An unexplored angle: T cell antigen discoveries reveal a marginal contribution of proteasome splicing to the immunogenic MHC class I antigen pool.

In the current era of T cell-based immunotherapies, it is crucial to understand which types of MHC-presented T cell antigens are produced by tumor cells. In addition to linear peptide antigens, chimeric peptides are generated through proteasome-catalyzed peptide splicing (PCPS). Whether such spliced peptides are abundantly presented by MHC is highly disputed because of disagreement in computational analyses of mass spectrometry data of MHC-eluted peptides. Moreover, such mass spectrometric analyses cannot elucidate how much spliced peptides contribute to the pool of immunogenic antigens. In this Perspective, we explain the significance of knowing the contribution of spliced peptides for accurate analyses of peptidomes on one hand, and to serve as a potential source of targetable tumor antigens on the other hand. Toward a strategy for mass spectrometry independent estimation of the contribution of PCPS to the immunopeptidome, we first reviewed methodologies to identify MHC-presented spliced peptide antigens expressed by tumors. Data from these identifications allowed us to compile three independent datasets containing 103, 74, and 83 confirmed T cell antigens from cancer patients. Only 3.9%, 1.4%, and between 0% and 7.2% of these truly immunogenic antigens are produced by PCPS, therefore providing a marginal contribution to the pool of immunogenic tumor antigens. We conclude that spliced peptides will not serve as a comprehensive source to expand the number of targetable antigens for immunotherapies.

Toxic element determination in selected cosmetic products: health risk assessment.

The aim of this research was to determine the content of arsenic (As), cadmium (Cd), lead (Pb), and nickel (Ni) in selected lipsticks and face foundations of different price categories and the health risk assessment associated with these toxic elements via dermal and oral exposure. The samples (10 lipstick and 10 face foundations) were purchased from local markets in Belgrade, Serbia. The samples were prepared by acid digestion and analyzed by atomic absorption spectrometry (flame atomization for Cd, Pb, and Ni and electrothermal atomization for As). Arsenic was found in 50% of lipstick samples and in only two face foundation samples with the highest concentration of 0.28 mg/kg in the lipstick sample. Lead concentration was in the range of 1.15 to 5.12 mg/kg in ten samples. Nickel was found in five samples out of 20, with the highest concentration of 4.20 mg/kg. Cadmium was found in only one face foundation sample in the cheaper price range (1.11 mg/kg). The obtained results indicate that concentrations of As, Pb, Cd, and Ni were within the permissible limits according to Serbian legislation. Health risk associated with these elements was assessed as non-carcinogenic and carcinogenic risk. Obtained hazard quotients (HQs) and hazard indexes (HIs) were below 1, indicating the absence of significant non-carcinogenic health risk due to exposure to these toxic elements (TEs). The carcinogenic risk results show that investigated cosmetic products can be considered low-risky due to the possibility of causing malignant disease.

Evaluation of the usefulness of COVID-19 antigen tests in primary health care on the example of Kashubian Medical Centre in Sierakowice.

Introduction: The SARS-CoV-2 pandemic is described as a global health crisis. The most typical symptoms of infection prompt most patients to visit a primary care clinic (PCC). From December 2020, COVID-19 can be diagnosed in European Union countries on the basis of a positive antigen test result. These tests are widely used at the primary care level. Material and methods: The analysis covered the period from 01.09.2021 to 28.02.2022. Statistical analysis was performed on the results of a study of 1,849 patients who underwent antigen testing in primary care clinics at the Kashubian Medical Centre (KCM) in Sierakowice and data published by the Ministry of Health on the results of tests performed from the whole country, Pomeranian Voivodeship and Kartuzy County. Results: Statistical analysis showed that the results of studies conducted in KCM in Sierakowice (antigen-only tests) were consistent with the results of studies conducted in Kartuzy County, Pomeranian Voivodeship and nationwide (molecular PCR - Polymerase Chain Reaction and antigen tests). Conclusions: Rapid antigen tests are a useful diagnostic tool in the fight against the SARS-CoV-2 pandemic because of their easy availability and simplicity of performance, and their widespread dissemination, especially in primary care settings, could contribute to multibillion-dollar savings in the health care system.

