Search

A symmetric gait pattern in humans reflects near-identical movement in bilateral limbs during walking. However, little is known about how gait symmetry changes on different inclines. This study aimed to address this knowledge gap using the central pattern generator and internal model hypotheses. Eighteen healthy young adults underwent five 2-minute walking trials (inclines of +15%, +8%, 0%, −8%, and −15%). Dependent variables included step time, step length, step width, maximum heel clearance, time to peaks of maximum heel clearance, their corresponding coefficients of variation (CV), and respective symmetry indices (SI). Significant differences were observed in SI of step length (p = .022), step length variability (p

The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation. DNL343 reduced CNS ISR activity and neurodegeneration in a dose-dependent manner in two established in vivo models – the optic nerve crush injury and an eIF2B loss of function (LOF) mutant – demonstrating neuroprotection in both and preventing motor dysfunction in the LOF mutant mouse. Treatment with DNL343 at a late stage of disease in the LOF model reversed elevation in plasma biomarkers of neuroinflammation and neurodegeneration and prevented premature mortality. Several proteins and metabolites that are dysregulated in the LOF mouse brains were normalized by DNL343 treatment, and this response is detectable in human biofluids. Several of these biomarkers show differential levels in CSF and plasma from patients with vanishing white matter disease (VWMD), a neurodegenerative disease that is driven by eIF2B LOF and chronic ISR activation, supporting their potential translational relevance. This study demonstrates that DNL343 is a brain-penetrant ISR inhibitor capable of attenuating neurodegeneration in mouse models and identifies several biomarker candidates that may be used to assess treatment responses in the clinic.

Se Young Jung,1,2 Hui-Woun Moon,2 Da Som Me Park,2 Sumi Sung,3 Hyesil Jung4 1Department of Family Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 2Office of eHealth Research and Business, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 3Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; 4Department of Nursing, College of Medicine, Inha University, Incheon, Republic of KoreaCorrespondence: Hyesil Jung, Department of Nursing, College of Medicine, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 2221, Republic of Korea, Tel +82-32-860-8206, Fax +82-32-874-5880, Email hsjung@inha.ac.krBackground: Inpatients commonly experience problems with elimination due to incontinence, urinary retentions, and complications with indwelling catheters. Although elimination care (EC) is an important nursing area, few studies explore the burden of EC on nurses.Aim: To identify the burden on EC by analyzing nurses’ opinions using sequential explanatory mixed method.Methods: This research was conducted using a sequential explanatory mixed-methods design. A total of 59 nurses at a tertiary hospital in South Korea participated in the study from January 1 to March 31, 2022. For quantitative analysis, information about number of delays of work due to EC, required time for serving bedpan or diaper changes, percentage of EC per shift, and percentage of patients who need EC was collected through a survey. For qualitative analysis, focus group interviews were conducted to identify factors that put a burden on EC. Important themes were derived by analyzing nurses’ opinions on EC.Results: For nurses in intensive care units, general wards, and integrated nursing care wards, the number of work delays due to EC was 3.6 ± 1.5, 2.3 ± 1.2, and 4.8 ± 2.4 (p< 0.01), respectively. The mean percentage of EC work out of total nursing tasks per shift was 36.2 ± 19.0, 29.3 ± 14.4, and 43.8 ± 14.1 (p=0.02), respectively. The mean percentage of patients requiring EC out of patients a nurse cares was 85.4 ± 16.6, 41.3 ± 26.1, and 58.8 ± 21.9 (p< 0.01), respectively. Following qualitative analysis, four themes related to nurses’ EC burden were derived: physical burden, frequent care needs, delay of other jobs due to EC, and complications. Among them, frequent care needs were found to be the primary factor requiring consideration to reduce nurses’ burden.Conclusion: This research found that EC is one of the most burdensome tasks that nurses want to avoid. To alleviate their burden, effective EC protocol or smart medical devices assisting with EC should be developed.Keywords: nursing, elimination care, mixed-methods approach

