On the Origin and Evolution of the Mosquito Male-determining Factor Nix.

The mosquito family Culicidae is divided into 2 subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Aedes albopictus, 2 important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from 3 highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133 to 165 million years ago (MYA). Heterologous expression of 1 of 3 divergent Nix open reading frames (ORFs) in Ae. aegypti resulted in partial masculinization of genetic females as evidenced by morphology and doublesex splicing. Phylogenetic analysis suggests Nix is related to femaleless (fle), a recently described intermediate sex-determining factor found exclusively in anopheline mosquitoes. Nix from all species has a conserved structure, including 3 RNA-recognition motifs (RRMs), as does fle. However, Nix has evolved at a much faster rate than fle. The RRM3 of both Nix and fle are distantly related to the single RRM of a widely distributed and conserved splicing factor transformer-2 (tra2). The RRM3-based phylogenetic analysis suggests this domain in Nix and fle may have evolved from tra2 or a tra2-related gene in a common ancestor of mosquitoes. Our results provide insights into the evolution of sex determination in mosquitoes and will inform broad applications of mosquito-control strategies based on manipulating sex ratios toward nonbiting males.

What Factors are Associated With Conversion to Knee Arthroplasty After Subchondroplasty?

BACKGROUND: Subchondral bone marrow lesions identified on knee MRI are believed to play a role in osteoarthritis-associated pain. The subchondroplasty procedure is an arthroscopically assisted procedure for treating such lesions to avoid larger procedures such as knee arthroplasty. However, the survivorship free of conversion to arthroplasty and the factors associated with an increased likelihood of conversion of subchondroplasty to arthroplasty have not been well defined. QUESTIONS/PURPOSES: We performed this study to (1) determine the 5-year survivorship of subchondroplasty free from conversion to knee arthroplasty (unicompartmental or total) and (2) identify variables that were associated with progression to knee arthroplasty after a subchondroplasty procedure. METHODS: In all, 216 patients who underwent a subchondroplasty procedure performed by one surgeon with subchondroplasty experience at a single-center, multilocation facility between September 2014 and August 2017 were retrospectively evaluated to estimate survivorship free from conversion to knee arthroplasty at 5 years. The mean ± SD age and BMI at the time of subchondroplasty procedure were 59 ± 11 years and 33 ± 8 kg/m 2 , respectively; 60% (129 of 216) of the patients were women. Other variables collected were smoking status and grade and location of chondral lesions. The electronic medical record was reviewed to determine whether the patient had a knee arthroplasty after subchondroplasty. Survivorship free from conversion to knee arthroplasty at 5 years was calculated from a Kaplan-Meier survivorship estimator. Factors associated with progression to knee arthroplasty were examined using t-tests and chi-square analyses. Variables showing evidence of an association with knee arthroplasty were explored further using a Kaplan-Meier survivorship estimator (n = 190). RESULTS: Kaplan-Meier survivorship free from conversion to knee arthroplasty was 73% (95% CI 67% to 79%) at 5 years after subchondroplasty. We found that age older than 50 years and Grade 4 chondral lesions were associated with conversion to knee arthroplasty. Patients with a Grade 4 chondral lesion had 5-year survivorship of 62% (95% CI 54% to 71%) and 59% (95% CI 50% to 69%) for those older than 50 years with a Grade 4 chondral lesion. CONCLUSION: Currently, we recommend a detailed, informed discussion of the risks versus benefits with patients who are considering a subchondroplasty procedure, particularly patients aged 50 years and older and those with Grade 4 chondral lesions. Future randomized trials, including those that compare the subchondroplasty procedure with arthroscopy alone or nonoperative management options, are still needed to confirm the efficacy and role of the subchondroplasty procedure in patients with knee osteoarthritis, because only such prospective studies can determine the success of the procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Differences in Habitual and Maximal Gait Velocity Across Age Groups: A Cross-Sectional Examination.

