Effects of intrauterine extracellular vesicle microRNAs on embryonic gene expression in low-fertility cows.

Embryo survival and pre-implantation development depend on uterine luminal fluid, which is believed to play a role in early embryonic death and infertility in cows. Extracellular vesicles (EVs) in the uterine luminal fluid contain microRNAs (miRNAs), crucial mediators of intercellular communication. miRNAs regulate conceptus-maternal interactions and participate in embryonic development by suppressing gene expression. Therefore, we hypothesized that miRNAs in the intrauterine EVs of low-fertility cows would hinder embryonic survival and development. EVs were collected from the bovine uterine luminal fluid of both normal- and low-fertility cows 7 days post-estrus. Small RNA-sequencing analysis of miRNAs isolated from these EVs identified eight miRNAs that were highly expressed in normal-fertility cows (normal-fertility miRNAs) and eight with elevated expression in low-fertility cows (low-fertility miRNAs). These two sets of miRNAs were transfected into hatched blastocysts via lipofection. RNA-seq following lipofection with low-fertility miRNAs identified 424 differentially expressed genes (DEGs) relative to the control; in contrast, following lipofection with normal-fertility miRNAs, seven DEGs were identified. Pathway analysis of the DEGs identified following lipofection with low-fertility miRNAs revealed substantial enrichment of mitogen-activated protein kinase (MAPK) signaling. Expression of activator protein 1 (AP1) and interferon-tau (IFNT) mRNA was significantly lower in the low-fertility miRNA transfection group than in the control. IFNT is essential for maternal pregnancy recognition. Therefore, miRNAs in intrauterine EVs from low-fertility cows at 7 days post-estrus may inhibit embryo development and suppress IFNT expression by altering MAPK signaling.

Smartphone-Based Digital Peer Support for a Walking Intervention Among Public Officers in Kanagawa Prefecture: Single-Arm Pre- and Postintervention Evaluation.

BACKGROUND: Digital peer support, defined as peer support delivered through technology such as smartphone apps, may be promising to promote activity in the form of step counts. Interactions among users have a positive impact on retention rates, and apps with social elements show significant improvements in daily step count. However, the feasibility of digital peer support in promoting physical activity (PA) is unknown; therefore, its effectiveness on step count and the clinical implications remain unconfirmed. OBJECTIVE: This study aimed to assess the feasibility of digital peer support over a 3-month intervention period using the retention rate as the outcome. Moreover, changes in daily step count and physical measurements were compared between pre- and postintervention. METHODS: The study design was a 3-month 1-arm intervention with participants from local government offices in Kanagawa, Japan. We used an available smartphone app, Minchalle, as the tool for the group intervention. Participants were required to report their daily step count to a maximum of 5 members composed exclusively of study participants. The primary outcome was the retention rate. Secondary outcomes included daily step count, the rate of achieving daily step goals, physical measurements, and lifestyle characteristics. Descriptive statistics and the Pearson coefficient were used to examine the relationship between goal achievement and step count, as well as changes in step count and various variables including physical measurements. RESULTS: Of the 63 participants, 62 completed the intervention. The retention rate was 98% (62/63). The average daily step count during the intervention was 6993 (SD 2328) steps, an 1182-step increase compared with the count observed 1 week before the intervention began. The rate of achieving the daily step count during the intervention was 53.5% (SD 26.2%). There was a significant correlation (r=0.27, P=.05) between achieving daily step goals and increasing daily step count. Comparative analyses showed that changes in weight (68.56, SD 16.97 kg vs 67.30, SD 16.86 kg; P<.001), BMI (24.82, SD 4.80 kg/m2 vs 24.35, SD 4.73 kg/m2; P<.001), somatic fat rate (28.50%, SD 7.44% vs 26.58%, SD 7.90%; P=.005), systolic blood pressure (130.42, SD 17.92 mm Hg vs 122.00, SD 15.06 mm Hg; P<.001), and diastolic blood pressure (83.24, SD 13.27 mm Hg vs 77.92, SD 11.71 mm Hg; P=.002) were significantly different before and after the intervention. Similarly, the daily amount of PA significantly improved from 5.77 (SD 3.81) metabolic equivalent (MET)-hours per day to 9.85 (SD 7.84) MET-hours per day (P<.001). CONCLUSIONS: This study demonstrated that digital peer support is feasible for maintaining a high retention rate and can, therefore, effectively promote PA. It can be a promising tool to improve daily step count, subjective PA, and clinical outcomes, such as weight and somatic fat rate. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000042520; https://tinyurl.com/46c4nm8z.

