of differences in perception in terms of importance between the SLTs with or without experience in PC, but more studies are needed to support this aspect. The patient's communication ability is one of the cornerstones of PC quality. Through their actions, speech-language professionals could empower the patient with strategies so that they can autonomously and self-determinedly express their experiences and most significant needs.

Photobiomodulation therapy on chemo- and radiotherapy induced oral conditions: an umbrella review.

OBJECTIVES: Photobiomodulation (PBM) is a laser-based therapy used to promote tissue repair, reduce inflammation and pain, and has been extensively studied in chemo- and radiotherapy-induced oral mucositis (OM). This review examines the level of evidence of systematic reviews (SRs) that have investigated PBM in such cases of OM. MATERIALS AND METHODS: SRs evaluating PBM for both the treatment and prevention of OM in patients undergoing chemotherapy and/or radiotherapy and published before November 30, 2023, on PubMed, Cochrane, Embase, Web of Science, LILACS, TRIP and Open Grey databases were eligible for inclusion. We assessed the level of methodological and meta-analytic procedures. RESULTS: Of the 1201 SRs, 21 that met the inclusion criteria were included. The quality of evidence was assessed using the Assessing the Measurement Tool to Assess Systematic Reviews (AMSTAR2), and the majority was of critically low quality (n = 15, 71.4%) with only 28.5% of low quality. A total of 40 meta-analytic estimates were obtained and analyzed. Approximately 87.5% of the meta-analysis were significant (n = 33), but only one meta-analyses had a strength of "highly suggestive", while the rest were classified as "weak". When analyzing the overlap values, the covered area was 12.14% and the corrected covered area was 7.75%, indicating a moderate overlap. Only 4 SRs had a very high overlap and one had a high overlap. CONCLUSION: The efficacy of PBM in the treatment of chemotherapy-induced OM is supported by low to critically low quality SRs and meta-analysis of low strength. This review highlights important areas that need to be addressed in future research on this topic. REGISTRATION: CRD42023484013 (PROSPERO).

The impact of nintedanib and pirfenidone on lung function and survival in patients with idiopathic pulmonary fibrosis in real-life setting.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2-5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. METHODS: A real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020. Two groups (under nintedanib or pirfenidone) were analyzed at diagnosis through their clinical features and radiological patterns. Lung function was assessed at diagnosis (time 0) and after 6, 12 and 24 months of treatment. We also compared this antifibrotic cohort with an older naïve antifibrotic cohort, mainly treated with immunosuppressive drugs and/or N- acetylcysteine. Survival was analyzed and prognostic features were also studied. Statistical analysis was performed with IBM® SPSS®. RESULTS: A cohort of 108 patients under antifibrotics (nintedanib n = 54; pirfenidone n = 54) was assessed. Lung function analysis showed an overall stabilization in FVC and DLCO mean predicted percentages at 6, 12 and 24 months of treatment. The mean decline in FVC and DLCO, at 12 months, was -40.95 ± 438.26 mL and -0.626 ± 1.31 mL/min/mmHg, respectively. However, during this period, 34.2% of the patients died mostly due to acute exacerbation associated with a poorer lung function at diagnosis. Mean survival in the naïve antifibrotic cohort was significantly lower than in the antifibrotic cohort (39.9 months versus 58.2 months; p < 0.005). Regarding lung function evolution and survival, we found no differences between definitive or probable UIP radiological patterns, both on patients under nintedanib and pirfenidone (p = 0.656). CONCLUSIONS: In this real-life observational study, the positive impact of antifibrotic therapy on the IPF clinical course and on survival was corroborated. Regarding efficacy, there was no difference between patients taking nintedanib or pirfenidone. The need for an early treatment was also demonstrated, since a worse outcome is clearly associated with lower lung volumes and lower diffusing capacity at diagnosis.

Urgent versus Non-Urgent Transcatheter Aortic Valve Implantation Outcomes.

