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OBJECTIVES/GOALS: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. This study examined the relationship between CD4 nadir and brain atrophy. METHODS/STUDY POPULATION: Fifty-nine people with HIV participated in the cross-sectional study (mean age, 56.5 ± 5.8; age range, 41-69; 15 females; 46 African-Americans). High resolution structural MRI images were obtained using a 3T Siemens scanner. From a comprehensive 7-domain neuropsychological test battery, a global deficit score (GDS) and HAND diagnoses were determined for each participant. The correlation between CD4 nadir (the lowest ever lymphocyte CD4 count) and cortical thickness was investigated using a vertex-wise non-parametric approach with a conservative statistical threshold of p < 0.05 (FWE-corrected). RESULTS/ANTICIPATED RESULTS: Out of the 59 participants, 12 met standard Frascati criteria for asymptomatic neurocognitive impairment (ANI) and two met the criteria for mild neurocognitive disorder (MND). Across all participants, low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions. Higher GDS (indicating worse global neurocognitive function) was associated with bilateral frontal cortical thinning, and the association largely persisted in the subset of participants who did not meet HAND criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. This spatial profile might contribute to the prevalence/phenotypes of HAND in the cART era, such as the frequently observed deficits in the executive domain.
The Large and Small Magellanic Cloud (LMC and SMC) are the most luminous dwarf galaxy satellites of the Milky Way. Thanks to their close proximity (50-60 kpc), they provide one of the best opportunities to study in detail the kinematics of resolved stellar populations in an interacting pair of galaxies. Large photometric surveys like the ongoing Gaia mission and the near-infrared VISTA survey of the Magellanic Cloud system (VMC) will have a significant impact on our insight into the Magellanic system. We have combined the individual strengths of VMC and Gaia DR2 data to improve our understanding of the internal kinematics of the galaxies. In this study, we present results from our ongoing project dedicated to measure and analyse the proper motions of large samples of stars across the Magellanic Clouds, efficiently removing Milk Way foreground stars utilising distances derived with the StarHorse code.
Non-suicidal self-injury (NSSI) behaviors are self-injurious behaviors inflicted without intending death. Literature has shown the relationship between stressful life events (SLE) and NSSI behaviors. The Strengths and Difficulties Questionnaire-Dysregulation Profile (SDQ-DP) is defined as an index of self-regulatory problems, related to higher risk for suicidal ideation and attempts in adolescents. In this study the relationship between SDQ-DP and NSSI behaviors, mediated by SLE in a clinical sample of children and adolescents is analyzed. A cross-sectional study was conducted on 239 subjects (aged from 11 to 17) to test the mediation model. SDQ-DP significantly correlates with NSSI behaviors (Wald = 6.5477, p = .0105); SDQ-DP significantly correlates with SLE (T = 5.7229, p < .001); SLE significantly correlates NSSI behaviors, and the relation remains significant whilst controlling for SDQ-DP (Wald = 4.1715, p = .041); the relation between SDQ-DP and NSSI behaviors stops being significant whilst controlling for the potential mediator (SLE) (Wald = 2.9951, p = .0835). Study of indirect effect supports the mediation model (.0585 CI [.0016, .1266]). Findings are compatible with the complete mediation scenario. These results point out the importance of self-regulatory problems in coping strategies with regards to SLE and the development of NSSI behaviors.
To determine the prevalence of and modifiable factors associated with prediabetes in the Comcáac Indians.
Cross-sectional study where prediabetes was defined using fasting plasma glucose, 2 h plasma glucose and glycated Hb (HbA1c). Physical, anthropometric and biochemical measurements, medical record, socio-economic, dietary and physical activity information were collected. The modifiable factors associated with prediabetes were assessed using multiple logistic regression.
Comcáac Indian communities of Punta Chueca and El Desemboque, Sonora, Mexico.
Adults (n 227) aged 20 years or older.
The sex- and age-adjusted prevalence (95 % CI) of prediabetes was 47·1 (40·8, 53·5) % in the overall population; age-adjusted prevalence was 47·3 (35·6, 59·0) % in men and 46·7 (39·1, 54·3) % in women. The modifiable factors associated with a risk of prediabetes (OR; 95 % CI) were light-intensity physical activity (per 1 h/week increase: 1·04; 1·01, 1·07) and insulin resistance (homeostasis model assessment of insulin resistance score >6·1 v. <4·1: 4·62; 1·37, 15·51). Increased consumption of a traditional dietary pattern based on fish and seafood, low-fat cereals, fruits and vegetables was a protective factor (0·49; 0·31, 0·79). All variables were modelled together and adjusted for age and sex.
The high prediabetes prevalence found in the Comcáac community is alarming because it represents a large number of people who are at risk for type 2 diabetes. The identification of modifiable factors associated with prediabetes that are specific to this population may be useful for designing effective strategies to prevent prediabetes.
There is a need for clinical tools to identify cultural issues in diagnostic assessment.
To assess the feasibility, acceptability and clinical utility of the DSM-5 Cultural Formulation Interview (CFI) in routine clinical practice.
Mixed-methods evaluation of field trial data from six countries. The CFI was administered to diagnostically diverse psychiatric out-patients during a diagnostic interview. In post-evaluation sessions, patients and clinicians completed debriefing qualitative interviews and Likert-scale questionnaires. The duration of CFI administration and the full diagnostic session were monitored.
Mixed-methods data from 318 patients and 75 clinicians found the CFI feasible, acceptable and useful. Clinician feasibility ratings were significantly lower than patient ratings and other clinician-assessed outcomes. After administering one CFI, however, clinician feasibility ratings improved significantly and subsequent interviews required less time.
