A study on the formative usability testing for modular powered wheelchair.

The increasing prevalence of mobility impairments underscores the urgent need for accessible and affordable mobility aids. To overcome the mobility limitations of people with disabilities, there is an increasing need for the development of lightweight and portable powered wheelchairs that can be easily loaded. This study aimed to perform an early health technology assessment and a formative usability evaluation on a modular (detachable) powered wheelchair. It aimed to gauge device satisfaction among users, pinpoint areas for improvement, and detect any unforeseen errors to inform future development. Engaging 16 participants, including powered wheelchair users, healthcare professionals, and caregivers, the research evaluated the wheelchair's functionality in various scenarios, emphasizing safety, effectiveness, and convenience. Statistical analyses of task performance and satisfaction surveys highlighted that, while powered wheelchair users successfully completed tasks focusing on driving and power control, healthcare professionals and caregivers encountered difficulties with the wheelchair's assembly and disassembly. Despite general positivity, the surveys indicated mixed satisfaction levels regarding safety, validity, and convenience, with specific issues related to frame durability, seat comfort, and control mechanisms. These findings suggest that refining the wheelchair's design and addressing user concerns could significantly enhance satisfaction and mobility services. Future efforts will include a thorough review of an advanced prototype and further satisfaction assessments.

We believe that our study makes a significant contribution to the literature by addressing a critical gap in the understanding of user-centric design and usability testing for powered wheelchairs.By emphasizing the importance of early assessments and incorporating user feedback into the development process, our research offers practical insights for creating more accessible and user-friendly mobility solutions.This contribution is particularly relevant in the context of advancing assistive technology and improving the quality of life for individuals with disabilities.

Astrocytic autophagy plasticity modulates Aß clearance and cognitive function in Alzheimer's disease.

BACKGROUND: Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta (Aß) in Alzheimer's disease (AD). However, reactive astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study to find out whether Aß-induced proteotoxic stress affects the expression of autophagy genes and the modulation of autophagic flux in astrocytes, and if yes, how Aß-induced autophagy-associated genes are involved Aß clearance in astrocytes of animal model of AD. METHODS: Whole RNA sequencing (RNA-seq) was performed to detect gene expression patterns in Aß-treated human astrocytes in a time-dependent manner. To verify the role of astrocytic autophagy in an AD mouse model, we developed AAVs expressing shRNAs for MAP1LC3B/LC3B (LC3B) and Sequestosome1 (SQSTM1) based on AAV-R-CREon vector, which is a Cre recombinase-dependent gene-silencing system. Also, the effect of astrocyte-specific overexpression of LC3B on the neuropathology in AD (APP/PS1) mice was determined. Neuropathological alterations of AD mice with astrocytic autophagy dysfunction were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through novel object recognition test (NOR) and novel object place recognition test (NOPR). RESULTS: Here, we show that astrocytes, unlike neurons, undergo plastic changes in autophagic processes to remove Aß. Aß transiently induces expression of LC3B gene and turns on a prolonged transcription of SQSTM1 gene. The Aß-induced astrocytic autophagy accelerates urea cycle and putrescine degradation pathway. Pharmacological inhibition of autophagy exacerbates mitochondrial dysfunction and oxidative stress in astrocytes. Astrocyte-specific knockdown of LC3B and SQSTM1 significantly increases Aß plaque formation and GFAP-positive astrocytes in APP/PS1 mice, along with a significant reduction of neuronal marker and cognitive function. In contrast, astrocyte-specific overexpression of LC3B reduced Aß aggregates in the brain of APP/PS1 mice. An increase of LC3B and SQSTM1 protein is found in astrocytes of the hippocampus in AD patients. CONCLUSIONS: Taken together, our data indicates that Aß-induced astrocytic autophagic plasticity is an important cellular event to modulate Aß clearance and maintain cognitive function in AD mice.

Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving.