INTRODUCTION: There are limited data about the outcomes of nonelective transcatheter aortic valve implantation (TAVI). Some studies suggest that these patients (pts) have worst results. Our purpose was to compare outcomes in pts submitted to urgent versus elective TAVI. METHODS: Retrospective analysis of 298 consecutive pts submitted to TAVI between 2018 and 2021 in a single tertiary center. Baseline characteristics and outcomes were collected and compared between elective and nonelective TAVI. RESULTS: Pts submitted to urgent TAVI (79 pts) had worse baseline characteristics, with higher EuroScore risk (9.26 vs. 5.17%, p < 0.0001), STS score (7.09 vs. 4.4%, p < 0.0001), and NT pro-natriuretic peptide B (10,168 vs. 3,241 pg/mL, p = 0.001), lower left ventricle ejection fraction (45 vs. 52%, p = 0.003), more diabetes (46.8 vs. 32.4%, p = 0.0.22), peripheral artery disease (21.5 vs. 6.8%, p < 0.0001), and poor vascular accesses (18.4 vs. 7.4%, p = 0.007). Urgent TAVI was associated with higher mortality (25.3 vs. 15.1%, p = 0.043), 30-day cardiovascular mortality (17.5 vs. 4%, p = 0.001), life-threatening bleeding (11.5 vs. 4.1%, p = 0.018), vascular complications (11.5 vs. 4.6%, p = 0.031), and longer hospital stay (28 vs. 12 days, p < 0.0001), but not with intensive care unit or post-TAVI hospital stay (5 vs. 4 days, p = 0.197 and 11 vs. 10 days, p = 0.572). When adjusted to differences in baseline characteristics, urgent TAVI was only associated with longer hospital stay (p < 0.0001). CONCLUSION: Pts submitted to urgent TAVI have worse short-term outcomes, but this seems to be attributable to the worse baseline characteristics instead of the urgent nature of the procedure.

New Hybrid Phenalenone Dimer, Highly Conjugated Dihydroxylated C28 Steroid and Azaphilone from the Culture Extract of a Marine Sponge-Associated Fungus, Talaromyces pinophilus KUFA 1767.

An undescribed hybrid phenalenone dimer, talaropinophilone (3), an unreported azaphilone, 7-epi-pinazaphilone B (4), an unreported phthalide dimer, talaropinophilide (6), and an undescribed 9R,15S-dihydroxy-ergosta-4,6,8 (14)-tetraen-3-one (7) were isolated together with the previously reported bacillisporins A (1) and B (2), an azaphilone derivative, Sch 1385568 (5), 1-deoxyrubralactone (8), acetylquestinol (9), piniterpenoid D (10) and 3,5-dihydroxy-4-methylphthalaldehydic acid (11) from the ethyl acetate extract of the culture of a marine sponge-derived fungus, Talaromyces pinophilus KUFA 1767. The structures of the undescribed compounds were elucidated by 1D and 2D NMR as well as high-resolution mass spectral analyses. The absolute configuration of C-9' of 1 and 2 was revised to be 9'S using the coupling constant value between C-8' and C-9' and was confirmed by ROESY correlations in the case of 2. The absolute configurations of the stereogenic carbons in 7 and 8 were established by X-ray crystallographic analysis. Compounds 1,2, 4-8, 10 and 11 were tested for antibacterial activity against four reference strains, viz. two Gram-positive (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), as well as three multidrug-resistant strains, viz. an extended-spectrum ß-lactamase (ESBL)-producing E. coli, a methicillin-resistant S. aureus (MRSA) and a vancomycin-resistant E. faecalis (VRE). However, only 1 and 2 exhibited significant antibacterial activity against both S. aureus ATCC 29213 and MRSA. Moreover, 1 and 2 also significantly inhibited biofilm formation in S. aureus ATCC 29213 at both MIC and 2xMIC concentrations.

Outcomes and predictors of periprocedural stroke after transcatheter aortic valve implantation.

