TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.

A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress.

Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH-30, play an important role in mediating cellular response to a variety of stress conditions, including nutrient deprivation, oxidative stress, and pathogen infection. In this study, we identify a novel mechanism of TFEB/HLH-30 regulation through a cysteine-mediated redox switch. Under stress conditions, TFEB-C212 undergoes oxidation, allowing the formation of intermolecular disulfide bonds that result in TFEB oligomerization. TFEB oligomers display increased resistance to mTORC1-mediated inactivation and are more stable under prolonged stress conditions. Mutation of the only cysteine residue present in HLH-30 (C284) significantly reduced its activity, resulting in developmental defects and increased pathogen susceptibility in worms. Therefore, cysteine oxidation represents a new type of TFEB post-translational modification that functions as a molecular switch to link changes in redox balance with expression of TFEB/HLH-30 target genes.

A systematic review on the application of machine learning models in psychometric questionnaires for the diagnosis of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder is one of the most prevalent neurodevelopmental disorders worldwide. Recent studies show that machine learning has great potential for the diagnosis of attention deficit hyperactivity disorder. The aim of the present article is to systematically review the scientific literature on machine learning studies for the diagnosis of attention deficit hyperactivity disorder, focusing on psychometric questionnaire tools. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were adopted. The review protocol was registered in the PROSPERO database. A search was conducted in three databases-Web of Science Core Collection, Scopus and Pubmed-with the aim of identifying studies that apply ML techniques to support the diagnosis of attention deficit hyperactivity disorder. A total of 17 empirical studies were found that met the established inclusion criteria. The results showed that machine learning can be used to increase the accuracy of attention deficit hyperactivity disorder diagnosis. Machine learning techniques are useful and effective strategies that can complement traditional diagnostics in patients with attention deficit hyperactivity disorder.

Incorporation of Carboxylate Pendant Arms into 18-Membered Macrocycles: Effects on [nat/203Pb]Pb(II) Complexation.

We present a detailed investigation on the coordination chemistry of [nat/203Pb]Pb(II) with chelators H4PYTA and H4CHX-PYTA. These chelators belong to the family of ligands derived from the 18-membered macrocyclic backbone PYAN and present varying degrees of rigidity due to the presence of either ethyl or cyclohexyl spacers. A complete study of the stable Pb(II) complexes is carried out via NMR, X-Ray crystallography, stability constant determination and computational studies. While these studies indicated that Pb(II) complexation is achieved, and the thermodynamic stability of the resulting complexes is very high, a certain degree of fluxionality does exist in both cases. Nevertheless, radiolabeling studies were carried out using SPECT (single photon emission computed tomography) compatible isotope lead-203 (203Pb, t1/2=51.9 h), and while both chelators complex the radioisotope, the incorporation of carboxylate pendant arms appears to be detrimental towards the stability of the complexes when compared to the previously described amide analogues. Additionally, incorporation of a cyclohexyl spacer does not improve the kinetic inertness of the system.

Incidence of brain metastasis according to patient race and primary cancer origin: a systematic review.

PURPOSE: A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers. METHODS: Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence. RESULTS: Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer. CONCLUSIONS: These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type.

Influence of Stigma on Engagement in HIV Care and Adherence to Antiretroviral Therapy in Specialized HIV Clinics Targeting Men Who Have Sex with Men and Transgender Women in Lima, Peru.

HIV stigma is a social determinant of health that can influence multiple health outcomes, including adherence to antiretroviral therapy (ART), engagement in HIV care, and viral suppression levels in people with HIV (PWH). In Peru, where the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW), stigma may play an important role in healthcare engagement. To understand the relationship between stigma and two outcome variables, ART adherence and engagement in HIV care in 400 MSM and TGW, we assessed factors from the Behavioral Model for Vulnerable Populations at two HIV clinics that tailor services for sexual and gender minorities. While some predisposing, need, and enabling resource factors were associated with optimal (≥ 90%) ART adherence or engagement in HIV care, none of the stigma subscales were correlated, suggesting that when LGBTQ-affirming care is provided to MSM/TGW, stigma may not influence HIV-related outcomes.

