Neighbourhood relationships moderate the positive association between family caregiver burden and psychological distress in Japanese adults: a cross-sectional study.

OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

Incident fracture associated with increased risk of mortality even after adjusting for frailty status in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

Frail elderly individuals have elevated risks of both fracture and mortality. We found that incident fractures were associated with an increased risk of death even after adjusting for pre-fracture frailty status as represented by physical performance tests and laboratory tests for common geriatric diseases in community-dwelling elderly Japanese men. INTRODUCTION: While fractures reportedly increase the risk of mortality, frailty may complicate this association, generating a false-positive result. We evaluated this association after adjusting for pre-fracture levels of frailty. METHODS: We examined 1998 community-dwelling ambulatory men aged ≥65 years at baseline in the Fujiwara-kyo Osteoporosis Risk in Men Study for frailty status as represented by activities of daily living (ADL), physical performance tests (grip strength, one-foot standing balance with eyes open, timed 10-m walk), and laboratory sera tests. Participants were then followed for 5 years for incident clinical fractures and death. Effects of incident fracture on death were determined by Cox proportional hazards model with the first fracture during follow-up as a time-dependent predictor and with frailty status indices as covariates. RESULTS: We identified 111 fractures in 99 men and 138 deaths during the follow-up period (median follow-up, 4.5 years). Participants with incident fractures did not have significantly worse frailty statuses, but did show a significantly higher cumulative mortality rate than those without fractures (p = 0.0047). Age-adjusted hazard ratio (HR) of death for incident fracture was 3.57 (95 % confidence interval: 2.05, 6.24). When adjusted for physical performance, this decreased to 2.77 (1.51, 5.06), but remained significant. The HR showed no significant change when adjusted for laboratory test results (3.96 (2.26, 6.94)). Exclusion of deaths within the first 24 months of follow-up did not alter these results. CONCLUSION: Incident clinical fracture was associated with an elevated risk of death independently of pre-fracture levels of frailty in community-dwelling elderly men.

Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrome, which is caused by mutations in KMT2D or KDM6A, genes also involved in histone methylation. KMT2A mutations and clinical features are summarized in our six patients together with eight previously reported patients. Furthermore, clinical comparison of the two syndromes is discussed in detail.

Molecular genetic analysis of 30 families with Joubert syndrome.

Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the 'molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.

