Placebo in sports nutrition: a proof-of-principle study involving caffeine supplementation.

We investigated the effects of supplement identification on exercise performance with caffeine supplementation. Forty-two trained cyclists (age 37 ± 8 years, body mass [BM] 74.3 ± 8.4 kg, height 1.76 ± 0.06 m, maximum oxygen uptake 50.0 ± 6.8 mL/kg/min) performed a ~30 min cycling time-trial 1 h following either 6 mg/kgBM caffeine (CAF) or placebo (PLA) supplementation and one control (CON) session without supplementation. Participants identified which supplement they believed they had ingested ("caffeine", "placebo", "don't know") pre- and post-exercise. Subsequently, participants were allocated to subgroups for analysis according to their identifications. Overall and subgroup analyses were performed using mixed-model and magnitude-based inference analyses. Caffeine improved performance vs PLA and CON (P ≤ 0.001). Correct pre- and post-exercise identification of caffeine in CAF improved exercise performance (+4.8 and +6.5%) vs CON, with slightly greater relative increases than the overall effect of caffeine (+4.1%). Performance was not different between PLA and CON within subgroups (all P > 0.05), although there was a tendency toward improved performance when participants believed they had ingested caffeine post-exercise (P = 0.06; 87% likely beneficial). Participants who correctly identified placebo in PLA showed possible harmful effects on performance compared to CON. Supplement identification appeared to influence exercise outcome and may be a source of bias in sports nutrition.

Variations in caries diagnoses and treatment recommendations and their impacts on the costs of oral health care.

OBJECTIVE: To evaluate the reproducibility of caries detection and treatment planning among public health dentists and estimate the possible impact of their decisions on financial costs. RESEARCH DESIGN AND SETTINGS: Thirty nine dentists working in the public health service of Piracicaba, São Paulo, Brazil made a combined visual-radiographic caries examination of 40 occlusal surfaces of extracted permanent teeth mounted on two dental mannequins and proposed treatment plans for each tooth. Histological validation then evaluated the diagnoses validity and the suitability of the treatment plans. OUTCOME MEASURES: Inter-examiner agreement was calculated by Cohen's Kappa statistics. The sensitivity and specificity of caries detection and treatment decision were calculated. The costs of dental treatment plans for public health system were calculated from a Brazilian public health service fee scale. RESULTS: Inter-examiner agreement for caries detection was moderate (kappa = 0.42) while for treatment decisions it was fair (kappa = 0.29). The sensitivity and specificity were 0.69 and 0.65 for caries detection and 0.56 and 0.65 for treatment decision respectively. Dentists overestimated the presence and depth of carious lesions and there was a tendency to treat enamel lesions using invasive therapeutic procedures. Mean treatment cost across the two cases was 32US$ (range 9-65) while the histologically validated cost was 23US$. CONCLUSION: The variability in caries detection and treatment decision negatively affected the cost of the dental treatment.

Development of an auxiliary resource for diagnosis of dental caries in epidemiological surveys.

OBJECTIVE: Early dental caries diagnosis within the changing global pattern of dental caries development requires the use of auxiliary resources and adjuncts to diagnosis. The aim of this study was to introduce an alternative resource for drying teeth to enable early diagnosis of dental caries in epidemiological surveys. METHODS: Polyurethane tips and three-in-one syringes were fitted to nebulizers and non-professional portable compressors for dental surface drying. The output air pressure of these sets was compared with the output pressure from the three-in-one syringe in a dental office. RESULTS: Although the output pressure from the alternative resources was lower than the output pressure from the dental office equipment, the dental surfaces were dried satisfactorily, allowing the early diagnosis of the dental caries. CONCLUSION: When a dental setting is not available, these alternative resources for drying teeth can be used satisfactorily.

Accuracy of orthognathic surgery with customized titanium plates-Systematic review.

