Factors influencing terrestriality in primates of the Americas and Madagascar.

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (body mass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Cannabidiol induces systemic analgesia through activation of the PI3Kγ/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism.

BACKGROUND: Cannabidiol (CBD) is the second most abundant pharmacologically active component present in Cannabis sp. Unlike Δ-9-tetrahydrocannabinol (THC), it has no psychotomimetic effects and has recently received significant interest from the scientific community due to its potential to treat anxiety and epilepsy. CBD has excellent anti-inflammatory potential and can be used to treat some types of inflammatory and neuropathic pain. In this context, the present study aimed to evaluate the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain and determine the endogenous mechanisms involved with this analgesia. METHODS: Neuropathic pain was induced by sciatic nerve constriction surgery, and the nociceptive threshold was measured using the paw compression test in mice. RESULTS: CBD produced dose-dependent antinociception after intraperitoneal injection. Selective inhibition of PI3Kγ dose-dependently reversed CBD-induced antinociception. Selective inhibition of nNOS enzymes reversed the antinociception induced by CBD, while selective inhibition of iNOS and eNOS did not alter this antinociception. However, the inhibition of cGMP production by guanylyl cyclase did not alter CBD-mediated antinociception, but selective blockade of ATP-sensitive K+ channels dose-dependently reversed CBD-induced antinociception. Inhibition of S-nitrosylation dose-dependently and completely reversed CBD-mediated antinociception. CONCLUSION: Cannabidiol has an antinociceptive effect when administered systemically and this effect is mediated by the activation of PI3Kγ as well as by nitric oxide and subsequent direct S-nitrosylation of KATP channels on peripheral nociceptors.

Convergent Mutations and Single Nucleotide Variants in Mitochondrial Genomes of Modern Humans and Neanderthals.

The genetic contributions of Neanderthals to the modern human genome have been evidenced by the comparison of present-day human genomes with paleogenomes. Neanderthal signatures in extant human genomes are attributed to intercrosses between Neanderthals and archaic anatomically modern humans (AMHs). Although Neanderthal signatures are well documented in the nuclear genome, it has been proposed that there is no contribution of Neanderthal mitochondrial DNA to contemporary human genomes. Here we show that modern human mitochondrial genomes contain 66 potential Neanderthal signatures, or Neanderthal single nucleotide variants (N-SNVs), of which 36 lie in coding regions and 7 result in nonsynonymous changes. Seven N-SNVs are associated with traits such as cycling vomiting syndrome, Alzheimer's disease and Parkinson's disease, and two N-SNVs are associated with intelligence quotient. Based on recombination tests, principal component analysis (PCA) and the complete absence of these N-SNVs in 41 archaic AMH mitogenomes, we conclude that convergent evolution, and not recombination, explains the presence of N-SNVs in present-day human mitogenomes.

Sensory and muscular functions of the pelvic floor in women with endometriosis - cross-sectional study.

PURPOSE: The aim of this study was to analyze the sensory and muscle functions of the pelvic floor in women with endometriosis, trying to improve overall knowledge/findings regarding pelvic floor muscle functions in patients with endometriosis. METHODS: Sample size calculated as 92 patients with endometriosis, aged between 18 and 45 years, not virgin, without other causes of pain and could not be pregnant. Patients underwent the Pelvic Floor Sensorial and Muscle Function Exam (EFSMAP). Descriptive data were recorded with mean and standard deviation, median (range), and absolute and relative frequency. The Kolmogorov-Smirnov test was used to observe the normality of quantitative variables. The significance level adopted for this study was 5%. RESULTS: Of 92 women assessed, 93.3% had pain and 75% had increased tone in the levator ani muscle; 50.4% had impaired pelvic floor relaxation with median strength of 3 by the Oxford scale and endurance of 2 s. CONCLUSIONS: The patients had a high prevalence of pain and dysfunction of the pelvic floor muscles, such as low muscle endurance and difficulty to relax. It shows that these patients should be referred to a pelvic floor physiotherapist, as soon as they have the diagnosis of endometriosis, to be assessed to prevent and/or treat pelvic floor impairments.

