Ultrasonographic features of the skin and subcutis: correlations with the severity of breast cancer-related lymphedema.

PURPOSE: Assessing the severity of breast cancer-related lymphedema (BCRL) requires various clinical tools, yet no standardized methodology is available. Ultrasonography shows promise for diagnosing lymphedema and evaluating its severity. This study explored the clinical utility of ultrasonography in patients with BCRL. METHODS: In this retrospective cross-sectional study, patients with unilateral BCRL were examined. The analyzed data included demographics, lymphedema location, International Society of Lymphology (ISL) stage, surgical history, treatment regimens, and arm circumference. Skin, subcutis, and muscle thicknesses were assessed ultrasonographically at predetermined sites, and the percentage of excess thickness was calculated. Multivariate logistic regression analysis was employed to identify associations between ultrasonographic measurements and advanced lymphedema (ISL 2 or 3). The Lymphedema Quality of Life arm questionnaire was used to evaluate patient-reported outcomes regarding lymphedema and their correlations with ultrasonographic findings. RESULTS: Among 118 patients, 71 were classified as ISL 0-1 and 47 as ISL 2-3. Patients with advanced lymphedema were older, had higher nodal stages, underwent more axillary lymph node dissections, and had higher rates of dominant-arm lymphedema. Multivariate logistic regression revealed significant associations of greater skin thickness (adjusted odds ratio [OR], 4.634; 95% confidence interval [CI], 1.233 to 17.419), subcutis thickness (adjusted OR, 7.741; 95% CI, 1.649 to 36.347), and subcutis echogenicity (adjusted OR, 4.860; 95% CI, 1.517 to 15.566) with advanced lymphedema. Furthermore, greater skin thickness (P=0.016) and subcutis echogenicity (P=0.023) were correlated with appearance-related discomfort. CONCLUSION: Ultrasonographic measurements were significantly associated with advanced lymphedema in BCRL. Ultrasonography represents a valuable diagnostic and severity assessment tool for lymphedema.

Psychometric validation of the short version of the Information Needs in Cardiac Rehabilitation scale through a first global assessment.

AIMS: Tailored education is recommended for cardiac patients, yet little is known about information needs in areas of the world where it is most needed. This study aims to assess (i) the measurement properties of the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale and (ii) patient's information needs globally. METHODS AND RESULTS: In this cross-sectional study, English, simplified Chinese, Portuguese, or Korean versions of the INCR-S were administered to in- or out-patients via Qualtrics (January 2022-November 2023). Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated recruitment. Importance and knowledge sufficiency of 36 items were rated. Links to evidence-based lay education were provided where warranted. A total of 1601 patients from 19 middle- and high-income countries across the world participated. Structural validity was supported upon factor analysis, with five subscales extracted: symptom response/medication, heart diseases/diagnostic tests/treatments, exercise and return-to-life roles/programmes to support, risk factors, and healthy eating/psychosocial management. Cronbach's alpha was 0.97. Construct validity was supported through significantly higher knowledge sufficiency ratings for all items and information importance ratings for all subscales in cardiac rehabilitation (CR) enrolees vs. non-enrolees (all P < 0.001). All items were rated as very important-particularly regarding cardiac events, nutrition, exercise benefits, medications, symptom response, risk factor control, and CR-but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ranged from 30.0 to 67.4%, varying by region and income class. Ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine. CONCLUSION: Identification of information needs using the valid and reliable INCR-S can inform educational approaches to optimize patients' health outcomes across the globe.

Patients need information to manage their heart diseases, such as what to do if they have chest pain, what a heart attack is, and how to take their medicine to lower the chances they will have another one, so a study of the information needs of over 1600 heart patients from around the globe was undertaken for the first time. Using the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale­which was shown to be a good measurement tool through the study and hence may improve patient education­patients reported they most wanted information about heart events, heart-healthy eating, exercise benefits, their pills, symptom response, risk factor control, and cardiac rehabilitation­but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ratings for each item ranged from 30.0 to 67.4%, also varying by region and income class; perceived knowledge sufficiency ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine.

Efficient production of (S)-limonene and geraniol in Saccharomyces cerevisiae through the utilization of an Erg20 mutant with enhanced GPP accumulation capability.

