Preventable incidence cases from non-communicable diseases attributable to insufficient physical activity in Chile.

OBJECTIVES: Lack of sufficient physical activity (PA) has been associated with an increased risk of several non-communicable diseases (NCDs) and all-cause mortality. This study aimed to estimate the number of preventable incidence cases of NCDs attributable to insufficient PA in the Chilean population. STUDY DESIGN: Comparative risk assessment modelling study. METHODS: This study examined data from 5834 participants aged ≥20 years from the Chilean National Survey (2016-2017). PA was assessed by the Global Physical Activity Questionnaire (GPAQ), and metabolic equivalent of tasks (METs) were assigned according to PA intensity. Estimated incidence cases of NCDs in Chile in 2019 were obtained from the Global Burden of Disease study. Relative risks for breast cancer, colon cancer, ischaemic heart disease, diabetes and stroke were obtained from a published meta-analysis and applied to the prevalence of insufficient PA estimates through the potential impact fraction equation. RESULTS: High levels of PA (≥8000 MET-min/week) could potentially avoid more than 22,000 (64.6 %) incidence NCD cases, ranging from 498 (10.1 %) preventable cases of breast cancer to 5629 (14.7 %) cases of diabetes. Other modelled scenarios also showed to reduce the incidence cases of all five NCDs but to a lesser extent; where at least PA recommendation was achieved, preventable NCDs were reduced by 6522 cases (18.7 %), and where a 10 % relative reduction in insufficient PA level in the population was achieved, preventable NCDs were reduced by 651 (1.8 %) cases. CONCLUSIONS: The study results provide estimates for the incidence cases of preventable NCDs attributable to insufficient PA, highlighting the important role of PA in NCD prevention in Chile.

Cut-off points for isometric handgrip and low limb explosive strength in relation to indicators of overweight/obesity in people with intellectual disabilities: analysis by age groups.

BACKGROUND: The prevalence of overweight/obesity has been increasing globally and in people with Intellectual Disabilities (IDs), this problem is exacerbated even more, which added to a low physical condition that contributes to the deterioration of functionality and increases the risk of developing chronic diseases in the course of life. Therefore, the aim of this study was to establish cut-off points for levels of isometric handgrip and low limb explosive strength in children, adolescents and adults, which identify overweight/obesity in people with IDs and their respective associations. METHODS: The sample was made up of 131 individuals with IDs, belonging to four special and community educational centres in the city of Santiago, Chile. Body mass index (BMI) and waist-to-height ratio (WHR) were used as indicators of overweight/obesity. Handgrip strength was used as a measure of isometric strength, and countermovement jump was used as a measure of low limb explosive strength. For the comparison of variables by age group, the analysis of Ancova, Kruskal-Wallis and chi-square tests were used. The total area under the receiver operating characteristic curve of isometric handgrip and low limb explosive strength was identified as an indicator of overweight/obesity according to age groups. A logistic regression model was used to quantify the effect that strength categories below the cut-off point have on the risk of overweight and obesity. RESULTS: Significant differences were observed between the age groups for body weight, height, BMI and WHR, as well as in the levels of absolute handgrip strength and vertical jump with countermovement (P ≤ 0.05). Children showed the lowest cut-off points for absolute and relative strength. The adolescent group showed the highest cut-off points for relative strength and countermovement jump and adults showed the highest value for absolute strength as indicators of overweight/obesity. Different associations between cut-off points with BMI and WHR were found. CONCLUSIONS: Adolescents showed the highest cut-off point for relative strength and countermovement jump, and adults showed the highest value for absolute strength, according to overweight/obesity indicators (BMI and WHR). It is suggested to adjust resistance training programmes according to age categories for the prevention of overweight/obesity in people with IDs.

"A man without money getting a sexual partner? It doesn't exist in our community": male partners' perspectives on transactional sexual relationships in Uganda and Eswatini.

Research on transactional sexual relationships has largely focused on women's perspectives. Better understanding the men's views-especially regarding relationships with adolescent girls and young women-can inform HIV prevention efforts. In 2017, 134 in-depth interviews were conducted with the male partners of girls and young women aged 19-47 years, 94 in Uganda and 40 in Eswatini. Respondents were recruited at venues such as bars where men and potential partners meet and through other young women. Most respondents believed that providing money/gifts was the way to establish relationships with women in their communities, a context that some found undesirable. Young women were mainly perceived as actively pursuing transactional sex for material goods, but respondents also described economically impoverished women who were manipulated into relationships. Men described conflict with longer term partners as a driver to seeking younger partners, who were more compliant. Transaction dominates the male partners of adolescent girls and young women's understanding of sexual relationships, and inequitable power dynamics are reinforced by seeking younger partners. However, some respondents' discontent with this dynamic suggests an opportunity for change. HIV prevention programmes should directly address the underlying drivers of transactional relationships (e.g. gender norms) and work with men who question the practice.