Prior work, primarily focusing on habitual gait velocity, has demonstrated a cost while walking when coupled with a cognitive task. The cost of dual-task walking is exacerbated with age and complexity of the cognitive or motor task. However, few studies have examined the dual-task cost associated with maximal gait velocity. Thus, this cross-sectional study examined age-related changes in dual-task (serial subtraction) walking at two velocities. Participants were classified by age: young-old (45-64 years), middle-old (65-79 years), and oldest-old (≥80 years). They completed single- and dual-task walking trials for each velocity: habitual (N = 217) and maximal (N = 194). While no significant Group × Condition interactions existed for habitual or maximal gait velocities, the main effects for both condition and age groups were significant (p < .01). Maximal dual-task cost (p = .01) was significantly greater in the oldest-old group. With age, both dual-task velocities decreased. Maximal dual-task cost was greatest for the oldest-old group.

Sit-to-Stand Power Across the Lifespan: A Cross-Sectional Analysis.

Lower-body power measured by a linear position transducer during the sit-to-stand (STS) movement declines with age and may be a predictor of physical disability in older adults. The purpose of this study was to establish normative data for STS power across the lifespan and to determine if differences exist between age cohorts, sexes, and age cohort-sex subgroups. Adults (N = 557) aged 18-89 were divided into five age cohorts and performed the STS connected to a linear position transducer, which calculated power and velocity during the movement. Significantly lower (p < .01) velocity was observed in a younger age cohort in females than males, whereas males saw a significant average power decrement (p < .01) in a younger age cohort than females. STS power norms give clinicians a metric predicting physical disability and may be of particular interest to males as their power production begins to decline at an earlier age.

Effects of fundamental movement skills based dual-task and dance training on single- and dual-task walking performance in older women with dementia.

OBJECTIVE: The purpose of this study was to compare the effects of fundamental movement skills (FMS)-based dual-task training and dance training on spatio-temporal characteristics of gait performance under single- and dual-task walking conditions among older women with dementia. METHOD: Thirty-eight elderly females with dementia were randomly assigned to one of two groups: (1) dual-task intervention (DTI, age: 73 ± 6.5 years) or (2) Iranian dance intervention (IDI, age: 72.52 ± 6.01 years). Both groups participated in a 10-week intervention program (3 sessions per week, each lasting 50 min). Gait performance parameters (gait speed, cadence, and stride length) and dual-task costs (DTC) were examined using a gait analysis system. The participants completed three walking trials under two conditions: single- and dual-task. The video data was analyzed using motion analysis software (Frame-DIAS II, DKH, DKH Inc., Tokyo, Japan). RESULTS: The results showed that both groups significantly improved in terms of all gait variables, and DTC decreased (p < .001) from pre- to post-test for both conditions. However, the main effects for the group and the group-by-time interactions were not significantly different between the two groups (p > .05). CONCLUSION: These findings showed that DTI and IDI effectively improved gait performance following a 10-week intervention for older women with dementia. Therefore, it is suggested that either training program could decrease DTC and increase gait speed, stride length, and cadence among older females with dementia.

Cache Valley Virus in Aedes japonicus japonicus Mosquitoes, Appalachian Region, United States.

We detected Cache Valley virus in Aedes japonicus, a widely distributed invasive mosquito species, in an Appalachian forest in the United States. The forest contained abundant white-tailed deer, a major host of the mosquito and virus. Vector competence trials indicated that Ae. j. japonicus mosquitoes can transmit this virus in this region.

An Evaluation of Functional Sit-to-Stand Power in Cohorts of Healthy Adults Aged 18-97 Years.

This investigation examined differences in functional sit-to-stand power/velocity between cohorts of adults aged 18-97 years. This study included 264 healthy adults classified into four cohorts (18-40, C1; 60-69, C2; 70-79, C2; ≥ 80, C4). Participants completed the sit-to-stand task five times. Power and velocity were measured via the TENDO power analyzer. Absolute average power was maintained from C1-C3, but decreased (p < .01) in C4. Absolute peak power decreased between C1-C2 (p < .01), was similar between C2-C3, and decreased in C4 (p < .01). Relative (to body weight) average and peak power decreased between C1-C2 (p < .01), was similar between C2-C3, and decreased in C4 (p < .01). Average velocity was similar between C1 and C2, but decreased in C3 (p < .01) and C4 (p < .01), respectively. Peak velocity was significantly different between all cohorts (p < .01). Declines in functional power may plateau during the seventh and eighth decades, accelerating after 80 years.

