Temporal shifts to the gut microbiome associated with cognitive dysfunction following high-fat diet consumption in a juvenile model of traumatic brain injury.

The gut-brain axis interconnects the central nervous system (CNS) and the commensal bacteria of the gastrointestinal tract. The composition of the diet consumed by the host influences the richness of the microbial populations. Traumatic brain injury (TBI) produces profound neurocognitive damage, but it is unknown how diet influences the microbiome following TBI. The present work investigates the impact of a chow diet versus a 60% fat diet (HFD) on fecal microbiome populations in juvenile rats following TBI. Twenty-day-old male rats were placed on one of two diets for 9 days before sustaining either a Sham or TBI via the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA). Fecal samples were collected at both 1- and 9-days postinjury. Animals were cognitively assessed in the novel object recognition tests at 8 days postinjury. Fecal microbiota DNA was isolated and sequenced. Twenty days of HFD feeding did not alter body weight, but fat mass was elevated in HFD compared with Chow rats. TBI animals had a greater percentage of entries to the novel object quadrant than Sham counterparts, P < 0.05. The Firmicutes/Bacteroidetes ratio was significantly higher in TBI than in the Sham, P < 0.05. Microbiota of the Firmicutes lineage exhibited perturbations by both injury and diet that were sustained at both time points. Linear regression analyses were performed to associate bacteria with metabolic and neurocognitive endpoints. For example, counts of Lachnospiraceae were negatively associated with percent entries into the novel object quadrant. Taken together, these data suggest that both diet and injury produce robust shifts in microbiota, which may have long-term implications for chronic health.NEW & NOTEWORTHY Traumatic brain injury (TBI) produces memory and learning difficulties. Diet profoundly influences the populations of gut microbiota. Following traumatic brain injury in a pediatric model consuming either a healthy or high-fat diet (HFD), significant shifts in bacterial populations occur, of which, some are associated with diet, whereas others are associated with neurocognitive performance. More work is needed to determine whether these microbes can therapeutically improve learning following trauma to the brain.

Investigating luxS gene expression in lactobacilli along lab-scale cocoa fermentations.

Previous metagenomic analyses have suggested that lactobacilli present potential for Quorum Sensing (QS) in cocoa fermentation, and in the present research, laboratory scale fermentations were carried out to monitor the expression of luxS, a universal marker of QS. For that, 96 h-fermentations were studied, as follows: F0 (non inoculated control), F1 (inoculated with yeasts, lactic acid bacteria, and acetic acid bacteria), F2 (inoculated with yeasts and acetic acid bacteria), F3 (inoculated with yeasts only). The parameters evaluated were: plate counting, quantification of key enzymes and analysis of volatile organic compounds associated with key sensory descriptors, using headspace gas chromatography-mass spectrometry (GC-MS). Furthermore, QS was estimated by the quantification of the expression of luxS genes by Reverse Transcriptase Real-Time PCR. The results demonstrated that microbial succession occurred in pilot scale fermentations, but no statistical differences for microbial enumeration and α-diversity index were observed among experiments and control. Moreover, it was not possible to make conclusive correlations of enzymatic profile and fermenting microbiota, likely due to the intrinsic activity of plant hydrolases. Regarding to the expression of luxS genes, in Lactiplantibacillus plantarum they were active along the fermentation, but for Limosilactobacillus fermentum, luxS was expressed only at early and middle phases. Correlation analysis of luxS expression and production of volatile metabolites evidenced a possible negative association of Lp. Plantarum with fermentation quality. In conclusion, these data corroborate former shotgun metagenomic analysis by demonstrating the expression of luxS by lactobacilli in pilot scale cocoa fermentation and evidence Lp. Plantarum is the main lactic acid bacteria related to its expression.

Analysis of environmental variables and deforestation in the amazon using logistical regression models.

