A Concise and Useful Guide to Understand How Alpha1 Adrenoceptor Antagonists Work.

Adrenoceptors are the receptors for catecholamines, adrenaline, and noradrenaline. They are divided in α (α1 and α2) and ß (ß1, ß2 and ß3). α1-adrenoceptors are subdivided in α1A, α1B and α1D. Most tissues express mixtures of α1-adrenoceptors subtypes, which appear to coexist in different densities and ratios, and in most cases, their responses are probably due to the activation of more than one type. The three subtypes of α1-adrenoceptors are G-protein-coupled receptors (GPCR), specifically coupled to Gq/11. Additionally, the activation of these receptors may activate other signaling pathways or different components of these pathways, which leads to a great variety of possible cellular effects. The first clinically used α1 antagonist was Prazosin for Systemic Arterial Hypertension (SAH). It was followed by its congeners, Terazosin and Doxazosin. Nowadays, there are many classes of α-adrenergic antagonists with different selectivity profiles. In addition to SAH, the α1-adrenoceptors are used to treat Benign Prostatic Hyperplasia (BPH) and urolithiasis. This antagonism may be part of the mechanism of action of tricyclic antidepressants. Moreover, the activation of these receptors may lead to adverse effects such as orthostatic hypotension, similar to what happens with antidepressants and with some antipsychotics. Structure-activity relationships can explain, in part, how antagonists work and how selective they can be for each one of the subtypes. However, it is necessary to develop new molecules which antagonize the α1- adrenoceptors or make chemical modifications in these molecules to improve the selectivity and pharmacokinetic profile and/or reduce the adverse effects of known drugs.

Babesiosis and Theileriosis in North America.

Babesia and Theileria are apicomplexan parasites that cause established and emerging diseases in humans, domestic and wild animals. These protozoans are transmitted by Ixodid ticks causing babesiosis or theileriosis, both characterized by fever, hemolytic anemia, jaundice, and splenomegaly. In North America (NA), the most common species affecting humans is B. microti, which is distributed in the Northeastern and Upper Midwestern United States (US), where the tick vector Ixodes scapularis is established. In livestock, B. bovis and B. bigemina are the most important pathogens causing bovine babesiosis in tropical regions of Mexico. Despite efforts toward eradication of their tick vector, Rhipicephalus microplus, B. bovis and B. bigemina present a constant threat of being reintroduced into the southern US and represent a continuous concern for the US cattle industry. Occasional outbreaks of T. equi, and T. orientalis have occurred in horses and cattle, respectively, in the US, with significant economic implications for livestock including quarantine, production loss, and euthanasia of infected animals. In addition, a new species, T. haneyi, has been recently discovered in horses from the Mexico-US border. Domestic dogs are hosts to at least four species of Babesia in NA that may result in clinical disease that ranges from subclinical to acute, severe anemia. Herein we review the pathogenesis, diagnosis, and epidemiology of the most important diseases caused by Babesia and Theileria to humans, domestic and wild animals in Canada, the US, and Mexico.

Características y factores asociados al maltrato percibido en internos de medicina en Perú / Characteristics and associated factors with mistreatment perception in medical interns in Peru

RESUMEN Objetivo: Determinar las características y factores asociados a la percepción de maltrato en internos de medicina del Perú. Materiales y métodos : Estudio multicéntrico, transversal y analítico. Se encuestaron a internos de medicina de dieciocho hospitales del Perú. Se aplicó una encuesta entre marzo y abril del 2016 que incluían características sociodemográficas y una escala que media la percepción de maltrato psicológico, físico y sexual. Se realizaron modelos lineales generalizados y se estimaron razones de prevalencia crudas y ajustadas (RPa) con intervalos de confianza al 95%. Resultados : Participaron 418 internos de medicina. El maltrato psicológico, físico y sexual percibido fue de 91,9%; 55,5% y 34%, respectivamente. Los factores asociados con el maltrato psicológico fueron proceder de una universidad privada (RPa:1,07; IC95%:1,01- 1,13), respecto al maltrato físico fueron la edad (RPa: 1,08; IC95%: 1,05-1,12), realizar internado en un hospital de la selva (RPa: 1,27; IC95%: 1,03-1,56) y en un hospital del Seguro Social (RPa:0,66; IC95%:0,44-0,94) y para el maltrato sexual el ser mujer (RPa:1,52; IC95%:1,15-2,01). Conclusiones : Existe una alta percepción de maltrato reportado por los internos de medicina siendo el psicológico el más frecuente. Existen diferencias en la percepción de maltrato psicológico y físico según el tipo de financiamiento de la universidad de procedencia y del hospital donde se realiza el internado. Una alta frecuencia de maltrato sexual fue reportada por mujeres luego de los tres primeros meses del internado hospitalario.