Sex-specific effect of prenatal alcohol exposure on N-methyl-D-aspartate receptor function in orbitofrontal cortex pyramidal neurons of mice.

BACKGROUND: Alcohol consumption during pregnancy can produce behavioral and cognitive deficits that persist into adulthood. These include impairments in executive functions, learning, planning, and cognitive flexibility. We have previously shown that moderate prenatal alcohol exposure (PAE) significantly impairs reversal learning, a measure of flexibility mediated across species by different brain areas that include the orbital frontal cortex (OFC). Reversal learning is likewise impaired by genetic or pharmacological inactivation of GluN2B subunit-containing N-methyl-D-aspartate receptors (NMDARs). In the current study, we tested the hypothesis that moderate PAE persistently alters the number and function of GluN2B subunit-containing NMDARs in OFC pyramidal neurons of adult mice. METHODS: We used a rodent model of fetal alcohol spectrum disorders and left offspring undisturbed until adulthood. Using whole-cell, patch-clamp recordings, we assessed NMDAR function in slices from 90- to 100-day-old male and female PAE and control mice. Pharmacologically isolated NMDA receptor-mediated evoked excitatory postsynaptic currents (NMDA-eEPSCs) were recorded in the absence and presence of the GluN2B antagonist, Ro25-6981(1 µM). In a subset of littermates, we evaluated the level of GluN2B protein expression in the synaptic fraction using Western blotting technique. RESULTS: Our results indicate that PAE females show significantly larger (~23%) NMDA-eEPSC amplitudes than controls, while PAE induced a significant decrease (~17%) in NMDA-eEPSC current density of pyramidal neurons recorded in slices from male mice. NMDA-eEPSC decay time was not affected in PAE-exposed mice from either sex. The contribution of GluN2B subunit-containing NMDARs to the eEPSCs was not significantly altered by PAE. Moreover, there were no significant changes in protein expression in the synaptic fraction of either PAE males or females. CONCLUSIONS: These findings suggest that low-to-moderate PAE modulates NMDAR function in pyramidal neurons in a sex-specific manner, although we did not find evidence that the effect is mediated by dysfunction of synaptic GluN2B subunit-containing NMDARs.

Quantitative interactions between Candida albicans and the mutans streptococci in patients with Down Syndrome.

BACKGROUND: Oral microorganisms produce damage through the transfer to bloodstream, colonizing other tissues or direct damage in the oral cavity. Aim to study the quantitative interactions between C. albicans and the mutans streptococci and ms serotypes in the saliva of the oral cavity of patients with Down syndrome (DS). MATERIAL AND METHODS: Included 120 patients of both genders, 60 patients with Down syndrome (DS) and 60 pa- tients as a control group (CG). Samples of saliva were taken, and bacteria and fungi were grown on TYCSB and Saboureaud agar. Microbiological, serological and quantitative analyses were performed to determine the kind of isolated of microorganisms corresponding to the ms c, e, f and k for species S. mutans and d and g for S. sobrinus and C. albicans. Electronic scanning microscopy was employed to visualize and confirm the colonies under study. Statistics analysis included t-test proofs for matched data test, Scheffé and ANOVA. RESULTS: Forming units (CFU) per mL of saliva of C. albicans a significant difference was observed among DS

Assessment of knowledge and autonomy for the transition from adolescent toward adult care. / Evaluación de conocimientos y autonomía para la transición de adolescentes hacia la atención de adultos.