Targeted protein degradation in the mitochondrial matrix and its application to chemical control of mitochondrial morphology.

Dysfunction of mitochondria is implicated in various diseases, including cancer and neurodegenerative disorders, but drug discovery targeting mitochondria and mitochondrial proteins has so far made limited progress. Targeted protein degradation (TPD) technologies represented by proteolysis targeting chimeras (PROTACs) are potentially applicable for this purpose, but most existing TPD approaches leverage the ubiquitin-proteasome system or lysosomes, which are absent in mitochondria, and TPD in mitochondria (mitoTPD) remains little explored. Herein, we describe the design and synthesis of a bifunctional molecule comprising TR79, an activator of the mitochondrial protease complex caseinolytic protease P (ClpP), linked to desthiobiotin. This compound successfully induced the degradation of monomeric streptavidin (mSA) and its fusion proteins localized to the mitochondrial matrix. Furthermore, in cells overexpressing mSA fused to short transmembrane protein 1 (mSA-STMP1), which enhances mitochondrial fission, our mitochondrial mSA degrader restored the mitochondrial morphology by reducing the level of mSA-STMP1. A preliminary structure-activity relationship study indicated that a longer linker length enhances the degradation activity towards mSA. These findings highlight the potential of mitoTPD as a tool for drug discovery targeting mitochondria and for research in mitochondrial biology, as well as the utility of mSA as a degradation tag for mitochondrial protein.

Efficacy of exercise with the hybrid assistive limb lumbar type on physical function in mobility-limited older adults: A 5-week randomized controlled trial.

BACKGROUND: Sarcopenia and frailty often worsen in older adults because of declines in activities of daily living and social connections that are associated with chronic diseases and traumatic injuries such as falls and fractures. Exercise intervention for sarcopenia can take >3 months to improve muscle mass, muscle strength, and walking speed. Thus, a specialized intervention system for shorter periods of time is needed. In this study, we aimed to evaluate the short-term efficacy of an exercise program using the wearable cyborg Hybrid Assistive Limb (HAL) lumbar type in physical function in mobility-limited older adults who do not require transition to long-term care. METHODS: This randomized, single-blind, parallel-group study involved 79 community-dwelling older adults with physical frailty or locomotive syndrome assigned to an intervention group (n = 40) with the HAL lumbar type exercise program or a control group (n = 39) without the exercise program. The intervention group underwent trunk training (including trunk and hip flexion, standing and sitting from a single sitting position, and squats) and gait training (treadmill and parallel bars) twice a week for 5 weeks while wearing the HAL lumbar type. The 10-m usual and maximum walking speeds, Timed Up and Go test results, 5-times chair-standing test results, 5-question Geriatric Locomotive Function Scale (GLFS-5) scores, body-fat percentage, and muscle mass were measured before and after the intervention and analyzed using the intention-to-treat method. RESULTS: The intervention (23 % male; mean age, 74.7 ± 4.7 years) and control (21 % male; mean age, 75.1 ± 4.1 years) groups did not differ significantly in baseline characteristics. Seventy-seven participants completed the program; two withdrew for personal reasons. The mean difference (standard error) between the groups for the primary outcome (usual walking speed) was 0.35 (0.04) m/s; the time-by-group interaction was significant (p < 0.001). Secondary outcomes (maximum walking speed, Timed Up and Go test results, 5-times chair-standing test results, and GLFS-5 scores) significantly improved in the intervention group. Body composition was unchanged in both groups. CONCLUSIONS: A 5-week exercise program using the HAL lumbar type is a promising option for community-dwelling older adults with limited mobility who do not require nursing care, resulting in clinically meaningful improvements in most physical functions within a short period.

