APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Bursts from the past: Intrinsic properties link a network model to zebra finch song.

Neuronal intrinsic excitability is a mechanism implicated in learning and memory that is distinct from synaptic plasticity. Prior work in songbirds established that intrinsic properties (IPs) of premotor basal-ganglia-projecting neurons (HVC X ) relate to learned song. Here we find that temporal song structure is related to specific HVC X IPs: HVC X from birds who sang longer songs including longer invariant vocalizations (harmonic stacks) had IPs that reflected increased post-inhibitory rebound. This suggests a rebound excitation mechanism underlying the ability of HVC X neurons to integrate over long periods of time and represent sequence information. To explore this, we constructed a network model of realistic neurons showing how in-vivo HVC bursting properties link rebound excitation to network structure and behavior. These results demonstrate an explicit link between neuronal IPs and learned behavior. We propose that sequential behaviors exhibiting temporal regularity require IPs to be included in realistic network-level descriptions.

Progressive Supranuclear palsy (PSP) disease progression, management, and healthcare resource utilization: a retrospective observational study in the US and Canada.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disease with rapid progression and currently limited treatment options. A comprehensive understanding of disease progression, management, and healthcare resource utilization is limited, and further research is challenging due to the small population of patients. To address these challenges in conducting PSP research, individuals with PSP were recruited using a multichannel approach tailored specifically to the PSP community. We performed a retrospective observational study using data abstracted from participant medical records collected from multiple patient care centers. RESULTS: Seventy-two individuals with PSP were eligible for inclusion. On average, 144 medical documents per participant were collected from an average of 2.9 healthcare centers per participant, with a mean study period of 7.9 years. Among participants with a date of symptom onset documented in the medical records, the median time for the onset of the first fall was 2.0 years (IQR 3.2) before diagnosis, the median onset of unsteady gait or gait impairment was 1.2 years (IQR 1.8) before diagnosis, and the median onset of mobility problems was 0.8 years (IQR 1.8) before diagnosis. The most widely utilized healthcare resources, with at least 85% of participants using each of these resources at some point during the disease course, were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries and procedures (85%). CONCLUSIONS: This retrospective study adds to the current understanding of PSP symptoms, comorbidities, and healthcare resource utilization (HRU) across the disease journey. By involving individuals with PSP and their caregivers or legally authorized representatives in the research process, this study was unique in its approach to participant recruitment and enabled individuals to participate in research without the need for travel. We collected medical documents from multiple healthcare centers, allowing for broad data collection covering the entire disease journey. This approach to the collection of real-world data may be used to generate valuable insights into many aspects of disease progression and management in PSP and many other rare diseases.

Access to legacy-oriented interventions at end of life for pediatric oncology patients: A decedent cohort review.

BACKGROUND: Legacy-oriented interventions have the potential to offer pediatric oncology patients and families comfort at end of life and during bereavement. Certified child life specialists often provide these services, and presently little is known about whether disparities exist in the provision of legacy-oriented interventions. METHODS: In this retrospective decedent cohort study, we examined demographic and clinical characteristics from a sample of 678 pediatric oncology patients who died between 2015 and 2019. Bivariate analysis assessed differences between patients who received any versus no legacy-oriented intervention. Uni- and multivariable logistic regression models assessed associations of baseline characteristics and likelihood of receiving legacy-oriented intervention. Further multivariable analysis explored joint effects of significant variables identified in the univariable analysis. RESULTS: Fifty-two percent of patients received a legacy-oriented intervention. Older adolescents (≥13 years) were less likely (odds ratio [OR]: 1.73, p = .007) to receive legacy-oriented interventions than younger ones. Patients with home/hospice deaths were also less likely (OR: 19.98, p < .001) to receive interventions compared to patients who passed away at SJCRH locations. Hispanic patients (OR: 1.53, p = .038) and those in palliative care (OR: 10.51, p < .001) were more likely to receive interventions. No significant race association was noted. CONCLUSION: All children and adolescents with cancer deserve quality care at end of life, including access to legacy-oriented interventions, yet nearly half of patients in this cohort did not receive these services. By identifying demographic and clinical characteristics associated with decreased odds of receiving legacy-oriented interventions, healthcare professionals can modify end-of-life care processes to improve access. Introducing legacy-oriented interventions early and increasing exposure in community spaces may enhance access to legacy-oriented interventions for pediatric oncology patients.

