Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study.

BACKGROUND: Janus kinase 1 inhibition may alleviate hidradenitis suppurativa (HS)-associated inflammation and improve symptoms. OBJECTIVE: To assess efficacy and safety of povorcitinib (selective oral Janus kinase 1 inhibitor) in HS. METHODS: This placebo-controlled phase 2 study randomized patients with HS 1:1:1:1 to receive povorcitinib 15, 45, or 75 mg or placebo for 16 weeks. Primary and key secondary end points were mean change from baseline in abscess and inflammatory nodule count and percentage of patients achieving HS Clinical Response at week 16. RESULTS: Of 209 patients randomized (15 mg, n = 52; 45 mg, n = 52; 75 mg, n = 53; placebo, n = 52), 83.3% completed the 16-week treatment. At week 16, povorcitinib significantly reduced abscess and inflammatory nodule count from baseline (least squares mean [SE] change: 15 mg, -5.2 [0.9], P = .0277; 45 mg, -6.9 [0.9], P = .0006; 75 mg, -6.3 [0.9], P = .0021) versus placebo (-2.5 [0.9]). More povorcitinib-treated patients achieved HS Clinical Response at week 16 (15 mg, 48.1%, P = .0445; 45 mg, 44.2%, P = .0998; 75 mg, 45.3%, P = .0829) versus placebo (28.8%). A total of 60.0% and 65.4% of povorcitinib- and placebo-treated patients had adverse events. LIMITATIONS: Baseline lesion counts were mildly imbalanced between groups. CONCLUSION: Povorcitinib demonstrated efficacy in HS, with no evidence of increased incidence of adverse events among doses.

XP-Endo Finisher behaviour and irrigant temperature in intracanal environment: Clinical measurements.

AIM: To evaluate the behaviour of the XP-Endo Finisher and the variation in the intracanal temperature of the irrigant at rest and when activated over time. METHODOLOGY: Differential scanning calorimetry (DSC) determined the transformation temperatures of XP-Endo Finisher instruments. A digital thermocouple was used to measure the temperature of the irrigant inside the pulp chamber. Two measurements were performed for each tooth (n = 12): with the irrigant at rest and during XP-Endo agitation for 60 s to observe the temperature evolution. The data were statistically analysed using a t-test with a confidence level of 95%. RESULTS: DSC results suggested that the XP-Endo Finisher had a mixed R-phase and austenitic structure at room temperature. The temperature values at predetermined time points (0, 10, 40, 70, 120 and 240 s) were measured, and no statistical difference was observed between the values of the resting and activated solutions at any of the selected points (p > .05). For the protocol performed with the XP-Endo file, the mean irrigant temperature observed at instrument insertion inside the root canal was 28.65°C. After 60 s of agitation, the temperature was 34.02°C. The solution temperature stabilized inside the canal only after 211 s at 35.5°C. The mean maximum irrigation solution temperature recorded inside the canal was 35.5°C without agitation and after XP-endo agitation (p > .05). CONCLUSIONS: Although the XP-Endo Finisher system does not promote heating of the irrigation solution, file expansion responsible for improved instrument cleaning starts at a temperature below the expected value.

Effects of Different Resistance Training Frequencies on Body Composition, Muscular Strength, Muscle Quality, and Metabolic Biomarkers in Sarcopenic Older Women.

ABSTRACT: Dos Santos, VR, Antunes, M, dos Santos, L, Nascimento, MA, Pina, FLC, Carneiro, NH, Trindade, MCC, Venturini, D, Barbosa, DS, and Cyrino, ES. Effects of different resistance training frequencies on body composition, muscular strength, muscle quality, and metabolic biomarkers in sarcopenic older women. J Strength Cond Res 38(9): e521-e528, 2024-Resistance training (RT) can ameliorate outcomes related to sarcopenia by promoting beneficial changes in muscular strength, skeletal muscle mass (SMM), and muscle quality. This study compared the effects of 12 weeks of RT performed 2 and 3 sessions a week on body composition, muscular strength, muscle quality, and metabolic biomarkers in sarcopenic older women. Thirty-four sarcopenic older women (>60 years) were randomly assigned to perform a whole-body RT program, either 2 (G2X, n = 18) or 3 (G3X, n = 16) sessions a week during 12 weeks (8 exercises, single set of 10-15 repetitions). Body composition, muscular strength, muscle quality, and metabolic biomarkers were assessed before and after the intervention. Both groups increased (p < 0.05) 1 repetition maximum total muscular strength (G2X = +20.4% and G3X = +21.0%), SMM (G2X = +4.0% and G3X = +7.0%), and improved muscle quality (G2X = +16.7% and G3X = +13.6%), with no differences between groups (p > 0.05). No change over time was found for IGF-1 and testosterone (p > 0.05). Our results suggest that 12 weeks of RT performed at a lower weekly frequency is as effective as a higher frequency in improving muscular strength, SMM, and muscle quality in sarcopenic older women.

Effect of resistance training on bioelectrical phase angle in older adults: a systematic review with Meta-analysis of randomized controlled trials.

Resistance training has been proposed as a valid practice to counteract the aging effect on body mass and its components, which can be easily evaluated though the bioelectrical impedance analysis. This study aimed to achieve a systematic review with meta-analysis on the impact of resistance training on bioelectrical proprieties in older adults.A literature review was done in four electronic databases up to 1 January 2022. The inclusion criteria were: (i) participants aged ≥ 60 years; (ii) resistance training lasted ≥ 8 weeks; (iii) measurement of raw bioelectrical parameters in randomized controlled study designs.The outcomes of the trial had to be bioelectrical phase angle (PhA), resistance (R), and reactance (Xc). The methodological quality was assessed using the Rosendal scale.Overall, seven studies with a total of 344 participants were eligible for the analysis. The quality assessment yielded a score of 71.3%. Bioelectrical PhA (0.52 degree [95%CI 0.32, 0.71], p < 0.001) and Xc (3.58 ohms [95%CI 1.97, 5.19], p < 0.001) increased, whereas R decreased (-28.50 ohms [95%CI -41.39, -15.60], p < 0.001) after the resistance training programs.In this meta-analysis, resistance training promoted increases of PhA, which result from an increase in Xc concomitant with a reduction in R. According to the bioimpedance vector analysis, resistance-trained people experienced a beneficial leftward vector displacement, whilst inactivity induced a rightward vector displacement within the R-Xc graph. In future, more sophisticated and rigorous studies that address specific criteria, methods and targeted designs are required to identify which equipment and protocols allow for an optimization of the resistance training effects.Registration code in PROSPERO: CRD42020168057.

No Association Between Interleukin 6 and Inducible Nitric Oxide Synthase Polymorphisms and Dengue Infection: A Case-Control Study.

BACKGROUND: Dengue is a life-threatening disease. The factors that lead to severe cases are not completely understood. The host immune system is involved in the response to infections and plays an important role in dengue infection. IL-6 and iNOS are components of the immune system and genetic polymorphisms in these genes may be involved in dengue virus infection. The study aimed to investigate the association of genetic polymorphisms in the IL6 and iNOS genes and dengue. METHODS: We performed a case-control study using 60 dengue-infected individuals and 119 healthy controls. Polymorphisms in the IL6 (T15A) and iNOS (-1173CT) genes were amplified by Real-Time PCR. Statistical analyses were performed using BioEstat 5.0. RESULTS: We identified that the frequency of T/A genotype of IL6 was higher in dengue fever patients and C/T genotype of iNOS was higher in dengue hemorrhagic fever patients, however, no association was found between these polymorphisms and dengue. CONCLUSION: Polymorphisms in iNOS and IL6 were not associated with dengue infection.

Immobilization of the metagenomic lipase, LipG9, on porous pellets of poly-hydroxybutyrate produced by the double emulsion solvent evaporation technique.

This work aimed to produce porous poly-hydroxybutyrate (PHB) pellets in order to evaluate the pellets as a support for immobilization of the metagenomic lipase, LipG9. Four types of pelletized PHB particles with different morphological characteristics were obtained using the double emulsion and solvent evaporation technique (DESE). The micropores of these PHB pellets had similar average diameters (about 3 nm), but the pellets had different specific surface areas: 11.7 m2 g-1 for the PHB powder, 8.4 m2  g-1 for the control pellets (Ø < 0.5 mm, produced without the pore forming agent), 10.0 m2  g-1 for the small pellets (Ø < 0.5 mm), 9.5 m2  g-1 for the medium pellets (0.5 < Ø < 0.8 mm) and 8.4 m2  g-1 for the large pellets (Ø > 1.4 mm). Purified LipG9 was immobilized by adsorption on these pellets, and the results were compared with those obtained with PHB powder. The highest immobilization yield (83%) was obtained for the medium PHB pellets, followed by large (76%) and small (55%) PHB pellets. The activity of LipG9 immobilized on the pellets, for the synthesis of ethyl oleate in n-hexane, was highest for the medium pellets (22 U g-1 ). The immobilization yield was high for PHB powder (99%) but the esterification activity was slightly lower (20 U g-1 ). These results show that pelletized PHB beads can be used for the immobilization of lipases, with the advantage that pelletized PHB will perform better than PHB powder in large-scale enzyme bioreactors.