Background Sensory-motor perturbations have been widely used to assess astronauts’ balance in standing during pre-/post- spaceflight. However, balance control during walking, where most falls occur, was less studied in these astronauts. A study found that applying either visual or platform oscillations reduced the margin of stability (MOS) in the anterior-posterior direction (MOSap) but increased MOS in the medial-lateral direction (MOSml) as a tradeoff. This tradeoff induced an asymmetric gait. This study extended the current knowledge to investigate overall stability under unpredictable environments. This study aimed to determine (1) whether quasi-random treadmill perturbations with or without full vision support would result in a significant reduction in MOSap but an increase in MOSml and (2) regardless of whether vision support was provided, quasi-random treadmill perturbations might result in asymmetric gait patterns. Methods Twenty healthy young adults participated in this study. Three experimental conditions were semi-randomly assigned to these participants as follows: (1) the control condition (Norm), walking normally with their preferred walking speed on the treadmill; (2) the treadmill perturbations with full vision condition (Slip), walking on the quasi-random varying-treadmill-belt-speeds with full vision support; and (3) the treadmill perturbations without full vision condition (Slip_VisionBlocked, blackout vision through customized vision-blocked goggles), walking on the quasi-random varying-treadmill-belt-speeds without full vision support. The dependent variables were MOSap, MOSml, and respective symmetric indices. A one-way repeated ANOVA measure or Friedman Test was applied to investigate the differences among the conditions mentioned above. Results There was an increase in MOSap in Slip (p = 0.001) but a decrease in MOSap in Slip_VisionBlocked (p = 0.001) compared to Norm condition. The MOSml was significantly greater in both Slip and Slip_VisionBlocked conditions compared to the Norm condition (p = 0.011; p

This study examines the relationship between the wingbeat frequency of flying insects and ambient temperature, leveraging data from over 302,000 insect observations obtained using a near-infrared optical sensor during an eight-month field experiment. By measuring the wingbeat frequency as well as wing and body optical cross-sections of each insect in conjunction with the ambient temperature, we identified five clusters of insects and analyzed how their average wingbeat frequencies evolved over temperatures ranging from 10 °C to 38 °C. Our findings reveal a positive correlation between temperature and wingbeat frequency, with a more pronounced increase observed at higher wingbeat frequencies. Frequencies increased on average by 2.02 Hz/°C at 50 Hz, and up to 9.63 Hz/°C at 525 Hz, and a general model is proposed. This model offers a valuable tool for correcting wingbeat frequencies with temperature, enhancing the accuracy of insect clustering by optical and acoustic sensors. While this approach does not account for species-specific responses to temperature changes, our research provides a general insight, based on all species present during the field experiment, into the intricate dynamics of insect flight behavior in relation to environmental factors.

Abstract Background Genetic mutations underlying familial Alzheimer’s disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain. Methods We engineered a novel App knock-in mouse model (App SAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous App SAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays. Results Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App SAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged. Discussion Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.

Background Eighty-eight percent of the persons with bilateral vestibular dysfunction have reported at least one fall within the past 5 years. The apparent alternations due to the bilateral vestibular dysfunctions (BVD) are the gait characteristics, such as slower walking speed, prolonged stance phase, and shorter step length. Unexpectedly, due to the prevalence of this BVD being relatively low, attention is not obtained as same as in other vestibular disorders. Moreover, how does walking on different inclines, part of daily activities, alter the gait characteristics under the unreliable bilateral vestibular systems? Previous studies used vibration-based stimulations (VS) as a perturbation to understand the postural control during walking while the bilateral vestibular systems were perturbed. Therefore, this study attempted to extend the knowledge to understand the alternations in spatial-temporal gait characteristics under perturbed bilateral vestibular systems while walking on different inclines. Methods Nineteen healthy young adults participated in this study. Eight walking conditions were randomly assigned to each participant: 0%, 3%, 6%, and 9% grade of inclines with/without VS. The preferred walking speed was used for gait analysis. The dependent variables were stance time, double support time, step length, step time, step width, foot clearance, and respective variabilities. All dependent variables were defined by two critical gait events: heel-strike and toe-off. Pre-Hoc paired comparisons with Bonferroni corrections were used to prioritize the dependent variables. A two-way repeated measure was used to investigate the effect of VS and the effect of inclines on the selected dependent variables from Pre-Hoc analysis. Post-Hoc comparisons were also corrected by the Bonferroni method. Results The step length, step time, foot clearance, and foot clearance variability were selected by the Pre-Hoc analysis because the corrected paired t-test demonstrated a significant VS effect (p < 0.05) on these gait parameters at least one of four inclines. The significant interaction between the effect of VS and the effect of inclines was found in step length (p = 0.005), step time (p = 0.028), and foot clearance variability (p = 0.003). The results revealed that implementing a VS increased step length and step time when walking on 0%, 3%, and 9% of grade inclines. In particular, the foot clearance variability was found when walking on 9% of grade inclines. Conclusion The observations in the current study suggested that VS increased the step length, step time, foot clearance, and foot clearance variability while walking on inclines. These results suggested that these gait parameters might be promising targets for future clinical investigations in patients with BVD while walking on different inclines. Importantly, the increases in spatial-temporal gait performance under bilateral VS might be an indicator of gait improvement while walking on different inclines.