RATIONALE: Incubation of cocaine craving refers to the progressive intensification of cue-induced craving during abstinence from cocaine self-administration. We showed previously that homomeric GluA1 Ca2+-permeable AMPARs (CP-AMPAR) accumulate in excitatory synapses of nucleus accumbens core (NAcc) medium spiny neurons (MSN) after ∼1 month of abstinence and thereafter their activation is required for expression of incubation. Therefore, it is important to understand mechanisms underlying CP-AMPAR plasticity. OBJECTIVES: We hypothesize that CP-AMPAR upregulation represents a retinoic acid (RA)-dependent form of homeostatic plasticity, previously described in other brain regions, in which a reduction in neuronal activity disinhibits RA synthesis, leading to GluA1 translation and CP-AMPAR synaptic insertion. We tested this using viral vectors to bidirectionally manipulate RA signaling in NAcc during abstinence following extended-access cocaine self-administration. RESULTS: We used shRNA targeted to the RA degradative enzyme Cyp26b1 to increase RA signaling. This treatment accelerated incubation; rats expressed incubation on abstinence day (AD) 15, when it is not yet detected in control rats. It also accelerated CP-AMPAR synaptic insertion measured with slice physiology. CP-AMPARs were detected in Cyp26b1 shRNA-expressing MSN, but not control MSN, on AD15-18. Next, we used shRNA targeted to the major RA synthetic enzyme Aldh1a1 to reduce RA signaling. In MSN expressing Aldh1a1 shRNA, synaptic CP-AMPARs were reduced in late withdrawal (AD42-60) compared to controls. However, we did not detect an effect of this manipulation on incubated cocaine seeking (AD40). CONCLUSIONS: These findings support the hypothesis that increased RA signaling during abstinence contributes to CP-AMPAR accumulation and incubation of cocaine craving.

TAZ deficiency exacerbates psoriatic pathogenesis by increasing the histamine-releasing factor.

BACKGROUND: Transcriptional coactivator with PDZ-biding motif (TAZ) is widely expressed in most tissues and interacts with several transcription factors to regulate cell proliferation, differentiation, and death, thereby influencing organ development and size control. However, very little is known about the function of TAZ in the immune system and its association with inflammatory skin diseases, so we investigated the role of TAZ in the pathogenesis of psoriasis. RESULTS: Interestingly, TAZ was expressed in mast cells associated, particularly in lysosomes, and co-localized with histamine-releasing factor (HRF). TAZ deficiency promoted mast cell maturation and increased HRF expression and secretion by mast cells. The upregulation of HRF in TAZ deficiency was not due to increased transcription but to protein stabilization, and TAZ restoration into TAZ-deficient cells reduced HRF protein. Interestingly, imiquimod (IMQ)-induced psoriasis, in which HRF serves as a major pro-inflammatory factor, was more severe in TAZ KO mice than in WT control. HRF expression and secretion were increased by IMQ treatment and were more pronounced in TAZ KO mice treated with IMQ. CONCLUSIONS: Thus, as HRF expression was stabilized in TAZ KO mice, psoriatic pathogenesis progressed more rapidly, indicating that TAZ plays an important role in preventing psoriasis by regulating HRF protein stability.

Molecular evolutionary characteristics of severe acute respiratory syndrome coronavirus 2 and the relatedness of epidemiological and socio-environmental factors.

After the first outbreak, SARS-CoV-2 infection continues to occur due to the emergence of new variants. There is limited information available on the comparative evaluation of evolutionary characteristics of SARS-CoV-2 among different countries over time, and its relatedness to epidemiological and socio-environmental factors within those countries. We assessed comparative Bayesian evolutionary characteristics for SARS-CoV-2 in eight countries from 2020 to 2022 using BEAST version 2.6.7. Additionally, the relatedness between virus evolution factors and both epidemiological and socio-environmental factors was analyzed using Pearson's correlation coefficient. The estimated substitution rates in the gene encoding S protein of SARS-CoV-2 exhibited a continuous increase from 2020 to 2022 and were divided into two distinct groups in 2022 (p value < 0.05). Effective population size (Ne) generally showed decreased patterns by time. Notably, the change rates of the substitution rates were negatively correlated with the cumulative vaccination rates in 2021. A strict and rapid vaccination policy in the United Arab Emirates dramatically reduced the evolution of the virus, compared to other countries. Also, the average yearly temperature in countries were negatively correlated with the substitution rates. The changes of six epitopes in SARS-CoV-2 were related to various socio-environmental factors. We figured out comparative virus evolutionary traits and the association of epidemiological and socio-environmental factors especially cumulative vaccination rates and average temperature.

TAZ deficiency impairs the autophagy-lysosomal pathway through NRF2 dysregulation and lysosomal dysfunction.

Transcriptional coactivator with a PDZ-binding motif (TAZ) plays a key role in normal tissue homeostasis and tumorigenesis through interaction with several transcription factors. In particular, TAZ deficiency causes abnormal alveolarization and emphysema, and persistent TAZ overexpression contributes to lung cancer and pulmonary fibrosis, suggesting the possibility of a complex mechanism of TAZ function. Recent studies suggest that nuclear factor erythroid 2-related factor 2 (NRF2), an antioxidant defense system, induces TAZ expression during tumorigenesis and that TAZ also activates the NRF2-mediated antioxidant pathway. We thus thought to elucidate the cross-regulation of TAZ and NRF2 and the underlying molecular mechanisms and functions. TAZ directly interacted with NRF2 through the N-terminal domain and suppressed the transcriptional activity of NRF2 by preventing NRF2 from binding to DNA. In addition, the return of NRF2 to basal levels after signaling was inhibited in TAZ deficiency, resulting in sustained nuclear NRF2 levels and aberrantly increased expression of NRF2 targets. TAZ deficiency failed to modulate optimal NRF2 signaling and concomitantly impaired lysosomal acidification and lysosomal enzyme function, accumulating the abnormal autophagy vesicles and reactive oxygen species and causing protein oxidation and cellular damage in the lungs. TAZ restoration to TAZ deficiency normalized dysregulated NRF2 signaling and aberrant lysosomal function and triggered the normal autophagy-lysosomal pathway. Therefore, TAZ is indispensable for the optimal regulation of NRF2-mediated autophagy-lysosomal pathways and for preventing pulmonary damage caused by oxidative stress and oxidized proteins.

MPoMA protects against lung epithelial cell injury via p65 degradation.

Numerous cases of lung injury caused by viral infection were reported during the coronavirus disease-19 pandemic. While there have been significant efforts to develop drugs that block viral infection and spread, the development of drugs to reduce or reverse lung injury has been a lower priority. This study aimed to identify compounds from a library of compounds that prevent viral infection that could reduce and prevent lung epithelial cell damage. We investigated the cytotoxicity of the compounds, their activity in inhibiting viral spike protein binding to cells, and their activity in reducing IL-8 production in lung epithelial cells damaged by amodiaquine (AQ). We identified N-(4-(4-methoxyphenoxy)-3-methylphenyl)-N-methylacetamide (MPoMA) as a non-cytotoxic inhibitor against viral infection and AQ-induced cell damage. MPoMA inhibited the expression of IL-8, IL-6, IL-1ß, and fibronectin induced by AQ and protected against AQ-induced morphological changes. However, MPoMA did not affect basal IL-8 expression in lung epithelial cells in the absence of AQ. Further mechanistic analysis confirmed that MPoMA selectively promoted the proteasomal degradation of inflammatory mediator p65, thereby reducing intracellular p65 expression and p65-mediated inflammatory responses. MPoMA exerted potent anti-inflammatory and protective functions in epithelial cells against LPS-induced acute lung injury in vivo. These findings suggest that MPoMA may have beneficial effects in suppressing viral infection and preventing lung epithelial cell damage through the degradation of p65 and inhibition of the production of inflammatory cytokines.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Seoul, Korea.

BACKGROUND: The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the endemic phase may vary from that during the previous pandemic phase. We evaluated the risk of infection in a general population with laboratory-confirmed coronavirus disease 2019 (COVID-19) in a community setting in Korea. MATERIALS AND METHODS: This study included 1,286 individuals who had been in contact with an index COVID-19 case between January 24, 2020, and June 30, 2022. Variables such as age, sex, nationality, place of contact, level of contact, the status of exposed cases, period, and level of mask-wearing were assessed. RESULTS: Among 1,286 participants, 132 (10.30%) were confirmed to have COVID-19. With increasing age, the risk of the exposed persons contracting COVID-19 from index cases tended to increase (P <0.001), especially for people in their 70s (odds ratio, 1.24; 95% confidence interval, 1.11-1.40; P <0.001). We found an increasing trend in the risk of a COVID-19 exposed case becoming a secondary infection case (P <0.001) in long-term care facilities where the attack rate was high. CONCLUSION: The risk of COVID-19 transmission is high in long-term care facilities where many older adults reside. Intensive management of facilities at risk of infection and strict mask-wearing of confirmed COVID-19 cases are necessary to prevent the risk of COVID-19 infection.

The microglial innate immune protein PGLYRP1 mediates neuroinflammation and consequent behavioral changes.

Peptidoglycan recognition protein 1 (PGLYRP1) is a pattern-recognition protein that mediates antibacterial actions and innate immune responses. Its expression and role in neuroinflammatory conditions remain unclear. We observed the upregulation of PGLYRP1 in inflamed human and mouse spinal cord and brain, with microglia being the primary cellular source. Experiments using a recombinant PGLYRP1 protein show that PGLYRP1 potentiates reactive gliosis, neuroinflammation, and consequent behavioral changes in multiple animal models of neuroinflammation. Furthermore, shRNA-mediated knockdown of Pglyrp1 gene expression attenuates this inflammatory response. In addition, we identify triggering receptor expressed on myeloid cell-1 (TREM1) as an interaction partner of PGLYRP1 and demonstrate that PGLYRP1 promotes neuroinflammation through the TREM1-Syk-Erk1/2-Stat3 axis in cultured glial cells. Taken together, our results reveal a role for microglial PGLYRP1 as a neuroinflammation mediator. Finally, we propose that PGLYRP1 is a potential biomarker and therapeutic target in various neuroinflammatory diseases.

Intranasal administration enhances size-dependent pulmonary phagocytic uptake of poly(lactic-co-glycolic acid) nanoparticles.

BACKGROUND: Nanoparticles exhibit distinct behaviours within the body, depending on their physicochemical properties and administration routes. However, in vivo behaviour of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, especially when administered nasally, remains unexplored; furthermore, there is a lack of comparative analysis of uptake efficiency among different administration routes. Therefore, here, we aimed to comprehensively investigate the real-time in vivo behaviour of PLGA nanoparticles across various administration routes. PLGA-NH2 nanoparticles of three sizes were synthesised using an oil-in-water single-emulsion method. We assessed their uptake by murine macrophage RAW264.7 cells using fluorescence microscopy. To enable real-time tracking, we conjugated p-SCN-Bn-deferoxamine to PLGA-NH2 nanoparticles and further radiolabelled them with 89Zr-oxalate before administration to mice via different routes. Nanoparticle internalisation by lung immune cells was monitored using fluorescence-activated cell sorting analysis. RESULTS: The nanoparticle sizes were 294 ± 2.1 (small), 522.5 ± 5.58 (intermediate), and 850 ± 18.52 nm (large). Fluorescent labelling did not significantly alter the nanoparticle size and charge. The level of uptake of small and large nanoparticles by RAW264.7 cells was similar, with phagocytosis inhibition primarily reducing the internalisation of large particles. Positron emission tomography revealed that intranasal delivery resulted in the highest and most targeted pulmonary uptake, whereas intravenous administration led to accumulation mainly in the liver and spleen. Nasal delivery of large nanoparticles resulted in enhanced uptake by myeloid immune cells relative to lymphoid cells, whereas dendritic cell uptake initially peaked but declined over time. CONCLUSIONS: Our study provides valuable insights into advancing nanomedicine and drug delivery, with the potential for expanding the clinical applications of nanoparticles.

Phenolic changes in a combined herbal extract of Lithospermum erythrorhizon, Houttuynia cordata, and Spirodela polyrhiza and alleviation of DNCB-induced atopic dermatitis in BALB/c mice.

Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of this study was to determine whether an herb combination of Lithospermum erythrorhizon (LE), Houttuynia cordata (HC), and Spirodela polyrhiza (SP) has a superior anti-AD effect. Forty-two compounds were identified in LE, HC, SP, and a combined herb extract of LE, HC, and SP (LHS) using ultra-high-pressure liquid chromatography (UHPLC)-Orbitrap mass spectrometer (MS). The concentration of flavonoid glycosides including orientin (luteolin-8-C-glucoside), quercetin-3-O-rhamnoside, and luteolin-7-O-glucoside in the LHS was increased than in individual extracts. Furthermore, the treatment of LHS most effectively inhibited the increase of epidermal thickness, the number of mast cells, and the release of immunoglobulin E compared with that with each extract. These results suggest that the potential anti-AD effects of the LHS are due to the changes of bioactive compounds by the combination of herbs. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01329-7.

Divergent Learning-Related Transcriptional States of Cortical Glutamatergic Neurons.

