Unusual Photochemistry in Aromatic Dithioimides: Quantitative Thione Reduction Promoted by Ether Solvents.

We report a mechanistic investigation of an aromatic dithioimide (2SS) displaying puzzling yet efficient photochemistry in ether solvents. Perplexingly, 2SS dissolved in ether solvents in a sealed and degassed vial was photochemically converted to the corresponding diimide (2OO), as determined by 1H NMR following product extraction. With no external sources of oxygen in the sample, could the oxygen in 2OO be from the ether itself? To study this unprecedented proposition, we attempt to uncover the ether's involvement in this reaction. As seen by laser-flash photolysis, 2SS appears to first react with the solvent from its singlet excited state. Following the reaction by NMR under rigorously oxygen- and water-free conditions led to the identification of a photoreductive pathway that quantitatively transformed one thione into a methylene to yield 2SH2. Subsequent oxidation of 2SH2 or irradiation of 2SS under air proved that molecular oxygen was indeed necessary to observe an oxidative pathway leading to 2OO, ruling out the initially proposed involvement of an ether oxygen. An explanation of 2SS desulfurization was further revealed through the study of solvent by-products by GC-MS analysis. Supported by DFT calculations, a mechanism is proposed to involve a chain reaction initiated by photochemically generated ether radical.

Immune cells surveil aberrantly sialylated O-glycans on megakaryocytes to regulate platelet count.

Immune thrombocytopenia (ITP) is a platelet disorder. Pediatric and adult ITP have been associated with sialic acid alterations, but the pathophysiology of ITP remains elusive, and ITP is often a diagnosis of exclusion. Our analysis of pediatric ITP plasma samples showed increased anti-Thomsen-Friedenreich antigen (TF antigen) antibody representation, suggesting increased exposure of the typically sialylated and cryptic TF antigen in these patients. The O-glycan sialyltransferase St3gal1 adds sialic acid specifically on the TF antigen. To understand if TF antigen exposure associates with thrombocytopenia, we generated a mouse model with targeted deletion of St3gal1 in megakaryocytes (MK) (St3gal1MK-/-). TF antigen exposure was restricted to MKs and resulted in thrombocytopenia. Deletion of Jak3 in St3gal1MK-/- mice normalized platelet counts implicating involvement of immune cells. Interferon-producing Siglec H-positive bone marrow (BM) immune cells engaged with O-glycan sialic acid moieties to regulate type I interferon secretion and platelet release (thrombopoiesis), as evidenced by partially normalized platelet count following inhibition of interferon and Siglec H receptors. Single-cell RNA-sequencing determined that TF antigen exposure by MKs primed St3gal1MK-/- BM immune cells to release type I interferon. Single-cell RNA-sequencing further revealed a new population of immune cells with a plasmacytoid dendritic cell-like signature and concomitant upregulation of the immunoglobulin rearrangement gene transcripts Igkc and Ighm, suggesting additional immune regulatory mechanisms. Thus, aberrant TF antigen moieties, often found in pathological conditions, regulate immune cells and thrombopoiesis in the BM, leading to reduced platelet count.

Refractory autoimmune cytopenias in pediatric Evans syndrome with underlying systemic immune dysregulation.

Evans syndrome is a rare but challenging disorder in children; and despite rapidly growing evidence for targetable systemic immune dysregulation driving these "idiopathic" autoimmune cytopenias, precision diagnosis and management remains sub-optimal among these patients. We analyzed retrospective clinical data for 60 pediatric ES patients followed at 3 large tertiary referral centers in the United States over a recent 6-year period and found that definable underlying systemic immune dysregulation was identified in only 42% of these patients throughout the course of clinical care. Median time from ES diagnosis to identification of the underlying systemic immune dysregulation disorder was 1.3 years (<1 month for rheumatologic disease, 2.3 years for CVID, 3.4 years for ALPS, and 7.4 years for monogenic disorders of immune regulation). Notably, a significantly higher percentage of patients in whom a definitive immune dysregulation disorder was ultimately identified required ≥3 cytopenia-directed therapies (92%) and also second- and third-line immunomodulatory agents (84%), vs those in whom no unifying immune dysregulation was diagnosed (65%, and 35%, respectively)-indicating that autoimmune cytopenias as a manifestation of systemic immune dysregulation are more treatment-refractory and severe. These data underline the importance of identifying the underlying systemic immune dysregulation and providing targeted therapy in pediatric ES.