This systematic review aimed to evaluate the accuracy of customized titanium plates in orthognathic surgery compared to standard outcome in virtual surgical planning. PRISMA and JBI guidelines were followed. Research protocol was registered in PROSPERO. Six databases and two gray literature repositories were used as sources of research articles. Descriptive clinical studies, that performed orthognathic surgery using custom titanium plates, were included. Risk of bias was assessed by "The Joanna-Briggs Institute Critical Appraisal tools for use in Systematic Reviews Checklist for Case Series". Of the 11,916 studies initially identified, seven met the eligibility criteria and were included. The studies were published between 2015 and 2019. Most of the studies (57%) had a low risk of bias, while one had a high risk of bias. Total sample included 74 patients with 63 bimaxillary surgeries and 11 unimaxillary surgeries. All studies showed acceptable accuracy within previously established clinical parameters. Although the eligible articles assessed the accuracy of the orthognathic surgery with respect to virtual planning, the wide variability of evaluation methodologies made it impossible to calculate a combined accuracy measure. It was not possible to perform a meta-analysis, so a pragmatic recommendation on the use of these plates is not possible.

Complement binding by two developmental stages of Leishmania major promastigotes varying in expression of a surface lipophosphoglycan.

The binding of complement by two developmentally distinct stages of Leishmania major has been studied. Noninfective log phase growth (LOG) promastigotes (serum sensitive) activate complement with deposition of covalently bound C3b onto the surface of the parasite. Infective, peanut agglutinin (PNA-) metacyclic stage promastigotes (serum resistant) also bear mainly C3b after incubation in serum, but a major portion of deposited C3 is present as a 110 X 10(3) mol wt C3 fragment. Whereas deposition of C3b on LOG promastigotes is mediated through the alternative pathway. PNA- parasites are unable to activate the alternative pathway in nonimmune serum. C3 is released from the parasite surface by proteolytic cleavage, at a rate which is nearly threefold greater for LOG than for PNA- promastigotes. Immunoprecipitation experiments show that the developmentally regulated lipophosphoglycan is a major C3 acceptor on both LOG and PNA- parasites. These experiments, which are the first to compare the form and processing of complement on infective and noninfective promastigotes of Leishmania, provide a framework for further definition of the differential C3 receptor-dependent uptake and survival of these parasites within mononuclear phagocytes.

Recognizing death: the phagocytosis of apoptotic cells.

Although apoptotic cell death is widespread, dying cells are rarely seen in situ because of their rapid clearance by neighbouring phagocytes. Phagocytic recognition of apoptotic cells is less well understood than the death programme itself, but an increasing number of recent studies are highlighting its importance. This review discusses the nature of the receptors that have been implicated in apoptotic cell phagocytosis, the mechanisms of uptake and the immunological consequences of apoptotic cell ingestion.

Fasting: a major limitation for resistance exercise training effects in rodents.

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats.

Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults.

The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

Cell surface nanoanatomy of Leishmania major as revealed by fracture-flip. A surface meshwork of 44 nm fusiform filaments identifies infective developmental stage promastigotes.

Fracture-flip (Anderson-Forsman and Pinto da Silva, J. Cell Sci. 90, 531-541; 1988) was used to reveal the nanoanatomy of the surface of Leishmania major promastigotes. Over the cell surface of infective metacyclic promastigotes we identify a meshwork of 44 nm long, fusiform filaments. These filaments are not seen in noninfective stages of the parasite. Replica-staining immunocytochemistry with monoclonal antibody against infective metacyclic lipophosphoglycan shows a uniform distribution of protein A-colloidal gold complexes over the cell surface. Thin sections show that acquisition of the high molecular weight lipophosphoglycan is reflected in a thicker glycocalyx. Conventional freeze-fracture shows that in infective metacyclic promastigotes there is a reversal of the partition of intramembrane particles--an additional morphological marker for the infective developmental stage. We hypothesize that the fusiform filaments represent metacyclic developmental lipophosphoglycan.

Class A scavenger receptors and the phagocytosis of apoptotic cells.

Apoptotic cells are rarely seen in situ because of rapid clearance by phagocytes. A number of receptors have been implicated in the recognition and ingestion of dying cells. Class A scavenger receptors (SRs) are multi-domained membrane glycoproteins that can endocytose modified lipoproteins and bind a wide range of ligands. There is growing evidence that they contribute to several biological processes. We present data that suggest class A SRs are involved in the phagocytosis of apoptotic cells.

Macrophage membrane molecules: markers of tissue differentiation and heterogeneity.

