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Kinetoplastid parasites are responsible for serious diseases in humans and livestock such as Chagas disease and sleeping sickness (caused by Trypanosoma cruzi and Trypanosoma brucei, respectively), and the different forms of cutaneous, mucocutaneous and visceral leishmaniasis (produced by Leishmania spp). The limited number of antiparasitic drugs available together with the emergence of resistance underscores the need for new therapeutic agents with novel mechanisms of action. The use of agents binding to surface glycans has been recently suggested as a new approach to antitrypanosomal design and a series of peptidic and non-peptidic carbohydrate-binding agents have been identified as antiparasitics showing efficacy in animal models of sleeping sickness. Here we provide an overview of the nature of surface glycans in three kinetoplastid parasites, T. cruzi, T. brucei and Leishmania. Their role in virulence and host cell invasion is highlighted with the aim of identifying specific glycan–lectin interactions and carbohydrate functions that may be the target of novel carbohydrate-binding agents with therapeutic applications.
Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos.
Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders.
In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02).
It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.
The Murcia Twin Registry (MTR) is the only population-based registry in Spain. Created in 2006, the registry has been growing more than a decade to become one of the references for twin research in the Mediterranean region. The MTR database currently comprises 3545 adult participants born between 1940 and 1977. It also holds a recently launched satellite registry of university students (N = 204). Along five waves of data collection, the registry has gathered questionnaire and anthropometric data, as well as biological samples. The MTR keeps its main research focus on health and health-related behaviors from a public health perspective. This includes lifestyle, health promotion, quality of life or environmental conditions. Future short-term development points to the expansion of the biobank and the continuation of the collection of longitudinal data.
Hurricane Maria caused catastrophic damage in Puerto Rico, increasing the risk for morbidity and mortality in the post-impact period. We aimed to establish a syndromic surveillance system to describe the number and type of visits at 2 emergency health-care settings in the same hospital system in Ponce, Puerto Rico.
We implemented a hurricane surveillance system by interviewing patients with a short questionnaire about the reason for visit at a hospital emergency department and associated urgent care clinic in the 6 mo after Hurricane Maria. We then evaluated the system by comparing findings with data from the electronic medical record (EMR) system for the same time period.
The hurricane surveillance system captured information from 5116 participants across the 2 sites, representing 17% of all visits captured in the EMR for the same period. Most visits were associated with acute illness/symptoms (79%), followed by injury (11%). The hurricane surveillance and EMR data were similar, proportionally, by sex, age, and visit category.
The hurricane surveillance system provided timely and representative data about the number and type of visits at 2 sites. This system, or an adapted version using available electronic data, should be considered in future disaster settings.
The aim of this study was to describe individuals seeking care for injury at a major emergency department (ED) in southern Puerto Rico in the months after Hurricane Maria on September 20, 2017.
After informed consent, we used a modified version of the Natural Disaster Morbidity Surveillance Form to determine why patients were visiting the ED during October 16, 2017–March 28, 2018. We analyzed visits where injury was reported as the primary reason for visit and whether it was hurricane-related.
Among 5 116 patients, 573 (11%) reported injury as the primary reason for a visit. Of these, 10% were hurricane-related visits. The most common types of injuries were abrasions, lacerations, and cuts (43% of all injury visits and 50% of hurricane-related visits). The most common mechanisms of injury were falls, slips, trips (268, 47%), and being hit by/or against an object (88, 15%). Most injury visits occurred during the first 3 months after the hurricane.
Surveillance after Hurricane Maria identified injury as the reason for a visit for about 1 in 10 patients visiting the ED, providing evidence on the patterns of injuries in the months following a hurricane. Public health and emergency providers can use this information to anticipate health care needs after a disaster.
