Miracle-dz/UniFAR-FTUs huggingface dataset:
A Polyphenol-Enriched Supplement Exerts Potent Epigenetic-Protective Activity in a Cell-Based Model of Brain Ischemia

Bioactive components, due in part to their epigenetic properties, are beneficial for preventing several human diseases including cerebrovascular pathologies. However, no clear demonstration supports the idea that these molecules still conserve their epigenetic effects when acting at very low concentrations reproducing the brain levels achieved after oral administration of a micronutrient supplement. In the present study, we used a cellular model of brain ischemia to investigate the neuroprotective and epigenetic activities of a commercially available micronutrient mixture (polyphenol-enriched micronutrient mixture, PMM) enriched in polyphenols ((-)-epigallocatechin-3-gallate, quercetin, resveratrol), α-lipoic acid, vitamins, amino acids and other micronutrients. Mimicking the suggested dietary supplementation, primary cultures of mouse cortical neurons were pre-treated with PMM and then subjected to oxygen glucose deprivation (OGD). Pre-treatment with PMM amounts to provide bioactive components in the medium in the nanomolar range potently prevented neuronal cell death. The protection was associated with the deacetylation of the lysin 310 (K310) on NF-κB/RelA as well as the deacetylation of H3 histones at the promoter of Bim, a pro-apoptotic target of ac-RelA(K310) in brain ischemia. Epigenetic regulators known to shape the acetylation state of ac-RelA(K310) moiety are the histone acetyl transferase CBP/p300 and the class III histone deacetylase sirtuin-1. In view of that evidence, the protection we here report unveils the efficacy of bioactive components endowed with either inhibitory activity on CBP/p300 or stimulating activity on the AMP-activated protein kinase–sirtuin 1 pathway. Our results support a potential synergistic effect of micronutrients in the PMM, suggesting that the intake of a polyphenol-based micronutrient mixture can reduce neuronal vulnerability to stressful conditions at concentrations compatible with the predicted brain levels reached by a single constituent after an oral dose of PMM.
Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE®, EMBASE® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m2; 95% CI 1.3–4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9–4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.
The Legionella effector RavD binds phosphatidylinositol-3-phosphate and helps suppress endolysosomal maturation of the Legionella-containing vacuole

Upon phagocytosis into macrophages, the intracellular bacterial pathogen Legionella pneumophila secretes effector proteins that manipulate host cell components, enabling it to evade lysosomal degradation. However, the bacterial proteins involved in this evasion are incompletely characterized. Here we show that the L. pneumophila effector protein RavD targets host membrane compartments and contributes to the molecular mechanism the pathogen uses to prevent encounters with lysosomes. Protein–lipid binding assays revealed that RavD selectively binds phosphatidylinositol-3-phosphate (PI(3)P) in vitro. We further determined that a C-terminal RavD region mediates the interaction with PI(3)P and that this interaction requires Arg-292. In transiently transfected mammalian cells, mCherry-RavD colocalized with the early endosome marker EGFP-Rab5 as well as the PI(3)P biosensor EGFP-2×FYVE. However, treatment with the phosphoinositide 3-kinase inhibitor wortmannin did not disrupt localization of mCherry-RavD to endosomal compartments, suggesting that RavD's interaction with PI(3)P is not necessary to anchor RavD to endosomal membranes. Using superresolution and immunogold transmission EM, we observed that, upon translocation into macrophages, RavD was retained onto the Legionella-containing vacuole and was also present on small vesicles adjacent to the vacuole. We also report that despite no detectable effects on intracellular growth of L. pneumophila within macrophages or amebae, the lack of RavD significantly increased the number of vacuoles that accumulate the late endosome/lysosome marker LAMP-1 during macrophage infection. Together, our findings suggest that, although not required for intracellular replication of L. pneumophila, RavD is a part of the molecular mechanism that steers the Legionella-containing vacuole away from endolysosomal maturation pathways.
Impact of partial substitution of NaCl by KCl, and MgCl2 on physicochemical and sensory properties of cooked sausages during storage

Objective To determine the effect of three salting treatments (control, 100% NaCl; T1, 60% NaCl and 40% KCl; T2, 50% NaCl, 40% KCl, and 10% MgCl2) on meat quality of sausages during storage. Methods Various types of curing salts were used for processing of salamis. Physico-chemical and sensory evaluation of the sausages were analyzed during 4 weeks of ripening. Results The pH values and salinity contents were the highest in control, while they were the lowest in T2 at 4 weeks (p<0.05). Control and T1 had less thiobarbituric acid reactive substances than T2 at 2 weeks (p<0.05). The volatile basic nitrogen levels in T1 were similar to control and lower than T2 at 2 and 4 weeks (p<0.05). Moreover, T1 samples were redder and had a higher saturation index (C*) value when compared to the others. T2 showed greater hardness, gumminess and chewiness when compared with the control (p<0.05). Control was comparable to T1 for sensory attributes. Conclusion Sodium chloride may be partially substituted with potassium chloride without negatively influencing meat quality of sausages up to 4 weeks of storage. These results could help to develop low-sodium sausages.
Exotic Fermented Dairy Foods.