RESUMEN: El estigma hacia el VIH es un determinante social de la salud que puede influir en múltiples desenlaces, incluyendo la adherencia a la terapia antirretroviral (TAR), el compromiso con la atención del VIH y los niveles de supresión viral en personas viviendo con VIH (PVV). En el Perú, donde la epidemia del VIH se concentra en hombres que tienen sexo con hombres (HSH) y mujeres transgénero (MT), el estigma puede desempeñar un papel importante en el compromiso con la atención médica. Para comprender la relación entre el estigma y dos variables de resultado, la adherencia al TAR y el compromiso con la atención del VIH en 400 HSH y MT, evaluamos factores del Modelo de Comportamiento para Poblaciones Vulnerables en dos clínicas de VIH que adaptan sus servicios para minorías sexuales y de género. Si bien algunos factores predisponentes, de necesidad y de recursos habilitantes se asociaron con una adherencia óptima (≥ 90%) al TAR o al compromiso con la atención del VIH, ninguna de las sub-escalas de estigma estuvieron correlacionadas, sugiriendo que cuando se brinda atención que afirma a la comunidad LGBTQ a HSH/MT, el estigma puede no influir en los desenlaces relacionados con el VIH.

Endeavor toward Redox-Responsive Transition Metal Contrast Agents Based on the Cross-Bridge Cyclam Platform.

We present the synthesis and characterization of a series of Mn(III), Co(III), and Ni(II) complexes with cross-bridge cyclam derivatives (CB-cyclam = 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) containing acetamide or acetic acid pendant arms. The X-ray structures of [Ni(CB-TE2AM)]Cl2·2H2O and [Mn(CB-TE1AM)(OH)](PF6)2 evidence the octahedral coordination of the ligands around the Ni(II) and Mn(III) metal ions, with a terminal hydroxide ligand being coordinated to Mn(III). Cyclic voltammetry studies on solutions of the [Mn(CB-TE1AM)(OH)]2+ and [Mn(CB-TE1A)(OH)]+ complexes (0.15 M NaCl) show an intricate redox behavior with waves due to the MnIII/MnIV and MnII/MnIII pairs. The Co(III) and Ni(II) complexes with CB-TE2A and CB-TE2AM show quasi-reversible features due to the CoIII/CoII or NiII/NiIII pairs. The [Co(CB-TE2AM)]3+ complex is readily reduced by dithionite in aqueous solution, as evidenced by 1H NMR studies, but does not react with ascorbate. The [Mn(CB-TE1A)(OH)]+ complex is however reduced very quickly by ascorbate following a simple kinetic scheme (k0 = k1[AH-], where [AH-] is the ascorbate concentration and k1 = 628 ± 7 M-1 s-1). The reduction of the Mn(III) complex to Mn(II) by ascorbate provokes complex dissociation, as demonstrated by 1H nuclear magnetic relaxation dispersion studies. The [Ni(CB-TE2AM)]2+ complex shows significant chemical exchange saturation transfer effects upon saturation of the amide proton signals at 71 and 3 ppm with respect to the bulk water signal.

Exploring the Limits of Ligand Rigidification in Transition Metal Complexes with Mono-N-Functionalized Pyclen Derivatives.

We report the synthesis of a new family of side-bridged pyclen ligands. The incorporation of an ethylene bridge between two adjacent nitrogen atoms was reached from the pyclen-oxalate precursor described previously. Three new side-bridged pyclen macrocycles, Hsb-3-pc1a, sb-3-pc1py, and Hsb-3-pc1pa, were obtained with the aim to assess their coordination properties toward Cu2+ and Zn2+ ions. We also prepared their nonreinforced analogues H3-pc1a, 3-pc1py, and H3-pc1pa as comparative benchmarks. The two series of ligands were characterized and their coordination properties were investigated in detail. The Zn2+ and Cu2+ complexes with the nonside-bridged series H3-pc1a, 3-pc1py, and H3-pc1pa were successfully isolated and their structures were assessed by X-ray diffraction studies. In the case of the side-bridged family, the synthesis of the complexes was far more difficult and, in some cases, unsuccessful. The results of our studies demonstrate that this difficulty is related to the extreme stiffening and basicity of such side-bridged pyclens.

Relevance of Oxocyclam from Palladium(II) Coordination to Radiopharmaceutical Development.