Expression of SARS-CoV-2 entry molecules ACE2, NRP1, TMPRSS2, and FURIN in the reproductive tissues of male macaques.

Coronavirus disease 2019 (COVID-19) reportedly affects male reproductive function by causing spermatogenesis dysfunction and suppressing testosterone secretion. However, the relationship between COVID-19 and impaired reproductive function, such as whether these effects on reproductive function are a direct effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in male reproductive organs or an indirect effect of high fever, is not known. Here, we examined whether the cell entry molecules of SARS-CoV-2, namely, ACE2, NRP1, TMPRSS2, and FURIN, are expressed in the male reproductive organs using the testes and accessory gonads of macaques during the breeding season. RT-PCR expression analysis showed that the testes alone expressed all four molecules. Immunohistochemical staining of testis tissue sections revealed that ACE2 is expressed in Leydig cells and the apical region of Sertoli cells, whereas NRP1 is expressed in the cell bodies surrounding the Leydig and Sertoli cell nuclei. FURIN is mainly expressed in Leydig cells, secondary spermatocytes, and spermatids. However, TMPRSS2 immunopositive cells were not observed. Therefore, it was not possible to observe cells expressing all four molecules in the gonads and accessory gonads of male primates. These results suggest that SARS-CoV-2 is unlikely to directly affect spermatogenesis in primates or proliferate in cells of the seminiferous tubules and undergo release into the semen through the previously known ACE2-mediated infection route. However, the expression of three molecules, including ACE2, was observed in Leydig cells, suggesting that testosterone synthesis and secretion may be affected when primates, including humans, are infected with SARS-CoV-2.

Carnosine supplementation in cryopreservation solution improved frozen-thawed bovine embryo viability.

Cryopreservation adversely affects embryo quality and viability in vitro. We investigated the effects of cryopreservation solutions supplemented with the antioxidant carnosine on frozen-thawed bovine embryo viability. Bovine blastocysts were produced in vitro and cryopreserved using slow freezing. The rates of re-expanded and hatched blastocysts in the 50 µg/ml carnosine-supplemented group at 4, 24, and 48 h after thawing were higher than those in the control (P < 0.05) group. In frozen-thawed embryos, cryopreservation solution supplemented with carnosine (50 µg/ml) significantly reduced reactive oxygen species (ROS) production (P < 0.05), decreased TUNEL-positive apoptotic cells (P < 0.05), and increased the mRNA expression of BCL2 (P < 0.05), an apoptosis suppressor gene. The expression of translocase of outer mitochondrial membrane 20 (TOMM20), which is involved in protein mitochondrial transport, in the carnosine (50 µg/ml)-treated embryos was significantly higher than that in the control group (P < 0.05). ATP production in frozen-thawed embryos in the 50 µg/ml carnosine-supplemented group was significantly higher than that in the control group (P < 0.05), however no significant difference in the total number of cells per embryo among the groups was observed. These results suggest that supplementing the cryopreservation solution with carnosine can improve the viability of frozen-thawed bovine embryos by reducing oxidative damage.

Quality-of-life survey of pancreatic cancer patients: a comparison between general public and physicians.

Background: Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public. Methods: A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients' health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values. Results: Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: -0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios. Conclusions: The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.

The relationship between loneliness and blood glucose: a cross-sectional survey among Japanese.

Recently, researchers have uncovered a correlation between loneliness and both the development and management of diabetes. Nevertheless, previous studies employing an unvalidated loneliness questionnaire impair result accuracy. Furthermore, this aspect has not been researched in the Japanese population. Therefore, this cross-sectional study analyzed data from the Kanagawa prospective "ME-BYO" Cohort Study (ME-BYO cohort) to investigate the correlation between loneliness, as measured by 20 items on the UCLA Loneliness Scale, and blood glucose levels. A total of 666 participants were included in the analysis, with a mean age of 54.1 years and a mean BMI of 23 kg/m2. Half of the participants had obtained an education level beyond high school. The mean household income and physical activity level were reported as 6.83 million Japanese yen and 12.3 METs-h/day, respectively. Model 1 of the linear regression analysis determined that there was no significant association between the loneliness scale and HbA1c (p = 0.512). After adjusting for age, gender, BMI (model 2), sitting time, physical activity level (model 3), housemates, household income, and final education (model 4), and controlling for social support, quality of life, and depression (model 5), the results showed no significant association, with a p-value of 0.823, 0.791, 0.792, and 0.816, respectively. Thus, the study found no link between loneliness and HbA1c in the high SES population. This finding contradicts previous results and may be attributed to the impact of population characteristics, SES status, or genetic backgrounds.