ABSTRACT Objective: To determine the characteristics and factors associated with the perception of abuse in medicine interns of Peru. Material and Methods : This is a cross-sectional multicenter and analytical study. Medicine interns from eighteen Peruvian hospitals were interviewed. A survey was administered between March and April 2016, which included socio-demographic characteristics and a scale measuring psychological and physical abuse, as well as sexual harassment perception. Generalized linear models were used and crude and adjusted prevalence rates (aPR) were estimated, with 95% confidence intervals (CI). Results: 418 medical interns participated in the study. Psychological and physical abuses were perceived by 91,9% and 55,5% of the studied population. Sexual harassment was perceived by 34% of all interviewed interns. Associated factors with psychological abuse were studied in a private university (aPR: 1.07; 95% CI: 1.01-1.13). Factors associated with physical abuse were age (aPR: 1.08; 95% IC: 1.05-1.12), performing internship in an Amazonian area hospital (aPR: 1,27; 95% CI: 1,03-1,56), and in a Social Security Hospital (aPR: 0,66; 95% CI: 0,44-0,94); and for sexual harassment, being female was the main associated factor (aPR: 1,52; 95% CI: 1,15-2,01). Conclusions: There is a high perception of abuse experienced by medicine interns, being psychological abuse the most frequent condition. There are some differences in the perception of psychological and physical abuse, according to the medical school the interns come from, as well as with respect to the healthcare facility where internship is performed. A high frequency of sexual harassment was reported by female interns after three months of having started their training period.

Physiological changes in the hemolymph of juvenile shrimp Litopenaeus vannamei to sublethal nitrite and nitrate stress in low-salinity waters.

Juveniles of the shrimp Litopenaeus vannamei (3.3 ±â€¯0.4 g) were exposed separately to nitrite (0.0, 1.1, 2.6, and 5.3 mg/L nitrogen as nitrite [NO2--N]) and nitrate (0, 90, 225 and 400 mg/L nitrogen as nitrate [NO3--N]) concentrations equivalent to 0, 10, 25, and 50% of the LC50-96 h value of NO2--N and NO3--N in low salinity water (3 g/L). Shrimps responded to nitrite and nitrate according to changes in oxyhemocyanin, glucose, lactate and ion levels in the hemolymph after 6, 12, 24, and 48 h of exposure. Oxyhemocyanin levels decreased with increasing nitrite and nitrate levels and were higher at 50% exposure to the contaminants. Compared to the control, glucose and lactate increased significantly at 50% exposure to nitrite and nitrate, particularly at 12 and 24 h. Na+ in the hemolymph changed with nitrite and nitrate, while K+ only changed ˜with nitrite.

Toxicity of ammonia, nitrite and nitrate to Litopenaeus vannamei juveniles in low-salinity water in single and ternary exposure experiments and their environmental implications.

Information on toxicity of nitrogen compounds for Litopenaeus vannamei in coastal ecosystems and culture under low salinity is scarce. Acute toxicity trials were conducted in L. vannamei to determine the single and combined effects of ammonia, nitrite and nitrate at a salinity of 3 g/L. The 96 h-LC50 was 29.0 mg/L for total ammonia nitrogen (TAN); 10.6 mg/L for nitrogen as nitrite (NO2--N); and 900 mg/L for nitrogen as nitrate (NO3--N). The joint effects of ammonia, nitrite and nitrate exposure were antagonistic at 24-72 h; and additive from 72 to 96 h. The proposed safety levels of single exposure to TAN, NO2--N and NO3--N for L. vannamei are 1.45, 0.53 and 45.0 mg/L, respectively. When in mixture, the proposed level of TAN/NO2--N/NO3--N is 0.05 TU (Toxicity Unit) corresponding to 0.48, 0.08 and 14.6 mg/L of TAN, NO2--N and NO3--N, respectively.

