Characteristics of Acute Cartilage Response After Mechanical Loading in Patients with Early-Mild Knee Osteoarthritis.

This study determined whether the acute cartilage response, assessed by cartilage thickness and echo intensity, differs between patients with early-mild knee osteoarthritis (OA) and healthy controls. We recruited 56 women aged ≥ 50 years with Kellgren-Lawrence (KL) grade ≤ 2 (age, 70.6 ± 7.4 years; height, 153.7 ± 5.2 cm; weight, 51.9 ± 8.2 kg). Based on KL grades and knee symptoms, the participants were classified into control (KL ≤ 1, asymptomatic, n = 27) and early-mild knee OA groups (KL 1 and symptomatic, KL 2, n = 29). Medial femoral cartilage thickness and echo intensity were assessed using ultrasonographic B-mode images before and after treadmill walking (15 min, 3.3 km/h). To investigate the acute cartilage response, repeated-measures analysis of covariance (groups × time) with adjusted age, external knee moment impulse, steps during treadmill walking, and cartilage thickness at pre-walking was performed. A significant interaction was found at the tibiofemoral joint; after walking, the cartilage thickness was significantly decreased in the early-mild knee OA group compared to the control group (p = 0.002). At the patellofemoral joint, a significant main effect of time was observed, but no interaction was detected (p = 0.802). No changes in cartilage echo intensity at either the tibiofemoral or patellofemoral joints, and no interactions were noted (p = 0.295 and p = 0.063). As acute cartilage response after walking, the thickness of the medial tibiofemoral joint in the early-mild knee OA was significantly reduced than that in the control group. Thus, greater acute deformation after walking might be a feature found in patients with early-mild knee OA.

Subjective sleep onset latency is influenced by sleep structure and body heat loss in human subjects.

The present study examined the relationship between subjective sleep onset latency (SOL), sleep structure, changes in skin and body temperature, and subjective evaluation of sleep in healthy young adults to elucidate the pathophysiological mechanisms of insomnia. A total of 28 participants (age 21.54 [0.50] years) with no sleep problems participated in a 1-h polysomnographic recording that obtained objective sleep parameters during the daytime while skin and body temperatures were recorded. The distal-proximal skin temperature gradient (DPG) was calculated. Subjective parameters, such as subjective SOL, sleep time, and restorative sleepiness, were evaluated before and after sleep. Most participants estimated their sleep latency as being longer than their actual SOL (13.7 versus 7.6 min). Objective SOL was significantly correlated with each sleep stage parameter whereas subjective SOL was negatively correlated with Stage N2 sleep duration (Rho = -0.454, p = 0.020), slow-wave activity and delta power (Rho = -0.500, p = 0.011 and Rho = -0.432, p = 0.031, respectively), and ΔDPG (the degree of reduction of heat loss before and after lights-off). Stepwise regression analysis showed that ΔDPG was the strongest predictive factor in explaining the length of subjective SOL. The degree of heat dissipation before and after lights-off contributed most to the sensation of falling asleep in healthy young adults. This finding may be helpful for elucidating the physiological mechanisms of insomnia and its treatment.

Understanding muscle coordination during gait based on muscle synergy and its association with symptoms in patients with knee osteoarthritis.

OBJECTIVE: We aimed to investigate the muscle coordination differences between a control group and patients with mild and severe knee osteoarthritis (KOA) using muscle synergy analysis and determine whether muscle coordination was associated with symptoms of KOA. METHOD: Fifty-three women with medial KOA and 19 control patients participated in the study. The gait analyses and muscle activity measurements of seven lower limb muscles were assessed using a motion capture system and electromyography. Gait speed and knee adduction moment impulse were calculated. The spatiotemporal components of muscle synergy were extracted using non-negative matrix factorization, and the dynamic motor control index during walking (walk-DMC) was computed. The number of muscle synergy and their spatiotemporal components were compared among the mild KOA, severe KOA, and control groups. Moreover, the association between KOA symptoms with walk-DMC and other gait parameters was evaluated using multi-linear regression analysis. RESULTS: The number of muscle synergies was lower in mild and severe KOA compared with those in the control group. In synergy 1, the weightings of biceps femoris and gluteus medius in severe KOA were higher than that in the control group. In synergy 3, the weightings of higher tibial anterior and lower gastrocnemius lateralis were confirmed in the mild KOA group. Regression analysis showed that the walk-DMC was independently associated with knee-related symptoms of KOA after adjusting for the covariates. CONCLUSIONS: Muscle coordination was altered in patients with KOA. The correlation between muscle coordination and KOA may be attributed to the knee-related symptoms. Key points • Patients with knee osteoarthritis (OA) experienced a deterioration in muscle coordination when walking. • Loss of muscle coordination was associated with severe knee-related symptoms in knee OA. • Considering muscle coordination as a knee OA symptom-related factor may provide improved treatment.