In this study, we applied a multivariate logistic regression model to identify deforested areas and evaluate the current effects on environmental variables in the Brazilian state of Rondônia, located in the southwestern Amazon region using data from the MODIS/Terra sensor. The variables albedo, temperature, evapotranspiration, vegetation index, and gross primary productivity were analyzed from 2000 to 2022, with surface type data from the PRODES project as the dependent variable. The accuracy of the models was evaluated by the parameters area under the curve (AUC), pseudo R2, and Akaike information criterion, in addition to statistical tests. The results indicated that deforested areas had higher albedo (25%) and higher surface temperatures (3.2 °C) compared to forested areas. There was a significant reduction of the EVI (16%), indicating water stress, and a decrease in GPP (18%) and ETr (23%) due to the loss of plant biomass. The most precise model (91.6%) included only surface temperature and albedo, providing important information about the environmental impacts of deforestation in humid tropical regions.

Clinicopathologic characteristics of young patients with lip squamous cell carcinoma: a retrospective study.

BACKGROUND: This retrospective study investigates the clinicopathological features and outcomes of young and elderly patients diagnosed with lip squamous cell carcinoma (LSCC). MATERIAL AND METHODS: Data from LSCC patients from Dr. Luiz Antonio Hospital in Natal, Brazil (2000-2015) were analyzed, grouping individuals below 40 and above 60 years old. Demographics, lifestyle habits, clinicopathologic characteristics, and treatment outcomes were examined using descriptive statistics, Chi-square and Fisher's tests, and Kaplan-Meier survival analysis. RESULTS: A total of 47 patients was analyzed, being 20 younger and 27 older, finding significant age-related differences (p = < 0.0001). Although in both groups the tumor was more common in males, older patients had a higher rate of females (29.6%) (p=0.0358) and smoking (70.4%) (p = 0.0043) and underwent more modalities of treatments (p = 0.0027). There were no significant differences in the other analyzed clinicopathologic factors, and survival rates did not differ significantly, though younger patients showed slightly better survival metrics in univariate analysis. CONCLUSIONS: LSCC exhibits some distinct clinicopathological features across different age groups, with significant differences in treatment modalities and progression rates. Age-specific approaches may be required to optimize treatment outcomes.

Estimating the burden of care for oral potentially malignant disorders and oral cancer in Brazilian dental practice.

BACKGROUND: Oral cancer (OC) and oral potentially malignant disorders (OPMD) pose significant challenges to public health in Brazil. This study aimed to estimate the prevalence of oral cancer (OC) and oral potentially malignant disorders (OPMD) among patients who would be treated by Brazilian dentists during their careers. MATERIAL AND METHODS: Data on the number of dentists in Brazil were extracted from the 2022 census data, while incidence rates for OC cases were sourced from the Brazilian National Cancer Institute (INCA). Population estimates for Brazil and data on dental check-up rates were obtained from relevant national sources. RESULTS: Our analysis indicates that a general dentist in Brazil can expect to encounter on average two to three OC patients and on average 675 patients with OPMDs over a 35-year career. Regional disparities were observed, with certain regions showing higher than the average number of encounters due to low density of dentists in some rural districts. CONCLUSIONS: Brazilian dentists are likely to confront a substantial number of OC and OPMD cases during their professional tenure, emphasizing the need for public health policies aimed at enhancing dental surgeons' education in oral cancer prevention and early detection.

Parasacral transcutaneous electrical neural stimulation versus urotherapy in primary monosymptomatic enuresis: A prospective randomized clinical trial.

OBJECTIVE: To evaluate the clinical response of parasacral transcutaneous electrical neural stimulation (parasacral TENS) associated with urotherapy in children with primary monosymptomatic nocturnal enuresis (PMNE) compared to urotherapy alone. MATERIAL AND METHODS: This prospective controlled clinical trial enrolled 72 children over 5 years of age with PMNE. Children were randomly divided into two groups, control group (CG), treated with urotherapy and scapular stimulation, and experimental group (EG), treated with urotherapy and parasacral TENS. In both groups, 20 sessions were performed, 3 times weekly, for 20 min each, with 10 Hz frequency, 700 µS pulse width and intesity determinated by the patient threshold. The percentages of dry nights were analyzed for 14 days before treatment (T0), after the 20th session (T1), 15 (T2), 30 (T3), 60 (T4), and 90 (T5) days after the end of the sessions. Patients of both groups were followed with intervals of 2 weeks in the first month and monthly for three consecutive months. RESULTS: Twenty-eight enuretic children, 14 girls (50%) with a mean age of 9.09 ± 2.23 years completed the study. There was no difference in mean age between groups. Mean percentage of dry nights in EG at T0 was 36%, at T1 49%, at T2 54%, at T3 54%, at T4 54%, and 57% at T5; while in CG, these percentages were 28%, 39%, 37%, 35%, 36%, and 36%, respectively. CONCLUSIONS: Parasacral TENS associated with urotherapy improves the percentage of dry nights in children with PMNE, although no patient had complete resolution of symptoms in this study.

