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.

[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.

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.

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.

Acute cholecystitis in old adults: the impact of advanced age on the clinical characteristics of the disease and on the surgical outcomes of laparoscopic cholecystectomy.

BACKGROUND: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established. METHODS: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis. RESULTS: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3. CONCLUSION: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC.

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.

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.

Gastric cancer surgery in South Korea: Past, present, and future.

Gastric cancer remains a significant global health concern and its surgical management approaches have undergone significant changes in South Korea and worldwide. Subtotal or total gastrectomy with D2 lymph node dissection is well established as a standard surgical procedure for gastric cancer. With the active implementation of cancer screening in South Korea, the proportion of early gastric cancer cases has significantly increased over the past few decades, leading to a steady increase in the survival rate among patients. Furthermore, recent advances in surgical instruments and techniques have made minimally invasive surgery increasingly prevalent, not only for early but also for advanced gastric cancer. We aim to provide a comprehensive overview of the evolution and current status of gastric cancer surgery in South Korea.

Completion of single-incision laparoscopic cholecystectomy using the modified Konyang standard method.

BACKGROUND: To date, a surgical method for single-incision laparoscopic cholecystectomy (SILC) has not been standardized. Therefore, this study aimed to introduce a standardized surgical method for SILC, in addition to reporting our experience over 10 years. METHODS: Patients who underwent SILC at a single institution between April 2010 and December 2019 were included in this study. We analyzed the patient demographics and surgical outcomes according to the surgical method used: phase 1 (Konyang standard method, KSM) comprising initial 3-channel SILC, phase 2 (modified KSM, mKSM) comprising 4-channel SILC with a snake retractor, and phase 3 (commercial mKSM, C-mKSM) using a commercial 4-channel port. RESULTS: Of 1372 patients (mean age, 51.3 years; 781 [56.9%] women), 418 (30.5%) surgeries were performed for acute cholecystitis (AC), 33 (2.4%) were converted to multiport or open cholecystectomy, and 49 (3.6%) developed postoperative complications. The mean operation time (OT) and length of postoperative hospital stay (LOS) were 51.9 min and 2.6 days, respectively. Overall, 325 patients underwent SILC with the KSM, 660 with the mKSM, and 387 with the C-mKSM. In the C-mKSM group, the number of patients with AC was the lowest (26.8% vs. 38.2% vs. 20.4%, p < 0.001) and the OT (51.7 min vs. 55.4 min vs. 46.1 min, p < 0.001), estimated blood loss (24.5 mL vs. 15.5 mL vs. 6.1 mL, p < 0.001), and LOS (2.8 days vs. 2.5 days vs. 2.3 days, p = 0.001) were significantly improved. The surgical outcomes were better in the non-AC group than in the AC group. CONCLUSION: Based on our 10 year experience, C-mKSM is a safe and feasible method of SILC in selected patients, although there were lower percentage of patients with AC compared to other groups.

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.

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.

Recent updates and current issues of sentinel node navigation surgery for early gastric cancer.

With the increase in the incidence of early gastric cancer (EGC), several endoscopic and laparoscopic approaches, such as endoscopic submucosal dissection and function-preserving gastrectomy, have been accepted as standard treatments. Sentinel node navigation surgery (SNNS) is an ideal surgical option for preservation of most parts of the stomach and consequent maintenance of normal gastric function to improve quality of life in patients with EGC. Although many previous studies and clinical trials have demonstrated the safety and feasibility of the sentinel node concept in gastric cancer, the clinical application of SNNS is debatable. Several issues regarding technical standardization and oncological safety need to be resolved. Recently several studies to resolve these problems are being actively performed, and SNNS might be an important surgical option in the treatment of gastric cancer in the future.

Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers.

When children around 2-year-old show leg bowing without lower-limb radiographic abnormalities for rickets, the leg bowing is classified as "physiologic" genu varum without conducting a blood test. However, it has recently been suggested that toddlers who are diagnosed with physiologic genu varum may in fact have some form of bone metabolic disorder. In this 1:2 case-control study, blood samples were obtained from 33 toddlers with genu varum without radiographic abnormalities for rickets and 66 age- and gender-matched healthy children. Serum alkaline phosphatase (sALP), intact parathyroid hormone (siPTH), 25-hydroxy vitamin D [s25(OH)D], calcium (sCa), and inorganic phosphate (sP) were measured. s25(OH)D of the subjects with genu varum (24.8 ng/ml) were significantly lower than those of the control (33.6 ng/ml) (p < 0.001). The frequency of vitamin D insufficiency/deficiency (< 20 ng/ml) of the subjects with genu varum (39%) was significantly higher than that in the control (14%) (p = 0.004) (odds ratio by vitamin D insufficiency/deficiency: 4.1 [1.5-11.1, p = 0.004]). sCa in subjects with genu varum (10.2 ng/ml) were significantly higher than in control (9.8 ng/ml) (p < 0.001), as were sALP (1057 IU/l) and siPTH (28.4 pg/ml) (740 IU/l and 8.8 pg/ml in control, respectively; p < 0.001). siPTH levels were associated with s25(OH)D levels in subjects with genu varum (r = - 0.57, p < 0.001), while no association was observed in the control (r = 0.11, p = 0.36). Genu varum without radiographic abnormalities of rickets was associated with both vitamin D and bone-metabolic disorders in toddlers, indicating that physiologic genu varum is not a physiologic condition in toddlers.

Association between leg bowing and serum alkaline phosphatase level regardless of the presence of a radiographic growth plate abnormality in pediatric patients with genu varum.

When children around 2 years of age show leg bowing and diseases are ruled out based on radiographic findings without conducting blood tests, they are classified as "physiologic" genu varum. Since whether or not physiologic genu varum is associated with bone metabolism is unclear, this study was conducted to clarify the association between genu varum and bone metabolism in children. Thirty-five pediatric patients with genu varm who visited our out-patient clinic were enrolled. While two of the 35 children had nutritional rickets, showing abnormalities on both blood test (ALP, ≥1000 IU/L; iPTH, >65 pg/mL and 25(OH)D, ≤20 ng/mL) and radiographs (such as cupping, fraying or splaying), five of 35 children showed abnormalities on blood tests but not radiographs. While metaphyseal-diaphyseal angle (MDA) correlated with serum 25-hydroxy vitamin D (r = -0.35, p = 0.04) and magnesium (r = -0.36, p = 0.04), MDA and femorotibial angle (FTA) correlated with alkaline phosphatase (r = 0.43, p = 0.01 and r = 0.51, p = 0.006, respectively). A ridge regression analysis adjusted for age and body mass index indicated that ALP was associated with MDA and FTA. A logistic regression analysis adjusted for age and BMI indicated that higher ALP influenced an MDA >11°, which indicates the risk for the progression of genu varum (odds ratio 1.002, 95% confidence interval 1.0003-1.003, p = 0.021). The higher ALP (+100 IU), the higher risk of an MDA >11° (odds ratio 1.22). In conclusion, genu varum is associated with the alkaline phosphatase level regardless of the presence of radiographic abnormalities in the growth plate in children.

Organocatalytic Asymmetric Mannich/Aza-Michael Cascade Reaction of δ-Formyl-α,ß-unsaturated Ketones with Cyclic N-Sulfimines: Enantioselective Synthesis of Benzosulfamidate-Fused Pyrrolidines.

A catalytic highly enantioselective Mannich/aza-Michael cascade reaction of δ-formyl-α,ß-unsaturated ketones with cyclic N-sulfimines, promoted by diphenylprolinol TMS ether as an organocatalyst, has been developed for the synthesis of chiral benzosulfamidate-fused pyrrolidines, which generated in good yields and with high diastero- and enantioselectivities. Further chemical transformations have been performed with chiral benzosulfamidate-fused pyrrolidines.

A novel patient-reported outcome measure for anterior cruciate ligament injury: evaluating the reliability, validity, and responsiveness of Japanese anterior cruciate ligament questionnaire 25.

PURPOSE: Despite objectively good results, up to 70 % of individuals may not return to their pre-injury level of sports activity after anterior cruciate ligament (ACL) reconstruction surgery. Although psychological responses have been shown to affect outcomes after ACL injury, an appropriate means of measuring their effects, in addition to functional status, has not been determined. The purpose of this study was to develop a patient-reported questionnaire for measuring psychological factors associated with outcomes after ACL injury and to evaluate its reliability, validity, and responsiveness. METHODS: After item analysis based on the results of two pilot studies and a short relevance assessment, 25 questionnaire items were selected for the Japanese Anterior Cruciate Ligament Injury Questionnaire 25 (JACL-25) and assessed for validity, reliability, and responsiveness in subjects with ACL injury. RESULTS: The JACL-25 had no floor or ceiling effects and no confounding factors. A Cronbach's alpha coefficient of 0.981 and a Guttman split-half coefficient of 0.983 indicated excellent reliability. Large standardized response means (1.30-1.62) and effect sizes (0.96-1.51) from the preoperative to postoperative period indicated good responsiveness. Construct structures were created, and these items were separated into three domains. Strong correlations between the JACL-25 and the International Knee Documentation Committee Subjective Knee Form (r s = -0.86), Lysholm Score (r s = -0.73), and Tegner Activity Scale (r s = -0.65) indicated good concurrent validity of the JACL-25. CONCLUSIONS: The present study demonstrated that the JACL-25 was valid, reliable, and responsive enough to evaluate psychological factors associated with outcomes in individuals with ACL injuries. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Effect of GABA Extract of Black Sticky Rice with Giant Embryo on Alcohol-Related Indices After Acute Alcohol Intake in Social Drinkers.

