Oxidative Syntheses of N,N-Dialkylhydroxylamines.

Despite the wide utility of hydroxylamines in organic synthesis, relatively few are commercially available, and there is a need for direct, efficient, and selective methods for their synthesis. Herein, we report two complementary methods to accomplish direct oxidation of secondary amines using UHP as an oxidant. The first method uses 2,2,2-trifluoroethanol (TFE) and a large excess of amine. Isolation of hydroxylamine products is enabled by selective salt formation, and recovery of excess amine is demonstrated. The second method uses hexafluoroacetone as an additive and is highlighted by the 1:1 stoichiometry between the oxidant and amine.

Insights on Structure-Passive Permeability Relationship in Pyrrole and Furan-Containing Macrocycles.

Macrocycles have recognized therapeutic potential, but their limited cellular permeability can hinder their development as oral drugs. To better understand the structure-permeability relationship of heterocycle-containing, semipeptidic macrocycles, a library was synthesized. These compounds were created by developing two novel reactions described herein: the reduction of activated oximes by LiBH4 and the aqueous reductive mono-N-alkylation of aldehydes using catalytic SmI2 and stoichiometric Zn. The permeability of the macrocycles was evaluated through a parallel artificial membrane permeability assay (PAMPA), and the results indicated that macrocycles with a furan incorporated into the structure have better passive permeability than those with a pyrrole moiety. Compounds bearing a 2,5-disubstituted pyrrole (endo orientation) were shown to be implicated in intramolecular H-bonds, enhancing their permeability. This study highlighted the impact of heterocycles moieties in semipeptides, creating highly permeable macrocycles, thus showing promising avenues for passive diffusion of drugs beyond the rule-of-five chemical space.

Clinical Features and the Outcome Evaluations of Keloid and Hypertrophic Scar Treatment with Triamcinolone Injection in Mekong Delta, Vietnam - A Cross-Sectional Study.

Background: Excessive scarring is a common problem that can have significant cosmetic and psychological consequences for patients. Intralesional injection therapy, such as the use of triamcinolone, has emerged as an effective treatment option for hypertrophic scars. The objective of this study was to describe the morphological features of hypertrophic scars, categorize them, and evaluate the efficacy of triamcinolone injection therapy in treating these scars. Materials and Methods: A cross-sectional descriptive study of 80 patients with hypertrophic scars treated with triamcinolone intralesional injection at Can Tho University of Medicine and Pharmacy Hospital from 5/2018 to 5/2021. Results: There were 80 patients in all, with a male/female ratio of 1/1.05 and a median age of 15-35. There were 129 scars in all, with scar age >1 year accounting for 83%, keloid scars accounting for 64%, and hypertrophic scars accounting for the remaining 36%. Scars are most commonly seen on the trunk, accounting for 53.5% of all scars, particularly on the anterior chest wall. When the source of scars was discovered, trauma and acne accounted for 24% and 23%, respectively, while the rest were predominantly spontaneous scars, accounting for 49%. Scarring and discomfort of mild to moderate severity were common clinical symptoms; scars larger than 5cm in size had more symptoms than scars smaller than 5cm. Prior to the therapy, the mean Vancouver Score Scale-VSS was 6.55±2.13. After 24 weeks of the therapy, 96.7% of patients had entirely improved itching symptoms, 75% had completely improved pain, and 25% still had minimal pain. After therapy, the mean Vancouver Score Scale-VSS was 2.55±1.81 (p<0.05). At week 24, 3.75% of patients experienced skin shrinkage, 3.75% experienced depigmentation, and 13.75% experienced vasodilation. Conclusion: Triamcinolone intralesional injection should be utilized as a first-line therapy for hypertrophic scarring.

The cross-sectional relationship among omega-3 fatty acid levels, cardiorespiratory fitness, and depressive symptoms from the Cooper Center Longitudinal Study.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are implicated in numerous illnesses including depression. The literature is mixed regarding the relationship between n-3 PUFA levels and depression, and studies based on self-reported dietary n-3 PUFA intake may not accurately reflect in vivo levels. METHOD: The current cross-sectional analysis examined the relationship between erythrocyte levels (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CESD), adjusting for health-related factors and omega-3 supplement use in 16,398 adults assessed at the Cooper Clinic in Dallas, Texas for preventative medical examinations between April 6, 2009, and September 1, 2020. A three-stage hierarchical linear regression was conducted to examine the EPA and DHA levels on CES-D before and after inclusion of cardiorespiratory fitness (CRF) and high sensitivity C-reactive protein (hs-CRP) in the model. RESULTS: DHA level, but not EPA level, was significantly associated with CES-D scores. Taking omega-3 supplements was associated with lower CES-D scores even when adjusting for CRF, while hs-CRP was non-significantly associated with CES-D scores. These findings suggest that DHA levels are related to depressive symptom severity. Omega-3 PUFA supplement use was associated with lower CES-D scores when controlling for EPA and DHA levels. CONCLUSION: The findings from this cross-sectional study suggest that lifestyle and/or other contextual factors unrelated to EPA and DHA levels may also be associated with depressive symptom severity. Longitudinal studies are needed to evaluate the role of health-related mediators among these relationships.

Anterior Chamber Washout During Ahmed Valve Glaucoma Surgery Reduces the Incidence of Hypertensive Phase.

