Discontinuation of Gender-Affirming Medical Treatments: Prevalence and Associated Features in a Nonprobabilistic Sample of Transgender and Gender-Diverse Adolescents and Young Adults in Canada and the United States.

PURPOSE: This study investigated the prevalence, correlates, and reasons for discontinuing gender-affirming medical treatment (GAMT) among transgender and gender-diverse adolescents and young adults living in Canada and the United States of America. METHODS: This exploratory study used data from an online survey of sexual and gender minority adolescents and young adults aged 15-29 years living in Canada or the United States of America (March-August 2022). The analytic sample was constituted by participants who responded to questions regarding starting and stopping GAMT, as well as reasons for stopping. Correlates of discontinuing GAMT were assessed using univariate logistic regression. RESULTS: The mean age of the analytic sample (N = 3,937) was 21.1 years. Participants were predominantly nonbinary (54.2%) and assigned female at birth (80.8%). 75.5% lived in Canada and 24.5% in the United States of America. Among those who had started GAMT, 121 of 720 (16.8%) reported having ever discontinued treatment. Forty five of 121 (37.2%) who ceased GAMT reported "Yes, but I wish I hadn't." The most frequently endorsed reasons for discontinuing GAMT were health reasons (37.3%), a change in gender identity (32.0%), and cost (16.0%). Greater age; nonbinary identity, 'other' gender identity; diagnosis of or self-identifying as living with schizophrenia; residing in the United States of America (relative to Canada); and endorsing a current Christian identity were associated with discontinuation. Ninety seven of 121 (80.2%) who discontinued GAMT reported a current transgender or gender-diverse identity. DISCUSSION: Given the dearth of information about the subpopulation who discontinue GAMT, this study advances candidate factors to inform future longitudinal research to better understand the multiple reasons and contexts for stopping GAMT.

High Flow Nasal Cannula in Patients With Cancer at the End of Life.

CONTEXT: High flow nasal cannula (HFNC) is frequently used to manage dyspnea in patients with cancer near the end of life. Because HFNC is restricted to the in-patient setting, patients on HFNC need to be liberated from it to be discharged from the hospital. OBJECTIVES: The purpose of this study is to assess the rate of successful liberation from HFNC in a palliative and supportive care unit (PSCU). METHODS: The study is a retrospective chart review of all 374 adult patients with cancer on HFNC admitted to a palliative and supportive care unit at a tertiary medical center from January 1, 2018 to December 31, 2020. We determined the proportion of patients who were liberated from HFNC (by day three and overall) and the proportion of patients discharged alive. RESULTS: The mean age of the patients was 64, 54% were male and 73% were white. Only 16% (95% CI: 13-20) of the patients were discharged alive. Liberation from HFNC by day three and overall was accomplished in 23% and 25% of the patients respectively. Comparing the patients who could be liberated from HFNC vs. those who could not by day three, 38% vs. 9% were discharged alive respectively; and overall, 62% vs. 1% respectively (P < 0.001 in both cases). CONCLUSION: Only a minority of patients with cancer at the end of life can be liberated from HFNC, and only a minority are discharged alive. This information is important when discussing goals of care with patients and their families before initiating HFNC.

Blood group type A secretors are associated with a higher risk of COVID-19 cardiovascular disease complications.

The SARS-CoV-2 virus causes COVID-19, an infection capable of causing severe disease and death but which can also be asymptomatic or oligosymptomatic. We investigated whether ABO blood group or secretor status was associated with COVID-19 severity. We investigated secretor status because expression of ABO glycans on secreted proteins and non-erythroid cells are controlled by a fucosyltransferase (FUT2), and inactivating FUT2 mutations result in a non-secretor phenotype which protects against some viral infections. Data combined from healthcare records and our own laboratory tests (n = 275) of hospitalized SARS-CoV-2 polymerase chain reaction positive patients confirmed higher than expected numbers of blood group A individuals compared to O (RR = 1.24, CI 95% [1.05, 1.47], p = 0.0111). There was also a significant association between group A and COVID-19-related cardiovascular complications (RR = 2.56, CI 95% [1.43, 4.55], p = 0.0011) which is independent of gender. Molecular analysis revealed that group A non-secretors are significantly less likely to be hospitalized than secretors. Testing of convalescent plasma donors, among whom the majority displayed COVID-19 symptoms and only a small minority required hospitalization, group A non-secretors were slightly over-represented. Our findings showed that group A non-secretors are not resistant to infection by SARS-CoV-2, but are more likely to experience a less severe form of associated disease.

Are long chain acyl CoAs responsible for suppression of mitochondrial metabolism in hibernating 13-lined ground squirrels?

Hibernation in 13-lined ground squirrels (Ictidomys tridecemlineatus) is associated with a substantial suppression of whole-animal metabolism. We compared the metabolism of liver mitochondria isolated from torpid ground squirrels with those from interbout euthermic (IBE; recently aroused from torpor) and summer euthermic conspecifics. Succinate-fuelled state 3 respiration, calculated relative to mitochondrial protein, was suppressed in torpor by 48% and 44% compared with IBE and summer, respectively. This suppression remains when respiration is expressed relative to cytochrome c oxidase activity. We hypothesized that this suppression was caused by inhibition of succinate transport at the dicarboxylate transporter (DCT) by long-chain fatty acyl CoAs that may accumulate during torpor. We predicted, therefore, that exogenous palmitoyl CoA would inhibit respiration in IBE more than in torpor. Palmitoyl CoA inhibited respiration ~70%, in both torpor and IBE. The addition of carnitine, predicted to reverse palmitoyl CoA suppression by facilitating its transport into the mitochondrial matrix, did not rescue the respiration rates in IBE or torpor. Liver mitochondrial activities of carnitine palmitoyl transferase did not differ among IBE, torpor and summer animals. Although palmitoyl CoA inhibits succinate-fuelled respiration, this suppression is likely not related exclusively to inhibition of the DCT, and may involve additional mitochondrial transporters such as the adenine-nucleotide transporter.

Regulation of succinate-fuelled mitochondrial respiration in liver and skeletal muscle of hibernating thirteen-lined ground squirrels.

Hibernating ground squirrels (Ictidomys tridecemlineatus) alternate between two distinct metabolic states throughout winter: torpor, during which metabolic rate (MR) and body temperature (Tb) are considerably suppressed, and interbout euthermia (IBE), during which MR and Tb briefly return to euthermic levels. Previous studies showed suppression of succinate-fuelled respiration during torpor in liver and skeletal muscle mitochondria; however, these studies used only a single, saturating succinate concentration. Therefore, they could not address whether mitochondrial metabolic suppression occurs under physiological substrate concentrations or whether differences in the kinetics of mitochondrial responses to changing substrate concentration might also contribute to mitochondrial metabolic regulation during torpor. The present study confirmed that succinate oxidation is reduced during torpor in liver and skeletal muscle at 37 and 10°C over a 100-fold range of succinate concentrations. At 37°C, this suppression resulted from inhibition of succinate dehydrogenase (SDH), which had a greater affinity for oxaloacetate (an SDH inhibitor) during torpor. At 10°C, SDH was not inhibited, suggesting that SDH inhibition initiates but does not maintain mitochondrial suppression during torpor. Moreover, in both liver and skeletal muscle, mitochondria from torpid animals maintained relatively higher respiration rates at low succinate concentrations, which reduces the extent of energy savings that can be achieved during torpor, but may also maintain mitochondrial oxidative capacity above some lower critical threshold, thereby preventing cellular and/or mitochondrial injury during torpor and facilitating rapid recruitment of oxidative capacity during arousal.

Molecular simulation of the thermophysical properties of N-functionalized alkylimidazoles.

Molecular simulations are used to probe the thermophysical properties of a series of N-functionalized alkylimidazoles, ranging from N-methylimidazole to N-heptylimidazole. These compounds have been previously synthesized, and their solvation properties have been shown to be potentially useful for CO(2) capture from industrial sources. In this work, we use first-principles calculations to fit electrostatic charges to the molecular models, which are then used to perform a series of molecular dynamics simulations. Over a range of different temperatures, we benchmark the simulated densities and heat capacities against experimental measurements. Also, we predict the Henry's constants for CO(2) absorption and probe the solvents' structures using molecular simulation techniques, such as fractional free volume analysis and void distributions. We find that our simulations are able to closely reproduce the experimental benchmarks and add additional insight into the molecular structure of these fluids, with respect to their observed solvent properties.

Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data.

UNLABELLED: The two main functions of bioinformatics are the organization and analysis of biological data using computational resources. Geneious Basic has been designed to be an easy-to-use and flexible desktop software application framework for the organization and analysis of biological data, with a focus on molecular sequences and related data types. It integrates numerous industry-standard discovery analysis tools, with interactive visualizations to generate publication-ready images. One key contribution to researchers in the life sciences is the Geneious public application programming interface (API) that affords the ability to leverage the existing framework of the Geneious Basic software platform for virtually unlimited extension and customization. The result is an increase in the speed and quality of development of computation tools for the life sciences, due to the functionality and graphical user interface available to the developer through the public API. Geneious Basic represents an ideal platform for the bioinformatics community to leverage existing components and to integrate their own specific requirements for the discovery, analysis and visualization of biological data. AVAILABILITY AND IMPLEMENTATION: Binaries and public API freely available for download at http://www.geneious.com/basic, implemented in Java and supported on Linux, Apple OSX and MS Windows. The software is also available from the Bio-Linux package repository at http://nebc.nerc.ac.uk/news/geneiousonbl.

Functional and cognitive outcome in prolonged refractory status epilepticus.

OBJECTIVE: To determine the functional and cognitive outcomes of patients with prolonged refractory status epilepticus (PRSE) lasting 7 or more days despite the use of anesthetic agents for seizure suppression. DESIGN: Retrospective analysis. SETTING: St Mary's Hospital, Mayo Clinic, Rochester, Minnesota. PARTICIPANTS: Fourteen patients with PRSE. INTERVENTION: Hospital follow-up interview. MAIN OUTCOME MEASURES: Survival rate of PRSE and functional and cognitive outcome of surviving patients based on the modified Rankin Scale (mRS) and Telephone Interview for Cognitive Status (TICS). RESULTS: Forty-three percent of patients (6 of 14) died during hospitalization for PRSE, and 57% (8 of 14) had died by the last follow-up. Of the 6 surviving patients, 4 showed improvement and 2 showed no change in mRS score (median mRS change, -1; range, 0 to -3). Owing to preexisting cognitive deficits, 1 patient could not complete the TICS. The 5 remaining patients scored a median of 34 on the TICS (range, 30-37; reference TICS score, >or=31; maximum TICS score, 41). Age, sex, PRSE duration, and etiology were not associated with chance of survival. CONCLUSIONS: Despite the high mortality rate, survival with meaningful functional and cognitive recovery is possible after PRSE. Prolonged duration of status epilepticus alone should not be considered a reason to discontinue treatment.

Photophobia, visual hallucinations, and REM sleep behavior disorder in progressive supranuclear palsy and corticobasal degeneration: a prospective study.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) have overlapping clinical features that can make clinical distinction between these two entities difficult. The present study compared the frequency of photophobia, visual hallucinations, and REM sleep behavior disorder (RBD) in patients clinically diagnosed with PSP to those clinically suspected to have CBD. Photophobia occurred in all 10 (100%) PSP patients vs 2 (18%) patients with clinically suspected CBD (p=0.0002). Visual hallucinations and RBD occurred in patients with PSP and CBD but were rare occurrences (5% for each symptom). The presence of photophobia is significantly more frequent in clinically diagnosed PSP than CBD and can be used as a feature in differentiating between the two diseases in clinical practice. Visual hallucinations and RBD occur infrequently in PSP and CBD and are not useful symptoms in clinical differentiation.

Mumps encephalitis: return with a vengeance.

The incidence of mumps cases has declined dramatically since the introduction of the measles, mumps, rubella vaccine. A recent outbreak, however, brings to attention the importance of recognizing the clinical symptoms and signs of mumps, because early isolation of patients may prevent spread of the disease. The authors present the case of a 50-year-old man with severe encephalitis found to be caused by the mumps virus.