Nutritional status and age at menarche in amazonian students.

OBJECTIVES: Age at menarche (MA) is a proxy for biological maturation and a parameter of socioeconomic changes. Worldwide, anticipation of menarche is associated with nutritional transition and excess weight. The objective of this study was to evaluate the MA in Amazonian students and its association with nutritional status, ethnicity, and socioeconomic level. METHODS: Cross-sectional study with 1,017 students aged 6 to 17 living in the city of Manaus, Brazil. MA was analyzed by status quo and recall; its association with body mass index (BMI), race, socioeconomic status, and adult height was examined. RESULTS: 559 (51.9%) participants had already experienced menarche. In 91.7%, menarche occurred between 10 and 14 years of age; the mean age at the onset of menarche was 11.9 years. Overweight (11.6 years) and obese (11.4 years) participants reached menarche earlier than those with normal weight (12 years) and lean (12.7 years) participants. The associations between MA and nutritional status showed that overweight and obesity are risk factors for the early occurrence of menarche. MA was not associated with socioeconomic status/parental education or race. However, excess weight was associated with earlier MA in all races and social classes. The adult height was slightly lower in girls with menarche before 12 years old (157.9 vs 159.4 cm). CONCLUSION: Regardless of socioeconomic level or ethnicity, excess weight was associated with earlier menarche in Amazonian students.

Detection of somatic and germline pathogenic variants in adult cohort of drug-resistant focal epilepsies.

OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-ß oligomers (AßO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AßO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AßO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AßO (90 µM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AßO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AßO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AßO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AßO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AßO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.

Normocephalic Children Exposed to Maternal Zika Virus Infection Do Not Have a Higher Risk of Neurodevelopmental Abnormalities around 24 Months of Age than Unexposed Children: A Controlled Study.

Although very few controlled studies are available, in utero Zika virus (ZIKV)-exposed children are considered at risk for neurodevelopmental abnormalities. We aimed to identify whether there is an excess risk of abnormalities in non-microcephalic children born to mothers with confirmed ZIKV infection compared with ZIKV-unexposed children from the same population. In a cross-sectional study nested in two larger cohorts, we compared 324 ZIKV-exposed children with 984 unexposed controls. Outcomes were assessed using the Bayley Screening Test III applied around 24 months of age. Relative risks for classifying children as emergent or at-risk for neurodevelopmental delay in at least one of five domains were calculated, adjusting for covariates. In four of the five domains, few children were classified as emergent (4-12%) or at-risk (0.3-2.16%) but for the expressive communication domain it was higher for emergent (19.1-42.9%). ZIKV-exposed children were half as frequently classified as emergent, including after adjusting for covariates [RR = 0.52 (CI 95% 0.40; 0.66)]. However, no difference was detected in the at-risk category [RR = 0.83 (CI 95% 0.48; 1.44)]. Normocephalic children exposed to the Zika virus during pregnancy do not have a higher risk of being classified as at risk for neurodevelopmental abnormalities at two years of age.

Type I and type IIb autoimmune chronic spontaneous urticaria: Using common clinical tools for endotyping patients with CSU.

Background: Mechanisms triggering the pathogenesis of chronic spontaneous urticaria (CSU) have been identified as type I autoallergic (which is associated with IgE antibodies against autoantigens) and type IIb autoimmune (which is driven by autoantibodies to FceR1 and/or IgE). Objective: Our aim was to define presumptive endotypes in patients with CSU by using tests amenable to use in routine clinical practice. Methods: A retrospective analysis of the medical records of 394 patients with CSU with or without chronic inducible urticaria or angioedema was performed. Patients were assigned to 1 of 4 groups as follows: (1) type I endotype of CSU, if they presented at least 1 of the following: allergic disease, total IgE level of at least 40UI/mL, and positive result of skin tests to inhalant allergen(s), (2) type IIb endotype of CSU, if they presented at least 1 of following: autoimmune disease, low total IgE level less than 40 IU/mL, positive autologous serum skin test result, positive for antinuclear antibodies in a titer of at least 1:160, and elevated level of anti-thyroid peroxidase, (3) overlap of type I/type IIb endotypes of CSU, if they presented with at least 1 marker of both type I and type IIb, and (4) non-type I/type IIb endotype of CSU, if they presented with none of the markers of type I or type IIb. Results: The mean age at onset of symptoms was 34 years; 82.2% of those with CSU were female, and angioedema and chronic inducible urticaria were found in 74.8% and 31.9% of patients, respectively. Of the patients with CSU, 38% presented with the type I endotype and 51% presented with type I/type IIb overlap, whereas 9% presented with the type IIb endotype and 2% presented with the non-type I/type IIb endotype. Eosinopenia was associated with type IIb and type I/type IIb overlap as opposed to the type I and non-type I/type IIb endotypes (P = .02). Conclusions: Most patients with CSU presented with features of the type 1 (autoallergic) endotype, whether associated with type IIb (autoimmune) endotype or not.