PRCIS: Intraoperative anterior chamber (AC) washout reduces the odds of hypertensive phase (HP) by 95% compared with those not receiving washout during Ahmed glaucoma implant (AGI), suggesting AC washout is an effective prophylaxis for postoperative HP. PURPOSE: To characterize the incidence of postoperative HP in patients receiving AC washout at the time of AGI. PATIENTS AND METHODS: A total of 24 patients with medically refractory glaucoma who underwent AGI surgery at a tertiary academic medical center in Southern California from December 2018 through March 2021 were included in this retrospective comparative case series. Patients who received a pediatric implant and underwent concurrent intraocular surgery or did not complete a minimum of 6 months of follow-up were excluded. Nine patient's eyes received AC washout and 15 controls that were analyzed through 6 months postprocedure. HP was defined as intraocular pressure (IOP) above 21 mm Hg within 6 months postprocedure with maximum tolerated medical therapy. AC washout was performed by irrigating the AC with a 5 mL balanced salt solution before placing the tube of the AGI into the AC. The rate of postoperative HP, defined as peak IOP >21 mm Hg, at 6 months follow-up, was observed as the primary outcome measure. RESULTS: Patients included in the study had a high mean preoperative IOP ( X̅ = 44.11, SD = 13.85). There were no baseline differences between the washout and control groups. The odds of HP were significantly reduced (odds ratio: 0.050; 95% CI: 0.004, 0.706; P = 0.027) for patients who underwent intraoperative AC washout compared with those who did not. Bivariate analysis of subject baseline characteristics revealed that only washout status was significantly different in subjects with HP compared with subjects without HP ( P = 0.015). A multivariate logistic regression model using washout status and autoimmune conditions as covariates was significant in predicting HP ( X2 (2) = 12.337, P = 0.002), with washout as a significant predictor when controlling for autoimmune comorbidities ( P = 0.027). CONCLUSIONS: AC washout significantly decreases the odds of HP after AGI surgery. AC washout with balanced salt solution adds minimal time and risks to surgery and therefore may be an effective adjunct during AGI placement.

A redox-enabled strategy for intramolecular hydroamination.

Metal- or acid-catalyzed intramolecular hydroamination and Cope-type intramolecular hydroamination, a distinct concerted approach using hydroxylamines, typically suffer from significant synthetic limitations. Herein we report a process for intramolecular hydroamination that uses a redox-enabled strategy relying on efficient in situ generation of hydroxylamines by oxidation, followed by Cope-type hydroamination, then reduction of the resulting pyrrolidine N-oxide. The steps are performed sequentially in a single pot, no catalyst is required, the conditions are mild, the process is highly functional group tolerant, and no chromatography is generally required for isolation. A robustness screen and a gram-scale example further support the practicality of this approach.

Anterior cingulate cortex in individuals with depressive symptoms: A structural MRI study.

Several magnetic resonance imaging (MRI) studies have reported reduction in anterior cingulate cortex (ACC) volume in individuals with major depressive disorder (MDD). However, some MRI studies did not find significant ACC volumetric changes in MDD, and sample sizes were generally small. This cross-sectional structural MRI study examined the relationship between current depressive symptoms and ACC volume in a large community sample of 1803 adults. A series of multiple linear regression analyses were conducted to predict right and left ACC volumes using Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores, intracranial volume, age, sex, race/ethnicity, alcohol use, tobacco use, and psychotropic medications as predictor variables. Right ACC volume was significantly negatively associated with QIDS-SR scores, while no significant association was found between left ACC volume and QIDS-SR scores. In addition, there was a significant negative association between QIDS-SR scores and right but not left ACC volumes in males, and no significant association between QIDS-SR scores and right or left ACC volumes in females. These findings suggest that right ACC volume is reduced in people with greater self-reported depressive symptom severity, and that this association is only significant in men.

Carboxyhemoglobin and its correlation to disease severity in cirrhotics.

GOAL: To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as compared with Model for End Stage Liver Disease (MELD) score, Child Pugh score, and clinical parameters. BACKGROUND: There are 2 sources of carbon monoxide (CO) in humans, exogenous sources include those such as tobacco smoke and inhaled motor vehicle exhaust. The endogenous source is via the heme-oxygenase pathway, in which a heme molecule is broken down into biliverdin with release of an iron (Fe) and CO molecule. Normal serum CO-Hb levels in nonsmokers is 0% to 1.5% and 4% to 9% in smokers. Activity of the heme-oxygenase pathway may be increased in the cirrhotic patient, as measured indirectly by exhaled CO and serum CO-Hb. This may be due to alterations in vascular tone in the splanchnic circulation in cirrhotics that may lead to elevated CO production. One published study also showed that those with spontaneous bacterial peritonitis had higher levels of both CO and CO-Hb. The MELD score uses prothrombin time (INR), creatinine, and bilirubin in the prediction of short-term mortality in decompensated cirrhotics while awaiting liver transplant. Measurement of endogenous CO-Hb may correlate to severity of liver disease. STUDY: Retrospective analysis was done of 113 adult patients who were evaluated for liver transplantation between September 1996 and July 2003 and had pulmonary function testing with CO-Hb as part of their evaluation. We excluded any patients with a history of smoking. Clinical parameters used for comparison included grade of esophageal varices (n=75), spleen size (n=51) measured on abdominal ultrasound or computed tomography scan, aminotransferases, and disease duration. Serum CO-Hb levels were measured from whole blood, sent refrigerated to ARUP laboratories (Salt Lake City, UT) and analyzed via spectrophotometry. Bivariate analysis was performed by means of the Pearson product moment correlation. RESULTS: The mean CO-Hb level was 2.1%, which is higher than the expected normal population controls. No correlation was found, however, with MELD score, Child Turcotte Pugh score, or other biochemical or clinical measurements of disease severity. CONCLUSIONS: Although CO and CO-Hb production may be increased in the cirrhotic patient, in this study no correlation was found to disease severity as measured by the MELD score. Further studies are needed to assess the role of CO in other complications of cirrhosis including infection and circulatory dysfunction.