We provide a comprehensive study of the coordination of oxocyclam with palladium(II), including presentation of a novel bifunctional analogue, p-H2N-Bn-oxocyclam, bearing an aniline pendant. The complexation of palladium(II) with oxocyclam was examined by various techniques, including NMR analysis and potentiometric titrations which revealed that the Pd(II) complex can adopt different configurations such as trans-I and trans-III. In addition, oxocyclam forms a thermodynamically stable palladium(II) complex, the stabilization being attributed to the deprotonation of the amide function. The crystal structures of [Pd(H-1oxocyclam)]+ and [Pd(oxocyclam)]2+ were obtained, revealing the structural details previously anticipated, including, in the second case, the presence of the proton on the carbonyl oxygen atom. Additionally, the study explored the redox behavior of the Pd(II)-oxocyclam complex through reduction and oxidation voltammograms at different pH values. Successful 109Pd-labeling of oxocyclam and p-H2N-Bn-oxocyclam at pH 3.5 demonstrated high labeling efficiencies, whatever the species formed. The stability of the radiocomplexes was assessed and moderate transchelation toward EDTA was observed. Overall, oxocyclam displayed favorable properties for Pd(II) coordination and radiolabeling, suggesting its potential as a chelating agent for this metal in palladium-based applications.

Short- and long-term outcomes of acute diverticulitis in patients with transplanted kidneys.

AIM: The safety of nonoperative treatment for patients with transplanted kidneys who develop acute diverticulitis is unclear. Our primary aim was to examine the long-term sequelae of nonoperative management in this group. METHOD: We performed a population-based retrospective cohort study using linked administrative databases housed at ICES in Ontario, Canada. We included adult (≥18 years) patients admitted with acute diverticulitis between April 2002 and December 2019. Patients with a functioning kidney transplant were compared with those without a transplant. The primary outcome was failure of conservative management (operation, drainage procedure or death due to acute diverticulitis) beyond 30 days. The cumulative incidence function and a Fine-Grey subdistribution hazard model were used to evaluate this outcome accounting for competing risks. RESULTS: We examined 165 patients with transplanted kidneys and 74 095 without. Patients with transplanted kidneys were managed conservatively 81% of the time at the index event versus 86% in nontransplant patients. Short-term outcomes were comparable, but cumulative failure of conservative management at 5 years occurred in 5.6% (95% CI 2.3%-11.1%) of patients with transplanted kidneys versus 2.1% (95% CI 2.0%-2.3%) in those without. Readmission for acute diverticulitis was also higher in transplanted patients at 5 years at 16.7% (95% CI 10.1%-24.7%) versus 11.6% (95% CI 11.3%-11.9%). Adjusted analyses showed increased failure of conservative management [subdistribution hazard ratio (sHR) 3.24, 95% CI 1.69-6.22] and readmissions (sHR 1.55, 95% CI 1.02-2.36) for patients with transplanted kidneys. CONCLUSION: Most patients with transplanted kidneys are managed conservatively for acute diverticulitis. Although long-term readmission and failure of conservative management is higher for this group than the nontransplant population, serious outcomes are infrequent, substantiating the safety of this approach.

Recommendations for Recovery of the COVID-19 Pandemic-related Diagnostic, Screening, and Procedure Backlog in Ontario: A Survey of Healthcare Leaders.

PURPOSE: The COVID-19 pandemic has resulted in a significant diagnostic, screening, and procedure backlog in Ontario. Engagement of key stakeholders in healthcare leadership positions is urgently needed to inform a comprehensive provincial recovery strategy. METHODS: A list of 20 policy recommendations addressing the diagnostic, screening and procedure backlog in Ontario were transformed into a national online survey. Policy recommendations were rated on a 7-point Likert scale (strongly agree to strongly disagree) and organized into those retained (≥75% strongly agree to somewhat agree), discarded (≥80% somewhat disagree to strongly disagree), and no consensus reached. Survey participants included a diverse sample of healthcare leaders with the potential to impact policy reform. RESULTS: Of 56 healthcare leaders invited to participate, there were 34 unique responses (61% response rate). Participants were from diverse clinical backgrounds, including surgical subspecialties, medicine, nursing, and healthcare administration and held institutional or provincial leadership positions. A total of 11 of 20 policy recommendations reached the threshold for consensus agreement with the remaining 9 having no consensus reached. CONCLUSION: Consensus agreement was reached among Canadian healthcare leaders on 11 policy recommendations to address the diagnostic, screening, and procedure backlog in Ontario. Recommendations included strategies to address patient information needs on expected wait times, expand health and human resource capacity, and streamline efficiencies to increase operating room output. No consensus was reached on the optimal funding strategy within the public system in Ontario or the appropriateness of implementing private funding models.