Haematology, physiological parameters, morphometry and parasitological status of rescued bearded capuchin monkeys (Sapajus libidinosus).

BACKGROUND: There are few studies on the physiology and haematology of rescued bearded capuchin monkeys. These are necessary to better understand the health and welfare status of the animals, including when performing reintroductions, and to avoid zoonoses. METHODS: We aimed to obtain physiological and haematological values, morphometry and parasitological status of 26 bearded capuchins in two rescue centres in Northeast Brazil. RESULTS: We found sex- and age-related differences in respiratory rate, body weight and body mass index, but not haematology. The haematological values obtained were significantly different from published data but within the reference intervals for the species. Animals infected with Ancylostoma spp. had significantly lower values in the parameters: haemoglobin concentration, mean corpuscular volume and mean corpuscular haemoglobin concentration than non-infected individuals. CONCLUSION: Physiological and haematological values of rescued capuchins were similar to those found in previous studies. Ancylostomiasis appears to cause alterations to haematological values of this species.

Whole-genome analysis of monozygotic Brazilian twins discordant for type 1 narcolepsy: a case report.

BACKGROUND: Narcolepsy type 1 (NT1) is a rare and chronic neurological disease characterized by sudden sleep attacks, overwhelming daytime drowsiness, and cataplexy. When associated with a sudden loss of muscle tone (cataplexy) narcolepsy is classified as type 1, while the absence of cataplexy indicates type 2. Genetic, degenerative, and immunological hypotheses to explain the pathophysiology of NT1 are still a matter of debate. To contribute to the understanding of NT1 genetic basis, here we describe, for the first time, a whole genome analysis of a monozygotic twin pair discordant for NT1. CASE PRESENTATION: We present the case of a pair of 17-year-old male, monozygotic twins discordant for NT1. The affected twin had Epworth Sleepiness Scale (ESS) of 20 (can range from 0 to 24), cataplexy, hypnagogic hallucinations, polysomnography without abnormalities, multiple sleep latency tests (MSLT) positive for narcolepsy, a mean sleep latency of 3 min, sleep-onset REM periods SOREMPs of 5, presence of allele HLA-DQB1*06:02, and Hypocretin-1 level of zero pg/mL (normal values are > 200 pg/mL). The other twin had no narcolepsy symptoms (ESS of 4), normal polysomnography, MSLT without abnormalities, presence of allele HLA-DQB1*06:02, and Hypocretin-1 level of 396,74 pg/mL. To describe the genetic background for the NT1 discordant manifestations in this case, we present the whole-genome analysis of this monozygotic twin pair. The whole-genome comparison revealed that both twins have identical NT1 pathogenic mutations in known genes, such as HLA-DQB1*06:02:01, HLA-DRB1*11:01:02/*15:03:01. The affected twin has the expected clinical manifestation while the unaffected twin has an unexpected phenotype. The unaffected twin has significantly more frameshift mutations as compared to the affected twin (108 versus 75) and mutations that affect stop codons (61 versus 5 in stop gain, 26 versus 2 in start lost). CONCLUSIONS: The differences observed in frameshift and stop codon mutations in the unaffected twin are consistent with loss-of-function effects and protective alleles, that are almost always associated with loss-of-function rare alleles. Also, overrepresentation analysis of genes containing variants with potential clinical relevance in the unaffected twin shows that most mutations are in genes related to immune regulation function, Golgi apparatus, MHC, and olfactory receptor. These observations support the hypothesis that NT1 has an immunological basis although protective mutations in non-HLA alleles might interfere with the expression of the NT1 phenotype and consequently, with the clinical manifestation of the disease.