Are more physical education classes related to less time in leisure-time sedentary behavior? An analysis including adolescents from 73 countries.

This study aimed to verify the association between the weekly frequency of physical education (PE) classes and leisure sitting time among adolescents. We analyzed data from 73 countries using the Global School-based Student Health Survey (283,233 adolescents between 11 and 18 years of age). Leisure sitting time and weekly frequency of PE classes were self-reported. Sex, age, and food insecurity were used as covariates and the analyses were stratified by world regions and country income level. Poisson regression models (random-effects meta-analysis) were used for the main analyses. In comparison with 1 PE class per week (reference group), those with no PE classes presented a lower prevalence of ≥ 3 h/d of leisure sitting time (PR [95%CI] = 0.94 [0.91; 0.98]). On the other hand, adolescents with 2 days (PR [95%CI] = 1.06 [1.02; 1.26]), 3-4 days (PR [95%CI] = 1.17 [1.12; 1.22]), and 5 days (PR [95%CI] = 1.08 [1.04; 1.11]) of PE classes presented a higher likelihood of ≥ 3 h/d of leisure sitting time. No clear differences were observed for the different world regions and country income levels. We conclude that a higher weekly frequency of PE classes is associated with increased leisure sitting time among adolescents worldwide.

Modulation of Disease-Associated Pathways in Hidradenitis Suppurativa by the Janus Kinase 1 Inhibitor Povorcitinib: Transcriptomic and Proteomic Analyses of Two Phase 2 Studies.

Janus kinase (JAK)/signal transducer and activator of transcription signaling (STAT) has been implicated in the pathophysiology of hidradenitis suppurativa (HS). This study evaluated treatment-related transcriptomic and proteomic changes in patients with moderate-to-severe HS treated with the investigational oral JAK1-selective inhibitor povorcitinib (INCB054707) in two phase 2 trials. Lesional skin punch biopsies (baseline and Week 8) were taken from active HS lesions of patients receiving povorcitinib (15 or 30 mg) once daily (QD) or a placebo. RNA-seq and gene set enrichment analyses were used to evaluate the effects of povorcitinib on differential gene expression among previously reported gene signatures from HS and wounded skin. The number of differentially expressed genes was the greatest in the 30 mg povorcitinib QD dose group, consistent with the published efficacy results. Notably, the genes impacted reflected JAK/STAT signaling transcripts downstream of TNF-α signaling, or those regulated by TGF-ß. Proteomic analyses were conducted on blood samples obtained at baseline and Weeks 4 and 8 from patients receiving povorcitinib (15, 30, 60, or 90 mg) QD or placebo. Povorcitinib was associated with transcriptomic downregulation of multiple HS and inflammatory signaling markers as well as the reversal of gene expression previously associated with HS lesional and wounded skin. Povorcitinib also demonstrated dose-dependent modulation of several proteins implicated in HS pathophysiology, with changes observed by Week 4. The reversal of HS lesional gene signatures and rapid, dose-dependent protein regulation highlight the potential of JAK1 inhibition to modulate underlying disease pathology in HS.

The Role of Probiotics and Their Metabolites in the Treatment of Depression.

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut-brain axis. While this microbiota-gut-brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota-gut-brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut-brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

Janus kinase 1 inhibitor INCB054707 for patients with moderate-to-severe hidradenitis suppurativa: results from two phase II studies.