The Amphibian Diacylglycerol O-acyltransferase 2 (DGAT2): a 'paleo-protein' with Conserved Function but Unique Folding.

Amphibians are, currently, considered the first vertebrates that had performed the aquatic to terrestrial transition during evolution; therefore, water balance and dehydration control were prerequisites for such environment conquering. Among anurans, Phyllomedusa is a well-studied genus, due to its peptide-rich skin secretion. Here, we have analyzed the skin secretion of Phyllomedusa distincta targeting the proteins present in the skin secretion. The major soluble protein was chromatographically isolated and utilized to immunize rabbits. Through proteomics approaches, we were able to identify such protein as being the diacylglycerol O-acyltransferase 2 (DGAT2), a crucial enzyme involved in lipid synthesis and in the skin water balance. Immunohistochemistry assays revealed the protein tissular distribution for different animal species, belonging to different branches of the phylogenetic tree. Specifically, there was positivity to the anti-DGAT2 on Amphibians' skin, and no antibody recognition on fish and mammals' skins. The DGAT2 multiple sequence alignment reveals some degree of conservation throughout the genera; however, there is a different cysteine pattern among them. Molecular modeling analyses corroborate that the different cysteine pattern leads to distinct 3D structures, explaining the different antibody recognition. Moreover, the protein phylogenetic analyses place the Xenopus DGAT2 (the available amphibian representative) next to the Coelacanthus enzyme, which have led the authors to term this a 'paleo-protein'. DGAT2 would be, therefore, an ancient protein, crucial to the terrestrial environment conquest, with a unique folding-as indicated by the molecular models and immunohistochemistry analyses-a consequence of the different cysteine pattern but with conserved biological function.

Acute Toxicity of Ammonia, Nitrite and Nitrate to Shrimp Litopenaeus vannamei Postlarvae in Low-Salinity Water.

Shrimp farming in low salinities waters is an alternative to increasing production, and counteracting disease problems in brackish and marine waters. However, in low-salinity waters, toxicity of nitrogen compounds increases, and there is no available data of its acute toxicity in shrimp postlarvae. This study determined the acute toxicity of ammonia, nitrite and nitrate in Litopenaeus vannamei postlarvae in 1 and 3 g/L salinity, as well as the safety levels. The LC50 confirms that nitrite is more toxic than ammonia and nitrate in low salinity waters, and that its toxicity increases with a decrease in salinity. The safe levels estimated for salinities of 1 and 3 g/L were 0.54 and 0.81 mg/L for total ammonia-N, 0.17 and 0.25 mg/L for NO2-N, and 5.6 and 21.5 mg/L for NO3-N, respectively.

Disrespect and abuse during childbirth in fourteen hospitals in nine cities of Peru.

OBJECTIVE: To assess the prevalence of disrespect and abuse during childbirth and its associated factors in Peru. METHODS: In an observational cross-sectional study, women were surveyed within 48 hours of live delivery at 14 hospitals located in nine Peruvian cities between April and July 2016. The survey was based on seven categories of disrespect and abuse proposed by Bowser and Hill. To evaluate factors associated with each category, prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated using adjusted Poisson models with robust variances. RESULTS: Among 1528 participants, 1488 (97.4%) had experienced at least one category of disrespect and abuse. Frequency of abandonment of care was increased with cesarean delivery (PR 1.27, 95% CI 1.03-1.57) but decreased in the jungle region (PR 0.27, 0.14-0.53). Discrimination was associated with the jungle region (PR 5.67, 2.32-13.88). Physical abuse was less frequent with cesarean than vaginal delivery (PR 0.23, 0.11-0.49). The prevalences of abandonment of care (PR 0.42, 0.29-0.60), non-consented care (PR 0.70, 0.57-0.85), discrimination (PR 0.40, 0.19-0.85), and non-confidential care (PR 0.71, 0.55-0.93) were decreased among women who had been referred. CONCLUSION: Nearly all participants reported having experienced at least one category of disrespect and abuse during childbirth care, which was associated with type of delivery, being referred, and geographic region.

Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control.

BACKGROUND: In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. METHODS: SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. RESULTS: Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level (P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. CONCLUSIONS: Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

The cutaneous secretion of the casque-headed tree frog Corythomantis greeningi: Biochemical characterization and some biological effects.

Corythomantis greeningi is a tree-frog endemic of the Brazilian semi-arid (Caatinga), mainly characterized by the flat, mineralized and spiny head, which is associated with phragmotic habits. It is already known that the skin secretion of this amphibian from both head and body is quite toxic and is used as an efficient chemical defence against predators. However, the biochemical characteristics and pharmacological effects of this secretion are still very little studied. We have tested the crude skin secretion, as well as the ten major fractions obtained by RP-HPLC for nociceptive and edema activity and for in vitro cytotoxicity using murine models. SDS-PAGE analyses demonstrated that the majority of proteins ranging through the gel lie between 55 and 30 kDa. LC-MS analysis showed multiple low molecular mass molecules (200-500 Da), which are consistent with masses of alkaloids and steroids. The crude skin secretion was able to induce fast and persistent edema accompanied by intense dose-dependent nociception. From the 10 tested fractions, five induced both edema and nociception, six fractions were able to induce only edema (80-170% control), and seven fractions induced only nociception (15-30 times compared to control). In addition, inhibition of cell growth (IC50) was demonstrated in murine fibroblasts and melanoma cells. From the data obtained, we confirmed that the skin secretion of C. greeningi is very toxic and is rich in compounds able to directly provoke local inflammation and nociception. Such characteristics are important as part of the chemical defensive repertory of this species.

Eccentric Torque-Producing Capacity is Influenced by Muscle Length in Older Healthy Adults.

Considering the importance of muscle strength to functional capacity in the elderly, the study investigated the effects of age on isokinetic performance and torque production as a function of muscle length. Eleven younger (24.2 ± 2.9 years) and 16 older men (62.7 ± 2.5 years) were subjected to concentric and eccentric isokinetic knee extension/flexion at 60 and 120° · s(-1) through a functional range of motion. The older group presented lower peak torque (in newton-meters) than the young group for both isokinetic contraction types (age effect, p < 0.001). Peak torque deficits in the older group were near 30 and 29% for concentric and eccentric contraction, respectively. Concentric peak torque was lower at 120° · s(-1) than at 60° · s(-1) for both groups (angular velocity effect, p < 0.001). Eccentric knee extension torque was the only exercise tested that showed an interaction effect between age and muscle length (p < 0.001), which suggested different torque responses to the muscle length between groups. Compared with the young group, the eccentric knee extension torque was 22-56% lower in the older group, with the deficits being lower in the shortened muscle length (22-27%) and higher (33-56%) in the stretched muscle length. In older men, the production of eccentric knee strength seems to be dependent on the muscle length. At more stretched positions, older subjects lose the capacity to generate eccentric knee extension torque. More studies are needed to assess the mechanisms involved in eccentric strength preservation with aging and its relationship with muscle length.

Reproductive health knowledge, attitudes and practices of adolescents attending an obstetric unit in Georgetown, Guyana.

