Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia.

Vincristine-induced peripheral neuropathy (VIPN) is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine induced pain. Our previous studies have shown that the tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel NaV1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) NaV1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons we now show an increase in TTX-R current density and a -7.3 mV hyperpolarizing shift in V1/2 of activation of NaV1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from NaV1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel NaV1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia.

Physical Activity and Multimorbidity Among Community-Dwelling Older Adults: A Systematic Review With Meta-Analysis.

OBJECTIVE: This study evaluated the relationship between physical activity (PA) and multimorbidity in community-dwelling older adults. DATA SOURCE: A systematic review and meta-analysis in the following databases: Pubmed, Lilacs, Scielo, Web of Science, Scopus, and AgeLine. STUDY INCLUSION AND EXCLUSION CRITERIA: It included observational studies investigating the association between physical activity and multimorbidity, with older adults, published until May 2021. Studies with institutionalized individuals or that assessed specific diseases were excluded. DATA EXTRACTION: Two reviewers independently extracted the studies based on previous inclusion and exclusion criteria, started by selecting titles, followed by abstracts and full-text reading. DATA SYNTHESIS: Meta-analysis results were reported as Odds Ratio (OR) with a 95% confidence interval using R language. The Newcastle Ottawa scale was used to assess the quality of the studies. RESULTS: Fifteen studies were included in the systematic review, from which 12 reported an inverse association between physical activity and multimorbidity. In the meta-analysis, from over 77 000 older adults, there was an inverse association between physical activity and multimorbidity [OR: .81; 95% CI: .73-.89]. We found significant results only for men in the analysis by sex. CONCLUSIONS: Low levels of physical activity were associated with a higher risk of multimorbidity in older adults. It is expected that public policies will be conducted aimed at the practice of physical activity among older adults.

NCD behavioral risk factors and mortality among older adults in Brazil.

BACKGROUNDS & AIMS: Literature shows that the most studied concurrent risk factors for mortality in elderly individuals are smoking, inadequate diet, alcohol consumption and physical inactivity. The combination of such habits can increase from 3 to 11 times the chance of death. To measure the association between concurrence of behavioral risk factors (BRF) for non-communicable diseases (NCD's) and mortality up to three years among the elderly. METHODS: Cohort study started in 2014 named "COMO VAI?" with community-dwelling aged ≥60 years in Pelotas, Rio Grande do Sul, Brazil. We investigated the deaths from all causes occurred until April 2017. The exposure was defined by the presence of physical inactivity, low-quality diet, alcohol consumption and smoking that composed a score ranging from 0 (none) to 4 (all). Cox proportional hazard regression models were used to evaluate the association between BRF concurrence and mortality. RESULTS: In 2014, 1451 elderly people were interviewed, 145 deaths were identified (10%) by April 2017. Higher risk of death was observed for the combinations of physical inactivity + smoking and low-quality diet + physical inactivity. The simultaneous presence of three or more BRF was associated with a nearly six-fold higher risk of death. CONCLUSIONS: Higher mortality during a 3-year period was observed among those with at least three BRF for NCD's.

Three-Dimensional Analysis of the Skull Base of Individuals With Cleft Lip and Palate.

AIMS: Identify variations of skull base measurements in individuals with dentofacial deformities associated or not with cleft lip and palate and compare the results with individuals without dentofacial deformities. METHODS AND RESULTS: The individuals were categorized into three different groups: dentofacial deformity without cleft malformation, dentofacial deformity associated with cleft lip and palate, and without facial deformity. The inclusion criteria were individuals over 18 years of age, without any intervention involving facial bones or structures of interest for the study and field of view encompassing from the glabella to the hyoid bone. Poor quality CT scans or lack of adequate medical records were considered exclusion criteria. In the analysis by computerized tomography using the Dolphin Imaging Software, the length determined by the Ba-S and S-N lines was evaluated, as well as the Ba-S-N angle formed by landmarks. RESULTS: The length of S-N was not statistically different between the groups, the Ba-S length and the Ba-S-N angle demonstrated statistical difference. CONCLUSION: There was statistically significant difference in the morphometry of the (Ba-S) between groups (FS) and (C). This suggests that the standard values for cephalometric analyzes involving these structures, especially to determine the treatment planning, should be used with caution.