BACKGROUND: Janus kinase (JAK)-mediated cytokine signalling contributes to local and systemic inflammation in hidradenitis suppurativa (HS). OBJECTIVES: To describe the safety and efficacy results from two multicentre phase II trials of the JAK1 inhibitor INCB054707 in patients with moderate-to-severe HS. METHODS: Patients received open-label INCB054707 15 mg once daily (QD; Study 1) or were randomized to INCB054707 30, 60 or 90 mg QD or placebo (3 : 1 within each cohort; Study 2) for 8 weeks. Eligible patients were aged 18-75 years and had moderate-to-severe HS (Hurley stage II/III disease), lesions present in at least two anatomical locations, and a total abscess and inflammatory nodule count ≥ 3. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures. RESULTS: Ten patients were enrolled in Study 1 (15 mg INCB054707) and 35 in Study 2 (INCB054707: 30 mg, n = 9; 60 mg, n = 9; 90 mg, n = 8; placebo, n = 9). Overall, 70% of patients in Study 1 and 81% of patients receiving INCB054707 in Study 2 experienced at least one treatment-emergent adverse event; 30% and 42% of patients, respectively, had at least one treatment-related adverse event. Among the evaluable patients, three (43%) in Study 1 and 17 (65% overall: 30 mg, 56%; 60 mg, 56%; 90 mg, 88%) receiving INCB054707 vs. 4 patients (57%) receiving placebo in Study 2 achieved HiSCR at week 8. CONCLUSIONS: INCB054707 was well tolerated, with responses observed in patients with moderate-to-severe HS. The safety and efficacy findings from these studies demonstrate proof of concept for JAK1 inhibition in HS. The studies are registered on ClinicalTrials.gov (NCT03569371 and NCT03607487).

Knockdown of OsNRT2.4 modulates root morphology and alters nitrogen metabolism in response to low nitrate availability in rice.

The expression patterns of the NRT2 genes have been well described; however, the role of OsNRT2.4 in root growth is not well known. In this study, we thus aimed at investigating the role of high-affinity NO3- transport OsNRT2.4 in root growth modulation. Through the amiRNA-mediated gene silencing technique, we successfully obtained osnrt2.4 knockdown lines to study the role of OsNRT2.4 on root growth under low nitrate conditions. We performed real-time PCR analysis to investigate the relative gene expression level in root and shoot, soluble metabolites, and measurement of root system. Knockdown of OsNRT2.4 decreased rice growth. The comparison with wild-type (WT) plants showed that (i) knockdown of OsNRT2.4 inhibited root formation under low NO3- supply; (ii) we demonstrated that the mutant lines had significantly increased NO3- uptake than WT plants when grown in different nitrate supplies; (iii) osnrt2.4 knockdown lines showed an alteration in nitrogen metabolism, and this affected the root growth; and (iv) the downregulation of OsNRT2.4 enhanced the expression of gene response of low external NO3- concentrations. Herein we provide new insights in OsNRT2.4 functions. Our data demonstrated that OsNRT2.4 plays a role in root growth, nitrogen metabolic pathway and probably have functions in nitrate transport from root to shoot under low nitrate availability in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01273-6.

Metabolomic profiling of Spathaspora passalidarum fermentations reveals mechanisms that overcome hemicellulose hydrolysate inhibitors.

Understanding the mechanisms involved in tolerance to inhibitors is the first step in developing robust yeasts for industrial second-generation ethanol (E2G) production. Here, we used ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and MetaboAnalyst 4.0 for analysis of MS data to examine the changes in the metabolic profile of the yeast Spathaspora passalidarum during early fermentation of hemicellulosic hydrolysates containing high or low levels of inhibitors (referred to as control hydrolysate or CH and strategy hydrolysate or SH, respectively). During fermentation of SH, the maximum ethanol production was 16 g L-1 with a yield of 0.28 g g-1 and productivity of 0.22 g L-1 h-1, whereas maximum ethanol production in CH fermentation was 1.74 g L-1 with a yield of 0.11 g g-1 and productivity of 0.01 g L-1 h-1. The high level of inhibitors in CH induced complex physiological and biochemical responses related to stress tolerance in S. passalidarum. This yeast converted compounds with aldehyde groups (hydroxymethylfurfural, furfural, 4-hydroxybenzaldehyde, syringaldehyde, and vanillin) into less toxic compounds, and inhibitors were found to reduce cell viability and ethanol production. Intracellularly, high levels of inhibitors altered the energy homeostasis and redox balance, resulting in lower levels of ATP and NADPH, while that of glycolytic, pentose phosphate, and tricarboxylic acid (TCA) cycle pathways were the most affected, being the catabolism of glucogenic amino acids, the main cellular response to inhibitor-induced stress. This metabolomic investigation reveals interesting targets for metabolic engineering of ethanologenic yeast strains tolerant against multiple inhibitors for E2G production. KEY POINTS: • Inhibitors in the hydrolysates affected the yeast's redox balance and energy status. • Inhibitors altered the glycolytic, pentose phosphate, TCA cycle and amino acid pathways. • S. passalidarum converted aldehyde groups into less toxic compounds.

Influence of cyclic loading in NiTi austenitic and R-phase endodontic files from a finite element perspective.