Joint mobilization and therapeutic exercises in the hands of patients with systemic sclerosis: A preliminary randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of Maitland's joint mobilization and therapeutic exercises on the functionality of the hands in patients with systemic sclerosis. DESIGN: Randomized controlled trial. SETTING: Tertiary university hospital. SUBJECTS: Twenty-four patients diagnosed with systemic sclerosis according to ACR/EULAR 2013 criteria; age ⩾18 years and Cochin Hand Functional Scale (COCHIN) score ⩾10. They were randomized to physical therapy group (n = 12) or control group (n = 12). INTERVENTIONS: The physical therapy group received joint mobilization and undertook therapeutic exercises, twice a week, for 12 weeks, and received a booklet with information about the disease. The control group only received the booklet about the disease. MAIN MEASURES: The primary outcome measure was functionality of the hands (COCHIN). The secondary outcomes measures were disability (SHAQ), pain (visual analogic scale), range of motion (HAMIS and Delta finger-to-palm), grip strength (JAMAR dynamometer), and quality of life (SF12). RESULTS: Twenty-two patients were female, with a mean age of 47.4 ± 11.1 years and 18 had limited cutaneous form. The physical therapy group showed a decrease of 11.33 points in the COCHIN in comparison with the control group (P = 0.09). There was a significant increase in range of motion by HAMIS (3.00 ± 1.48 vs 5.42 ± 2.64, P = 0.008), reduction in pain VAS (3.42 ± 2.78 vs 7.75 ± 2.53, P < 0.001), and increase in the physical component of SF12 (38.51 ± 9.60 vs 32.65 ± 9.10, P = 0.038). CONCLUSION: Maitland's joint mobilization and therapeutic exercises improved the functionality of the hands, reduced pain in the hands and wrists, increased range of motion, and improved quality of life in patients with systemic sclerosis.

Left Ventricular Function in the Initial Period After Severe Traumatic Brain Injury in Swine.

BACKGROUND: Cardiac dysfunction is common in the days after severe traumatic brain injury (TBI) and may contribute to hypotension episodes, leading to worse outcomes. Little is known about cardiac function in the minutes and hours immediately following TBI. By using fluid percussion TBI in a swine model, we aimed to characterize the immediate post injury cardiac function. METHODS: Intubated, anesthetized immature (25.8 ± 1.5 kg) female swine were subjected to severe fluid percussion TBI (4.2 ± 0.2 atm). Beginning at 45 min, simulating hospital arrival, all animals were resuscitated with normal saline (NS), mannitol, and phenylephrine as needed to maintain a cerebral perfusion pressure more than 60 mm Hg and intracranial pressure (ICP) less than 20 mm Hg. Primary outcomes of cardiac function were cardiac output measured by thermodilution and transesophageal echo measurements of cardiac function recorded at prespecified time points and tested for trends over time using linear regression with spline at the time of resuscitation onset. Secondary outcomes included hemodynamic measurements, ICP, and cerebral perfusion pressure. RESULTS: Eighteen animals were included. Post-TBI hemodynamic changes demonstrated an early decrease in mean arterial pressure and cerebral perfusion pressure with a corresponding increase in heart rate and ICP. Immediately after injury, there was a significant decrease in both left atrial area and tissue Doppler imaging e' of the LV lateral wall. In addition, there was a simultaneous increase in LV end diastolic diameter and increase in E/e' ratio of the lateral mitral annulus. All other transesophageal echo measurements demonstrated no significant changes throughout the duration of the experiment. CONCLUSIONS: Traumatic brain injury is associated with cardiac dysfunction and increased mortality, however there is still a limited understanding of the hemodynamic and echocardiographic response associated with TBI. In this study we demonstrate the hemodynamic and echocardiographic changes in the early stages of TBI in swine. The authors hope that these results may help better understanding on the management of patients with severe head injury.

Lung Cancer Mortality and the Availability of Chest Computerized Tomography: A Longitudinal Nationwide Study.

Lung-cancer screening with chest computerized tomography (CT) is not easy to introduce in low-medium resource countries due to cost issues. We investigated whether the increasing availability of chest CT exams in Brazil, in spite of no lung-cancer screening protocol, was associated with lung-cancer death rate along 10-year follow-up. We performed regressions to estimate the rate ratio between chest CT exams and lung-cancer deaths per 105 inhabitants. We stratified data per municipality. Regressions were adjusted for physicians and hospital beds per 105 inhabitants and per capita gross domestic product. Increasing availability of chest CT exams predicted decreasing lung-cancer death rate.

