Characterization of field-scale spray drift deposition and non-target plant biological sensitivity: a corn herbicide (mesotrione/s-metolochlor) case study.

BACKGROUND: This work reports a combined, field-scale spray drift deposition and plant bioassay study for a pre-mixture of the herbicides mesotrione and s-metolachlor. Wind direction data and field dimensions were used to evaluate the potential for spray drift to bypass downwind sampling devices. Variability in resulting spray drift across downwind distances was assessed alongside wind speed measured at on-site weather stations. Measured wind angles were used to geometrically adjust traveled drift particle distances and enabling isolation of wind direction impact from wind speed. Further, the use of single and multiple in-field monitoring locations was compared to quantify the benefit of higher-resolution meteorological sampling. RESULTS: Generally, increased wind speed resulted in significantly greater herbicide deposition at distances proximal to the edge of the spray zone. According to the drift deposition curves that included wind speed data from single and multiple onsite weather stations, trials with relatively higher wind speeds were associated with greater spray drift deposition at relatively close sampling distances downwind from the application area. Only marginal improvement of linear mixed-effects model fit was observed when including data from three weather stations, compared to the fit from a single weather station or absence of weather data in the model. Using tomato and lettuce plant bioassay species, the overall no-effect distance was 3.0 m (10 ft). CONCLUSION: Results from this study are informative to refine pesticide risk assessment for non-target plants and indicate that a single weather station is sufficient to capture potential influential effects from wind speed and direction on spray drift. © 2022 Society of Chemical Industry.

The potential utility of smell testing to screen for neurodegenerative disorders.

INTRODUCTION: Loss of smell is a common early feature of neurodegenerative diseases including Alzheimer's and Parkinson's disease. Identifying these conditions in their early stages is important to understand more about early pathophysiological events and the development of disease modifying therapies. Smell testing may be an effective future tool for screening large populations for early neurodegeneration. AREAS COVERED: In this review, we appraise the evidence for, and discuss the likelihood of, the use of smell testing in large screening programs to detect early neurodegeneration. We evaluate the predictive power of smell tests for neurodegenerative disease, compare performance to other established screening programs, and discuss ethical and practical considerations and limitations. EXPERT OPINION: Even if disease modifying therapies were available for neurodegenerative disease, smell tests alone are unlikely to have high enough predictive power to be used in a future screening program. However, we believe they could be a valuable component of a short battery of tests or part of a stepwise process that together could more accurately identify early neurodegeneration in large populations.

A novel capsule-based smell test fabricated via coaxial dripping.

In this paper, we demonstrate that aromatic oil capsules, produced by dripping droplets, can offer a simple, yet effective, testing tool to aid in the diagnosis of various diseases, in which the loss of smell is a key symptom. These include chronic neurological conditions such as Parkinson's and Alzheimer's diseases, and acute respiratory infections such as that caused by COVID-19. The capsules were fabricated by concentrically dripping oil/alginate droplets, from a coaxial nozzle, into an oppositely charged ionic liquid. This fabrication technique enables full control over the capsule size, the shell thickness and the volume of the encapsulated oil. After formation, liquid capsules were left to dry and form a solid crust surrounding the oil. The prototype test consists of placing a standardized number of capsules between adhesive strips that users crush and pull apart to release the smell. In addition to the fabrication method, a simple mathematical model was developed to predict the volume of encapsulated oil within the capsule in terms of the flow rate ratio and the nozzle size. Tensile tests show that capsule strength is inversely proportional to its size owing to an increase in the shell thickness. By increasing the alginate concentration, the load required to rupture the capsule increases, to the point where capsules are too stiff to be broken by a fingertip grip. Results from a preliminary screening test, within a group of patients with Parkinson's disease, found that smells were detectable using a 'forced choice' paradigm.

Type 1 Diabetes Mellitus and Celiac Disease: Distinct Autoimmune Disorders That Share Common Pathogenic Mechanisms.

BACKGROUND: The relatively common co-occurrence of type 1 diabetes (T1D) and celiac disease (CD) suggests these disorders share common pathogenic etiologies. SUMMARY: T1D and CD are strongly linked to closely related high-risk human lymphocyte antigens (HLA-DR-DQ). High-risk HLA molecules bind specific fragments of gluten or the islet self-antigen(s) and present these antigens to antigen-responsive T cells. In an appropriate proinflammatory environment, the autoimmune response results in destruction of the intestinal enterocyte and/or the pancreatic beta cell. Environmental factors have been implicated in the etiology of T1D and CD because (1) identical twins are only partially concordant for these disorders and (2) incidence rates of T1D and CD have been steadily rising for decades. Prospective studies in infants genetically predisposed to T1D and CD showed that antibody positivity to both disorders begins in the first 1-3 years of life. Viral infections and early exposure to gluten or cow's milk in the infant diet have been implicated in disease pathogenesis. However, delaying introduction of gluten in the infant diet until 12 months of age had no impact on the development of islet or celiac autoimmunity. Weaning nursing infants to hydrolyzed infant formula had no impact on the development of T1D. Viral infections have been suspected of playing a role in T1D pathogenesis for decades. A large international prospective study (TEDDY) has shown increased risk of T1D autoimmunity particularly when >5 respiratory infections or febrile infections have occurred in the 9 months preceding the appearance of islet antibodies. Provocative data in animal models of T1D suggest the microbiome may play an important role in the pathogenesis of T1D. Breastfeeding, diet, infections, antibiotics, and method of birth alter the composition of the microbiome. Human data indicate subtle differences in the microbiome of children with T1D autoimmunity, while intestinal dysbiosis has been clearly demonstrated in CD. Alterations of the integrity of the intestinal mucosa plays an important role in the pathogenesis of CD, and the NOD mouse model suggests an important role of a leaky intestinal epithelium in T1D as well. Key Message: Immunogenetics and the environment are closely interrelated in the pathogenesis of T1D and CD. Large well-designed prospective studies in at-risk populations informed by scientifically rigorous studies in animal models are likely to have the greatest impact on our understanding of the complex pathogenesis of these detrimental autoimmune disorders.

Cellular Targets and Receptor of Sexual Transmission of Zika Virus.

STUDY QUESTION: What is the mechanism of sexual transmission of Zika virus (ZIKV)? SUMMARY ANSWER: By utilizing exquisite reverse transcriptase-initiated in situ polymerase chain reaction (RT-in situ PCR), which enables an improved visualization of spermatozoa's subcellular compartment, we precisely localized the mid-piece of sperm that carry receptors for ZIKV. WHAT IS ALREADY KNOWN: ZIKV is transmitted sexually and recent studies have verified ZIKV presence in semen of previously Zika-infected patients for >6-month postinfection when ZIKV had disappeared from blood, saliva, and urine. Strong serial analyses of various body fluids suggest that ZIKV can be transmitted between sexual partners. Currently, there is limited information on the association of the virus with human semen cell types that may carry the virus. STUDY DESIGN, SIZE, DURATION: Analyses were carried out to localize ZIKV for subcellular localization of ZIKV on cell types. The Tyro3 receptor for ZIKV was colocalized by dual immunocytochemistry with specific monoclonal antibodies. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three semen specimens were purchased from a commercial sperm bank. Motile sperm was separated from nonmotile cells by the "swim-up" technique. Each of the semen fractions was infected with ZIKV at the multiplicity of infection of 0.1.0 and 1.0 and evaluated for the primary targets of ZIKV in the semen cells by RT-in situ PCR and confirmed by real-time RT-PCR. MAIN RESULTS AND THE ROLE OF CHANCE: ZIKV was present primarily at the mid-piece of mature spermatozoa in about 30% of the sperm. In addition, we determined that Tyro3 receptors, primarily expressed on mid-piece of human spermatozoa, play a role in ZIKV-binding and entry into spermatozoa. Our data strongly suggest a potential sexual/horizontal route of transmission for ZIKV primarily via infected sperms; most likely ZIKV enters the sperm via the Tyro3 receptor found at the mid-piece of the mature spermatozoa. LIMITATIONS, REASONS FOR CAUTION: We are uncertain as to what phase of spermatogenesis, that in human takes about 120 days, sperms are permissive to ZIKV. If permissiveness was very early during spermatogenesis males could be infectious for ∼120 days after the disappearance of viremia in an infected man. WIDER IMPLICATIONS OF THE FINDINGS: Our findings bring a new focus on the current affords to develop ZIKV vaccine. Why in the presence of anti-ZIKV antibodies infected men are still able to transmit the virus sexually? We suggest that only certain subclass of immunoglobulin (Ig)G (ie, IgG4) can cross the blood-Sertoli barrier therefore, a successful vaccine must provoke a subclass of IgG can quell ZIKV inside the seminiferous tubules.

A Case of HDR Syndrome and Ichthyosis: Dual Diagnosis by Whole-Genome Sequencing of Novel Mutations in GATA3 and STS Genes.

CONTEXT: Atypical presentations of complex multisystem disorders may elude diagnosis based on clinical findings only. Appropriate diagnostic tests may not be available or available tests may not provide appropriate coverage of relevant genomic regions for patients with complex phenotypes. Clinical whole-exome/-genome sequencing is often considered for complex patients lacking a definitive diagnosis. CASE DESCRIPTION: A boy who is now 7 years old presented as a newborn with congenital ichthyosis. At 6 weeks of age, he presented with failure to thrive and hypoparathyroidism. At 4 years of age, he was diagnosed with sensorineural hearing loss. Whole-genome sequencing identified novel mutations in GATA3, which causes HDR syndrome (hypoparathyroidism and deafness), and STS, which causes X -linked congenital ichthyosis. CONCLUSION: Whole-genome sequencing led to a definitive clinical diagnosis in a case where no other clinical test was available for GATA3, and no sequencing panel would have included both genes because they have disparate phenotypes. This case demonstrates the power of whole-genome (or exome) sequencing for patients with complex clinical presentations involving endocrine abnormalities.