The medial prefrontal cortex and the cardiac baroreflex activity: physiological and pathological implications.

The cardiac baroreflex is an autonomic neural mechanism involved in the modulation of the cardiovascular system. It influences the heart rate and peripheral vascular resistance to preserve arterial blood pressure within a narrow variation range. This mechanism is mainly controlled by medullary nuclei located in the brain stem. However, supramedullary areas, such as the ventral portion of medial prefrontal cortex (vMPFC), are also involved. Particularly, the glutamatergic NMDA/NO pathway in the vMPFC can facilitate baroreflex bradycardic and tachycardic responses. In addition, cannabinoid receptors in this same area can reduce or increase those cardiac responses, possibly through alteration in glutamate release. This vMPFC network has been associated to cardiovascular responses during stressful situations. Recent results showed an involvement of glutamatergic, nitrergic, and endocannabinoid systems in the blood pressure and heart rate increases in animals after aversive conditioning. Consequently, baroreflex could be modified by the vMPFC neurotransmission during stressful situations, allowing necessary cardiovascular adjustments. Remarkably, some mental, neurological and neurodegenerative disorders can involve damage in the vMPFC, such as posttraumatic stress disorder, major depressive disorder, Alzheimer's disease, and neuropathic pain. These pathologies are also associated with alterations in glutamate/NO release and endocannabinoid functions along with baroreflex impairment. Thus, the vMPFC seems to play a crucial role on the baroreflex control, either during pathological or physiological stress-related responses. The study of baroreflex mechanism under such pathological view may be helpful to establish causality mechanisms for the autonomic and cardiovascular imbalance found in those conditions. It can explain in the future the reasons of the high cardiovascular risk some neurological and neurodegenerative disease patients undergo. Additionally, the present work offers insights on the possible contributions of vMPFC dysfunction on baroreflex alterations, which, in turn, may raise questions in what extent other brain areas may play a role in autonomic deregulation under such pathological situations.

Synthesis, characterization, solution chemistry and anticancer activity of [NiCl2(Ph2P-N(R)-PPh2)] (R = 2-CH2Py, CH2Ph and p-tol) complexes.

In this work three Ni2+ complexes with general formula [NiCl2(Ph2P-N(R)-PPh2)], R = 2-CH2Py (Py = pyridine) - 1, CH2Ph (Ph = phenyl) - 2 and p-tol (p-tol = p-tolyl) - 3, were synthesized and characterized. These complexes were obtained in high yield by the reaction of NiCl2.6H2O and the corresponding diphenylphosphinoamine ligand (Ph2P-N(R)-PPh2) in CH2Cl2/MeOH (1:1) solution, at room temperature (∼25 °C), and characterized by 1H and 31P {1H} NMR, vibrational spectroscopy in the infrared region, electronic spectroscopy in the UV-Vis regions, elemental analysis (%C, %H, %N) and single-crystal X-ray diffraction. The solution chemistry was studied in CDCl3/dmso-d6 (dimethylsulfoxide) or neat dmso-d6 using complex 2 as a model. The complexes were evaluated as cytotoxic agents against two cancer cells lines, A549 (lung cancer cells), B16F10 (melanoma cells) and the health cells HaCaT (human epithelial keratinocytes).

Risk factors for mortality from sepsis in an intensive care unit in Ecuador: A prospective study.