Adolescent social instability stress leads to immediate and lasting sex-specific changes in the neuroendocrine-immune-gut axis in rats.

Social instability stress (SS; daily 1 h isolation and change of cage partner from postnatal day (P) 30-45) in adolescence produces elevations in corticosterone during the procedure in male and female rats, but no lasting changes in hypothalamic-pituitary-adrenal (HPA) responses to psychological stressors, although deficits in social and cognitive function are evident in adulthood. Here we investigated the effects of SS in corticosterone response to an immune challenge (lipopolysaccharide, LPS, 0.1 mg/kg), on gene expression in the hippocampus, and on gut microbiota, when tested soon- (P46) or long- (P70) after SS. The temporal pattern of corticosterone release after LPS differed between SS and control rats irrespective of the time since SS exposure in females, whereas in males, SS did not alter corticosterone release after LPS. Expression of genes in the hippocampus relevant to immune and HPA function differed between saline-treated SS and control rats depending on sex and time tested, but with lasting consequences of SS in both sexes. LPS-treatment altered hippocampal gene expression, with bigger effects of LPS evident in control than in SS female rats, and the opposite in male rats. Further, effects sometimes depended on the age at time of LPS treatment. SS and control rats differed in both fecal and colon microbiome composition in all but P46 males, and stress history, sex, and age influenced the effects of an immune challenge on the gut microbiome. In sum, adolescent stress history has consequences for immune function into adulthood that may involve effects on the gut microbiome.

Association between heel-rise test performance and clinical severity of chronic venous insufficiency.

BACKGROUND: Peripheral pump dysfunction is important in identifying manifestations of chronic venous insufficiency. The association with disease severity may define better treatment strategies. OBJECTIVE: To evaluate the association between peripheral muscular pump performance by heel-rise test, age, physical activity, use of compression stockings, and chronic venous insufficiency clinical severity. METHODS: Subjects with chronic venous insufficiency were enrolled in the study (n = 172) and evaluated by clinical-etiology-anatomy-pathophysiology severity and heel-rise test. RESULTS: In model 1 of logistic regression, number of heel-rise test repetitions, age, and physical activity explained 47% of clinical-etiology-anatomy-pathophysiology severity (p = 0.0001), physical activity contributed the most. In model 2, heel-rise test repetition rate, age, and physical activity explained 46.4% of clinical-etiology-anatomy-pathophysiology severity (p = 0.0001), repetition rate contributed the most. Conclusion: There was an inverse association between muscular pump performance and physical activity with clinical-etiology-anatomy-pathophysiology severity, muscular pump repetition rate contributed to a less severe outcome.

Zinc as a therapy in a rat model of autism prenatally induced by valproic acid.

Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition. Recent studies have suggested that valproic acid (VPA), an anti-epileptic drug with teratogenic activity, is related to autism. In rodents, VPA exposure during pregnancy induces autistic-like effects. Exposure to VPA may alter zinc metabolism resulting in a transient deficiency of zinc. Therefore, we selected zinc as a prenatal treatment to prevent VPA-induced impairments in a rat model of autism. Wistar female rats received either saline solution or VPA (400 mg/kg, i.p) on gestational day (GD) 12.5. To test the zinc supplementation effect, after 1 h of treatment with saline or VPA, a dose of zinc (2 mg/kg, s.c.) was injected. The offspring were tested for abnormal communication behaviors with an ultrasound vocalization task on postnatal day (PND) 11, repetitive behaviors and cognitive ability with a T-maze task on PND 29, and social interaction with a play behavior task on PND 30. Tyrosine hydroxylase protein (TH) expression was evaluated in the striatum. Prenatal VPA decreased ultrasonic vocalization, induced repetitive/restricted behaviors and cognitive inflexibility, impaired socialization, and reduced striatal TH levels compared with control group. Zinc treatment reduced VPA-induced autistic-like behaviors. However, we found no evidence of an effect of zinc on the VPA-induced reduction in TH expression. The persistence of low TH expression in the VPA-Zn group suggests that Zn-induced behavioral improvement in autistic rats may not depend on TH activity.