APOE3 Christchurch modulates ß-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer's cases.

A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer's disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch, we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation. ScRNA sequencing revealed regulation of Cadherin and Wnt signaling pathways by APOE3Ch, with immunostaining indicating elevated ß-catenin protein levels. Further in vitro reporter assays unexpectedly demonstrated that ApoE3Ch functions as a Wnt3a signaling enhancer. This work uncovered a neomorphic molecular mechanism of protection of ApoE3 Christchurch, which may serve as the foundation for the future development of protected case-inspired therapeutics targeting AD and tauopathies.

Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children.

In brief: In light of the increasing age of first-time fathers, this article summarizes the current scientific knowledge base on reproductive aging in the male, including sperm quality and health impacts for the offspring. The emerging role of NAD decline in reproductive aging is highlighted. Abstract: Over the past decades, the age of first-time fathers has been steadily increasing due to socio-economic pressures. While general mechanisms of aging are subject to intensive research, male reproductive aging has remained an understudied area, and the effects of increased age on the male reproductive system are still only poorly understood, despite new insights into the potential dire consequences of advanced paternal age for the health of their progeny. There is also growing evidence that reproductive aging is linked to overall health in men, but this review mainly focuses on pathophysiological consequences of old age in men, such as low sperm count and diminished sperm genetic integrity, with an emphasis on mechanisms underlying reproductive aging. The steady decline of NAD levels observed in aging men represents one of the emerging concepts in that regard. Because it offers some mechanistic rationale explaining the effects of old age on the male reproductive system, some of the NAD-dependent functions in male reproduction are briefly outlined in this review. The overview also provides many questions that remain open about the basic science of male reproductive aging.

Single-Cell Transcriptomic Analysis of Salivary Gland Endothelial Cells.

Vascular endothelial cells have important tissue-specific functions in fibrosis and regeneration. In the salivary gland, endothelial cells are required for proper development, but their roles within adult glands are largely unknown. To identify ligand-receptor interactions between endothelial cells and other cell types that may be important during fibrosis and regeneration, we used a reversible ductal ligation injury. To induce injury, a clip was applied to the primary ducts for 14 d, and to induce a regenerative response, the clip was subsequently removed for 5 d. To identify endothelial cell-produced factors, we used single-cell RNA sequencing of stromal-enriched cells from adult female submandibular and sublingual salivary glands. Transcriptional profiles of homeostatic salivary gland endothelial cells were compared to endothelial cells of other organs. Salivary gland endothelial cells expressed many unique genes and displayed the highest overlap in gene expression with other fenestrated endothelial cells from the colon, small intestine, and kidney. Comparison of the 14-d ligated, mock-ligated, and 5-d deligated stromal-enriched transcripts and lineage tracing revealed that endothelial cells retain their identity following ligation and recovery from injury. CellChat and NATMI were used to predict changes in ligand-receptor interactions from endothelial cells to other cells in response to ligation and deligation. CellChat and NATMI predicted that after ligation, interactions with fibroblasts, epithelial cells, and glial cells were increased, and following deligation, interactions with pericyte, glia, fibroblasts, and immune cells were increased. Some of the highest-ranked interactions predicted in ligated compared to mock endothelial cells were between glial cells via Col4a2-Cd93 and Jag2-Notch1, as well as epithelial cells via Pecam1-Cd38, while in deligated compared to ligated endothelial cells, the top interactions were between fibroblasts via Ntf3-Ntrk2, glial cells via Hspg2-Itgb1, and pericytes via Jam2-F11r. Understanding salivary gland endothelial cell signaling will inform future endothelial cell-based regenerative therapies.

A high burden of diabetes and ankle brachial index abnormalities exists in Mexican Americans in South Texas.