BACKGROUND: Teenage pregnancy continues to be a serious maternal health issue globally. Problems faced by teenage mothers are biological, social, and psychological, and may include sexual coercion and violence. This study sought to explore formally the knowledge, attitudes and practices of pregnant teenagers in Georgetown, Guyana, which has one of the highest rates of teenage pregnancy in Latin America and the Caribbean. METHODS: This was a cross-sectional, prospective study. After ethical approval had been granted, 50 pregnant girls attending Georgetown Public Hospital Corporation (GPHC) were interviewed during a 6-week period. Using a convenience sample approach, the principal investigator used a questionnaire to collect data. This was then analysed using Stata/SE V.9.2 and Microsoft Excel programs. FINDINGS: As well as overall poor sexual and reproductive health knowledge and high-risk sexual health practices, our study revealed a high rate of rape and sexual coercion among the 50 girls interviewed. Almost a quarter (22%) admitted to having been raped in the past, and 80% stated a lack of power in their sexual relationships. CONCLUSIONS: There is a need for more targeted sexual and reproductive health services for teenagers attending GPHC, and for more research into sexual violence among this group of women. The establishment of a screening and referral system for those at risk should begin to address specific issues and optimise health outcomes for the women and their babies.

Parathyroid Hormone-Related Peptide-Linked Hypercalcemia in a Melanoma Patient Treated With Ipilimumab: Hormone Source and Clinical and Metabolic Correlates.

A patient diagnosed with metastatic melanoma developed the paraneoplastic syndrome of humoral hypercalcemia of malignancy and cachexia after receiving ipilumumab. The cause of the hypercalcemia was thought to be secondary to parathyroid hormone-related peptide (PTHrP) as plasma levels were found to be elevated. The patient underwent two tumor biopsies: at diagnosis (when calcium levels were normal) and upon development of hypercalcemia and cachexia. PTHrP expression was higher in melanoma cells when hypercalcemia had occurred than prior to its onset. Metabolic characterization of melanoma cells revealed that, with development of hypercalcemia, there was high expression of monocarboxylate transporter 1 (MCT1), which is the main importer of lactate and ketone bodies into cells. MCT1 is associated with high mitochondrial metabolism. Beta-galactosidase (ß-GAL), a marker of senescence, had reduced expression in melanoma cells upon development of hypercalcemia compared to pre-hypercalcemia. In conclusion, PTHrP expression in melanoma is associated with cachexia, increased cancer cell lactate and ketone body import, high mitochondrial metabolism, and reduced senescence. Further studies are required to determine if PTHrP regulates cachexia, lactate and ketone body import, mitochondrial metabolism, and senescence in cancer cells.

Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: results from the EPIC-EURGAST study.

MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value = 1.7 × 10(-4) ; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value = 5.38 × 10(-3) ; OR = 0.56, 95% CI = 0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value = 5.40 × 10(-3) ; OR = 1.41, 95% CI = 1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.

Risk factors for febrile status epilepticus: a case-control study.

OBJECTIVE: To identify risk factors for developing a first febrile status epilepticus (FSE) among children with a first febrile seizure (FS). STUDY DESIGN: Cases were children with a first FS that was FSE drawn from the Consequences of Prolonged Febrile Seizures in Childhood and Columbia cohorts. Controls were children with a first simple FS and separately, children with a first complex FS that was not FSE. Identical questionnaires were administered to family members of the 3 cohorts. Magnetic resonance imaging protocol and readings were consistent across cohorts, and seizure phenomenology was assessed by the same physicians. Risk factors were analyzed using logistic regression. RESULTS: Compared with children with simple FS, FSE was associated with younger age, lower temperature, longer duration (1-24 hours) of recognized temperature before FS, female sex, structural temporal lobe abnormalities, and first-degree family history of FS. Compared with children with other complex FS, FSE was associated with low temperature and longer duration (1-24 hours) of temperature recognition before FS. Risk factors for complex FS that was not FSE were similar in magnitude to those for FSE but only younger age was significant. CONCLUSIONS: Among children with a first FS, FSE appears to be due to a combination of lower seizure threshold (younger age and lower temperatures) and impaired regulation of seizure duration. Clinicians evaluating FS should be aware of these factors as many episodes of FSE go unnoticed. Further work is needed to develop strategies to prevent FSE.

Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study.

This prospective multicenter study of 200 patients with fever-associated status epilepticus (FSE), of whom 136 underwent a nontraumatic lumbar puncture, confirms that FSE rarely causes cerebrospinal fluid (CSF) pleocytosis. CSF glucose and protein levels were unremarkable. Temperature, age, seizure focality, and seizure duration did not affect results. CSF pleocytosis should not be attributed to FSE.