STUDY QUESTION: How do the temperature and duration of storage affect ovaries during transportation? SUMMARY ANSWER: Fertility is reduced with the extension of the storage duration. WHAT IS KNOWN ALREADY: Live birth has been reported after ovarian transport overnight on ice before freezing ovarian tissue, but there have been no basic investigations of ovarian storage conditions focused on fertility. There are no guidelines on optimal ovarian storage conditions and the maximum storage time during transportation. STUDY DESIGN, SIZE AND DURATION: Experiments were performed using C57BL/6J mice. Ovaries of 4-week-old mice were harvested, stored at 4, 14, 37 °C or room temperature (RT) for 24 h, and subjected to histological examination. Next, ovaries were stored at 4 °C for 4, 8 or 24 h and subjected to histological examination. Then orthotopic transplantation of ovaries, stored at 4 °C for 4, 8 or 24 h, was performed in 6-week-old C57BL/6J mice, and fertility was assessed by in vitro fertilization and embryo transfer. Freshly harvested ovaries were used as controls for comparison with ovaries stored under the above-mentioned conditions and experiments were repeated at least three times. PARTICIPANTS/MATERIALS, SETTING AND METHODS: In experiments on the ovarian storage temperature, haematoxylin-eosin (HE) staining was performed for histological examination. In experiments on the storage duration, HE staining, the terminal deoxynucleotidyl transferase dUTP nick end labelling assay, Ki-67 staining and electron microscopy were performed, and the numbers of follicles were counted. Fertility was assessed from the number of oocytes, and the rates of fertilization, embryo development, implantation and live birth. MAIN RESULTS AND THE ROLE OF CHANCE: Histological changes were minimal after storage of ovaries at 4 °C for up to 24 h. At 4 °C, there were no significant changes in the number of MII oocytes, fertilization rate or blastocyst development rate with storage up to 24 h. The implantation rate was 82.7 ± 17.3% in the control group, while it was 82.2 ± 7.7, 14.6 ± 14.6 and 4.4 ± 4.4% after storage for 4, 8 or 24 h, respectively. After 8 or 24 h of storage, the implantation rate was significantly lower in than in the control group (P< 0.05). The rate of live pups was 24.8 ± 13.2% in the control group, while it was 23.9 ± 6.6, 4.2 ± 4.2 and 4.4 ± 4.4% after storage for 4, 8 or 24 h, respectively. After 8 or 24 h of storage, the rate of live pups was significantly lower than in the control group (P< 0.05). LIMITATIONS, REASONS FOR CAUTION: Further investigations are needed in mammals with ovaries of a similar size to human ovaries, and should include the assessment of fertility following transplantation of frozen and thawed ovaries. WIDER IMPLICATION OF THE FINDINGS: The present results suggest that prolonging the ovarian storage time reduces fertility in mice. Thus, ovaries should be frozen immediately after harvesting or transported as rapidly as possible to minimize damage. To allow young cancer patients to preserve fertility, regional medical centres need adequate ovarian tissue cryopreservation techniques. STUDY FUNDING/COMPETING INTERESTS: This study supported by Department of Obstetrics and Gynecology, St. Marianna University School of Medicine. The authors have no competing interests to declare.

Electric control of the spin Hall effect by intervalley transitions.

Controlling spin-related material properties by electronic means is a key step towards future spintronic technologies. The spin Hall effect (SHE) has become increasingly important for generating, detecting and using spin currents, but its strength--quantified in terms of the SHE angle--is ultimately fixed by the magnitude of the spin-orbit coupling (SOC) present for any given material system. However, if the electrons generating the SHE can be controlled by populating different areas (valleys) of the electronic structure with different SOC characteristic the SHE angle can be tuned directly within a single sample. Here we report the manipulation of the SHE in bulk GaAs at room temperature by means of an electrical intervalley transition induced in the conduction band. The spin Hall angle was determined by measuring an electromotive force driven by photoexcited spin-polarized electrons drifting through GaAs Hall bars. By controlling electron populations in different (Γ and L) valleys, we manipulated the angle from 0.0005 to 0.02. This change by a factor of 40 is unprecedented in GaAs and the highest value achieved is comparable to that of the heavy metal Pt.

Targeted next-generation sequencing in the diagnosis of neurodevelopmental disorders.

We developed a next-generation sequencing (NGS) based mutation screening strategy for neurodevelopmental diseases. Using this system, we screened 284 genes in 40 patients. Several novel mutations were discovered. Patient 1 had a novel mutation in ACTB. Her dysmorphic feature was mild for Baraitser-Winter syndrome. Patient 2 had a truncating mutation of DYRK1A. She lacked microcephaly, which was previously assumed to be a constant feature of DYRK1A loss of function. Patient 3 had a novel mutation in GABRD gene. She showed Rett syndrome like features. Patient 4 was diagnosed with Noonan syndrome with PTPN11 mutation. He showed complete agenesis of corpus callosum. We have discussed these novel findings.

De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy.

Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G > A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G > C, p.Asp252His and c.364G > A, p.Glu122Lys) in EEF1A2 found by whole-exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.

Autosomal recessive cystinuria caused by genome-wide paternal uniparental isodisomy in a patient with Beckwith-Wiedemann syndrome.