Analysis of microbial communities of ocular prostheses and anophthalmic sockets using 16S rRNA gene sequencing.

Ocular prostheses are liable to host microbial adhesion, which can favor conjunctival inflammation. Knowing the microbiota of the ocular prosthesis and anophthalmic socket is important for predicting infection-related pathogens. This study evaluated the microbiota of the prostheses and anophthalmic sockets of six individuals by 16S rRNA sequencing. The microbial abundance and diversity were analyzed using the Operational Taxonomic Units at the genus level. Forty-seven phyla, capturing 1,258 named genera, were recorded in the sample set. In both sites, the most frequent genera were Fusobacterium, Staphylococcus, Prevotella, and Streptococcus. The microbial abundance was higher for the anophthalmic socket than for the prosthesis. Alpha diversity showed no significant differences in bacterial richness or diversity between sites. Although the microbial abundance in the anophthalmic socket was higher, both sites had similar microbiota with high diversity and low dominance among the genera.

Satisfaction analysis of overground gait exoskeletons in people with neurological pathology. a systematic review.

BACKGROUND: People diagnosed with neurological pathology may experience gait disorders that affect their quality of life. In recent years, research has been carried out on a variety of exoskeletons in this population. However, the satisfaction perceived by the users of these devices is not known. Therefore, the objective of the present study is to evaluate the satisfaction perceived by users with neurological pathology (patients and professionals) after the use of overground exoskeletons. METHODS: A systematic search of five electronic databases was conducted. In order to be included in this review for further analysis, the studies had to meet the following criteria: [1] the study population was people diagnosed with neurological pathology; [2] the exoskeletons had to be overground and attachable to the lower limbs; and [3]: the studies were to include measures assessing either patient or therapist satisfaction with the exoskeletons. RESULTS: Twenty-three articles were selected, of which nineteen were considered clinical trials. Participants diagnosed with stroke (n = 165), spinal cord injury (SCI) (n = 102) and multiple sclerosis (MS) (n = 68). Fourteen different overground exoskeleton models were analysed. Fourteen different methods of assessing patient satisfaction with the devices were found, and three ways to evaluate it in therapists. CONCLUSION: Users' satisfaction with gait overground exoskeletons in stroke, SCI and MS seems to show positive results in safety, efficacy and comfort of the devices. However, the worst rated aspects and therefore those that should be optimized from the users' point of view are ease of adjustment, size and weight, and ease of use.

Sociodemographic and academic factors associated with unhealthy lifestyle among Brazilian nursing students.

This study aimed to identify sociodemographic and academic factors associated with unhealthy lifestyles among Brazilian undergraduate nursing students. A cross-sectional study was completed by 286 nursing students in Brazil. Multinomial logistic regression was conducted to examine the association between sociodemographic and academic variables with the latent lifestyle indicator. The model fit's validity was assessed using Akaike information coefficient estimation, Hosmer-Lemeshow test, and the ROC curve. A high health risk lifestyle was 2.7 times more likely among students aged 18-24 years than students aged 25 years or older (OR = 2.7, 95% CI = [1.18, 6.54] p = 0.02); 2.3 times more likely among students with ≥400 h of semester time (OR = 2.3, 95% CI = [0.93, 5.90], p = 0.07); and 3.8 times more likely among female students (OR = 3.8, 95% CI = [0.82, 8.12], p = 0.09). A moderate health risk lifestyle was 1.8 times more likely among students from the 6th to 10th semesters (OR = 1.8, 95% CI = [-0.95, 3.75], p = 0.07). Sociodemographic and academic factors were associated with unhealthy lifestyles. Health promotion efforts are necessary to improve nursing students' health behaviors.

Effects of ATLAS 2030 gait exoskeleton on strength and range of motion in children with spinal muscular atrophy II: a case series.