INTRODUCTION: In the last decades more and more children survive with complex health conditions, requiring a transition from pediatric to adult care. It is essential to have instruments that provide information on the level of preparation of patients for this process. OBJECTIVE: To create and validate a questionnaire to measure the readiness status of adolescent patients with chronic diseases in the transition process. PATIENTS AND METHOD: Based on international questionnaires, a self-report instrument was designed which was subjected to content validity by experts, and then to comprehension and feasibility tests in a pilot group. Subsequently, construct and reliability validation were performed through a factorial analysis after applied it to adolescents living with a chronic illness. RESULTS: After the analysis made by 11 experts and the pilot group with 8 patients, we obtained an instrument that was fully answered by 168 teenagers (Average age 14.4 years). After construct validation, a 24-items instrument of high clinical relevance was developed, with 9 items with acceptable psychometric properties, which were highlighted in the final questionnaire. CONCLUSION: a self-report instrument aimed to measure the readiness of adolescents during the transition process to adult care is presented. The reported psycho metric properties of the instrument were insufficient to consider it validated since the construct vali dity and reliability were only checked for 9 of the 24 items.

Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

BACKGROUND: We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H3 receptor number and function. METHODS: Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. RESULTS: Radiohistochemical studies in adult offspring revealed that specific [3 H]-A349821 binding to histamine H3 receptors was not different in PAE rats compared to controls. However, H3 receptor-mediated Gi /Go protein-effector coupling, as measured by methimepip-stimulated [35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H3 receptor population without significantly altering the affinities of H3 receptor subpopulations. In agreement with the [35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. CONCLUSIONS: These results suggest that a PAE-induced elevation in H3 receptor-mediated inhibition of glutamate release from perforant path terminals as 1 mechanism contributing the LTP deficits previously observed in the dentate gyrus of PAE rats, as well as providing a mechanistic basis for the efficacy of H3 receptor inverse agonists for ameliorating these deficits.

Prenatal Alcohol Exposure Leads to Enhanced Serine 9 Phosphorylation of Glycogen Synthase Kinase-3ß (GSK-3ß) in the Hippocampal Dentate Gyrus of Adult Mouse.

BACKGROUND: The goal of this study was to evaluate the expression and serine 9 phosphorylation of glycogen synthase kinase (GSK-3ß) within the adult hippocampal dentate gyrus (DG) in a preclinical mouse model of fetal alcohol spectrum disorders. GSK-3ß is a multifunctional kinase that modulates many hippocampal processes affected by gestational alcohol, including synaptic plasticity and adult neurogenesis. GSK-3ß is a constitutively active kinase that is negatively regulated by phosphorylation at the serine 9 residue. METHODS: We utilized a well-characterized limited access "drinking-in-the-dark" paradigm of prenatal alcohol exposure (PAE) and measured p(Ser9)GSK-3ß and total GSK-3ß within adult DG by Western blot analysis. In addition, we evaluated the expression pattern of both p(Ser9)GSK-3ß and total GSK-3ß within the adult hippocampal dentate of PAE and control mice using high-resolution confocal microscopy. RESULTS: Our findings demonstrate a marked 2.0-fold elevation of p(Ser9)GSK-3ß in PAE mice, concomitant with a more moderate 36% increase in total GSK-3ß. This resulted in an approximate 63% increase in the p(Ser9)GSK-3ß/GSK-3ß ratio. Immunostaining revealed robust GSK-3ß expression within Cornu Ammonis (CA) pyramidal neurons, hilar mossy cells, and a subset of GABAergic interneurons, with low levels of expression within hippocampal progenitors and dentate granule cells. CONCLUSIONS: These findings suggest that PAE may lead to a long-term disruption of GSK-3ß signaling within the DG, and implicate mossy cells, GABAergic interneurons, and CA primary neurons as major targets of this dysregulation.

Prenatal alcohol exposure alters synaptic activity of adult hippocampal dentate granule cells under conditions of enriched environment.

Prenatal alcohol exposure (PAE) results in fetal alcohol spectrum disorder (FASD), which is characterized by a wide range of cognitive and behavioral deficits that may be linked to impaired hippocampal function and adult neurogenesis. Preclinical studies in mouse models of FASD indicate that PAE markedly attenuates enrichment-mediated increases in the number of adult-generated hippocampal dentate granule cells (aDGCs), but whether synaptic activity is also affected has not been studied. Here, we utilized retroviral birth-dating coupled with whole cell patch electrophysiological recordings to assess the effects of PAE on enrichment-mediated changes in excitatory and inhibitory synaptic activity as a function of DGC age. We found that exposure to an enriched environment (EE) had no effect on baseline synaptic activity of 4- or 8-week-old aDGCs from control mice, but significantly enhanced the excitatory/inhibitory ratio of synaptic activity in 8-week-old aDGCs from PAE mice. In contrast, exposure to EE significantly enhanced the excitatory/inhibitory ratio of synaptic activity in older pre-existing DGCs situated in the outer dentate granule cell layer (i.e., those generated during embryonic development; dDGCs) in control mice, an effect that was blunted in PAE mice. These findings indicate distinct electrophysiological responses of hippocampal DGCs to behavioral challenge based on cellular ontogenetic age, and suggest that PAE disrupts EE-mediated changes in overall hippocampal network activity. These findings may have implications for future therapeutic targeting of hippocampal dentate circuitry in clinical FASD. © 2016 Wiley Periodicals, Inc.