Maximal, Not Habitual, Walking Velocity is More Highly Correlated to Functional Fitness of Community-Dwelling Older Adults.

The aim of this investigation was to determine the relationship between usual and maximal walking velocities with measures of functional fitness (FF). Fifty-seven older adults (78.2 ± 6.6 years) were recruited from a local retirement community. All participants completed the following assessments: 10-m usual and maximal walk, Short Physical Performance Battery (SPPB), 6-min walk (6MW), 8-foot up-and-go (UPGO), and 30-s chair stand. Based on their SPPB performance, low (≤ 9) and high (≥ 10) FF groups were formed. Among all participants, maximal walking velocity, not usual walking velocity, was significantly correlated with SPPB (r = .35; p < .05 and r = .19; p > .05, respectively). In the high functioning group, both maximal and usual walking velocities were correlated, but correlation coefficients were stronger for all variables for maximal walking velocity. These results suggest different walking conditions may be necessary to use for high and low functioning older adults; specifically, maximal walking velocity may be a preferred measure among high functioning older adults.

Morphological Differentiation of the Eggs of North American Container-Inhabiting Aedes Mosquitoes.

Aedes aegypti , Ae. albopictus, Ae. japonicus japonicus, and Ae. triseriatus eggs are described with the aid of color images and images from scanning electron microscopy. All eggs were broadly cigar shaped with Ae. triseriatus and Ae. j japonicus eggs being dull or matte black, while Ae. albopictus and Ae. aegypti eggs were shiny jet black. Aedes triseriatus eggs were lighter in color and had a rougher appearance when compared to those of Ae. j. japonicus. Aedes albopictus and Ae. aegypti eggs can be differentiated by the distinct presence of micropylar collars in Ae. aegypti. Our results reduce the need to rear these mosquitoes, reducing labor and time while providing an accurate identification of the vector mosquitoes.

La Crosse Virus in Aedes japonicus japonicus mosquitoes in the Appalachian Region, United States.

La Crosse virus (LACV), a leading cause of arboviral encephalitis in children in the United States, is emerging in Appalachia. For local arboviral surveillance, mosquitoes were tested. LACV RNA was detected and isolated from Aedes japonicus mosquitoes. These invasive mosquitoes may significantly affect LACV range expansion and dynamics.

Developing a measure of muscular power during a functional task for older adults.

BACKGROUND: Muscular power is an important aspect of many activities of daily living and declines at a faster rate than other fitness parameters (i.e. muscular strength and endurance). Assessing muscular power among older adults is problematic as many of the popular tests are contraindicated among older adults and field tests to assess muscular power among older adults have not been validated among older adults. Therefore, the aim of the present investigation was to determine the validity and reliability of a field test to measure of muscular power during a functional movement among community-dwelling older adults (≥ 65 years). METHODS: Twenty community-dwelling older adults (71.6 ± 5.6) volunteered to have their muscular power assessed during repeated sit-to-stand (STS) tasks. Each participant performed 10 STS with 60 s rest between trials. Muscular power was assessed during this functional movement with the Tendo as well as change in center of mass (COM) over time using cinematography. RESULTS: Relative power measured by Tendo was 5.34 ± 1.67 W/kg and values for COM were 5.39 ± 1.73 W/kg (p = .86). Cronbach's alpha for Tendo muscular power for repeated trials was .98. CONCLUSIONS: Tendo is a simple field method of determining muscular power among older adults and validation is essential. Results from this investigation support Tendo as a valid and reliable method for determining muscular power during a STS task among older adults. Clinicians may use this tool to evaluate and assess progress in older adults' power and physical functioning.

Prophylactic ankle taping: influence on treadmill-running kinematics and running economy.