ABSTRACT: To investigate risk factors for mortality from sepsis in an intensive care unit (ICU) in Quito-Ecuador and their association to adherence to Surviving Sepsis Campaign recommendations.Prospective cohort study of patients with severe sepsis/septic shock admitted to the ICU of a public Ecuadorian hospital from March, 2018 to March, 2019. Demographic, clinical, treatment, and outcome data were collected from patients' health records. Patients were divided into 2 groups according to ICU survival or death. Log-binomial regression models were used to identify risk factors for mortality.In total, 154 patients were included. Patients who died in the ICU (n = 42; 27.3%) had higher sequential organ failure assessment score (median 11.5 vs 9; P<.01), more organ dysfunction (median 4 vs 3; P<.0001), and received greater volumes of fluid resuscitation in the first 6 hours (median 800 vs 600 mL; P = .01). Dysfunction of > 2 organs was a risk factor for mortality (relative risks [RR] 3.80, 95% CI 1.33-10.86), while successful early resuscitation (RR 0.32, 95% CI 0.15-0.70), successful empirical antibiotic treatment (RR 0.38, 95%CI 0.18-0.82), and antibiotic de-escalation (RR 0.28, 95%CI 0.13-0.61) were protective factors.Dysfunction of >2 organs was a risk factor for mortality from sepsis while successful early resuscitation and appropriate antibiotic treatment were protective.

Weight/length ratio references and newborn body composition estimation at birth from a Brazilian cohort

Abstract Objectives: The objective was to calculate weight/length (W/L) ratio values and percentiles by sex and gestational age (GA) to estimate fat mass (FM), fat-free mass (FFM) and body fat percentage (BF%) as well as to compare these indices in preterm, small (SGA), and large (LGA) for GA, stunted and wasted infants from a Brazilian cohort of newborns, comparing with the INTERGROWTH-21st. Methods: Secondary, cross-sectional analysis of data obtained of 7427 live-born infants from the BRISA Cohort Study in the city of Ribeirão Preto, SP, Brazil in 2010. For body composition estimation, W/L ratio was used in multiple regression models. The 3rd, 50th, and 97th percentiles for W/L ratio and body composition measures (FM, FFM, and BF%) were calculated using fractional polynomial regression models. Results: Average W/L ratio was 6.50 kg/m (SD 0.87), while for FM, BF%, and FFM the corresponding values were 359.64 g (145.76), 10.90% (3.05) and 2798.84 g (414.84), respectively. SGA (< 3rd percentile), and wasted infants showed the lowest W/L ratios and measures of body composition. The 3rd, 50th, and 97th percentiles charts of W/L, FM, BF%, and FFM by GA and sex are presented. Conclusions: W/L ratio values of the RP-BRISA Cohort are higher than IG-21st. SGA (< 3rd) and wasted infants showed the lowest W/L ratio and measures of body composition. The body composition references presented here could be used to refine the nutritional assessment of Brazilian newborns and to facilitate comparisons across populations.

Epidemiology and factors associated with the severity of viral acute lower respiratory infection in children hospitalized in Manaus, Amazonas, in 2017-2018: An observational study.

ABSTRACT: To investigate the epidemiology and factors associated with the severity of viral acute lower respiratory infection (ALRI) in children hospitalized in Manaus, Amazonas, in 2017 to 2018.Retrospective cohort study of children hospitalized at the Hospital and Emergency Room Delphina Rinaldi Abdel Aziz, in Manaus, from April 01, 2017 to August 31, 2018, with a clinical diagnosis of ALRI and nasopharyngeal aspirates positive for at least 1 respiratory virus.One hundred forty-six children aged 0.2 to 66 months (median 7 months) were included. Patients were divided into 2 groups according to the disease severity classified by an adapted Walsh et al score: moderate disease, score 0-4, n = 66 (45.2%) and severe disease, score 5-7, n = 80 (54.8%). A greater number of viral ALRI cases were observed in the rainiest months. Respiratory syncytial virus was the most prevalent (n = 103, 70.3%), followed by metapneumovirus (n = 24, 16.4%), influenza virus (n = 17, 11.6%), parainfluenza virus (n = 11, 7.5%), and adenovirus (n = 4, 2.7%). Co-detections of 2 to 3 viruses were found in 12 (8.2%) patients. The presence of viral coinfection was an independent risk factor for disease severity (adjusted relative risk [RR] 1.53; 95% CI 1.10-2.14). Twelve patients (8.2%) died, all with severe disease. Risk factors for death were shock (adjusted RR 10.09; 95% CI 2.31-43.90) and need for vasoactive drugs (adjusted RR 10.63; 95% CI 2.44-46.31).There was a higher incidence of viral ALRI in Manaus in the rainy season. Respiratory syncytial virus was the most prevalent virus. The presence of viral coinfection was an independent risk factor for disease severity.