Sensitivity of GABAergic Tonic Currents to Acute Ethanol in Cerebellar Granule Neurons is Not Age- or δ Subunit-Dependent in Developing Rats.

BACKGROUND: The age of first exposure to ethanol (EtOH), as well as reduced sensitivity to its motor-impairing effects, are associated with a future predisposition to abuse EtOH. In adolescence, acute EtOH potentiates GABA transmission, including tonic inhibition mediated by δ-containing extrasynaptic GABAA receptors (GABAA Rs) in cerebellar granule neurons (CGNs), an effect that likely contributes to EtOH-induced motor impairment. Prenatal EtOH exposure is strikingly prevalent and is associated with increased EtOH abuse later in life; however, the acute effects of EtOH on GABA transmission in developing CGNs are unknown. METHODS: Using whole-cell patch-clamp electrophysiological techniques in acute brain slices, we examined the acute effects of EtOH on GABA transmission and functionally assessed the role of δ-containing GABAA Rs in CGNs of preweanling (postnatal day [P] 12 to 14) and postweanling (P28 to 30) male Sprague-Dawley rats. RESULTS: The magnitude of basal tonic currents were similar at both ages. However, 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride, an agonist with preferential affinity for δ-containing GABAA Rs, significantly potentiated tonic currents to a larger magnitude in CGNs from postweanlings compared to preweanlings. Conversely, acute application of EtOH (80 mM) significantly increased tonic currents and the frequency of spontaneous inhibitory postsynaptic currents to a similar extent in CGNs from pre- and postweanlings. CONCLUSIONS: These findings highlight the sensitivity of the developing cerebellum to EtOH. Furthermore, this study demonstrates age-dependent functional changes in a well-characterized circuitry that may contribute to the short- and long-term effects of prenatal exposure to EtOH.

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation.

Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-ß superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors.

Exposure of neonatal rats to alcohol has differential effects on neuroinflammation and neuronal survival in the cerebellum and hippocampus.

BACKGROUND: Fetal alcohol exposure is a leading cause of preventable birth defects, yet drinking during pregnancy remains prevalent worldwide. Studies suggest that activation of the neuroimmune system plays a role in the effects of alcohol exposure during the rodent equivalent to the third trimester of human pregnancy (i.e., first week of neonatal life), particularly by contributing to neuronal loss. Here, we performed a comprehensive study investigating differences in the neuroimmune response in the cerebellum and hippocampus, which are important targets of third trimester-equivalent alcohol exposure. METHODS: To model heavy, binge-like alcohol exposure during this period, we exposed rats to alcohol vapor inhalation during postnatal days (P)3-5 (blood alcohol concentration = 0.5 g/dL). The cerebellar vermis and hippocampus of rat pups were analyzed for signs of glial cell activation and neuronal loss by immunohistochemistry at different developmental stages. Cytokine production was measured by reverse transcriptase polymerase chain reaction during peak blood alcohol concentration and withdrawal periods. Additionally, adolescent offspring were assessed for alterations in gait and spatial memory. RESULTS: We found that this paradigm causes Purkinje cell degeneration in the cerebellar vermis at P6 and P45; however, no signs of neuronal loss were found in the hippocampus. Significant increases in pro-inflammatory cytokines were observed in both brain regions during alcohol withdrawal periods. Although astrocyte activation occurred in both the hippocampus and cerebellar vermis, microglial activation was observed primarily in the latter. CONCLUSIONS: These findings suggest that heavy, binge-like third trimester-equivalent alcohol exposure has time- and brain region-dependent effects on cytokine levels, morphological activation of microglia and astrocytes, and neuronal survival.

Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex--Recent Advances.