Associations of physical activity type, volume, intensity, and changes over time with all-cause mortality in older adults: The Seniors-ENRICA cohorts.

OBJECTIVE: To assess the association of physical activity (PA) type, volume, intensity, and changes over time with all-cause mortality in older adults. METHODS: We used data from 3518 and 3273 older adults recruited in the Seniors-ENRICA-1 and 2 cohorts. PA was assessed with the EPIC questionnaire. Participants reported how many hours they spent a week in walking, cycling, gardening, do-it-yourself (DIY), sports, and housework. Then, time at each intensity (moderate PA [MPA], vigorous PA [VPA], moderate-to-vigorous PA [MVPA] and total PA) was calculated. Changes in PA were calculated from the date of the baseline interview to Wave 1. All-cause mortality was ascertained up January 31, 2022. Analyses were performed with Cox regression models, adjusting for the main confounders. RESULTS: Walking, gardening, sports, and housework was associated with lower mortality (ranged 20%-46%). Also, MPA, VPA, MVPA was associated with lower risk of mortality (ranged 28%-53%). Analyses of PA change showed that, compared no PA participation (at baseline nor Wave 1), maintain walking, sports, and housework (ranged 28%-53%) and maintaining MPA, VPA, and MVPA (ranged 32%-36%) levels was linked to decreased mortality risk. Those who increased, maintained, or even decreased total PA had lower mortality (57%, 52%, and 36%, respectively) than those with consistently very low PA. CONCLUSIONS: The lower mortality was observed in those with a high baseline level of total PA. Maintaining PA levels such as walking, gardening, and housework, or at all analyzed intensities, was related to lower mortality.

Assessment of ADHD Subtypes Using Motion Tracking Recognition Based on Stroop Color-Word Tests.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder known for its significant heterogeneity and varied symptom presentation. Describing the different subtypes as predominantly inattentive (ADHD-I), combined (ADHD-C), and hyperactive-impulsive (ADHD-H) relies primarily on clinical observations, which can be subjective. To address the need for more objective diagnostic methods, this pilot study implemented a Microsoft Kinect-based Stroop Color-Word Test (KSWCT) with the objective of investigating the potential differences in executive function and motor control between different subtypes in a group of children and adolescents with ADHD. A series of linear mixture modeling were used to encompass the performance accuracy, reaction times, and extraneous movements during the tests. Our findings suggested that age plays a critical role, and older subjects showed improvements in KSWCT performance; however, no significant divergence in activity level between the subtypes (ADHD-I and ADHD-H/C) was established. Patients with ADHD-H/C showed tendencies toward deficits in motor planning and executive control, exhibited by shorter reaction times for incorrect responses and more difficulty suppressing erroneous responses. This study provides preliminary evidence of unique executive characteristics among ADHD subtypes, advances our understanding of the heterogeneity of the disorder, and lays the foundation for the development of refined and objective diagnostic tools for ADHD.

Lymphoepithelioma-like carcinoma: a rare case of rectal cancer.

Lymphoepithelioma-like carcinoma (LELC) is a histological variant that resembles nasopharyngeal lymphoepithelioma and occurs in various locations such as the salivary glands and lung. LELCs in the digestive tract are rare, accounting for only 2% of cases, being exceptional in the rectum. We present the case of an 84-year-old man with rectorrhagia, whitish malodorous discharge and constipation of one month's duration. Rectal examination identified a tumour. Colonoscopy revealed a rectal lesion that was confirmed by biopsy as malignant, and MRI showed an extensive rectal tumour. Histopathology revealed undifferentiated carcinoma with acute inflammatory infiltrate, consistent with LELC. Immunohistochemistry was positive for keratins 5/6, 18, 20, CEA and BER.EP4, while in situ hybridisation for Epstein-Barr virus (EBV) RNA was negative. The multidisciplinary decision included neoadjuvant radiotherapy and anterior rectal resection. The patient remains in complete response two years after treatment. Histologically, LELC is characterised by an acute inflammatory infiltrate interspersed with poorly differentiated neoplastic cells. The stomach is the most commonly affected region in the gastrointestinal tract, with more than 80% of gastric LELCs associated with EBV. To date, only four cases of rectal LELC have been reported, and its association with EBV was demonstrated in only one case. There are no standard treatments for rectal LELC, underscoring the need to gather more cases to understand its pathogenesis and develop effective treatment strategies.