COVID-19 outcomes in a large pediatric hematology-oncology center in Houston, Texas.

An understanding of the behavior of SARS-CoV-2 in pediatric hematology-oncology patients is essential to the optimal management of these patients during the COVID-19 pandemic. This study describes the characteristics and outcomes of COVID-19 disease in children with cancer or hematologic disorders treated at a large children's hospital. A retrospective cohort study was conducted at Texas Children's Cancer and Hematology Center from January 1, 2020 to September 30, 2020. All patients with a primary hematology-oncology diagnosis and SARS-CoV-2 positivity by reverse transcription polymerase chain reaction were identified. Clinical and laboratory data were obtained from the medical record. Descriptive analyses were performed to evaluate COVID-19-related outcomes and risk factors for severe disease in this population. We identified 109 patients with COVID-19 disease, including 52 hematology, 51 oncology, and 6 HSCT patients; median age was 10.3 years (IQR 4.4-15.9), and 58.7% were male. Seventy-four percent of the patients were managed in the outpatient setting. Patients with sickle cell disease were more likely to require hospitalization. ICU care was needed in 8% (n = 9) of the entire cohort, and mechanical ventilation was required in 6.4% (6 oncology patients, 1 hematology patient). COVID-19 contributed to the deaths of two cancer patients. No deaths occurred in hematology or HSCT patients. In conclusion, the risk of severe COVID-19 complications is slightly higher in pediatric hematology-oncology patients than in the general pediatric population but lower than initially feared. For most asymptomatic patients, primary disease management may continue as planned, but treatment decisions must be individualized.

Copper-Photocatalyzed Hydroboration of Alkynes and Alkenes.

The photocatalytic hydroboration of alkenes and alkynes is reported. The use of newly-designed copper photocatalysts with B2 Pin2 permits the formation a boryl radical, which is used for hydroboration of a large panel of alkenes and alkynes. The hydroborated products were isolated in high yields, with excellent diastereoselectivities and a high functional group tolerance under mild conditions. The hydroboration reactions were developed under continuous flow conditions to demonstrate their synthetic utility. The reaction mechanism was studied and suggested an oxidation reaction between an in situ formed borate and the Cu-photocatalyst in its excited state for the boryl radical formation.

Determinants of healthcare use by homeless people with schizophrenia or bipolar disorder: results from the French Housing First Study.

OBJECTIVES: There is limited evidence available on the health-seeking behaviours of individuals in relation to determinants of healthcare use. This study aimed to analyse the determinants of healthcare use (including both hospital and outpatient services) among homeless people with severe mental health illnesses. STUDY DESIGN: The study used data from a multicentre, randomised, controlled trial conducted in four large French cities (the French Housing First Study). METHODS: Data were drawn from 671 homeless people enrolled in the study between August 2011 and April 2014. Mobile mental health outreach teams recruited homeless individuals with severe mental health illnesses who were living on the street or in emergency shelters, hospitals or prisons. Data collection was performed during face-to-face interviews. Healthcare service use included hospitalisations, mental health and regular emergency department (ED) visits and outpatient visits to healthcare facilities or physicians' offices over a 6-month follow-up period. The data were analysed with zero-inflated (ZI) two-part models. RESULTS: In total, 61.1% of participants had at least one hospitalisation stay over the previous 6 months, with a mean of 25 (+/- 39.2) hospital days, and the majority (51%) had visited the ED (either for regular or mental health issues) during the same time period. The results confirmed the role of financial barriers (resources and health insurance) in seeking hospital care (P < 0.05). The main predictors for hospital use in the study population were a better social functioning score (odds ratio [OR]: 1.03; P < 0.001) and having schizophrenia (OR: 1.39; P < 0.01). Higher mental health scores (assessed by the Medical Outcomes Study 36-item Short Form Health Survey) (OR: 1.03, P < 0.01) and alcohol dependence (OR: 2.13; P < 0.01) were associated with not using ED healthcare services. Being 'absolutely homeless' predicted an increased use of the ED and a zero use of outpatient services. Inversely, no association with factors related to the homelessness trajectory was found in hospital ZI negative binomial models. CONCLUSION: This study is important because a comprehensive understanding of the determinants of healthcare use enables healthcare systems to adapt and develop. The efficiency of medicosocial interventions targeting the homeless population with mental health illnesses must also be assessed. CLINICAL TRIAL NUMBER: NCT01570712.