Cohabitation with a sick partner increases allergic lung inflammatory response in mice.

The bidirectional relationship between the nervous system and the immune system is relevant for homeostatic organism maintenance. Studies from our laboratory showed that 14days of cohabitation with a sick partner (injected with Ehrlich tumor cells-TAE) produced behavioral, neurochemical, endocrinological and immunological changes. This study analyzes the effects of cohabitation with an Ehrlich tumor-bearing animal on ovalbumin (OVA)-induced lung inflammatory response in mice. Pairs of male mice were divided into three groups: naïve, control and experimental. Animals of the naïve group were kept undisturbed being used for the assessment of basal parameters. One animal of each experimental and control pair of mice was immunized with OVA. On ED(0), these OVA-immunized animals received an OVA booster. At this day (D(0)) the experimental mice that were kept undisturbed were inoculated with 5×10(6) Ehrlich tumor cells; their immunized cage-mates were then referred as to CSP ("companion of sick partner"). The undisturbed mice of each control pair were i.p. treated on D(0) with 0.9% NaCl; their sensitized cage-mates were subsequently referred as CHP ("companion of health partner"). The OVA challenge was performed on CSP and CHP mice on ED(12) and ED(13); blood and tissue collection were performed on ED(14). Fourteen days after cohabitation, in comparison to the CHP mice, the CSP mice displayed the following: (1) an increased number of eosinophils and neutrophils in the BAL, (2) a decreased bone marrow cell count, (3) increased levels of IL-4 and IL-5 and decreased levels of IL-10 and IFN-γ in the BAL supernatant, (5) increased levels of IgG1-OVA, decreased levels of IgG2a-OVA and no changes in OVA-specific IgE in the peripheral blood, (6) increased expression of L-selectin in the BAL granulocytes, (7) decreased tracheal reactivity to methacholine measured in vitro, (8) no changes in plasma corticosterone levels and (9) increased levels of plasmatic noradrenaline. These results suggest that allergic lung inflammatory response exacerbation in CSP mice is a consequence of the psychological stress induced by forced cohabitation with the sick partner. Strong involvement of the sympathetic nervous system (SNS) through adrenaline and noradrenaline release and a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to be the mechanisms underlying the cell recruitment to the animal's airways.

Study of the distribution and abundance of the eggs of Aedes aegypti and Aedes albopictus according to the habitat and meteorological variables, municipality of São Sebastião, São Paulo State, Brazil.

BACKGROUND: This study focused on the distribution and abundance of the eggs of Aedes aegypti and Aedes albopictus. METHODS: Eighty ovitraps were exposed for four days of each month in peri- and intradomiciliary environments of 40 urban residences on 20 street blocks that were drawn monthly in Sebastião, SP, between February 2011 and February 2012. The monthly distribution of positive ovitrap indices (POI) and mean egg counts per trap (MET) of Ae. aegypti and Ae. albopictus were analyzed using the Kruskal-Wallis test, followed by the Dwass-Steel-Critchlow-Fligner (DSCF) test. Spearman's rank correlation coefficient and simple linear regression were used to determine the association between the meteorological variables of temperature and rainfall and the number of ovitraps with eggs and the egg count. RESULTS: The POI and MET of Ae. aegypti were higher in peridomiciliary premises. A positive correlation was found between the temperature and the number of ovitraps with eggs and the egg count of this species in domestic environments. There was no difference in the POI and MET of Ae. albopictus between the environments. A positive correlation was found between temperature and positive ovitraps of Ae. albopictus in peridomiciliary premises. The POI and MET of Ae. aegypti were higher than those of Ae. albopictus. CONCLUSIONS: Peridomiciliary premises were the preferred environments for oviposition of Ae. aegypti. The use of ovitraps for surveillance and vector control is reiterated.

Stability of external and internal implant connections after a fatigue test.