Raphe glucose-sensing serotonergic neurons stimulate KNDy neurons to enhance LH pulses via 5HT2CR: rat and goat studies.

Dysfunction of central serotonergic neurons is known to cause depressive disorders in humans, who often show reproductive and/or glucose metabolism disorders. This study examined whether dorsal raphe (DR) serotonergic neurons sense high glucose availability to upregulate reproductive function via activating hypothalamic arcuate (ARC) kisspeptin neurons (= KNDy neurons), a dominant stimulator of gonadotropin-releasing hormone (GnRH)/gonadotropin pulses, using female rats and goats. RNA-seq and histological analysis revealed that stimulatory serotonin-2C receptor (5HT2CR) was mainly expressed in the KNDy neurons in female rats. The serotonergic reuptake inhibitor administration into the mediobasal hypothalamus (MBH), including the ARC, significantly blocked glucoprivic suppression of luteinizing hormone (LH) pulses and hyperglycemia induced by intravenous 2-deoxy-D-glucose (2DG) administration in female rats. A local infusion of glucose into the DR significantly increased in vivo serotonin release in the MBH and partly restored LH pulses and hyperglycemia in the 2DG-treated female rats. Furthermore, central administration of serotonin or a 5HT2CR agonist immediately evoked GnRH pulse generator activity, and central 5HT2CR antagonism blocked the serotonin-induced facilitation of GnRH pulse generator activity in ovariectomized goats. These results suggest that DR serotonergic neurons sense high glucose availability to reduce gluconeogenesis and upregulate reproductive function by activating GnRH/LH pulse generator activity in mammals.

Relationship between Treatment Choices according to the Modified Osteoporotic Fracture Score and Posttreatment Radiographic Outcomes.

STUDY DESIGN: Retrospective observational study. PURPOSE: To evaluate the modified osteoporotic fracture (mOF) scores in three treatment groups and compare imaging findings in patients treated and not treated according to the mOF score-based treatment recommendation. OVERVIEW OF LITERATURE: The osteoporotic fracture (OF) score was established by the AO Spine to guide therapeutic decisions. To enhance its applicability, a mOF score was recently introduced. METHODS: Consecutive patients diagnosed with OFs at Fujieda Heisei Memorial Hospital were divided into three groups: nonsurgical therapy, balloon kyphoplasty (BKP), and open surgery groups. The mOF score was calculated, and the levels of independence and posttreatment imaging data were compared between patients treated and not treated according to the mOF score-based treatment recommendation. RESULTS: In total, 118 patients were included (nonsurgical therapy, n=57; BKP, n=48; open surgery, n=13), of whom 100 (85%) received treatment consistent with the mOF score-based treatment recommendation. In the BKP and open surgery groups, the mOF scorebased treatment recommendations were consistent with the actual treatment in 93% of the patients. However, in the nonsurgical group, the mOF score-based treatment recommendation was not consistent with the actual treatment in 25% of the patients. In this group, patients not treated according to the mOF score had significantly shorter vertebral body height, greater local kyphosis, and smaller sacral slope after treatment than patients treated according to the mOF score-based treatment recommendation. CONCLUSIONS: In the BKP and open surgery groups, the mOF scores were consistent with actual clinical selection. In the nonsurgical therapy group, patients not treated according to the mOF score-based treatment recommendation exhibited severe vertebral body deformity and a less well-balanced spine shape after treatment. The mOF score may help in selecting suitable treatments for OFs.

Characteristics of the most viewed Hybrid Assistive Limb-related videos on YouTube.