HIV/AIDS: the labour market implications of compulsory testing.

OBJECTIVE: It is intended in this brief paper to outline the policy direction that ought to be followed regarding the phenomenon of HIV/AIDS and the workplace. In essence, this is a viewpoint instructed by data and research and not anecdotal evidence. METHODS: This is not primary research as it utilizes secondary material from existing literature as well as data from government sources. The method is a strict narrative regarding the data and frequencies and there there are no sophisticated statistical packages used for data analysis. RESULTS: On examining the data, it is clear that young women are disproportionately represented in the HIV and unemployment data. CONCLUSION: It is therefore likely that if testing for the purposes of employment is allowed to continue, it will create a disincentive to seek employment and thus will help to drive the infection underground.

Changes in HIV Prevention and Sexual Experiences During the COVID-19 Pandemic: A Mixed-Methods Study.

BACKGROUND: STI and HIV services and infection rates were affected during the COVID-19 pandemic, because of changes in access to health care and individual behavior. Understanding how individuals made decisions around prevention and sexual activities during different phases of the pandemic is useful to addressing the rising rates of STIs and HIV. SETTING: Federally-qualified health center focused on sexual and gender minority health, Chicago IL, 2021. METHODS: Patients with a history of PrEP use who were contacted by the PrEP retention team as part of standard care were invited to complete an online survey. A subset of survey participants were then contacted to complete one-on-one interviews. Participants were asked about two distinct periods: November 2020 to January 2021 and February to June 2021. RESULTS: From the 356 survey participants (mostly young, insured, and experienced with PrEP), more than half maintained their number of sex partners during the early pandemic and most also maintained PrEP use; during the later pandemic; most reported more or the same number of sex partners and almost all maintained PrEP use. From interviews, we identified diverse and changing experiences regarding sexual practices throughout the pandemic; whereas many participants changed PrEP use in accordance with sexual practices, many others maintained PrEP use as a habit. COVID-19 prevention was also a factor in sexual activities, particularly prevaccination. CONCLUSION: Many PrEP users try to align their HIV prevention with their sexual exposures and establish PrEP as a long-term habit. Removing financial and access barriers is important to improve PrEP use and STI testing.

Toward more diverse, inclusive, and equitable neuromodulation.

Racial and ethnic disparities exist for many nervous system disorders that are intervention targets for neuromodulation investigators. Yet, to date, there has been both a lack of racial and ethnic diversity and a lack of emphasis on diversity in neuromodulation research. In this paper, we suggest three potential reasons for the lack of racial and ethnic diversity in neuromodulation research: 1) the lack of diversity in the neuromodulation workforce, 2) incompatibility between the technologies employed and phenotypic traits (e.g., hair texture) commonly present in minoritized populations, and 3) minoritized populations' reluctance to participate in clinical trials. We argue that increasing diversity in the neuromodulation workforce, in conjunction with mutual collaboration between current neuromodulation researchers and underrepresented communities in neuromodulation, can aid in removing barriers to diversity, equity, and inclusion in neuromodulation research. This is important, because greater diversity, equity, and inclusion in neuromodulation research brings with it the development of novel, yet safe and effective, treatment approaches for brain disorders and enhances the rigor and generalizability of discoveries in the field.