Yaelim Lee,1,2 Soeun Choi,3 Heejae Jung4 1College of Nursing, Catholic University of Korea, Seoul, Republic of Korea; 2Redcross College of Nursing, Chung-Ang University, Seoul, Republic of Korea; 3Department of Nursing, Yeouido St. Mary’s Hospital, Seoul, Republic of Korea; 4Department of Nursing, Seoul National University Hospital, Seoul, Republic of KoreaCorrespondence: Yaelim Lee, Department of Nursing, College of Nursing, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea, Tel +82-2-2258-8148, Fax +82-2-2258-8148, Email ylcaregiver@gmail.comBackground: Pregnant women at work often encounter barriers to participating in prenatal education or conducting appropriate self-care practices due to their working conditions.Purpose: We aimed at developing a mobile-based intervention application (SPWW) for Korean pregnant women at work and testing its usability and preliminary effects to enhance their self-care practices.Patients and Methods: The application was developed and tested with thirty-one pregnant women at work and thirteen women’s healthcare providers. The instruments used in this study were a modified Health Practices in Pregnancy Questionnaire II and a System Usability Scale. Descriptive analyses and t-tests were performed using SPSS 25.0. The participants’ open-ended answers were analyzed using ATLAS. ti 8.Results: We developed the application focusing on four self-care topics: healthy diet, physical activity, sufficient rest, and stress management. After using the application for two weeks, participants’ levels of exercise (p = 0.006), adequate fluid intake (p = 0.002), and limiting daily caffeine intake (p = 0.048) significantly improved. In addition to good usability scores, the suggestions for improvement made by the participants included diversifying the educational materials and adding individually customizable functions to the application.Conclusion: The application developed in this study enhanced self-care practices of pregnant women at work and showed adequate levels of usability. We expect the developmental process and details of the application provided in this study to serve as a sample guide for future studies.Keywords: pregnancy, prenatal care, telemedicine, internet-based intervention, Asian

Hyeji Jung,1 Hyojeong Lee,1 Dongwook Kim,1 Eunji Cheong,2 Young-Min Hyun,3 Je-Wook Yu,4 Ji Won Um1 1Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Korea; 2Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea; 3Department of Anatomy and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, Korea; 4Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, KoreaCorrespondence: Ji Won Um, Email jiwonum@dgist.ac.krBackground: Peripheral inflammation-triggered mild neuroinflammation impacts the brain and behavior through microglial activation. In this study, we performed an unbiased analysis of the vulnerability of different brain areas to neuroinflammation induced by systemic inflammation.Methods: We injected mice with a single low dose of LPS to induce mild inflammation and then analyzed microglial activation in 34 brain regions by immunohistochemical methods and whole-brain imaging using multi-slide scanning microscopy. We also conducted quantitative RT-PCR to measure the levels of inflammatory cytokines in selected brain regions of interest.Results: We found that microglia in different brain regions are differentially activated by mild, LPS-induced inflammation relative to the increase in microglia numbers or increased CD68 expression. The increased number of microglia induced by mild inflammation was not attributable to infiltration of peripheral immune cells. In addition, microglia residing in brain regions, in which a single low-dose injection of LPS produced microglial changes, preferentially generated pro-inflammatory cytokines.Conclusion: Our results suggest that mild neuroinflammation induces regionally different microglia activation, producing pro-inflammatory cytokines. Our observations provide insight into induction of possible region-specific neuroinflammation-associated brain pathologies through microglial activation.Keywords: neuroinflammation, microglia, inflammatory cytokines, lipopolysaccharide, regional vulnerability

[This corrects the article DOI: 10.1371/journal.pone.0240437.].

Background Plantar vibration has been widely used to strengthen the sensation of the somatosensory system, further enhancing balance during walking on a level surface in patients with stroke. However, previous studies with plantar vibration only involved the level surface, which neglected the importance of inclined/declined walking in daily life. Thus, combining the plantar vibration and inclined/declined walking might answer a critical research question: whether different types of plantar vibration had different effects on gait characteristics during walking on different inclines. Methods Eighteen healthy young adults were recruited. Fifteen walking conditions were assigned randomly to these healthy adults (no, sub-, and supra-threshold plantar vibration × five different inclines: +15%, +8%, 0%, −8%, −15% grade). A motion capture system with eight cameras captured 12 retro-reflective markers and measured the stride time, stride length, step width, and respective variabilities. Results A significant interaction between vibration and inclination was observed in the stride time (p < 0.0001) and step width (p = 0.015). Post hoc comparisons found that supra-threshold vibration significantly decreased the stride time (−8%: p < 0.001; −15%: p < 0.001) while the sub-threshold vibration significantly increased the step width (−8%: p = 0.036) in comparison with no plantar vibration. Conclusions When walking downhill, any perceivable (supra-threshold) vibration on the plantar area decreased the stride time. Also, the increase in step width was observed by non-perceivable (sub-threshold) plantar vibration while walking uphill. These observations were crucial as follows: (1) applying sub-threshold plantar vibrations during uphill walking could increase the base of support, and (2) for those who may need challenges in locomotor training, applying supra-threshold vibration during downhill walking could reach this specific training goal.