Monoterpenes and monoterpenoids such as (S)-limonene and geraniol are valuable chemicals with a wide range of applications, including cosmetics, pharmaceuticals, and biofuels. Saccharomyces cerevisiae has proven to be an effective host to produce various terpenes and terpenoids. (S)-limonene and geraniol are produced from geranyl pyrophosphate (GPP) through the enzymatic actions of limonene synthase (LS) and geraniol synthase (GES), respectively. However, a major hurdle in their production arises from the dual functionality of the Erg20, a farnesyl pyrophosphate (FPP) synthase, responsible for generating GPP. Erg20 not only synthesizes GPP by condensing isopentenyl pyrophosphate (IPP) with dimethylallyl pyrophosphate but also catalyzes further condensation of IPP with GPP to produce FPP. In this study, we have tackled this issue by harnessing previously developed Erg20 mutants, Erg20K197G (Erg20G) and Erg20F96W, N127W (Erg20WW), which enhance GPP accumulation. Through a combination of these mutants, we generated a novel Erg20WWG mutant with over four times higher GPP accumulating capability than Erg20WW, as observed through geraniol production levels. The Erg20WWG mutant was fused to the LS from Mentha spicata or the GES from Catharanthus roseus for efficient conversion of GPP to (S)-limonene and geraniol, respectively. Further improvements were achieved by localizing the entire mevalonate pathway and the Erg20WWG-fused enzymes in peroxisomes, while simultaneously downregulating the essential ERG20 gene using the glucose-sensing HXT1 promoter. In the case of (S)-limonene production, additional Erg20WWG-LS was expressed in the cytosol. As a result, the final strains produced 1063 mg/L of (S)-limonene and 1234 mg/L of geraniol by fed-batch biphasic fermentations with ethanol feeding. The newly identified Erg20WWG mutant opens doors for the efficient production of various other GPP-derived chemicals including monoterpene derivatives and cannabinoids.

Attitude Toward Virtual Rehabilitation and Active Video Games Among Therapists in Korea: A Nationwide Survey.

In this study, we conducted a survey targeting 191 physical therapists (PTs) and 159 occupational therapists (OTs) in South Korea to explore attitudes toward virtual rehabilitation. Utilizing the Korean version of the ADOPT VR by Glegg et al., OT exhibited significantly more experience with virtual reality (VR) and active video games (AVG) than PT. Therapists with VR/AVG experience scored significantly higher in most categories, and the scores in each category were significantly correlated with the Behavioral Intention category, reflecting the willingness to use VR/AVG. The biggest barriers identified were insufficient funds and setup assistance for the equipment. Differences in responses between the groups with and without VR/AVG experience were most prominent in terms of lack of interest and funding. Therapists' attitudes, perceptions, and intentions toward VR/AVG are crucial factors in the establishment and implementation of VR/AVG; thus, the results of this study provide valuable evidence for future policies related to VR/AVG in rehabilitation medicine.

Prevalence and impact of depression and anxiety among older myocardial infarction survivors: A nationwide cohort study.

BACKGROUND: Depression and anxiety may be significant prognostic factors after myocardial infarction (MI). Thus, we investigated depression and anxiety prevalence among older MI survivors and their impact on mortality, stroke, and recurrent MI. METHODS: This population-based cohort study used the Korean National Health Insurance Service database for data concerning individuals aged 66 years who participated in the National Screening Program from 2009 to 2016. Overall, 11,721 individuals with MI history and 58,605 age- and sex-matched controls were included and followed up until 2019. The presence of depression and anxiety was assessed 2 years before and after participation in the program. Mortality and major adverse outcomes, defined as a composite outcome comprising mortality, stroke, and recurrent MI, were analyzed. RESULTS: Depression and anxiety prevalence among MI survivors was 20.4 % and 30.3 %, respectively. Crude odds ratios for depression and anxiety, compared with the control group, were 1.207 (1.148-1.269) and 1.078 (1.032-1.126), respectively. During the follow-up, individuals with depression, anxiety, or both showed increased hazard ratios (HRs) for mortality and major adverse outcomes; after adjustments, their HRs were 1.442 (1.182-1.759), 1.129 (0.960-1.328), and 1.498 (1.263-1.776), respectively, for mortality and 1.505 (1.289-1.758), 1.158 (1.021-1.314), and 1.530 (1.337-1.751), respectively, for major adverse outcomes. LIMITATIONS: Although this was a nationwide cohort study, the MI, depression, and anxiety diagnoses were based on diagnostic codes. CONCLUSIONS: Higher depression and anxiety prevalence was observed among older MI survivors. Depression and anxiety occurrence correlated with increased adverse clinical outcomes after adjustments.