Prophylactic ankle taping (PAT) is commonly used in sport. Prophylactic ankle taping may restrict ankle motion, which would affect the kinetic chain and alter gait. The purpose of this study was to examine the effects of PAT on lower extremity (LE) kinematics and running economy during treadmill running. Twelve recreational runners (9 women, 3 men; M ± SD age = 31.33 ± 8.04 years, height = 1.67 ± 0.81 m, mass = 61.84 ± 9.38 kg) completed two 20-minute running sessions (PAT and no tape: control [CON]) at a self-selected pace. Before each run, reflective markers were placed along the right side of the body. Sagittal plane kinematic data (60 Hz) were captured 4 times, and expired gases were measured for 2-minute after each video capture during both trials. Stride frequency, stride length, LE kinematic variables at initial contact and end contact (EC) were calculated. Cardiorespiratory variables and heart rate were also measured. Running economy was normalized to oxygen uptake per unit body mass per kilometer (milliliter per kilogram per kilometer) as running speeds varied. At EC, the PAT hip angle significantly decreased (p = 0.01) by 3.82°, whereas CON decreased by 0.85°. The range of motion tended to decrease over the 20-minute run (p = 0.08). Heart rate significantly increased over time (6.7%) but was not different between conditions. Prophylactic ankle taping did not significantly affect the physiological measures associated with the metabolic cost of treadmill running or the other kinematic variables. These findings suggest that the hip angle continued to decrease during the PAT condition at push-off in recreational runners without impacting the metabolic cost of transport.

Estimating pathogen-spillover risk using host-ectoparasite interactions.

Pathogen spillover corresponds to the transmission of a pathogen or parasite from an original host species to a novel host species, preluding disease emergence. Understanding the interacting factors that lead to pathogen transmission in a zoonotic cycle could help identify novel hosts of pathogens and the patterns that lead to disease emergence. We hypothesize that ecological and biogeographic factors drive host encounters, infection susceptibility, and cross-species spillover transmission. Using a rodent-ectoparasite system in the Neotropics, with shared ectoparasite associations as a proxy for ecological interaction between rodent species, we assessed relationships between rodents using geographic range, phylogenetic relatedness, and ectoparasite associations to determine the roles of generalist and specialist hosts in the transmission cycle of hantavirus. A total of 50 rodent species were ranked on their centrality in a network model based on ectoparasites sharing. Geographic proximity and phylogenetic relatedness were predictors for rodents to share ectoparasite species and were associated with shorter network path distance between rodents through shared ectoparasites. The rodent-ectoparasite network model successfully predicted independent data of seven known hantavirus hosts. The model predicted five novel rodent species as potential, unrecognized hantavirus hosts in South America. Findings suggest that ectoparasite data, geographic range, and phylogenetic relatedness of wildlife species could help predict novel hosts susceptible to infection and possible transmission of zoonotic pathogens. Hantavirus is a high-consequence zoonotic pathogen with documented animal-to-animal, animal-to-human, and human-to-human transmission. Predictions of new rodent hosts can guide active epidemiological surveillance in specific areas and wildlife species to mitigate hantavirus spillover transmission risk from rodents to humans. This study supports the idea that ectoparasite relationships among rodents are a proxy of host species interactions and can inform transmission cycles of diverse pathogens circulating in wildlife disease systems, including wildlife viruses with epidemic potential, such as hantavirus.

Expression of anti-chikungunya single-domain antibodies in transgenic Aedes aegypti reduces vector competence for chikungunya virus and Mayaro virus.

