Catalytic conversion of chitin-based biomass to nitrogen-containing chemicals.

The exploration of renewable alternatives to fossil fuels for chemical production is indispensable to achieve the ultimate goals of sustainable development. Chitin biomass is an abundant platform feedstock that naturally bears both nitrogen and carbon atoms to produce nitrogen-containing chemicals (including organonitrogen ones and inorganic ammonia). The expansion of biobased chemicals toward nitrogen-containing ones can elevate the economic competitiveness and benefit the biorefinery scheme. This review aims to provide an up-to-date summary on the overall advances of the chitin biorefinery for nitrogen-containing chemical production, with an emphasis on the design of the catalytic systems. Catalyst design, solvent selection, parametric effect, and reaction mechanisms have been scrutinized for different transformation strategies. Future prospectives on chitin biorefinery have also been outlined.

One-pot chitin pulping using recyclable superbase-based protic ionic liquid.

The application of ionic liquids and deep eutectic solvents offers a promising opportunity for a more environmentally friendly and straightforward chitin purification process from crustacean shells. Nonetheless, the insufficient recyclability of these ionic solvents poses a challenge to the long-term sustainability of such extraction methods. Thus, there is a strong imperative to focus on employing easily recyclable ionic liquids for chitin isolation, enhancing the overall sustainability of the process. In this investigation, a direct chitin purification procedure that utilized pulping liquors consisting of the superbase-based protic ionic liquid 1,5-diazabicyclo[4.3.0]non-5-enium acetate and its precursor, acetic acid, was developed. It was demonstrated that these pulping liquors were capable of simultaneously deproteinate and demineralize shrimp shells to generate chitins with higher purity, degree of N-acetylation and crystallinity than commercially obtained chitin. More significantly, the pulping liquors can be recycled to their pure form in high quantity by simple distillation under reduced pressure, allowing the reuse of these mixtures, which give chitin of nearly identical purity.

Advances in Screening for Radiation-Associated Cardiotoxicity in Cancer Patients.

PURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects. RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and metabolomics, hold promise for earlier detection and more specific characterization of RICD. Advances in imaging and novel applications of biomarkers have potential to identify subclinical RICD and may reveal opportunities for early intervention. Further research is needed to elucidate optimal imaging screening modalities, biomarkers, and surveillance strategies.

Misconceptions and Facts about Heart Failure with Reduced Ejection Fraction.

Heart failure with reduced ejection fraction is a significant driver of morbidity and mortality. There are common misconceptions regarding the disease processes underlying heart failure and best practices for therapy. The terms heart failure with reduced ejection fraction and left ventricular systolic dysfunction are not interchangeable terms. Key therapies for heart failure with reduced ejection fraction target the underlying disease processes, not the left ventricular ejection fraction alone. The absence of congestion does not rule out heart failure. Patients with cardiac amyloidosis can also present with heart failure with reduced ejection fraction. A rise in serum creatinine in acute heart failure exacerbation is not associated with tubular injury. Guideline directed medical therapy should be continued during acute exacerbations of heart failure with reduced ejection fraction and should be started in the same hospitalization in new diagnoses. Marginal blood pressure is not a relative contraindication to optimal guideline directed medical therapy. Guideline directed medical therapy should be continued even if ejection fraction improves. There are other therapies that provide significant benefit besides the four key medications in guideline directed medical therapy.

Association of Male Hypogonadism With Risk of Hospitalization for COVID-19.

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh). Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh. Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021. Exposures: The primary exposure was gonadal status (hypogonadism, eugonadism, and TTh). Hypogonadism was defined as a total testosterone concentration below the limit of normal provided by the laboratory (which varied from 175 to 300 ng/dL [to convert to nanomoles per liter, multiply by 0.0347]). Main Outcomes and Measures: The primary outcome was rate of hospitalization for COVID-19. Statistical adjustments were made for group differences in age, body mass index, race and ethnicity, immunosuppression, and comorbid conditions. Results: Of the 723 study participants (mean [SD] age, 55 [14] years; mean [SD] body mass index, 33.5 [7.3]), 116 men had hypogonadism, 427 had eugonadism, and 180 were receiving TTh. Men with hypogonadism were more likely than men with eugonadism to be hospitalized with COVID-19 (52 of 116 [45%] vs 53 of 427 [12%]; P < .001). After multivariable adjustment, men with hypogonadism had higher odds than men with eugonadism of being hospitalized (odds ratio, 2.4; 95% CI, 1.4-4.4; P < .003). Men receiving TTh had a similar risk of hospitalization as men with eugonadism (odds ratio, 1.3; 95% CI, 0.7-2.3; P = .35). Men receiving inadequate TTh (defined as subnormal testosterone concentrations while receiving TTh) had higher odds of hospitalization compared with men who had normal testosterone concentrations while receiving TTh (multivariable adjusted odds ratio, 3.5; 95% CI, 1.5-8.6; P = .003). Conclusions and Relevance: This study suggests that men with hypogonadism were more likely to be hospitalized after COVID-19 infection compared with those with eugonadism, independent of other known risk factors. This increased risk was not observed among men receiving adequate TTh. Screening and appropriate therapy for hypogonadism need to be evaluated as a strategy to prevent severe COVID-19 outcomes among men.

Methylation with Dimethyl Carbonate/Dimethyl Sulfide Mixtures: An Integrated Process without Addition of Acid/Base and Formation of Residual Salts.

Dimethyl sulfide, a major byproduct of the Kraft pulping process, was used as an inexpensive and sustainable catalyst/co-reagent (methyl donor) for various methylations with dimethyl carbonate (as both reagent and solvent), which afforded excellent yields of O-methylated phenols and benzoic acids, and mono-C-methylated arylacetonitriles. Furthermore, these products could be isolated using a remarkably straightforward workup and purification procedure, realized by dimethyl sulfide's neutral and distillable nature and the absence of residual salts. The likely mechanisms of these methylations were elucidated using experimental and theoretical methods, which revealed that the key step involves the generation of a highly reactive trimethylsulfonium methylcarbonate intermediate. The phenol methylation process represents a rare example of a Williamson-type reaction that occurs without the addition of a Brønsted base.

Commentary on Post, et al. Ultra-early tranexamic acid after subarachnoid hemorrhage: A randomized controlled trial. Lancet 2021.

BACKGROUND: Tranexamic acid (TA) administration in aneurysmal subarachnoid hemorrhage (SAH) within the first 24 hours may reduce the incidence of early aneurysmal rebleeding. However, this is also the potential for an increased risk of delayed cerebral ischemia if TA is administered for more than 72 hours following the initial aneurysmal rupture. METHODS: In the ultra-early tranexamic acid after subarachnoid hemorrhage randomized controlled trial by Post et al., patients were randomized to receive TA within the first 24 hours, or until start of aneurysm treatment. These results were compared to a matched control group. RESULTS: Ultra-early administration (≤24 h) of TA reduced the incidence of rebleeding, and did not alter the incidence of delayed cerebral ischemia and/or extracranial thrombosis. Further, no significant differences were noted between the TA group and control arm in the incidence of good (modified Rankin scores 0-3) clinical outcomes at 6 months. CONCLUSION: Ultra-early administration of TA (≤24 h) resulted in a lower rate of recurrent hemorrhage, without increasing the incidence of delayed cerebral ischemia in SAH patients.

Hydrothermal Liquefaction of α-O-4 Aryl Ether Linkages in Lignin.

By using lignin model compounds with relevant key characteristic structural features, the reaction pathways of α-O-4 aryl ether linkages under hydrothermal conditions are elucidated. Experimental results and computational modeling suggest that the α-O-4 linkages in lignin undergo catalyzed hydrolysis and elimination to give phenolic and alkenylbenzene derivatives as major products in subcritical water. The decreased relative permittivity of water at these high temperatures and pressures facilitates the elimination reactions. The alkyl group on the α-carbon and the methoxy groups on the phenyl rings both have positive effects on the rate of conversion of α-O-4 linkages in native lignin.

Emergency endoscopic third ventriculostomy for blocked shunts? Univariate and multivariate analysis of independent predictors for failure.

OBJECTIVEHydrocephalus with a blocked ventriculoperitoneal (VP) shunt is a life-threatening condition. Emergency endoscopic third ventriculostomy (ETV) is a potential treatment option. The aim of the study was to identify independent risk factors associated with failure of ETV in treating patients with blocked shunts.METHODSThe authors retrospectively reviewed data from consecutive patients admitted for blocked shunt treated by ETV during the study period from 2000 to 2016. Univariate and multivariate analyses were performed to identify independent factors associated with failed ETV for blocked shunts, such as age, sex, history of CNS infection, number of previous shunt revisions, operations performed as an emergency or elective, number of specialists, and other factors.RESULTSIn total, 121 patients underwent ETV during the study period. Of these, 31 patients (25.6%) had ETV for treatment of a blocked shunt. In 25 (80.6%) of 31 ETV was performed as an emergency procedure. There was no significant difference in the success rate of ETV depending on whether it was performed as an emergency procedure (64% [16/25]) or an elective procedure (66.7% [4/6]; OR 0.062, 95% CI 0.001-2.708; p = 0.149). Univariate and multivariate analyses identified that history of a CNS infection was an independent risk factor for failure of ETV in treating patients with a blocked shunt (OR 0.030, 95% CI 0.001-0.888; p = 0.043).CONCLUSIONSEmergency ETV had a comparable success rate as elective ETV. A history of CNS infection is an independent predictor of ETV failure in treating patients with blocked shunts.

Unravelling Some of the Key Transformations in the Hydrothermal Liquefaction of Lignin.

Using both experimental and computational methods, focusing on intermediates and model compounds, some of the main features of the reaction mechanisms that operate during the hydrothermal processing of lignin were elucidated. Key reaction pathways and their connection to different structural features of lignin were proposed. Under neutral conditions, subcritical water was demonstrated to act as a bifunctional acid/base catalyst for the dissection of lignin structures. In a complex web of mutually dependent interactions, guaiacyl units within lignin were shown to significantly affect overall lignin reactivity.

Familial hypercholesterolemia in a large ambulatory population: Statin use, optimal treatment, and identification for advanced medical therapies.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease resulting in elevated serum low-density lipoprotein cholesterol (LDL-C) levels. Patients with FH have a very high lifetime risk of cardiovascular disease, but FH often goes unrecognized in clinical care. New treatments including PCSK9 inhibitors are now available for this population, and the use of the electronic record may be able to help identify potential patients for therapy. OBJECTIVES: The goal of this study was to determine the period prevalence of FH in a large ambulatory care population, including the homozygous form. In addition, use of cholesterol lowering therapy in individuals with FH was characterized. METHODS: A retrospective analysis was carried out among patients seen in an upper Midwest health care system between 2009 and 2012. In a search of electronic health records (EHR) and using the current National Lipid Association guidelines, FH patients (including homozygous cases) were identified based on age and highest LDL-C. Statin therapy was characterized according to current FH treatment guidelines. RESULTS: There were 391,166 individuals with available measures during the study timeframe. Of these, 841 were identified as having probable HeFH, representing a prevalence of 0.21% (about 1 in 470 patients) in this population. HoFH was identified as probable in 6 patients. For the total group, two-thirds of FH patients were on a statin, but only half were treated adequately. The remaining one-third of FH patients were not on statin therapy, with only 27% of those not on statin therapy having a documented statin intolerance. CONCLUSIONS: FH is often underdiagnosed and suboptimally treated in clinical practice. Statin therapy in this population rarely went beyond low-moderate doses. These findings support EHR-based population health efforts to initiate an FH cascade-screening model and ensure higher quality care for this high-risk population and identify those who may benefit from advanced therapy.

Masked N-Heterocyclic Carbene-Catalyzed Alkylation of Phenols with Organic Carbonates.

An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2 ), was investigated as a "green" and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs.

Usefulness of lipid apheresis in the treatment of familial hypercholesterolemia.

Lipid apheresis is used to treat patients with severe hyperlipidemia by reducing low-density lipoprotein cholesterol (LDL-C). This study examines the effect of apheresis on the lipid panel and cardiac event rates before and after apheresis. An electronic health record screen of ambulatory patients identified 11 active patients undergoing lipid apheresis with 10/11 carrying a diagnosis of FH. Baseline demographics, pre- and postapheresis lipid levels, highest recorded LDL-C, cardiac events, current medications, and first apheresis treatment were recorded. Patients completed a questionnaire and self-reported risk factors and interest in alternative treatment. There were significant reductions in mean total cholesterol (-58.4%), LDL-C (-71.9%), triglycerides (-51%), high-density lipoprotein (HDL) cholesterol (-9.3%), and non-HDL (-68.2%) values. Thirty-four cardiac events were documented in 8 patients before apheresis, compared with 9 events in 5 patients after apheresis. Our survey showed a high prevalence of statin intolerance (64%), with the majority (90%) of participants indicating an interest in alternative treatment options. Our results have shown that lipid apheresis primary effect is a marked reduction in LDL-C cholesterol levels and may reduce the recurrence of cardiac events. Apheresis should be compared to the newer alternative treatment modalities in a randomized fashion due to patient interest in alternative options.