Approximately 20% of Beckwith-Wiedemann syndrome (BWS) cases are caused by mosaic paternal uniparental disomy of chromosome 11 (pUPD11). Although pUPD11 is usually limited to the short arm of chromosome 11, a small minority of BWS cases show genome-wide mosaic pUPD (GWpUPD). These patients show variable clinical features depending on mosaic ratio, imprinting status of other chromosomes, and paternally inherited recessive mutations. To date, there have been no reports of a mosaic GWpUPD patient with an autosomal recessive disease caused by a paternally inherited recessive mutation. Here, we describe a patient concurrently showing the clinical features of BWS and autosomal recessive cystinuria. Genetic analyses revealed that the patient has mosaic GWpUPD and an inherited paternal homozygous mutation in SLC7A9. This is the first report indicating that a paternally inherited recessive mutation can cause an autosomal recessive disease in cases of GWpUPD mosaicism. Investigation into recessive mutations and the dysregulation of imprinting domains is critical in understanding precise clinical conditions of patients with mosaic GWpUPD.

Trabecular bone score may improve FRAX® prediction accuracy for major osteoporotic fractures in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

UNLABELLED: FRAX® is widely used to evaluate fracture risk of individuals in clinical settings. However, FRAX® prediction accuracy is not sufficient, and improvement is desired. Trabecular bone score, a bone microarchitecture index, may improve FRAX® prediction accuracy for major osteoporotic fractures in community-dwelling elderly Japanese men. INTRODUCTION: To improve fracture risk assessment in clinical settings, we evaluated whether the combination of FRAX® and Trabecular Bone Score (TBS) improves the prediction accuracy of major osteoporotic fractures (MOFs) in elderly Japanese men compared to FRAX® alone. METHODS: Two thousand and twelve community-dwelling men aged ≥65 years completed the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Baseline Study comprising lumbar spine (LS) and femoral neck areal bone mineral density (aBMD) measurements, and interviews regarding clinical risk factors required to estimate 10-year risk of MOF (hip, spine, distal forearm, and proximal humerus) using the Japanese version of FRAX® (v.3.8). TBS was calculated for the same vertebrae used for LS-aBMD with TBS iNsight software (v.2.1). MOFs that occurred during the follow-up period were identified by interviews or mail and telephone surveys. Prediction accuracy of a logistic model combining FRAX® score and TBS compared to FRAX® alone was evaluated by area under receiver-operating characteristic curves (AUCs), as well as category-free integrated discrimination improvement (IDI) and net reclassification improvement (NRI). RESULTS: We identified 22 men with MOFs during 8140 person-years (PY) of follow-up among 1872 men; 67 men who suffered from fractures other than MOFs were excluded. Participants with MOFs had significantly lower TBS (p = 0.0015) and higher FRAX® scores (p = 0.0089) than those without. IDI and NRI showed significant improvements in reclassification accuracy using FRAX® plus TBS compared to FRAX® alone (IDI 0.006 (p = 0.0362), NRI 0.452 (p = 0.0351)), although no difference was observed in AUCs between the two. CONCLUSIONS: TBS may improve MOF prediction accuracy of FRAX® for community-dwelling elderly Japanese men.

Greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in a population of elderly Japanese men with relatively low dietary calcium intake: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.

UNLABELLED: The effects of milk intake on bone health are not clear in elderly Asian men with low dietary calcium intake. This study showed that greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in community-dwelling elderly Japanese men. INTRODUCTION: The consumption of milk or dairy products is widely recommended for maintaining bone health regardless of gender or age. However, little evidence exists on the beneficial effects of milk intake on bone health in elderly Japanese men characterized with relatively low dietary calcium intake. Here we examined whether or not greater milk intake was associated with lower bone turnover, higher bone density, and stronger bone microarchitecture in community-dwelling elderly Japanese men. METHODS: Interviews were conducted to obtain information on medical history and lifestyle, including the amount of habitual milk intake, nutrient intake calculations based on a 1-week food diary, and measurements of areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS) using DXA images at LS, and biochemical markers of bone turnover in sera. Participants with a history of diseases or medications that affect bone metabolism, or with missing data, were excluded from the analysis. RESULTS: The median intake of milk in the 1479 participants (mean age, 73.0 ± 5.1 years) was one glass of milk per day. Bone turnover markers showed a decreasing trend (p < 0.05) and aBMD at TH (p = 0.0019) and FN (p = 0.0057) and TBS (p = 0.0017) showed increasing trends with greater milk intake after adjusting for demographic and behavioral confounding factors. This association was attenuated after further adjusting for nutrient intake, in particular, calcium intake. CONCLUSIONS: Greater milk intake was associated with lower bone turnover, higher aBMD, and higher TBS in community-dwelling elderly Japanese men.

