Functional and Combined Training Promote Body Recomposition and Lower Limb Strength in Postmenopausal Women: A Randomized Clinical Trial and a Time Course Analysis.

Encouraging healthy aging in postmenopausal women involves advocating for lifestyle modifications, including regular physical exercise like combined training (CT) and functional training (FT). Regarding this population, age-related alterations in body composition, such as decreased muscle mass and heightened adipose tissue, impact health. The aim of this study was to analyze the effects of FT and CT on body recomposition in postmenopausal women. About the methods, we randomly allocated 96 post-menopausal women to the FT, CT, or control group (CG). We measured body composition by bioimpedance and lower limb muscle strength by sit-to-stand test in five repetitions, respectively. The training protocol lasted 16 weeks, and we measured body composition and lower limb muscle strength every 4 weeks, totaling five assessments. Regarding results, we notice that both training groups increased lean mass from the 8th week of training. In addition, a reduction was observed in total fat percentage and an increase in appendicular lean mass from the 12th week of intervention. No differences were found for body mass. Furthermore, only the experimental groups increase muscle strength, starting from the 4th week of training. The conclusion was that FT and CT promote similar adaptations in body recomposition without affecting body mass in postmenopausal women.

NINJ1 induces plasma membrane rupture and release of damage-associated molecular pattern molecules during ferroptosis.

Ferroptosis is a regulated form of necrotic cell death caused by iron-dependent accumulation of oxidized phospholipids in cellular membranes, culminating in plasma membrane rupture (PMR) and cell lysis. PMR is also a hallmark of other types of programmed necrosis, such as pyroptosis and necroptosis, where it is initiated by dedicated pore-forming cell death-executing factors. However, whether ferroptosis-associated PMR is also actively executed by proteins or driven by osmotic pressure remains unknown. Here, we investigate a potential ferroptosis role of ninjurin-1 (NINJ1), a recently identified executor of pyroptosis-associated PMR. We report that NINJ1 oligomerizes during ferroptosis, and that Ninj1-deficiency protects macrophages and fibroblasts from ferroptosis-associated PMR. Mechanistically, we find that NINJ1 is dispensable for the initial steps of ferroptosis, such as lipid peroxidation, channel-mediated calcium influx, and cell swelling. In contrast, NINJ1 is required for early loss of plasma membrane integrity, which precedes complete PMR. Furthermore, NINJ1 mediates the release of cytosolic proteins and danger-associated molecular pattern (DAMP) molecules from ferroptotic cells, suggesting that targeting NINJ1 could be a therapeutic option to reduce ferroptosis-associated inflammation.

CD4+ Th1 and Th17 responses and multifunctional CD8 T lymphocytes associated with cure or disease worsening in human visceral leishmaniasis.

Introduction: In VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and a Th1 mediated immune response resulting in infection control. In contrast, an anti-inflammatory phenotype, associated with a predominant regulatory response, typically enables intracellular multiplication of Leishmania parasites and disease progression. Methods: To investigate the impact of chemotherapy on Th2 and Th17 immune responses in patients with visceral leishmaniasis (VL), we assessed all combinations of intracellular expression of IFN-γ, IL-10, IL-4 and IL-17 in the CD4+ and CD8+ T cell populations of peripheral blood mononuclear cell (PBMC) samples from patients, after antigenic stimulation with Leishmania lysate, throughout treatment and follow-up. As increases in spleen and liver sizes and decreases in hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes and platelets levels are strongly related to the disease, we studied the correlations between the frequencies of T cells producing the afore mentioned cytokines, individually and in combination, and these variables, as markers of disease or cure. Results: We found that the frequency of IFN-γ-producingCD4+ T cells increased until the end of chemotherapy with Glucantime® or AmBisome ®, while IL-10, IL-4 and IL-17-producing CD4+ T cells peaked on day 7 following the start of treatment. Although the frequency of CD4+IL-17+ cells decreased during treatment an increase was observed after clinical cure. The frequency of CD4+ T cells producing only IFN-γ or IL-17 correlated with blood monocytes levels. Frequencies of double-producers of IFN-γ and IL-10 or IL-4 correlated positively with eosinophils and platelets levels. Together, this suggest that IFN-γ drives the immune response towards Th1 at cure. In contrast, and associated with disease or Th2 response, the frequency of CD4+ IL-10+ cells correlated positively with spleen sizes and negatively with circulating monocyte levels, while the frequency of CD4+ producing both IL-4 and IL-10 correlated negatively with platelets levels. The frequency of CD8+ single-producers of IFN-γ increased from day 21 to 90 while that of single-producers of IL-10 peaked on day 7, of IL-4 on day 30 and of IL-17, on day 180. IFN-γ expression in CD8+ single- and double-producers of cytokines was indicative of an immune response associated with cure. In contrast, frequencies of CD8+ double-producers of IL-4 and IL-10, IL-4 and IL-17 and IL-10 and IL-17 and producers of three and four cytokines, were associated with disease and were low after the cure. Frequencies of CD8+ T cells producing IFN-γ alone or with IL-17 were positively correlated with platelets levels. In contrast, as markers of disease: 1) frequencies of single producers of IL-10 correlated negatively with leukocytes levels, 2) frequencies of double producers of IL-4 and IL-10 correlated negatively with platelet, leukocyte, lymphocyte and circulating monocyte levels, 3) frequencies of triple-producers of IFN-γ, IL-4 and IL-10 correlated negatively with platelet, leukocyte and neutrophil levels and 4) frequencies of producers of IFN-γ, IL-4, IL-10 and IL-17 simultaneously correlated positively with spleen size, and negatively with leukocyte and neutrophil levels. Discussion: Our results confirmed that the clinical improvement of VL patients correlates with the decrease of an IL-4 and IL-10 CD4+Th2 response, the recovery of CD4+ Th1 and Th17 responses and the frequency of CD8+ single-producers of IFN-γ and double producers of IFN-γ and IL-17.