Ventromedial prefrontal cortex CRF1 receptors modulate the tachycardic activity of baroreflex.

Ventral medial prefrontal cortex (vMPFC) glutamatergic neurotransmission has a facilitatory role on cardiac baroreflex activity which is mediated by NMDA receptors activation. Corticotrophin releasing factor receptors type1 and 2 (CRF1 and CRF2), present in the vMPFC, are colocalized in neurons containing glutamate vesicles, suggesting that such receptors may be involved in glutamate release in this cortical area. Therefore, our hypothesis is that the CRF1 and CRF2 receptors can modulate the baroreflex bradycardic and tachycardic responses. In order to prove this assumption, male Wistar rats had bilateral stainless steel guide cannula implanted into the vMPFC, and baroreflex was activated by intravenous infusion of phenylephrine or sodium nitroprusside through a vein catheter. A second catheter was implanted into the femoral artery for cardiovascular measurements. The CRF1 receptor antagonist administration in either infralimbic cortex (IL) or prelimbic cortex (PL), vMPFC regions, was unable to change the bradycardic responses but increased the slope of the baroreflex tachycardic activity. Microinjection of the CRF2 receptor antagonist into the IL and PL did not alter ether bradycardic nor tachycardic baroreflex responses. The administration of the non-selective CRF receptors agonist, urocortin in these areas, did not modify bradycardic responses but decreased tachycardia slope of the baroreflex. CRF1 receptor antagonist administration prior to non-selective CRF agonist in vMPFC prevented the tachycardic responses reduction. However, CRF2 receptor antagonism could not prevent the effect of CRF receptors agonist. These results suggest that IL and PL CRF1 but not CRF2 receptors have an inhibitory role on the baroreflex tachycardic activity. Furthermore, they have no influence on baroreflex bradycardic activity.

Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. METHODS: Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. RESULTS: Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. CONCLUSION: Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

Weight/length ratio references and newborn body composition estimation at birth from a Brazilian cohort.

OBJECTIVES: The objective was to calculate weight/length (W/L) ratio values and percentiles by sex and gestational age (GA) to estimate fat mass (FM), fat-free mass (FFM) and body fat percentage (BF%) as well as to compare these indices in preterm, small (SGA), and large (LGA) for GA, stunted and wasted infants from a Brazilian cohort of newborns, comparing with the INTERGROWTH-21st. METHODS: Secondary, cross-sectional analysis of data obtained of 7427 live-born infants from the BRISA Cohort Study in the city of Ribeirão Preto, SP, Brazil in 2010. For body composition estimation, W/L ratio was used in multiple regression models. The 3rd, 50th, and 97th percentiles for W/L ratio and body composition measures (FM, FFM, and BF%) were calculated using fractional polynomial regression models. RESULTS: Average W/L ratio was 6.50 kg/m (SD 0.87), while for FM, BF%, and FFM the corresponding values were 359.64 g (145.76), 10.90% (3.05) and 2798.84 g (414.84), respectively. SGA (< 3rd percentile), and wasted infants showed the lowest W/L ratios and measures of body composition. The 3rd, 50th, and 97th percentiles charts of W/L, FM, BF%, and FFM by GA and sex are presented. CONCLUSIONS: W/L ratio values of the RP-BRISA Cohort are higher than IG-21st. SGA (< 3rd) and wasted infants showed the lowest W/L ratio and measures of body composition. The body composition references presented here could be used to refine the nutritional assessment of Brazilian newborns and to facilitate comparisons across populations.