Endoplasmic reticulum stress-induced apoptosis contributes to articular cartilage degeneration via C/EBP homologous protein.

OBJECTIVE: When endoplasmic reticulum (ER) stress, i.e., the excessive accumulation of unfolded proteins in ER, endangers homeostasis, apoptosis is induced by C/EBP homologous protein (Chop). In osteoarthritis (OA) cartilage, Chop expression and apoptosis increase as degeneration progresses. We investigated the role of Chop in murine chondrocyte apoptosis and in the progression of cartilage degeneration. METHOD: We induced experimental OA in Chop-knockout (Chop(-/-)) mice by medial collateral ligament transection and meniscectomy and compared cartilage degeneration, apoptosis, and ER stress in Chop(-/-)- and wild-type (Chop(+/+)) mice. In our in vitro experiments we treated murine Chop(-/-) chondrocytes with the ER stress inducer tunicamycin (TM) and evaluated apoptosis, ER stress, and chondrocyte function. RESULTS: In vivo, the degree of ER stress was similar in Chop(-/-)- and Chop(+/+) mice. However, in Chop(-/-) mice apoptosis and cartilage degeneration were lower by 26.4% and 42.4% at 4 weeks, by 26.8% and 44.9% at 8 weeks, and by 26.9% and 32.3% at 12 weeks after surgery than Chop(+/+) mice, respectively. In vitro, the degree of ER stress induction by TM was similar in Chop(-/-)- and Chop(+/+) chondrocytes. On the other hand, apoptosis was 55.3% lower and the suppression of collagen type II and aggrecan mRNA was 21.0% and 23.3% less, and the increase of matrix metalloproteinase-13 mRNA was 20.0% less in Chop(-/-)- than Chop(+/+) chondrocytes. CONCLUSION: Our results indicate that Chop plays a direct role in chondrocyte apoptosis and that Chop-mediated apoptosis contributes to the progression of cartilage degeneration in mice.

Coffin-Siris syndrome is a SWI/SNF complex disorder.

Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder.

Dose escalation study of carboplatin-pemetrexed followed by maintenance pemetrexed for elderly patients with advanced nonsquamous nonsmall-cell lung cancer.

BACKGROUND: This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed. RESULTS: The combination of carboplatin at an area under the concentration-time curve (AUC) of 5, and 500 mg/m(2) pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68-216 days) and the median overall survival time was 461 days (95% CI 168-754 days). CONCLUSIONS: This combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m(2)) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC.

Impact of UCP1 and ß3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans.