BACKGROUND: Children with spinal muscular atrophy (SMA) present muscle weakness and atrophy that results in a number of complications affecting their mobility, hindering their independence and the development of activities of daily living. Walking has well-recognized physiological and functional benefits. The ATLAS 2030 exoskeleton is a paediatric device that allows gait rehabilitation in children with either neurological or neuromuscular pathologies with gait disorders. The purpose is to assess the effects in range of motion (ROM) and maximal isometric strength in hips, knees and ankles of children with SMA type II after the use of ATLAS 2030 exoskeleton. METHODS: Three children (mean age 5.7 ± 0.6) received nine sessions bi-weekly of 60 min with ATLAS 2030. ROM was assessed by goniometry and strength by hand-held dynamometer. All modes of use of the exoskeleton were tested: stand up and sit down, forward and backward walking, and gait in automatic and active-assisted modes. In addition, different activities were performed during the gait session. A descriptive analysis of all variables was carried out. RESULTS: The average time of use was 53.5 ± 12.0 min in all sessions, and all participants were able to carry out all the proposed activities as well as to complete the study. Regarding isometric strength, all the measurements increased compared to the initial state, obtaining the greatest improvements for the hip flexors (60.2%) and extensors muscles (48.0%). The ROM increased 12.6% in hip and 34.1% in the ankle after the study, while knee ROM remained stable after the study. CONCLUSION: Improvements were showed in ROM and maximal isometric strength in hips, knees and ankles after using ATLAS 2030 paediatric gait exoskeleton in all three children. This research could serve as a preliminary support for future clinical integration of ATLAS 2030 as a part of a long-term rehabilitation of children with SMA. TRIAL REGISTRATION: The approval was obtained (reference 47/370329.9/19) by Comunidad de Madrid Regional Research Ethics Committee with Medical Products and the clinical trial has been registered on Clinical Trials.gov: NCT04837157.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Behavioral Battery for Testing Candidate Analgesics in Mice. I. Validation with Positive and Negative Controls.

This study evaluated a battery of pain-stimulated, pain-depressed, and pain-independent behaviors for preclinical pharmacological assessment of candidate analgesics in mice. Intraperitoneal injection of dilute lactic acid (IP acid) served as an acute visceral noxious stimulus to produce four pain-related behaviors in male and female ICR mice: stimulation of 1) stretching, 2) facial grimace, 3) depression of rearing, and 4) depression of nesting. Additionally, nesting and locomotion in the absence of the noxious stimulus were used to assess pain-independent drug effects. These six behaviors were used to compare effects of two mechanistically distinct but clinically effective positive controls (ketoprofen and oxycodone) and two negative controls that are not clinically approved as analgesics but produce either general motor depression (diazepam) or motor stimulation (amphetamine). We predicted that analgesics would alleviate all IP acid effects at doses that did not alter pain-independent behaviors, whereas negative controls would not. Consistent with this prediction, ketoprofen (0.1-32 mg/kg) produced the expected analgesic profile, whereas oxycodone (0.32-3.2 mg/kg) alleviated all IP acid effects except depression of rearing at doses lower than those that altered pain-independent behaviors. For the negative controls, diazepam (1-10 mg/kg) failed to block IP acid-induced depression of either rearing or nesting and only decreased IP acid-stimulated behaviors at doses that also decreased pain-independent behaviors. Amphetamine (0.32-3.2 mg/kg) alleviated all IP acid effects but only at doses that also stimulated locomotion. These results support utility of this model as a framework to evaluate candidate-analgesic effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behavioral endpoints. SIGNIFICANCE STATEMENT: Preclinical assays of pain and analgesia often yield false-positive effects with candidate analgesics. This study used two positive-control analgesics (ketoprofen, oxycodone) and two active negative controls (diazepam, amphetamine) to validate a strategy for distinguishing analgesics from nonanalgesics by profiling drug effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behaviors in male and female mice.

Manipulating Pharmacodynamic Efficacy with Agonist + Antagonist Mixtures: In Vitro and In Vivo Studies with Opioids and Cannabinoids.