Relative Cross-Education Training Effects of Male Youth Exceed Male Adults.

ABSTRACT: Ben Othman, A, Anvar, SH, Aragão-Santos, JC, Behm, DG, and Chaouachi, A. Relative cross-education training effects of male youth exceed male adults. J Strength Cond Res 38(5): 881-890, 2024-Cross-education has been studied extensively with adults, examining the training effects on contralateral homologous muscles. There is less information on the cross-education effects on contralateral heterologous muscles and scant information comparing these responses between adults and youth. The objective was to compare cross-education training effects in male youth and adults to contralateral homologous and heterologous muscles. Forty-two male children (10-13-years) and 42 adults (18-21-years) were tested before and following an 8-week unilateral, dominant or nondominant arm, chest press (CP) training program or control group (14 subjects each). Unilateral testing assessed dominant and nondominant limb strength with leg press and CP 1 repetition maximum (1RM), knee extensors, elbow extensors (EE), elbow flexors, and handgrip maximum voluntary isometric contraction (MVIC) strength and shot put distance and countermovement jump height. Upper-body tests demonstrated large magnitude increases, with children overall exceeding adults ( p = 0.05- p < 0.0001, η2 : 0.51, 10.4 ± 11.1%). The dominant trained limb showed significantly higher training adaptations than the nondominant limb for the adults with CP 1RM ( p = 0.03, η2 : 0.26, 6.7 ± 11.5%) and EE ( p = 0.008, η2 : 0.27, 8.8 ± 10.3%) MVIC force. Unilateral CP training induced significantly greater training adaptations with the ipsilateral vs. contralateral limb ( p = 0.008, η2 : 0.93, 27.8 ± 12.7%). In conclusion, children demonstrated greater training adaptations than adults, upper-body strength increased with no significant lower-body improvements, and ipsilateral training effects were greater than contralateral training in adults.

Minimalist Training: Is Lower Dosage or Intensity Resistance Training Effective to Improve Physical Fitness? A Narrative Review.

BACKGROUND: Findings from original research, systematic reviews, and meta-analyses have demonstrated the effectiveness of resistance training (RT) on markers of performance and health. However, the literature is inconsistent with regards to the dosage effects (frequency, intensity, time, type) of RT to maximize training-induced improvements. This is most likely due to moderating factors such as age, sex, and training status. Moreover, individuals with limited time to exercise or who lack motivation to perform RT are interested in the least amount of RT to improve physical fitness. OBJECTIVES: The objective of this review was to investigate and identify lower than typically recommended RT dosages (i.e., shorter durations, lower volumes, and intensity activities) that can improve fitness components such as muscle strength and endurance for sedentary individuals or beginners not meeting the minimal recommendation of exercise. METHODS: Due to the broad research question involving different RT types, cohorts, and outcome measures (i.e., high heterogeneity), a narrative review was selected instead of a systematic meta-analysis approach. RESULTS: It seems that one weekly RT session is sufficient to induce strength gains in RT beginners with < 3 sets and loads below 50% of one-repetition maximum (1RM). With regards to the number of repetitions, the literature is controversial and some authors report that repetition to failure is key to achieve optimal adaptations, while other authors report similar adaptations with fewer repetitions. Additionally, higher intensity or heavier loads tend to provide superior results. With regards to the RT type, multi-joint exercises induce similar or even larger effects than single-joint exercises. CONCLUSION: The least amount of RT that can be performed to improve physical fitness for beginners for at least the first 12 weeks is one weekly session at intensities below 50% 1RM, with < 3 sets per multi-joint exercise.