Studies from several laboratories have shown that ethanol impairs cerebellar function, in part, by altering GABAergic transmission. Here, we discuss recent advances in our understanding of the acute effects of ethanol on GABA(A) receptor-mediated neurotransmission at cerebellar cortical circuits, mainly focusing on electrophysiological studies with slices from laboratory animals. These studies have shown that acute ethanol exposure increases GABA release at molecular layer interneuron-to-Purkinje cell synapses and also at reciprocal synapses between molecular layer interneurons. In granule cells, studies with rat cerebellar slices have consistently shown that acute ethanol exposure both potentiates tonic currents mediated by extrasynaptic GABA(A) receptors and also increases the frequency of spontaneous inhibitory postsynaptic currents mediated by synaptic GABA(A) receptors. These effects have been also documented in some granule cells from mice and nonhuman primates. Currently, there are two distinct models on how ethanol produces these effects. In one model, ethanol primarily acts by directly potentiating extrasynaptic GABA(A) receptors, including a population that excites granule cell axons and stimulates glutamate release onto Golgi cells. In the other model, ethanol acts indirectly by increasing spontaneous Golgi cell firing via inhibition of the Na(+)/K(+) ATPase, a quinidine-sensitive K(+) channel, and neuronal nitric oxide synthase. It was also demonstrated that a direct inhibitory effect of ethanol on tonic currents can be unmasked under conditions of low protein kinase C activity. In the last section, we briefly discuss studies on the chronic effect of ethanol on cerebellar GABA(A) receptor-mediated transmission and highlight potential areas where future research is needed.

Moderate prenatal alcohol exposure reduces plasticity and alters NMDA receptor subunit composition in the dentate gyrus.

Although it is well documented that heavy consumption of alcohol during pregnancy impairs brain development, it remains controversial whether moderate consumption causes significant damage. Using a limited access, voluntary consumption paradigm, we recently demonstrated that moderate prenatal alcohol exposure (MPAE) is associated with dentate gyrus-dependent learning and memory deficits that are manifested in adulthood. Here, we identified a novel mechanism that may underlie this effect of MPAE. We found that MPAE mice exhibit deficits in NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) in the dentate gyrus. Further, using semiquantitative immunoblotting techniques, we found that the levels of GluN2B subunits were decreased in the synaptic membrane, while levels of C2'-containing GluN1 and GluN3A subunits were increased, in the dentate gyrus of MPAE mice. These data suggest that MPAE alters the subunit composition of synaptic NMDARs, leading to impaired NMDAR-dependent LTP in the dentate gyrus.

Third trimester-equivalent ethanol exposure does not alter complex spikes and climbing fiber long-term depression in cerebellar Purkinje neurons from juvenile rats.

BACKGROUND: Studies indicate that exposure to ethanol (EtOH) during fetal development damages cerebellar Purkinje cells (PCs). PC proximal dendrites receive glutamatergic input from climbing fibers (CFs) originating at the inferior olive. CF input produces a characteristic response in PCs known as the complex spike (CS). During the first 2 weeks of life in rodents (equivalent to the human third trimester of pregnancy), CF-PC synapses undergo profound refinement. Here, we characterized the impact of EtOH exposure during this period on CF-evoked responses in PCs. METHODS: Using vapor chambers, neonatal rat pups and their mothers were exposed to air or EtOH for 4 h/d between postnatal day 2 (P2) and P12 (pup serum EtOH concentration, 0.16 g/dl). The function of CF-PC synapses was characterized using patch-clamp electrophysiological techniques in acute slices from the cerebellar vermis. Experiments were performed soon after EtOH withdrawal, when perisomatic CFs are still being eliminated (P15 to P17), and after weaning when CF dendritic translocation is almost complete (P21 to P34). RESULTS: Neither the baseline characteristics of the CS (Na(+) spike amplitude, area, coastline index, and afterhyperpolarization [AHP] amplitude) nor the type-1 metabotropic glutamate receptor (mGluR1)-mediated component of both the CS and AHP were significantly affected by EtOH exposure at P15 to P17 or P21 to P34. The mGluR1-dependent long-term depression (LTD) of CF-evoked excitatory postsynaptic currents was not significantly affected by EtOH exposure at P21 to P34. CONCLUSIONS: EtOH exposure during the third trimester equivalent neither affected basal characteristics of the CS nor CF-LTD at rat cerebellar PCs from juvenile rats.

First Report of Powdery Mildew (Podosphaera pannosa) of Roses in Sinaloa, Mexico.