Growth hormone replacement in patients with PHACE association and hypopituitarism.

Partially empty sella with growth hormone (GH) deficiency is rarely reported in association with PHACE (posterior fossa anomalies, cervicofacial infantile hemangiomas [IHs], arterial anomalies, cardiac defects, eye anomalies, and midline/ventral defects). Consequently, little is known about the effect of GH replacement on the proliferation and involution of IHs in children with PHACE. We describe two children with PHACE and partially empty sella, both of whom received GH replacement for treatment of hypopituitarism. In our first patient we observed erythema and prominence of the vasculature in the hemangioma shortly after initiation of therapy at age 20 months, although after 4 weeks of treatment the appearance of the hemangioma stabilized and little change was seen during eight additional years of therapy. In our second patient we noted enlargement of the hemangioma after starting low-dose GH at age 5 years, prompting discontinuation of GH replacement after 3 months of therapy. The hemangiomas continued to grow after discontinuation of GH treatment. GH administration in our patients was associated with erythema and prominence of IHs. Our findings suggest that GH replacement therapy may promote transient or more prolonged proliferation of IHs and should be administered with close clinical monitoring.

Major transport mechanisms of pyrethroids in residential settings and effects of mitigation measures.

The major pathways for transport of pyrethroids were determined in runoff studies conducted at a full-scale test facility in central California, USA. The 6 replicate house lots were typical of front lawns and house fronts of California residential developments and consisted of stucco walls, garage doors, driveways, and residential lawn irrigation sprinkler systems. Each of the 6 lots also included a rainfall simulator to generate artificial rainfall events. Different pyrethroids were applied to 5 surfaces­driveway, garage door and adjacent walls, lawn, lawn perimeter (grass near the house walls), and house walls above grass. The volume of runoff water from each house lot was measured, sampled, and analyzed to determine the amount of pyrethroid mass lost from each surface. Applications to 3 of the house lots were made using the application practices typically used prior to recent label changes, and applications were made to the other 3 house lots according to the revised application procedures. Results from the house lots using the historic application procedures showed that losses of the compounds applied to the driveway and garage door (including the adjacent walls) were 99.75% of total measured runoff losses. The greatest losses were associated with significant rainfall events rather than lawn irrigation events. However, runoff losses were 40 times less using the revised application procedures recently specified on pyrethroid labels.

Developmental changes in the behavioral and autonomic effects of kappa opioid receptor stimulation of the midbrain periaqueductal gray.

Kappa opioid receptors stimulation with U50,488 is known to modulate behaviors during the early postnatal period, but the specific neuroanatomical locus of many of these effects is unexplored. In the present study, we infused U50,488 into the midbrain periaqueductal gray (PAG) and investigated the effects of this drug on behavior and heart rate of 1-, 2-, and 3-week-old rats. U50,488 increased activity most potently in 1- and 2-week-old subjects. Ultrasonic vocalization (USV) production was increased in 1-week-old subjects, but not in 2- or 3-week-old pups. Heart rate changes were similarly seen in younger aged subjects. At 1 week, U50,488 decreased heart rate, but at 2 weeks it increased heart rate. There was no effect of this drug on heart rate at 3 weeks. At 1 week, USVs were more potently elicited from dorsal than lateral PAG infusion sites. No other site-specific effects within the PAG were seen. The age-related decline in behavioral effects elicited by U50,488 is consistent with other published reports, and to the extent that kappa receptor activity mediates infant separation responses, implicates the PAG as a modulator of those responses.

Emergence of the exploratory motive in rats.

As infant rats approach weaning, they must overcome their infantile attraction to the home nest and prepare to leave its safety to forage for food. Although nutritive needs may help to motivate pups to make this bold move, a newly emerging exploratory motive also may play a role. Three experiments are reported here which examine age-related changes in the exploratory motive. In the first experiment, preferences for a novel side over a familiar side of a two-sided testing chamber were examined in postnatal Days 15 (P15), 17 (P17), 19 (P19), and 21 (P21) rat pups. Subjects did not prefer to explore the novel side until P19. In the same test, no preference for a novel object was observed at any of the ages tested, suggesting that this preference, which is expressed in adulthood, does not emerge until a later age; however, additional studies are needed to verify this. In the second experiment, P15 subjects demonstrated their ability to discriminate the two sides of the testing chamber in a novelty-induced locomotion test. In the third experiment, the presence of a home-nest-associated object was shown to inhibit exploration of novel context in P15, but not P21, subjects. These data suggest that home nest egression may be more the consequence of the declining attractiveness of the home nest than of a growing exploratory motive.