The effect of nonrestorative sleep on incident hypertension 1-2 years later among middle-aged Hispanics/Latinos.

BACKGROUND: Insomnia is known to be a major risk factor for incident hypertension. Nonrestorative sleep (NRS), which refers to insufficiently rested sleep, has reported to associate with various diseases. This study aimed to investigate the longitudinal association between insomnia-related symptoms including NRS and incident hypertension 1-2 years later by age group (young, 18-39 years and middle-age, 40-64 years) using existing cohort data involving Hispanics/Latinos. METHODS: This study included 1100 subjects who had participated in both the Hispanic Community Health Study/Study of Latinos and its follow-up study, the Sueño Ancillary Study, and met additional eligibility criteria. Incident hypertension was assessed by self-reported history and/or the use of antihypertensives. The Women's Health Initiative Insomnia Rating Scale (WHIIRS) was used to evaluate insomnia-related symptoms (difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, difficulty returning to sleep, and NRS). Logistic regression analyses were conducted to assess the degree to which insomnia-related symptoms at baseline predicted incident hypertension. RESULTS: Among the participants (64% middle-aged, 36% young adults), 140 (12.7%) developed hypertension during the follow-up period. Among the sleep-related symptoms, only NRS predicted incident hypertension after adjusting for sociodemographic factors and physical condition (odds ratio: 1.88, 95% confidence interval: 1.10-3.21, p = 0.022) in middle-aged adults. None of the insomnia-related symptoms were associated with incident hypertension in the young adults. No association was found between WHIIRS-defined insomnia (total score ≥ 9) and incident hypertension in middle-aged adults or young adults. CONCLUSION: The present findings suggest the importance of focusing on NRS to help prevent the development of hypertension in middle-aged adults.

Ultrasonographic echo intensity in the medial femoral cartilage is enhanced prior to cartilage thinning in women with early mild knee osteoarthritis.

PURPOSE: We aimed to determine whether altered cartilage echo intensity is associated with knee osteoarthritis (OA) severity and whether the alteration occurs before thinning of the femoral cartilage in knee OA. METHODS: The medial femoral cartilage thickness and echo intensity of 118 women aged ≥ 50 years were assessed using an ultrasound imaging device. Based on the Kellgren-Lawrence (KL) grade and knee symptoms, participants were classified into five groups: control (asymptomatic grades 0-1), early OA (symptomatic grade 1), grade 2, grade 3, and grade 4. Analysis of covariance, with adjusted age and height, and the Sidak post hoc test were used to assess the differences in cartilage thickness and echo intensity in knees with varying OA severity. RESULTS: The echo intensity on longitudinal images, equivalent to the tibiofemoral weight-bearing surface, was significantly higher in the grade 2 group than that in the control group (p = 0.049). However, no significant difference was noted in cartilage thickness (n.s.). In the grades 3 and 4 groups, cartilage thickness became thinner as OA progressed (p < 0.001 and p < 0.001, respectively). However, the cartilage echo intensity was not significantly enhanced compared with that of the grade 2 group (n.s.). There were no significant differences in the cartilage thickness and echo intensity between the early OA and control groups on the longitudinal images (n.s.). CONCLUSIONS: The echo intensity of the medial femoral cartilage was high in patients with KL grade 2, without decreased thickness. Our findings suggested that higher echo intensity is a feature of early cartilage degeneration in mild knee OA. Further studies are needed to establish this feature as a useful screening parameter of early cartilage degeneration in knee OA. LEVEL OF EVIDENCE: Level III.