OBJECTIVE: The objective of this study was to compare the torque and detorque values of screw intermediates of external hexagon, internal hexagon, and Morse taper implants in single restorations before and after mechanical cycling. MATERIALS AND METHODS: The study sample was divided into three groups (n = 10) as follows: group EH - external hexagon implant, group IH - internal hexagon implant, and group MT - Morse taper implant. Universal abutments were screwed on the implants, and metal crowns were cemented onto the abutment. The samples were submitted to a mechanical testing of 1 million cycles, with a frequency of 8 cycles per second under a 400 N load. The application and registration of the screw torque (T0) and detorque (T1) values of the intermediate were performed before and after the test. The results were statistically evaluated by analysis of variance (ANOVA) and Tukey's test (α = 0.05). RESULTS: There was no difference between the values of T0 and T1 in the intra-group samples. However, the inter-group difference in T0 between the EH (12.8 N cm) and MT (18.6 N cm) groups and in T1 between the EH (10.4 N cm) and IH (13.8 N cm), EH and MT (19.4 N cm), and MT and IH (P = 0.001) groups were significant. The MT group showed a lower variation of T0 and T1. CONCLUSION: The internal implants, particularly MT, showed better stability in these cases when used for single restorations.

Compreendendo a equipe de enfermagem na assistência ao paciente esquizofrênico / Understanding the nursing team in the assistance to the schizophrenic patient

O objetivo é compreender a percepção da equipe de enfermagem na assistência ao paciente esquizofrênico. Estudo exploratório descritivo, realizado na enfermaria de psiquiatria de um hospital universitário. A coleta de dados foi realizada com quinze profissionais de enfermagem, com entrevista semiestruturada. Da análise dos dados emergiram três categorias: Olhar, que destaca o senso comum para nortear a assistência prestada; Cuidar, que reconhece a importância do relacionamento enfermeiro paciente, porém apartado dos seus pressupostos teóricos; e Sentir, em que o medo e a frustração influenciam a assistência. Evidenciou-se que os profissionais não conseguem organizar suas percepções acerca da relação com o paciente, devido à falta de suporte teórico e método para estabelecê-la, limitam-se a uma interpretação baseada no senso comum, que é uma fase para a constituição da ciência da enfermagem. Transpor o limite requer o preparo profissional para a prática, além das questões levantadas fomentarem novos estudos para consolidação do cuidado.

Peripheral calcifying cystic odontogenic tumour of the maxillary gingiva.

BACKGROUND: Odontogenic tumors are lesions that are derived from remnants of the components of the developing tooth germ. The calcifying cystic odontogenic tumor or calcifying odontogenic cyst is a benign cystic neoplasm of odontogenic origin that is characterized by an ameloblastoma-like epithelium and ghost cells. Calcifying cystic odontogenic tumor may be centrally or peripherally located, and its ghost cells may exhibit calcification, as first described by Gorlin in 1962. Most peripheral calcifying cystic odontogenic tumors are located in the anterior gingiva of the mandible or maxilla. CASE PRESENTATION: Authors report a rare case of a peripheral calcifying cystic odontogenic tumor of the maxillary gingiva. A 39-year-old male patient presented with a fibrous mass on the attached buccal gingiva of the upper left cuspid teeth. It was 0.7-cm-diameter, painless and it was clinically diagnosed as a peripheral ossifying fibroma. After an excisional biopsy, the diagnosis was peripheric calcifying cystic odontogenic tumor. The patient was monitored for five years following the excision, and no recurrence was detected. CONCLUSIONS: All biopsy material must be sent for histological examination. If the histological examination of gingival lesions with innocuous appearance is not performed, the frequency of peripheral calcifying cystic odontogenic tumor and other peripheral odontogenic tumors may be underestimated.

Presence of synthetic pharmaceuticals as adulterants in slimming phytotherapeutic formulations and their analytical determination.

Obesity that is associated with a high consumption of slimming substances is considered a public health problem around the world. In this context, the increasing consumption of phytotherapeutic formulations as alternative obesity treatments has revealed the presence of synthetic pharmaceuticals as adulterants. The illegally added adulterants are frequently anorexic, anxiolytic, and antidepressant pharmaceuticals. This review aims to describe the analytical methodologies utilized for the determination of adulterants in slimming phytotherapeutic formulations. Furthermore, this review describes some important adulteration cases, which occurred mainly in Europe, Asia, Brazil, and the USA.