Ethnic differences exist in the United States in the interrelated problems of diabetes (DM), peripheral arterial disease (PAD), and leg amputations. The purpose of this study was to determine the prevalence and risk factor associations for subclinical PAD in a population sample of Mexican Americans using the ankle brachial (ABI) index. The ABI-High (higher of the two ankle pressures/highest brachial pressure) and ABI-Low (lower of the two ankle pressures/highest brachial pressure) were calculated to define PAD. Toe brachial index (TBI) was also calculated. 746 participants were included with an age of 53.4 ± 0.9 years, 28.3 % had diabetes mellitus (DM), 12.6 % were smokers, and 51.2 % had hypertension (HTN). Using ABI-High ≤ 0.9, the prevalence of PAD was 2.7 %. This rose to 12.7 % when an ABI-Low ≤ 0.9 was used; 4.0 % of the population had an ABI-High > 1.4. The prevalence of TBI < 0.7 was 3.9 %. DM was a significant risk factor for ABI-High ≤ 0.9 and ABI-High > 1.4, and TBI < 0.7. Increased age, HTN, smoking was associated with ABI-High ≤ 0.9, while being male was associated with ABI-High > 1.4. Increased age, smoking, and lower education were all associated with abnormal TBI. Despite relatively younger mean age than other studied Hispanic cohorts, the present population has a high burden of ABI abnormalities. DM was a consistent risk factor for PAD. These abnormalities indicate an important underlying substrate of vascular and metabolic disease that may predispose this population to the development of symptomatic PAD and incident amputations.

On-Off-On Fluorometric Detection of Hg(II) and L-Cysteine Using Red Emissive Nitrogen-Doped Carbon Dots for Environmental and Clinical Sample Analysis.

This research introduces a novel fluorescence sensor 'on-off-on' employing nitrogen-doped carbon dots (N-CDs) with an 'on-off-on' mechanism for the selective and sensitive detection of Hg(II) and L-cysteine (L-Cys). N-CDs was synthesized using citric acid as the carbon precursor and urea as the nitrogen source in dimethylformamide (DMF) solvent, resulting in red emissive characteristics under UV light. Comprehensive spectroscopic analyses, including UV-Vis, fluorescence, FT-IR, XRD, XPS, Raman, and Zeta potential techniques, validated the structural and optical characteristics of the synthesized N-CDs. The maximum excitation and emission of N-CDs were observed at 548 and 622 nm, respectively. The quantum yield of N-CDs was calculated to be 16.1%. The fluorescence of N-CDs effectively quenches upon the addition of Hg(II) due to the strong coordination between Hg(II) and the surface functionalities of N-CDs. Conversely, upon the subsequent addition of L-Cys, the fluorescence of N-CDs was restored. This restoration can be attributed to the stronger affinity of the -SH group in L-Cys towards Hg(II) relative to the surface functionalities of N-CDs. This dual-mode response enabled the detection of Hg(II) and L-Cys with impressive detection limits of 15.1 nM and 8.0 nM, respectively. This sensor methodology effectively detects Hg(II) in lake water samples and L-Cys levels in human urine, with a recovery range between 99 and 101%. Furthermore, the N-CDs demonstrated excellent stability, high sensitivity, and selectivity, making them a promising fluorescence on-off-on probe for both environmental monitoring of Hg(II) and clinical diagnostics of L-Cys.

Turn-Off Fluorometric Determination of Bilirubin Using Facile Synthesized Nitrogen-Doped Carbon Dots as a Fluorescent Probe.

Bilirubin plays a significant role in human health management, particularly in the case of jaundice. Because of the need for the monitoring of bilirubin levels in jaundice patients, the development of a robust sensitive method becomes essential. Here, we describe the development of a highly sensitive and selective turn-off fluorometric detection method for bilirubin in blood serum samples using nitrogen-doped carbon dots (N-CDs). N-CDs was synthesized by the pyrolysis process, using citric acid and L-asparagine as the carbon and nitrogen sources, respectively. The prepared N-CDs solution showed highly intense blue emission with good stability. The HR-TEM image of N-CDs revealed spherical dot-like structures with an average size calculated to be 7.16 nm. Further, the surface functional groups of N-CDs were analyzed by FT-IR, Raman, XRD, and XPS techniques. Fluorescence spectra showed the maximum emission intensity at 443 nm (λex). The linear range of addition was performed from 1 to 150 µM, and the limit of detection (LOD) was determined to be 1.97 nM. The emission of N-CDs was quenched by Förster Resonance Energy Transfer (FRET) by adding bilirubin. These N-CDs showed extraordinary sensitivity and selectivity in the detection of bilirubin. Hence, this fluorescent probe has been proven successful in detecting the concentration of free bilirubin in human serum samples.

Leading indicators of readiness among the general Army and Special Operations Forces: Predictive and psychometric analysis of the Global Assessment Tool.