Pharmacodynamic efficacy of drugs to activate their receptors is a key determinant of drug effects, and intermediate-efficacy agonists are often useful clinically because they retain sufficient efficacy to produce therapeutically desirable effects while minimizing undesirable effects. Molecular mechanisms of efficacy are not well understood, so rational drug design to control efficacy is not yet possible; however, receptor theory predicts that fixed-proportion mixtures of an agonist and antagonist for a given receptor can be adjusted to precisely control net efficacy of the mixture in activating that receptor. Moreover, the agonist proportion required to produce different effects provides a quantitative scale for comparing efficacy requirements across those effects. To test this hypothesis, the present study evaluated effectiveness of fixed-proportion agonist/antagonist mixtures to produce in vitro and in vivo effects mediated by µ-opioid receptors (MOR) and cannabinoid type 1 receptors (CB1R). Mixtures of 1) the MOR agonist fentanyl and antagonist naltrexone and 2) the CB1R agonist CP55,940 and antagonist/inverse agonist rimonabant were evaluated in an in vitro assay of ligand-stimulated guanosine 5'-O-(3-[35S]thio)triphosphate binding and an in vivo assay of thermal nociception in mice. For both agonist/antagonist pairs in both assays, increasing agonist proportions produced graded increases in maximal mixture effects, and lower agonist proportions were sufficient to produce in vivo than in vitro effects. These findings support the utility of agonist-antagonist mixtures as a strategy to control net efficacy of receptor activation and to quantify and compare efficacy requirements across a range of in vitro and in vivo endpoints. SIGNIFICANCE STATEMENT: Manipulation of agonist proportion in agonist/antagonist mixtures governs net mixture efficacy at the target receptor. Parameters of agonist/antagonist mixture effects can provide a quantitative metric for comparison of efficacy requirements across a wide range of conditions.

An epidemiological index for drought vulnerability in the Rio Grande do Norte State, Brazil.

In the Northeast Brazil (NEB), the impacts of climate extreme events such as severe droughts are aggravated by poverty and poor socioeconomic conditions. In this region, such events usually result in the spread of endemic diseases, problems in water distribution, and agricultural losses, often leading to an increase in the population's vulnerability. Thus, this study aims to evaluate the microregions of the Rio Grande do Norte (RN) state, in the NEB, according to the Epidemiological Index for Drought Vulnerability (EIDV). We mapped and classified the microregions according to three dimensions of vulnerability: risk, susceptibility, and adaptive capacity. We also verified potential associations between drought risk and epidemiological vulnerability. The EIDV was calculated by considering the three dimensions of vulnerability as mutually exclusive events and applying the third axiom of probability. Then we carried out a cluster analysis in order to classify the microregions according to similarities in the EIDV. Odds ratio were also calculated in order to evaluate the odds of microregions having a high susceptibility to diseases and high vulnerability given the drought risk. Results showed that the Pau dos Ferros, Seridó Ocidental, Seridó Oriental, and Umarizal microregions were the most vulnerable, while Natal and Litoral Sul were the least vulnerable. Regarding the dimensions of vulnerability, we observed that almost the entire RN state exhibited high drought risk. Pau dos Ferros and Umarizal had the highest susceptibility and Litoral Nordeste presented the worst adaptive capacity to the effects of drought on health. The EIDV revealed that the population of the RN state needs improvements in living conditions and health, since socioeconomic status is one of the factors that most influence the vulnerability of microregions, which in turn is aggravated by drought risk.

Toxicity of silver nanoparticles on different tissues in adult Danio rerio.

Although silver nanoparticles (AgNP) are among the most studied nanomaterials by virtue of their broad application in many areas, little is known about their overall toxicity to aquatic organisms after their contamination of the water environment. This study aimed to analyze the effect of the exposure (96 h) to different AgNP concentrations on Danio rerio (zebrafish) tissues. AgNP were synthesized and characterized by transmission electron microscopy (TEM), showing spherical AgNP of 30.00 ± 16.80 nm size. The effects of different AgNP concentrations (1, 3, and 5 µg L-1) on brain, muscle, gill, and liver tissues of zebrafish were investigated. The results show a significant decrease in brain and muscle acetylcholinesterase (AChE) activity. Liver and gill catalase (CAT) activity also decreased significantly. At the highest exposure concentration, muscle AChE was more inhibited (37.3%) than brain AChE (26.4%) and gill CAT was more inhibited (67.4%) than liver CAT (51.2%). D. rerio also showed gill morphological changes such as fusion of secondary lamellae, curvature, dilated marginal channel, and epithelial lifting. This study indicates that gill CAT together with morphological studies are potential biomarkers for AgNP.