Objectives. YouTube is one of the most popular video-sharing tools and is used as a forum for sharing information about experiences with new technology-based exercise programs, such as the wearable cyborg Hybrid Assistive Limb (HAL). This study aimed to analyze the content and quality of HAL-related videos viewed by people to clarify the content required by YouTube viewers. Methods. We searched HAL-related YouTube videos and selected the top 100 most viewed videos. The number of views, video length, upload date, content, and uploaders of each video were recorded. In addition, DISCERN was used to evaluate the quality of videos. Results. Of the 100 videos, the most shared content was the training videos on HAL (n = 58). The videos uploaded by YouTubers had a significantly higher number of views than those uploaded by other uploaders (hospital, company, and municipality) (p < .001). Furthermore, they had significantly higher DISCERN Questions 16 scores, which serve as the basis for the overall evaluation of the publication's overall quality (p < .001). Conclusion. HAL-related videos on YouTube, featuring the experiences and feedback of YouTubers who are HAL users, are favored more by viewers than by service providers.

Differences in the Demographics and Clinical Characteristics between the Ossification of the Posterior Longitudinal Ligament and Ossification of the Ligamentum Flavum in Patients Who Underwent Thoracic Spinal Surgery for Compressive Myelopathy.

Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are related diseases associated with the ossification of spinal ligaments that can occasionally lead to thoracic myelopathy. We retrospectively analyzed the clinical data of 34 consecutive patients who underwent thoracic spinal surgeries for OPLL and/or OLF at our hospital between July 2010 and June 2022, and statistically compared data between patients with thoracic OPLL (TOPLL; n = 12) and those with thoracic OLF (TOLF; n = 22). The mean age of the TOPLL group was significantly lower than that of the TOLF group (53.7 vs. 68.4 years). The TOPLL group exhibited a greater female predominance than the TOLF group (58.3% vs. 18.2%). The median body mass index of the TOPLL group was significantly higher than that of the TOLF group (33.0 vs. 26.0 kg/m2). Patients with TOPLL significantly required instrumented fusion and repetitive surgical intervention more than those with TOLF (83.3% vs. 9.1%; 50.0% vs. 0.0%). Although neurological deterioration just after the intervention was more common in patients with TOPLL (41.7% vs. 4.6%), no difference was observed in thoracic Japanese Orthopaedic Association score and recovery rate in the chronic phase between TOPLL and TOLF. The TOPLL group had a younger onset, female dominance, and a greater degree of obesity when compared with the TOLF group. The surgery for TOPLL is challenging, considering that it requires long-range decompression and fusion, subsequent operations, careful management, and long-term follow-up, when compared to TOLF, which necessitates only simple decompression.

Screening for prostate cancer in a city in Japan: age-specific prostate-specific antigen cutoff thresholds.

PURPOSE: Older men have higher prostate-specific antigen levels than younger men. However, the current Japanese Urological Association guidelines recommend secondary screening at a cutoff value of 4.0 ng/mL, even in older men. Here, we reexamined the cutoffs for older men using a prostate screening cohort in Japan and first performed an analysis to determine the indication cutoffs for detecting positive biopsies. METHODS: Data from 68,566 prostate cancer screenings in the city in 2018 were combined with cancer registration data. The optimal prostate-specific antigen levels to predict prostate cancer in different age groups were calculated using receiver operating characteristic curves after determining whether a cancer was registered within one year of screening. RESULTS: At the conventional prostate-specific antigen threshold of 4.0 ng/mL, the sensitivity, specificity, and negative predictive value were 94.9%, 91.7%, and 91.7%, respectively. The optimal prostate-specific antigen cutoff values for patients aged 50-59 years, 60-69 years, 70-79 years, and over 80 years were 3.900 ng/mL, 4.014 ng/mL, 4.080 ng/mL, and 4.780 ng/mL, respectively. CONCLUSIONS: The sensitivity and specificity of prostate cancer screening in the city were high, indicating a highly accurate screening. The prostate-specific antigen threshold was 4.78 ng/mL in patients older than 80 years. A higher prostate-specific antigen threshold may be useful in men over 80 years of age to avoid excess biopsy and reduce costs. Our results suggest that the current Japanese method of using PSA 4.0 ng/mL as a cutoff regardless of age may not be preferable for older men.

