Resistance Training Reduces Blood Pressure Putative Molecular Mechanisms.

Arterial hypertension is a multifactorial clinical condition characterized by higher blood pressure levels. The main treatment for controlling high blood pressure consists of drug therapy, but the scientific literature has been pointing to the efficiency of aerobic and resistance exercises acting in a therapeutic and/or preventive way to reduce and control the blood pressure levels. Resistance training is characterized by sets and repetitions on a given muscle segment that uses overload, such as machine weights, bars, and dumbbells. As it successfully affects a number of variables associated to practitioners' functional and physiological features as well as emotional and social variables, resistance training has been a crucial part of physical exercise programs. Several reports highlight the various adaptive responses it provides, with a focus on the improvement in strength, balance, and muscular endurance that enables a more active and healthy lifestyle. Resistance training programs that are acute, sub-chronic, or chronic can help people with varying ages, conditions, and pathologies reduce their arterial hypertension. However, molecular mechanisms associated with resistance training to reduce blood pressure still need to be better understood. Thus, we aimed to understand the main effects of resistance training on blood pressure as well as the associated molecular mechanisms.

Antibacterial and Antiviral Properties of Chenopodin-Derived Synthetic Peptides.

Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an Andean plant with high nutritional and therapeutic properties. Here, we used computer- and physicochemical-based strategies and designed four peptides derived from the primary structure of Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1 does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are assembled in the membrane. Whereas, some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides.

Predictability of single versus double-barrel vascularized fibula flaps and dental implants in mandibular reconstructions: A systematic review and meta-analysis of prospective studies.

STATEMENT OF PROBLEM: Patients with vascularized bone flaps from the fibula have reduced bone height, in which case a higher prosthetic abutment is needed for their implant-supported prosthesis. Although the double-flap technique seems promising, systematic reviews and meta-analyses of prospective studies are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the grafted areas of single barrel fibular flaps (SBFF) and double-barrel fibular flaps (DBFF) by considering failure rates, dental implant complications, and bone union at the osteotomy sites. MATERIAL AND METHODS: A systematic review and meta-analysis was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, population, intervention, control, and outcomes (PICO) question, and the National Health and Medical Research Council scales. The event rate of complications and failures was calculated with a confidence interval (CI) of 95%. RESULTS: A total of 13 prospective studies with 441 participants and 330 graft sites were identified. A total of 235 participants had SBFF with 445 implants, and 95 had DBFF with 164 implants. The overall combined graft failure rates were 4.2% for SBFF and 3.2% for DBFF. The complication rate was 10% for SBFF and 1.9% for DBFF. Implant failure was at 4.7% in the SBFF group and 3.4% in the DBFF group. CONCLUSIONS: Complication rates and implant failures were similar for SBFF and DBFF. Therefore, for long-term oral rehabilitation, both SBFF and DBFF are suitable procedures for mandibular reconstruction.

Return-to-performance in elite soccer players after Achilles tendon ruptures: a study using a weighted plus/minus metric and matched-control analysis.

PURPOSE: Studies have shown decreased match participation and shortened careers in athletes suffering Achilles tendon ruptures (ATRs), but assessment using a true performance metric is lacking. Plus/minus (PM) metrics provide a practical and objective approach to player performance assessment and are commonly used in other sports. This study aimed to quantify and compare individual player performance variations in elite football league players who sustained ATRs and returned to play within 1 year compared to those without ATRs, using a PM metric. METHODS: Player and team data were sourced from Transfermarkt.com. Male players sustaining ATRs between 2007 and 2018 were identified through injury reports. A control group (CTRL) was matched by position, age, height, and league, with a 6:1 ratio of controls to ATR subjects. The day of injury was considered "time zero". Year -1 corresponds to the 360 days preceding injury, and Year 1 to the interval between 360 and 720 days after. Performance in the player's main team was evaluated using a previously validated weighted PM metric. Only data from Year -1 and Year 1 were used for ATR versus CTRL group comparisons. Statistical significance was set at p < 0.05. RESULTS: The ATR group included 125 athletes. Data from more than 76,000 matches were analyzed. No statistically significant differences in net weighted PM metric between Year -1 and Year 1 were found. CONCLUSION: No differences were found between athletes suffering from ATRs and controls regarding the weighted PM metric. LEVEL OF EVIDENCE: III.

Intense Caloric Restriction from Birth Prevents Cardiovascular Aging in Rats.