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related alphaviruses that cause acute febrile illness accompanied by an incapacitating polyarthralgia that can persist for years following initial infection. In conjunction with sporadic outbreaks throughout the sub-tropical regions of the Americas, increased global travel to CHIKV- and MAYV-endemic areas has resulted in imported cases of MAYV, as well as imported cases and autochthonous transmission of CHIKV, within the United States and Europe. With increasing prevalence of CHIKV worldwide and MAYV throughout the Americas within the last decade, a heavy focus has been placed on control and prevention programs. To date, the most effective means of controlling the spread of these viruses is through mosquito control programs. However, current programs have limitations in their effectiveness; therefore, novel approaches are necessary to control the spread of these crippling pathogens and lessen their disease burden. We have previously identified and characterized an anti-CHIKV single-domain antibody (sdAb) that potently neutralizes several alphaviruses including Ross River virus and Mayaro virus. Given the close antigenic relationship between MAYV and CHIKV, we formulated a single defense strategy to combat both emerging arboviruses: we generated transgenic Aedes aegypti mosquitoes that express two camelid-derived anti-CHIKV sdAbs. Following an infectious bloodmeal, we observed significant reduction in CHIKV and MAYV replication and transmission potential in sdAb-expressing transgenic compared to wild-type mosquitoes; thus, this strategy provides a novel approach to controlling and preventing outbreaks of these pathogens that reduce quality of life throughout the tropical regions of the world.

A Novel Digital Digit-Symbol Substitution Test Measuring Processing Speed in Adults At Risk for Alzheimer Disease: Validation Study.

BACKGROUND: Assessing cognitive constructs affected by Alzheimer disease, such as processing speed (PS), is important to screen for potential disease and allow for early detection. Digital PS assessments have been developed to provide widespread, efficient cognitive testing, but all have been validated only based on the correlation between test scores. Best statistical practices dictate that concurrent validity should be assessed for agreement or equivalence rather than using correlation alone. OBJECTIVE: This study aimed to assess the concurrent validity of a novel digital PS assessment against a gold-standard measure of PS. METHODS: Adults aged 45-75 years (n=191) participated in this study. Participants completed the novel digital digit-symbol substitution test (DDSST) and the Repeatable Battery for the Assessment of Neuropsychological Status coding test (RBANS-C). The correlation between the test scores was determined using a Pearson product-moment correlation, and a difference in mean test scores between tests was checked for using a 2-tailed dependent samples t test. Data were analyzed for agreement between the 2 tests using Bland-Altman limits of agreement and equivalency using a two one-sided t tests (TOST) approach. RESULTS: A significant moderate, positive correlation was found between DDSST and RBANS-C scores (r=.577; P<.001), and no difference in mean scores was detected between the tests (P=.93). Bias was nearly zero (0.04). Scores between the tests were found to display adequate agreement with 90% of score differences falling between -22.66 and 22.75 (90% limits of agreement=-22.91 to 22.99), and the scores were equivalent (P=.049). CONCLUSIONS: Analyses indicate that the DDSST is a valid digital assessment of PS. The DDSST appears to be a suitable option for widespread, immediate, and efficient PS testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04559789; https://clinicaltrials.gov/ct2/show/NCT04559789.

Exploring the immunogenicity of an insect-specific virus vectored Zika vaccine candidate.

Zika virus (ZIKV) is an important re-emerging flavivirus that presents a significant threat to human health worldwide. Despite its importance, no vaccines are approved for use in humans. Insect-specific flaviviruses (ISFVs) have recently garnered attention as an antigen presentation platform for vaccine development and diagnostic applications. Here, we further explore the safety, immunogenicity, and efficacy of a chimeric ISFV-Zika vaccine candidate, designated Aripo-Zika (ARPV/ZIKV). Our results show a near-linear relationship between increased dose and immunogenicity, with 1011 genome copies (i.e., 108 focus forming units) being the minimum dose required for protection from ZIKV-induced morbidity and mortality in mice. Including boosters did not significantly increase the short-term efficacy of ARPV/ZIKV-vaccinated mice. We also show that weanling mice derived from ARPV/ZIKV-vaccinated dams were completely protected from ZIKV-induced morbidity and mortality upon challenge, suggesting efficient transfer of maternally-derived protective antibodies. Finally, in vitro coinfection studies of ZIKV with Aripo virus (ARPV) and ARPV/ZIKV in African green monkey kidney cells (i.e., Vero-76) showed that ARPV and ARPV/ZIKV remain incapable of replication in vertebrate cells, despite the presence of active ZIKV replication. Altogether, our data continue to support ISFV-based vaccines, and specifically the ARPV backbone is a safe, immunogenic and effective vaccine strategy for flaviviruses.