OBJECTIVES: This study aims to evaluate the effects of cyclic loading on the bending moments and the developed stress state of austenitic and R-phase endodontic files through finite element analysis. MATERIALS AND METHODS: The mechanical properties of two groups of NiTi wires, austenite and R-phase, were measured in samples at two different conditions: uncycled and cycled. The cycled condition was achieved by subjecting samples of the two groups to 80% of the corresponding fatigue life under rotating bending efforts. The measured mechanical properties were then used in the finite element analysis, where the boundary and loading conditions were set to replicate a standard bending test. RESULTS: The results showed that mechanical cycling leads to decreasing stress levels and bending moments in the simulated files, especially in the austenitic ones. In comparison with austenite, R-phase presented a more stable mechanical behavior during cycling. CONCLUSIONS: The results show that the moment and stress calculated for an instrument under bending can be considerably decreased after some cyclic work. CLINICAL RELEVANCE: The fatigue related to the clinical use of an endodontic file decreases the moment (as well as the forces) imposed by the instrument during the shaping of a curved root canal. This decrease is directly related to the type of atomic array present in the alloy.

Effects of Exercise on Sleep in Older Adults: An Overview of Systematic Reviews and Meta-Analyses.

We aimed to systematically analyze reviews of randomized clinical trials that investigate the overall effect of exercise and of different types of exercise on sleep in older adults. Meta-analysis was performed to obtain the standardized mean difference of the effect of the different types of exercise. Twenty systematic reviews published between 2012 and 2020 met the inclusion criteria of this overview. Moderate significant effects of exercise were observed on overall sleep quality and its subjective components (quality, duration, latency, habitual efficiency, medication use, and daytime dysfunction). Among the types of exercise, sensitivity analysis revealed significant effects of Pilates, Tai Chi, and Baduanjin Qigong on sleep quality. Exercise has a positive effect on sleep quality in older people. Our findings are extremely important, especially for decision makers in the health area, permitting the planning of actions and evidence-based decision making. PROSPERO registration number: CRD42020222469.

Comparative genomics and phylogenomics of the Ralstonia solanacearum Moko ecotype and its symptomatological variants.

Banana tree bacterial wilt is caused by the Ralstonia solanacearum Moko ecotype. These strains vary in their symptom progression in banana, and are classified as typical Moko variants (phylotype IIA and IIB strains from across Central and South America), Bugtok variant (Philippines), and Sergipe facies (the states of Sergipe and Alagoas, Brazil). This study used comparative genomic and phylogenomic approaches to identify a correlation between the symptom progression of the Moko ecotypes based on the analysis of 23 available genomes. Average nucleotide identity and in silico DNA-DNA hybridization revealed a high correlation (>96% and >78%, respectively) between the genomes of Moko variants. Pan-genome analysis identified 21.3% of inheritable regions between representatives of the typical Moko and Sergipe facies variants, which could be traced to an abundance of exclusive homolog clusters. Moko ecotype genomes shared 1,951 orthologous genes, but representatives with typical symptoms did not display unique orthologues. Moreover, Bugtok disease and Sergipe facies genomes did not share any unique genes, suggesting convergent evolution to a shared symptom progression. Overall, genomic and phylogenomic analyses were insufficient to differentiate the Moko variants based on symptom progression.

Understanding the differences in 2G ethanol fermentative scales through omics data integration.

In this work, we evaluated the fermentative performance and metabolism modifications of a second generation (2G) industrial yeast by comparing an industrial condition during laboratory and industrial scale fermentations. Fermentations were done using industrial lignocellulosic hydrolysate and a synthetic medium containing inhibitors and analyses were carried out through transcriptomics and proteomics of these experimental conditions. We found that fermentation profiles were very similar, but there was an increase in xylose consumption rate during fermentations using synthetic medium when compared to lignocellulosic hydrolysate, likely due to the presence of unknown growth inhibitors contained in the hydrolysate. We also evaluated the bacterial community composition of the industrial fermentation setting and found that the presence of homofermentative and heterofermentative bacteria did not significantly change the performance of yeast fermentation. In parallel, temporal differentially expressed genes (tDEG) showed differences in gene expression profiles between compared conditions, including heat shocks and the presence of up-regulated genes from the TCA cycle during anaerobic xylose fermentation. Thus, we indicate HMF as a possible electron acceptor in this rapid respiratory process performed by yeast, in addition to demonstrating the importance of culture medium for the performance of yeast within industrial fermentation processes, highlighting the uniquenesses according to scales.

Chikungunya Virus Infection Outcome: A Systematic Review of Host Genetics.

