A rapid motor task-based screening tool for parkinsonism in community-based studies

The prevalence of parkinsonism in developing countries is largely unknown due to difficulty in ascertainment because access to neurologists is often limited. Develop and validate a parkinsonism screening tool using objective motor task-based tests that can be administered by non-clinicians. In a cross-sectional population-based sample from South Africa, we evaluated 315 adults, age \u3e40, from an Mn-exposed (smelter) community, using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3), Purdue grooved pegboard, and kinematic-UPDRS3-based motor tasks. In 275 participants (training dataset), we constructed a linear regression model to predict UPDRS3. We selected motor task summary measures independently associated with UPDRS3 ( \u3c 0.05). We validated the model internally in the remaining 40 participants from the manganese-exposed community (test dataset) using the area under the receiver operating characteristic curve (AUC), and externally in another population-based sample of 90 participants from another South African community with only background levels of environmental Mn exposure. The mean UPDRS3 score in participants from the Mn-exposed community was 9.1 in both the training and test datasets (standard deviation = 6.4 and 6.1, respectively). Together, 57 (18.1%) participants in this community had a UPDRS3 ≥ 15, including three with Parkinson\u27s disease. In the non-exposed community, the mean UPDRS3 was 3.9 (standard deviation = 4.3). Three (3.3%) had a UPDRS3 ≥ 15. Grooved pegboard time and mean velocity for hand rotation and finger tapping tasks were strongly associated with UPDRS3. Using these motor task summary measures and age, the UPDRS3 predictive model performed very well. In the test dataset, AUCs were 0.81 (95% CI 0.68, 0.94) and 0.91 (95% CI 0.81, 1.00) for cut points for neurologist-assessed UPDRS3 ≥ 10 and UPDRS3 ≥ 15, respectively. In the external validation dataset, the AUC was 0.85 (95% CI 0.73, 0.97) for UPDRS3 ≥ 10. AUCs were 0.76-0.82 when excluding age. A predictive model based on a series of objective motor tasks performs very well in assessing severity of parkinsonism in both Mn-exposed and non-exposed population-based cohorts

An evidence synthesis of covert online strategies regarding intimate partner violence

This systematic review synthesises evidence of how people use the internet to deploy covert strategies around escaping from, or perpetrating, Intimate Partner Violence (IPV). Online tools and services can facilitate individuals leaving abusive relationships, yet they can also act as a barrier to departure. They may also enable abusive behaviours. A comprehensive literature search of published and unpublished studies in electronic databases was conducted. Two researchers independently screened abstracts and full-texts for study eligibility and evaluated the quality of included studies. The systematic review includes 22 studies (9 qualitative and 11 cross-sectional studies, a Randomized control trial and a Non-randomized study), published between 2004 and 2017. Four covert behaviours linked to covert online strategies around IPV were identified: presence online, granular control, use of digital support tools and services, stalking and surveillance. The same technology that provides individuals with easy access to information and supportive services related to IPV, such as digital devices, tools and services, also enables perpetrators to monitor or harass their partners. This review takes a rigorous interdisciplinary approach to synthesising knowledge on the covert strategies adopted by people in relation to IPV. It has particular relevance to practitioners who support survivors in increasing awareness of the role of digital technologies in IPV, to law enforcement agencies in identifying new forms of evidence of abuse, and in enabling designers of online/social media applications to take the needs and vulnerabilities of IPV survivors into account

Severity of parkinsonism associated with environmental manganese exposure

BACKGROUND: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020. METHODS: A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an accelerometry-based kinematic test and a grooved pegboard test. We compared performance on the UPDRS3, grooved pegboard, and the accelerometry-based kinematic test between the settlements using linear regression, adjusting for covariates. We also measured airborne PM RESULTS: Mean PM CONCLUSIONS: Environmental airborne Mn exposures at levels substantially lower than current occupational exposure thresholds in the United States may be associated with clinical parkinsonism

Subduction Initiation Recorded in the Dadeville Complex of Alabama and Georgia, Southeastern United States