BACKGROUND: Risk factors for stroke after transcatheter aortic valve implantation (TAVI) are currently incompletely understood. PURPOSE: To identify possible predictors of early post-TAVI stroke and explore its short-term outcomes. METHODS: Retrospective analysis of consecutive patients (pts) submitted to TAVI between 2009 and 2020 in a tertiary center. Baseline characteristics, procedural information and stroke in first 30 days after TAVI were collected. In-hospital and 12 months outcomes were analyzed. RESULTS: A total of 512pts (56,1% female, mean age of 82 ± 6years.) were included. In the first 30 days after TAVI 19pts (3,7%) had a stroke. In univariate analysis stroke was associated with higher body mass index (29 vs 27kg/m2, p=0.035), higher triglyceridemia (> 117,5mg/dL, p=0,002), lower high-density lipoprotein (< 38,5mg/dL, p=0,009) and porcelain aorta (36,8% vs 15,5%, p=0,014) and more frequent use of post-dilatation (58,8% vs 32%, p=0,021). In multivariate analysis, triglycerides > 117,5mg/dL (p=0,032, OR = 3,751) and post-dilatation (p=0,019, OR = 3,694) were the independent predictors. Stroke after TAVI was associated with longer intensive care unit stay (12 vs 4 days, p<0,001) and post-TAVI hospital stay (25 vs 10 days, p<0,0001), higher intra-hospital mortality (21,1% vs 4,3%, p=0,003), cardiovascular 30-day mortality (15,8% vs 4,1%, p=0,026) and 1-year stroke (13,2% vs 1,1%, p=0,003). CONCLUSION: Periprocedural and 30-day stroke is a relatively uncommon but potentially devastating complication after TAVI. In this cohort, 30-day stroke rate after TAVI was 3.7%. Hypertriglyceridemia and post-dilatation were found to be the only independent risk predictors. Outcomes after stroke, including 30-day mortality, were significantly worse.

Proactive infliximab is more effective than vedolizumab in inducing fecal calprotectin remission in inflammatory bowel disease.

BACKGROUND: Current evidence suggests vedolizumab (VDZ) may be as effective as Infliximab (IFX) in inflammatory bowel disease. It is unknown if proactive therapeutic drug monitoring (PTDM) of IFX may improve these results. METHODS: Case-control study including consecutive patients with primary response to conventional IFX (n = 70), proactive IFX (n = 148), and VDZ (n = 95). PTDM was performed at week 14 and every other infusion, aiming at a trough level between 5 and 10 µg/ml. The primary outcome was fecal calprotectin (Fc) remission (<250 µg/g) at 1 year of treatment. Secondary outcomes included Fc remission at week 14 (proactive IFX/VDZ), clinical remission, treatment discontinuation, hospitalization, and surgery at 1-year of follow-up. RESULTS: Proactive IFX was superior to conventional IFX and VDZ in inducing Fc remission at 1-year (69.4% vs 47.1% vs 37.9%, p = .003 and p < .001). Results remained significant in biologic naïve patients (70.8% vs 44.4% vs 51.4%, p = .001 and p = .043) but comparisons between conventional IFX and VDZ were not significant (p = .265 and p = .664). In multivariate analysis correcting for prior biologic exposure, proactive IFX was more effective than conventional IFX (OR 2.480 95%CI [1.367-4.499], p = .003) and VDZ (OR 3.467 95%CI [1.578-7.617], p = .002) in inducing Fc remission. Amongst secondary outcomes, only clinical remission was significant between proactive IFX and VDZ in the overall cohort (80.4% vs 55.8%, p < .001) and in biologic naïve patients (80.2% vs 62.9%, p = .043). Fc remission at 1-year was associated with better results in most secondary outcomes. CONCLUSION: Proactive IFX was superior to VDZ in inducing Fc remission at 1-year, which was associated with improved clinical outcomes.SUMMARYCurrent evidence suggests that vedolizumab may be as effective as Infliximab in the treatment of patients with inflammatory bowel disease.There have been no studies comparing vedolizumab with proactively optimized Infliximab based on trough levels.We confirm that conventional IFX is as effective as vedolizumab but proactive IFX appears superior to vedolizumab in inducing fecal calprotectin remission.Fecal calprotectin remission associates with better clinical outcomes.

Assessment of skeletal age in youth female soccer players: Agreement between Greulich-Pyle and Fels protocols.

OBJECTIVE: The purpose of the study was to evaluate the agreement between the Fels and Greulich-Pyle methods for the assessment of skeletal age (SA) in female youth soccer players. METHODS: The sample included 441 Portuguese players 10.08-16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand-wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich-Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups: late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods. RESULTS: Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under-13: kappa = 0.48; under-14: kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under-17: 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method. CONCLUSIONS: GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status.

New Alkylpyridinium Anthraquinone, Isocoumarin, C-Glucosyl Resorcinol Derivative and Prenylated Pyranoxanthones from the Culture of a Marine Sponge-Associated Fungus, Aspergillus stellatus KUFA 2017.