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

First report of Giardia duodenalis in pet rabbits in Brazil.

Giardia duodenalis is a flagellate protozoan that multiplies in the small intestine of a wide variety of hosts, animals and humans. It has a worldwide distribution, however it is considered a neglected disease by the World Health Organization (WHO). Nowadays, rabbits are being chosen as pets, especially by children. There are already reports of the occurrence of G. duodenalis in rabbits from other countries, but research has not been carried out in Brazil yet. Thus, the objective of our work was to verify the occurrence and molecularly characterize G. duodenalis that affect pet rabbits, through the polymerase chain reaction (PCR) in the northwest region of the state of São Paulo, Brazil. Fecal samples from 100 rabbits were collected, which later underwent a process of DNA extraction and amplification by nested-PCR (nPCR), using the SSU rRNA gene, and ß-giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi) to determine the assemblage. A questionnaire was answered by the owners with information about gender, age, deworming, diarrhea, water source, food, place of residence and contact with other animals. From those samples, 40 were positive for G. duodenalis. Good quality of the SSU rRNA gene by nPCR were obtained from two samples. For the first time, we report the occurrence of G. duodenalis assemblage A on pet rabbits in Brazil.

Unlocking the potential of snake venom-based molecules against the malaria, Chagas disease, and leishmaniasis triad.

Malaria, leishmaniasis and Chagas disease are vector-borne protozoal infections with a disproportionately high impact on the most fragile societies in the world, and despite malaria-focused research gained momentum in the past two decades, both trypanosomiases and leishmaniases remain neglected tropical diseases. Affordable effective drugs remain the mainstay of tackling this burden, but toxicicty, inneficiency against later stage disease, and drug resistance issues are serious shortcomings. One strategy to overcome these hurdles is to get new therapeutics or inspiration in nature. Indeed, snake venoms have been recognized as valuable sources of biomacromolecules, like peptides and proteins, with antiprotozoal activity. This review highlights major snake venom components active against at least one of the three aforementioned diseases, which include phospholipases A2, metalloproteases, L-amino acid oxidases, lectins, and oligopeptides. The relevance of this repertoire of biomacromolecules and the bottlenecks in their clinical translation are discussed considering approaches that should increase the success rate in this arduous task. Overall, this review underlines how venom-derived biomacromolecules could lead to pioneering antiprotozoal treatments and how the drug landscape for neglected diseases may be revolutionized by a closer look at venoms. Further investigations on poorly studied venoms is needed and could add new therapeutics to the pipeline.

Monte Carlo calculation of whole body counter efficiency factors for different computational phantoms.

Individual monitoring can provide an estimate of the radioactivity present in the body of the exposed individuals. Periodic monitoring of occupationally exposed individuals is of great importance in case of accidental incorporation. Computational phantoms and Monte Carlo codes are often used to complement the calibration method of counting systems in internal dosimetry. Here, counting efficiency (CE) factors for a WBC system were calculated using MC simulations. The WBC system with a NaI(Tl) detector and the BOMAB phantom was modeled using three MC codes. After validation, the models were used to obtain CE values for a wide range of energies, and a CE curve was generated for the WBC system. To estimate the effects of anatomical differences on the measurement process, two anthropomorphic voxel phantoms were modeled using the VMC code. For the detector position with the highest CE value, the differences when comparing BOMAB results with the MaMP and Yale results were (-1 ± 6)% and (-1 ± 3)%, respectively. The results confirm that the use of the BOMAB phantom is a good approach for the calibration of the whole-body counter system. Measurements should be made at detector position with the highest CE values, and it is recommended to use the mean Monte Carlo CE values calculated in this work.

Clinical Assessment of Biphasic Calcium Phosphate in Granules and Paste Forms in Human Maxillary Sinus Bone Augmentation: A Randomized, Split-Mouth Clinical Trial.

The aim of the present study is to compare the biphasic calcium phosphate (BCP) using two different forms-(1) granules and (2) paste-in human maxillary sinus bone reconstruction as a split-mouth study using histomorphometric and immunolabeling for osteocalcin. Ten patients with bilateral maxillary posterior partial edentulism were selected in order to reconstruct bone height. They were divided into two groups: BCPG and BCP-P. After six months of bone healing, biopsies were harvested to assess the new bone formation and immunostaining for osteocalcin. The BCP g group had the following results: mean of bone formation in pristine bone 49.4 ± 21.6%, intermediate 49.4 ± 16.2%, and apical 55.3 ± 21.4%. The group BCP-P had a mean of 41.9 ± 17.3% in the pristine bone region, 37.5 ± 7.8% for intermediate, and 39.0 ± 13.5% for apical. The osteocalcin immunolabeling was high for both groups, demonstrating bone calcification. Thus, the two biomaterials present suitable results for the placement of dental implants.