Interrater Agreement of CT Grading of Blunt Splenic Injuries: Does the AAST Grading Need to Be Reimagined?

Introduction: The Revised Organ Injury Scale (OIS) of the American Association for Surgery of Trauma (AAST) is the most widely accepted classification of splenic trauma. The objective of this study was to evaluate inter-rater agreement for CT grading of blunt splenic injuries. Methods: CT scans in adult patients with splenic injuries at a level 1 trauma centre were independently graded by 5 fellowship trained abdominal radiologists using the AAST OIS for splenic injuries - 2018 revision. The inter-rater agreement for AAST CT injury score, as well as low-grade (IIII) versus high-grade (IV-V) splenic injury was assessed. Disagreement in two key clinical scenarios (no injury versus injury, and high versus low grade) were qualitatively reviewed to identify possible sources of disagreement. Results: A total of 610 examinations were included. The inter-rater absolute agreement was low (Fleiss kappa statistic 0.38, P < 0.001), but improved when comparing agreement between low and high grade injuries (Fleiss kappa statistic of 0.77, P < .001). There were 34 cases (5.6%) of minimum two-rater disagreement about no injury vs injury (AAST grade ≥ I). There were 46 cases (7.5%) of minimum two-rater disagreement of low grade (AAST grade I-III) versus high grade (AAST grade IV-V) injuries. Likely sources of disagreement were interpretation of clefts versus lacerations, peri-splenic fluid versus subcapsular hematoma, application of adding multiple low grade injuries to higher grade injuries, and identification of subtle vascular injuries. Conclusion: There is low absolute agreement in grading of splenic injuries using the existing AAST OIS for splenic injuries.

Machine Learning Detection and Characterization of Splenic Injuries on Abdominal Computed Tomography.

BACKGROUND: Multi-detector contrast-enhanced abdominal computed tomography (CT) allows for the accurate detection and classification of traumatic splenic injuries, leading to improved patient management. Their effective use requires rapid study interpretation, which can be a challenge on busy emergency radiology services. A machine learning system has the potential to automate the process, potentially leading to a faster clinical response. This study aimed to create such a system. METHOD: Using the American Association for the Surgery of Trauma (AAST), spleen injuries were classified into 3 classes: normal, low-grade (AAST grade I-III) injuries, and high-grade (AAST grade IV and V) injuries. Employing a 2-stage machine learning strategy, spleens were initially segmented from input CT images and subsequently underwent classification via a 3D dense convolutional neural network (DenseNet). RESULTS: This single-centre retrospective study involved trauma protocol CT scans performed between January 1, 2005, and July 31, 2021, totaling 608 scans with splenic injuries and 608 without. Five board-certified fellowship-trained abdominal radiologists utilizing the AAST injury scoring scale established ground truth labels. The model achieved AUC values of 0.84, 0.69, and 0.90 for normal, low-grade injuries, and high-grade splenic injuries, respectively. CONCLUSIONS: Our findings demonstrate the feasibility of automating spleen injury detection using our method with potential applications in improving patient care through radiologist worklist prioritization and injury stratification. Future endeavours should concentrate on further enhancing and optimizing our approach and testing its use in a real-world clinical environment.

Cost-effectiveness analysis of molecular testing in minimally invasive samples to detect endometrial cancer in women with postmenopausal bleeding.

INTRODUCTION: New approaches are being developed to early detect endometrial cancer using molecular biomarkers. These approaches offer high sensitivities and specificities, representing a promising horizon to develop early detection strategies. OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of introducing molecular testing to detect endometrial cancer in women with postmenopausal bleeding compared to the current strategy using the national healthcare service perspective. METHODS: A Markov model was developed to assess the two early detection strategies. The model predicts the number of hysterectomies, lifetime expectancy, quality-adjusted life-years, endometrial cancer prevalence and incidence, mortality from endometrial cancer and the lifetime cost of screening, diagnosis, and treatment. Strategies were compared using the incremental cost-effectiveness ratio. RESULTS: The molecular strategy reduces 1.9% of the overall number of hysterectomies and the number of undetected cancer cases by 65%. Assuming a molecular test cost of 310€, the molecular strategy has an incremental cost of -32,952€ per QALY gained, being more effective and less expensive than the current strategy. CONCLUSIONS: The introduction of molecular testing to diagnose endometrial cancer in women presenting postmenopausal bleeding provides more health benefit at a lower cost, and therefore has the potential to be cost-effective.

Characterizing the Impact of Procedure Funding on the Covid-19 Generated Procedure Gap in Ontario: A Population-Based Analysis.

BACKGROUND: Surgical procedures in Canada were historically funded through global hospital budgets. Activity-based funding models were developed to improve access, equity, timeliness, and value of care for priority areas. COVID-19 upended health priorities and resulted in unprecedented disruptions to surgical care, which created a significant procedure gap. We hypothesized that activity-based funding models influenced the magnitude and trajectory of this procedure gap. METHODS: Population-based analysis of procedure rates comparing the pandemic (March 1, 2020-December 31, 2021) to a prepandemic baseline (January 1, 2017-February 29, 2020) in Ontario, Canada. Poisson generalized estimating equation models were used to predict expected rates in the pandemic based on the prepandemic baseline. Analyses were stratified by procedure type (outpatient, inpatient), body region, and funding category (activity-based funding programs vs. global budget). RESULTS: In all, 281,328 fewer scheduled procedures were performed during the COVID-19 period compared with the prepandemic baseline (Rate Ratio 0.78; 95% CI 0.77-0.80). Inpatient procedures saw a larger reduction (24.8%) in volume compared with outpatient procedures (20.5%). An increase in the proportion of procedures funded through activity-based programs was seen during the pandemic (52%) relative to the prepandemic baseline (50%). Body systems funded predominantly through global hospital budgets (eg, gynecology, otologic surgery) saw the least months at or above baseline volumes, whereas those with multiple activity-based funding options (eg, musculoskeletal, abdominal) saw the most months at or above baseline volumes. CONCLUSIONS: Those needing procedures funded through global hospital budgets may have been disproportionately disadvantaged by pandemic-related health care disruptions.

Probing Tyrosine Nitration with a Small TbIII -Metallopeptide.

Tyrosine nitration, a post-translational modification (PTM) that takes place under nitrosative stress conditions, occurs through a non-enzymatic peroxynitrite-mediated reaction. Although protein nitration has long been considered an irreversible PTM involved in nitrosative stress-associated diseases, it has also been suggested to be a regulatory mechanism of signal transduction. Therefore, the development of tools that help to understand this protein modification is of great interest. Herein, we explore a TbIII -chelating metallopeptide to monitor tyrosine nitration. The luminescence of this probe decreases significantly between its non-nitrated and nitrated states, and this reduction in the luminescence intensity is directly related to the degree of tyrosine nitration after treatment with peroxynitrite. Remarkably, the luminescence intensity changes after nitration are not affected in the presence of complex biological media, which makes it a promising tool for understanding this protein modification.

Development of an in-house bone marrow collection kit: The Catalan bone marrow transplantation group experience.

BACKGROUND AND OBJECTIVES: Bone marrow (BM) harvesting is one of the essential sources of stem cells for haematopoietic stem cell transplantation. In 2019, commercial BM collection kits became unavailable in Europe. Consequently, we created an in-house BM collection kit as an alternative. MATERIALS AND METHODS: We compared two groups of BM collections. The first collections were taken using an in-house kit from June 2022 through February 2023 and the second with a commercial kit from February 2021 through May 2022. These all took place at seven collection centres (CC). We analysed the harvest quality (cell blood count, CD34+ cells, viability, potency and sterility), the incidents occurring with each kit and the time to neutrophil and platelet engraftment in recipients. RESULTS: A total of 23 donors underwent BM harvesting with the in-house kit and 23 with the commercial one. Both cohorts were comparable regarding donor characteristics, CC and time to procedure. No statistical differences were found in harvest quality between the in-house and commercial kits. A new transfusion set was required in three BM harvests (13%) with the in-house kit because of filter clogging. The median time to neutrophil and platelet engraftment was 21 days for both cohorts and 29 days (in-house) and 33 days (commercial), p = 0.284, respectively. CONCLUSION: The in-house BM collection kit offers a real approach to solve the diminished supply of commercial kits. A higher risk of filter clogging was observed compared with commercial kits due to the lack of 850 and 500 µm filters.