Rose (Rosa spp.) is the most important ornamental plant cultivated in greenhouse and open fields in Mexico but its quality has been limited by powdery mildew (PM). High incidence and disease damage is common during winter in Sinaloa, Mexico (temperature range 18 to 25°C and prolonged episodes of relative humidity ≥90%). The fungus attacks leaves and flowers and grows abundantly on the pedicels, sepals, and receptacles, especially when the flower bud is unopened (2). Field advisors in Mexico have referred to Sphaerotheca pannosa (Wallr. ex Fr.) Lév. as a causal agent of the disease. However, there has not been solid scientific evidence to support this statement. Morphometric and molecular analysis were conducted to elucidate the identity of the fungal isolates collected from 2012 through 2013 in northern Sinaloa. PM specimens included eight different rose varieties. Conidiophores and conidia were observed under a compound microscope. The mycelium had a mean diameter of 4.7 to 6.0 µm; conidiophores (Euoidium type) 2 to 5 celled, occasionally 6 celled emerged from the superficial mycelium; conidiophores were unbranched with conidia produced in chains from the apex. The average length of the conidiophores was 54.9 to 98.0 µm; the foot cell of the conidiophores was straight and was 24.9 to 53.6 µm long with a diameter from 8.2 to 9.8 µm across its medium part. Conidia originated from unswollen conidiogenous cells, with fibrosin bodies, formed in long chains, and were cylindrical to ovoid, 25.8 to 30.4 µm long and 13.9 to 17.3 µm wide. The outline of the conidial chains was crenate. Conidia exhibited a slight constriction at one end. The germ tubes emerged from a shoulder of the conidia. The outer wall of partially collapsed conidia showed longitudinal and transversal wrinkling and slight constrictions at the ends; the terminal end of the conidia was concentrically ridged. For molecular characterization, the ITS region of the specimens was amplified with primers ITS1F and ITS4. Phylogenetic analysis was performed with MEGA 6.0 (bootstrap = 1,000) using Kimura 2 parameter (K2P) substitution model. The resulting phylogeny grouped our specimens (GenBank KM001665 to 69) within a clade of Podosphaera pannosa (Wall.: Fr.) de Bary (formerly known as Sphaerotheca pannosa) sequences (e.g., AB525938; bootstrap (1,000) = 98). Phylogenetic and morphometric data are in agreement with descriptions of the anamorphic P. pannosa (1,3). Morphological studies indicate that P. macularis (previously known as S. humuli) and P. pannosa are not indistinctly different (2). Phylogenetic analysis showed relationship to P. pannosa, but not to P. macularis. Typical symptoms caused by P. pannosa were observed. Morphological studies (4) reported the anamorph of P. pannosa on Rosa spp. in central Mexico. To date, no report exists on the molecular identification of P. pannosa associated to roses in northern Sinaloa, Mexico. Future research directions should focus on finding the teleomorph of the fungus to support its identity, and to explore disease management tools such as effective fungicides and developing resistant rose cultivars. References: (1) U. Braun et al. Page 13 in: The Powdery Mildews: A Comprehensive Treatise. APS Press, St. Paul, MN, 2002. (2) R. K. Horst. Compendium of Rose Diseases. APS Press, St. Paul, MN, 1983. (3) L. Leus et al. J. Phytopathol. 154:23, 2006. (4) Yañez-Morales et al. Some new reports and new species of powdery mildew from Mexico. Schlechtendalia 19:46, 2009.

Optogenetic stimulation of corticostriatal circuits improves behavioral flexibility in mice with prenatal alcohol exposure.

Fetal alcohol spectrum disorder (FASD) is the most common preventable form of developmental and neurobehavioral disability. Animal models have demonstrated that even low to moderate prenatal alcohol exposure (PAE) is sufficient to impair behavioral flexibility in multiple domains. Previously, utilizing a moderate limited access drinking in the dark paradigm, we have shown that PAE 1) impairs touchscreen pairwise visual reversal in male adult offspring 2) leads to small but significant decreases in orbitofrontal (OFC) firing rates 3) significantly increases dorsal striatum (dS) activity and 4) aberrantly sustains OFC-dS synchrony across early reversal. In the current study, we examined whether optogenetic stimulation of OFC-dS projection neurons would be sufficient to rescue the behavioral inflexibility induced by PAE in male C57BL/6J mice. Following discrimination learning, we targeted OFC-dS projections using a retrograde adeno-associated virus (AAV) delivered to the dS which expressed channel rhodopsin (ChR2). During the first four sessions of reversal learning, we delivered high frequency optogenetic stimulation to the OFC via optic fibers immediately following correct choice responses. Our results show that optogenetic stimulation significantly reduced the number of sessions, incorrect responses, and correction errors required to move past the early perseverative phase for both PAE and control mice. In addition, OFC-dS stimulation during early reversal learning reduced the increased sessions, correct and incorrect responding seen in PAE mice during the later learning phase of reversal but did not significantly alter later performance in control ChR2 mice. Taken together these results suggest that stimulation of OFC-dS projections can improve early reversal learning in PAE and control mice, and these improvements can persist even into later stages of the task days later. These studies provide an important foundation for future clinical approaches to improve executive control in those with FASD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Persistent pulmonary abnormalities after 18 months of SARS-CoV-2 pneumonia.