Evidence for the involvement of opioid and cannabinoid systems in the peripheral antinociception mediated by resveratrol.

Despite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated. The aim of this study was to evaluate the involvement of opioid and cannabinoid systems in RES-induced peripheral antinociception. Paw withdrawal method was used and hyperalgesia was induced by carrageenan (200 µg/paw). All drugs were given by intraplantar injection in male Swiss mice (n = 5). RES (100 µg/paw) administered in the right hind paw induced local antinociception that was antagonized by naloxone, non-selective opioid receptor antagonist, and clocinnamox, µOR selective antagonist. Naltrindole and nor-binaltorfimine, selective antagonists for δOR and kOR, respectively, did not reverse RES-induced peripheral antinociception. CB1R antagonist AM251, but not CB2R antagonist AM630, antagonized RES-induced peripheral antinociception. Peripheral antinociception of RES intermediate-dose (50 µg/paw) was increased by: (i) bestatin, inhibitor of endogenous opioid degradation involved-enzymes; (ii) MAFP, inhibitor of anandamide amidase; (iii) JZL184, inhibitor of 2-arachidonoylglycerol degradation involved-enzyme; (iv) VDM11, endocannabinoid reuptake inhibitor. Acute and peripheral administration of RES failed to affect the amount of µOR, CB1R and CB2R. Experimental data suggest that RES induces peripheral antinociception through µOR and CB1R activation by endogenous opioid and endocannabinoid releasing.

Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole.

BACKGROUND: Recently, we demonstrated that the antipsychotic dopaminergic and serotoninergic agonist aripiprazole induced peripheral antinociception. However, the mechanism underlying this effect has not been fully established. Here, our aim was to identify possible relationships between this action of aripiprazole and the endocannabinoid system. METHODS: All drugs were given locally into the right hind paw of male Swiss mice weighing 30-35 g in a volume of 20 µL. The hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2 µg). Aripiprazole was injected 10 minutes before the measurement, and an irreversible inhibitor of anandamide hydrolase (MAFP), an inhibitor for monoacylglycerol lipase (JZL184), and an anandamide reuptake inhibitor (VDM11) were given 10 minutes before the aripiprazole. Nociceptive thresholds were measured using an algesimetric apparatus in the third hour after prostaglandin E2 injection. Data were analyzed by ANOVA and Bonferroni tests. RESULTS: The antinociceptive effect induced by aripiprazole (100 µg) was blocked by cannabinoid 1 or 2 receptor antagonists AM251 (40 µg [P < .01], 80 µg [P < .0001], and 160 µg [P < .0001]) and AM630 (100 µg [P < .0001], 200 µg [P < .0001], and 400 µg [P < .0001]), respectively. The peripheral antinociception induced by aripiprazole (25 µg) was enhanced by administration of the inhibitor of fatty acid amide hydrolase (MAFP, 0.5 µg [P < .0001]) or monoacylglycerol lipase (JZL184, 4 µg [P < .0001]). Moreover, a similar enhancement was observed with the anandamide reuptake inhibitor (VDM11, 2.5 µg [P < .0001]). CONCLUSIONS: These results provide evidence for the involvement of the endocannabinoid system in peripheral antinociception induced by aripiprazole treatment.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point-of-care (POC) coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, have increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has only modestly declined over the last decade, remaining at ≥50% in high-risk patients. Given these limitations, and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists (SCA) has formed the Blood Conservation in Cardiac Surgery Working Group to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients.