Translation, Cultural Adaptation, and Validation of a Korean Version of the Information Needs in Cardiac Rehabilitation Scale.

OBJECTIVE: : To translate and culturally adapt the Information Needs in Cardiac Rehabilitation (INCR) questionnaire into Korean and perform psychometric validation. METHODS: : The original English version of the INCR, in which patients are asked to rate the importance of 55 topics, was translated into Korean (INCR-K) and culturally adapted. The INCR-K was tested on 101 cardiac rehabilitation (CR) participants at Kangwon National University Hospital and Seoul National University Bundang Hospital in Korea. Structural validity was assessed using principal component analysis, and Cronbach's alpha of the areas was computed. Criterion validity was assessed by comparing information needs according to CR duration and knowledge sufficiency according to receipt of education. Half of the participants were randomly selected for 1 month of re-testing to assess their responsiveness. RESULTS: : Following cognitive debriefing, the number of items was reduced to 41 and ratings were added to assess participants' sufficient knowledge of each item. The INCR-K structure comprised eight areas, each with sufficient internal consistency (Cronbach's alpha>0.7). Criterion validity was supported by significant differences in mean INCR-K scores based on CR duration and knowledge sufficiency ratings according to receipt of education (p<0.05). Information needs and knowledge sufficiency ratings increased after 1 month of CR, thus supporting responsiveness (p<0.05). CONCLUSION: : The INCR-K demonstrated adequate face, content, cross-cultural, structural, and criterion validities, internal consistency, and responsiveness. Information needs changed with CR, such that multiple assessments of information needs may be warranted as rehabilitation progresses to facilitate patient-centered education.

Women's Cardiac Rehabilitation Barriers: Results of the International Council of Cardiovascular Prevention and Rehabilitation's First Global Assessment.

BACKGROUND: Cardiac rehabilitation (CR) programs are underutilized globally, especially by women. In this study we investigated sex differences in CR barriers across all world regions, to our knowledge for the first time, the characteristics associated with greater barriers in women, and women's greatest barriers according to enrollment status. METHODS: In this cross-sectional study, the English, Simplified Chinese, Arabic, Portuguese, or Korean versions of the Cardiac Rehabilitation Barriers Scale was administered to CR-indicated patients globally via Qualtrics from October 2021 to March 2023. Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated participant recruitment. Mitigation strategies were provided and rated. RESULTS: Participants were 2163 patients from 16 countries across all 6 World Health Organization regions; 916 (42.3%) were women. Women did not report significantly greater total barriers overall, but did in 2 regions (Americas, Western Pacific) and men in 1 (Eastern Mediterranean; all P < 0.001). Women's barriers were greatest in the Western Pacific (2.6 ± 0.4/5) and South East Asian (2.5 ± 0.9) regions (P < 0.001), with lack of CR awareness as the greatest barrier in both. Women who were unemployed reported significantly greater barriers than those not (P < 0.001). Among nonenrolled referred women, the greatest barriers were not knowing about CR, not being contacted by the program, cost, and finding exercise tiring or painful. Among enrolled women, the greatest barriers to session adherence were distance, transportation, and family responsibilities. Mitigation strategies were rated as very helpful (4.2 ± 0.7/5). CONCLUSIONS: CR barriers-men's and women's-vary significantly according to region, necessitating tailored approaches to mitigation. Efforts should be made to mitigate unemployed women's barriers in particular.

Investigation of the efficacy of low-frequency repetitive transcranial magnetic stimulation on upper-limb motor recovery in subacute ischemic stroke without cortical involvement: a protocol paper for a multi-center, double-blind randomized controlled trial.