Self-assessments are commonly used to track Army readiness in specialized communities, but they are rarely analyzed for reliability and predictive validity. Before introducing new assessments, existing ones should be reevaluated. We examined the Global Assessment Tool (GAT), an annual Army-required self-assessment with multiple psychosocial and health behavior short scales. Psychometric analyses on nine scales included item response theory (IRT) and measurement invariance models across total Army (n = 743,057) and special operations forces (SOF; n = 3,478) cohorts. Predictive analyses examined demographic-adjusted associations between GAT scales and one-year incident medical non-readiness (MNR). Most scales had adequate reliability, although some exhibited highly skewed distributions, which likely increased measurement error. Most scales exhibited metric and scalar measurement equivalence across total Army and SOF groups. Scores from scales measuring positive characteristics were associated with lower odds of MNR (good coping, flexibility, optimism, positive affect, work engagement, friendship, organization trust; adjusted odds ratios ≤ 0.75); scores from scales measuring negative characteristics were associated with increased odds of MNR (poor sleep, depression, negative affect, loneliness; adjusted odds ratios ≥ 1.4). Associations were similar across Army and SOF cohorts. In conclusion, self-report data can potentially contribute to command surveillance, but iterative quality-checks are necessary after deployment.

Numerical Simulations of Carbon-Fibre Impregnation with a Polymer as an Anisotropic Permeability Medium.

The impregnation process of carbon fibres with polymers is challenging to model due to the system's complexity, particularly concerning the following aspects: the complex rheology of the polymeric matrices and the presence of solid, continuous fibres, both with anisotropic properties, and the interaction between solid and fluid, which can change the displacement of fibres into a cyclic dependence. In this work, an interesting approach was considered by setting the fibres as a porous medium whose properties were calculated with microscale/macroscale cycle modelling. In the microscale modelling stage, two main assumptions can be made: (i) a homogeneous distribution with a representative cell or (ii) a stochastic distribution of fibres. The solution to the abovementioned flow and fibre distribution problem can severely differ with only a slight change in a single parameter for a given set of processing parameters. Therefore, the influence of some of them during the fibre impregnation process was evaluated, allowing a shortcut for the polymer through a gap between fibres and the bottom wall of the extrusion die. The range of investigated values regarding the gap enables one to cover good impregnation conditions up to the occurrence of the shortcut and consequent poor impregnation quality. These studies were performed with numerical simulations with circa 126,000 degrees of freedom, considering the discretisation mesh elements and the unknowns (pressure and two velocity components).

The combined effects of coping and pain interference on army readiness.

Introduction: Chronic pain and associated interference with daily activities are common in the military and impact Force readiness. Chronic pain affects one-third of service members and is a leading cause of medical non-readiness (MNR) in the military. Research suggests that underlying psychological mechanisms related to trait coping styles and pain interference (PI) affect functional outcomes, but little research exists examining this relationship within an Army population. The purpose of this study was to examine the combined effects of PI and coping on U.S. Army soldier readiness by using annual well-being data from the Global Assessment Tool (GAT) and medical non-readiness (MNR) based on duty restriction records. Methods: The sample comprised 866,379 soldiers who completed the GAT between 2014 and 2017 with no duty restrictions at the time of baseline GAT completion; subjects were observed through 2018 for duty restrictions. Parametric survival regression models with a Weibull distribution predicted demographic-adjusted hazards of MNR by dichotomized PI (no PI/PI) and beneficial/non-beneficial use of GAT coping components (good coping, bad coping, catastrophizing-flexibility, and catastrophizing-hopelessness). Incident MNR was evaluated for all duty restrictions, and stratified by selected body systems (upper extremity, lower extremity, psychiatric). Results: Among soldiers with PI, hazards were higher in those reporting non-beneficial coping styles (bad coping, hopelessness) and lower in those reporting beneficial coping styles (good coping, flexibility). Across all coping styles, PI/coping interactions were particularly strong for catastrophizing-hopelessness and when examining MNR from psychiatric conditions. Discussion: These findings suggest some synergistic associations between pain and coping that may impact pain-related occupational disability. Coping skills may be an effective interventional target for chronic pain reduction/prevention within military programs, such as the Master Resilience Training Course offered to soldiers in the Army. Further research should assess whether early coping style interventions can reduce pain-related outcomes.