Background: Chikungunya virus (CHIKV) is a global concern, inducing chikungunya fever and trigging an arthritogenic chronic phase beyond some severe forms. Outcomes of CHIKV infections in humans are dependent on genetic variations. Here, a systematic review was performed to show evidence of genetic variations on infection outcomes of patients. Methods: Searches were performed in Scopus, SciELO, MEDLINE/PubMed, Web of Science, OneFile (GALE), Periódicos CAPES and ScienceDirect Journals databases. The PICOS approach was used to assess the eligibility of records. A meta-analysis was also conducted to show an association between described alleles/genes and CHIKV infection outcome. Results: Reviews of genetic variants were conducted on genes: CD 209, OAS1, OAS2, OAS3, MIF, TLR-3, TLR-7, TLR-8, MYD-88, KIR, HLA-B; HLA-C; DRB1 and DQB1. Studies were performed on Gabon, Singapore, and India, including Indians, Malay, Gabonese and Chinese ethnicities and published between 2009-2017. The meta-analysis was performed with DRB1 *01; *03; *04; *07; *10; *11; *13; *14 and *15 and DQB1 *02; *03; *05 and *06 alleles with Indian population sample. Sampling power was >80% and a significant positive association between DRB1*14 and CHIKV infection was found (OR = 1.67, 95% CI = 1.04-2.67; p = .03). Conclusion: Majority of the studies were conducted in India. Meta-analysis suggests that DRB1*14 is related to the susceptibility of symptomatic CHIKV infection in Indian population. The literature about CHIKV infection and genetic variations is scarce. The precise role of genetic variation in CHIKV is not clear yet. Further studies are necessary to provide more concrete evidences.

Modifying effects of menthol against benzo(a)pyrene-induced forestomach carcinogenesis in female Swiss mice.

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon widespread in the environment and closely associated to tobacco use, which is an important risk factor for highly incident stomach cancer. Menthol, a monoterpene extracted from Mentha genus species, has multiple biological properties, including anti-inflammatory and gastroprotective properties, but its effects on carcinogenesis are still to be fully understood. Thus, we evaluated the modifying effects of Ment against BaP-induced forestomach carcinogenesis. Female Swiss mice received BaP by intragastrical (i.g.) administration (50 mg/kg of body weight [b wt], 2×/week), from weeks 1-5 weeks. Concomitantly, mice received Menthol at 25 (Ment25) or 50 (Ment50) mg/kg b wt (i.g, 3×/week). Animals were euthanized at weeks 5 (n = 5 mice/group) or 30 (n = 10 mice/group). At week 5, both Ment doses reduced peripheral leukocyte blood genotoxicity 4 h after the last BaP administration, but only Ment50 attenuated this biomarker 8 h after the last BaP administration. In accordance to these findings, both Ment interventions attenuated BaP-induced increase in the percentage of H2A.X-positive forestomach epithelial cells. Moreover, Ment50 reduced cell proliferation and apoptosis (i.e., Ki-67 and caspase-3, respectively) in forestomach epithelium but exerted no significant effects on NFκB, and Nrf2 protein levels. At week 30, Ment50 reduced by ~55% the incidence of BaP-induced forestomach diffuse hyperplasia and multiplicity of forestomach tumors (squamous cell papillomas and carcinomas). Our findings indicate that Ment50, administered during initiation phase, attenuates forestomach carcinogenesis by reducing early genotoxicity, cell proliferation, and apoptosis induced by BaP.

Effect of Resistance Training Intensity on Blood Pressure in Older Women.

This study aimed to compare the effects of resistance training performed with low versus moderate loads on systemic resting blood pressure (BP) in older women. A total of 29 women (72.6 ± 5.1 years) were randomized into two groups: low load (LOW, n = 15) and moderate load (MOD, n = 14). An 8-week whole-body resistance training program was carried out 3 days/week (eight exercises, three sets, 10 or 15 repetition maximum). The LOW and MOD groups trained with a relative load of 15 and 10 repetition maximum, respectively. Outcome measures included resting systolic and diastolic BP. After 8 weeks, both groups presented significant changes (p < .05) in systolic BP (LOW = -3.0%; MOD = -4.6%) and mean BP (LOW = -1.9%; MOD = -3.1%). There was no change for diastolic BP in the posttest in both groups. The results suggest that low and moderate loads are equally effective for promoting decreases in resting BP in older women.

Properties and Application of Cell-Free DNA as a Clinical Biomarker.

Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.