Assessment of fore-, mid-, and rear-foot alignment and their association with knee symptoms and function in patients with knee osteoarthritis.

OBJECTIVE: Hallux valgus, flatfoot, and rearfoot eversion are well-known major complications of knee osteoarthritis (OA). However, there is no consensus on the association between these foot malalignments and knee symptoms or function. Thus, this study aimed to examine the association between foot alignment and knee symptoms or function in patients with knee OA. METHODS: Female patients aged ≥ 50 years with symptomatic knee OA participated in this study. Knee symptoms and function were assessed using the Knee Society Scoring System (KSS). Hallux valgus, navicular/foot ratio, and leg heel alignment were used as the forefoot, midfoot, and rearfoot alignment indices, respectively. The navicular/foot ratio was defined as the ratio of the navicular height to the total foot length. We performed multiple linear regression analysis to examine the associations between foot alignment and knee symptoms or function. RESULTS: Seventy-eight participants participated our study. KSS symptom score was significantly associated with navicular/foot ratio (regression coefficient [ß], -0.30; 95% confidence interval [CI], -109.2 to -20.5; P = 0.005), knee extensor strength (ß, 0.32; 95% CI, 0.02 to 0.09; P = 0.004), and age (ß, 0.24; 95% CI, 0.01 to 0.32; P = 0.036). KSS function score was not associated with foot alignments but with knee extensor strength (ß, 0.40; 95% CI, 0.10 to 0.33; P = 0.001) and body mass index (ß, -0.35; 95% CI, -2.82 to -0.66; P = 0.002). CONCLUSIONS: Knee symptoms were significantly associated with midfoot alignment in patients with medial knee OA. This suggests that lower navicular height in patients with medial knee OA may relate with the alleviation of knee symptoms. Key Points • In patients with medial knee OA, midfoot alignment was significantly associated with knee symptoms in patients with medial knee OA; however, knee function was not associated with foot alignment. • Lower navicular height in patients with medial knee OA may relate with the alleviation of knee symptoms.

Enhanced echo intensity in vastus medialis is associated with worsening of functional disabilities and symptoms in patients with knee osteoarthritis: a 3 years longitudinal study.

Patients with knee osteoarthritis (OA) experience muscle quality loss, and is characterized by the enhanced echo intensity (EI) of the vastus medialis (VM) muscles and a high extracellular water-to-intracellular water (ECW/ICW) ratio of the thigh. This study aimed to elucidate the association between muscle degeneration and the worsening of functional disabilities and symptoms in patients with KOA over 3 years duration. Thirty-three patients with KOA who completed follow-up over 3 years were included in the analysis. The knee scoring system (KSS) was used to evaluate the functional abilities and symptoms. Based on the 3 years change in KSS scores, patients were classified into progressive or non-progressive groups. Muscle thickness (MT) and EI of the VM were determined using ultrasonography. The ECW/ICW ratio was measured using segmental-bioelectrical impedance spectroscopy. Multivariable logistic regression analyses were conducted with the groups as the dependent variables and VM-MT, VM-EI, and ECW/ICW ratio at baseline as independent variables, including potential confounders. Thirteen (39.4%) patients showed progressive features. VM-EI at baseline was significantly associated with the progression of functional disabilities (adjusted odds ratio [OR] 1.24; 95% confidence interval [CI] 1.03 - 1.50) and symptoms (adjusted OR 1.13; 95% CI 1.01 - 1.25). Enhanced VM-EI was associated with the worsening of functional disabilities and symptoms in patients with KOA over a period of 3 years. Therefore, the assessment of VM-EI using ultrasonography is a useful indicator for predicting the future worsening of KOA.

Effect of age on shear modulus, muscle thickness, echo intensity of the upper limb, lower limb, and trunk muscles in healthy women.