Different resistance training volumes on strength, functional fitness, and body composition of older people: A systematic review with meta-analysis.

Aging causes several changes in the body, reducing strength and muscle mass, which leads to a decline in function. Resistance training (RT) is used to counteract these changes. However, there is still ongoing debate about the optimal volume of RT in the context of aging. We systematically reviewed articles that assessed the impact of different volumes of RT on muscular strength, functional fitness, and body composition of older people. We conducted a systematic search in the PubMed/MEDLINE, Scopus, Embase, Web of Science, Cochrane Library, LILACS, PEDro, and Google Scholar databases, using keywords related to the older population and various RT volumes. We performed meta-analyses for each outcome separately using intervention time in weeks for subgroup analyses. We employed random effects models for all meta-analyses and expressed the results as standardized mean differences (Hedges' g). We included 31 studies, encompassing a total of 1.744 participants. The sample size ranged from 18 to 376, with an average size of 56 participants. Participants' ages ranged from 60 to 83 years. On average, HV-RT (High-Volume Resistance Training) induced significant adaptations in muscle strength of the upper limbs (g = 0.36; 95 % CI = 0.11-0.61) and lower limbs (g = 0.41; 95 % CI = 0.23-0.59), with superiority more pronounced after 12 weeks of training. Regarding functional fitness, there was a tendency favoring HV-RT (g = 0.41; 95 % CI = 0.23-0.59). Thus, HV-RT outperforms LV-RT (Low-Volume Resistance Training) in enhancing muscle strength, particularly in longer interventions with independent older adults.

Functional Training and Dual-Task Training Improve the Executive Function of Older Women.

Functional training (FT) is a type of multicomponent training with emphasis on activities of daily living that stimulate different physical capacities in only one session. Dual-task training (DTT) is a type of training that simultaneously applies cognitive and motor stimuli. We investigated the effects of sixteen weeks of FT and DTT and eight weeks of detraining on older women's inhibitory control, working memory, and cognitive flexibility. Sixty-two older women (66.9 ± 5.4 years; 27.7 ± 3.9 kg/m2) completed a 16-week intervention program comprising the FT (n = 31) and DTT (n = 31), and 43 returned after the detraining period. We used the Stroop Color Word Color test to evaluate inhibitory control, the Corsi Block Test to assess working memory, and the Trail Making Test to evaluate cognitive flexibility. Only DTT reduced the congruent response time between the pre-test and post-test (d= -0.64; p < 0.001), with no difference between the post-test and the detraining values (d = 1.13; p < 0.001). Both groups reduced the incongruent response time between the pre-test and post-test (FT: d = -0.61; p = 0.002; DTT: d= -0.59; p = 0.002) without a difference between groups. There were no significant differences in working memory and cognitive flexibility. Sixteen weeks of FT and DTT increased the inhibitory control of older women but not the working memory and cognitive flexibility, and these effects persisted after eight weeks of detraining.

Are Acute Effects of Foam-Rolling Attributed to Dynamic Warm Up Effects? A Comparative Study.