Identification of microorganisms in partially fed female horn flies, Haematobia irritans.

The horn fly Haematobia irritans (Linnaeus, 1758) (Diptera: Muscidae) is one of the most important ectoparasites of cattle. The parasitism of horn flies interferes with cattle feeding, thus reducing weight gain and milk production. Additionally, horn flies are mechanical vectors of pathogens that cause disease in cattle. The aims of this study were to identify microorganisms in partially fed female horn flies through mining of expressed sequence tags (ESTs) and to characterize microorganism prevalence using real-time RT-PCR. Seven unigenes containing 24 ESTs were homologous to infectious agents. Microorganisms identified in partially fed female horn flies ESTs included Nora virus (3 unigenes; 8 ESTs), Wolbachia endosymbionts (3 unigenes; 3 ESTs), and Mycobacterium bovis (1 unigene; 13 ESTs). These results expanded the repertoire of microorganisms that could cause persistent infections or be mechanically transmitted by horn flies and support further studies on the role of horn flies in the epidemiology of these pathogens in Mexico.

Control of tick infestations in cattle vaccinated with bacterial membranes containing surface-exposed tick protective antigens.

Vaccines containing the Rhipicephalus (Boophilus) microplus BM86 and BM95 antigens protect cattle against tick infestations. Tick subolesin (SUB), elongation factor 1a (EF1a) and ubiquitin (UBQ) are new candidate protective antigens for the control of cattle tick infestations. Previous studies showed that R. microplus BM95 immunogenic peptides fused to the Anaplasma marginale major surface protein (MSP) 1a N-terminal region (BM95-MSP1a) for presentation on the Escherichia coli membrane were protective against R. microplus infestations in rabbits. In this study, we extended these results by expressing SUB-MSP1a, EF1a-MSP1a and UBQ-MSP1a fusion proteins on the E. coli membrane using this system and demonstrating that bacterial membranes containing the chimeric proteins BM95-MSP1a and SUB-MSP1a were protective (>60% vaccine efficacy) against experimental R. microplus and Rhipicephalus annulatus infestations in cattle. This system provides a novel, simple and cost-effective approach for the production of tick protective antigens by surface display of antigenic protein chimera on the E. coli membrane and demonstrates the possibility of using recombinant bacterial membrane fractions in vaccine preparations to protect cattle against tick infestations.

Aging reduces complexity of heart rate variability assessed by conditional entropy and symbolic analysis.

Increasing age is associated with a reduction in overall heart rate variability as well as changes in complexity of physiologic dynamics. The aim of this study was to verify if the alterations in autonomic modulation of heart rate caused by the aging process could be detected by Shannon entropy (SE), conditional entropy (CE) and symbolic analysis (SA). Complexity analysis was carried out in 44 healthy subjects divided into two groups: old (n = 23, 63 ± 3 years) and young group (n = 21, 23 ± 2). It was analyzed SE, CE [complexity index (CI) and normalized CI (NCI)] and SA (0V, 1V, 2LV and 2ULV patterns) during short heart period series (200 cardiac beats) derived from ECG recordings during 15 min of rest in a supine position. The sequences characterized by three heart periods with no significant variations (0V), and that with two significant unlike variations (2ULV) reflect changes in sympathetic and vagal modulation, respectively. The unpaired t test (or Mann-Whitney rank sum test when appropriate) was used in the statistical analysis. In the aging process, the distributions of patterns (SE) remain similar to young subjects. However, the regularity is significantly different; the patterns are more repetitive in the old group (a decrease of CI and NCI). The amounts of pattern types are different: 0V is increased and 2LV and 2ULV are reduced in the old group. These differences indicate marked change of autonomic regulation. The CE and SA are feasible techniques to detect alteration in autonomic control of heart rate in the old group.

Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

BACKGROUND: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. DESIGN: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained). METHODS: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. RESULTS: Exercise training significantly and similarly increased FBF and peak VO(2) in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. CONCLUSION: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.