Abstract Hydrogen is a promising future sustainable fuel candidate with boundless opportunities. Research into photoelectrochemical (PEC) water splitting based on a lead halide perovskite (LHP) has progressed significantly with the aim of more efficient solar hydrogen production. Herein, we unite a well‐known photo‐absorbing LHP with cost‐effective water‐splitting catalysts, and we introduce two types of monolithic LHP‐based PEC devices that act as a photocathode and a photoanode for the hydrogen evolution reaction and oxygen evolution reaction, leading to efficient unbiased overall water splitting. Through the integration of these two monolithic LHP‐based photoelectrodes, an unbiased solar‐to‐hydrogen conversion efficiency of 10.64% and a photocurrent density of 8.65 mA cm−2 are achieved.

Abstract The term “SOS response” was first coined by Radman in 1974, in an intellectual effort to put together the data suggestive of a concerted gene expression program in cells undergoing DNA damage. A large amount of information about this cellular response has been collected over the following decades. In this review, we will focus on a few of the relevant aspects about the SOS response: its mechanism of control and the stressors which activate it, the diversity of regulated genes in different species, its role in mutagenesis and evolution including the development of antimicrobial resistance, and its relationship with mobile genetic elements.

Dinah Rindorf,1 Sara Larsen,1 Lotte Ockert,1 Helene Jung,2 Claus Dahl3 1Ambu a/S, Ballerup, Denmark; 2Department of Urology, Hospital Lillebaelt, Vejle, Denmark; 3Department of Urology, Capio Ramsey Santé, Hellerup, DenmarkCorrespondence: Dinah RindorfAmbu a/S, Baltorpbakken 13, Ballerup, 2750, DenmarkTel +4550737830Email dihr@ambu.comPurpose: Single-use endoscopes have been subjected to increase awareness in recent years, and several new single-use cystoscopes (eg Ambu® aScope 4 Cysto) have entered the market. However, the market readiness for such single-use cystoscopes remains unknown. This study investigates the worldwide market readiness for single-use cystoscopes among urologists and procurement managers (PMs) from Europe, Japan, and the US.Materials and Method: An online survey using QuestionPro® was distributed to urologists and PMs in France, Germany, Italy, Japan, Spain, the UK, and the US between March 10, 2020 and July 14, 2020. All surveys were translated into the respective local language. Statistical analyses were performed using the software package Stata/SE version 16.1, StataCorp. Fisher’s exact test was used to analyze categorical variables and simple linear regression was applied to continuous variables.Results: A total of 415 urologists and PMs completed the survey (343 [82.7%] urologists and 72 [17.3%] PMs). Seventy (16.9%) were from Japan, 100 (24.1%) were from the US, and 245 (59.0%) were evenly distributed across the following European countries: France, Germany, Italy, Spain, and the UK. On average, respondents indicated that they would consider converting to single-use in 44.5% of their cystoscopy procedures. Respondents anticipated significantly higher conversion (p< 0.05) when they (1) used single-use ureteroscopes in their department, (2) were concerned about cystoscopy-related infection as a result of contaminated cystoscopes, (3) were members of their institution’s value committee, or (4) considered cost-transparency to be important when purchasing cystoscopes.Conclusion: This study investigated the marked readiness for single-use cystoscopes according to urologists and PMs worldwide. Respondents indicated a willingness to convert to single-use cystoscopes in nearly half (44.5%) of their cystoscopy procedures. Respondents that were concerned about cystoscopy-related infections as a result of contaminated cystoscopes indicated a significantly higher anticipated conversion rate (p< 0.05).Keywords: single-use, cystoscopy, market readiness, single-use endoscopes, cystoscopy-related infection, urologist

