2-Aminophenanthroline Ligands Enable Mild, Undirected, Iridium-Catalyzed Borylation of Alkyl C-H Bonds.

The catalytic, undirected borylation of alkyl C-H bonds typically occurs at high reaction temperatures or with excess substrate, or both, because of the low reactivity of alkyl C-H bonds. Here we report a new iridium system comprising 2-anilino-1,10-phenanthroline as the ligand that catalyzes the borylation of alkyl C-H bonds with little to no induction period and with high reaction rates. This superior activation and reactivity profile of 2-aminophenanthroline-ligated catalysts leads to broader reaction scope, including reactions of sensitive substrates, such as epoxides and glycosidic acetals, enhanced diastereoselectivity, and higher yields of borylated products. These catalysts also enable the borylation of alkanes, amines, and ethers at room temperature for the first time. Mechanistic studies imply that facile N-borylation occurs under the reaction conditions and that iridium complexes containing N-boryl aminophenanthrolines are competent precatalysts for the reaction.

Socio-economic inequalities in physical activity among Japanese adults during the COVID-19 pandemic.

OBJECTIVES: This study aimed to explore the socio-economic inequalities in physical activity (PA) based on domains of daily life, such as work, transport, recreation and sedentary life, among Japanese adults during the COVID-19 pandemic. STUDY DESIGN: This was a cross-sectional study. METHODS: This study used data from the 2020 National Sport and Lifestyle Survey, conducted by the Sasakawa Sports Foundation. Data of 2,296 (1,103 women) participants were analysed. PAs were assessed using the Global Physical Activity Questionnaire. Educational level and household income were used as indicators of socio-economic status. We calculated the slope index of inequality (SII) and relative index of inequality (RII). RESULTS: We detected absolute and relative inequalities for household income in all PA domains, except for work-related PA. The higher the participants' income, the longer they engaged in transport- and recreation-related PA and sedentary behaviour. Recreation-related PA had a larger disparity than other domains, with SII at 20.8% (95% confidence interval [CI] -28.4 to -13.1) and RII at 0.58 (95% CI 0.47-0.71). At the educational level, each inequality was observed in work- and recreation-related PA and sedentary behaviour. The higher the participants' educational level, the longer they engaged in recreation-related PA and sedentary behaviour. However, work-related PA was longer at lower educational levels, with RII at 1.90 (95% CI 1.48-2.44). The inequality in recreation-related PA was also relatively large (SII 23.3%, 95% CI -30.9 to -15.7; RII 0.54, 95% CI 0.45-0.66). CONCLUSION: Our study revealed significant socio-economic disparities in each PA domain, particularly in recreational PA. These results suggest a widening gap because of the COVID-19 pandemic.

Associations between 24-h movement behaviors and self-rated health: a representative sample of school-aged children and adolescents in Okinawa, Japan.

OBJECTIVES: This study aimed to determine the associations between adherence to 24-h movement behavior guidelines and self-rated health (SRH) among Japanese adolescents according to their age group. STUDY DESIGN: This was a cross-sectional study. METHODS: Probability proportional sampling data, which were collected from six regions of Okinawa Prefecture, Japan, considering the number of schools, included 2408 fifth-grade students (aged 10-11 years) in 31 elementary schools and 4360 eighth-grade students (aged 13-14 years) in 30 junior high schools. SRH, moderate-to-vigorous physical activity (MVPA), screen time (ST), sleep duration, and confounding factors (sex, weight status, family affluence, parental support, school satisfaction, and school demands) were self-reported. RESULTS: The logistic regression models showed that adherence to ST and sleep recommendations in elementary school students was associated with a high prevalence of good health only, whereas adherence to only MVPA, only sleep, ST and sleep, MVPA and sleep, and all three recommendations were associated with a high prevalence of good health among junior high school students. All combinations that included achievement of the recommended sleep duration were associated with SRH. CONCLUSIONS: Achieving 24-h movement behavior guidelines, particularly sleep recommendations, is associated with better perceived health in school-aged children, especially in adolescents.

n→π* Interactions Modulate the Disulfide Reduction Potential of Epidithiodiketopiperazines.

Epithiodiketopiperazines (ETPs) are a structurally complex class of fungal natural products with potent anticancer activity. In ETPs, the diketopiperazine ring is spanned by a disulfide bond that is constrained in a high-energy eclipsed conformation. We employed computational, synthetic, and spectroscopic methods to investigate the physicochemical attributes of this atypical disulfide bond. We find that the disulfide bond is stabilized by two n→π* interactions, each with large energies (3-5 kcal/mol). The n→π* interactions in ETPs make disulfide reduction much more difficult, endowing stability in physiological environments in a manner that could impact their biological activity. These data reveal a previously unappreciated means to stabilize a disulfide bond and highlight the utility of the n→π* interaction in molecular design.

Borinic Acid Catalyzed Stereo- and Regioselective Couplings of Glycosyl Methanesulfonates.

In the presence of a diarylborinic acid catalyst, glycosyl methanesulfonates engage in regio- and stereoselective couplings with partially protected pyranoside and furanoside acceptors. The methanesulfonate donors are prepared in situ from glycosyl hemiacetals, and are coupled under mild, operationally simple conditions (amine base, organoboron catalyst, room temperature). The borinic acid catalyst not only influences site-selectivity via activation of 1,2- or 1,3-diol motifs, but also has a pronounced effect on the stereochemical outcome: 1,2-trans-linked disaccharides are obtained selectively in the absence of neighboring group participation. Reaction progress kinetic analysis was used to obtain insight into the mechanism of glycosylation, both in the presence of catalyst and in its absence, while rates of interconversion of methanesulfonate anomers were determined by NMR exchange spectroscopy (EXSY). Together, the results suggest that although the uncatalyzed and catalyzed reactions give rise to opposite stereochemical outcomes, both proceed by associative mechanisms.

Socioeconomic inequalities in toothbrushing behaviours in young children: a children's lifestyle survey in a representative population of A city, Okinawa prefecture, Japan.

PURPOSE: We have less understanding of which socioeconomic status (SES) indicators may be reflective of latent socioeconomic inequalities in toothbrushing behaviours, especially finishing-toothbrushing by parents in young children. The aim of this study was to reveal the socioeconomic inequalities in children's toothbrushing and finishing-toothbrushing by parents and if it varies by SES indicators. METHODS: We used data from 'Survey on Children's Life' conducted by A city of Okinawa Prefecture, Japan. The multiple imputed data of 902 (boys, 453) included self-reported children's toothbrushing behaviour and finishing-toothbrushing by parents in three-to six-year-old children. SES was assessed using self-reported household income and parental educational attainment. Absolute and relative inequalities in toothbrushing behaviours were quantified using the slope index of inequality (SII) and relative index of inequality (RII), respectively. RESULTS: There were significant absolute and relative inequalities of children's toothbrushing for household income (SII and RII were 0.241 and 2.73, respectively), of finishing-toothbrushing by parents for household income (SII and RII were 0.133 and 3.28, respectively), and educational attainment (SII and RII were 0.166 and 5.55, respectively). The same inequality trends were observed after adjusting for covariates (child's age and sex, family structure, breakfast and dinner frequency, and sleep duration). CONCLUSION: Socioeconomic inequalities in children's toothbrushing and finishing-toothbrushing by parents varied according to SES indicators.

Total synthesis of himastatin.

The natural product himastatin has an unusual homodimeric structure that presents a substantial synthetic challenge. We report the concise total synthesis of himastatin from readily accessible precursors, incorporating a final-stage dimerization strategy that was inspired by a detailed consideration of the compound's biogenesis. Combining this approach with a modular synthesis enabled expedient access to more than a dozen designed derivatives of himastatin, including synthetic probes that provide insight into its antibiotic activity.