Over the last decade, acute increases in range of motion (ROM) in response to foam rolling (FR) have been frequently reported. Compared to stretching, FR-induced ROM increases were not typically accompanied by a performance (e.g., force, power, endurance) deficit. Consequently, the inclusion of FR in warm-up routines was frequently recommended, especially since literature pointed out non-local ROM increases after FR. However, to attribute ROM increases to FR it must be ensured that such adaptations do not occur as a result of simple warm-up effects, as significant increases in ROM can also be assumed as a result of active warm-up routines. To answer this research question, 20 participants were recruited using a cross-over design. They performed 4x45 seconds hamstrings rolling under two conditions; FR, and sham rolling (SR) using a roller board to imitate the foam rolling movement without the pressure of the foam rolling. They were also tested in a control condition. Effects on ROM were tested under passive, active dynamic as well as ballistic conditions. Moreover, to examine non-local effects the knee to wall test (KtW) was used. Results showed that both interventions provided significant, moderate to large magnitude increases in passive hamstrings ROM and KtW respectively, compared to the control condition (p = 0.007-0.041, d = 0.62-0.77 and p = 0.002-0.006, d = 0.79-0.88, respectively). However, the ROM increases were not significantly different between the FR and the SR condition (p = 0.801, d = 0.156 and p = 0.933, d = 0.09, respectively). No significant changes could be obtained under the active dynamic (p = 0.65) while there was a significant decrease in the ballistic testing condition with a time effect (p < 0.001). Thus, it can be assumed that potential acute increases in ROM cannot be exclusively attributed to FR. It is therefore speculated that warm up effects could be responsible independent of FR or imitating the rolling movement, which indicates there is no additive effect of FR or SR to the dynamic or ballistic range of motion.

Structural basis of NINJ1-mediated plasma membrane rupture in cell death.

Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture as the defining terminal event1-7. Plasma membrane rupture was long thought to be driven by osmotic pressure, but it has recently been shown to be in many cases an active process, mediated by the protein ninjurin-18 (NINJ1). Here we resolve the structure of NINJ1 and the mechanism by which it ruptures membranes. Super-resolution microscopy reveals that NINJ1 clusters into structurally diverse assemblies in the membranes of dying cells, in particular large, filamentous assemblies with branched morphology. A cryo-electron microscopy structure of NINJ1 filaments shows a tightly packed fence-like array of transmembrane α-helices. Filament directionality and stability is defined by two amphipathic α-helices that interlink adjacent filament subunits. The NINJ1 filament features a hydrophilic side and a hydrophobic side, and molecular dynamics simulations show that it can stably cap membrane edges. The function of the resulting supramolecular arrangement was validated by site-directed mutagenesis. Our data thus suggest that, during lytic cell death, the extracellular α-helices of NINJ1 insert into the plasma membrane to polymerize NINJ1 monomers into amphipathic filaments that rupture the plasma membrane. The membrane protein NINJ1 is therefore an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death.

A single-set functional training program increases muscle power, improves functional fitness, and reduces pro-inflammatory cytokines in postmenopausal women: A randomized clinical trial.

Introduction: Aging can be associated with reduced muscle power, functional decline, and increased plasma concentrations of proinflammatory cytokines. Functional training (FT) can improve muscle power, functional fitness and reduce plasma cytokines. However, the functional training optimal volume required to produce these adaptations must be clarified. Our study analyzed the effects of multiple-set functional training (MSFT) and single-set functional training (SSFT) on postmenopausal women's muscle power, functional fitness, and inflammatory profile. Methods: Forty-three women were randomly allocated into three groups: multiple-set functional training (n = 16, age 64.13 ± 5.17), single-set functional training (n = 14, age 63.79 ± 4.88), and control group (CG, n = 13, age 64.62 ± 5.44). The bench press and squat exercises evaluated upper and lower limb muscle power. The following tests assessed functional fitness: putting on and taking off a T-shirt, gallon-jug shelf-transfer, standing up and walking around the house, five times sit-to-stand, and 400-m walk. Plasma cytokine (TNF-α, IL-6, and IL 10) concentrations were measured by flow cytometry. Results: Single-set functional training and multiple-set functional training increased upper and lower limbs muscle power and improved functional fitness, except for the putting on and taking off a T-shirt test. Multiple-set functional training reduced TNF-α and IL-6, while single-set functional training reduced only TNF-α. IL-10 was unaffected by exercise. Discussion: Single-set functional training and multiple-set functional training, therefore, promoted similar muscle power and functional fitness improvements over 24 weeks. Multiple-set functional training was more effective than single-set functional training, reducing both TNF and IL-6, while single-set functional training only decreased TNF-α.

Alternative Flexibility Training.

Over the last approximately 20 years, research has reported on performance impairments following prolonged durations of static stretching. This has led to a paradigm shift towards dynamic stretching. There has also been a greater emphasis using foam rollers, vibration devices, and other techniques. Recent commentaries and meta-analyses suggest that stretching need not be listed as a fitness component as other activities such as resistance training can provide similar range of motion benefits. The commentary aims to review and compare the effects of static stretching and alternative exercises for improving range of motion.