Bleeding after cardiac surgery is a common and serious complication leading to transfusion of multiple blood products and resulting in increased morbidity and mortality. Despite the publication of numerous guidelines and consensus statements for patient blood management in cardiac surgery, research has revealed that adherence to these guidelines is poor, and as a result, a significant variability in patient transfusion practices among practitioners still remains. In addition, although utilization of point of care coagulation monitors and the use of novel therapeutic strategies for perioperative hemostasis, such as the use of coagulation factor concentrates, has increased significantly over the last decade, they are still not widely available in every institution. Therefore, despite continuous efforts, blood transfusion in cardiac surgery has declined only modestly over the last decade, remaining at 50% or greater in high-risk patients. Given these limitations and in response to new regulatory and legislature requirements, the Society of Cardiovascular Anesthesiologists has formed the Blood Conservation in Cardiac Surgery Working Group in order to organize, summarize, and disseminate the available best-practice knowledge in patient blood management in cardiac surgery. The current publication includes the summary statements and algorithms designed by the working group, after collection and review of the existing guidelines, consensus statements, and recommendations for patient blood management practices in cardiac surgery patients. The overall goal is creating a dynamic resource of easily accessible educational material that will help to increase and improve compliance with the existing evidence-based best practices of patient blood management by cardiac surgery care teams.

Histone Deacetylase 1 Is Essential for Rod Photoreceptor Differentiation by Regulating Acetylation at Histone H3 Lysine 9 and Histone H4 Lysine 12 in the Mouse Retina.

Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas, we used a pharmacological approach that showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12) but not lysine 27 of histone 3 (H3K27) and led to maintained expression of progenitor-specific genes such as Vsx2 and Hes1 with concomitant block of expression of rod-specific genes. ChiP experiments confirmed these changes in the promoters of a group of progenitor genes. Based on our results, we suggest that HDAC1-specific inhibition prevents progenitor cells of the retina from exiting the cell cycle and differentiating. HDAC1 may be an essential epigenetic regulator of the transition from progenitor cells to terminally differentiated photoreceptors.

Peltatoside Isolated from Annona crassiflora Induces Peripheral Antinociception by Activation of the Cannabinoid System.

Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., a plant widely used in folk medicine. This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1 cannabinoid receptor interaction. Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action. The mouse paw pressure test was used and hyperalgesia was induced by intraplantar injection of carrageenan (200 µg/paw). All used drugs were administered by intraplantar administration in Swiss male mice (n = 6). Peltatoside (100 µg/paw) elicited a local inhibition of hyperalgesia. The peripheral antinociceptive action of peltatoside was antagonized by the CB1 cannabinoid antagonist AM251 (160 µg/paw), but not by CB2 cannabinoid antagonist AM630 (100 µg/paw). In order to assess the role of endocannabinoids in this peripheral antinociceptive effect, we used (i) [5Z,8Z,11Z,14Z]-5,8,11,14-eicosatetraenyl-methyl ester phosphonofluoridic acid, an inhibitor of anandamide amidase; (ii) JZL184, an inhibitor for monoacylglycerol lipase, the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol; and (iii) VDM11, an endocannabinoid reuptake inhibitor. MAFP, JZL184, and VDM11 did not induce antinociception, respectively, at the doses 0.5, 3.8, and 2.5 µg/paw, however, these three drugs were able to potentiate the peripheral antinociceptive effect of peltatoside at an intermediary dose (50 µg/paw). Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1 receptors, involving endocannabinoids in this process.

Curcumin photodynamic effect in the treatment of the induced periodontitis in rats.

This study assessed the effect of curcumin as a photosensitizer in antimicrobial photodynamic therapy (aPDT) for the treatment of induced periodontitis in rats. Periodontitis was induced via a ligature around the mandibular first molar on the left side of 96 rats. The ligature was removed 7 days later, and the animals were randomized into four groups: NT, no local treatment; CUR, irrigation with curcumin solution (40 µM); LED, irradiation with a light-emitting diode (LED, InGaN, 465-485 nm, 200 mW/cm2, 60 s); and aPDT, irrigation with curcumin solution (40 µM) followed by irradiation with LED. Eight animals from each group were euthanized at 7, 15, and 30 days post-treatment. Treatments were assessed using alveolar bone loss (ABL) in the furcation region using histological, histometric, and immunohistochemical analyses. Rats treated with aPDT exhibited less ABL at 7 days compared to the NT group, moderate pattern immunolabeling for osteoprotegerin at 30 days, and a pattern of immunolabeling for RANKL from moderate to low. Treatments resulted in smaller numbers of TRAP-positive cells compared to the NT group. aPDT as monotherapy using curcumin as a photosensitizer and LED as the light source was effective in the treatment of induced periodontitis in rats.

