Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.     

Increased Trailing Limb Angle is Associated with Regular and Stable Trunk Movements in Patients with Hemiplegia

ObjectivesIn post-stroke patients, shifts in the center of gravity may affect joint movement patterns of the paraplegic lower limb during walking. The impact of changes in ankle dorsiflexion angle and trailing limb angle due to slight weight-shifting is unknown. This study aimed to investigate the effect of the abovementioned parameters on gait characteristics measured by trunk acceleration.Materials and methodsDuring walking, the ankle dorsiflexion angle and trailing limb angle were assessed using two-dimensional motion analysis. Shifts in the center of gravity were assessed to evaluate symmetry, regularity, and sway of trunk movements by calculating the harmonic ratio, autocorrelation coefficient, and root mean square using a wearable trunk accelerometer.ResultsAnkle dorsiflexion angle showed a significant negative correlation with the root mean square of the anteroposterior axis (r = -0.460, p = 0.005). Trailing limb angle was significantly correlated with the autocorrelation coefficient of the vertical axis (r = 0.585, p < 0.001) and root mean square of the vertical (r = -0.579, p < 0.001), mediolateral (r = -0.474, p = 0.004), and anteroposterior axes (r = -0.548, p = 0.001). Trailing limb angle was a significant predictor (autocorrelation coefficient vertical axis, p = 0.001; root mean square vertical axis, p = 0.001; mediolateral axis, p = 0.007; anteroposterior axis, p = 0.001).ConclusionsTrailing limb angle can indicate the acquisition of forward propulsion during walking; an increase in it may contribute to improvements of the regular vertical movement ability and stability of the center of gravity sway.     

The emergence of human Powassan virus infection in North America

Powassan virus (POWV) is a tickborne flavivirus discovered in Ontario, Canada in 1958 that causes long-term neurological sequelae in about half the reported cases and death in a little more than 10 % of cases. The incidence of POWV disease is rising in the United States but there is limited understanding of the scope and causes of recent changes in POWV epidemiology. We focus on quantifying the increase in human POWV disease incidence and infection prevalence in the United States. We also examine differences in the frequency of symptomatic cases and asymptomatic or mildly symptomatic cases, as well as limitations in national and state surveillance for POWV infection. We searched SCOPUS for all articles containing original POWV prevalence research, case studies, or literature reviews published in English. Case studies were supplemented by Morbidity and Mortality Weekly Report POWV data from the Centers for Disease Control and Prevention (CDC) and surveillance information from state health department websites. An increase in the number of POWV cases has been reported in the United States over the past 50 yr, and the geographic range of human POWV cases has expanded. The age distribution of symptomatic POWV cases has shifted, with significantly more individuals over 40 yr old being diagnosed after 1998. The emergence of POWV is due in large part to: (i) a change in transmission of POWV from a vector that rarely bites people (Ixodes cookei) to a new vector that often bites people (Ixodes scapularis) and has expanded its geographic range, (ii) enhanced surveillance efforts for arboviruses, and (iii) a greater awareness of POWV infection.     

Bio-accumulation and health risk assessment of heavy metals in different edible fish species from Hurghada City,Red Sea,Egypt

BackgroundHeavy metal contamination has become a serious issue in this century especially detected in fish organs. Due to the presence of radioactive compounds in agricultural and sewage effluent, which destroys aquatic ecosystems, threatening human livelihoods. Health hazards associated with low and high consumption consumers assessed in five commercial fish species collected from Hurghada City, Egypt, during winter and summer, 2020. Atomic absorption spectrophotometer technique used for determination heavy meals in different organs and expressed as μg/g wet weight.ResultsHeavy metal concentrations in muscle ranged between:(0.054–0.109), (0.260–1.043), (0.264–0.897), (5.895–11.898), (0.381–0.970), (13.582–29.133) and (0.332–0.589) µg/g for Cd, Pb, Mn, Zn, Cu, Fe and Ni respectively, which were lower than those of gills and liver. These concentrations were within WHO, FAO/WHO, and EU standards. Consumption of edible species was lower than the (TDIs) established by the (JECFA) and Egyptian Standards. Even though THQ and TTHQ values were < 1 while, in children with highly consumer were> 1.ConclusionThis study concluded that intake of Red Sea fish is safe for human health. It is critical for consumers to be aware of the consequences of excessive fish consumption, particularly children with highly consumer, which represent possible health risks.     