Effects of twenty-eight months of detraining imposed by the COVID-19 pandemic on the functional fitness of older women experienced in concurrent and functional training.

PURPOSE: To assess the impacts of 28 months of detraining imposed by the COVID-19 pandemic on the functional fitness of older women practicing functional or concurrent training. MATERIAL AND METHODS: A clinical trial was conducted with 16 weeks of intervention and 28 months of detraining imposed by the COVID-19 pandemic. Ninety-five participants were allocated to functional training (FT - 32), concurrent training (CT - 31), or the control group (CG - 32). All the dependent variables were measured pre-training, post-training, and after the detraining period. The functional fitness was assessed by the put on and take off a t-shirt (PTS - upper limbs), timed up and go (TUG - dynamic balance), five times sit-to-stand (FTSST - lower-limb muscle power), gallon-jug shelf-transfer (GJST - global function), and 10 m walk (W10 m - walking ability) tests. RESULTS: Sixty-three women remained after the detraining period, twenty-four in the FT (66.0 ± 3.8 years), twenty in the CT (65.0 ± 4.3 years), and nineteen in the CG (69.6 ± 5.9 years). Comparing the detraining vs. the pre-intervention, the FT and CT showed a smaller reduction than CG for the PTS (ßFT = -2.296; ßCT = -1.914), timed up and go (ßFT = -0.705; ßCT = -0.600), five times sit-to-stand (ßFT = -1.970; ßCT = -2.970), gallon-jug shelf-transfer (ßFT = -1.512; ßCT = -1.003), without differences in the 10 m walk. Also, the concurrent training showed a smaller reduction than the functional training in the FTSST (ß = 1.000). CONCLUSION: Even after a long detraining period imposed by the COVID-19 pandemic, FT and CT practices were effective strategies for maintaining the functional fitness of older women.

Soil Organic Matter Molecular Composition Shifts Driven by Forest Regrowth or Pasture after Slash-and-Burn of Amazon Forest.

Slash-and-burn of Amazon Forest (AF) for pasture establishment has increased the occurrence of AF wildfires. Recent studies emphasize soil organic matter (SOM) molecular composition as a principal driver of post-fire forest regrowth and restoration of AF anti-wildfire ambience. Nevertheless, SOM chemical shifts caused by AF fires and post-fire vegetation are rarely investigated at a molecular level. We employed pyrolysis-gas chromatography-mass spectrometry to reveal molecular changes in SOM (0-10, 40-50 cm depth) of a slash-burn-and-20-month-regrowth AF (BAF) and a 23-year Brachiaria pasture post-AF fire (BRA) site compared to native AF (NAF). In BAF (0-10 cm), increased abundance of unspecific aromatic compounds (UACs), polycyclic aromatic hydrocarbons (PAHs) and lipids (Lip) coupled with a depletion of polysaccharides (Pol) revealed strong lingering effects of fire on SOM. This occurs despite fresh litter deposition on soil, suggesting SOM minimal recovery and toxicity to microorganisms. Accumulation of recalcitrant compounds and slow decomposition of fresh forest material may explain the higher carbon content in BAF (0-5 cm). In BRA, SOM was dominated by Brachiaria contributions. At 40-50 cm, alkyl and hydroaromatic compounds accumulated in BRA, whereas UACs accumulated in BAF. UACs and PAH compounds were abundant in NAF, possibly air-transported from BAF.

From field to laboratory: isolation, genetic assessment, and parasitological behavior of Schistosoma mansoni obtained from naturally infected wild rodent Holochilus sciureus (Rodentia, Cricetidae), collected in Northeastern Brazil.

Wild rodent species are naturally infected by Schistosoma mansoni; however, the genetic characterization of the parasite, its parasitological features, and its role in human schistosomiasis are poorly understood. In this study, we isolated and characterized Schistosoma from naturally infected Holochilus sciureus, called HS strain, collected from a schistosomiasis endemic region in Maranhão State, Brazil. To isolate the parasite, miracidia obtained from the livers of H. sciureus were used to infect Biomphalaria glabrata of sympatric (called SB) and allopatric (called BH) strains, and the produced cercariae were subcutaneously inoculated into hamsters and/or BALB/c mice. Parasitological kinetics in experimentally infected hosts were evaluated, and the tRNACys-12S (referred to as 16S herein) and cox 1 regions of mtDNA from isolated worms were amplified and sequenced. Only miracidia obtained from infected mice, but not from hamsters, were capable of infecting B. glabrata, allowing maintenance of the isolated parasite. Cox1 and 16S mtDNA sequences showed 100% similarity with S. mansoni, and phylogenetic analysis showed that the HS strain of S. mansoni forms an assemblage with isolates from America and Kenya, confirming the conspecificity. Experimental infection of B. glabrata SB with S. mansoni HS resulted in two peaks of cercariae shedding at 45 and 70 days post-infection (dpi) and caused higher mortality than in B. glabrata BH. The worm recovery rate in mice was approximately 13%, and the peak of egg elimination occurred at the 10th week post-infection. Therefore, S. mansoni obtained from H. sciureus was successfully isolated, genetically characterized, and maintained in mice, allowing further study of this schistosome strain.