Introduction: The incidence of stroke is increasing steadily due to factors such as population aging. Approximately 80% of stroke survivors have motor disorders affecting their daily lives. Repetitive transcranial magnetic stimulation (rTMS) has been reported to maximize functional recovery after stroke along with exercise intervention in upper limb rehabilitation treatment. However, whether rTMS affects the recovery of upper limb function in patients with stroke remains unclear. Therefore, in this trial, we will investigate the efficacy of low-frequency rTMS in patients with subcortical and brainstem ischemic stroke. Methods: This study has been designed as a multi-center, double-blind, randomized controlled trial to compare the efficacy of low-frequency rTMS over the contralesional M1 with sham stimulation. Overall, 88 participants will be allocated to the intervention or control group in a 1:1 ratio, with stratification according to their initial upper extremity Fugl-Meyer assessment (UE-FMA) score. The participants will receive either 30 min of real rTMS (intervention group) or sham rTMS (control group), followed by 30 min of occupational therapy for 10 consecutive workdays. All the participants will receive the same amount of rehabilitation therapy throughout the intervention period. Evaluations will be performed at baseline (T0), at the end of treatment (T1), and 4 weeks after the end of treatment (T2), including the box and block test (BBT), UE-FMA, Korean version of the Modified Barthel Index, and NIH Stroke Scale scores, Finger tapping test, Brunnstrom stage, modified Ashworth scale, and grip strength. The primary outcome will be the change in the BBT score between T0 and T2. Conclusion: This study will provide evidence on the efficacy of low-frequency rTMS in motor function recovery of the upper limb in patients with subacute, subcortical, and brainstem ischemic stroke. Clinical trial registration: ClinicalTrials.gov, identifier [NCT05535504].

Regulation of acetate tolerance by small ORF-encoded polypeptides modulating efflux pump specificity in Methylomonas sp. DH-1.

BACKGROUND: Methanotrophs have emerged as promising hosts for the biological conversion of methane into value-added chemicals, including various organic acids. Understanding the mechanisms of acid tolerance is essential for improving organic acid production. WatR, a LysR-type transcriptional regulator, was initially identified as involved in lactate tolerance in a methanotrophic bacterium Methylomonas sp. DH-1. In this study, we investigated the role of WatR as a regulator of cellular defense against weak organic acids and identified novel target genes of WatR. RESULTS: By conducting an investigation into the genome-wide binding targets of WatR and its role in transcriptional regulation, we identified genes encoding an RND-type efflux pump (WatABO pump) and previously unannotated small open reading frames (smORFs), watS1 to watS5, as WatR target genes activated in response to acetate. The watS1 to watS5 genes encode polypeptides of approximately 50 amino acids, and WatS1 to WatS4 are highly homologous with one predicted transmembrane domain. Deletion of the WatABO pump genes resulted in decreased tolerance against formate, acetate, lactate, and propionate, suggesting its role as an efflux pump for a wide range of weak organic acids. WatR repressed the basal expression of watS genes but activated watS and WatABO pump genes in response to acetate stress. Overexpression of watS1 increased tolerance to acetate but not to other acids, only in the presence of the WatABO pump. Therefore, WatS1 may increase WatABO pump specificity toward acetate, switching the general weak acid efflux pump to an acetate-specific efflux pump for efficient cellular defense against acetate stress. CONCLUSIONS: Our study has elucidated the role of WatR as a key transcription factor in the cellular defense against weak organic acids, particularly acetate, in Methylomonas sp. DH-1. We identified the genes encoding WatABO efflux pump and small polypeptides (WatS1 to WatS5), as the target genes regulated by WatR for this specific function. These findings offer valuable insights into the mechanisms underlying weak acid tolerance in methanotrophic bacteria, thereby contributing to the development of bioprocesses aimed at converting methane into value-added chemicals.

Critical roles of metal-ligand complexes in the controlled synthesis of various metal nanoclusters.

Metal nanoclusters (NCs), an important class of nanoparticles (NPs), are extremely small in size and possess quasi-molecular properties. Due to accurate stoichiometry of constituent atoms and ligands, NCs have strong structure-property relationship. The synthesis of NCs is seemingly similar to that of NPs as both are formed by colloidal phase transitions. However, they are considerably different because of metal-ligand complexes in NC synthesis. Reactive ligands can convert metal salts to complexes, actual precursors to metal NCs. During the complex formation, various metal species occur, having different reactivity and fraction depending on synthetic conditions. It can alter their degree of participation in NC synthesis and the homogeneity of final products. Herein, we investigate the effects of complex formation on the entire NC synthesis. By controlling the fraction of various Au species showing different reactivity, we find that the extent of complex formation alters reduction kinetics and the uniformity of Au NCs. We demonstrate that this concept can be universally applied to synthesize Ag, Pt, Pd, and Rh NCs.

Trends in the incidence and prevalence of dysphagia requiring medical attention among adults in South Korea, 2006-2016: A nationwide population study.

The prevalence of dysphagia is increasing, resulting in socioeconomic burden, but previous reports have only been based on a limited populations. Therefore, we aimed to investigate the nationwide incidence and prevalence of dysphagia requiring medical attention to provide adequate information for healthcare planning and resource allocation. In this nationwide retrospective cohort study, the data of adults aged ≥20 years recorded from 2006 to 2016 were sourced from the Korean National Health Insurance Service database. Medical claim codes based on ICD-10-CM were used to define dysphagia and possible causes. The annual incidence and prevalence of dysphagia were calculated. Cox regression was used to estimate dysphagia risk in people with possible dysphagia etiology. Survival analysis was performed to estimate the mortality and hazard ratio of dysphagia. The crude annual incidence of dysphagia increased continuously from 7.14 in 2006 to 15.64 in 2016. The crude annual prevalence of dysphagia in 2006 was 0.09% and increased annually to 0.25% in 2016. Stroke (odds ratio [OR]: 7.86, 95% confidence interval [CI]: 5.76-6.68), neurodegenerative disease (OR: 6.20, 95% CI: 5.76-6.68), cancer (OR: 5.59, 95% CI: 5.17-6.06), and chronic obstructive pulmonary disease (OR: 2.94, 95% CI: 2.71-3.18) were associated with a high risk of dysphagia. The mortality in the dysphagia group was 3.12 times higher than that in the non-dysphagia group (hazard ratio: 3.12, 95% CI: 3.03-3.23). The incidence and prevalence of dysphagia requiring medical attention are increasing annually. The increasing trend was conspicuous in the geriatric population. The presence of stroke, neurodegenerative disease, cancer, and chronic obstructive pulmonary disease is associated with a high risk of dysphagia. Therefore, adequate screening, diagnosis, and management of dysphagia in the older population must be emphasized in geriatric healthcare.

Attitude Toward Telerehabilitation Among Physical and Occupational Therapists in Korea: A Brief Descriptive Report.

The attitude toward telerehabilitation (TR) among therapists (191 physical therapists and 159 occupational therapists) in Korea was surveyed. The survey consisted of 15 questions in the following 8 domains: awareness(AW), attitude (AT), perceived usefulness (PU), perceived behavioral control (PBC), self-efficacy (SE), facilitating conditions (FC), barriers (B), and behavioral intention (BI). Therapists with experience in TR responded with higher scores in all domains except B, regardless of their specialty. The most perceived barriers to TR were unmatched insurance fees and a lack of technical support. Experience with TR was a major factor in attitude and behavior intention toward TR.

Dysphagia Requiring Medical Attention in Parkinson's Disease: A Korean Population-Based Study.

BACKGROUND: Patients with Parkinson's disease (PD) experience both motor and non-motor symptoms, including dysphagia. Although PD is closely associated with dysphagia, the prevalence or risk of dysphagia in PD is unclear, especially in Asian countries. METHODS: The prevalence of PD and dysphagia with PD in the general population was analyzed using the Korean National Health Insurance Service (NHIS) database. The prevalence per 100,000 persons of PD and dysphagia with PD from 2006 to 2015 was analyzed in the general population aged ≥ 40 years. Patients newly diagnosed with PD between 2010 and 2015 were compared with those without PD. RESULTS: The prevalence of PD and dysphagia in patients with PD increased continuously during the study period and was highest in the ninth decade of life. The percentage of patients with dysphagia in patients with PD increased with age. Patients with PD showed an adjusted hazard ratio of 3.132 (2.955-3.320) for dysphagia compared to those without PD. CONCLUSION: This nationwide study showed increasing trends in the prevalence of PD and dysphagia among patients with PD in Korea between 2006 and 2015. The risk of dysphagia was three times higher in patients with PD than that in those without PD, highlighting the importance of providing particular attention.

Incidence of dysphagia requiring medical attention in various types of cancers: A nationwide population-based cohort study.

PURPOSE: Most previous reports on dysphagia in cancer have focused on specific cancer types, particularly head and neck cancer. Therefore, we aimed to investigate the incidence of dysphagia in patients with various cancers using a nationwide database in South Korea. METHODS: This was a retrospective cohort study using the National Health Insurance Service database. Claim codes were used for the selection criteria and operational definitions. The total population data from 2010 to 2015 were extracted. The crude incidence of dysphagia was calculated per 1,000 person-years. The multivariate adjusted Cox proportional hazards regression was used to determine the effects of different cancers on the incidence of dysphagia. RESULTS: People with cancer had a lower income and suffered from a higher risk of comorbidities compared to people without cancer. The risk of dysphagia increased in all types of cancers, particularly in the oral cavity and pharynx (hazard ratio [HR]: 20.65, 95% confidence interval [CI]: 17.73-24.06), esophagus (HR: 18.25, 95% CI: 15.66-21.26), larynx (HR: 12.87, 95% CI: 10.33-16.02), and central nervous system (HR: 12.42, 95% CI: 10.33-14.94). CONCLUSIONS: The risk of dysphagia was significantly higher in the cancer group than in the non-cancer group. As the survival of cancer patients is improving with the development of new treatments, more attention should be paid to dysphagia in the management of cancer. Prompt and appropriate multidisciplinary interventions for dysphagia are necessary to improve the recovery and quality of life in cancer patients.

The effect of a telephone-based intervention on physical activity after stroke.

Despite the effectiveness of telephone-based interventions for medical adherence and improved blood pressure, studies on the effect of such interventions on physical activity (PA) are needed. Therefore, we investigated the impact of a telephone-based intervention on PA in patients with subacute stroke. This pre-post study included patients who participated in an education program for stroke rehabilitation before being discharged to home, with a modified Rankin scale (mRS) score of ≤ 3. Patients hospitalized in 2020 (intervention group) received a nurse-led telephone-based intervention with a PA measurement once monthly during the 3 months after discharge. Those hospitalized in 2019 (historical controls) only received a PA measurement 3 months after discharge. Physical activity was assessed via a questionnaire by phone. In addition, demographics, medical history, smoking, mRS scores, and Patient Health Questionnaire-9 data were collected. The study included 139 participants (73 in intervention, 66 in control). The intervention group had a higher proportion of patients with mRS of 0-1 and a shorter length of hospital stay than the historical controls. Three months post-discharge, a significantly higher proportion of participants were physically active in the intervention group (48 [71.6%] vs. control group, 25 [34.7%]). In addition, the intervention group had a significantly higher median energy expenditure (924 vs. 297 MET-min/week) than the control group. The OR of the intervention for achieving 'physically active' individuals was 4.749 (95% CI, 2.313-9.752) before and 5.222 (95% CI, 1.892-14.419) after adjusting for possible confounders. A telephone-based intervention improved PA three months after stroke. Further studies with larger sample size and long-term follow-up are needed.

White matter tracts involved in subcortical unilateral spatial neglect in subacute stroke.