Adolescent acquired thrombotic thrombocytopenic purpura: An analysis of the Pediatric Health Information System database.

The outcomes and characteristics of acquired thrombotic thrombocytopenic purpura (TTP) in adolescents is poorly understood due to an absence of studies focused on this population. To better understand the life-threatening disorder in this age, we performed an analysis of adolescent patients (ages 10-21) with TTP in the Pediatric Health Information Systems database from 2009 to 2020. The primary outcomes evaluated were in-hospital mortality and rate of TTP relapse. Secondary outcomes included rates of hemorrhagic and thrombotic complications during hospitalizations for TTP. Patients were included if they had a thrombotic microangiopathy diagnostic code, ADAMTS13 lab obtained, and received therapeutic plasmapheresis. Patients that received treatment for other non-TTP microangiopathies were excluded. A total of 99 patients with 123 hospitalizations for TTP treatment were identified. In-patient mortality occurred in 6 % (n = 6) and TTP relapse in 20 % (n = 20) of the cohort. Median time from initial admission to relapse was 33 days (IQR 15, 92). A hemorrhagic complication was identified in 29 % (n = 36) and thrombotic complication in 15 % (n = 19) of the cohort. The presence of underlying comorbidities was not associated with TTP relapse and only a diagnosis of cancer was associated with increased mortality. The rate of mortality and relapse in adolescent TTP is lower than that seen in adult registries. Long term prospective studies are needed to understand the long-term consequences of adolescent onset acquired TTP.

Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination.

Introduction: While antidepressants are one of the first-line treatments for depression, the mechanisms underlying antidepressant action are unclear. Furthermore, the extent to which antidepressants impact emotional and cognitive dysfunction in depression requires more fine-grained approaches toward measuring these impacts in humans. Depression is associated with emotion and mood dysregulation in addition to cognitive deficits. Depressed individuals experience general memory impairment as well as a negativity bias in episodic memory, where negative events are better remembered than positive or neutral events. One potential mechanism hypothesized to underlie the negativity bias in memory is dysfunctional hippocampal pattern separation, in which depressed individuals tend to show impaired general pattern separation but enhanced negative pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation in humans and provide a powerful approach to develop a mechanistic account for cognitive dysfunction in depression. While antidepressants have been examined primarily in rodent models in the context of hippocampal pattern separation, this has yet to be examined in humans. Methods: Here, we investigated how antidepressant usage and their perceived efficacy was associated with emotional mnemonic discrimination, given our prior work indicating a negativity bias for mnemonic discrimination in individuals with greater depressive symptoms. Results: We found that individuals who reported a greater improvement in their depressive symptoms after taking antidepressants (responders) showed reduced negative and enhanced neutral mnemonic discrimination compared to those with little to no improvement (non-responders). Perceived antidepressant efficacy was the strongest predictor of a reduction in the negativity bias for mnemonic discrimination, even when controlling for current depressive symptoms, antidepressant type, and other relevant factors. Discussion: These results suggest that antidepressants, when effective, can shift memory dynamics toward healthy function.

Targeted proximity-labelling of protein tyrosines via flavin-dependent photoredox catalysis with mechanistic evidence for a radical-radical recombination pathway.

Flavin-based photocatalysts such as riboflavin tetraacetate (RFT) serve as a robust platform for light-mediated protein labelling via phenoxy radical-mediated tyrosine-biotin phenol coupling on live cells. To gain insight into this coupling reaction, we conducted detailed mechanistic analysis for RFT-photomediated activation of phenols for tyrosine labelling. Contrary to previously proposed mechanisms, we find that the initial covalent binding step between the tag and tyrosine is not radical addition, but rather radical-radical recombination. The proposed mechanism may also explain the mecha-nism of other reported tyrosine-tagging approaches. Competitive kinetics experiments show that phenoxyl radicals are generated with several reactive intermediates in the proposed mechanism-primarily with the excited riboflavin-photocatalyst or singlet oxygen-and these multiple pathways for phenoxyl radical generation from phenols increase the likelihood of radical-radical recombination.

Risk factors and prognostic significance of platelet count abnormalities in children with HIV infection on antiretroviral therapy.

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH). DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014. METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with selected clinical variables. We constructed Kaplan-Meier curves and a Cox proportional hazards model to evaluate the impact of T/T on survival. RESULTS: Two thousand, one hundred and nine children were sampled. The incidence density of thrombocytopenia was 1 per 57.9 (95% confidence interval [CI] 50.3-66.8) CWH-years. Thrombocytopenia was higher in children with WHO Stage III/IV, lower in children on zidovudine, and had no association with use of lamivudine or nevirapine, CD4 + suppression, age, and nutrition status. Thrombocytopenia was independently associated with 2.2-fold higher mortality (95% CI 1.62-3.08). The incidence density of thrombocytosis was 1 per 11.4 (95% CI 10.7-12.1) CWH-years. Thrombocytosis was associated with higher CD4 + cell count, younger age, and use of lamivudine or nevirapine, and did not impact survival. CONCLUSIONS: Platelet count is a clinically valuable biomarker of HIV clinical progression and mortality. Laboratory studies are necessary to elucidate the mechanisms of T/T.

Demonstration of a high-field short-period superconducting helical undulator suitable for future TeV-scale linear collider positron sources.

The first demonstration of a full-scale working undulator module suitable for future TeV-scale positron-electron linear collider positron sources is presented. Generating sufficient positrons is an important challenge for these colliders, and using polarized e(+) would enhance the machine's capabilities. In an undulator-based source polarized positrons are generated in a metallic target via pair production initiated by circularly polarized photons produced in a helical undulator. We show how the undulator design is developed by considering impedance effects on the electron beam, modeling and constructing short prototypes before the successful fabrication, and testing of a final module.

Synthesis and evaluation of coastal and marine biodiversity spatial information in the United Arab Emirates for ecosystem-based management.

The United Arab Emirates (UAE) host valuable coastal and marine biodiversity that is subjected to multiple pressures under extreme conditions. To mitigate impacts on marine ecosystems, the UAE protects almost 12% of its Exclusive Economic Zone. This study mapped and validated the distribution of key coastal and marine habitats, species and critical areas for their life cycle in the Gulf area of the UAE. We identified gaps in the current protection of these ecological features and assessed the quality of the data used. The overall dataset showed good data quality, but deficiencies in information for the coastline of the north-western emirates. The existing protected areas are inadequate to safeguard key ecological features such as mangroves and coastal lagoons. This study offers a solid basis to understand the spatial distribution and protection of marine biodiversity in the UAE. This information should be considered for implementing effective conservation planning and ecosystem-based management.

A Behavior Sequence Analysis of Perceptions of Alcohol-Related Violence Surrounding Drinking Establishments.

Alcohol-related violence surrounding the nighttime economy puts increased pressure and workload on security and police forces. Research surrounding alcohol-related violence consistently identifies risk factors, such as the organizational practices and physical characteristics of drinking establishments, as influential in the generation of violent behavior. The current research uses sequence analysis to investigate dynamic patterns of events perceived to lead to a violent incident. The research was collected using questionnaires across university students with customer experience of the modern nighttime economy. The findings show perceptions of maladaptive patterns of events that may lead to violent incidents in different environments (a brightly lit bar and a nightclub). Analysis demonstrated that participants thought those involved in a violent incident would have consumed large amounts of alcohol throughout the night, fueled by predrinking and irresponsible serving practices of staff. Frustration inducing events were also common stages in the sequences leading to a violent outcome. Finally, staff intervention in violent situations was also considered to be an important predictor of violence, with forceful removal of individuals from premises often considered to be the final event preceding a violent incident. The present sequences analysis supports the suggestion that the organizational practices and physical characteristics of a drinking establishment influence the risk of violent activity and helps identify where initiatives aiming to reduce levels of violence could be effectively targeted.