Prevention of non-suicidal self-injury: construction and validation of educational material.

OBJECTIVE: to develop and validate educational material to strengthen adolescent health care on non-suicidal self-injury. METHOD: methodological research designed in three stages: (1) construction of the material based on a mixed study on needs related to the theme through social networks and an umbrella review on health care related to non-suicidal self-injury; (2) validation with 10 experts in mental health and/or self-inflicted violence selected through the Lattes Platform; (3) evaluation by the target public, with health professionals being invited, without restriction of training. Validation and evaluation data were collected by using a sociodemographic questionnaire and the Suitability Assessment of Materials for evaluation of health-related information for adults. We used descriptive statistics, content validity index, and Gwet's AC1 test. RESULTS: the material obtained good general acceptance and reliability in the validation by the experts (AC1= 0.633; p=0.0000) and in the evaluation by the target public (AC1=0.716; p=0.0000). All professionals pointed out the personal contribution and educational potential of the material. CONCLUSION: we highlight the construction of science-based educational material to strengthen the health care for adolescents with non-suicidal self-injury. KEYPOINTS: (1) Scientific data-based construction of educational material for prevention of non-suicidal self-injury (NSSI). (2) General acceptance and reliability in the validation of the material by experts. (3) Acceptance and reliability in the evaluation of the material by health professionals. (4) Dissemination of material for health education initiatives to prevent NSSI.

The Meaning of Suicidal Behaviour for Portuguese Nursing Students.

BACKGROUND: The nursing perspectives on suicidal behaviors may influence the quality of assistance and suicidal prevention. This phenomenon is scarcely investigated among nursing students. AIMS: The aim of this study is to understand the meanings of suicidal behavior for Portuguese undergraduate students. METHODS: This qualitative study utilized Grounded Theory and Symbolic Interactionism. We collected data in Portugal in 2017-2018 with 13 undergraduate students. RESULTS: Students compared suicidal behavior to "A complex and close haze" and considered it "A neglected phenomenon". Suicidal behavior was predominantly perceived as an emotional distress that requires assistance. The students compared the person and society as "The car and the road: behavior influenced by communication and interaction" and valorized social dimensions and repercussions of suicidal behavior. LIMITATIONS: Lack of triangulation in the data and the sampling restricted to nursing students of a single institution are considered limitations of this study. CONCLUSIONS: This study can contribute to the development of academic education strategies and psychosocial support for nursing students.

Bodyweight and Combined Training Reduce Chronic Low-Grade Inflammation and Improve Functional Fitness of Postmenopausal Women.

Exercise is an important tool against the deleterious effects of aging. Among the possibilities of exercise, bodyweight training (BWT) has been highlighted in the last years as a safe option to improve the health of older people. We compared the effects of 24 weeks of BWT and combined training (CT) on low-grade systematic inflammation and functional fitness in postmenopausal women. For this, 40 women were allocated and submitted to CT (n = 20, 64.43 ± 3.13 years, 29.56 ± 4.80 kg/m²) and BWT (n = 20, 65.10 ± 4.86 years, 28.76 ± 4.26 kg/m²). We measured inflammation by the interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) assessments. For functional fitness, we used tests similar to activities of daily living. At the end of the 16 weeks, data from 24 women were analyzed, CT (n = 14) and BT (n = 10). Both groups reduced TNF-α and IL-6 levels, without differences in IL-10. Regarding functional fitness, both groups demonstrated improvements in all tests after 24 weeks, except for rise from prone position and the 400-meter walk test for CT. In summary, CT and BWT are effective in reducing the plasma concentration of pro-inflammatory cytokines and improving functional fitness in postmenopausal women.