Objectives: L-Glutamine is FDA-approved for sickle cell disease (SCD), yet the mechanism(s)-of-action are poorly understood. We performed a pharmacokinetics (pK) study to determine the metabolic fate of glutamine supplementation on plasma and erythrocyte amino acids in patients with SCD. Design: A pK study was performed where patients with SCD fasting for > 8 h received oral L-glutamine (10 g). Blood was analyzed at baseline, 30/60/90 min/2/3/4/8 hrs. A standardized diet was administered to all participants at 3 established time-points (after 2/5/7hrs). A subset of patients also had pK studies performed without glutamine supplementation to follow normal diurnal fluctuations in amino acids. Setting: Comprehensive SCD Center in Oakland, California Results: Five patients with SCD were included, three of whom performed pK studies both with and without glutamine supplementation. Average age was 50.6 ± 5.6 years, 60% were female, 40% SS, 60% SC. Plasma glutamine levels increased significantly after oral glutamine supplementation, compared to minimal fluctuations with diet. Plasma glutamine concentration peaked within 30-min of ingestion (p = 0.01) before decreasing to a plateau by 2-h that remained higher than baseline by 8 h. Oral glutamine also increased plasma arginine concentration, which peaked by 4-h (p = 0.03) and remained elevated through 8-h. Erythrocyte glutamine levels began to increase by 8-h, while erythrocyte arginine concentration peaked at 4-h. Conclusions: Oral glutamine supplementation acutely improved glutamine and arginine bioavailability in both plasma and erythrocytes. This is the first study to demonstrate that glutamine therapy increases arginine bioavailability and may provide insight into shared mechanisms-of-action between these conditionally-essential amino acids.

Hanna Jung, Youngok Lee Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of KoreaCorrespondence: Youngok LeeDepartment of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82-53-200-5665Fax +82-53-426-4765Email yolee1210@knu.ac.krAbstract: The presence of thrombocytopenia in cyanotic congenital heart disease (CCHD) is an uncommon, but well-known condition. We present a patient with pulmonary atresia with ventricular septal defect (PA with VSD) requiring a multi-stage operation. We were unsure whether the patient’s hypoxia was the cause of his thrombocytopenia, as the hypoxia was relatively mild. His thrombocytopenia improved following reoxygenation after the Rastelli operation (total correction of PA with VSD). From these findings, we suggest that if a patient with CCHD presents with thrombocytopenia without an obvious cause, hypoxia-induced thrombocytopenia should be considered, regardless of the degree of hypoxia, platelet count, or hematocrit percentage.Keywords: cardiac surgery, congenital heart defect, cyanosis, pulmonary atresia with ventricular septal defect, thrombocytopenia

Hanna Jung, Gun Jik Kim, Tak-hyuk Oh Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of KoreaCorrespondence: Tak-hyuk OhDepartment of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82-53-200-5665Fax +82-53-426-4765Email ohhidongii@gmail.comAbstract: Mucormycosis is a rare, life-threatening, and opportunistic fungal infection that usually occurs in immunocompromised patients. Rhinocerebral and pulmonary manifestations are the common form. The rare form of gastrointestinal mucormycosis occur in all parts of the alimentary tract, with emphasis on the stomach being the most common site. Primary gastric mucormycosis following traumatic injury is an extremely rare form that is usually lethal; thus, only a few cases of survival have been reported even after early diagnosis and aggressive surgical resection, combined with antifungal treatment. We herein report a case of delayed-onset gastric mucormycosis in a polytrauma patient without predisposing factors, which was successfully treated by antifungal medical therapy alone with no surgical debridement.Keywords: antifungal antibiotics, fungal infection, melena, mucormycosis, multiple trauma

Given the growing interest in human exploration of space, it is crucial to identify the effects of space conditions on biological processes. Here, we analyze the transcriptomic response of Caenorhabditis elegans to simulated microgravity and observe the maintained transcriptomic response after returning to ground conditions for four, eight, and twelve days. We show that 75% of the simulated microgravity-induced changes on gene expression persist after returning to ground conditions for four days while most of these changes are reverted after twelve days. Our results from integrative RNA-seq and mass spectrometry analyses suggest that simulated microgravity affects longevity-regulating insulin/IGF-1 and sphingolipid signaling pathways. Finally, we identified 118 genes that are commonly differentially expressed in simulated microgravity- and space-exposed worms. Overall, this work provides insight into the effect of microgravity on biological systems during and after exposure.