The CFI was included in DSM-5 as a feasible, acceptable and useful cultural assessment tool.
Chemical genetics describes the use of molecules as “chemical probes” to investigate biological systems [1–3]. In contrast with traditional genetics, in which gene knockouts on the level of the DNA are used, chemical genetics uses biologically active small molecules to directly attenuate the corresponding biological macromolecular (usually protein) product. Thus, the ready availability of bioactive small molecules is of crucial importance in chemical genetics studies. Such small molecules can be identified by screening compound collections (libraries) in suitably designed assays. This chapter describes the use of diversity-oriented synthesis (DOS) to prepare structurally diverse small molecule libraries. Structurally diverse libraries show a greater variety in not only their physiochemical properties but also, and of most relevance here, in their biological activities. Herein we describe some of the most effective strategies that have been used in DOS library design and preparation.
Small molecules, chemical genetics, and chemical genomics
Chemical genetics experiments can be performed in either a forward or a reverse sense (Figure 4.1). The first step of both approaches requires the identification of a small molecule that either induces a desired phenotype (forward chemical genetics) or modulates the function of a specific protein of interest (reverse chemical genetics). Thus, in the former case, investigations proceed from phenotype to protein, whereas in the latter case, investigations progress from protein to phenotype.
Sleep is a process occurring in all living animals. Although it is still controversial whether insects and other animals sleep alike; there is no doubt that they rest, as many studies in Drosophila melanogaster have shown. In this context, several seminal studies have documented species-dependent variations in sleep patterns. These findings along with obvious non-learned characteristics of sleep in general, such as the total time of sleep, the alternating NREM–REM sleep pattern, among many others, suggest strong regulation by genes. Clearly, the way genes may influence sleep physiology is via proteins. Hence, the importance of proteins in the regulation of sleep is observed in every minute event occurring to trigger or to maintain sleep. In this chapter we discuss families of proteins that are grouped by their effect on food ingestion, immunological response, trophic activity, and intracellular signaling, all of them affecting the sleep–waking cycle. Although we do not fully discuss the mechanisms of action, we put our effort in highlighting their effects on sleep. Along with the proteins and their effects we have listed those genes encoding them. We also show examples of proteins and the way they affect sleep. Hence, we hope that the overall message that readers will gather from this chapter is the importance of several proteins in the regulation of sleep. Also, by observing the effects of each family of proteins we can infer at least some functions of sleep and, finally, that sleep is a multigenic trait.
Lactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, was characterized in a previous study. The objective of this study was to evaluate its sensitivity to antibiotics and its potential toxicity and translocation ability after oral administration to mice. For this puropose, 40 Balb/C mice were divided in two groups (n=20 per group). One group was treated orally with 1010 colony forming units (cfu)/mouse/day of Lb. fermentum CECT5716 during 28 d. The other group only received the excipient and was used as control. Food intake, body weight, bacterial translocation and different biochemical and haematological parameters were analysed. Oral administration of Lb. fermentum CECT5716 to mice had no adverse effects on mice. There were no significant differences in body weight or food intake between control and probiotic-treated mice. No bacteraemia was observed and there was no treatment-associated bacterial translocation to liver or spleen. Stress oxidative markers were not different in control and probiotic-treated mice. These results suggest that the strain Lb. fermentum CECT5716 is non-pathogenic for mice even in doses 10,000 times higher (expressed per kg of body weight) than those normally consumed by humans.
Extrinsic factors such as maternal microbiota, bacterial load of the environment, diet and medication modulate the intestinal microbiota. Maturation and function of the immune system is influenced by established gut microbiota. In this work we describe the immunological effects of the dietary deprivation of fermented foods of healthy volunteers. Significant decreases in faecal lactobacillus and total aerobes counts and concentration of short chain fatty acids were observed following deprivation of fermented food of the normal diet. Moreover, a decrease in phagocytic activity in leukocytes was observed after two weeks of restricted diet. Therefore, the dietary deprivation of fermented foods could induce a decrease in innate immune response that might affect the capacity to respond against infections. The ingestion of a probiotic product containing the strains Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711 or a standard yogurt containing a conventional starter Lactobacillus delbrueckii sp. bulgaricus counteracted the fall in the immune response, although the probiotic product was more effective than the standard yogurt.
Atelognathus nitoi is a microendemic leptodactylid frog restricted to the area surrounding the pond Laguna Verde in the Nahuel Huapi National Reserve, north-west Patagonia, Argentina. Its habitat is potentially threatened by a number of anthropogenic and natural factors. The aim of this study was to obtain basic knowledge of the biology and habitat of the species, which would be useful for selecting management measures to ensure its conservation. The area was surveyed during all four seasons in 1996 and 1997 and Laguna Verde was sampled intensively in winter and in summer. Atelognathus nitoi is distributed patchily. The preferred microhabitats of adults and juveniles are the most humid areas of the forest. Reproduction and larval development occurs only in lentic environments. Laguna Verde is the only known permanent waterbody suitable for reproduction every year. During rainy years reproduction can also take place in temporary ponds. Action towards the conservation of A. nitoi should be aimed at preserving both the terrestrial and aquatic habitats. Laguna Verde appears to be a key site for the A. nitoi source population and plays an essential part in the conservation of this species. In terrestrial habitats it is vital to preserve the heterogeneity of the lower strata in the forest. The knowledge gained through this study has allowed the authors to suggest protective measures to mitigate or eliminate the impact of certain stressors on the ecology of the species.
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