Postpartum long-acting reversible contraceptive use among active-duty, female US Army soldiers.

BACKGROUND: Postpartum use of long-acting reversible contraception has been found to be effective at increasing interpregnancy intervals, reducing unintended pregnancies, and optimizing health outcomes for mothers and babies. Among female active-duty military service members, reproductive planning may be particularly important, yet little is known about postpartum long-acting reversible contraceptive use among active-duty soldiers. OBJECTIVE: This study aimed to (1) quantify postpartum uptake of long-acting reversible contraception among active-duty female US Army soldiers and (2) identify demographic and military-specific characteristics associated with use. STUDY DESIGN: This retrospective cohort study used longitudinal data of all digitally recorded health encounters for active-duty US Army soldiers from 2014 to 2017. The servicewomen included in our analysis were aged 18 to 44 years with at least one delivery and a minimum of 4 months of total observed time postdelivery within the study period. We defined postpartum long-acting reversible contraception use as initiation of use within the delivery month or in the 3 calendar months following delivery and identified likely immediate postpartum initiation via the proxy of placement recorded during the same month as delivery. We then evaluated predictors of postpartum long-acting reversible contraception use with multivariable logistic regression. RESULTS: The inclusion criteria were met by 15,843 soldiers. Of those, 3162 (19.96%) initiated the use of long-acting reversible contraception in the month of or within the 3 months following delivery. Fewer than 5% of these women used immediate postpartum long-acting reversible contraception. Among women who initiated postpartum long-acting reversible contraceptive use, 1803 (57.0%) received an intrauterine device, 1328 (42.0%) received an etonogestrel implant, and 31 received both (0.98%). Soldiers of younger age, self-reported White race, and those who were married or previously married were more likely to initiate long-acting reversible contraception in the postpartum period. Race-stratified analyses showed that self-reported White women had the highest use rates overall. When compared with these women, the adjusted odds of postpartum use among self-reported Black and Asian or Pacific Islander women were 18% and 30% lower, respectively (both P<.001). There was also a trend of decreasing postpartum use with increasing age within each race group. Differences observed between age groups and race identities could partially be attributed to differential use of permanent contraception (sterilization), which was found to be significantly more prevalent among both women aged 30 years or older and among women who identified as Black. CONCLUSION: Among active-duty US Army servicewomen, 1 in 5 used postpartum long-acting reversible contraception, and fewer than 5% of these women used an immediate postpartum method. Within this population with universal healthcare coverage, we observed relatively low rates of use and significant differences in the uptake of effective postpartum long-acting contraceptive methods across self-reported race categories.

Physical Fitness in Relationship to Depression and Post-Traumatic Stress Disorder During Pregnancy Among U.S. Army Soldiers.

Background: Depression and post-traumatic stress disorder (PTSD) are prevalent in pregnancy, especially among military members. These conditions can lead to adverse birth outcomes, yet, there's a paucity of evidence for prevention strategies. Optimizing physical fitness is one understudied potential intervention. We explored associations between prepregnancy physical fitness and antenatal depression and PTSD in soldiers. Materials and Methods: This was a retrospective cohort study of active-duty U.S. Army soldiers with live births between 2011 and 2014, identified with diagnosis codes from inpatient and outpatient care. The exposure was each individual's mean Army physical fitness score from 10 to 24 months before childbirth. The primary outcome was a composite of active depression or PTSD during pregnancy, defined using the presence of a code within 10 months before childbirth. Demographic variables were compared across four quartiles of fitness scores. Multivariable logistic regression models were conducted adjusting for potential confounders selected a priori. A stratified analysis was conducted for depression and PTSD separately. Results: Among 4,583 eligible live births, 352 (7.7%) had active depression or PTSD during pregnancy. Soldiers with the highest fitness scores (Quartile 4) were less likely to have active depression or PTSD in pregnancy (Quartile 4 vs. Quartile 1 adjusted odds ratio 0.55, 95% confidence interval 0.39-0.79). Findings were similar in stratified analyses. Conclusion: In this cohort, the odds of active depression or PTSD during pregnancy were significantly reduced among soldiers with higher prepregnancy fitness scores. Optimizing physical fitness may be a useful tool to reduce mental health burden on pregnancy.

Cotton leafroll dwarf disease: An enigmatic viral disease in cotton.