Refined Chelator Spacer Moieties Ameliorate the Pharmacokinetics of PSMA-617.

Prostate-specific membrane antigen (PSMA) binding tracers are promising agents for the targeting of prostate tumors. To further optimize the clinically established radiopharmaceutical PSMA-617, novel PSMA ligands for prostate cancer endoradiotherapy were developed. A series of PSMA binding tracers that comprise a benzyl group at the chelator moiety were obtained by solid-phase synthesis. The compounds were labeled with 68Ga or 177Lu. Competitive cell-binding assays and internalization assays were performed using the cell line C4-2, a subline of the PSMA positive cell line LNCaP (human lymph node carcinoma of the prostate). Positron emission tomography (PET) imaging and biodistribution studies were conducted in a C4-2 tumor bearing BALB/c nu/nu mouse model. All 68Ga-labeled ligands were stable in human serum over 2 h; 177Lu-CA030 was stable over 72 h. The PSMA ligands revealed inhibition potencies [Ki] (equilibrium inhibition constants) between 4.8 and 33.8 nM. The percentage of internalization of the injected activity/106 cells of 68Ga-CA028, 68Ga-CA029, and 68Ga-CA030 was 41.2 ± 2.7, 44.3 ± 3.9, and 53.8 ± 5.4, respectively; for the comparator 68Ga-PSMA-617, 15.5 ± 3.1 was determined. Small animal PET imaging of the compounds showed a high tumor-to-background contrast. Organ distribution studies revealed high specific uptake in the tumor, that is, approximately 34.4 ± 9.8% of injected dose per gram (%ID/g) at 1 h post injection for 68Ga-CA028. At 1 h p.i., 68Ga-CA028 and 68Ga-CA030 demonstrated lower kidney uptake than 68Ga-PSMA-617, but at later time points, kidney time-activity curves converge. In line with the preclinical data, first diagnostic PET imaging using 68Ga-CA028 and 68Ga-CA030 revealed high-contrast detection of bone and lymph node lesions in patients with metastatic prostate cancer. The novel PSMA ligands, in particular CA028 and CA030, are promising agents for targeting PSMA-positive tumor lesions as shown in the preclinical evaluation and in a first patient, respectively. Thus, clinical translation of 68Ga-CA028 and 68Ga/177Lu-CA030 for diagnostics and endoradiotherapy of prostate cancer in larger cohorts of patients is warranted.

Effects of functional and combined training on subsets of memory T cells and functional fitness of postmenopausal women: A randomized controlled trial.

This study investigated the effects of functional (FT) and combined (CT) training on memory T cells and functional fitness of postmenopausal women. 108 participants were randomly allocated to the control (CG), FT and CT groups. Functional fitness was assessed through physical tests similar to daily activities, such as dressing on and taking off a t-shirt (DTTS), 10-meter walking and countermovement jump. The CCR7 and CD45RA surface markers were used to characterize the memory T cells. Regarding the frequency of memory T cells, both training protocols reduced the percentage of CD4+ Terminally Differentiated Effector Memory T Cells Re-Expressing CD45RA (TEMRA) (FT: -38.73 %, p = 0.0455; CT: -30.43 %, p = 0.0036) and CD8+ TEMRA cells (FT: -22.24 %, p < 0.0013; CT: -13.13 %, p = 0.0051). Also, both FT and CT increased the percentage of central memory (TCM) CD4+ (FT: +55.22 %, p = 0.0104; CT: +68.03 %, p = 0.0167) and CD8+ (FT: +142.00 %, p < 0.0001; CT: +83.76 %, p = 0.0001) T cells. Furthermore, FT and CT increased the percentages of CD8+ effector memory T cells (TEM) (FT: +63.58 %, p < 0.0001; CT: +14.12 %, p = 0.0041). Regarding functional fitness, both training protocols reduced the time required to perform the DTTS (FT: -19.71 %, p < 0.0001; CT: -14.69 %, p < 0.0001) and 10-m walk tests (FT: -13.05 %, p < 0.0001; CT: -12.83 %, p < 0.0001), in addition to improving jumping ability (FT: +29.97 %, p < 0.0001; CT: +20.00 %, p < 0.0001), both compared to the pre-test or to the CG. Therefore, both FT and CT seem to be equally effective alternatives for promoting the reduction of CD4+ and CD8+ TEMRA cells, increasing the frequency of TCM and TEM cells, and improving functional fitness of postmenopausal women.