High-throughput sequencing of immunoglobulin heavy chain for minimal residual disease detection in B-lymphoblastic leukemia.

INTRODUCTION: Minimal residual disease (MRD) is a cornerstone for stratification of upfront B-lymphoblastic leukemia (B-ALL) treatment protocols to decrease relapse risk. Although its detection by flow cytometry (FC) and real-time quantitative polymerase has clinical usefulness, evidence suggests that methods with increased sensitivity could lead to improved outcomes. The aim of this study was to develop an amplicon-based assay followed by high-throughput sequencing of the immunoglobulin heavy chain variable region for MRD detection in B-ALL. METHODS: We analyzed 84 samples, 27 from diagnosis, 5 from relapse, 40 from post-treatment samples, and 12 from healthy controls. RESULTS: Our assay was able to identify more neoplastic clones at diagnosis than Sanger sequencing including incomplete DJ rearrangements. From the 40 MRD samples evaluated 21 were positive by our new approach on high-throughput sequencing assay, but only 15 of these were positive by FC. The remaining 19 were negative by the two techniques. CONCLUSION: We have developed a novel approach on high-sensitive assay for MRD detection in B-ALL, which could add clinical value in the management of patients, especially in cases negative for MRD by FC.

Comprehensive evaluation of risk factors for neonatal hearing loss in a large Brazilian cohort.

OBJECTIVES: To determine the incidence and risk factors of hearing loss (HL) in Brazilian neonates. STUDY DESIGN: 11,900 neonates were screened for hearing and congenital CMV (cCMV). Low and high-risk babies who did not pass their hearing screening and infants with cCMV were scheduled for a diagnostic audiologic evaluation. RESULTS: The incidence of HL was 2 per 1000 live-born infants (95% CI: 1-3). HL was higher in high-risk neonates than in low risk babies (18.6 vs. 0.3/1000 live births, respectively). Among infants exposed to isolated risk factors, association of HL with craniofacial abnormalities/syndromes (RR = 24.47; 95% CI: 5.9-100.9) and cCMV (RR = 9.54; 95% CI: 3.3-27.7) were observed. HL was 20 to 100-fold more likely in neonates exposed to ototoxic drugs in combination with cCMV or craniofacial/congenital anomalies. CONCLUSIONS: Strategies for the prevention of cCMV and exposure to ototoxic drugs may decrease the incidence of HL in this population.

HPV genotype is a prognosticator for recurrence of respiratory papillomatosis in children.

OBJECTIVES: This study aimed to compare the prognosis according to age, genotype or human papillomavirus (HPV) variant in patients with recurrent respiratory papillomatosis (RRP). DESIGN: Non-concurrent cohort. PARTICIPANTS: Forty one patients with RRP. SETTING: Tertiary referral hospital. MAIN OUTCOME MEASURES: Disease severity was defined by the number of surgeries performed, and Derkay score at surgeries, obtained from medical records. HPV was detected and genotyped, and HPV-6 variants were also assessed. RESULTS: Fifteen (36.58%) individuals belonged to the juvenile RRP group (JoRRP, less than 18 years), while 26 patients (63.41%) were allocated at the adult group (AoRRP, equal or more than 18 years). JoRRP patients needed, in average, a higher number of surgeries to control the disease than AoRRP patients (mean difference: 3.36). Also, JoRRP patients showed a higher Derkay score at each surgery (mean difference: 3.76). There was no significant difference in the number of surgeries when we compared patients infected with HPV-6 or HPV-11, neither in accordance to HPV-6 variants. Patients with HPV-11 presented a higher mean Derkay score at surgery than those with HPV-6 (mean difference: 4.39); when co-variated by age, we observed that this difference occurred only among JoRRP patients (mean difference: 6.15). CONCLUSIONS: Age of onset of RRP has an important impact on number of surgeries to control disease. Patients with JoRRP and HPV-11 tend to present worse Derkay score at each surgery. HPV genotype among adults and HPV-6 variants had no impact on the outcome of the disease.

Bed nucleus of the stria terminalis modulates baroreflex cardiac activity: an interaction between alpha-1 receptors and NMDA/nitric oxide pathway.