Fine Pore-Structure Engineering by Ligand Conformational Control of Naphthalene Diimide-Based Semiconducting Porous Coordination Polymers for Efficient Chemiresistive Gas Sensing.

Exploring new porous coordination polymers (PCPs) that have tunable structure and conductivity is attractive but remains challenging. Herein, fine pore structure engineering by ligand conformation control of naphthalene diimide (NDI)-based semiconducting PCPs with π stacking-dependent conductivity tunability is achieved. The π stacking distances and ligand conformation in these isoreticular PCPs were modulated by employing metal centers with different coordination geometries. As a result, three conjugated PCPs (Co-pyNDI, Ni-pyNDI, and Zn-pyNDI) with varying pore structure and conductivity were obtained. Their crystal structures were determined by three-dimensional electron diffraction. The through-space charge transfer and tunable pore structure in these PCPs result in modulated selectivity and sensitivity in gas sensing. Zn-pyNDI can serve as a room-temperature operable chemiresistive sensor selective to acetone.

Challenges to reducing post-consumer plastic rejects from the MSW selective collection at two MRFs in São Paulo city, Brazil.

​The present study is concerned with an overview of the main aspects of the selective collection from the municipal solid waste in São Paulo City and the limitations of its two automated Material Recovery Facilities (MRFs) to tackle the problem of reducing recyclable plastic waste sent to landfills as rejects. The research aimed to characterize the composition of screened mass flows of as-received mixes from the selective collection at the two MRFs through in situ random collection campaigns. The results of the gravimetric analysis have shown that both MRFs provided higher recovery yields (> 40%) for paper, cardboard, Tetrapack®, ferrous and non-ferrous metals (aluminium), akin to some post-consumer plastics (PET, HDPE/LDPE and PP) that ranged from 38% for PP up to 89% for HDPE, Losses in recovery yields of recyclable plastics after the screening process resulted from lack of clear resin label identification, inefficient materials sortation by households and poor recognition capabilities of the MRFs screening devices to target and segregate specific types of plastics such as PS and vinylic. Packaging design complexity, multi-layered material diversity, and food contaminated post-consumer packaging pose further challenges to improve the plastics recovery capabilities of the two MRFs.

Four typical personal care products in a municipal wastewater treatment plant in China: Occurrence, removal efficiency, mass loading and emission.

The occurrence, removal efficiency, mass loading and environmental emission of four categories (benzotriazoles; parabens; antimicrobials; benzophenones) of personal care products were simultaneously determined along the whole process line through an integrated approach (involving both dissolved and adsorbed phase) at a typical wastewater treatment plant in Hunan Province, Southern China. The results showed the prevalence of 13 and 11 target compounds in wastewater and suspended particulate matter, respectively. Twelve substances were detected in the sludge with the mean concentrations ranging from 0.12 to 591.23 ng/g dry weight. Benzotriazoles were the dominant compounds existing in water and antimicrobials were readily being absorbed onto suspended particulate matter and sludge. The overall removal efficiencies of compounds in the total treatment were -84.06%-98.53%. Mass balance results revealed that 85.17%-98.73% of the parabens and benzophenones were removed by degradation, while antimicrobials were removed by being adsorbed onto sludge. However, benzotriazoles could not be efficiently removed and the mass loss was lower than 61.03%. Although ultraviolet radiation played a limited role in removing most target compounds, it still had an impact on removing antimicrobials, 5,6-dimethyl-1H-benzotriazole and 2-hydroxy-4-methoxybenzophenone. The total mass loading and emission of personal care products were 506.35 mg/d/1000 people and 357.56 mg/d/1000 people, respectively. This work would help understand the removal approaches and real pollution of personal care products in the water environment.

Power Gaps Among Stakeholders in Israel's Primary Care and the Role of Primary Care Physicians' Relative Power in Their Intention to Use Video-Consultations with Patients.