Cultured dairy products are on the ascendency in the United States. The yogurt market has grown almost 600% over the last decade. There is also renewed interest in products containing Lactobacillus acidophilus . For innovative development to be competitive in the U.S. food market, the cultured dairy products industry has to look to exotic fermented dairy products which could be adapted for the American palate. Three such products are dicussed, which with slight modifications and imaginative flavoring may have a very good potential in the American market.
The Emotion Regulation Questionnaire: Psychometric Properties in General Community Samples

Abstract The Emotion Regulation Questionnaire (ERQ) is a 10-item self-report measure of 2 emotion regulation strategies, cognitive reappraisal and expressive suppression. It is a widely used measure of emotion regulation, but its factor structure has rarely been examined outside of university student samples, and some authors have recently questioned its factorial validity in general community samples. In this study, we examine the psychometric properties of the ERQ (original English version) in 3 Australian general community samples (N = 300, 400, 348). Confirmatory factor analyses in each sample demonstrated that the traditional 2-factor model (comprised of cognitive reappraisal and expressive suppression factors) was replicable and an excellent fit to the data. In all samples, ERQ cognitive reappraisal (α = .89–.90) and expressive suppression (α = .76–.80) scores had acceptable to excellent levels of internal consistency reliability. As expected, cognitive reappraisal scores were significantly negatively correlated with psychological distress and alexithymia, whereas expressive suppression scores were significantly positively correlated with psychological distress and alexithymia. We conclude that, similar to previous findings in student samples, the ERQ has strong psychometric properties in general community samples and can therefore be used confidently regardless of participants’ student status.
Effects of chemical preservation on bulk and amino acid isotope ratios of zooplankton, fish, and squid tissues.

RATIONALE It is imperative to understand how chemical preservation alters tissue isotopic compositions before using historical samples in ecological studies. Specifically, although compound-specific isotope analysis of amino acids (CSIA-AA) is becoming a widely used tool, there is little information on how preservation techniques affect amino acid δ15 N values. METHODS We evaluated the effects of chemical preservatives on bulk tissue δ13 C and δ15 N and amino acid δ15 N values, measured by gas chromatography/isotope ratio mass spectrometry (GC/IRMS), of (a) tuna (Thunnus albacares) and squid (Dosidicus gigas) muscle tissues that were fixed in formaldehyde and stored in ethanol for 2 years and (b) two copepod species, Calanus pacificus and Eucalanus californicus, which were preserved in formaldehyde for 24-25 years. RESULTS Tissues in formaldehyde-ethanol had higher bulk δ15 N values (+1.4, D. gigas; +1.6‰, T. albacares), higher δ13 C values for D. gigas (+0.5‰), and lower δ13 C values for T. albacares (-0.8‰) than frozen samples. The bulk δ15 N values from copepods were not different those from frozen samples, although the δ13 C values from both species were lower (-1.0‰ for E. californicus and -2.2‰ for C. pacificus) than those from frozen samples. The mean amino acid δ15 N values from chemically preserved tissues were largely within 1‰ of those of frozen tissues, but the phenylalanine δ15 N values were altered to a larger extent (range: 0.5-4.5‰). CONCLUSIONS The effects of preservation on bulk δ13 C values were variable, where the direction and magnitude of change varied among taxa. The changes in bulk δ15 N values associated with chemical preservation were mostly minimal, suggesting that storage in formaldehyde or ethanol will not affect the interpretation of δ15 N values used in ecological studies. The preservation effects on amino acid δ15 N values were also mostly minimal, mirroring bulk δ15 N trends, which is promising for future CSIA-AA studies of archived specimens. However, there were substantial differences in phenylalanine and valine δ15 N values, which we speculate resulted from interference in the chromatographic resolution of unknown compounds rather than alteration of tissue isotopic composition due to chemical preservation.
The impact of comorbid pain and depression in the United States: results from a nationally representative survey