Occupational eye injury and risk reduction: Kentucky workers' compensation claim analysis 1994-2003.

BACKGROUND: Occupational eye injuries are a significant source of injury in the workplace. Little population-based research in the area has been conducted, and is necessary for developing and prioritizing effective interventions. METHODS: Workers' compensation data from the state of Kentucky for the years 1994-2003 were analysed by demographics, injury nature and cause, cost, and occupational and industrial characteristics. The US Bureau of Labor Statistics' Current Population Survey was utilised to compute injury rates for demographic and occupational groups. RESULTS: There were 10,545 claims of ocular injury, representing 6.29 claims per 10,000 workers on average annually. A substantial drop in the claim rate was found after the state passed monetary penalties for injuries caused by employer negligence or OSHA violations. Claims by men were over three times more likely than those by women to have associated claim costs (OR 0.52; 95% CI 0.32 to 0.85; p = 0.009). The highest eye injury rates per 10,000 of 13.46 (95% CI 12.86 to 14.07) were found for the helpers/labourers occupation, and of 19.95 (95% CI 18.73 to 21.17) for the construction industry. The total cost of claim payments over the period was over $3,480,000, and average cost per claim approximated $331. CONCLUSIONS: Eye injuries remain a significant risk to worker health, especially among men in jobs requiring intensive manual labour. Evidence showed that increased legislative regulation led to a decline in eye injuries, which was consistent with other recent findings in the area. Additionally, targeting groups most at risk, increasing worker training, providing effective eye protection equipment, and developing workplace safety cultures may together reduce occupational eye injuries.

Metal-Free-Visible Light C-H Alkylation of Heteroaromatics via Hypervalent Iodine-Promoted Decarboxylation.

A metal-free photoredox C-H alkylation of heteroaromatics from readily available carboxylic acids using an organic photocatalyst and hypervalent iodine reagents under blue LED light is reported. The developed methodology tolerates a broad range of functional groups and can be applied to the late-stage functionalization of drugs and drug-like molecules. The reaction mechanism was investigated with control experiments and photophysical experiments as well as DFT calculations.

Specific-heat measurements of the gap structure of the organic superconductors kappa-(ET)2Cu[N(CN)2]Br and kappa-(ET)2Cu(NCS)2.

We present high resolution heat capacity measurements of the organic superconductors kappa-(ET)(2)Cu[N(CN)(2)]Br and kappa-(ET)(2)Cu(NCS)(2) in fields up to 14 T. We use the high field data to determine the normal state specific heat and hence extract the behavior of the electronic specific heat C(el) in the superconducting state in zero and finite fields. We find that in both materials for T/T(c) less or similar 0.3, C(el)(H=0) approximately T2 indicating d-wave superconductivity. The data are well described by a strong coupling d-wave model from our base temperature (T/T(c) approximately 0.1) right up to T(c). Our data help to resolve the controversy regarding the order parameter symmetry in these materials.

Serum HE4 Level as a Biomarker to Predict the Recurrence of Gynecologic Cancers.

BACKGROUND: HE4 may be a valuable early indicator of the recurrence of gynecologic cancers. Numerous studies have shown that high expression levels of serum HE4 correlate with ovarian and endometrial cancer recurrence. High HE4 levels may be an independent factor to predict these cancers' poor prognosis. OBJECTIVE: This literature review investigates the relationship between serum HE4 levels and the recurrence of ovarian and endometrial cancer. CONCLUSION: HE4 displays malignant behavior by promoting cancer cells to skip from G1 phase to S phase, maintaining cell viability, encouraging cell proliferation, inhibiting cell apoptosis, and increasing resistance to drug treatments. Further studies are required to verify that elevated serum HE4 levels correlate with the recurrence of ovarian and endometrial cancer.