Introduction: Although some correlates of primary care physicians (PCPs) telemedicine adoption have been studied, little is known about whether the intention to use video-consultations (VCs) relates to how PCPs view their power, relative to other stakeholder groups in primary care. The aim of this study was (1) to describe PCPs', patients', and policy makers' (PMs) views of their power and (2) to explore how PCPs views of power are associated with their intention to use VC. Methods: A convergent parallel mixed-methods design was used. Interviews were conducted with five focus groups that comprised 42 patients; five focus groups with 52 PCPs; and 24 individual interviews with PMs. A total of 508 patients, 311 PCPs, and 141 PMs completed the questionnaire, assessing intention to use VC and stakeholders' relative power. The qualitative data were analyzed using the thematic method; survey data were analyzed using quantitative methods. Results: All stakeholder groups rated PCPs' power as significantly lower, relative to that of patients and managers. PCPs' intention to use telemedicine was found to be significantly related to perceived power gaps between them and patients (r = -0.24, p < 0.001) and between them and managers (r = -0.45, p < 0.001). Themes revealed in the analysis describing how PCPs' low power influences their intention to use VC were as follows: PCPs' low-impact telemedicine-related decisions, increased work overload, "big brother" control, and Health Maintenance Organization demands for telemedicine mandatory usage. Conclusions: To successfully adopt VC, efforts should be made to increase PCPs' relative power, by strengthening their involvement in decision-making procedures and by increasing PCPs' control over their work environment.

Application and Comparison of Different Prognostic Scoring Systems in Patients Who Underwent Cardiologist-Managed Percutaneous Cardiopulmonary Support.

BACKGROUND: Temporary mechanical support, including percutaneous cardiopulmonary support (PCPS), is crucial for reversing patients' compromised hemodynamic function. Knowledge about whether cardiologists can directly manage patients receiving PCPS and about the predictive values of different prognostic scores is insufficient. METHODS: We examined the data and in-hospital mortality of 45 eligible patients receiving cardiologist-managed PCPS from July 2012 to January 2019 in our institute. We compared different prognostic scores [namely Survival After Veno-arterial ECMO (SAVE), modified SAVE, prEdictioN of Cardiogenic shock OUtcome foR acute myocardial infarction patients salvaGed by VA-ECMO (ENCOURAGE), and Sequential Organ Failure Assessment (SOFA) scores] through area under the receiver operating characteristic curve (AUC) analysis. RESULTS: The patients' mean age was 64.3 ± 11.3 years, and 71.1% were men. The overall in-hospital survival rate was 35.6%. Compared to survivors, nonsurvivors were more likely to have an ischemic etiology, cardiopulmonary resuscitation, and higher lactate levels. Survivors had higher SAVE (-5.9 vs. -11.4) and modified SAVE (4.2 vs. -7.1) scores than nonsurvivors (both p = 0.001), but SOFA (9.7 vs. 10.3) and ENCOURAGE (24.8 vs. 26.8) scores were similar (both p > 0.1). In multivariate models, only modified SAVE score remained statistically significant (hazard ratio: 0.96, 95% confidence interval: 0.93-1.00; p = 0.047). Modified SAVE score showed the best risk discrimination (AUC = 0.78). CONCLUSIONS: Establishing regular and continual training protocols can enable cardiologists to perform emergency PCPS (without on-site surgery) and daily care for patients with refractory cardiogenic shock. The modified SAVE score facilitates risk stratification and future decision-making processes.

Effect of PHRs and PCPs on Microalgal Growth, Metabolism and Microalgae-Based Bioremediation Processes: A Review.

In this review, the effect of pharmaceuticals (PHRs) and personal care products (PCPs) on microalgal growth and metabolism is reported. Concentrations of various PHRs and PCPs that cause inhibition and toxicity to growths of different microalgal strains are summarized and compared. The effect of PHRs and PCPs on microalgal metabolism (oxidative stress, enzyme activity, pigments, proteins, lipids, carbohydrates, toxins), as well as on the cellular morphology, is discussed. Literature data concerning the removal of PHRs and PCPs from wastewaters by living microalgal cultures, with the emphasis on microalgal growth, are gathered and discussed. The potential of simultaneously bioremediating PHRs/PCPs-containing wastewaters and cultivating microalgae for biomass production in a single process is considered. In the light of reviewed data, the feasibility of post-bioremediation microalgal biomass is discussed in terms of its contamination, biosafety and further usage for production of value-added biomolecules (pigments, lipids, proteins) and biomass as a whole.

An educational initiative in response to identified PrEP prescribing needs among PCPs in the Southern U.S.

Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but many primary care physicians (PCPs) have not incorporated PrEP into practice. While PrEP may be a key strategy to reducing high HIV transmission rates in the southern US, knowledge about PrEP prescribing patterns among PCPs in this region is lacking. An online survey was sent to a large network of PCPs at an academic medical center in North Carolina in October 2015. The survey was repeated in September 2016, after an educational intervention that included on-site trainings at 14 PCP offices. Chi-square tests were used to compare PrEP prescribing patterns among providers. The initial survey was sent to 389 PCPs, with 115 (30%) responding. Of these, 78% reported seeing men who have sex with men (MSM). Only 17% had prescribed PrEP. The most frequently identified barrier was lack of knowledge (60%). When the survey was repeated after the educational initiative, 79 PCPs (20%) responded. Of these, 90% reported seeing MSM, and 35% had prescribed PrEP. PCPs who had attended a training were more likely to have prescribed PrEP (OR 4.84, CI 1.77-13.21). In conclusion, PrEP prescribing among PCPs in the southern US is low. A survey among PCPs identified lack of knowledge as a barrier to prescribing, motivating an institutional-wide educational campaign in response. Further efforts are needed to continue to raise awareness and educate PCPs in the South about PrEP.

Synthetic Musks: A Class of Commercial Fragrance Additives in Personal Care Products (PCPs) Causing Concern as Emerging Contaminants.

Synthetic musks (SMs) are promising fragrance additives used in personal care products (PCPs). The widespread presence of SMs in environmental media remains a serious risk because of their harmful effects. Recently, the environmental hazards of SMs have been widely reported in various environmental samples including those from coastal and marine regions. This paper provides a systematic review of SMs, including their classification, synthetic routes, analysis and occurrence in environmental samples, fate and toxicity in the environment, as well as the associated risk assessment and pollution control. Research gaps and future opportunities were also identified with the hope of raising interest in this topic.

Commercial personal care product mixtures exhibit hormetic concentration-responses to Vibrio qinghaiensis sp.-Q67.

The biological effects related to personal care products (PCPs) are almost induced by some active ingredients in the PCPs rather than the PCP itself. In this study, 23 common and widely used toner, skin water, and make-up water (TSM) commodities were directly taken as mixture samples, and Vibrio qinghaiensis sp.-Q67 (Q67) was used as the test organism. The toxicities of the TSMs to Q67 were determined via microplate toxicity analysis at 0.25 h and 12 h. Each TSM commodity can be regarded as a complicated mixture (relative concentration is 1). It was shown that the concentration-response curves (CRCs) of 23 TSMs are monotonic sigmoid-shaped (S-shaped) at 0.25 h, the CRCs of six TSMs are also S-shaped but the other 17 TSMs are non-monotonic hormetic or J-shaped at 12 h. In addition, to effectively characterize the nature of the stimulation and inhibition phases, it is suggested that five parameters such as the ECL (the median stimulation effective concentration (left)), Emin (the maximum stimulation effect), ECmin (the maximum stimulation effective concentration), ZEP (zero effect point where the effect is 0 and the concentration is ZEP), and EC50 can depict the non-monotonic CRC. To the best of our knowledge, this is the first study about the hormetic CRCs of commercial PCP mixtures.

Long-term clinical results of acute myocardial infarction at the left main trunk requiring percutaneous cardiopulmonary support.

The clinical results of patients with acute myocardial infarction (AMI) at the left main trunk (LMT) remain unclear, especially in cases requiring percutaneous cardiopulmonary support (PCPS). Twenty seven cases of AMI at the LMT requiring emergent PCPS were retrospectively investigated. These 27 patients were aged 44-83 years (65.6 ± 8.6 years) and 20 (81.5%) were men. Peak creatine kinase (CK) leakage ranged from 538 to 34,010 IU/l (13,553 ± 7656 IU/l). Eight (29.6%) patients were discharged without mechanical support. Ten (37.0%) patients underwent left ventricular assist device (LVAD) implantation, five of whom with preoperative organ failure could not survive more than 6 months after implantation. The other nine (33.3%) patients died of low output syndrome or brain damage. The overall survival rates were 53.7, 41.3, 33.0, and 28.3% at 3 months, 6 months, 1 year, and 2 years, respectively. