Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Homologue Composition of Technical Chlorinated Paraffins Used in Several Countries over the Last 50 Years─SCCPs Are Still Out There.

Chlorinated paraffins (CPs) are widely produced chemicals, with certain CP subgroups facing global restrictions due to their environmental dispersion, persistence, bioaccumulation, and toxicity. To evaluate the effectiveness of these international restrictions, we assessed the homologue group contribution and the mass fraction of short-chain CPs (SCCPs: C10-C13), medium-chain CPs (MCCPs: C14-C17), and long-chain CPs (LCCPs: ≥C18) in 36 technical CP mixtures used worldwide over the last 50 years. Using low-resolution mass spectrometry (LC-ESI-MS/MS), we quantified 74 CP homologue groups (C10Cl4-C20Cl10). Additionally, high-resolution mass spectrometry (LC-ESI-QTOF-MS) screening was employed to identify unresolved CP contents, covering 375 CP homologue groups (C6Cl4-C30Cl30). Overall, 1 sample was mainly composed of

First assessment of atmospheric pollution by trace elements and particulate matter after a severe collapse of a tailings dam, Minas Gerais, Brazil: An insight into biomonitoring with Tillandsia usneoides and a public health dataset.

In this study, samples of bromeliad Tillandsia usneoides (n = 70) were transplanted and exposed for 15 and 45 days in 35 outdoor residential areas in Brumadinho (Minas Gerais state, Brazil) after one of the most severe mining dam collapses in the world. Trace elements aluminum (Al), arsenic (As), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni) and zinc (Zn) were quantified by atomic absorption spectrometry. Scanning electron microscope generated surface images of T. usneoides fragments and particulate matter (PM2.5, PM10 and PM > 10). Aluminum, Fe and Mn stood out from the other elements reflecting the regional geological background. Median concentrations in mg kg-1 increased (p < 0.05) between 15 and 45 days for Cr (0.75), Cu (1.23), Fe (474) and Mn (38.1), while Hg (0.18) was higher at 15 days. The exposed-to-control ratio revealed that As and Hg increased 18.1 and 9.4-fold, respectively, not showing a pattern associated only with the most impacted sites. The PM analysis points to a possible influence of the prevailing west wind on the increase of total particles, PM2.5 and PM10 in transplant sites located to the east. Brazilian public health dataset revealed increase in cases of some cardiovascular and respiratory diseases/symptoms in Brumadinho in the year of the dam collapse (1.38 cases per 1000 inhabitants), while Belo Horizonte capital and its metropolitan region recorded 0.97 and 0.37 cases, respectively. Although many studies have been carried out to assess the consequences of the tailings dam failure, until now atmospheric pollution had not yet been evaluated. Furthermore, based on our exploratory analysis of human health dataset, epidemiological studies are required to verify possible risk factors associated with the increase in hospital admissions in the study area.

Quantum chemical descriptors based on semiempirical methods for large biomolecules.

In this Review, we reviewed the efforts to expand the applications of conceptual density functional theory reactivity descriptors and hard and soft acid and base principles for macromolecules and other strategies that focused on low-level quantum chemistry methods. Currently, recent applications are taking advantage of modifications of these descriptors using semiempirical electronic structures to explain enzymatic catalysis reactions, protein-binding processes, and structural analysis in proteins. We have explored these new solutions along with their implementations in the software PRIMoRDiA, discussing their impact on the field and its perspectives. We show the main issues in the analysis of the electronic structure of macromolecules, which are the application of the same calculation protocols used for small molecules without considering particularities in those large systems' electronic configuration. The major result of our discussions is that the use of semiempirical methods is crucial to obtain such a type of analysis, which can provide a powerful dimension of information and be part of future low-cost predictive tools. We expect semiempirical methods continue playing an important role in the quantum chemistry evaluation of large molecules. As computational resources advance, semiempirical methods might lead us to explore the electronic structure of even larger biological macromolecular entities and sets of structures representing larger timescales.

[Integrative medicine and geriatrics : towards a convergence?] / Médecine intégrative et gériatrie : vers une convergence ?

In recent years integrative medicine has been the subject of growing interest among the overall population as well as the medical and scientific community. According to the Swiss health survey, approximately 40 % of the Swiss population regularly use complementary therapies. The fields of application of integrative medicine in geriatrics seem large (pain, cognitive disorders, end-of-life support, anxiety, etc.). Although scientific evidence is progressing in this area, studies targeting the population > 65 years old are still limited. The aim of this article is to expose some examples of complementary medicine applications in in geriatric care and the potential for rapprochement between integrative medicine and geriatric.

La médecine intégrative fait l'objet d'un intérêt accru au sein de la population et de la communauté médicale et scientifique ces dernières années. Selon l'Enquête suisse sur la santé, environ 40 % de la population suisse a régulièrement recours à des thérapies complémentaires. Les domaines d'application des médecines intégratives dans les soins gériatriques semblent vastes (douleurs, troubles du sommeil, accompagnement de fin de vie, anxiété, etc.). Les études ciblant spécifiquement la population de 65 ans et plus dans ce domaine restent encore limitées à notre connaissance. Cet article a pour but de présenter quelques exemples d'applications de médecine complémentaire dans la prise en charge des syndromes gériatriques et sensibiliser au potentiel de rapprochement entre la médecine intégrative et la gériatrie.

Infection by Moniliophthora perniciosa reprograms tomato Micro-Tom physiology, establishes a sink, and increases secondary cell wall synthesis.

Witches' broom disease of cacao is caused by the pathogenic fungus Moniliophthora perniciosa. By using tomato (Solanum lycopersicum) cultivar Micro-Tom (MT) as a model system, we investigated the physiological and metabolic consequences of M. perniciosa infection to determine whether symptoms result from sink establishment during infection. Infection of MT by M. perniciosa caused reductions in root biomass and fruit yield, a decrease in leaf gas exchange, and down-regulation of photosynthesis-related genes. The total leaf area and water potential decreased, while ABA levels, water conductance/conductivity, and ABA-related gene expression increased. Genes related to sugar metabolism and those involved in secondary cell wall deposition were up-regulated upon infection, and the concentrations of sugars, fumarate, and amino acids increased. 14C-glucose was mobilized towards infected MT stems, but not in inoculated stems of the MT line overexpressing CYTOKININ OXIDASE-2 (35S::AtCKX2), suggesting a role for cytokinin in establishing a sugar sink. The up-regulation of genes involved in cell wall deposition and phenylpropanoid metabolism in infected MT, but not in 35S::AtCKX2 plants, suggests establishment of a cytokinin-mediated sink that promotes tissue overgrowth with an increase in lignin. Possibly, M. perniciosa could benefit from the accumulation of secondary cell walls during its saprotrophic phase of infection.

Perivascular clusters of Th2 cells and M2 macrophages in allergic contact dermatitis to methylchloroisothiazolinone and methylisothiazolinone.

BACKGROUND: Methylisothiazolinone (MI) and Methylchloroisothiazolinone (MCI) are among the most common skin sensitizers, yet the immunological events that occur during MCI/MI allergic contact dermatitis (ACD) are still poorly understood. OBJECTIVES: To analyse dendrocytes, macrophage subtypes and T cells in skin during the elicitation phase of MCI/MI ACD. METHODS: Thirteen patients with positive patch test reactions to MCI/MI (ACD group) and 11 individuals with negative patch test results were selected. Skin biopsies were only performed at 48 hours of patch testing. Immunohistochemistry was conducted to assess T cells, dendrocytes (Factor XIIIa), M1 (p-Stat1, CD68) and M2 (c-Maf, CD163) macrophages. Transcriptional analyses were performed for cytokines and related factors, and further compared to atopic dermatitis samples (n=4). Immunofluorescence assays addressed T cells location, along with IL-4 or IL-13, within the skin. RESULTS: MCI/MI elicited dermal dendrocytes and macrophages, pronouncedly the M2 subtype. T cells, majorly CD4+ T cells, accumulated in the perivascular areas. Similarly, abundant IL-4 protein was detected in these areas. There was an upregulation of IL-4 and IL-13 mRNA expression, a mild increase in IFNG mRNA levels and a down-regulation of RORC in the ACD group. Immunofluorescence revealed dermal clusters of T cells co-localized with IL-4. CONCLUSIONS: M2 macrophages and Th2 cells participate in the immunopathogenesis of MCI/MI ACD. Dermal dendrocytes and M2 macrophages may assist the formation of CD4+ T cells perivascular clusters. These findings render a mechanistic insight into the MCI/MI reaction. Further analysis at different timepoints of patch testing is required to fully comprehend this ACD kinetics.

Perfluoroalkylated compounds in the eggs and feathers of resident and migratory seabirds from the Antarctic Peninsula.

In this study, we investigated factors that influence the differences in exposure of perfluoroalkyl acids (PFAAs) from eight species of Antarctic seabirds, including Pygoscelis penguins, Stercorarius maccormicki, and Macronectes giganteus. We analyzed the relationship between foraging ecology (based on δ13C, δ15N, and δ34S values) and PFAAs accumulated in eggs and breast feathers. Ten out of 15 targeted PFAAs were detected in eggs compared to eight in feathers. Mean ∑PFAA concentrations in feathers ranged from 0.47 in P. antarcticus to 17.4 ng/g dry weight (dw) in S. maccormicki. In eggs, ∑PFAA concentrations ranged from 3.51 in P. adeliae to 117 ng/g dw in S. maccormicki. The highest concentrations of most PFAAs were found in trans-equatorial migrators such as S. maccormicki, probably due their high trophic position and higher concentrations of PFAAs in the Northern Hemisphere compared to the Southern Hemisphere. Based on stable isotopes correlations, our results suggest that the trophic position (δ15N) and the foraging area (δ13C and δ34S) influence PFAAs concentrations in Antarctic seabirds. Our results point to the possibility that long-distance migratory birds may have as bio-vectors in the transport of pollutants, including PFCAs, in Antarctic environments, although this must be further confirmed in future studies using a mass balanced approach, such as extractable organofluorine (EOF).

First year after the Brumadinho tailings' dam collapse: Spatial and seasonal variation of trace elements in sediments, fishes and macrophytes from the Paraopeba River, Brazil.

On January 2019, the B1 iron ore tailings' dam collapsed in Brumadinho, Brazil, being one of the worst mining-related disasters, with 270 human deaths (11 of them still missing) and 12.106 m3 of tailings released to the environment. The tailings devastated the Córrego do Feijão brook and reached the adjacent Paraopeba River, the region's main watercourse and a major tributary of the São Francisco basin. Although physicochemical parameters of the river were strongly impacted, and acute toxicological effects have been reported from exposure experiments, contamination of aquatic biota had not yet been assessed. Therefore, the aim of this study was to evaluate contamination by trace elements (As, Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn) in sediment, fish and macrophytes along the Paraopeba River, upstream and downstream from the dam failure site, during the dry and wet season. With the exception of Cd and Hg, all elements in sediment samples had lower median concentrations downstream. An inverse pattern was observed for the aquatic biota, with significant higher concentrations of Fe, Mn, Ni and Zn in fishes, and increased concentrations of most elements in macrophytes, indicating an increase in element bioavailability. A significant seasonal variation was observed with increased concentrations of As (dry season) and Pb (wet season) in fish samples, with the same trend occurring in macrophytes. Concentrations of potentially toxic elements in fish samples in wet weight (Cr: 1.80 ± 1.31 mg kg-1, Hg: 0.21 ± 0.11 mg kg-1 and Pb: 0.79 ± 0.80 mg kg-1) were lower than those reported before the disaster. Furthermore, As and Pb concentrations exceeded the safety threshold for fish consumption in 3% and 41% of samples, respectively, representing a matter of concern for public health.

Rinsing with Statherin-Derived Peptide Alters the Proteome of the Acquired Enamel Pellicle.

Changes in the proteomic profile of the acquired enamel pellicle (AEP) formed for 3 min or 2 h after rinsing with a peptide containing the 15 N-terminal residues of statherin, with serines 2 and 3 phosphorylated (StatpSpS), were evaluated. Nine volunteers participated in 2 consecutive days. Each day, after professional tooth cleaning, they rinsed for 1 min with 10 mL of phosphate buffer containing 1.88 × 10-5 M StatpSpS or phosphate buffer only (control). The acquired pellicle formed on enamel after 3 min or 2 h was collected with electrode filter papers soaked in 3% citric acid. After protein extraction, samples were analyzed by quantitative shotgun label-free proteomics. In the 3-min AEP, 19 and 131 proteins were uniquely identified in the StatpSpS and control groups, respectively. Proteins typically found in the AEP were only found in the latter. Only 2 proteins (neutrophil defensins) were increased upon treatment with StatpSpS, while 65 proteins (among which are several typical AEP proteins) were decreased. In the 2-h AEP, 50 and 108 proteins were uniquely found in StatpSpS and control groups, respectively. Hemoglobin subunits and isoforms of keratin were only found in the StatpSpS group, while cystatin-C, cathepsin D, and cathepsin G, isoforms of heat shock 70 and protocadherin were exclusively found in the control group. In addition, 23 proteins were increased upon treatment with StatpSpS, among which are histatin-1, serum albumin, and isoforms of neutrophil defensin and keratin, while 77 were decreased, most of them were typical AEP proteins. In both evaluated periods, rinsing with StatpSpS profoundly changed the proteomic profile of the AEP, which might impact the protective role of this integument against carious or erosive demineralization. This study provides important insights on the dynamics of the protein composition of the AEP along time, after rinsing with a solution containing StatpSpS.