OBJECTIVE: To describe persistent pulmonary abnormalities detected on HRCT after 18 months of SARS-CoV-2 pneumonia, and to determine their extension and correlation with pulmonary function. PATIENTS AND METHODS: A prospective cross-sectional study with an initial cohort of 90 patients in follow-up due to persisting lung abnormalities on imaging, functional respiratory impairment and/or respiratory symptoms. Of these, 31 (34%) were selected for analysis due to the persistence of their lung abnormalities on HRCT at 18 months after infection. A double reading was performed for each HRCT (62 observations). RESULTS: Of the 31 patients included: 20 (65%) were men; mean age was 67 years; 17 (55%) were smokers/ex-smokers. The mean hospitalisation time was 38 days. Eighteen (58%) patients were admitted to intensive care units. Five patients (16%) suffered an acute pulmonary thromboembolism and three (9.7%) had a pneumothorax. The mean time between the onset of pneumonia and the follow-up HRCT was 20.34 months. Nineteen percent of patients suffered from total lung function abnormalities; and ground-glass opacities and reticulation were present in 12% and 4.5% respectively. The findings of the 62 readings were: ground-glass opacities (100%), reticulation (83%), subpleural curvilinear lines (62%), parenchymal bands (34%), traction bronchiectasis (69%), displacement of vessels/fissures (46%) and honeycombing (4.9%). Pulmonary function 18 months after the acute episode revealed a mean FVC of 92% of predicted value, with an FVC < 80% of predicted value in 11 patients (35.4%). Mean DLCO was 71% of predicted value, with a DLCO < 80% in 22 patients (70%). We observed a statistically significant relationship between total lung function abnormalities on HRCT and FVC (P < 0.05), and a trend towards statistical significance with DLCO (P = 0.051); there was a statistically significant relationship between the presence of ground-glass opacities and FEV1/FVC (P < 0.01). The relationships between reticulation and FVC, FVC%, FEV1, FEV1% and DLCO% were also considered statistically significant (P < 0.05). CONCLUSION: Persistent interstitial lung abnormalities are seen on HRCT for a subset of patients infected with SARS-CoV-2 pneumonia. Seventy percent of these patients suffered a slight decrease in DLCO.

Maternal alcohol drinking patterns predict offspring neurobehavioral outcomes.

The timing, rate, and quantity of gestational alcohol consumption, collectively referred to here as Maternal Drinking Patterns (MDPs), are of known importance to fetal developmental outcomes. However, few studies have directly evaluated the impact of MDPs on offspring behavior. To do so, we used specialized equipment to record the precise amount and timing of alcohol consumption in pregnant dams, and then characterized MDPs using Principle Component Analysis (PCA). We next tested offspring on behaviors we have previously identified as impacted by prenatal alcohol exposure, and evaluated them where possible in the context of MDPs. Male alcohol exposed mice exhibited longer latencies to fall on the rotarod compared to their controls, which we attribute to a delayed decrease in body weight-gain. This effect was mediated by MDPs within the first 15 min of alcohol access (i.e. alcohol frontloading), where the highest performing male offspring came from dams exhibiting the highest rate of alcohol frontloading. Female alcohol exposed mice displayed reduced locomotor activity in the open field compared to controls, which was mediated by MDPs encompassing the entire drinking session. Surprisingly, total gestational alcohol exposure alone was not associated with any behavioral outcomes. Finally, we observed allodynia in alcohol exposed mice that developed more quickly in males compared to females, and which was not observed in controls. To our knowledge, this report represents the highest resolution assessment of alcohol drinking throughout gestation in mice, and one of few to have identified relationships between specific alcohol MDPs and neurobehavioral outcomes in offspring.