Abstract Medullary thyroid carcinoma (MTC) accounts up to 10% of all thyroid cancers, but is responsible for a disproportionate number of deaths. While surgery is the only curative treatment for MTC, indications for lateral neck lymph node (LLN) dissection are controversial. We performed a retrospective review to describe clinical outcomes in 93 MTC patients from July 1995 to March 2015. We analyzed their clinicopathologic factors, and cut‐off values of tumor size and calcitonin levels were calculated using a receiver operating characteristic curve. Using the instances of lymph node metastases, the tumor size cut‐off value was 0.95 cm (area under curve, AUC = 0.697) in patients with ipsilateral central lymph node (CLN) metastases, 2.25 cm (AUC = 0.793) in contralateral CLN metastases, and 1.75 cm (AUC = 0.753) in ipsilateral LLN metastases. The cut‐off values of preoperative calcitonin levels were 226.6 pg/mL (AUC = 0.746) in ipsilateral CLN, 755.0 pg/mL (AUC = 0.840) in contralateral CLN metastases, and 237.0 pg/mL (AUC = 0.775) in ipsilateral LLN metastases. This study supports the notion that ipsilateral LLN metastases occur before contralateral CLN metastases. Therefore, ipsilateral LLN dissection should be considered in patients with contralateral CLN metastases. The extent of surgery should be based on the status of LN metastases, preoperative basal calcitonin level, and tumor size to help individualize the extent of surgery.

Neurodegeneration mediates neurological disability in inflammatory demyelinating diseases of the CNS. The role of innate immune cells in mediating this damage has remained controversial with evidence for destructive and protective effects. This has complicated efforts to develop treatment. The time sequence and dynamic evolution of the opposing functions are especially unclear. Given limits of in vivo monitoring in human diseases such as multiple sclerosis (MS), animal models are warranted to investigate the association and timing of innate immune activation with neurodegeneration. Using noninvasive in vivo retinal imaging of experimental autoimmune encephalitis (EAE) in CX3CR1GFP/+–knock-in mice followed by transcriptional profiling, we are able to show 2 distinct waves separated by a marked reduction in the number of innate immune cells and change in cell morphology. The first wave is characterized by an inflammatory phagocytic phenotype preceding the onset of EAE, whereas the second wave is characterized by a regulatory, antiinflammatory phenotype during the chronic stage. Additionally, the magnitude of the first wave is associated with neuronal loss. Two transcripts identified — growth arrest–specific protein 6 (GAS6) and suppressor of cytokine signaling 3 (SOCS3) — might be promising targets for enhancing protective effects of microglia in the chronic phase after initial injury.

The aim of this study was to determine the effects of tannin-rich peanut skin (PS) supplementation on growth performance, ruminal and blood metabolites, and carcass traits associated with internal parasite infection in meat goats under confined conditions. Twenty-one Kiko crossbred male goats were blocked by body weight (BW) and randomly assigned to one of 3 treatment groups. Experimental diets contained different levels of peanut (Arachis hypogaea) skin replacing alfalfa (Medicago sativa) pellets (ALP) in a control diet. Experimental treatments included: 30% ALP (control), 15% PS and 15% ALP, and 30% PS. Peanut skin was incorporated in the grain mix portion of the diets. Animals were fed once daily, and the intake was adjusted every 3 to 4 d. Each animal was each artificially infected with 5,000 larvae of the 3rd stage of barber's pole worm (Haemonchus contortus). Body weights, dry matter intake (DMI), and fecal samples for fecal egg counts (FEC) were taken at d 0, 12, 23, and 41. Rumen fluid and blood samples were collected at d 45. The performance period lasted 45 d and at the completion of the study, goats were harvested, and carcass characteristics, abomasal worm counts were measured. The results showed that DMI, BW, carcass traits, and meat color were not affected by PS supplementation, whereas average daily gain (ADG, P

Duchenne muscular dystrophy (DMD) is a congenital myopathy caused by mutations in the dystrophin gene. DMD pathology is marked by myositis, muscle fiber degeneration, and eventual muscle replacement by fibrosis and adipose tissue. Satellite cells (SC) are muscle stem cells critical for muscle regeneration. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes SC proliferation, regulates lymphocyte trafficking, and is irreversibly degraded by sphingosine phosphate lyase (SPL). Here, we show that SPL is virtually absent in normal human and murine skeletal muscle but highly expressed in inflammatory infiltrates and degenerating fibers of dystrophic DMD muscle. In mdx mice that model DMD, high SPL expression is correlated with dysregulated S1P metabolism. Perinatal delivery of the SPL inhibitor LX2931 to mdx mice augmented muscle S1P and SC numbers, reduced leukocytes in peripheral blood and skeletal muscle, and attenuated muscle inflammation and degeneration. The effect on SC was also observed in SCID/mdx mice that lack mature T and B lymphocytes. Transcriptional profiling in the skeletal muscles of LX2931-treated vs. control mdx mice demonstrated changes in innate and adaptive immune functions, plasma membrane interactions with the extracellular matrix (ECM), and axon guidance, a known function of SC. Our cumulative findings suggest that by raising muscle S1P and simultaneously disrupting the chemotactic gradient required for lymphocyte egress, SPL inhibition exerts a combination of muscle-intrinsic and systemic effects that are beneficial in the context of muscular dystrophy.