Prognostic value of the immunohistochemical expression of vascular endothelial growth factors in malignant salivary gland neoplasms: a systematic review and meta-analysis.

BACKGROUND:  The immunohistochemical expression of vascular endothelial growth factor is a prognostic marker in several cancer types. In salivary gland tumors, the association between vascular endothelial growth factor and prognosis remains unclear. The purpose of this study was to perform a systematic review and meta-analysis to assess whether the immunohistochemical expression of vascular endothelial growth factor in patients with salivary gland neoplasms presents prognostic value. MATERIAL AND METHODS: Immunohistochemical studies assessing the predictive value of vascular endothelial growth factor in salivary gland neoplasms were systematically reviewed using PubMed, Scopus, Embase, Cochrane Library, and Web of Science databases. It was assessed any survival rates. The fixed-effect model with an adjusted hazard ratio (HR) and 95% confidence intervals (95% CI) as effect measures were performed in the meta-analysis. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of the included studies, and the evidence quality was assessed by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivary gland neoplasms was associated with shortened survival (HR=5.37, 95% CI: 2.67-10.83, P = 0.00001). In addition, the presence of vascular endothelial growth factor was tightly associated with tumor size, lymph node metastasis, clinical stage, perineural invasion, vascular invasion, poor local control of the disease, and recurrence. CONCLUSIONS: The immunohistochemical overexpression of vascular endothelial growth factor in patients with salivary gland neoplasms has prognostic value and was associated with decreased survival time. However, more primary well-designed studies are necessary to increase the level of evidence.

Pathogenicity of Aphelenchoides Pseudogoodeyi on the Ornamental Plants Asplenium Nidus and Lilium Speciosum in Brazil.

Aphelenchoides pseudogoodeyi has recently been reported in association with seeds of forage grasses and rice in Brazil and senescent strawberry plants, in the United States. This nematode is likely a mycophagous species; however, so far, its pathogenicity potential to plants is unclear. This study aimed to verify the pathogenicity of A. pseudogoodeyi to two species of ornamental plants. The experiments were conducted by inoculating A. pseudogoodeyi onto Bird's-Nest Fern (Asplenium nidus) and Oriental Lily (Lilium speciosum) leaves, using two inoculation methods (with and without injury). After 40 days of inoculation (DAI) in Bird's-Nest Fern and 5, 10, 20 and 40 DAI in Oriental Lily, the pathogenicity and the host efficiency were evaluated by symptoms observation and by severity, final nematode population and reproductive factor (RF), respectively. Additionally, a histopathological study was performed by inoculating A. pseudogoodeyi onto Bird's-Nest Fern for observing anatomical alterations. A. pseudogoodeyi was able to cause local necrotic lesions on both Bird's-Nest Fern and Oriental Lily leaves. However, the presence of injury was essential to enable A. pseudogoodeyi to penetrate and cause those symptoms in both plant species. Also, the total population of A. pseudogoodeyi decreased drastically over time and RF was <1, which characterized these species as poor-host or resistant plants. A. pseudogoodeyi penetrated into the foliar tissue and induced a total destruction of the mesophyll and collapse of the cells, with the formation of large intercellular spaces. It is concluded that A. pseudogoodeyi is an opportunistic pathogen as injury was required to induce symptoms in Bird's-Nest Fern and Oriental Lily.

A novel de novo heterozygous ALPL nonsense mutation associated with adult hypophosphatasia.