The Dadeville Complex of Alabama and Georgia (southeastern United States) represents the largest suite of exposed mafic-ultramafic rocks in the southern Appalachians. Due to poor preservation, chemical alteration, and tectonic reworking, a specific tectonic origin for the Dadeville Complex has been difficult to deduce. We obtained new whole-rock and mineral geochemistry coupled with zircon U-Pb geochronology to investigate the magmatic and metamorphic processes recorded by the Dadeville Complex, as well as the timing of these processes. Our data reveal an up-stratigraphic evolution in the geochemistry of the volcanic rocks, from forearc basalts to boninites. Our new U-Pb zircon crystallization data—obtained from three amphibolite samples—place the timing of forearc/protoarc volcanism no later than ca. 467 Ma. New thermobarometry suggests that the Dadeville Complex rocks subsequently experienced deep, high-grade metamorphism, at pressure-temperature conditions of \u3e7 kbar and \u3e760 °C. The data presented here support a model for formation of the Dadeville Complex in the forearc region of a subduction zone during subduction initiation and protoarc development, followed by deep burial/underthrusting of the complex during orogenesis

Genetic effects on alcohol dependence risk : Re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47% (95% CI 28–55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0–14) to shared environmental factors, and 53% (95% CI 45–63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD

El género Porphyra (Bangiaceae, Rhodophyta) en la costa del Pacífico de México. IV. Porphyra pendula E.Y. Dawson

The occurrence and seasonality of Porphyra pendula E.Y. Dawson (Bangiaceae, Rhodophyta) in its macroscopic phase, is reported for the Pacific coast of Mexico, based on sampling conducted during November 2002 to May 2003, and specimens housed in national and foreign herbaria. We describe in detail the vegetative and reproductive structure of the thallus, as well as its habitat and geographic distribution of the species. The specimens of P. pendula from Isla Carmen, Los Planes and Calerita, represent newly reported populations from the Gulf of California. Based on data obtained from herbarium specimens and observations of a population in Calerita, Baja California Sur, we concluded that P. pendula, in its macroscopic phase, is a seasonal species occurring from January to March (winter to the beginning of spring).Se registra la presencia y estacionalidad de la fase macroscópica de Porphyra pendula E.Y. Dawson (Bangiaceae, Rhodophyta) para la costa del Pacífico de México, con base en material recolectado durante el periodo de noviembre del 2002 a mayo del 2003 y un análisis de ejemplares depositados en herbarios nacionales y extranjeros. Se describen en forma detallada los caracteres morfo-anatómicos y estructuras reproductoras de los talos; así como su hábitat y distribución geográfica. Los especímenes de P. pendula de Isla Carmen, Los Planes y Calerita representan poblaciones nuevas de ésta especie en el Golfo de California. Considerando la revisión de especimenes de herbario y el seguimiento de una población en Calerita, Baja California Sur, se determinó que la estacionalidad de P. pendula en su fase macroscópica es de enero a marzo (invierno-principios de primavera)

Patterns of gene recombination shape var gene repertoires in Plasmodium falciparum: comparisons of geographically diverse isolates

BACKGROUND: Var genes encode a family of virulence factors known as PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) which are responsible for both antigenic variation and cytoadherence of infected erythrocytes. Although these molecules play a central role in malaria pathogenesis, the mechanisms generating variant antigen diversification are poorly understood. To investigate var gene evolution, we compared the variant antigen repertoires from three geographically diverse parasite isolates: the 3D7 genome reference isolate; the recently sequenced HB3 isolate; and the IT4/25/5 (IT4) parasite isolate which retains the capacity to cytoadhere in vitro and in vivo. RESULTS: These comparisons revealed that only two var genes (var1csa and var2csa) are conserved in all three isolates and one var gene (Type 3 var) has homologs in IT4 and 3D7. While the remaining 50 plus genes in each isolate are highly divergent most can be classified into the three previously defined major groups (A, B, and C) on the basis of 5' flanking sequence and chromosome location. Repertoire-wide sequence comparisons suggest that the conserved homologs are evolving separately from other var genes and that genes in group A have diverged from other groups. CONCLUSION: These findings support the existence of a var gene recombination hierarchy that restricts recombination possibilities and has a central role in the functional and immunological adaptation of var genes

Biallelic Loss-of-Function Variants in BICD1 Are Associated with Peripheral Neuropathy and Hearing Loss

Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype