Catalytic enantioselective [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones.

A highly efficient asymmetric [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones has been developed. This innovative reaction employs an organocatalytic approach, utilizing a hydrogen-bonding bifunctional squaramide-based catalyst. The process enables precise synthesis of chiral polyheterotricyclic oxazolidines and 1,3-oxazinane derivatives, revealing intricate structures with incorporated chiral quaternary centers. Remarkably, this method delivers high yields and exceptional enantioselectivities and diastereoselectivities, achieving up to 99% yield, >20 : 1 dr, and >99% ee.

Stereoselective [4+3]-Cycloaddition of 2-Amino-ß-nitrostyrenes with Azaoxyallyl Cations to Access Functionalized 1,4-Benzodiazepin-3-ones.

The 1,4-benzodiazepine structural framework is a fascinating element commonly found in biologically active and pharmaceutically relevant compounds. A highly efficient method for synthesizing 1,4-benzodiazepin-3-ones is described, involving a [4+3]-cycloaddition reaction between 2-amino-ß-nitrostyrenes and α-bromohydroxamate, with Cs2CO3 used as a base. This process yielded the desired 1,4-benzodiazepines in good yields. Furthermore, an organocatalytic asymmetric [4+3]-cycloaddition was successfully accomplished using a bifunctional squaramide-based catalyst. This approach enabled the enantioselective synthesis of chiral 1,4-benzodiazepines with commendable yields and moderate enantioselectivities, reaching up to 80% yield and 72% ee.

Organocatalytic Enantioselective Synthesis of Polycyclic Benzosultams from 2-Amino-ß-nitrostyrenes with Cyclic N-Sulfonyl Ketimines.

A highly efficient enantioselective [4 + 2] cycloaddition of 2-amino-ß-nitrostyrenes with cyclic N-sulfonyl ketimines has been developed. This reaction utilizes an organocatalytic approach, employing a multiple-hydrogen-bonding bifunctional squaramide-based catalyst. The process allows for the precise synthesis of chiral polycyclic benzosultams, showcasing intricate structures that incorporate chiral quaternary centers. Noteworthy outcomes of this method include high yields with excellent enantioselectivities and diastereoselectivities (up to 97% yield, 96% ee, and >20:1 dr).

[4+2]-Cycloaddition of 2-Aminophenyl Enones with Cyclic N-Sulfimines to Access Enantioenriched Ring-Fused Aminals.

Ring-fused aminal is an interesting structural skeleton in biologically active and pharmaceutically relevant compounds. A novel and efficient method for synthesizing benzosulfamidate-fused tetrahydroquinazolines is described. By employing the [4+2]-cycloaddition of 2-aminophenyl enones with cyclic N-sulfimines in the presence of DMAP as a base, the desired benzosulfamidate-fused tetrahydroquinazolines were obtained in good yields with high diastereoselectivities. Furthermore, an organocatalytic asymmetric [4+2]-cycloaddition was successfully achieved using a squaramide-based catalyst, enabling the enantioselective synthesis of chiral ring-fused tetrahydroquinazolines with high yields and enantio- as well as diastereoselectivities (up to 89 % yield, 94 % ee, and >30 : 1 dr).

Organocatalytic Asymmetric [4 + 2]-Cycloadditions of 2-Aminophenyl Enones with Isatin-Derived Ketimines: Diastereo- and Enantioselective Synthesis of Spirooxindole-Tetrahydroquinazolines.

A novel method for the enantioselective synthesis of spiro N,N-heterocyclic oxindoles has been developed, employing asymmetric [4 + 2]-cycloadditions of 2-aminophenyl enones with isatin-derived ketimines. This method employs an organocatalytic approach, utilizing a bifunctional squaramide-based catalyst. It enables the precise synthesis of chiral spirooxindole-tetrahydroquinazolines with intricate structures, featuring chiral quaternary centers. This process achieves remarkable results, including high yields and exceptional levels of enantioselectivity and diastereoselectivity (up to 96% yield, 95% ee, and >20:1 dr).

Rate of alcohol-induced blackout experience and its negative consequences among Korean university students.

An alcohol-induced blackout suggested to be related to a rapid increase in blood alcohol concentration and it is closely related to long-term memory creation. Blackout has been experienced by 35% of the general population and over 50% of university student population. In addition, it has been shown that blackout could be a precursor of injury risk. However, the rate of blackout and blackout related negative consequences in Korean university students have rarely been studied. Therefore, the objective of this study was to determine the blackout experience rate and its negative consequences among students from four universities in Korea. A survey was conducted among university students located in Pusan, Korea in 2013. Demographic and blackout related information were collected through self-report questionnaire, including blackout experience, age of first blackout, and negative consequences of blackout. Descriptive statistical analysis was performed for collected data. Of a total of 470 subjects (Male = 217, Female = 253) surveyed, 190 (40.4%) subjects had experienced a blackout at some points in their lives. The majority (86.3%) of them experienced the first blackout between 20-25 years old. Among those who had experienced a blackout, 57.0% reported that they could not remember how they went home at the end of the night, 8.1%, 7.6%, 3.1%, and 2.2% reported that they had bodily injuries, argument, physical or personal fight, and sexual-related incidences, respectively. This study shows that many Korean university students have experienced blackouts and related negative events. These results suggest that more systematic drinking control strategy is required for Korean university students.

Synthesis of 5,6-Dihydropyrazolo[5,1-a]isoquinolines through Tandem Reaction of C,N-Cyclic Azomethine Imines with α,ß-Unsaturated Ketones.

An innovative and efficient approach has been developed for the synthesis of 5,6-dihydropyrazolo[5,1-a]isoquinolines. This one-pot tandem reaction involves the reaction of C,N-cyclic azomethine imines with α,ß-unsaturated ketones, using K2CO3 as the base and DDQ as the oxidant. The process results in functionalized 5,6-dihydropyrazolo[5,1-a]isoquinolines with good yields. This convenient one-step method encompasses a tandem [3 + 2]-cycloaddition, detosylation, and oxidative aromatization.

Synthesis of Benzotriazepin-1-ones via Decarboxylative [4 + 3]-Annulation of Isatoic Anhydrides with Nitrile Imines.

A novel and streamlined approach to synthesizing benzotriazepin-1-ones has been developed through a hexafluoroisopropanol-promoted decarboxylative cascade reaction between isatoic anhydrides and hydrazonoyl chloride. The [4 + 3] annulation of hexafluoroisopropyl 2-aminobenzoates with nitrile imines, generated in situ, is a key feature of this innovative reaction. This approach has offered a simple and efficient method for synthesizing a broad range of structurally intricate and highly functional benzotriazepinones.

[4 + 2] Annulation of δ-Hydroxy/δ-Sulfonamido-α,ß-Unsaturated Ketones with Azlactones for Diastereoselective Synthesis of Highly Substituted 3-Amino-δ-Lactones and 3-Amino-δ-Lactams.

The first base-mediated [4 + 2] annulation of δ-hydroxy-α,ß-unsaturated ketones with azlactones has been developed, through which 3,4-disubstituted 3-amino-δ-lactones were obtained in good yields and with excellent diastereoselectivities. This approach was also applied to the [4 + 2] annulation of δ-sulfonamido-α,ß-unsaturated ketones, which provided a practical protocol for constructing biologically important 3-amino-δ-lactam frameworks.

Estimation of the vitamin D (VD) status of pregnant Japanese women based on food intake and VD synthesis by solar UV-B radiation using a questionnaire and UV-B observations.

Although vitamin D (VD; serum 25 hydroxyvitamin D) deficiency (< 20 ng/mL) is widespread among Japanese women, the VD status among pregnant women is unknown. This study aimed to determine the VD status of pregnant Japanese women during different meteorological seasons and to determine the factors controlling VD status. A total of 309 pregnant Japanese women were recruited at 28 weeks of gestation at the gynecology department of a university hospital in Tokyo between August 2018 and October 2019. Blood samples were collected to measure serum 25(OH)D levels. Two questionnaires were completed: a brief self-administered dietary history questionnaire (BDHQ) and an outdoor exposure history questionnaire to determine skin sunlight exposure and the use of sunscreen. Among the recruited subjects, 268 were included in the statistical analysis. The average VD intake from food was 9.0 µg/day, the average VD synthesis from UV-B was 15.2 µg/day, and the average sum of VD intake and nominal VD synthesis was 24.1 µg/day; this exceeded the recommended 2011 Dietary Reference Intake for the USA and Canada (15.0 µg/day). However, the average serum 25(OH)D level (11.4 ng/mL) was very low, indicating widespread VD deficiency. Serum 25(OH)D and VD synthesis by solar UV-B were significantly correlated only during the high UV-B season. The 25(OH)D level was weakly correlated with the VD intake from food in all seasons. We obtained a statistically significant correlation between serum 25(OH)D level and VD intake from food using the BDHQ. We also obtained a statistically significant correlation between the serum 25(OH)D level and VD synthesis from solar UV-B exposure, especially during the high UV-B season. Our logistic regression analysis model predicted VD deficiency in 88.0% of subjects. Our method might be possible to be used to predict the VD status of pregnant Japanese women, although another validation cohort is needed to verify the ability of the estimation equation.

Chemodivergent 1,3-Dipolar Cycloadditions of C,N-Cyclic Azomethine Imines with γ-Sulfonamido-α,ß-Unsaturated Ketones to Synthesize Tricyclic Dinitrogen-Fused Heterocycles.

1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with γ-NHTs-α,ß-unsaturated ketones were developed to synthesize tricyclic dinitrogen-fused heterocycles. Highly functionalized tricyclic tetrahydroisoquinolines were readily obtained in good to high yields in the [3 + 2]-cycloaddition reaction of N-Bz-protected C,N-cyclic azomethine imines with γ-NHTs-α,ß-unsaturated ketones under mild reaction conditions. Moreover, DABCO-catalyzed cycloaddition of N-Ts-protected C,N-cyclic azomethine imines with γ-NHTs-α,ß-unsaturated ketones followed by cleavage of the tosyl group is a convenient route to synthesize tetrahydropyrazolo [5,1-a]isoquinolines in good yields with excellent diastereoselectivities.

Organocatalytic Asymmetric [3 + 2]-Annulations of γ-Sulfonamido/γ-Hydroxy-α,ß-Unsaturated Ketones with Cyclic N-Sulfimines: Synthesis of Chiral Polyheterotricyclic Imidazolidines and Oxazolidines.

The first organocatalytic asymmetric [3 + 2]-annulation of γ-sulfonamido-α,ß-unsaturated ketones with cyclic N-sulfimines has been developed, and enantioenriched functionalized polyheterotricyclic imidazolidines were obtained in good yields and with excellent enantioselectivities. This approach was also extended to the asymmetric [3 + 2]-annulation of γ-hydroxy-α,ß-unsaturated ketones, affording enantioenriched polyheterotricyclic oxazolidines. In addition, base-catalyzed [3 + 2]-annulations of γ-sulfonamido/γ-hydroxy-α,ß-unsaturated ketones with cyclic N-sulfimines were re-investigated under mild reaction conditions for the synthesis of racemic polyheterotricyclic imidazolidines and oxazolidines with excellent diastereoselectivities.

Effect of Extract of Black Sticky Rice with Giant Embryo on Alcohol Cravings of Korean Social Drinkers: A 12-Week Randomized, Placebo-Controlled Trial.

We investigated the effect of black sticky rice with giant embryo (BSRGE) extract known to contain high levels of gamma-aminobutyric acid (GABA) on alcohol cravings in social drinkers. A total of 41 subjects were divided into a BSRGE extract group (G group: n = 21) and a placebo group (P group: n = 20), and a randomized placebo-controlled experiment was performed for 12 weeks. The G group took the BSRGE extracts that contained 30 mg of GABA per day. (1) In the Pennsylvania Alcohol Craving Scale, there was a tendency for time and group interaction between the two groups (P = .087) on the total score. (2) In the Obsessive-Compulsive Drinking Scale (OCDS), there was a significance for time and group interaction between the G and P groups (P = .011) on the obsessive subscale. The total score of the OCDS showed significant time and group interactions between the G and P groups (P = .011). Our results showed that the extract of BSRGE containing a high level of GABA significantly reduced alcohol cravings in Korean social drinkers.

Acetabular cartilage abnormalities in elderly patients with femoral neck fractures.

INTRODUCTION: Both hemiarthroplasty (HA) and total hip arthroplasty (THA) are widely accepted surgical procedures for hip replacement following displaced femoral neck fractures. However, in cases involving an intact joint line before surgery, the choice between HA and THA remains debatable. This study investigated the prevalence of acetabular cartilage and labral abnormalities in elderly patients with femoral neck fractures. METHODS: Thirty-seven patients underwent hip arthroplasty for femoral neck fractures between April 2020 and February 2021. After excluding 4 patients, 33 patients (6 men and 27 women; mean age = 82.2 [range = 67-98] years) with fractures in 12 left and 21 right hips were included. After femoral head removal during arthroplasty, the acetabulum was macroscopically examined for the presence of cartilage and labral lesions. Acetabular cartilage abnormalities were classified as either overall degeneration or partial damage according to the cartilage damage classification system. RESULTS: Acetabular cartilage abnormalities, including overall degeneration or partial damage, were found in all hips (100%). Out of the 33 hips, overall degeneration, partial damage, and labral abnormalities were detected in 32 (96.9%), 16 (48.4%), and 9 (27.2%) hips, respectively. DISCUSSION: In this study, most elderly patients with femoral neck fractures exhibited acetabular cartilage and labral abnormalities, which were already present at the time of surgery. Therefore, surgeons should carefully examine these abnormalities as they may impact postoperative outcomes such as pain and function.

Frequent fractures and sclerotic thick bands on physes related to oral alendronate treatments.

Bisphosphonate treatment has known effects of improving bone mineral density and preventing fractures in children with steroid-induced osteoporosis. However, there have been reports that high-dosage pamidronate therapy induces osteopetrosis in the borders of bones. A 10-year-old boy undergoing long-term treatment with oral alendronate developed frequent fractures throughout adolescence while playing basketball. Radiographs showed osteosclerotic bands on the metaphyses of his long bones and vertebrae, and fractures were evident in the regions surrounding the osteosclerotic lesions: a stress fracture in the fourth metatarsal, anterior limbus vertebra (T12), spondylolysis (L3 and L5), and osteochondritis dissecans of the left lateral femoral condyle. Alendronate had been taken for a period of 6 years when the treatment was discontinued. Approximately 18 months after discontinuation, sclerotic bands remained evident; however, 4 years after discontinuation, sclerotic banding still surrounded the wing of the ilium but appeared diminished in the knees. In children and adolescents who engage in sports activities and are being treated with steroids and bisphosphonates, the possibility of pathological stress fractures should be considered.

Capsaicin Reduces Ethanol Consumption in C57BL/6 but not DBA/2 Mice.

Objective: Capsaicin, the pungent analgesic substance of hot peppers which produces a burning sensation and pain is known to affect Substance P and central opioid activities. This experiment was designed to test the effect of capsaicin on alcohol consumption in C57BL/6 and DBA/2 mice. These two strains are known to differ in both their alcohol consumption and their endogenous opioid distribution and response to alcohol. It is hypothesized that this effect may be mediated by both increases Substance P and decreases beta-endorphin. Methods: After i.p. administration of 0.01 and 0.001 mg/kg of capsaicin with a vehicle or the vehicle alone as the control for eight days in C57BL/6 and DBA/2 mice on limited access alcohol model, Capsaicin's effects on 2-hour alcohol, 22-hours water, 24-hours food intake and body weight were studied. Results: In this study, as expected, C57BL/6 mice drank significantly more alcohol than DBA/2 mice under baseline conditions. Capsaicin at both doses tested significantly reduced baseline alcohol consumption in C57BL/6 but not DBA/2 mice. These effects were selective for alcohol as capsaicin did not disrupt food or water consumption. Conclusion: These results demonstrate that capsaicin differentially affects those mechanisms underlying alcohol consumption in two strains of mice known to differ in their preference for and consumption of alcohol. This effect is hypothesized to be related to differences in the response of the endogenous opioid system.

Effects of Pre-Donated Autologous Blood Transfusion on Peri-Operative Hemoglobin Concentration and Mid-Term Health Outcomes in Primary Total Knee Arthroplasty.

The effects of auto-BT in primary TKA on the perioperative hemoglobin (Hb) concentration and mid-term health outcomes are unknown. This study was performed to analyze the detailed changes in the perioperative Hb concentration before and after the operation (days 0-14 postoperatively), cardiovascular events, and mortality rate within 1 and 5 years postoperatively. One hundred patients undergoing primary TKA with auto-BT using 800 mL of preoperatively collected blood at the authors' institution were included. The mean Hb concentration before and after autologous blood collection was 12.7 ± 1.1 and 11.7 ± 1.2 g/dL, respectively. After primary TKA with auto-BT, the mean Hb concentration on day 0, 1, 3, 7, and 14 was 10.2 ± 1.2, 9.9 ± 1.2, 10.4 ± 1.3, 10.5 ± 1.3, and 11.0 ± 1.3 g/dL, respectively. Only one (1%) patient required additional allogenic blood transfusion. No patients developed cardiovascular events, and the 1- and 5-year postoperative mortality rate was 1.0% and 2.0%, respectively. Primary TKA with auto-BT showed relatively small perioperative changes in the Hb concentration, a low incidence of cardiovascular events, and a low mortality rate within 1 and 5 years postoperatively. These findings suggest that auto-BT, in which blood is preoperatively collected, is beneficial for patient safety and health, even if its cost-effectiveness may be debatable.

Changes of drinking behavior in Korean pregnant women for the last 20 year.

BACKGROUND: The purpose of this study is to investigate the drinking behavior of Korean pregnant women in 2017 and to compare the changes of drinking status with the results of the research conducted in 1997 and 2008. METHODS: Pregnant women at one obstetrics and gynecology hospital and one university hospital were the subjects of the study. They were filled out questionnaire. RESULTS: The rate of positive responses to CAGE increased 16.0% in 2008 and 16.3% in 2017 compared to 11.8% in 1997 (P = 0.046). Blackout history rate was keep increasing from 1997 to 2017 (8.8% versus 27.7% versus 36.3%, P < 0.001). The rate of family history of alcohol was nearly doubled in 2017 (30.3%) compared to 1997 (17.6%) and 2008 (16.3) (P < 0.001). The rate of pregnant women who drink alcohol during pregnancy decreased from 57.5% in 1997 to 39.5% in 2008 and decreased to 25.6% in 2017 (P < 0.001). The rate of pregnant women who drink alcohol after knowing the pregnancy was decreased in 2017 (6.9%) compared to 2008 (23.5%) (P < 0.001). CONCLUSION: According to the results of the study in 2017, the rate of pregnant women who drink alcohol after pregnancy was decreased compared to 1997 and 2008. However drinking behavior severity has increased in 2017.

Squaramide-Catalyzed Asymmetric Intramolecular Oxa-Michael Reaction of α,ß-Unsaturated Carbonyls Containing Benzyl Alcohol: Construction of Chiral 1-Substituted Phthalans.

Organocatalytic enantioselective intramolecular oxa-Michael reactions of benzyl alcohol bearing α,ß-unsaturated carbonyls as Michael acceptors are presented herein. Using cinchona squaramide-based organocatalyst, enones as well as α,ß-unsaturated esters containing benzyl alcohol provided their corresponding 1,3-dihydroisobenzofuranyl-1-methylene ketones and 1,3-dihydroisobenzofuranyl-1-methylene esters in excellent yields with high enantioselectivities. In addition, enantioenriched 1,3-dihydroisobenzofuranyl-1-methylene ketone could be obtained from the Wittig/oxa-Michael reaction cascade of 1,3-dihydro-2-benzofuran-1-ol.

Radiographic assessment of the tibiofemoral relationship in anterior cruciate ligament deficient knees.

BACKGROUND: The intercondylar roof line is one of the indicators used during anterior cruciate ligament (ACL) reconstruction to see the relation to the position of the tibial tunnel. The tibial tunnel can be made posteriorly in the anteriorly subluxated tibia. During ACL reconstruction, the tibiofemoral relationship of the opposite or normal knee should be considered. The purpose of this study was to examine the radiographic tibiofemoral relationship of the sagittal plane in a standing position in ACL deficient knees. METHODS: In this study, 64 patients were evaluated for inclusion. Lateral radiographs of the injured and uninjured knee were obtained preoperatively in a standing position. The knee was fully extended with the opposite foot on a step, asking the patients to bear weight fully on one leg. The tibiofemoral relationship was evaluated in the radiographs. RESULTS: The mean value of anterior tibial subluxation was 1.2 mm in the injured side and -1.6 mm in the uninjured side. The tibia was located in a significantly anterior position in the injured knee (p < 0.0001). The mean distance of the space for the ACL was 9.7 mm in the injured side and 10.7 mm in the uninjured side (p < 0.01). Roof-plateau angle averaged 63.6° in the injured side and 67.4° in the uninjured side (p < 0.001). CONCLUSION: The tibiofemoral relationship of the ACL deficient knee was different from that of normal knee in the standing position. The relationship of the normal knee should be considered during ACL reconstruction and the risk of secondary lesions in the ACL deficient knee in activities of daily life should be considered.