PURPOSE: This study aimed to examine the effect of age on the mechanical properties, muscle size, and muscle quality in the upper and lower limb and trunk muscles. METHODS: We evaluated the shear modulus (G), muscle thickness (MT), and echo intensity (EI) of the upper and lower limb and trunk muscles of 83 healthy women (21-83-year-old). The G values of some limb muscles were measured in relaxed and stretched positions. RESULTS: Regarding the effect of age on G at the distinct positions, the G of the upper limb muscles were not significantly correlated with age in the relaxed and stretched positions. In contrast, the G of the iliacus showed a significant negative correlation in both positions. Additionally, the G of the rectus femoris had a significant negative correlation only in the relaxed position. Regarding differences among body parts, the G of the lower limb and oblique abdominal muscles showed a significant negative correlation, but no correlation in the upper limb, rectus abdominis, and back muscles. Moreover, MT showed a significant negative correlation with age in the lower limb, abdominal, and erector spinae muscles, but no correlation was detected in the upper limb and lumbar multifidus muscles. EI had a significant positive correlation in all the muscles. CONCLUSION: The effect of age on G depended on body parts, and the G of the lower limb and oblique abdominal muscles negatively associated with age. Additionally, G in the relaxed position may be more susceptible to aging than G in the stretched position.

The association between subjective-objective discrepancies in sleep duration and mortality in older men.

A discrepancy in subjective and objective estimations of sleep duration, which often diverge, could have long-term adverse effects on health outcomes in older adults. Using data from 2674 older adult men (≥ 65 years of age) of the Osteoporotic Fractures in Men Sleep Study, we assessed the longitudinal association between misperception index (MI), calculated as MI = (objective sleep duration - subjective sleep duration)/objective sleep duration, and all-cause mortality. During the follow-up with a mean (standard deviation) of 10.8 (4.2) years, 1596 deaths were observed. As a continuous variable, MI showed a linear relationship with all-cause mortality after adjusting for multiple covariates, including polysomnography-measured objective sleep duration [fully adjusted hazard ratio (HR), 0.69; 95% confidence interval [CI], 0.56-0.84]. As a categorical variable, the lowest MI quartile (vs. the interquartile MI range) was associated with increased mortality (fully adjusted HR, 1.28; 95% CI, 1.12-1.46), whereas the highest MI quartile was not associated with mortality (fully adjusted HR, 0.97; 95% CI, 0.85-1.11). The subjective overestimation of sleep duration may be a risk factor for all-cause mortality in older men. Future studies should examine why subjective overestimation of sleep duration is associated with all-cause mortality from a physiological perspective.

Identification of novel orthonairoviruses from rodents and shrews in Gabon, Central Africa.

In Africa, several emerging zoonotic viruses have been transmitted from small mammals such as rodents and shrews to humans. Although no clinical cases of small mammal-borne viral diseases have been reported in Central Africa, potential zoonotic viruses have been identified in rodents in the region. Therefore, we hypothesized that there may be unrecognized zoonotic viruses circulating in small mammals in Central Africa. Here, we investigated viruses that have been maintained among wild small mammals in Gabon to understand their potential risks to humans. We identified novel orthonairoviruses in 24.6 % of captured rodents and shrews from their kidney total RNA samples. Phylogenetic analysis revealed that the novel viruses, Lamusara virus (LMSV) and Lamgora virus, were closely related to Erve virus, which was previously identified in shrews of the genus Crocidura and has been suspected to cause neuropathogenic diseases in humans. Moreover, we show that the LMSV ovarian tumour domain protease, one of the virulence determination factors of orthonairoviruses, suppressed interferon signalling in human cells, suggesting the possible human pathogenicity of this virus. Taken together, our study demonstrates the presence of novel orthonairoviruses that may pose unrecognized risks of viral disease transmission in Gabon.

Associations of nonrestorative sleep and insomnia symptoms with incident depressive symptoms over 1-2 years: Longitudinal results from the Hispanic Community Health Study/Study of Latinos and Sueño Ancillary Study.