Fear of COVID-19 influences physical activity practice: a study in a Brazilian sample.

The suspension of social activities combined with health insecurity, uncertainty and fear of COVID-19 may influence physical activity practice. We aimed to investigate the relationship between the fear of COVID-19 and anxiety on physical activity patterns during the pandemic period. This cross-sectional study was performed in a sample of 520 Brazilian participants recruited by online sampling and snowball method. We assessed demographic variables, health perceptions, anxiety, fear of COVID-19 and physical activity characteristics. Both fear scores and anxiety were higher in woman (p < 0.0001). We observed a remarkable reduction in the frequency and intensity of physical activity and a modification in the exercise practice environment (from gym or sports centers to home-based physical activity) (p < 0.05). Sedentary (sitting) behavior increased during pandemic both in the weekdays and in the weekend (p < 0.0001). Participants who have never been infected were more prone of being classified in higher levels for physical activity (OR: 1.916, CI = 1.043-3.521) versus those who were previously infected (p = 0.05). Participants with a low or moderate level of physical activity before the pandemic presented lower chances of being classified as high physical activity level during the pandemic in comparison to those with high level before pandemic (p < 0.001). The Fear of Covid-19 score was negatively associated with the physical activity level (the higher the fear, the lower the level of physical activity); that is, for every increase in scale score, the odds of vigorous physical activity decreased 3%. In conclusion, fear of COVID-19 and previous contact with the virus negatively influenced physical activity practice.

Calculation of absorbed dose in paediatric phantoms using Monte Carlo techniques for 18F-FDG and 99mTc-DMSA and the new TIAC.

The radiopharmaceuticals most commonly used in nuclear medicine are 18F-FDG and 99mTc-DMSA, both of which are administered to paediatric and adult patients using the same time activity coefficient. However, the IAEA recommends specific paediatric dosimetry. The aim of this work (TW) was to estimate the absorbed dose for 18F-FDG and 99mTc-DMSA using two paediatric voxel phantoms (Baby and Child) by Monte Carlo techniques. Biokinetic data for both radiopharmaceuticals were obtained from ICRP 128. In addition, the new time-integrated activity coefficient (TIAC) values from a recent publication were examined for the following organs: Brain, urinary bladder wall, liver, heart wall, and lung. The absorbed dose per injected activity (AD/IA) and effective dose per injected activity (E/IA) values were calculated for both phantoms and the results were compared with simulated data of paediatric phantoms from ICRP 128, MIRDcalc software and available literature. Regarding AD/IA in organs, differences of up to 61% and 115% were found for the Baby phantom and 120% and 167% for the Child phantom using 18F-FDG and 99mTc-DMSA, respectively. For FDG using the new TIAC, a maximum difference of 244% was observed. For E/IA, the maximum differences were 27% and 31% for the Baby and Child phantoms, respectively, for FDG and DSMA. In this study, new dosimetric data were calculated using Baby and Child phantoms and the newly recommended TIAC.

KETO[18F]FDG -VAP-P1: In vivo studies of a potential PET radiotracer for diagnosis of inflammation.

The biodistribution of radiotracer peptide KETO[18F]FDG-VAP-P1 was evaluated by ex vivo radiation count in organs and in vivo PET imaging of healthy mice. The peptide was quickly eliminated by the kidneys. The local inflammation caused by a sterile polyurethane sponge was evaluated by PET images. In addition, dosimetry estimates of KETO[18F]FDG-VAP-P1 tracer are determined for mice using Monte Carlo simulations. Thus, the results of this study indicate that KETO[18F]FDG-VAP-P1 is a potential radiotracer for inflammation imaging.