Experience-dependent gene expression reshapes neural circuits, permitting the learning of knowledge and skills. Most learning involves repetitive experiences during which neurons undergo multiple stages of functional and structural plasticity. Currently, the diversity of transcriptional responses underlying dynamic plasticity during repetition-based learning is poorly understood. To close this gap, we analyzed single-nucleus transcriptomes of L2/3 glutamatergic neurons of the primary motor cortex after 3 d motor skill training or home cage control in water-restricted male mice. "Train" and "control" neurons could be discriminated with high accuracy based on expression patterns of many genes, indicating that recent experience leaves a widespread transcriptional signature across L2/3 neurons. These discriminating genes exhibited divergent modes of coregulation, differentiating neurons into discrete clusters of transcriptional states. Several states showed gene expressions associated with activity-dependent plasticity. Some of these states were also prominent in the previously published reference, suggesting that they represent both spontaneous and task-related plasticity events. Markedly, however, two states were unique to our dataset. The first state, further enriched by motor training, showed gene expression suggestive of late-stage plasticity with repeated activation, which is suitable for expected emergent neuronal ensembles that stably retain motor learning. The second state, equally found in both train and control mice, showed elevated levels of metabolic pathways and norepinephrine sensitivity, suggesting a response to common experiences specific to our experimental conditions, such as water restriction or circadian rhythm. Together, we uncovered divergent transcriptional responses across L2/3 neurons, each potentially linked with distinct features of repetition-based motor learning such as plasticity, memory, and motivation.

Anticancer Activity of Astaxanthin-Incorporated Chitosan Nanoparticles.

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC50) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells.

Shewanella goraebulensis sp. nov., isolated from sea water.

A novel Gram-stain-negative, facultatively anaerobic and rod-shaped bacterial strain, designated as DAU312T, was isolated from the sea water of the eastern coast of the Republic of Korea. Optimal growth was observed at 25 °C, pH 7.0-8.0 and with NaCl concentrations of 2.0 % (w/v). Catalase and oxidase activities were detected. On the basis of 16S rRNA gene sequences, strain DAU312T showed the highest similarity (99.2 %) to the type strain Shewanella electrodiphila MAR441T. The complete genome sequence of strain DAU312T contains 4 893 483 bp and 40.5 mol% G+C. Phylogenetic analyses based on 16S rRNA gene sequences and the up-to-date bacterial core genes showed that strain DAU312T, S. electrodiphila MAR441T and S. olleyana were all part of the same monophyletic clade. Their average nucleotide identity, digital DNA-DNA hybridization and two-way average amino acid identity values with each other and type strains of close Shewanella species were 83.4-77.5 %, 27.3-22.0 % and 89.8-81.2 %, respectively. The major cellular fatty acids (>10 %) were iso-C15 : 0, summed feature 3 (C16 : 1 ω7с and/or C16 : 1 ω6с) and C16 : 0. Phosphatidylethanolamine and phosphatidylglycerol were the main polar lipids. The respiratory quinones were Q-7, Q-8, MK-7 and MMK-7. Based on these polyphasic taxonomic findings, the name Shewanella goraebulensis sp. nov. is suggested for strain DAU312T, which is considered to represent a novel species of the genus Shewanella. The type strain is DAU312T (=KCTC 72427 T=JCM 35744T=KCCM 43478T).

The impact of Renin-Angiotensin System Inhibitors on bone fracture risk: a nationwide nested case-control study.

BACKGROUND: The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort. METHODS: We employed a nested case-control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence. RESULTS: Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59-0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49-0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs. CONCLUSIONS: The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures.

Structural basis for T cell immunoglobulin and mucin protein 3 and Toxascaris leonina galectin complex.

T-cell immunoglobulin and mucin protein 3 (Tim-3), also known as Hepatitis A virus cellular receptor 2, has been discovered to have a negative regulatory effect on murine T-cell responses. Galectin-9 exhibits various biological effects, including cell aggregation, eosinophil chemoattraction, activation, and apoptosis, observed in murine thymocytes, T-cells, and human melanoma cells. Such approach demonstrated that Galectin-9 acts as a binding partner on Tim-3 and mediates the T-cell inhibitory effects. Tl-gal is a homologous protein to galectin-9, isolated from the adult stage of the canine gastrointestinal nematode parasite Toxascaris leonina. However, molecular mechanism between Tim-3 and galectin-9 is still remain unknown. Here, we describe the cryo-electron microscopy and X-ray structures and interactions of the Tim-3 and Tl-gal complex as well as their biochemical and biophysical characterization. In the structure, Ser46 residue of Tl-gal NCRD was bound to Asp25 residue of hTim-3. Compared to our previous study, the binding site of the complex is the same as the sugar binding site (the Ser46 residue) of Tl-gal. In addition, analysis of the complex structure revealed that the four Tl-gal molecules were in an open form packing and one mTim-3 peptide was bound to one Tl-gal molecule. These observations suggest that how Tl-gal binds hTim3 is essential to understanding the molecular mechanism for the Tim-3-galectin 9 interaction that regulates immune responses. This could potentially serve as a therapeutic target for inflammatory diseases.