Using genetic, clinical, biochemical, and radiographic assessment and bioinformatic approaches, we present an unusual case of adult HPP caused by a novel de novo heterozygous nonsense mutation in the alkaline phosphatase (ALPL). INTRODUCTION: Hypophosphatasia (HPP) is caused by genetic alterations of the ALPL gene, encoding the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Here, the purpose was to perform clinical and molecular investigation in a 36-year-old Caucasian woman suspected to present adult HPP. METHODS: Medical and dental histories were obtained for the proposita and family members, including biochemical, radiographic, and dental assessments. ALPL mutational analysis was performed by the Sanger sequencing method, and the functional impact prediction of the identified mutations was assessed by bioinformatic methods. RESULTS: We identified a novel heterozygous nonsense mutation in the ALPL gene (NM_000478.6:c.768G>A; W[TGG]>*[TGA]) associated with spontaneous vertebral fracture, severe back pain, musculoskeletal pain, low bone density, and short-rooted permanent teeth loss. Functional prediction analysis revealed that the Trp256Ter mutation led to a complete loss of TNSALP crown domain and extensive loss of other functional domains (calcium-binding domain, active site vicinity, and zinc-binding site) and over 60% loss of homodimer interface residues, suggesting that the mutant TNSALP molecules are nonfunctional and form unstable homodimers. Genotyping of the ALPL in the proposita's parents, sister, and niece revealed that in this case, HPP occurred due to a de novo mutation. CONCLUSION: The present study describes a novel genotype-phenotype and structure-function relationship for HPP, contributing to a better molecular comprehension of HPP etiology and pathophysiology.

Mechanisms and functional impact of Group I metabotropic glutamate receptor modulation of excitability in mouse MNTB neurons.

We examined effects of Group I metabotropic glutamate receptors on the excitability of mouse medial nucleus of the trapezoid body (MNTB) neurons. The selective agonist, S-3,5-dihydroxyphenylglycine (DHPG), evoked a dose-dependent depolarization of the resting potential, increased membrane resistance, increased sag depolarization, and promoted rebound action potential firing. Under voltage-clamp, DHPG evoked an inward current, referred to as IDHPG , which was developmentally stable through postnatal day P56. IDHPG had low temperature dependence in the range 25-34°C, consistent with a channel mechanism. However, the I-V relationship took the form of an inverted U that did not reverse at the calculated Nernst potential for K+ or Cl- . Thus, it is likely that more than one ion type contributes to IDHPG and the mix may be voltage dependent. IDHPG was resistant to the Na+ channel blockers tetrodotoxin and amiloride, and to inhibitors of iGluR (CNQX and MK801). IDHPG was inhibited 21% by Ba2+ (500 µM), 60% by ZD7288 (100 µM) and 73% when the two antagonists were applied together, suggesting that KIR channels and HCN channels contribute to the current. Voltage clamp measurements of IH indicated a small (6%) increase in Gmax by DHPG with no change in the voltage dependence. DHPG reduced action potential rheobase and reduced the number of post-synaptic AP failures during high frequency stimulation of the calyx of Held. Thus, activation of post-synaptic Group I mGlu receptors modifies the excitability of MNTB neurons and contributes to the reliability of high frequency firing in this auditory relay nucleus.

Energetic and thermodynamical aspects of the cyclodextrins-cannabidiol complex in aqueous solution: a molecular-dynamics study.

Cyclodextrins (CDs) are well-known carriers for encapsulating hydrophobic molecules, while among cannabinoids, cannabidiol (CBD) has attracted considerable attention due to its therapeutic capability. In this framework, we employed molecular dynamics and docking techniques for investigating the interaction energy and thermodynamical issues between different CDs (α, ß, and γ type) and CBD immersed in water and a solution mimicking a physiological environment. We quantified the energetic aspects, for different thermal conditions, in which both aqueous solutions interact with CBDs and CDs and the CBD-CDs complex itself. In order to approximate the physiological conditions, our simulations also included the mammalian temperature. The calculations revealed significant interaction energy between lactate and the CD surface and a movement of lactate toward CD as well. We observed an almost constant number of lactate molecules forming clusters without exhibiting a temperature dependence. Next, the degree of CBD-CDs complexation at four different temperatures was analyzed. The results showed that the complexation depends on the medium, becoming weaker with the temperature increment. Our findings highlighted that the entropy contribution is relevant for CBD-α-CD and CBD-ß-CD, while CBD-γ-CD is practically insensitive to temperature changes for both solutions. In both water and artificial physiological solutions, the γ-CD appears more stable than the other complexes. Overall, CBD achieved partial encapsulation considering α-CD and ß-CD, showing a temperature dependence, while γ-CD remained fully immersed no matter the thermal level assumed. We also discuss the pharmacological relevance and physiological implications of these findings.