Co-precipitation of anthocyanin in PHBV by the SEDS technique.

Anthocyanins are pigments of plant origin responsible for most blue, purple and all shades of red found in flowers, fruits and some stems and roots of plants, besides comprising a class of potent antioxidant phenolic compounds. Due to the relevance of anthocyanins this work aims to encapsulate anthocyanin extracted from the wine lees through the Solution Enhanced Dispersion by Supercritical Fluids (SEDS) technique and to evaluate the thermal stability of encapsulated versus non-encapsulated anthocyanin. The highest encapsulation efficiency obtained was approximately 66%. Submicron size particles ranging from 0.22 to 0.30 µm were obtained and they were free of residual organic solvent. In relation to the thermal stability, it was verified that the particles degraded about six times less than the non-encapsulated sample, which allows numerous applications since one of the barriers of anthocyanin use is its sensitivity to high temperatures.

Quality of honeys from different botanical origins.

Botanical origin is one of the principal factors influencing the composition and quality of honey. This study aimed to evaluate different single-flower (assa-peixe, coffee, eucalyptus, laranjeira, and vassourinha), polyfloral (silvestre), extrafloral (sugarcane), and honeydew (bracatinga) honeys with regard to their chemical, physicochemical, and physical properties; rheological behavior; bioactive compounds; and antioxidant activity. In addition, we assessed their sensory characteristics using the acceptance test and the check-all-that-apply test (CATA). All honeys were compliant with current legislation and presented Newtonian behavior. The honeys of assa-peixe, laranjeira, and coffee presented the highest viscosity, sugarcane honey showed the highest antioxidant activity, and the bracatinga honey had the highest phenolic compound content. With respect to sensory characteristics, floral honeys presented higher acceptability than did honeydew and extrafloral honeys, because honey from honeydew was negatively influenced by its bitter, alcoholic, and astringent taste and extrafloral honey by its burnt smell. These findings indicate that the botanical origin directly influences the characteristics of honeys and can be considered a factor for their differentiation.

[A mixed intra-hospital mobile team of geriatrics and palliative care: The Neuchâtel experience]. / Équipe mobile mixte gériatrie et soins palliatifs intrahospitalièreL'expérience neuchâteloise.

The increasing life expectancy, the earlier detection of terminal illnesses and the increasing complexity of care pathways led us to propose an innovative response within the Neuchâtel Hospital Network (RHNe), in the form of a mixed intra-hospital mobile team (GSPmob), composed of doctors and nurses from geriatrics and palliative care. Through geriatric and palliative assessment, we are able to highlight the patient's different medical problems. Our team, after two years of existence, has met our patients' needs as well as the hospital teams' needs. And yet we encountered certain challenges. Our current objective is to describe our experience by presenting our results and difficulties.

L'augmentation de l'espérance de vie, la détection plus précoce de maladies terminales et la complexification des parcours de soins nous ont amenés à proposer une réponse innovante au sein du Réseau hospitalier neuchâtelois, sous forme d'une équipe mobile mixte intrahospitalière, de médecins et infirmiers issus de la gériatrie ou des soins palliatifs (équipe mobile mixte de gériatrie et de soins palliatifs). Grâce aux évaluations gériatriques et palliatives, cette équipe permet la détection et la prise en charge de différentes problématiques spécifiques chez les patients. Depuis près de 2 ans d'existence, malgré les défis qui restent à relever, notre équipe répond à un réel besoin des patients et des équipes soignantes. L'objectif est ici de décrire notre expérience en présentant nos résultats et nos difficultés.

Ventral hippocampus inactivation enhances the extinction of active avoidance responses in the presence of safety signals but leaves discrete trial operant active avoidance performance intact.

The acquisition of active avoidance (AA) behavior is typically aided by the presence of two signals-the warning signal, which predicts the future occurrence of an aversive event (e.g., shocks), and the safety signal, which is presented upon successful avoidance of oncoming shocks. While the warning signal could be conceived to act as a Pavlovian fear cue, and is likely mediated by brain areas that underlie Pavlovian fear cue conditioning, the neural substrates underlying safety signaling are less clear, largely due to the unavailability of AA tasks that are devoid of an explicit warning signal. The present study sought to investigate the role of the ventral hippocampus (VH) in safety signaled AA performance acquired without an explicit warning signal, using a novel discrete trial paradigm. Adult male Long Evans rats were divided into two groups and trained to acquire AA responses with, or without a safety signal. Analysis of the acquisition and stable state performance data revealed that the availability of a safety signal alone did not improve the acquisition or performance of AA responses. Furthermore, post-training, reversible VH inactivation did not impact stable state avoidance behavior. However, extinction of avoidance responses was facilitated in the group trained with a safety signal, and this effect was further potentiated by VH inactivation. Additional elevated plus maze (EPM), light-dark box, and locomotor tests demonstrated that VH inactivation reduced anxiety without affecting locomotor activity. Taken together, these results demonstrate the importance of VH in the extinction of persistent pathological avoidance behavior when safety is signaled.

Semiempirical methods do Fukui functions: Unlocking a modeling framework for biosystems.

Obtaining reactivity information from the molecular electronic structure of a chemical system is a computationally intensive process. As a way of probing reactivity information around that, there exist electron density response variables, such as the Fukui functions (FFs), which are well-established descriptors that summarize the local susceptibility to react. These properties only require few single-point quantum chemical calculations, but even then, the intrinsic high cost and unfavorable computational complexity with respect to the number of atoms in the system makes this approach available only to small fragments and systems. In this study, we explore the computation of FFs, showing that semiempirical quantum chemical methods can be used to obtain the reactivity information equivalent to that of a Density Functional Theory (DFT) functional, for the eight entire polypeptide chains. The combination of semiempirical methods with the frozen orbital approximation allows for the obtention of these reactivity descriptors for biological systems with reasonable accuracy and speed, unlocking the utilization of these methods for such systems. These results for the frozen orbital approximation can be additionally improved when other molecular orbitals from the frontier band are employed in the computation. We also show the potential of this computational protocol in the ligand-protein complexes of HIV-1 protease, predicting which of those ligands are active inhibitors.

Genome-wide characterization of the laccase gene family in Setaria viridis reveals members potentially involved in lignification.

MAIN CONCLUSION: Five laccase genes are potentially involved in developmental lignification in the model C4 grass Setaria viridis and their different tissue specificities suggest subfunctionalization events. Plant laccases are copper-containing glycoproteins involved in monolignol oxidation and, therefore, their activity is essential for lignin polymerization. Although these enzymes belong to large multigene families with highly redundant members, not all of them are thought to be involved in lignin metabolism. Here, we report on the genome-wide characterization of the laccase gene family in the model C4 grass Setaria viridis and further identification of the members potentially involved in monolignol oxidation. A total of 52 genes encoding laccases (SvLAC1 to SvLAC52) were found in the genome of S. viridis, and phylogenetic analyses showed that these genes were heterogeneously distributed among the characteristic six subclades of the family and are under relaxed selective constraints. The observed expansion in the total number of genes in this species was mainly caused by tandem duplications within subclade V, which accounts for 68% of the whole family. Comparative phylogenetic analyses showed that the expansion of subclade V is specifically observed for the Paniceae tribe within the Panicoideae subfamily in grasses. Five SvLAC genes (SvLAC9, SvLAC13, SvLAC15, SvLAC50, and SvLAC52) fulfilled the criteria established to identify lignin-related candidates: (1) phylogenetic proximity to previously characterized lignin-related laccases from other species, (2) similar expression pattern to that observed for lignin biosynthetic genes in the S. viridis elongating internode, and (3) high expression in S. viridis tissues undergoing active lignification. In addition, in situ hybridization experiments not only confirmed that these selected SvLAC genes were expressed in lignifying cells, but also that their expression showed different tissue specificities, suggesting subfunctionalization events within the family. These five laccase genes are strong candidates to be involved in lignin polymerization in S. viridis and might be good targets for lignin bioengineering strategies.

Proinflammatory and regulatory mechanisms in allergic contact dermatitis caused by methylchloroisothiazolinone and methylisothiazolinone.

BACKGROUND: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the cause of an increasing number of contact allergies. Understanding the mechanisms by which MCI/MI induces proinflammatory and regulatory factors production is necessary to understand the outcome of allergic contact dermatitis (ACD). OBJECTIVES: To evaluate the dysfunction of proinflammatory cytokines and regulatory factors in the positive MCI/MI patch test at the transcriptional and protein expression levels. Moreover, to analyse the cytokines production induced by MI in peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: The selected patients had positive MCI/MI patch test results. The expression of proinflammatory factors was evaluated by q-PCR and immunochemistry at 48 hours of positive MCI/MI patch test. The MCI/MI- or MI- induced secretion of IL-1ß, TNF and IL-6 by PBMC was analysed by flow cytometry. RESULTS: The results showed a decreased TLR4 expression with upregulated IL6, FOXP3, IL10 and TGFß mRNA expression as assessed by q-PCR at the site of the MCI/MI skin reaction. We detected increased protein levels of TLR4, FOXP3 and IL-10 in the dermis layer in the ACD reaction by immunocitochemistry. Moreover, MCI/MI induced proinflammatory cytokine production by PBMC through the NF-κB signalling pathway. CONCLUSION: Considering the altered innate immune response triggered by MCI/MI sensitization, these findings indicate that the regulatory process at the induction phase of ACD is a crucial mechanism. Given the increase in occupational and domestic exposure to MCI/MI, the underlying immunological mechanisms should be understood.

PRIMoRDiA: A Software to Explore Reactivity and Electronic Structure in Large Biomolecules.

Plenty of enzymes with structural data do not have their mechanism of catalysis elucidated. Reactivity descriptors, theoretical quantities generated from resolved electronic structure, provide a way to predict and rationalize chemical processes of such systems. In this Application Note, we present PRIMoRDiA (PRIMoRDiA Macromolecular Reactivity Descriptors Access), a software built to calculate the reactivity descriptors of large biosystems by employing an efficient and accurate treatment of the large output files produced by quantum chemistry packages. Here, we show the general implementation details and the software main features. Calculated descriptors were applied for a set of enzymatic systems in order to show their relevance for biological studies and the software potential for use in large scale. Also, we test PRIMoRDiA to aid in the interaction depiction between the SARS-CoV-2 main protease and a potential inhibitor.

Elucidating Enzymatic Catalysis Using Fast Quantum Chemical Descriptors.

In general, computational simulations of enzymatic catalysis processes are thermodynamic and structural surveys to complement experimental studies, requiring high level computational methods to match accurate energy values. In the present work, we propose the usage of reactivity descriptors, theoretical quantities calculated from the electronic structure, to characterize enzymatic catalysis outlining its reaction profile using low-level computational methods, such as semiempirical Hamiltonians. We simulate three enzymatic reactions paths, one containing two reaction coordinates and without prior computational study performed, and calculate the reactivity descriptors for all obtained structures. We observed that the active site local hardness does not change substantially, even more so for the amino-acid residues that are said to stabilize the reaction structures. This corroborates with the theory that activation energy lowering is caused by the electrostatic environment of the active sites. Also, for the quantities describing the atom electrophilicity and nucleophilicity, we observed abrupt changes along the reaction coordinates, which also shows the enzyme participation as a reactant in the catalyzed reaction. We expect that such electronic structure analysis allows the expedient proposition and/or prediction of new mechanisms, providing chemical characterization of the enzyme active sites, thus hastening the process of transforming the resolved protein three-dimensional structures in catalytic information.

Addition of specific hip strengthening exercises to conventional rehabilitation therapy for low back pain: a systematic review and meta-analysis.

OBJECTIVE: To examine the effectiveness of hip strengthening exercises in reducing pain and disability in persons with low back pain. METHODS: We searched for randomized controlled clinical trials on MEDLINE, the Physiotherapy Evidence Database, the Cochrane Central Register of Controlled Trials, LILACS, Scielo and CINAHL from the earliest date available to June 2020. Studies that included hip strengthening exercises for persons with low back pain and included pain and/or disability as an outcome measure were evaluated by two independent reviewers. Mean difference (MD), and 95% confidence interval (CI) were estimated by random effect models. RESULTS: Five studies met the eligibility criteria (309 patients). Four studies included hip strengthening in conjunction with other interventions, while one study evaluated hip strengthening as a standalone intervention. Hip strengthening exercises improved pain (MD -5.4 mm, 95% CI: -8.9 to -1.8 mm), and disability (MD -2.9; 95% CI: -5.6 to -0.1) in persons with low back pain compared to interventions in which hip strengthening was not utilized. The quality of evidence for the pain outcome, was assessed as being moderate. The quality of evidence for the outcome of self-reported disability, was assessed as being low. CONCLUSION: Addition of specific hip strengthening exercises to conventional rehabilitation therapy may be beneficial for improving pain and disability in persons with low back pain.