Background: Unilateral spatial neglect (USN) is common and associated with poor motor and cognitive outcomes as well as impaired quality of life following stroke. Traditionally, the neural substrates underlying USN have been thought to be cortical areas, such as the posterior parietal cortex. However, patients with stroke involving only subcortical structures may also present with USN. While only a few studies have reported on USN in subcortical stroke, the involvement of white matter tracts related to brain networks of visuospatial attention is one possible explanation for subcortical neglect. Therefore, this study aimed to investigate which specific white matter tracts are neural substrates for USN in patients with subcortical stroke. Methods: Twenty-two patients with subcortical stroke without cortical involvement who were admitted to the Department of Rehabilitation Medicine at Seoul National University Bundang Hospital were retrospectively enrolled. Nine subjects were subclassified into a "USN(+)" group, as they had at least two positive results on three tests (the Schenkenberg line bisection test, Albert's test, and house drawing test) and a score of 1 or higher on the Catherine Bergego scale. The remaining 13 subjects without abnormalities on those tests were subclassified into the "USN(-)" group. Stroke lesions on MRI were manually drawn using MRIcron software. Lesion overlapping and atlas-based analyses of MRI images were conducted. The correlation was analyzed between the overlapped lesion volumes with white matter tracts and the severity of USN (in the Albert test and the Catherine Bergego scale). Results: Lesions were more widespread in the USN(+) group than in the USN(-) group, although their locations in the right hemisphere were similar. The atlas-based analyses identified that the right cingulum in the cingulate cortex, the temporal projection of the superior longitudinal fasciculus, and the forceps minor significantly overlapped with the lesions in the USN(+) group than in the USN(-) group. The score of the Catherine Bergego scale correlated with the volume of the involved white matter tracts. Conclusion: In this study, white matter tracts associated with USN were identified in patients with subcortical stroke without any cortical involvement. Our study results, along with previous findings on subcortical USN, support that USN may result from damage to white matter pathways.

Editor's Choice - Effect of Physical Activity and Tobacco Use on Mortality and Morbidity in Patients with Peripheral Arterial Disease After Revascularisation: A Korean Nationwide Population Based Cohort Study.

OBJECTIVE: To investigate the effects of physical activity (PA) and tobacco use on adverse clinical outcomes after revascularisation for peripheral arterial disease (PAD) in the Western Pacific region, where PAD cases and tobacco use are among the highest in the world. METHODS: This was a retrospective cohort study using the Korean National Health Insurance Service (NHIS) database and included patients who had received revascularisation for PAD between 2010 and 2015. They were categorised as active or inactive based on the number of days per week they engaged in PA and as current or non-tobacco users (self report). The primary outcome was all cause mortality. Secondary outcomes included major adverse outcome (a composite of all cause mortality, myocardial infarction, and stroke) and major adverse limb event (MALE, a composite of amputation and recurrent revascularisation). RESULTS: The relatively healthy cohort comprised 8 324 patients (mean age 64.7 years; 76.9% male) following revascularisation for PAD. Among them, 32.7% were inactive and 26.4% were tobacco users. Active patients had better outcomes than inactive patients (all cause mortality adjusted hazard ratio [adjHR] 0.766; 95% CI 0.685 - 0.855, major adverse outcome adjHR 0.795; 95% CI 0.719 - 0.878, MALE adjHR 0.858; 95% CI 0.773 - 0.953). Tobacco users had poorer outcomes than non-users (all cause mortality adjHR 1.279; 95% CI 1.124 - 1.456, major adverse outcome adjHR 1.263; 95% CI 1.124 - 1.418, MALE adjHR 1.291; 95% CI 1.143 - 1.458). CONCLUSION: Even after receiving revascularisation for PAD, a sizable proportion of patients were physically inactive and used tobacco, leading to adverse clinical outcomes such as death, cardiovascular morbidity, and amputation in Korea. These modifiable risk factors should be addressed systematically, and a comprehensive approach including supervised exercise programmes and tobacco cessation is needed in patients with PAD.

High prevalence of physical inactivity after heart valve surgery and its association with long-term mortality: A nationwide cohort study.