Abstract Background and aims The co-morbidity between pain and depression is a target of interest for treatment. However most of the published literature on the topic has used clinical cohorts as the population of interest. The goal of this study was to use a nationally representative sample to explore how health outcomes varied across pain and depression status in a cohort sampled from the general US population. Methods This was a cross-sectional analysis of adults ≥18 years in the 2009–2010 National Health and Nutrition Examination Survey. The cohort was stratified into: no pain/depression, pain alone, depression alone, and pain with depression. The primary outcome was self-reported general health status, and secondary outcomes were healthcare visits, overnight hospital stays and functional limitation. Survey weighted logistic regression was used to adjust for potential confounders. Results The cohort consisted of 4,213 individuals, of which 186 (4.4%) reported concurrent pain and depression. 597 (14.2%) and 253 (6.0%) were classified with either pain or depression alone, respectively. The majority of individuals with co-morbid pain and depression reported poor health (65.1%, p<0.001) and were significantly more likely than those with neither condition to rate their health as poor after adjustment (OR: 7.77, 95% CI: 4.24–14.26, p<0.001). Those with pain only or depression only were also more likely to rate their health as poor, albeit to a lesser extent (OR: 2.21, 95% CI: 1.21–2.34, p<0.001; OR: 3.75, 95% CI: 2.54–5.54, p<0.001, respectively). A similar pattern was noted across all secondary outcomes. Most notably, those with co-morbid pain and depression were the most likely to endorse functional limitation (OR: 13.15, 95% CI: 8.00–21.61, p<0.001). Comparatively, a similar trend was noted amongst those with pain only or depression only, though with a reduced effect size (OR: 4.23, 95% CI: 3.12–4.77, p<0.001; OR: 5.13, 95% CI: 3.38–7.82, p<0.001). Conclusions Co-morbid pain and depression in the general population resulted in markedly worse outcomes versus isolated pain or depression. Further, the effect appears to be synergistic. Given the substantial burdens of pain and depression, future treatments should aim to address both conditions simultaneously. Implications As a result of the co-morbidity between pain and depression, patients presenting with either condition should increase the index of suspicion among clinicians and prompt screening for the reciprocal condition. Early intervention for co-morbid pain and depression has the potential to mitigate future incidence of chronic pain and major depression.
Principles of Current Vertebrate Neuromorphology

Causal analysis of molecular patterning at neural plate and early neural tube stages has shown that the central nervous system (CNS) of vertebrates is essentially organized into transverse neural segments or neuromeres and longitudinal zones which follow the curved axis of the brain. The intersection of the longitudinal and transverse patterning processes in the embryonic brain leads to the formation of a checkerboard pattern of distinct progenitor domains called “fundamental morphological units” (FMUs). The topologically invariant pattern formed by the ventricular surfaces of the FMUs of a given taxon represents the “Bauplan” or “blueprint” of the brain of that taxon. The FMUs initially represent thin epithelial fields; during further development they are transformed into three-dimensional radial units, extending from the ventricular surface to the meningeal surface. It is of note that the boundaries of the neuromeres, longitudinal zones, and radial units all strictly adhere to a non-Cartesian coordinate system inherent to the CNS of all vertebrates. The major neural histogenetic processes, including cellular proliferation, radial migration, and differentiation, as well as the formation of grisea (cell masses, nuclei, and cortices), occur principally within the confines of the FMUs, although tangential migration may also take cells to distant sites. Hence, recognition and delimitation of these units is essential for the identification and interpretation of grisea. An outline of the procedure to be followed in these processes of identification and interpretation is presented, and a list of the pertinent homology criteria is provided.
The influence of kinematics of engine-driven nickel-titanium instruments on root canal shape assessed by micro-computed tomography: a systematic review

Abstract Aim: To evaluate if the kinematics of engine-driven instruments affect the root canal shape. Method: The systematic review was registered in PROSPERO (CRD 42017077043). A broad search was performed for articles published before 26 September 2018 in the electronic databases: pubmed, scopus, web of science and Lilacs using MeSH and free terms. Only in vitro studies with human teeth that evaluated root canal shape by volume, surface area and unprepared surface area using reciprocating and rotary system assessed by micro-computed tomography were included. A modified checklist for randomized controlled trials from the Joanna Briggs Institute was used to assess the risk of bias. Results: Twenty-one articles were selected. According to quality assessment, all studies were considered ‘moderate methodological quality’. Eighteen articles analysed volume increase, only four studies showed statistically significant difference, three indicating that the reciprocating movement obtained a greater increase in volume than the rotary system and one rotary system obtained a greater increase. Twelve studies analysed surface area, only three studies showed statistically significant difference, two presented a reciprocating system revealing greater amount of surface area and one showed a rotary system obtained a greater amount of surface area. Ten articles evaluated unprepared surface area, two studies that analysed total length, one study presented that the rotary system revealed lower unprepared surface area while another study showed reciprocating with less unprepared area. One study analysed middle and apical third, and observed that the rotary system presented lower unprepared surface area in the middle third. Conclusions: Both the rotary and reciprocating kinematics produce changes in volume and surface area and leave unprepared areas in the root canal, however reciprocating system showed greater increase of volume and surface area, while the rotary system maintains less unprepared surface area.
Multifocal Necrotizing Leukoencephalopathy: Expanding the Clinicopathologic Spectrum