The Use of Telemedicine for Screening and Addressing Social Needs in a Primary Care Pediatric Population in Brooklyn, New York.

The objective of this study was to analyze temporal changes in social needs (SN), comparing those who received routine annual in-person care to those receiving SN screenings through a combination of tele-social care and in-person care biannually. Our prospective cohort study used a convenience sample of patients from primary care practices. Baseline data were collected from April 2019 to March 2020. The intervention group (n = 336) received SN screening and referral telephone outreach from June 2020 to August 2021. The control group (n = 2890) was screened, in person, during routine visits at baseline and summer 2021. We used a repeated-measures logistic regression with general estimating equations to assess incremental change in individual SN for the intervention group. Food, housing, legal and benefit needs increased and peaked at the beginning of the pandemic and decreased after interventions (P < 0.001). There was a 32% decrease in the odds of food insecurity for those in the intervention group compared to the control group (adjusted OR 0.668, 95% confidence interval 0.444-1.004, P = 0.052), and a 75% decrease in the odds of housing insecurity (adjusted OR 0.247, 95% confidence interval 0.150-0.505, P < 0.001). During COVID-19, there was an increase in SN followed by a decrease after interventions were offered. Those who completed tele-social care showed greater improvements in social needs than those in routine care, with the greatest improvements in food and housing needs.

Clostridium ventriculi in a cynomolgus monkey with acute gastric dilatation and rupture: A case report.

Acute gastric dilatation (AGD) is one of the most prevalent and life-threatening diseases in nonhuman primates worldwide. However, the etiology of this syndrome has not been determined. Recently, sudden death occurred in a 7-year-old female cynomolgus monkey with a history of fecal microbiota transplantation using diarrheic stools. The monkey had undergone surgery previously. On necropsy, gastric dilatation and rupture demonstrated a tetrad arrangement on histopathologic examination. On 16S rRNA sequencing, a high population of Clostridium ventriculi was identified in the duodenum adjacent to stomach but not in the colon. This paper is the first report of Clostridium ventriculi infection in a cynomolgus macaque with acute gastric dilatation and rupture.

Indoor air quality and its determinants in underground shopping malls in Korea.

Underground shopping malls (USMs) are often open or semi-open environments with interconnected passageways, resulting in the sharing of indoor air. However, indoor air quality (IAQ) within these spaces can vary due to many diverse emission sources. We investigated the relationships between IAQ and geographical areas, as well as IAQ and store types, within USMs, in Korea. In 2020, we studied 10 different USMs, with a total of 128 outlets. We conducted comprehensive IAQ assessments (including measurements of fine particles (PM2.5), aldehydes, and volatile organic compounds (VOCs)) in stores, passages, and outdoor areas. The stores were categorized into three types: clothing, fashion accessories, and food services. Additionally, we measured environmental factors such as CO2 levels and presence of storefront walls. PM2.5 levels were higher outdoors, whereas aldehyde and VOC levels exhibited elevations within passages and the interior of stores than in the outdoor environment. The store-to-passage ratios for PM2.5, individual aldehydes, and VOC concentrations ranged from 1.06 to 4.93. Formaldehyde and total VOC (TVOC) concentrations were found to be elevated in clothing and fashion accessory stores, whereas PM2.5 concentrations were more prominent in food service establishments. Specific individual compounds, including propionaldehyde, hexaldehyde, benzene, n-heptane, toluene, n-octane, xylene, d-limonene, n-undecane, n-dodecane, and ethylbenzene concentrations exhibited associations with store types. Multivariate regression models demonstrated positive associations between most aldehydes and VOCs with CO2 concentrations and presence of storefront walls. This study underscored variations within USMs based on area and store type. Aldehyde and VOC concentrations were notably higher in clothing and fashion accessory stores than in food service outlets; these elevations were closely linked to CO2 levels and presence of storefront walls. These findings suggest that monitoring CO2 levels within USM stores, optimizing air-conditioning systems, and designing future stores without storefront walls can collectively contribute to an overall improvement of IAQ within USMs.