The effect of a digital health coaching and health education protocol on cognition in adults at-risk for Alzheimer's.

Several modifiable lifestyle factors have been linked to cognitive ability and the risk of developing Alzheimer's disease and related dementias (ADRD). Health coaching (HC) is an intervention that addresses lifestyle factors associated with cognition. The effectiveness of an HC protocol was evaluated and compared with a health education (HE) intervention, representing the current standard of care, in a sample of 216 adults between the ages of 45 and 75 years who were at-risk for developing ADRD. Outcomes examined were global cognition, neuropsychological cognition, and Alzheimer's risk. HC participants received personalized coaching from a health coach focusing on nutrition, physical activity, sleep, stress, social engagement, and cognitive activity. HE participants received biweekly education materials focusing on the same modifiable lifestyle factors addressed by HC. Participants were assessed at baseline and again 4 months later. Self-reported global cognition scores improved only in the HC group (16.18 to 15.52, p = .03) and neuropsychological cognitive ability improved in the HE group (104.48 to 108.76, p < .001). When non-adherence in the HC group was accounted for, however, the mean change in neuropsychological score was similar between groups (p > .05), self-reported global cognition demonstrated an even larger mean improvement in the HC group (16.20 to 15.41, p = .01), and the HC group saw an improvement in ADRD protective risk score (- 10.39 to - 11.45, p = .007). These results indicate that HC and HE can both improve cognition, but HC may be more effective and may yield increased protection against ADRD risk.

Re-engineering aryl methylcarbamates to confer high selectivity for inhibition of Anopheles gambiae versus human acetylcholinesterase.

To identify potential human-safe insecticides against the malaria mosquito we undertook an investigation of the structure-activity relationship of aryl methylcarbamates inhibitors of acetylcholinesterase (AChE). Compounds bearing a ß-branched 2-alkoxy or 2-thioalkyl group were found to possess good selectivity for inhibition of Anopheles gambiae AChE over human AChE; up to 530-fold selectivity was achieved with carbamate 11d. A 3D QSAR model is presented that is reasonably consistent with log inhibition selectivity of 34 carbamates. Toxicity of these compounds to live Anopheles gambiae was demonstrated using both tarsal contact (filter paper) and topical application protocols.

La Crosse virus infection alters blood feeding behavior in Aedes triseriatus and Aedes albopictus (Diptera: Culicidae).

The effects of La Crosse virus (LACV) infection on blood feeding behavior in Aedes triseriatus (Say) and Aedes albopictus (Skuse) were investigated in the laboratory by measuring the size of the bloodmeal imbibed and the extent of refeeding by virus-infected and uninfected mosquitoes. LACV-infected Ae. triseriatus and Ae. albopictus took significantly less blood compared with uninfected mosquitoes. Twice as many virus-infected Ae. triseriatus mosquitoes refed compared with uninfected individuals (18 vs. 9%; P < 0.05); however, virus infection had no significant effect on the refeeding rate of Ae. albopictus. Reduction in bloodmeal size followed by an increased avidity for refeeding may lead to enhanced horizontal transmission of the LACV by its principal vector, Ae. triseriatus.

The effects of a downhill running bout on running economy.

This study investigated whether downhill (DH) running (10-min @ 214.4 m·min(-1) and -10% grade) would elicit acute and delayed effects on running economy (RE) upon completion of DH running (RE2) and daily over 72 h (RE3, RE4, RE5). Fifteen runners (8 female, 7 male) completed the protocol. RE was measured during level running performed at 70% VO2peak. A baseline RE test (RE1) was used for comparison. Muscle soreness was significantly elevated at RE3 and RE4 vs. RE1. Oxygen uptake was significantly elevated at RE2 relative to RE3, RE4 and RE5 but was not different from RE1. Heart rate was similarly elevated at RE2. Measures of ankle, knee and hip joint angles at heel strike and toe off were not affected at any time-point in a subset of subjects (N = 6). A short DH running bout did not elicit significant delayed adverse effects on oxygen uptake or gait parameters relative to baseline.