Atenção integral à população trans: panorama da atuação do cirurgião-dentista na atenção primária à saúde / Comprehensive care for the trans population: importance of the dentist's role in primary health care

A sigla LGBTQIA+ engloba identidades relacionadas à orientação sexual e de gênero, representando aqueles que se desviam dos padrões cis heteronormativos e binários. Esta população, em especial a trans, enfrenta silenciamento e estigmatização no acesso aos serviços de saúde, incluindo a saúde bucal, devido à discriminação e à falta de conhecimento dos profissionais. Estudos apontam que a saúde bucal dessa população é pior do que a média da população em geral e transtornos mentais são mais comuns nessa população, afetando os cuidados com a higiene bucal e se relaciona a condições como disfunção temporomandibular (DTM) e dor orofacial. Além disso, a população trans apresenta taxas mais altas de abuso de substâncias nocivas à saúde bucal, como álcool, tabaco e drogas ilícitas, que estão associados ao desenvolvimento de neoplasias orais. A terapia hormonal de afirmação de gênero (THAG), utilizada por trans, pode afetar a saúde bucal, levando à inflamação gengival e dor. A adoção de abordagem multidisciplinar é fundamental para fornecer cuidados adequados e inclusivos, sendo essencial considerar também os impactos psicossociais na saúde bucal. Na busca por cuidados de saúde, é crucial a abordagem do risco de infecções sexualmente transmissíveis (ISTs) e da violência interpessoal. É fundamental que os cirurgiões-dentistas estejam preparados para o acolhimento e tratamento dessa população de forma inclusiva, oferecendo cuidados preventivos, diagnóstico precoce e encaminhamento adequado. Ainda, um olhar sensível deve ser voltado às questões de identidade de gênero, uso correto de pronomes e nome social e a criação de ambiente seguro e livre de discriminação

The acronym LGBTQIA+ encompasses identities related to sexual orientation and gender, representing those who deviate from cis-heteronormative and binary standards. The LGBTQIA+ population, especially the transgender persons, faces silencing and stigmatization in accessing health services, including oral health, due to discrimination and a lack of knowledge of professionals. Studies indicate that the oral health of this population is worse than the average of the general population and mental disorders are more common in this population, affecting oral hygiene care and being related to conditions such as temporomandibular disorders (TMD) and orofacial pain. In addition, transgender persons have higher rates of substance abuse that are harmful to oral health, such as alcohol, tobacco, and illicit drugs, which are associated with the development of oral neoplasms. Gender-affirming hormone therapy (GAHT), used by transgender person, can affect oral health, leading to gum inflammation and pain. The adoption of a multidisciplinary approach is essential to provide adequate and inclusive care, and it is essential to consider the psychosocial impacts on oral health. In seeking healthcare, addressing the risk of sexually transmitted infections (STIs) and interpersonal violence is crucial. It is essential that dentists are prepared to receive and treat this population in an inclusive way, offering preventive care, early diagnosis, and appropriate referral. In addition, a sensitive look must be turned to questions of gender identity, social names, correct pronouns, and creating a safe and discrimination-free environment

Eco-Friendly Silver Nanoparticles Synthesized from a Soybean By-Product with Nematicidal Efficacy against Pratylenchus brachyurus.

This study explores an eco-friendly approach to synthesizing silver nanoparticles (AgNPs) using soybean leaf extracts, employing a reaction with silver nitrate at 65 °C for 2.5 h. Optimal results were achieved at extract concentrations of 3.12 and 6.25 mg of the leaf mL-1, termed 3.12AgNP and 6.25AgNP, respectively. UV-Vis spectrophotometric analysis between 350 and 550 nm exhibited a peak at 410-430 nm, along with a color transition in the suspensions from pale yellow to brown, indicating successful synthesis. Dynamic light scattering (DLS) further delineated the favorable properties of these AgNPs, including nanometric dimensions (73-104 nm), negative charge, and moderate polydispersity, portraying stable and reproducible synthesis reactions. The bioreduction mechanism, possibly expedited by leaf extract constituents such as amino acids, phenolic acids, and polysaccharides, remains to be fully elucidated. Notably, this study underscored the potent nematicidal effectiveness of biosynthesized AgNPs, especially 6.25AgNP, against Pratylenchus brachyurus, which is a common plant-parasitic nematode in tropical soybean cultivation regions. In vitro tests illustrated significant nematicidal activity at concentrations above 25 µmol L-1, while in vivo experiments displayed a pronounced nematode population diminishment in plant roots, particularly with a 6.25AgNP rhizosphere application at concentrations of 500 µmol L-1 or twice at 250 µmol L-1, attaining a reproduction factor below 1 without any morphological nematode alterations. This research highlights the potential of 6.25AgNPs derived from soybean leaf extracts in forging sustainable nematicidal solutions, marking a significant stride toward eco-friendly phytonematode management in soybean cultivation. This novel methodology signals a promising avenue in harnessing botanical resources for nematode control and propelling a greener agricultural horizon.