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (−0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.

BackgroundPoor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT).MethodsOverweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured.ResultsIn the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia.ConclusionNutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.

Abstract Background Liquid cultures have been commonly used in space, toxicology, and pharmacology studies of Caenorhabditis elegans. However, the knowledge about transcriptomic alterations caused by liquid cultivation remains limited. Moreover, the impact of different genotypes in rapid adaptive responses to environmental changes (e.g., liquid cultivation) is often overlooked. Here, we report the transcriptomic and phenotypic responses of laboratory N2 and the wild-isolate AB1 strains after culturing P0 worms on agar plates, F1 in liquid cultures, and F2 back on agar plates. Results Significant variations were found in the gene expressions between the N2 and AB1 strains in response to liquid cultivation. The results demonstrated that 8–34% of the environmental change-induced transcriptional responses are transmitted to the subsequent generation. By categorizing the gene expressions for genotype, environment, and genotype-environment interactions, we identified that the genotype has a substantial impact on the adaptive responses. Functional analysis of the transcriptome showed correlation with phenotypical changes. For example, the N2 strain exhibited alterations in both phenotype and gene expressions for germline and cuticle in axenic liquid cultivation. We found transcript evidence to approximately 21% of the computationally predicted genes in C. elegans by exposing the worms to environmental changes. Conclusions The presented study reveals substantial differences between N2 and AB1 strains for transcriptomic and phenotypical responses to rapid environmental changes. Our data can provide standard controls for future studies for the liquid cultivation of C. elegans and enable the discovery of condition-specific genes.

Il-Young Jang,1,2 Chang Ki Lee,3 Hee-Won Jung,4,5 Sang Soo Yu,2 Young Soo Lee,1 Eunju Lee,1 Dae Hyun Kim6,7 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2PyeongChang Health Center & County Hospital, PyeongChang, Gangwon-Do, Republic of Korea; 3Goldman Urology Clinic, Seoul, Republic of Korea; 4Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; 5Geriatric Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-Do, Republic of Korea; 6Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 7Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA Purpose: Frailty is an important consideration in the management of lower urinary tract symptoms and erectile dysfunction in older men; frailty increases vulnerability to treatment-related adverse outcomes, but its burden is not known. The authors aimed to examine the burden of frailty and associated geriatric conditions in community-dwelling older men.Patients and methods: A cross-sectional study was conducted with 492 community-dwelling older men (mean age, 74.2 years; standard deviation, 5.6 years). All the participants were administered the International Prostate Symptom Score (IPSS) (range: 0–35) and a five-item version of the International Index of Erectile Function (IIEF-5) (range: 5–25). Frailty phenotype was assessed based on exhaustion, inactivity, slowness, weakness, and weight loss. Prevalence of frailty phenotype and geriatric conditions were assessed by the IPSS severity category (mild, 0–7; moderate, 8–19; severe, 20–35 points) and the first IIEF-5 question, which assesses the confidence in erectile function (low, 1–2; moderate, 3; high, 4–5 points).Results: Older men with severe urologic symptoms had a high prevalence of frailty. According to the IPSS questionnaire, the prevalence of frailty was 7.3% (21/288) in the mild category, 16.3% (26/160) in the moderate category, and 43.2% (19/44) in the severe category. Participants in the severe IPSS category showed high prevalence of dismobility (45.5%), multimorbidity (43.2%), malnutrition risk (40.9%), sarcopenia (40.9%), and polypharmacy (31.8%). According to erectile confidence based on the first IIEF-5 question, the prevalence of frailty was 18.7% (56/300) for low confidence, 5.3% (6/114) for moderate confidence, and 5.1% (4/78) for high confidence. Participants with low confidence in erectile function showed high prevalence of sarcopenia (39.0%), multimorbidity (37.7%), dismobility (35.7%), malnutrition risk (33.3%), and polypharmacy (23.0%).Conclusion: The prevalence of frailty and geriatric conditions was higher in older men with severe urologic symptoms. A frailty screening should be routinely administered in urology practices to identify older men who are vulnerable to treatment-related adverse events. Keywords: erectile dysfunction, frailty, geriatric assessment, lower urinary tract symptoms, risk management