TAXONOMY: Cotton leafroll dwarf virus (CLRDV) is a member of the genus Polerovirus, family Solemoviridae. Geographical Distribution: CLRDV is present in most cotton-producing regions worldwide, prominently in North and South America. PHYSICAL PROPERTIES: The virion is a nonenveloped icosahedron with T = 3 icosahedral lattice symmetry that has a diameter of 26-34 nm and comprises 180 molecules of the capsid protein. The CsCl buoyant density of the virion is 1.39-1.42 g/cm3 and S20w is 115-127S. Genome: CLRDV shares genomic features with other poleroviruses; its genome consists of monopartite, single-stranded, positive-sense RNA, is approximately 5.7-5.8 kb in length, and is composed of seven open reading frames (ORFs) with an intergenic region between ORF2 and ORF3a. TRANSMISSION: CLRDV is transmitted efficiently by the cotton aphid (Aphis gossypii Glover) in a circulative and nonpropagative manner. Host: CLRDV has a limited host range. Cotton is the primary host, and it has also been detected in different weeds in and around commercial cotton fields in Georgia, USA. SYMPTOMS: Cotton plants infected early in the growth stage exhibit reddening or bronzing of foliage, maroon stems and petioles, and drooping. Plants infected in later growth stages exhibit intense green foliage with leaf rugosity, moderate to severe stunting, shortened internodes, and increased boll shedding/abortion, resulting in poor boll retention. These symptoms are variable and are probably influenced by the time of infection, plant growth stage, varieties, soil health, and geographical location. CLRDV is also often detected in symptomless plants. CONTROL: Vector management with the application of chemical insecticides is ineffective. Some host plant varieties grown in South America are resistant, but all varieties grown in the United States are susceptible. Integrated disease management strategies, including weed management and removal of volunteer stalks, could reduce the abundance of virus inoculum in the field.

Changes in the gut microbiota of rats after exposure to the fungicide Mancozeb.

Mancozeb is a fungicide commonly used in pest control programs, especially to protect vineyards. Its toxicity has already been evidenced in several studies. However, its influence on the composition and diversity of the gut microbiota remains unknown. In this work, the adverse impact of Mancozeb on the intestinal microbiota was investigated using a rodent model. Adult male Sprague Dawley rats were randomized into three groups: Control (standard diet), MZ1 (Mancozeb dose: 250 mg/kg bw/day), and MZ2 (Mancozeb dose: 500 mg/kg bw/day). After 12 weeks of experiment, animals were euthanized, and feces present in the intestine were collected. After fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ System. Alpha and beta diversity analysis showed significant differences between Control and Mancozeb groups (MZ1 e MZ2), but no difference between MZ1 and MZ2 was observed. Seven genera significantly increased in abundance following Mancozeb exposure, while five genera decreased. Co-occurrence analyses revealed that the topological properties of the microbial networks, which can be used to infer co-occurrence interaction patterns among microorganisms, were significantly lower in both groups exposed to Mancozeb when compared to Control. In addition, 23 differentially abundant microbial metabolic pathways were identified in Mancozeb-treated groups mainly related to a change in energy metabolism, LPS biosynthesis, and nucleotide biosynthesis. In conclusion, the exposure to Mancozeb presented side effects by changing the composition of the microbiota in rats, increasing bacterial diversity regardless of the dose used, reducing the interaction patterns of the microbial communities, and changing microbial metabolic pathways.

Efficient All-Electron Time-Dependent Density Functional Theory Calculations Using an Enriched Finite Element Basis.

We present an efficient and systematically convergent approach to all-electron real-time time-dependent density functional theory (TDDFT) calculations using a mixed basis, termed as enriched finite element (EFE) basis. The EFE basis augments the classical finite element basis (CFE) with a compactly supported numerical atom-centered basis, obtained from atomic ground-state DFT calculations. Particularly, we orthogonalize the enrichment functions with respect to the classical finite element basis to ensure good conditioning of the resultant basis. We employ the second-order Magnus propagator in conjunction with an adaptive Krylov subspace method for efficient time evolution of the Kohn-Sham orbitals. We rely on a priori error estimates to guide our choice of an adaptive finite element mesh as well as the time step to be used in the TDDFT calculations. We observe close to optimal rates of convergence of the dipole moment with respect to spatial and temporal discretizations. Notably, we attain a 50-100 times speedup for the EFE basis over the CFE basis. We also demonstrate the efficacy of the EFE basis for both linear and nonlinear responses by studying the absorption spectra in sodium clusters, the linear to nonlinear response transition in the green fluorescence protein chromophore, and the higher harmonic generation in the magnesium dimer. Lastly, we attain good parallel scalability of our numerical implementation of the EFE basis for up to ∼1000 processors, using a benchmark system of a 50-atom sodium nanocluster.