Superior cardiometabolic and cellular adaptive responses to multiple versus single daily sessions of high-intensity interval training in Wistar rats.

This study aimed to compare in rats the cardiometabolic and cellular adaptative responses to 8 weeks of high-intensity interval training (HIIT) performed in a single (1xHIIT) or three shorter daily sessions (3xHIIT). Male Wistar rats were assigned to untrained (n = 10), 1xHIIT (n = 10), and 3xHIIT (n = 10) groups. Both HIIT groups performed 15 min of a treadmill run five times per week for 8 weeks. The 1xHIIT performed single daily sessions of 15 min, and the 3xHIIT performed three daily sessions of 5 min with an interval of 4 h between sessions. Resting VO2 and VO2max were measured using a metabolic chamber; blood pressure and heart rate were measured by plethysmography; body composition was estimated by DEXA; Glucose and insulin tolerance tests were performed; after euthanasia, hearts, gastrocnemius, and visceral fat were harvested for analysis of cardiac function, histology, and morphology. Mitochondrial densities of the gastrocnemius and left ventricle muscles were determined by electron microscopy. 3xHIIT induced similar positive adaptative responses to 1xHIIT on resting VO2 and VO2max, cardiac function, and mitochondria density. 3xHIIT was superior to 1xHIIT in reducing visceral fat weight and adipocyte size and improving insulin tolerance. Multiple short daily bouts of HIIT may be superior to single HIIT daily sessions in improving cardiometabolic and cellular adaptations in rats.

Which Histometric Analysis Approach Is More Reliable for Assessing Histological Bone Tissue Samples?

This study aims to evaluate the grid of Merz and ImageJ methods for histometric quantification, verifying which is more reliable and defining which is most suitable based on the time required to perform. Thirty histological samples of maxillary sinuses grafted with xenografts were evaluated using an optical light microscope attached to an image capture camera and connected to a microcomputer. The images were digitalized and recorded as a TIFF image, and the new bone formation was evaluated using the grid of Merz and ImageJ. The Bland-Altman analysis was used to identify the agreement between the methods and determine suitable future research options. The timing of the quantification was also performed to identify a possible advantage. The mean value for the quantification analysis timing for the grid of Merz was 194.9 ± 72.0 s and for ImageJ was 871.7 ± 264.4, with statistical significance between the groups (p = 0.0001). The Bland-Altman analysis demonstrated a concordance between the methods, due to the bias being next to the maximum concordance (-1.25) in addition to the graphic showing the scattering points next to the mean of differences and inside of limits of agreement. Thus, it was demonstrated that the grid of Merz presents reliable outcomes and advantages over the ImageJ methodology regarding the time spent to contour the areas of interest.

Evaluation of Two Beta-Tricalcium Phosphates with Different Particle Dimensions in Human Maxillary Sinus Floor Elevation: A Prospective, Randomized Clinical Trial.

This study aimed to compare two beta-tricalcium phosphates with different particle sizes in human maxillary sinuses lifting. The immunolabeling of cells for RUNX2 and VEGF were performed to evaluate the osteoblast precursor cells and the vascular formation after 6 months of bone repair. Ten maxillary sinuses were grafted with autogenous bone graft (Group 1), 10 were grafted with ChronOs® (Group 2), and 10 were grafted with BETA-TCP® (Group 3). After 6 months of bone healing, biopsies were obtained to assess the new bone formed by histomorphometric and immunohistochemical evaluation for RUNX2 and VEGF. The mean bone formation for Group 1 was 51.4 ± 17.4%. Group 2 presented 45.5 ± 9.9%, and Group 3 conferred 35.4 ± 8.0% of new bone formation. The RUNX2 offered low for Groups 1 and 2 with high cellular activity for osteoblast in Group 3. The VEGF immunolabeling was moderate for Groups 1 and 2 and intense for Group 3. In conclusion, it was possible to show that the bone substitutes evaluated in the present study presented suitable outcomes for bone regeneration, being an alternative for the autogenous bone graft in maxillary sinus bone height reconstruction.

Seasonal Training Load Monitoring Among Elite Level Soccer Players: Perceived Exertion and Creatine Kinase Variations Between Microcycles.