BACKGROUND: This study was performed to evaluate the effect and safety of a high-gamma-aminobutyric acid-containing extract (GABA extract) of black sticky rice with giant embryo (BSRGE) on alcohol-related indices after acute alcohol intake in social drinkers. METHODS: Subjects were randomized to the GABA extract (G) group, GABA extract and alcohol drinking (GA) group, or placebo intake and alcohol drinking (PA) group in a double-blind design. All subjects were administered GABA extract (200 mg GABA) or placebo at 9 am on study days 2 and 3, respectively. Subjects in the GA and PA groups were administered an equivalent dose of alcohol that was diluted in a drinking beverage for a total amount of 240 ml at 11 am on day 3. Blood alcohol concentration (BAC) and the Biphasic Alcohol Effects Scale were measured just before alcohol drinking, and 6 times after alcohol drinking. RESULTS: The peak and area under the curve (AUC) of the total stimulation scale score after alcohol intake in females were significantly higher in the GA than in the PA group, whereas no significant difference was found between the 2 groups in males. The peak and AUC of the total score on the sedation scale after alcohol intake in males were significantly lower in the GA than in the PA group, whereas both were significantly higher in the GA than in the PA group of females. The AUC for BAC in males was significantly lower in the GA than in the PA group, whereas no significant difference was found in females. No adverse events were reported in any of the groups including the G group. CONCLUSIONS: Coadministration of a GABA extract to social drinkers while drinking alcohol is supposed to affect alcohol-related indices in terms of pharmacodynamics and pharmacokinetics and did not induce any adverse events.

Open prospective study of ziprasidone in patients with schizophrenia with depressive symptoms: a multicenter study.

AIMS: The goal of this study was to examine the efficacy and safety of ziprasidone to treat depressive symptoms in Korean patients with schizophrenia who showed stable symptoms. METHODS: In this 8-week, open-label, prospective, non-randomized, multicenter study, 34 patients with schizophrenia who showed a stable response to previous medications, maintained a stable dose, and who had depressive symptoms, were recruited. Ziprasidone was the only antipsychotic agent allowed for 8 weeks after a 2-7-week washout period. RESULTS: Steady decreases were observed on the Montgomery-Asberg Depression Rating Scale, the Calgary Depression Scale for Schizophrenia, the Positive and Negative Syndrome Scale, and the Clinical Global Impression-Severity Scale scores. The Montgomery-Asberg Depression Rating Scale score was 20.26 ± 4.77 at baseline and 12.21 ± 7.94 at the end-point (P < 0.01). The Calgary Depression Scale for Schizophrenia score was 9.76 ± 4.11 at baseline and 5.00 ± 3.94 at the end-point (P < 0.01). The Positive and Negative Syndrome Scale total score was 75.24 ± 22.63 at baseline and 66.53 ± 24.28 at the end-point (P < 0.01). The Clinical Global Impression-Severity Scale score was 3.44 ± 0.66 at baseline and 3.15 ± 0.86 at the end-point (P < 0.05). No significant differences were observed for total scores on the Simpson and Angus Rating Scale, the Barnes Akathisia Rating Scale, or the Abnormal Involuntary Movement Scale between the baseline and end-point. CONCLUSIONS: Ziprasidone was effective for improving depressive symptom scores and was well tolerated. Switching to ziprasidone is a good strategy in patients with schizophrenia who are experiencing depressive symptoms.

Asymmetric organocatalytic cascade reaction of aldehydes with 2-amino-ß-nitrostyrenes: synthesis of chiral tetrahydroquinolines and dihydroquinolines.

An organocatalytic enantioselective Michael addition/aza-cyclization cascade reaction of aldehydes with 2-amino-ß-nitrostyrenes has been developed for the construction of fully substituted chiral tetrahydroquinolines. The reaction, promoted by diphenylprolinol TMS ether as an organocatalyst, generated the chiral tetrahydroquinolines in good to high yield with excellent diastereo- and enantioselectivities (up to >30:1 dr, >99% ee). The method also provided an alternative access to chiral 1,4-dihydroquinolines, which are difficult to synthesize by other methodologies.