The bed nucleus of the stria terminalis (BNST) is a forebrain structure, involved in the modulation of neuroendocrine, cardiovascular and autonomic responses. One of the responses is baroreflex activity, which consists in a neural mechanism responsible for keeping the blood pressure within a narrow range of variation. It has been reported that blockade of BNST α1-adrenoceptors increased the bradycardic component of baroreflex. In addition, such receptors are able to modulate glutamate release in this structure. Interestingly, BNST NMDA receptor antagonism and neuronal nitric oxide synthase (nNOS) inhibition led to the same effect of the α1-adrenoceptors blockade on baroreflex bradycardic response. Therefore, the hypothesis of the present study is that BNST noradrenergic transmission interacts with NMDA/NO pathway through α1 adrenoceptors to modulate the baroreflex activity. Male Wistar rats had stainless steel guide cannulas bilaterally implanted in the BNST. Subsequently, a catheter was inserted into the femoral artery for cardiovascular recordings, and into the femoral vein for assessing baroreflex activation. Injection of the noradrenaline reuptake inhibitor reboxetine in the BNST did not modify the tachycardic, but significantly decreased the bradycardic component of baroreflex. Administration of an α1, but not an α2 antagonist into the BNST prior to reboxetine prevented this effect. Likewise, previous injection of NMDA/NO pathway blockers inhibited the effect of reboxetine on bradycardic response. In conclusion, it was demonstrated for the first time the existence of an interaction between BNST noradrenergic, glutamatergic and nitrergic neurotransmissions in the modulation of bradycardic baroreflex response.

Secretory production in Escherichia coli of a GH46 chitosanase from Chromobacterium violaceum, suitable to generate antifungal chitooligosaccharides.

A chitosanase (CvCsn46) from Chromobacterium violaceum ATCC 12472 was produced in Escherichia coli, purified, and partially characterized. When subjected to denaturing polyacrylamide gel electrophoresis, the enzyme migrated as two protein bands (38 and 36 kDa apparent molecular masses), which were both identified as CvCsn46 by mass spectrometry. The enzyme hydrolyzed colloidal chitosan, with optimum catalytic activity at 50 °C, and two optimum pH values (at pH 6.0 and pH 11.0). The chitosanolytic activity of CvCsn46 was enhanced by some ions (Ca2+, Co2+, Cu2+, Sr2+, Mn2+) and DTT, whereas Fe2+, SDS and ß-mercaptoethanol completely inhibited its activity. CvCsn46 showed a non-Michaelis-Menten kinetics, characterized by a sigmoidal velocity curve (R2 = 0.9927) and a Hill coefficient of 3.95. ESI-MS analysis revealed that the hydrolytic action of CvCsn46 on colloidal chitosan generated a mixture of low molecular mass chitooligosaccharides, containing from 2 to 7 hexose residues, as well as D-glucosamine. The chitosan oligomers generated by CvCsn46 inhibited in vitro the mycelial growth of Lasiodiplodia theobromae, significantly reducing mycelium extension and inducing hyphal morphological alterations, as observed by scanning electron microscopy. CvCsn46 was characterized as a versatile biocatalyst that produces well-defined chitooligosaccharides, which have potential to control fungi that cause important crop diseases.

Nitric oxide in the insular cortex modulates baroreflex responses in a cGMP-independent pathway.

Insular cortex is a brain structure involved in the modulation of autonomic activity and cardiovascular function. The nitric oxide/cyclic guanosine-3',5'-monophosphate pathway is a prominent signaling mechanism in the central nervous system, controlling behavioral and physiological responses. Nevertheless, despite evidence regarding the presence of nitric oxide-synthesizing neurons in the insular cortex, its role in the control of autonomic and cardiovascular function has never been reported. Thus, the present study aimed to investigate the involvement of nitric oxide/cyclic guanosine-3',5'-monophosphate pathway mediated by neuronal nitric oxide synthase (nNOS) activation within the insular cortex in the modulation of baroreflex responses in unanesthetized rats. For this, we evaluated the effect of bilateral microinjection of either the nitric oxide scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase inhibitor Nω-Propyl-l-arginine or the soluble guanylate cyclase inhibitor ODQ into the insular cortex on the bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and the tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of either NPLA or carboxy-PTIO into the insular cortex increased the reflex bradycardic response, whereas the reflex tachycardia was decreased by these treatments. Bilateral microinjection of the soluble guanylate cyclase inhibitor into the insular cortex did not affect any parameter of baroreflex function evaluated. Overall, our findings provide evidence that insular cortex nitrergic signaling, acting via neuronal nitric oxide synthase, plays a prominent role in control of baroreflex function. However, control of reflex responses seems to be independent of soluble guanylate cyclase activation.