Incidence of Ankylosing Spondylitis Among Male and Female United States Army Personnel.

OBJECTIVE: Incidence rates of ankylosing spondylitis (AS) among males versus females are poorly understood. Results of prior research have been mixed, including findings of a 3:1 incidence ratio for males versus females, but with increasing AS rates among females. The objective was to estimate the incidence of AS among members of the US military. METHODS: We estimated the incidence of AS in a retrospective cohort study of diverse, working-age US military service members during March 2014 to June 2017 (n = 728,556) who underwent clinical practice guideline-directed screening for chronic back pain. Incident AS cases were identified using diagnostic codes from electronic medical and administrative records. RESULTS: In contrast to some prior studies, AS incidence was similar among males and females (incidence rate ratio 1.16, P = 0.23; adjusted odds ratio [OR] 0.79 [95% confidence interval (95% CI) 0.61-1.02]; P = 0.072). AS rates increased approximately monotonically with age. Consistent with prior research, the AS incidence rate was greater in the White population than in the Black population (adjusted OR 1.39 [95% CI 1.01-1.66]; P = 0.04). CONCLUSION: In this study population, the incidence of AS was similar for the sexes. Previous observations of male predominance have typically been derived from clinic populations that are less representative of the US race/ethnicity distribution and based on disease ascertainment tools that may have identified subjects later in their disease course. Our study population also differed in being subject to organized screenings for musculoskeletal symptoms. Our findings suggest that sex may not predict AS incidence in the US population.

Association of intraplacental oxygenation patterns on dual-contrast MRI with placental abnormality and fetal brain oxygenation.

OBJECTIVES: Most human in-vivo placental imaging techniques are unable to distinguish and characterize various placental compartments, such as the intervillous space (IVS), placental vessels (PV) and placental tissue (PT), limiting their specificity. We describe a method that employs T2* and diffusion-weighted magnetic resonance imaging (MRI) data to differentiate automatically placental compartments, quantify their oxygenation properties and identify placental lesions (PL) in vivo. We also investigate the association between placental oxygenation patterns and fetal brain oxygenation. METHODS: This was a prospective study conducted between 2018 and 2021 in which dual-contrast clinical MRI data (T2* and diffusion-weighted MRI) were acquired from patients between 20 and 38 weeks' gestation. We trained a fuzzy clustering method to analyze T2* and diffusion-weighted MRI data and assign placental voxels to one of four clusters, based on their distinct imaging domain features. The new method divided automatically the placenta into IVS, PV, PT and PL compartments and characterized their oxygenation changes throughout pregnancy. RESULTS: A total of 27 patients were recruited, of whom five developed pregnancy complications. Total placental oxygenation level and T2* did not demonstrate a statistically significant temporal correlation with gestational age (GA) (R2 = 0.060, P = 0.27). In contrast, the oxygenation level reflected by T2* values in the placental IVS (R2 = 0.51, P = 0.0002) and PV (R2 = 0.76, P = 1.1 × 10-7 ) decreased significantly with advancing GA. Oxygenation levels in the PT did not show any temporal change during pregnancy (R2 = 0.00044, P = 0.93). A strong spatial-dependent correlation between PV oxygenation level and GA was observed. The strongest negative correlation between PV oxygenation and GA (R2 = 0.73, P = 4.5 × 10-7 ) was found at the fetal-vessel-dominated region close to the chorionic plate. The location and extent of the placental abnormality were automatically delineated and quantified in the five women with clinically confirmed placental pathology. Compared to the averaged total placental oxygenation, placental IVS oxygenation level best reflected fetal brain oxygenation level during fetal development. CONCLUSION: Based on clinically feasible dual-MRI, our method enables accurate spatiotemporal quantification of placental compartment and fetal brain oxygenation across different GAs. This information should improve our knowledge of human placenta development and its relationship with normal and abnormal pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.