Chemoselective α-Sulfidation of Amides Using Sulfoxide Reagents.

The direct α-sulfidation of tertiary amides using sulfoxide reagents under electrophilic amide activation conditions is described. Employing convenient and readily available reagents, selective functionalization takes place to generate isolable sulfonium ions en route to α-sulfide amides. Mechanistic studies identified activated sulfoxides as promoters of the desired transformation and enabled the extension of the methodology from benzylic to aliphatic amide substrates.

Borinic acid-catalyzed stereo- and site-selective synthesis of ß-glycosylceramides.

A method for activation of unprotected ceramides towards stereo- and site-selective glycosylation is described. Two-point binding of a diarylborinic acid catalyst to the ceramide accelerates its reactions with 'armed' glycosyl methanesulfonate donors, resulting in the formation of a ß-glycosidic linkage at the primary OH group.

Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer.

BACKGROUND: We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer. METHODS: Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide. RESULTS: Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028). CONCLUSIONS: One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

LET distributions from CR-39 plates on Space Shuttle missions STS-84 and STS-91 and a comparison of the results of the CR-39 plates with those of RRMD-II and RRMD-III telescopes.

The LET distributions during the Space Shuttle missions STS-84 (altitude 270-412 km, average 375 km; inclination angle, 51.6 degrees) and STS-91 (altitude 328-397 km, average 373 km; inclination angle, 51.6 degrees) were measured using CR-39 plastic nuclear track detectors. A correction for the dip-angle dependence of the track-formation sensitivity of the CR-39 plates was applied to the data analysis. The absorbed doses and the dose equivalents around RRMD Detector Units, estimated from the LET distributions in the LET region of 4-200 keV/micrometers, fluctuated with standard deviations of +/- 21% to +/- 35% in both flight experiments. The LET distributions obtained from the CR-39 plates agreed well with that obtained from RRMD-II in STS-91. However, the particle fluxes obtained from RRMD-III in STS-84 and STS-91 were two or three times higher than those obtained from RRMD-II and the CR-39 plates. It was concluded that the LET distributions obtained from RRMD-II and the CR-39 plates in the present flight experiments did not include the contribution of target-fragmented secondary heavy particles produced by low-LET particles, such as relativistic or semi-relativistic protons and helium ions, whereas RRMD-III was able to detect these secondary particles because of its low triggering level.

Measurements of LET distribution and dose equivalent onboard the Space Shuttle IML-2 (STS-65) and S/MM#4 (STS-79).

Space radiation dosimetry measurements have been made onboard the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2: 28.5 degrees x 300 km: 14.68 days) and the STS-79 in the 4th Shuttle MIR mission (S/MM#4: 51.6 degrees x 300-400km: 10.2 days). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD-I for IML-2 and RRMD-II with improved triggering system for S/MM#4)" utilizing silicon semi-conductor detectors and the other detectors are conventional passive detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. The main contribution to dose equivalent for particles with LET > 5.0 keV/micrometer (IML-2) and LET > 3.5 keV/micrometer (S/MM#4) is seen to be due to galactic cosmic rays (GCRs) and the contribution of the South Atlantic Anomaly (SAA) is less than 5% (IML-2: 28.5 degrees x 300 km) and 15% (S/MM#4: 51.6 degrees x 400 km) in the above RRMD LET detection conditions. For the whole LET range (> 0.2 kev/micrometer) obtained by TLDs and CR-39 in these two typical orbits (a small inclination x low altitude and a large inclination x high altitude), absorbed dose rates range from 94 to 114 microGy/day, dose equivalent rates from 186 to 207 microSv/day and average quality factors from 1.82 to 2.00 depending on the locations and directions of detectors inside the Spacelab at the highly protected IML-2 orbit (28.5 degrees x 300 km), and also, absorbed dose rates range from 290 to 367 microGy/day, dose equivalent rates from 582 to 651 microSv/day and average quality factors from 1.78 to 2.01 depending on the dosimeter packages around the RRMD-II "Detector Unit" at the S/MM#4 orbit (5l.6 degrees x 400km). In general, it is seen that absorbed doses depend on the orbit altitude (SAA trapped particles contribution dominant) and dose equivalents on the orbit inclination (GCR contribution dominant). The LET distributions obtained by two different types of active and passive detectors, RRMDs and CR-39, are in good agreement for LET of 15 - 200 kev/micrometer and difference of these distributions in the regions of LET < 15 kev/micrometer and LET > 200 kev/micrometer can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks and chemical etching conditions.