Association between gestational night blindness and serum retinol in mother/newborn pairs in the city of Rio de Janeiro, Brazil.

OBJECTIVE: Gestational night blindness (XN) is associated with increased risk of reproductive morbidity and mortality. This study investigated the prevalence of gestational XN among postpartum women treated in a public maternity hospital in the city of Rio de Janeiro, Brazil and evaluated its association with maternal and neonatal (cord blood) serum retinol concentrations. METHODS: XN was evaluated retrospectively, using an interview according to guidelines of the World Health Organization, in 222 postpartum women (< or = 6 h after delivery) after singleton births who had low obstetric risk. Serum retinol concentrations were measured according to the modified Bessey method, with a cutoff point lower than 1.05 micromol/L for inadequate serum retinol concentration. RESULTS: Prevalence of gestational XN was 18%, and inadequate maternal and cord blood serum retinol concentrations were found in 24.4% and 45.5% of samples, respectively. The results associated gestational XN with inadequate maternal serum retinol concentration (P = 0.000), and an association was observed between maternal and neonatal serum retinol concentrations (P = 0.000). A poor association was observed between maternal XN and serum levels of retinol in newborn children (P = 0.06). CONCLUSIONS: The results suggest that prevalence of gestational XN and inadequate serum retinol concentration among postpartum women and newborns is a concern, calling attention to the need for studies in other parts of Brazil. In addition, the risk of inadequate serum retinol in newborns was significantly higher among infants of postpartum women with serum retinol levels below 1.05 micromol/L. Gestational XN was associated with inadequate levels of maternal serum retinol, and the results suggest a poor relation between maternal XN and vitamin A nutritional status of newborns.

Intraplacental retinol distribution.

With the objective of evaluating intraplacental vitamin A distribution, 234 placental samples were collected, corresponding to six samples from each of the placentas analyzed: two from the lateral maternal portion, one from the central maternal portion, two from the lateral fetal portion, and one from the central fetal portion. Samples were obtained from 39 adult puerperal mothers with low-risk pregnancies, without vitamin A deficiency or night blindness. Retinol content determination was achieved through spectrophotometry. Retinol values obtained for each region were correlated with the most probable value for each placenta (P < 0.001). Despite differences in retinol content between samples, statistical data analysis showed that intra-tissue variation had no influence on the conversion of data into information. Consequently, any portion of the placenta may be used for retinol level determination purposes, due to the correlation between all portions and the most probable value. The findings of the present study represent an advance for surveys intending to incorporate the collection and dosage of placental vitamin A levels into their analyses, thus increasing the arsenal of pre-pathological or subclinical vitamin A deficiency markers, which can allow for earlier intervention on the maternal-infant group.

Gestational nightblindness among women attending a public maternity hospital in Rio de Janeiro, Brazil.

This study evaluated the prevalence of gestational nightblindness among postpartum women seen at the University Maternal Hospital of the Federal University in Rio de Janeiro, Brazil and the association of this symptom with a biochemical indicator (serum retinol levels) and sociodemographic, anthropometric and antenatal care variables. In total, 262 postpartum women, who did not receive vitamin A supplementation during pregnancy, were interviewed. Gestational nightblindness was diagnosed through the standardized interview as proposed by WHO. Serum retinol levels were evaluated by spectrophotometry. Gestational nightblindness relating to low levels of serum retinol (<1.05 micromol/L, p = 0.000) was diagnosed in 17.9% of subjects interviewed. Less than five antenatal care appointments (odds ratio [OR] = 2.179; confidence interval [CI] 95% = 1.078 - 4.402) and a history of one or more miscarriage(s) (OR = 2.306; CI 95% = 1.185 - 4.491) were predictors for gestational nightblindness. These findings justify the need for nutritional counselling, aimed at improving the vitamin A nutritional status, especially among pregnant women with a history of previous miscarriages and poor antenatal care.