The primary aim of the investigation was to determine the daily load variations between the microcycles of an entire season of an elite group of professional soccer players. The second aim of this study was to determine the relationships between Foster's rating of perceived exertion (RPE), the Hooper index (HI) and CK levels over the weekly microcycles of the season. Thirty-five male professional soccer players participated in this study (3 goalkeepers, 6 wide defenders, 4 central defenders, 9 midfielders, 8 wide midfielders and 4 forwards) (25.7 ± 5.0 years, 182.3 ± 6.4 cm; 79.1 ± 7.0 kg). Significant differences between months in the variables of HI (p = 0.001; ES = 0.052), minT (p = 0.001; ES = 0.066), IL (p = 0.001; ES = 0.052, minimum effect) and CK (p = 0.002; ES = 0.031) were found. Comparison of the HI (p = 0.044; ES = 0.002), minT (p = 0.001; ES = 0.045), and IL (p = 0.001; ES = 0.045) revealed significant differences between microcycles. No significant differences were found in CK (p = 0.710; ES = 0.001) across the period. A significantly higher internal training load and fatigue perception in microcycles with only one official match was found. The greater load occurred 3 to 4 days before the game. In addition, it can be concluded that the first quarter of the season seemed to induce a greater physical demand on elite professional players.

Traditional and Computational Screening of Non-Toxic Peptides and Approaches to Improving Selectivity.

Peptides have positively impacted the pharmaceutical industry as drugs, biomarkers, or diagnostic tools of high therapeutic value. However, only a handful have progressed to the market. Toxicity is one of the main obstacles to translating peptides into clinics. Hemolysis or hemotoxicity, the principal source of toxicity, is a natural or disease-induced event leading to the death of vital red blood cells. Initial screenings for toxicity have been widely evaluated using erythrocytes as the gold standard. More recently, many online databases filled with peptide sequences and their biological meta-data have paved the way toward hemolysis prediction using user-friendly, fast-access machine learning-driven programs. This review details the growing contributions of in silico approaches developed in the last decade for the large-scale prediction of erythrocyte lysis induced by peptides. After an overview of the pharmaceutical landscape of peptide therapeutics, we highlighted the relevance of early hemolysis studies in drug development. We emphasized the computational models and algorithms used to this end in light of historical and recent findings in this promising field. We benchmarked seven predictors using peptides from different data sets, having 7-35 amino acids in length. According to our predictions, the models have scored an accuracy over 50.42% and a minimal Matthew's correlation coefficient over 0.11. The maximum values for these statistical parameters achieved 100.0% and 1.00, respectively. Finally, strategies for optimizing peptide selectivity were described, as well as prospects for future investigations. The development of in silico predictive approaches to peptide toxicity has just started, but their important contributions clearly demonstrate their potential for peptide science and computer-aided drug design. Methodology refinement and increasing use will motivate the timely and accurate in silico identification of selective, non-toxic peptide therapeutics.

Causative Agents of American Tegumentary Leishmaniasis Are Able to Infect 3T3-L1 Adipocytes In Vitro.

Although macrophages have long been considered key players in the course of Leishmania infections, other non-professional phagocytes have lately been shown to maintain low levels of the parasite in safe intracellular niches. Recently, it was demonstrated that the adipose tissue is capable of harboring Old World L. (L.) infantum in mice. However, there is no evidence of experimental adipocyte infection with New World Leishmania species so far. In addition, it was not known whether adipocytes would be permissive for formation of the unique, large and communal parasitophorous vacuoles that are typical of L. (L.) amazonensis in macrophages. Here we evaluated the ability of L. (L.) amazonensis and L. (V.) braziliensis promastigotes and amastigotes to infect 3T3-L1 fibroblast-derived adipocytes (3T3-Ad) using light and transmission electron microscopy. Our results indicate that amastigotes and promastigotes of both species were capable of infecting and surviving inside pre- and fully differentiated 3T3-Ad for up to 144 h. Importantly, L. (L.) amazonensis amastigotes resided in large communal parasitophorous vacuoles in pre-adipocytes, which appeared to be compressed between large lipid droplets in mature adipocytes. In parallel, individual L. (V.) braziliensis amastigotes were detected in single vacuoles 144 h post-infection. We conclude that 3T3-Ad may constitute an environment that supports low loads of viable parasites perhaps contributing to parasite maintenance, since amastigotes of both species recovered from these cells differentiated into replicative promastigotes. Our findings shed light on the potential of a new host cell model that can be relevant to the persistence of New World Leishmania species.