An unreported isocoumarin, (3S,4R)-4-hydroxy-6-methoxymellein (2), an undescribed propylpyridinium anthraquinone (4), and an unreported C-glucosyl resorcinol derivative, acetyl carnemycin E (5c), were isolated, together with eight previously reported metabolites including p-hydroxybenzaldehyde (1), 1,3-dimethoxy-8-hydroxy-6-methylanthraquinone (3a), 1,3-dimethoxy-2,8-dihydroxy-6-methylanthraquinone (3b), emodin (3c), 5[(3E,5E)-nona-3,5-dien-1-yl]benzene (5a), carnemycin E (5b), tajixanthone hydrate (6a) and 15-acetyl tajixanthone hydrate (6b), from the ethyl acetate extract of the culture of a marine sponge-derived fungus, Aspergillus stellatus KUFA 2017. The structures of the undescribed compounds were elucidated by 1D and 2D NMR and high resolution mass spectral analyses. In the case of 2, the absolute configurations of the stereogenic carbons were determined by comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. The absolute configurations of the stereogenic carbons in 6a and 6b were also determined, for the first time, by X-ray crystallographic analysis. Compounds 2, 3a, 3b, 4, 5a, 5b, 5c, 6a, and 6b were assayed for antibacterial activity against four reference strains, viz. two Gram-positive (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), as well as three multidrug-resistant strains. However, only 5a exhibited significant antibacterial activity against both reference and multidrug-resistant strains. Compound 5a also showed antibiofilm activity against both reference strains of Gram-positive bacteria.

Antibacterial and Antibiofilm Properties of Self-Assembled Dipeptide Nanotubes.

Over recent decades, multidrug-resistant pathogens have become a global concern, with WHO even considering it one of the biggest threats to global health, food security, and development today, which led to the search for alternative antibacterial agents. A special class is formed by peptides composed by the diphenylalanine motif whose antibacterial properties result from their supramolecular arrangement into nanotubes. However, several other dipeptides that also form nanotubes have been largely overlooked. Here, we present the antibacterial activity of four dipeptide nanotubes. The results point to diverse mechanisms through which dipeptide nanotubes exert their effect against bacteria. Antibacterial activity was similar for dipeptide nanotubes sufficiently wide to allow water flux while dipeptides displaying smaller channels were inactive. This suggests that two of the tested dipeptides, L-Phe-L-Phe (FF, diphenylalanine) and L-Leu-L-Ser (LS), are pore forming structures able to induce membrane permeation and affect cellular hydration and integrity. Of these two dipeptides, only FF demonstrated potential to inhibit biofilm formation. The amyloid-like nature and hydrophobicity of diphenylalanine assemblies are probably responsible for their adhesion to cell surfaces preventing biofilm formation and bacteria attachment.

E-Learning Impact on Veterinary Medical Student's Mental Health during the COVID-19 Pandemic.

Veterinary medical students are known to have significant levels of mental illness. The COVID-19 pandemic and the shift to online learning have brought increased psychological stress. We used a web-based survey to ask 415 veterinary medical students from Portugal about the impact of the pandemic and online learning on their anxiety levels. Results were analyzed using logistic regressions and Spearman's correlation. Results indicated that 15.4% had no symptoms of anxiety, 39.5% experienced mild anxiety, 21.4% had moderate anxiety, and 23.6% experienced severe anxiety. Having difficulty sleeping, the stress associated with confinement, and family conflicts were risk factors for anxiety, while being male was found to be protective. Most veterinary medical students (77%) were satisfied with online learning. The university's adaptation to online teaching and time spent participating in online classes were significantly associated with anxiety. Due to the known fragility of veterinary medical students' mental health, this group should be monitored and supported closely during life-disrupting events such as public health emergencies.

Growth and maturity status of young male table tennis players.

A maturity-associated gradient among adolescent athletes in many sports tends to favour early maturing participants. This study was aimed to describe inter-individual variance in growth and skeletal maturation among male youth table tennis. The sample included 99 players registered in competitive clubs for at least 2 years. Chronological age (CA) ranged 10.00-14.63 years. Stature and body mass were plotted relative to US references. Skeletal age (SA) was estimated with the Fels method. Maturity status was given as SA minus CA. Somatic maturation was derived from predicted age at peak height velocity. Mean values for stature and weight were above the reference medians from 10 to 13 years and at the median in the oldest group. In general, SA was in advance to CA (CA: 12.45 ± 1.28 years; SA: 13.44 ± 2.37 years). The majority of the players were early maturing according to SA (52%) and average maturing based on the somatic indicator (80%). The results suggested that table tennis tends to retain taller and heavier participants who are somewhat advanced in skeletal maturity. Participation in youth table tennis and opportunities to win need to consider age- and maturity-associated variations, particularly regarding bands for competitions.