BACKGROUND: Nonrestorative sleep (NRS), defined as insufficiently rested or refreshed sleep, is considered to play an important role in the development of depression. The aim of this study is to investigate the predictive ability of insomnia-related symptoms, including NRS, for incident depressive symptoms (DEPs) in a longitudinal manner. METHODS: We used data of 1196 samples aged 18-64 years who participated in both the Hispanic Community Health Study/Study of Latinos conducted in 2008-2010 and the follow-up study (Sueño Ancillary Study) conducted in 2010-2013. DEPs and insomnia-related symptoms (difficulty initiating sleep [DIS], difficulty maintaining sleep [DMS], early morning awakening [EMA], difficulty returning to sleep [DRS], and NRS) were evaluated by the 10-item Center for Epidemiologic Studies Depression Scale and the Women's Health Initiative Insomnia Rating Scale, respectively. A logistic regression analysis was used to evaluate the predictive ability of each insomnia-related symptom at baseline for incident DEPs in couple-years. RESULTS: In the univariate logistic regression analysis, all insomnia-related symptoms had significant associations with incident DEPs (DIS, odds ratio [OR] = 1.6; DMS, OR = 1.6; EMA, OR = 1.5; DRS, OR = 1.9; NRS, OR = 2.5). After adjusting for sociodemographic factors and the confounding effects of other insomnia-related symptoms, only NRS (OR = 2.2, 95% confidence interval = 1.4-3.5, p = .001) was significantly associated with incident DEPs. CONCLUSIONS: NRS was a risk factor for incident DEPs, which includes a predictive ability for other insomnia-related symptoms. Our results suggest that focusing on NRS is an effective strategy for preventing depression in public health promotions.

Mortality associated with nonrestorative short sleep or nonrestorative long time-in-bed in middle-aged and older adults.

Associations of sleep duration with human health could differ depending on whether sleep is restorative. Using data from 5804 participants of the Sleep Heart Health Study, we examined the longitudinal association of sleep restfulness combined with polysomnography-measured total sleep time (TST) or time in bed (TIB), representing different sleeping behaviors, with all-cause mortality. Among middle-aged adults, compared with restful intermediate TST quartile, the lowest TST quartile with feeling unrested was associated with higher mortality (hazard ratio [HR], 1.54; 95% confidence interval [CI] 1.01-2.33); the highest TST quartile with feeling rested was associated with lower mortality (HR, 0.55; 95% CI 0.32-0.97). Among older adults, the highest TIB quartile with feeling unrested was associated with higher mortality, compared with restful intermediate TIB quartile (HR, 1.57; 95% CI 1.23-2.01). Results suggest a role of restorative sleep in differentiating the effects of sleep duration on health outcomes in midlife and beyond.

Association of Subjective Quality and Quantity of Sleep with Quality of Life among a General Population.

This study aimed to determine whether both subjective sleep quality and sleep duration are directly associated with quality of life (QOL), as well as indirectly associated with QOL through insomnia symptoms. Individuals aged 20-69 years without mental illness (n = 9305) were enrolled in this web-based cross-sectional survey. The Short Form-8 was used to assess physical and mental QOL. We used the Pittsburgh Sleep Quality Index (PSQI) and extracted items related to subjective sleep quality and sleep duration. Insomnia symptoms were also extracted from the PSQI. The hypothesized models were tested using structural equation modeling. Worse sleep quality, but not shorter sleep duration, was related to worse physical QOL. Both worse sleep quality and shorter sleep duration were related to worse mental QOL. Insomnia symptoms mediated these relationships. Subgroup analyses revealed a U-shaped relationship between sleep duration and physical/mental QOL. However, the relationship between sleep quality and physical/mental QOL was consistent regardless of sleep duration. The results suggest that subjective sleep quality has a more coherent association with QOL than subjective sleep duration. Because of its high feasibility, a questionnaire on overall sleep quality could be a useful indicator in future epidemiological studies of strategies for improving QOL.

iPSC screening for drug repurposing identifies anti-RNA virus agents modulating host cell susceptibility.