Age group differences in psychological distress and leisure-time exercise/socioeconomic status during the COVID-19 pandemic: a cross-sectional analysis during 2020 to 2021 of a cohort study in Japan.

Objective: This study aimed to determine the association between psychological distress and leisure-time exercise/socioeconomic status by age group, using data from a cohort study in Japan during the COVID-19 pandemic. Methods: This cross-sectional study was conducted among participants in the ME-BYO cohort, aged 20-85 years, living or working in Kanagawa, Japan. A questionnaire was disseminated to 1,573 participants (51.7% men) between December 2020 and March 2021. The questionnaire items included psychological distress (using the 6-item Kessler Psychological Distress Scale [K6]), leisure-time exercise, and socioeconomic status. Multivariate analyses were conducted using logistic regression analysis for each age group. Results: We found that 47.4% of 20-39-year-olds, 40.6% of 40-64-year-olds, and 28.3% of 65-85-year-olds experienced psychological distress (K6: ≥5 points). For those aged 20-39 years, leisure-time exercise (odds ratio [OR] (95% confidence interval) = 0.45 (0.28-0.73)) and higher annual household income [0.53 (0.32-0.90)] were associated with less psychological distress. For those aged 40-64 years, older age was associated with less psychological distress, while full-time work [1.98 (1.05-9.71)] was associated with more psychological distress. In the 65-85-year age group, higher education and higher annual income tended to be associated with less psychological distress. For those over 40 years of age, living with other(s) was associated with reduced psychological distress. Conclusion: In the general population of Japan, not engaging in leisure-time exercise and low income affect psychological distress among young adults. Further detailed studies are needed to consider overall physical activity, job type, and work style.

Treatment with Ligilactobacillus murinus lowers blood pressure and intestinal permeability in spontaneously hypertensive rats.

One feature of hypertension is a microbial imbalance with increased intestinal permeability. In this study, we examined whether an alteration in the microbiota affects blood pressure and intestinal permeability in spontaneously hypertensive rats (SHRs). We performed a 16S metagenome analysis of feces from 10- to 15-week-old SHRs using a synthetic long-read sequencing approach, and found a candidate for the microbiome treatment, Ligilactobacillus murinus (L. murinus), that was robustly decreased. Oral administration of L. murinus to SHRs for 2 weeks significantly inhibited blood pressure elevation and improved endothelium-dependent vasodilation but did not attenuate enhanced vascular contraction in SHR mesenteric arteries. The proximal colon of SHRs exhibited increased intestinal permeability with decreased levels of the tight junction protein claudin 4, morphological changes such as decreased intestinal crypts and elevated TNF-α levels, which was reversed by treatment with L. murinus. Consistent with these intestinal phenotypes, plasma lipopolysaccharides levels were elevated in SHR but decreased following L. murinus administration. We concluded that oral administration of L. murinus to SHRs exerts protective effects on intestinal permeability via restoration of claudin 4 expression and reversal of morphologic disorder, which may improve low-grade endotoxemia and thus reduce development of hypertension via recovery of endothelial vasodilating functions.

Analysis of Neurogenic Bowel and Bladder Dysfunction Following Decompression Surgery for Cervical Spondylotic Myelopathy: A Prospective Cohort Study.