5-HT1A receptors of the prelimbic cortex mediate the hormonal impact on learned fear expression in high-anxious female rats.

Hormones highly influence female behaviors. However, research on this topic has not usually considered the variable hormonal status. The prelimbic cortex (PrL) is commonly engaged in fear learning. Connections from and to this region are known to be critical in regulating anxiety, in which serotonin (5-HT) plays a fundamental role, particularly through changes in 5-HT1A receptors functioning. Also, hormone fluctuations can greatly influence anxiety in humans and anxiety-related behavior in rodents, and this influence involves the functioning of 5-HT brain systems. The present investigation sought to determine whether fluctuations in ovarian hormones relative to the estrous cycle would influence the expression of learned fear in female rats previously selected as low- (LA) or high-anxious (HA). Furthermore, we investigate the role of the 5-HT system of the PrL, particularly the 5-HT1A receptors, as a possible modulator of estrous cycle influence on the expression of learned fear through intra-PrL microinjections of 5-HT itself or the full 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamine)tetralin). Behavioral changes were assessed using the fear-potentiated startle (FPS) procedure. The results showed that fear intensity is associated with hormonal decay, being more accentuated during the estrus phase. This increase in fear levels was found to be negatively correlated with the expression of potentiated startle. In rats prone to anxiety and tested during the proestrus and estrus phases, 5-HT mechanisms of the PrL seem to play a regulatory role in the expression of learned fear. These results were not replicated in the LA rats. Similar but less intense results were found regarding the early and late diestrus. Our data indicate that future studies on this subject need to take into account the dissociation between low- and high-responsive females to understand how hormones affect emotional behavior.

Ultrasound Identification of the Guidewire in the Brachiocephalic Vein for the Prevention of Inadvertent Arterial Catheterization During Internal Jugular Central Venous Catheter Placement.

BACKGROUND: Imaging the guidewire with ultrasonography in the internal jugular vein during central venous catheterization often is used to verify proper guidewire placement and to aid in prevention of inadvertent arterial catheterization. It is known, however, that inadvertent arterial catheterization can occur despite imaging the guidewire in the internal jugular vein because the guidewire may continue through the far wall of the internal jugular vein and into an adjacent artery. We propose confirmation of the guidewire in the brachiocephalic vein with ultrasonography as a more reliable method of confirming proper guidewire placement. METHODS: A prospective feasibility study of 200 adult cardiothoracic surgery patients undergoing internal jugular vein catheterization was performed to determine whether the guidewire could be imaged with ultrasonography in the brachiocephalic vein. The guidewire was imaged in the internal jugular vein in a short-axis view, and the transducer was then angled caudally under the clavicle, following the guidewire into the brachiocephalic vein. RESULTS: The right internal jugular vein was catheterized in 193 patients and the left internal jugular in 7 patients. The brachiocephalic vein was successfully imaged in all but 2 patients. In 3 patients, the guidewire could not be clearly identified in the brachiocephalic vein because of interference from the leads of a heart rhythm device (pacemaker or defibrillator) or preexisting catheter. In 2 patients, the guidewire was not seen initially in the brachiocephalic vein because of coiling in the internal jugular vein, and in 1 patient because of the guidewire passing into the right subclavian vein, but all 3 were subsequently imaged in the brachiocephalic vein after repositioning. CONCLUSIONS: During internal jugular vein catheterization, the brachiocephalic vein was imaged with ultrasonography in 99% of patients (the lower 1-sided 99% confidence limit is 96%). The guidewire was imaged in the brachiocephalic vein in all cases except when leads from a heart rhythm device caused interference, although in some patients with leads, the guidewire could be imaged without difficulty. The absence of the guidewire from the brachiocephalic vein was indicative of a malpositioned guidewire.

International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database--the quality controlled standard tool for routine identification of human and animal pathogenic fungi.

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org/ and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.