Comparison of birth weight, length, and head circumference between the BRISA-RP and Intergrowth-21st cohorts, / Comparação de peso, comprimento e perímetro cefálico ao nascer entre Coorte BRISA-RP e Intergrowth-21st,

Abstract Objectives: (a) To determine the 3rd, 50th, and 97th percentiles of weight, length, and head circumference of newborns from the Ribeirão Preto BRISA cohort, according to gender and gestational age, and compare them with the Intergrowth-21st standard; (b) To estimate the small for gestational age ( < 3rd percentile), large for gestational age ( > 97th percentile), stunting (length < 3rd percentile), and wasting (body mass index < 3rd percentile). Methods: Observational study of a cohort of 7702 newborns between 01/01/2010 and 12/31/2010 in the city of Ribeirão Preto, SP, Brazil. The 3rd, 50th, and 97th percentiles were determined for the anthropometric measurements using fractional polynomial regression. Results: The weight difference between Ribeirão Preto and Intergrowth-21st was small, being more pronounced in preterm infants (mean difference between the two populations of +266 g); for full-term newborns, there was a mean difference of +66 g, and for post-term infants, of -113 g. For length, the mean variation was always <1 cm; whereas for head circumference, preterm newborns showed a variation >1 cm, and full-term and post-term newborns showed a variation of <1 cm. The small and large for gestational age detection rates were 2.9% and 4.3%, respectively. Stunting affected 6.5% of all newborns and wasting, 1.5%, with a predominance in girls and in full-term pregnancies; both conditions were present in 0.4% of the sample. Conclusions: Newborns from Ribeirão Preto, when compared to the Intergrowth-21 standard, are heavier, longer, and have a larger head circumference until they reach full-term.

Resumo Objetivos: Determinar os percentis 3, 50 e 97 de peso, comprimento e perímetro cefálico de recém-nascidos da Coorte BRISA Ribeirão Preto, segundo sexo e idade gestacional, e comparar com o padrão Intergrowth-21st; b) Estimar os fenótipos pequeno para idade gestacional (< percentil 3), grande para idade gestacional (> percentil 97), stunting (comprimento < percentil 3) e waisting (índice de massa corporal < percentil 3). Método: Estudo observacional de uma coorte de 7.702 recém-nascidos entre 01/01 e 31/12/2010 na cidade de Ribeirão Preto, SP, Brasil. Os percentis 3, 50 e 97 para as medidas antropométricas foram determinados com regressão polinomial fracionária. Resultados: A diferença de peso entre Ribeirão Preto e Intergrowth-21st foi pequena, mais acentuada nos recém-nascidos pré-termo (diferença média entre as duas populações foi de + 266 gramas); para os recém-nascidos a termo a diferença média foi de + 66 gramas e para os pós-termo de -113 gramas. Para comprimento, a variação média foi sempre < 1 cm; enquanto que para perímetro cefálico os recém-nascidos pré-termo apresentaram variação > 1 cm e os recém-nascidos a termo e pós-termo tiveram variação < 1 cm. As taxas de detecção de pequeno e grande para idade gestacional foram 2,9% e 4,3%, respectivamente. Stunting afetou 6,5% de todos os recém-nascidos e waisting 1,5%, com predomínio em meninas e em gestações a termo; ambas as condições estavam presentes em 0,4% da amostra. Conclusões: Os recém-nascidos de Ribeirão Preto, quando comparados com o padrão Intergrowth-21st, apresentam-se mais pesados, mais longos e com maior circunferência craniana até chegarem a termo.