Role of AIP56 disulphide bond and its reduction by cytosolic redox systems for efficient intoxication.

Apoptosis-inducing protein of 56 kDa (AIP56) is a major virulence factor of Photobacterium damselae subsp. piscicida, a gram-negative pathogen that infects warm water fish species worldwide and causes serious economic losses in aquacultures. AIP56 is a single-chain AB toxin composed by two domains connected by an unstructured linker peptide flanked by two cysteine residues that form a disulphide bond. The A domain comprises a zinc-metalloprotease moiety that cleaves the NF-kB p65, and the B domain is involved in binding and internalisation of the toxin into susceptible cells. Previous experiments suggested that disruption of AIP56 disulphide bond partially compromised toxicity, but conclusive evidences supporting the importance of that bond in intoxication were lacking. Here, we show that although the disulphide bond of AIP56 is dispensable for receptor recognition, endocytosis, and membrane interaction, it needs to be intact for efficient translocation of the toxin into the cytosol. We also show that the host cell thioredoxin reductase-thioredoxin system is involved in AIP56 intoxication by reducing the disulphide bond of the toxin at the cytosol. The present study contributes to a better understanding of the molecular mechanisms operating during AIP56 intoxication and reveals common features shared with other AB toxins.

Anthraquinones, Diphenyl Ethers, and Their Derivatives from the Culture of the Marine Sponge-Associated Fungus Neosartorya spinosa KUFA 1047.

Previously unreported anthraquinone, acetylpenipurdin A (4), biphenyl ether, neospinosic acid (6), dibenzodioxepinone, and spinolactone (7) were isolated, together with (R)-6-hydroxymellein (1), penipurdin A (2), acetylquestinol (3), tenellic acid C (5), and vermixocin A (8) from the culture of a marine sponge-associated fungus Neosartorya spinosa KUFA1047. The structures of the previously unreported compounds were established based on an extensive analysis of 1D and 2D NMR spectra as well as HRMS data. The absolute configurations of the stereogenic centers of 5 and 7 were established unambiguously by comparing their calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 2 and 5-8 were tested for their in vitro acetylcholinesterase and tyrosinase inhibitory activities as well as their antibacterial activity against Gram-positive and Gram-negative reference, and multidrug-resistant strains isolated from the environment. The tested compounds were also evaluated for their capacity to inhibit biofilm formation in the reference strains.

Prognostic effect and modulation of cardiac sympathetic function in heart failure patients treated with cardiac resynchronization therapy.

BACKGROUND: Cardiac autonomic dysfunction as assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy is associated with poor prognosis in heart failure (HF) patients. Although cardiac resynchronization therapy (CRT) has emerged as an effective therapy in improving outcomes on HF patients, its effect on cardiac sympathetic nervous function is still not fully understood. We aimed to study the value of pre-implantation 123I-mIBG late heart-to-mediastinum ratio (HMR) as a predictor of response and outcomes after CRT and to correlate modification in this parameter with CRT response and functional improvement. METHODS AND RESULTS: BETTER-HF (Benefit of exercise training therapy and cardiac resynchronization in HF patients) is a prospective randomized clinical trial including HF patients submitted CRT (mean LVEF 24 ± 8%, 74% NYHA class ≥ III) who underwent a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. One-hundred and twenty-one patients were included. Echocardiographic response was observed in 54% and composite outcome of cardiac mortality, cardiac transplant or heart failure hospitalization in 24% of patients. Baseline late HMR was an independent predictor of CRT response (regression coefficient 2.906, 95% CI 0.293-3.903, P .029) and outcomes (HR 0.066 95% CI 0.005-0.880, P .040). At follow-up, 123I-mIBG imaging showed positive changes in cardiac sympathetic nerve activity only in responders to CRT (1.36 ± 0.14 prior vs. 1.42 ± 0.16 after CRT, P .039). There was a significant correlation between improvement in late HMR and improvement in peak oxygen consumption (r 0.547, P < .001). CONCLUSION: In our study, baseline cardiac denervation predicted response and clinical outcomes after CRT implantation. Cardiac sympathetic function was improved only in patients who responded to CRT and these positive changes were correlated with improvement in functional capacity.

Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies.

The development of pharmacologically active compounds based on bis(thiosemicarbazones) (BTSC) and on their coordination to metal centers constitutes a promising field of research. We have recently explored this class of ligands and their Cu(II) complexes for the design of cancer theranostics agents with enhanced uptake by tumoral cells. In the present work, we expand our focus to aliphatic and aromatic BTSC Zn(II) complexes bearing piperidine/morpholine pendant arms. The new complexes ZnL1-ZnL4 were characterized by a variety of analytical techniques, which included single-crystal X-ray crystallography for ZnL2 and ZnL3. Taking advantage of the fluorescent properties of the aromatic complexes, we investigated their cellular uptake kinetics and subcellular localization. Furthermore, we tried to elucidate the mechanism of action of the cytotoxic effect observed in human cancer cell line models. The results show that the aliphatic complexes (ZnL1 and ZnL2) have a symmetrical structure, while the aromatic counterparts (ZnL3 and ZnL4) have an asymmetrical nature. The cytotoxic activity was higher for the aromatic BTSC complexes, as well as the cellular uptake, evaluated by measurement of intracellular Zn accumulation. Among the most active complexes, ZnL3 presented the fastest uptake kinetics and lysosomal localization assessed by live-cell microscopy. Detailed studies of its impact on cellular production of reactive oxygen species and impairment of lysosomal membrane integrity reinforced the influence of the pendant piperidine in the biological performance of aromatic BTSC Zn(II) complexes.

Relationship of left ventricular global longitudinal strain with cardiac autonomic denervation as assessed by 123I-mIBG scintigraphy in patients with heart failure with reduced ejection fraction submitted to cardiac resynchronization therapy : Assessment of cardiac autonomic denervation by GLS in patients with heart failure with reduced ejection fraction submitted to CRT.

BACKGROUND: Heart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by 123I-mIBG scintigraphy in advanced HF. METHODS/RESULTS: BETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of - 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). CONCLUSION: Myocardial contractility as assessed by GLS is moderately correlated with AD as assessed by 123I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.

Negative affect and eating psychopathology: the moderator effect of gender.

PURPOSE: This study examined the moderator role of gender in the relationship between negative affect and eating psychopathology as well as gender differences in these variables. METHODS: A community sample of 285 students (61.8% females), aged 13-25, was recruited in middle and high schools and universities. They filled instruments that assess negative affect and eating disordered symptoms (restraint, eating concern, shape concern, weight concern, and global scale). RESULTS: Females scored higher both in all subscales and the global scale of eating psychopathology. The restraint subscale was the only subscale showing non-significant differences between females and males. Controlling for BMI, moderation analyses revealed that gender moderated the relationship between negative affect and eating psychopathology, except for restraint behavior. CONCLUSIONS: To deal with negative affect, females engage in more cognitive symptoms associated with disordered eating than males, but both endorse equally in eating restraint. These findings suggest that interventions focused on emotion regulation could help to reduce eating disordered symptoms among females and males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Host cell autophagy contributes to Plasmodium liver development.

Autophagy plays an important role in the defence against intracellular pathogens. However, some microorganisms can manipulate this host cell pathway to their advantage. In this study, we addressed the role of host cell autophagy during Plasmodium berghei liver infection. We show that vesicles containing the autophagic marker LC3 surround parasites from early time-points after invasion and throughout infection and colocalize with the parasitophorous vacuole membrane. Moreover, we show that the LC3-positive vesicles that surround Plasmodium parasites are amphisomes that converge from the endocytic and autophagic pathways, because they contain markers of both pathways. When the host autophagic pathway was inhibited by silencing several of its key regulators such as LC3, Beclin1, Vps34 or Atg5, we observed a reduction in parasite size. We also found that LC3 surrounds parasites in vivo and that parasite load is diminished in a mouse model deficient for autophagy. Together, these results show the importance of the host autophagic pathway for parasite development during the liver stage of Plasmodium infection.