Monoclonal antibodies directed against murine macrophage differentiation antigens provide tools to characterize novel glycoproteins, their expression by different macrophage subpopulations in situ and regulation by cytokines and other agents in vitro. Studies are in progress to determine ligands for these molecules, and to establish possible functions. We summarize current knowledge of the following molecules: F4/80, a glycoprotein with homology to the G-protein linked transmembrane 7 hormone receptor family; macrosialin, a member of the lysosomal-associated membrane protein [lamp] family with a macrophage-specific mucin-like extracellular domain also present in its human homologue, CD68; sialoadhesin, a sialic acid binding lectin with multiple Ig superfamily domains; mannosyl receptor, a lectin-like molecule with multiple C-type lectin domains; type 3 complement receptor, a beta 2 integrin involved in cell migration and adhesion; scavenger receptor, a transmembrane homotrimer with a collagenous domain.

The importance of vaginal infection on recurrent cystitis in women.

Forty-one women with a clinical history of recurrent urinary infection were studied. The aim of this study was to correlate the importance of vaginal infection and theincreased incidence of urinary infection. By using statistical methods, we came to the conclusion that the presence of vaginal infection is not related to the recurrence of urinary infection. Vaginal contaminations certainly permit the increase of urinary infection; there must be other host-related factors, however, that are more important for the recurrence of urinary infection.

Treatment of recurrent cystitis in women by internal urethrotomy or antimicrobial agents.

Seventy-one women suffering from recurrent cystitis were analysed. The patients were randomly distributed into two groups, in accordance with the treatment given. Forty-one were treated medically and thirty were subjected to internal urethrotomy with the Otis urethrotome and antimicrobial agents. The results of treatment for urinary infection were:85.4% in the first group and 73.3% in the second group. There was no statistically significant difference between the results of the two groups analysed. The symptomatology showed 65.8% of the cases asymptomatic in the group treated medically and 36.7% in the surgical-medicinal group. The difference between the results of the two groups was statistically significant according to the symptomatology. Therefore, medical treatment of recurring cystitis in women was superior to surgical-medicinal treatment.

[Clinical aspects and development of dilated cardiomyopathy in infants and children]. / Aspectos clínicos e evolutivos da miocardiopatia dilatada nos lactentes e na infância.

PURPOSE: The evaluation of the clinical aspects of the dilated cardiomyopathy (DCM) in infants and children regarding, mainly, to the evolution and prognostic of this disease. PATIENTS AND METHODS: 38 patients divided in two groups: A) 22 infants till 22 (11.60 +/- 6.50) months of age, 15 female, and B) 15 children of 2 to 12 years of age (5.23 +/- 3.13) the majority males (10). A retrospective study was carried out based on the data from the patients's records. It was performed, in all the cases, a clinical, electrocardiographic, echocardiographic (M module and two dimensional echocardiography) and radiologic evaluation. RESULTS: The dyspnea on exercise (included sucking) was the predominant symptom in 15 (65.22%) patients of the A group and 10 (66.67%) of the B group followed by perilabial cyanosis in 7 (30.43%) and 6 (40%) patients, respectively. In the A group the clinical diagnostic hypothesis was inspecific myocarditis (IM) in 12 (52.17%), endocardial fibroelastosis (EFE), in 8 (34.79%), and "idiopathic" dilated cardiomyopathy (IDCM) in 3 (13.04%). In the B group to the diagnostic conclusion of myocarditis was made in 10 patients (66.67%)--5 of them IM--EFE in 3 (20%); and IDCM in 2 (13.33%). The average time of evolution was 5.48 months in the A group and 18.56 in the B group. In the A group the evolution was excellent in 3 (3.04%), good in 10 (43.46%), stable in 2 (8.70%) and bad in 1 (4.35%). In the B group, excellent in 8 (53.33%), good in 2 (20%) stable in 1 (6.67%). No bad evolution in this group. There was a decrease in the A group (4.34%); 6 patients in this group (26.09%) and 3 (20%) of the B group interrupt the follow-up. CONCLUSION: 1) The prognosis of infants with DCM including those with the diagnostic hypothesis of EFE seems to be less adverse than it could be supposed to be; 2) the prognostic in children with the diagnosis of DCM established above 2 years of age seems to be good; 3) the differential clinical diagnosis between EFE and IM is difficult and with no accuracy; 4) it is possible that the IM could be more prevalent in infants till 6 months of age than we suppose it was.

Fasting: a major limitation for resistance exercise training effects in rodents

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats.

Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults

The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

Ion channels in volume regulation of clonal kidney cells.