[Histopathological prognostic factors in 146 patients with renal cell carcinoma: comparison between incidental and non-incidental cases].

To characterize the prognostic factors among pathological structural pattern, cell type, infiltration, and incidental or non-incidental renal cell carcinoma (RCC), we reviewed the records of 146 patients with RCC who underwent nephrectomy at our institute. The patients were 26 to 86 years old (mean age 58). The men-to-women ratio was 3.2:1. The tumor originated in the right kidney in 83 patients and in the left in 63. The solid pattern was associated with poorer survival than other patterns (p < 0.01). Spindle or pleomorphic cell type had poorer survival than common type (p < 0.01). The number of incidentally discovered RCC has increased since 1986, and survival is better than in non-incidental RCC, because of smaller tumor size, low stage tumor (stages 1, 2; 83.6%), and fewer papillary or solid type. In addition, there were no spindle or pleomorphic cell type, grade 3 or INF gamma-positive case. Survival is good even when the tumor is large.

[Clinical study on Fournier's gangrene--value of "through and through drainage"].

From 1991 to 1994, we experienced 5 patients with Fournier's gangrene. Their age, associated diseases, etiology, area of the disease, microbiologic findings, treatment and prognosis were reviewed. Patient age ranged from 25 to 72 years, with a mean age of 47 years. An associated disease process could be identified in all patients. Two patients had diabetes mellitus, 1 systemic lupus erythematosus, 1 chronic alcoholism and 1 multiple myeloma. The etiology of the infectious process was presumed to be wound infection in 2 patients and indwelling urethral catheter in 2 patients. All patients were treated with broad-spectrum antibiotics. Extensive débridement with later skin graft was done in 2 patients. Multiple Penrose-drains were placed subcutaneously after limited removal of necrotic tissue in 3 patients. In these 3 patients, redness and swelling reduced quickly, the wound was cured without defects of skin except 1 patient who had multiple myeloma and was in a very serious condition. Although inflammation reduced after the placement of drains, the patient with multiple myeloma died of sepsis and DIC. The majority of patients with Fournier's gangrene are immunocompromised. Although extensive débridement is commonly performed as the surgical treatment, defects of the skin seem to have some disadvantages, such as the need for the skin graft and the chance of secondary wound infection. In the narrow excision of necrotic tissue and drainage of involved areas by multiple Penrose-drains, skin defects are minimum, and the effectiveness of the surgical management seems to be competitive with the wide débridement.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case report of complete inversion of the bladder in an old woman].

A 77-year-old Japanese woman was admitted to our hospital complaining of small urinary volume. Physical examination revealed a light red, edematous, pyriform mass, approximately 7 cm in diameter at the vulva. An orifice posterior to the base of the mass was catheterized and 20 ml of urine was obtained. Roentgenograms of contrast material injection to the orifice demonstrated a space of 20 ml. A diagnosis of complete inversion of the bladder was made. Under epidural anesthesia, attempts were made to reduce the mass through the urethra. The manual reduction proved to be difficult, but was successful by manual compression of the bladder wall and squeezing it back through the urethra, which took approximately 60 minutes. Complete transurethral inversion of the bladder is so rare that not much of the pathogenesis is clarified. In our patient, senility, obesity, multiple labor and surgeries are assumed to have resulted in laxity of the pelvic wall which would be one of the major risk factors for this condition.