STUDY DESIGN: A prospective observational study. OBJECTIVES: To investigate preoperative prevalence of neurogenic bowel dysfunction and neurogenic bladder in patients with degenerative cervical myelopathy (DCM) and examine the degree and timing of symptom improvement after cervical decompression surgery. Factors contributing to symptom improvement were also analyzed. METHODS: Among 75 patients with DCM who underwent cervical decompression, Constipation Scoring System (CSS) score, International Prostate Symptoms Score (IPSS), and Japanese Orthopaedic Association (JOA) score were assessed before surgery and 1, 3, 6, and 12 months after. Prevalence rates were calculated. Data regarding patient age, sex, disease status, disease duration, lesion level, and score changes was prospectively recorded and analyzed. RESULTS: The prevalence rates of defecation and urinary dysfunction before surgery were 41.3% and 34.7%, respectively. Among the patients with defecation dysfunction, the number of patients who improved 1, 3, 6, and 12 months after surgery was 10, 9, 9, and 6, respectively. Among the patients with urinary dysfunction, the corresponding number of patients was 12, 10, 11, and 11, respectively. None of the factors we examined were significantly associated with improvement in either CSS or IPSS score; however, improvement of lower extremity JOA score tended to be associated with improvement in both. CONCLUSIONS: The prevalence of symptoms of defecation and urinary dysfunction in patients with DCM was 41.3% and 34.7%, respectively. Decompression surgery improved symptoms in 20% to 46% of patients.

Unrecognized dural tear during percutaneous endoscopic lumbar surgery confirmed with myelography.

Iatrogenic dural tear is usually recognized during the surgery. We describe a rare case of unrecognized dural tear caused by percutaneous endoscopic lumbar surgery at another hospital clearly confirmed with dynamic myelography. Although magnetic resonance imaging of the lumbar spine showed no obvious fluid collection suggesting dural tear, dynamic myelography revealed leakage of intradural subarachnoid contrast medium along root sleeve into the intervertebral disc space. In the setting of endoscopic spine surgery, incidental dural tear might be overlooked due to the narrow and fluid-filled surgical field. Dynamic myelography is useful to evaluate the precise condition caused by unrecognized dural tear.

Isosteric Replacement of Ester Linkage of Lysophospholipids with Heteroaromatic Rings Retains Potency and Subtype Selectivity.

Our group has reported various derivatives of lysophosphatidylserine (LysoPS) as potent and subtype-selective agonists for G-protein-coupled receptors (GPCRs). However, the ester linkage between the glycerol moiety and fatty acid or fatty acid surrogate is present in all of them. In order to develop these LysoPS analogs as drug candidates, appropriate pharmacokinetic consideration is essential. Here, we found that the ester bond of LysoPS is highly susceptible to metabolic degradation in mouse blood. Accordingly, we examined isosteric replacement of the ester linkage with heteroaromatic rings. The resulting compounds showed excellent retention of potency and receptor subtype selectivity, as well as increased metabolic stability in vitro.

Postoperative intractable leg pain caused by dislocation of drainage tube.

Background: A wide variety of conditions can cause recurrent postoperative lumbar radiculopathy. Case Description: A 49-year-old female developed sudden recurrent postoperative right leg pain after a right-sided L5S1 microdiskectomy for a herniated disc. Emergent magnetic resonance and computed tomography studies demonstrated migration of the drainage tube into the right L5S1 lateral recess compromising the S1 nerve root. Following drain removal, the patient's right reg pain immediately resolved. Conclusion: Migration of a lumbar wound drain into the operated lateral recess following a lumbar diskectomy may result in acute, recurrent/intractable radicular pain that was readily resolved with drain removal.

The ME-BYO index: A development and validation project of a novel comprehensive health index.

Quantifying health status and identifying modifiable factors are essential for effective and individualized prevention of age-related conditions and for promoting health during aging. The ME-BYO concept from Kanagawa Prefecture, one of Japan's largest prefectures, can be used to establish a healthy aging society. In disease etiology, ME-BYO considers the status of an individual's body and mind as changing continuously from healthy to sick instead of being a dichotomy between the two. ME-BYO conceptualizes the entire process of this change. The ME-BYO index was developed in 2019 to comprehensively and numerically measure and visualize an individual's current health status and future disease risk by quantifying data on the four domains of metabolic function, locomotor function, cognitive function, and mental resilience. The ME-BYO index has been implemented in the personal health management application "My ME-BYO." However, scientific validation of this index and the development of a practical application using healthcare data remain to be completed. In 2020, our research team started a project to refine the ME-BYO index using data from the Kanagawa ME-BYO prospective cohort study, which is a large population-based genomic cohort study. This project will scientifically evaluate the ME-BYO index and develop a practical application for promoting healthy aging.