Human pathogenic RNA viruses are threats to public health because they are prone to escaping the human immune system through mutations of genomic RNA, thereby causing local outbreaks and global pandemics of emerging or re-emerging viral diseases. While specific therapeutics and vaccines are being developed, a broad-spectrum therapeutic agent for RNA viruses would be beneficial for targeting newly emerging and mutated RNA viruses. In this study, we conducted a screen of repurposed drugs using Sendai virus (an RNA virus of the family Paramyxoviridae), with human-induced pluripotent stem cells (iPSCs) to explore existing drugs that may present anti-RNA viral activity. Selected hit compounds were evaluated for their efficacy against two important human pathogens: Ebola virus (EBOV) using Huh7 cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Vero E6 cells. Selective estrogen receptor modulators (SERMs), including raloxifene, exhibited antiviral activities against EBOV and SARS-CoV-2. Pioglitazone, a PPARγ agonist, also exhibited antiviral activities against SARS-CoV-2, and both raloxifene and pioglitazone presented a synergistic antiviral effect. Finally, we demonstrated that SERMs blocked entry steps of SARS-CoV-2 into host cells. These findings suggest that the identified FDA-approved drugs can modulate host cell susceptibility against RNA viruses.

Numerical Study on Spray Drying Process: Effect of Nonuniform Temperature Field and Interaction between Droplets on Evaporation Rates of Individual Droplets.

Spray drying process is widely used to produce particulate materials in the pharmaceutical industries, such as porous materials for direct compression, solid dispersion for improvement of drug dissolution properties, micro encapsulation to stabilize active compounds, taste masking, preparation of dry powder for inhalation. However, as many factors affect the physical properties of dried particles and the spray drying processes have complex behaviors in which heat and mass transfer occur simultaneously, the detailed mechanisms of dry particle generation have yet to be sufficiently elucidated. In this study, computational fluid dynamics was used to simulate water droplet evaporation in a spray dryer, and the evaporation kinetics of "individual droplets" in the droplet aggregate (group) were analyzed. The numerical simulation revealed that each droplet had different evaporation rates owing to the following two reasons. First, the driving force of evaporation, ΔT, changed every moment as the droplets traveled through different temperature fields in the drying tower. Second, it was calculated the driving force for droplet evaporation differed from the ideal system because the evaporation of other droplets changed the fluid characteristics around the droplets. The obtained results are important findings that lead to the understanding the spray drying process to design and manufacture the pharmaceutical products.

Periocular skin warming promotes body heat loss and sleep onset: a randomized placebo-controlled study.

Periocular skin warming was reported to have favorable effects on subjective and objective sleep quality. We hypothesized that enhancing body heat loss by periocular skin warming would reduce sleep onset and improve sleep quality. Eighteen healthy volunteers were asked to maintain wakefulness with their eyes closed for 60 min after applying either a warming or sham eye mask, followed by a 60-min sleep period. Compared to the sham, periocular warming increased the distal skin temperature and distal-proximal skin temperature gradient only during the 30-min thermal manipulation period. In the subsequent sleep period, periocular warming facilitated sleep onset, increased stage 2 sleep and electroencephalographic delta activity during the first half of the sleep period relative to the sham. These results suggest that periocular skin warming may accelerate and deepen sleep by enhancing physiological heat loss via the distal skin, mimicking physiological conditions preceding habitual sleep.

Diurnal repeated exercise promotes slow-wave activity and fast-sigma power during sleep with increase in body temperature: a human crossover trial.

The effects of exercise on sleep have been explored from various perspectives, but little is known about how the effects of acute exercise on sleep are produced through physiological functions. We used a protocol of multiple daytime sessions of moderate-intensity aerobic exercise and examined the subsequent effects on sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Fourteen healthy men who did not exercise regularly were evaluated under the baseline (no exercise) and exercise conditions on a within-subject crossover basis. Under the exercise condition, each participant performed a 40-min aerobic workout at 40% of maximal oxygen intake, four times between morning and early evening. We observed a 33% increase in slow-wave sleep (SWS; P = 0.005), as well as increases in slow-wave activity (SWA; P = 0.026), the fast-sigma power/SWA ratio (P = 0.005), and subjective sleep depth and restorativeness the following morning. Moreover, both CBT and the DPG increased during sleep after exercise (P = 0.021 and P = 0.047, respectively). Regression analysis identified an increased nocturnal DPG during sleep after exercise as a factor in the increase in SWA. The fast-sigma/SWA ratio correlated with CBT. The performance of acute exercise promotes SWS with nocturnal elevation in the DPG. Both CBT and fast-sigma power may play a role in the specific physiological status of the body after exercise. NEW & NOTEWORTHY We used multiple daytime sessions of moderate-intensity aerobic exercise to examine the effects on the sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Significant increases in slow-wave activity (SWA), CBT, DPG, fast-sigma power, and subjective parameters were observed during the night and the following morning. Nocturnal DPG is a factor in the increased SWA.