BACKGROUND: Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. The activity and prevalence of BAT decrease with age in humans. OBJECTIVE: To examine the effects of single nucleotide polymorphisms of the genes for uncoupling protein 1 (UCP1) and ß3-adrenergic receptor (ß3AR), key molecules of BAT thermogenesis, on age-related decline of BAT activity and accumulation of body fat in humans. METHODS: One hundred ninety-nine healthy volunteers (20-72 years old (y.o.)) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) after 2-h cold exposure to assess BAT activity. The visceral and subcutaneous fat areas at the abdominal level were estimated from the CT images. They were genotyped for -3826 A/G polymorphism of the UCP1 gene and 64 Trp/Arg mutation of the ß3AR gene. RESULTS: BAT was detected in 88 subjects out of 199 (44%), more in younger (30 y.o., 55%) than older subjects (>40 y.o., 15%). BAT prevalence of older subjects tended to be lower in the UCP1 G/G group than the A allele group (A/A and A/G), and also in the ß3AR Arg allele group (Trp/Arg and Arg/Arg) than the Trp/Trp group. When compared subjects who had two or more base substitutions on the two genes (the 2-4 allele group) with those who had less than two base substitutions (the 0-1 allele group), BAT prevalence was comparable in younger subjects (62% vs 50%) but lower in older subjects (0% vs 24%, P<0.05). Visceral fat area of the 2-4 allele group was higher than that of the 0-1 allele group (P<0.05) in older subjects, but not in younger subjects. CONCLUSION: UCP1 -3826 A/G and ß3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age.

Changes in renal glucose transporters in an animal model of metabolic syndrome.

Considering the similarity between structural, hemodynamic, and functional changes of obesity-related renal disease and diabetic nephropathy, we hypothesized that renal glucose transporter changes occur in obesity as in diabetes. The aim of the work was to evaluate GLUT1 and GLUT2 in kidneys of an animal model of metabolic syndrome. Neonate spontaneously hypertensive rats (SHR), n=15/group, were treated with monosodium glutamate (5 mg/g) (MetS) for 9 days and compared with saline-treated Wistar-Kyoto (C) and SHR (H) rats. Lee index, systolic arterial pressure (SAP), glycemia, insulin resistance, triglycerides, and HDL cholesterol were evaluated at 3 and 6 months. Medullar GLUT1 and cortical GLUT2 were analyzed by Western blot. MetS vs. C and H rats had the highest Lee index (p<0.001) and insulin resistance (3-months C: 4.3±0.7, H: 3.9±0.9, MetS: 2.7±0.6; 6-months C: 4.2±0.6, H: 3.8±0.5, MetS: 2.4±0.6% · min⁻¹, p<0.001), similar glycemia, and the lowest HDL-cholesterol at 6-months (p<0.001). In the MetS and H rats, SAP was higher vs. C at 3-months (p<0.001) and 6-months (C: 151±15, H: 190±11, MetS: 185±13 mm Hg, p<0.001) of age. GLUT1 was Ì´ 13× lower (p<0.001) at 3-months, reestablishing its content at 6-months in MetS group, while GLUT2 was 2× higher (p<0.001) in this group at 6-months of age. Renal GLUT1 and GLUT2 are modulated in kidney of rats with metabolic syndrome, where obesity, insulin resistance and hypertension coexist, despite normoglycemia. Like in diabetes, cortical GLUT2 overexpression may contribute to the development of kidney disease.

Comparison of short-term outcomes of robotic and laparoscopic transabdominal peritoneal repair for unilateral inguinal hernia: a propensity-score matched analysis.

PURPOSE: This study aimed to compare perioperative outcomes of robotic and laparoscopic transabdominal peritoneal repair (TAPP) for unilateral inguinal hernia. METHODS: This single institutional retrospective cohort study used de-identified data of patients who underwent robotic TAPP (R-TAPP) or laparoscopic TAPP (L-TAPP) for unilateral inguinal hernia between January 1, 2016 and October 31, 2021. Two cohorts were propensity matched, and data were analyzed. The learning curve was evaluated in the R-TAPP group. RESULTS: Among 938 patients analyzed, 704 were included. After propensity-score matching, 80 patients were included in each group. The difference in operative time between R-TAPP and L-TAPP groups was 10 min (99.5 and 89.5 min, p = 0.087); however, console/laparoscopic time was similar (67 and 66 min, p = 0.71). The dissection time for medial-type hernia in the R-TAPP group was marginally shorter than that in the L-TAPP group (17 and 27 min, p = 0.056); however, there was no difference for lateral-type hernia (38.5 and 40 min p = 0.37). Perioperative variables, including estimated blood loss, postoperative hospital stay, and postoperative pain, had no significant difference, and chronic pain, which needed medication or intervention, was not observed in each group. The number of cases needed to achieve plateau performance was 7-10 in the R-TAPP group. CONCLUSION: This study suggests that R-TAPP was safely introduced, and its perioperative outcomes were not inferior to those of L-TAPP. A shorter dissection time for medial-type hernia might be due to the robot's advantages, and a fast-learning curve could help with the early standardization of the procedure.

Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.

SUMMARY: Recent animal studies have demonstrated that undercarboxylated osteocalcin upregulates insulin secretion via osteoblast-insulin signaling. However, it remains unclear whether such a pathway exists in humans. This study showed that serum undercarboxylated osteocalcin levels were inversely associated with fasting plasma glucose, hemoglobin A(1c), and homeostasis model assessment of insulin resistance (HOMA-IR) levels in community-dwelling elderly Japanese men. INTRODUCTION: Undercarboxylated osteocalcin (ucOC) was reported to increase insulin secretion and improve glucose tolerance via osteoblast-insulin signaling in animal-based studies. Whether this pathway also exists in humans is unknown. We aimed to clarify whether serum ucOC levels are associated with glycemic status and insulin resistance in the general Japanese population. METHODS: We included 2,174 Japanese men (≥65 years) who were able to walk without aid from others and lived at home in four cities of Nara Prefecture. We excluded participants with a history of diseases or medications that affect bone metabolism, other than type 2 diabetes mellitus (T2DM). Fasting plasma glucose, glycated hemoglobin A(1c), and HOMA-IR levels were determined as outcome measures. RESULTS: Of the 1,597 participants included in the analysis, both intact OC (iOC) and ucOC levels showed significant inverse correlations with all outcome measures, even after adjusting for potential confounders. Mean values of outcome measures showed a significant decreasing trend with higher quintiles of iOC or ucOC after adjusting for confounders. This trend remained significant for ucOC quintiles after further adjustment for iOC levels, but was not significant for iOC quintiles after adjusting for ucOC levels. These results were attenuated, but still apparent, after excluding participants receiving drug therapy for T2DM. CONCLUSIONS: Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies.

Association between vitamin K intake from fermented soybeans, natto, and bone mineral density in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

SUMMARY: A cross-sectional analysis of 1,662 community dwelling elderly Japanese men suggested that habitual natto intake was significantly associated with higher bone mineral density (BMD). When adjustment was made for undercarboxylated osteocalcin levels, this association was insignificant, showing the natto-bone association to be primarily mediated by vitamin K. INTRODUCTION: Low vitamin K intake is associated with an increased risk of hip fracture, but reports have been inconsistent on its effect on BMD. Our first aim was to examine the association between BMD and intake of fermented soybeans, natto, which contain vitamin K1 (20 µg/pack) and K2 (380 µg/pack). Our second aim was to examine the association between undercarboxylated osteocalcin (ucOC), a biomarker of vitamin K intake, and BMD to evaluate the role of vitamin K in this association. METHODS: Of the Japanese men aged ≥65 years who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men study, 1,662 men without diseases or medications known to affect bone metabolism were examined for associations between self-reported natto intake or serum ucOC levels with lumbar spine or hip BMD. RESULTS: The subjects with greater intake of natto showed significantly lower level of serum ucOC. Analysis after adjustment for confounding variables showed an association of greater intake of natto with both significantly higher BMD and lower risk of low BMD (T-score < -1 SD) at the total hip and femoral neck. This association became insignificant after further adjustment for ucOC level. CONCLUSION: Habitual intake of natto was associated with a beneficial effect on bone health in elderly men, and this association is primarily due to vitamin K content of natto, although the lack of information on dietary nutrient intake, including vitamin K1 and K2, prevented us from further examining the association.