Este artículo discute las evidencias de violencia perimortem y las relaciones espaciales de partes esqueletales recuperadas en la Estructura Funeraria 4 del sector I del sitio de Punta de la Peña 9 (Antofagasta de la Sierra, Catamarca, Argentina). Esta estructura, que contiene varios individuos correspondientes a la segunda mitad del primer milenio dC, presenta evidencias de haber sido reabierta en al menos dos eventos de inhumación, lo que produjo alteraciones de los patrones mortuorios y desarticulación de partes anatómicas. Estas reaperturas se relacionan con una dinámica particular de las prácticas de entierro en Antofagasta de la Sierra. Se trata del primer entierro secundario múltiple identificado para el área, el cual incluye a su vez los primeros casos de trauma intencional y muerte en condiciones violentas. Se inhumaron al menos siete individuos de ambos sexos y de distintos rangos de edad, cuatro de los cuales presentan lesiones perimortem en los cráneos, evidencia directa de situaciones de violencia interpersonal para los grupos agropastoriles de este período.
Canalplasty for auditory exostoses is reserved for symptomatic patients. This study reviewed the outcomes of our technique regarding cicatricial stenosis.
A chart review was conducted on patients undergoing canalplasty for auditory exostoses between 2002 and 2017. The surgical technique is described.
The study comprised 43 adults (50 operated ears). Exostoses were bilateral in 40 cases (94 per cent) and occlusive in 33 (66 per cent). After drilling, the external auditory meatus was covered with a graft in 34 cases (68 per cent) and a silicone sheet was used in 32 (64 per cent). Cicatricial stenosis appeared in eight cases (16 per cent). Skin grafts were not used in six of these eight cases (p < 0.04), and silicone sheets were used only in one of these eight (p < 0.01).
Canalplasty is challenging because of its potential complications. Our data showed that the use of skin grafts and silicone sheets to cover the bared external auditory meatus was associated with a lower rate of cicatricial stenosis.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
From simple averaging to more sophisticated registration and restoration strategies, such as super-resolution (SR), there exist different computational techniques that use a series of images of the same object to generate enhanced images where noise and other distortions have been reduced. In this work, we provide qualitative and quantitative measurements of this enhancement for high-angle annular dark-field scanning transmission electron microscopy imaging. These images are compared in two ways, qualitatively through visual inspection in real and reciprocal space, and quantitatively, through the calculation of objective measurements, such as signal-to-noise ratio and atom column roundness. Results show that these techniques improve the quality of the images. In this paper, we use an SR methodology that allows us to take advantage of the information present in the image frames and to reliably facilitate the analysis of more difficult regions of interest in experimental images, such as surfaces and interfaces. By acquiring a series of cross-sectional experimental images of magnetite (Fe3O4) thin films (111), we have generated interpolated images using averaging and SR, and reconstructed the atomic structure of the very top surface layer that consists of a full monolayer of Fe, with topmost Fe atoms in tetrahedrally coordinated sites.
Using validated psychological assessment instruments, this study examined the psychological distress associated with potential language barriers experienced by over 135 000 Puerto Rican residents who either temporarily or permanently migrated to the continental United States with the landfall of Hurricane Maria in 2017.
Participants were Puerto Rican residents (n = 107) who remained in Puerto Rico (control) or left the island for at least 3 months because of Hurricane Maria (migrants). Participants completed an online survey in their preferred language (Spanish or English), which assessed self-reported English language proficiency, Kessler Psychological Distress Scale (K6), Posttraumatic Stress Disorder Checklist for DSM 5, Patient Health Questionnaire 9-item depression scale, and the Generalized Anxiety Disorder 7-item scale. It was hypothesized that migrants with lower self-reported English proficiency would have comparatively higher indices of post-disaster distress than those with a higher proficiency.
Dividing the migrant group by preferred language for questionnaire completion, the Fisher’s exact test showed significant differences in prevalence of severe mental distress, as defined by K6 scores above 13, between the Spanish-preferring migrants (30.4%), English-preferring migrants (0%), and controls (9.6%).
Our results support a possible correlation between decreased language proficiency in post-disaster migrants and a higher risk factor for severe mental distress.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.