Periocular skin warming elevates the distal skin temperature without affecting the proximal or core body temperature.

Periocular skin warming reportedly improves the objective and subjective sleep quality in adults with mild difficulty in falling asleep. To clarify the effects of periocular warming, we examined the distal skin temperatures (hands and feet), proximal skin temperature (infraclavicular region) and core body temperature as well as the distal-proximal skin temperature gradient (DPG). Nineteen healthy males underwent two experimental sessions, wherein they used a warming or sham eye mask under a semi-constant routine protocol in a crossover manner. Participants were instructed to maintain wakefulness with their eyes closed for 60 minutes after wearing the eye mask. The warming eye mask increased the periocular skin temperature to 38-40 °C for the first 20 minutes, whereas the temperature remained unchanged with the sham mask. Compared to that of the sham eye mask, the warming eye mask significantly increased the temperatures of the hands and feet and the DPG, whereas the proximal skin and core body temperatures were unaffected. Subjective sleepiness and pleasantness were significantly increased by the warming eye mask. These results represent physiological heat loss associated with sleep initiation without affecting the proximal skin or core body temperatures, suggesting that thermal stimulation in certain areas can provoke similar changes in remote areas of the body.

Genetic characterization of Lassa virus strains isolated from 2012 to 2016 in southeastern Nigeria.

Lassa virus (LASV) is endemic in parts of West Africa where it causes Lassa fever (LF), a viral hemorrhagic fever with frequent fatal outcomes. The diverse LASV strains are grouped into six major lineages based on the geographical location of the isolated strains. In this study, we have focused on the lineage II strains from southern Nigeria. We determined the viral sequences from positive cases of LF reported at tertiary hospitals in Ebonyi and Enugu between 2012 and 2016. Reverse transcription-polymerase chain reaction (RT-PCR) showed that 29 out of 123 suspected cases were positive for the virus among which 11 viral gene sequences were determined. Phylogenetic analysis of the complete coding sequences of the four viral proteins revealed that lineage II strains are broadly divided into two genetic clades that diverged from a common ancestor 195 years ago. One clade, consisting of strains from Ebonyi and Enugu, was more conserved than the other from Irrua, although the four viral proteins were evolving at similar rates in both clades. These results suggested that the viruses of these clades have been distinctively evolving in geographically separate parts of southern Nigeria. Furthermore, the epidemiological data of the 2014 outbreak highlighted the role of human-to-human transmission in this outbreak, which was supported by phylogenetic analysis showing that 13 of the 16 sequences clustered together. These results provide new insights into the evolution of LASV in southern Nigeria and have important implications for vaccine development, diagnostic assay design, and LF outbreak management.

Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.

In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs). IFNT treatment induced 348 differentially expressed genes (DEGs); however, there are few DEGs in IFNT2 or IFNTc1 treated EECs, indicating that IFNT2-induced DEGs were similar to those induced by IFNTc1 treatment. In in silico analysis, we identified four IFNT2- and IFNTc1-induced pathways: 1) type II interferon signaling, 2) proteasome degradation, 3) type III interferon signaling, and 4) DNA damage response. We further demonstrated that IFNT2 and IFNTc1 up-regulated several transcription factors, among which forkhead box S1 (FOXS1) was identified as the most highly expressed gene. Furthermore, the knockdown of FOXS1 in IFNT2- or IFNTc1-treated EECs similarly down-regulated 9 genes including IRF3 and IRF9, and up-regulated 9 genes including STAT1, STAT2, and IRF8. These represent the first demonstration that effects of each IFNT on EECs were studied, and suggest that endometrial response as well as signaling mechanisms were similar between two IFNT variants existed in utero.