Feeding condensed tannin (CT)-containing diets such as sericea lespedeza (Lespedeza cuneata) and reducing stress have been reported to improve meat quality and food safety in goats. In a completely randomized design with split-plot, thirty-six uncastrated male Spanish goats were assigned to 3 dietary treatments (n = 12/treatment): ground ‘Serala’ sericea lespedeza hay (SER), bermudagrass (Cynodon dactylon) hay (BG), or bermudagrass hay—dewormed goats (BG-DW; Control) at 75% of intake, with a corn-based supplementation (25%) for 8 weeks. Prior to slaughter, goats were either transported for 90 min to impose stress or held in pens. Basophil counts were lower (p < 0.01) in the SER group compared to BG or BG-DW groups suggesting a better anti-inflammatory capacity due to polyphenols in the SER diet. Compared to BG-DW group, cortisol level was higher (p < 0.05) and norepinephrine was lower (p < 0.05) in the SER group. The SER group had the lowest aerobic plate counts (APC) in both rumen and rectum (p < 0.01). Longissimus dorsi muscle initial pH was not affected by diet or stress. Feeding sericea hay to goats may have beneficial effects, such as enhanced antioxidant and anti-inflammatory properties during stress and reduced gut microbial counts, without changing meat quality characteristics.

Moa Jeong,1 Hyung Koo Kang,1 Pamela Song,2 Hye Kyeong Park,1 Hoon Jung,1 Sung-Soon Lee,1 Hyeon-Kyoung Koo1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea Purpose: Hand grip strength (HGS) is a simple way of predicting the risk of cardiovascular disease and all-cause mortality in the general population. However, the practical significance of grip strength in patients with COPD is uncertain. The aim of this study was to compare HGS between subjects with and without COPD and to evaluate its clinical relevance in patients with COPD by using a national survey.Methods: Data were collected from the Korean National Health and Nutrition Examination Survey. The study included 421 adults with COPD and 2,542 controls who completed questionnaires, spirometry, and a HGS test. HGS was compared between subjects with and without COPD, and the association between grip strength, lung function, and quality of life (QoL) was evaluated.Results: The mean HGS was 33.3±9.1 kg in the COPD group and 29.9±9.5 kg in the non-COPD group; adjusted HGS was 30.9±0.33 kg and 30.9±0.11 kg, respectively (P=0.99). HGS was not related to forced vital capacity (β=0.04, P=0.70) or forced expiratory volume in 1 second (β=0.11, P=0.24) in multivariable analysis. HGS was independently associated with the EQ-5D index, but the relationship was stronger in the COPD group (β=0.30, P

Abstract Inhibitor of DNA binding (Id) proteins play important roles in regulating cardiac development via paracrine signaling. Id1/Id3 knockout mice die at mid-gestation with multiple cardiac defects. Single Id knockout studies have not reported cardiomyopathies. To bypass embryonic lethality we used Tie2CRE-mediated recombination to conditionally delete Id1 against global Id3 ablation (Id cDKOs), which develops adult-onset dilated cardiomyopathy. We confirm upregulation of thrombospondin-1 (TSP1) in Id cDKO hearts. Colocalization studies reveal increased TSP1 expression in the vicinity of endothelial cells and near regions of endocardial fibrosis/disruption. Downstream fibrotic molecules were upregulated. Endocardial capillary density was reduced with evidence of vascular distention. Treatment of Id cDKO cardiac explants with LSKL, a peptide antagonist of TSP1 activation of TGFβ, reversed the increased expression of fibrotic molecules. We conducted bone marrow transplant experiments in which we transferred bone marrow cells from Id cDKO mice into lethally irradiated WT mice. The majority of WT recipients of Id cDKO bone marrow cells phenocopied Id cDKO cardiac fibrosis 4 months post-transplantation. Injection of LSKL into adult Id cDKO mice led to downregulation of fibrotic molecules. The results prompt caution when bone marrow transfers from individuals potentially carrying mutations in the Id axis are applied in clinical settings.

A 2.7 kg, 11-year-old, castrated male Maltese dog was presented for evaluation of a 2-year history of intractable coughing, dyspnoea and cyanosis. A diagnosis of tracheal collapse with myxomatous mitral valve disease was made on the basis of inspiratory and expiratory thoracic radiographs, fluoroscopy and echocardiography. Measurement for stent size selection was performed on thoracic radiographs. A 10 mm (diameter) × 70 mm (length) self-expanding double-wire woven uncovered nitinol stent was used for intratracheal implantation and was deployed under fluoroscopic guidance. On thoracic radiography seven days after surgery, the position of the stent remained unchanged. On presentation six months after surgery, the owner reported that the dog was doing well without medical management. Although studies of various intraluminal stents have been reported in dogs, to the authors' knowledge, use of a double-wire woven uncovered nitinol stent has not been reported previously for the management of a dog with tracheal collapse. Since this particular type of stent with unfixed individual cells provided proper airway patency without stent fracture in the dog in this report, this stent might be used as an alternative to other commercially available nitinol stents in cases of thoracic inlet collapse.