AIMS: Physical activity (PA) and systematic efforts, such as cardiac rehabilitation, are recommended by several national guidelines for those who have received heart valve surgery. However, only a few studies have demonstrated real-world situations, such as changes in the PA level after heart valve surgery, and their effects on long-term outcomes. We designed this study to investigate the changes in PA after heart valve surgery and their associations with mortality using nationwide representative data. METHODS: This study was performed using the Korean National Health Insurance Service database. We included patients who received heart valve surgery from 2009 to 2015 and underwent regular health checkups before and after surgery. Subjects were grouped according to their PA level before and after the surgery. Information on all-cause mortality was obtained until 31 December 2016, with a maximum follow-up period of 5 years. RESULTS: Of the 6587 subjects, 3258 (49.5%) were physically inactive after surgery. Among patients who were physically active (n = 3070), 1196 (39.0%) became inactive after surgery. The postoperative 'inactive' group showed higher mortality than the 'active' group (hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.08-1.83). The 'inactive/inactive' group showed the highest risk of mortality (HR: 1.69, 95% CI: 1.19-2.40) compared with the 'active/active' group. CONCLUSIONS: Insufficient PA level after heart valve surgery is associated with higher risk of mortality. However, maintaining sufficient PA after heart valve surgery may be challenging for many patients. Therefore, systematic efforts, such as cardiac rehabilitation, should be considered in those who received heart valve surgery.

Differential activation mechanisms of two isoforms of Gcr1 transcription factor generated from spliced and un-spliced transcripts in Saccharomyces cerevisiae.

Gcr1, an important transcription factor for glycolytic genes in Saccharomyces cerevisiae, was recently revealed to have two isoforms, Gcr1U and Gcr1S, produced from un-spliced and spliced transcripts, respectively. In this study, by generating strains expressing only Gcr1U or Gcr1S using the CRISPR/Cas9 system, we elucidate differential activation mechanisms of these two isoforms. The Gcr1U monomer forms an active complex with its coactivator Gcr2 homodimer, whereas Gcr1S acts as a homodimer without Gcr2. The USS domain, 55 residues at the N-terminus existing only in Gcr1U, inhibits dimerization of Gcr1U and even acts in trans to inhibit Gcr1S dimerization. The Gcr1S monomer inhibits the metabolic switch from fermentation to respiration by directly binding to the ALD4 promoter, which can be restored by overexpression of the ALD4 gene, encoding a mitochondrial aldehyde dehydrogenase required for ethanol utilization. Gcr1U and Gcr1S regulate almost the same target genes, but show unique activities depending on growth phase, suggesting that these isoforms play differential roles through separate activation mechanisms depending on environmental conditions.

Efficient production of d-lactate from methane in a lactate-tolerant strain of Methylomonas sp. DH-1 generated by adaptive laboratory evolution.

BACKGROUND: Methane, a main component of natural gas and biogas, has gained much attention as an abundant and low-cost carbon source. Methanotrophs, which can use methane as a sole carbon and energy source, are promising hosts to produce value-added chemicals from methane, but their metabolic engineering is still challenging. In previous attempts to produce lactic acid (LA) from methane, LA production levels were limited in part due to LA toxicity. We solved this problem by generating an LA-tolerant strain, which also contributes to understanding novel LA tolerance mechanisms. RESULTS: In this study, we engineered a methanotroph strain Methylomonas sp. DH-1 to produce d-lactic acid (d-LA) from methane. LA toxicity is one of the limiting factors for high-level production of LA. Therefore, we first performed adaptive laboratory evolution of Methylomonas sp. DH-1, generating an LA-tolerant strain JHM80. Genome sequencing of JHM80 revealed the causal gene watR, encoding a LysR-type transcription factor, whose overexpression due to a 2-bp (TT) deletion in the promoter region is partly responsible for the LA tolerance of JHM80. Overexpression of the watR gene in wild-type strain also led to an increase in LA tolerance. When d form-specific lactate dehydrogenase gene from Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 was introduced into the genome while deleting the glgA gene encoding glycogen synthase, JHM80 produced about 7.5-fold higher level of d-LA from methane than wild type, suggesting that LA tolerance is a critical limiting factor for LA production in this host. d-LA production was further enhanced by optimization of the medium, resulting in a titer of 1.19 g/L and a yield of 0.245 g/g CH4. CONCLUSIONS: JHM80, an LA-tolerant strain of Methylomonas sp. DH-1, generated by adaptive laboratory evolution was effective in LA production from methane. Characterization of the mutated genes in JHM80 revealed that overexpression of the watR gene, encoding a LysR-type transcription factor, is responsible for LA tolerance. By introducing a heterologous lactate dehydrogenase gene into the genome of JHM80 strain while deleting the glgA gene, high d-LA production titer and yield were achieved from methane.