Multifocal necrotizing leukoencephalopathy (MNL) is a rare condition typically described in patients undergoing chemotherapy or with HIV/AIDS. As a pathologic entity, it is characterized by multiple small foci of necrosis typically within white matter of the pons and occasionally in other areas. Herein we describe findings in 6 patients with MNL, 5 diagnosed at postmortem examination and 1 by surgical biopsy. Histopathologic features were characteristic, with generally small foci of necrosis, most frequently within the pontine base, although larger lesions were seen in the frontal white matter and basal ganglia. Axonal swellings, occasional dystrophic calcification and minimal microglial activity or reactive responses were common. Glial fibrillary acidic protein immunoreactivity was absent or markedly reduced within the lesions although it remained well defined in the surrounding areas. The underlying clinical circumstances ranged from HIV/AIDS, hematologic malignancy, chemotherapy for malignancies to postcardiac transplant, the latter reported for the first time. A significant common thread identified in our cases was altered immune status. A second common factor, which has also been previously implicated, was the presence of significant ongoing infection or sepsis. The role of concurrent inflammatory processes, specifically proinflammatory cytokine release in the context of these complex clinical scenarios is discussed with possible pathogenetic considerations.
Do Most Patients With a Spontaneous Cerebrospinal Fluid Leak Have Idiopathic Intracranial Hypertension?

BACKGROUND The association between cerebrospinal fluid (CSF) leaks at the skull base and raised intracranial pressure (ICP) has been reported since the 1960s. It has been suggested that spontaneous CSF leaks might represent a variant of idiopathic intracranial hypertension (IIH). We review the evidence regarding the association between spontaneous CSF leaks and IIH, and the role of ICP in the pathophysiology of nontraumatic skull base defects. We also discuss the management of ICP in the setting of CSF leaks and IIH. EVIDENCE ACQUISITION References were identified by searches of PubMed from 1955 to September 2018 with the terms "idiopathic intracranial hypertension" and "cerebrospinal fluid leak. " Additional references were identified using the terms "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," and by hand search of relevant articles. RESULTS A CSF leak entails the egress of CSF from the subarachnoid spaces of the skull base into the surrounding cavitary structures. Striking overlaps exist regarding demographic, clinical, and radiological characteristics between IIH patients and those with spontaneous CSF leaks, suggesting that some (if not most) of these patients have IIH. However, determining whether a patient with spontaneous CSF leak may have IIH may be difficult, as signs and symptoms of raised ICP may be obviated by the leak. The pathophysiology is unknown but might stem from progressive erosion of the thin bone of the skull base by persistent pulsatile high CSF pressure. Currently, there is no consensus regarding the management of ICP after spontaneous CSF leak repair when IIH is suspected. CONCLUSIONS IIH is becoming more widely recognized as a cause of spontaneous CSF leaks, but the causal relationship remains poorly characterized. Systematic evaluation and follow-up of patients with spontaneous CSF leaks by neuro-ophthalmologists will help clarify the relation between IIH and spontaneous CSF leaks.
The Hierarchical Taxonomy of Psychopathology (HiTOP): A Dimensional Alternative to Traditional Nosologies

The reliability and validity of traditional taxonomies are limited by arbitrary boundaries between psychopathology and normality, often unclear boundaries between disorders, frequent disorder co-occurrence, heterogeneity within disorders, and diagnostic instability. These taxonomies went beyond evidence available on the structure of psychopathology and were shaped by a variety of other considerations, which may explain the aforementioned shortcomings. The Hierarchical Taxonomy Of Psychopathology (HiTOP) model has emerged as a research effort to address these problems. It constructs psychopathological syndromes and their components/subtypes based on the observed covariation of symptoms, grouping related symptoms together and thus reducing heterogeneity. It also combines co-occurring syndromes into spectra, thereby mapping out comorbidity. Moreover, it characterizes these phenomena dimensionally, which addresses boundary problems and diagnostic instability. Here, we review the development of the HiTOP and the relevant evidence. The new classification already covers most forms of psychopathology. Dimensional measures have been developed to assess many of the identified components, syndromes, and spectra. Several domains of this model are ready for clinical and research applications. The HiTOP promises to improve research and clinical practice by addressing the aforementioned shortcomings of traditional nosologies. It also provides an effective way to summarize and convey information on risk factors, etiology, pathophysiology, phenomenology, illness course, and treatment response. This can greatly improve the utility of the diagnosis of mental disorders. The new classification remains a work in progress. However, it is developing rapidly and is poised to advance mental health research and care significantly as the relevant science matures.