OBJECTIVES: Clonal kidney cells (Vero cells) are extensively utilized in the manufacture of biological preparations for disease diagnostics and therapeutics and also in preparation of vaccines. In all cells, regulation of volume is an essential function coupled to a variety of physiological processes and is a topic of interest. The objective here was to investigate involvement of ion channels in the process of volume regulation of Vero cells. METHODS: Involvement of ion channels in cell volume regulation was studied using video-microscopy and flow cytometry. Pharmacologically unaltered cells of different sizes, which are presumably at different phases of the cell cycle, were used. RESULTS: Ion transport inhibitors altered all phases of regulatory volume decrease (RVD) of Vero cells, rate of initial cell swelling, V(max) and volume recovery. Effects were dependent on type of inhibitor and on cell size (cell cycle phase). Participation of aquaporins in RVD was suggested. Inhibitors decelerated growth, arresting Vero cells at the G(0) /G(1) phase boundary. Electrophysiological study confirmed presence of volume-activated Cl(-) channels and K(+) channels in plasmatic membranes of the cells. CONCLUSION: Vero cells of all sizes maintained the ability to recover from osmotic swelling. Activity of ion channels was one of the key factors that controlled volume regulation and proliferation of the cells.

Phagocytosis stimulates alternative glycosylation of macrosialin (mouse CD68), a macrophage-specific endosomal protein.

Macrosialin (mouse CD68), a macrophage-specific member of the lysosomal-associated membrane protein family, displays N-linked glycosylation and a heavily sialylated, mucin-like domain. We show that phagocytosis of zymosan by inflammatory peritoneal macrophages potently alters glycan processing of macrosialin in vitro. The phagocytic glycoform is not induced by other forms of endocytosis and depends on particle internalization. Zymosan uptake does not influence macrosialin protein synthesis, but increases the specific incorporation of D-[2-3H]mannose, D-[6-3H]galactose, N-acetyl-D-[1-3H]glucosamine and L-[5,6-3H]fucose by 2-15-fold. The phagocytic glycoform displays increased binding of agglutinins from peanut, Amaranthus caudatus and Galanthus nivalis, whereas binding of the sialic-acid-specific Maakia amurensis agglutinin is slightly reduced. Digestion by N-Glycanase abolishes the incorporation of [3H]mannose label and Galanthus nivalis agglutinin binding activity, but preserves the incorporation of galactose and N-acetylglucosamine and specific lectin binding. We also show that phagocytosis increases the complexity and length of O-linked chains. The data presented highlight the importance of differential glycosylation in the biology of macrosialin, phagosomes and macrophages in general.

The generation of infective stage Leishmania major promastigotes is associated with the cell-surface expression and release of a developmentally regulated glycolipid.

A monoclonal antibody, 3F12, was generated which reacted specifically against infective or metacyclic stage Leishmania major promastigotes, but not with noninfective promastigotes obtained from log phase cultures. The antibody recognized a cell surface and released molecule that could be metabolically labeled with [14C]glucose, [3H]mannose, [3H]galactose, and [3H]palmitic acid, but not with [35S]methionine or [3H]leucine. The molecule was the major species surface-labeled by [3H]sodium borohydride after periodate treatment. The glycolipid appeared to be shed primarily as free carbohydrate because 70% of the released material partitioned in the aqueous fraction after phase separation in TX-114. The molecule could be distinguished from the L. major glycolipid which has already been extensively described because its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was of higher relative m.w. However, a close relationship between the two molecules was indicated by the finding that another monoclonal antibody, WIC-79.3, recognized both forms of the glycolipid; one produced and released only by log phase promastigotes, and one produced and released only by metacyclic promastigotes. The loss of agglutination with peanut agglutinin which has been shown to accompany metacyclogenesis was found to be caused by the loss of expression of the log form of the glycolipid which in most cases appeared to be the result of the developmental modification of this molecule. A survey of a number of virulent and avirulent. L. major strains and clones reinforced an absolute association between the ability of these promastigotes to initiate infection in BALB/c mice and their expression and release of the 3F12-binding, developmentally regulated form of the glycolipid. Not only does this glycolipid serve as the first well defined molecular marker for infective stage metacyclic promastigotes, but its unique structure is very likely to contribute to the adaptive changes that allow these parasites to survive within the vertebrate host.