Genomic and phenotypic delineation of congenital microcephaly

PurposeCongenital microcephaly (CM) is an important birth defect with long term neurological sequelae. We aimed to perform detailed phenotypic and genomic analysis of patients with Mendelian forms of CM.MethodsClinical phenotyping, targeted or exome sequencing, and autozygome analysis.ResultsWe describe 150 patients (104 families) with 56 Mendelian forms of CM. Our data show little overlap with the genetic causes of postnatal microcephaly. We also show that a broad definition of primary microcephaly —as an autosomal recessive form of nonsyndromic CM with severe postnatal deceleration of occipitofrontal circumference—is highly sensitive but has a limited specificity. In addition, we expand the overlap between primary microcephaly and microcephalic primordial dwarfism both clinically (short stature in >52% of patients with primary microcephaly) and molecularly (e.g., we report the first instance of CEP135-related microcephalic primordial dwarfism). We expand the allelic and locus heterogeneity of CM by reporting 37 novel likely disease-causing variants in 27 disease genes, confirming the candidacy of ANKLE2, YARS, FRMD4A, and THG1L, and proposing the candidacy of BPTF, MAP1B, CCNH, and PPFIBP1.ConclusionOur study refines the phenotype of CM, expands its genetics heterogeneity, and informs the workup of children born with this developmental brain defect.     

Residual survival and local dispersal drive reinfestation by Triatoma dimidiata following insecticide application in Guatemala

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted by triatomine insect vectors. In Guatemala, insecticide spraying is an integral part of management of the main vector, Triatoma dimidiata. Spraying typically has low efficacy, which may be due to incomplete elimination from infested houses, within-village dispersal, or influx from other villages or sylvan environments. To evaluate how these mechanisms contribute to reinfestation, we conducted a time-course analysis of T. dimidiata infestation, abundance and household genetic structure in two nearby villages in Jutiapa, Guatemala; houses in the first village were surveyed, treated with insecticide if infested and then re-surveyed at eight and 22 months following spraying, while the second village served as an untreated control to quantify changes associated with seasonal dispersal. Insects were genotyped at 2–3000 SNP loci for kinship and population genetic analyses. Insecticide application reduced overall infestation and abundance, while the untreated village was stable over time. Nevertheless, within two years 35.5% of treated houses were reinfested and genetic diversity had largely recovered. Insects collected from reinfested houses post-spraying were most closely related to pre-spray collections from the same house, suggesting that infestations had not been fully eliminated. Immigration by unrelated insects was also detected within a year of spraying; when it occurred, dispersal was primarily local from neighboring houses. Similar dispersal patterns were observed following the annual dispersal season in the untreated village, with high-infestation houses serving as sources for neighboring homes. Our findings suggest that the efficacy of pyrethroid application is rapidly diminished by both within-house breeding by survivors and annual cycles of among-house movement. Given these patterns, we conclude that house structural improvements, an integral part of the Ecohealth approach that makes houses refractory to vector colonization and persistence, are critical for long-term reduction of T. dimidiata infestation.     

Review of the environmental prenatal exposome and its relationship to maternal and fetal health

Environmental chemicals comprise a major portion of the human exposome, with some shown to impact the health of susceptible populations, including pregnant women and developing fetuses. The placenta and cord blood serve as important biological windows into the maternal and fetal environments. In this article we review how environmental chemicals (defined here to include man-made chemicals [e.g., flame retardants, pesticides/herbicides, per- and polyfluoroalkyl substances], toxins, metals, and other xenobiotic compounds) contribute to the prenatal exposome and highlight future directions to advance this research field. Our findings from a survey of recent literature indicate the need to better understand the breadth of environmental chemicals that reach the placenta and cord blood, as well as the linkages between prenatal exposures, mechanisms of toxicity, and subsequent health outcomes. Research efforts tailored towards addressing these needs will provide a more comprehensive understanding of how environmental chemicals impact maternal and fetal health.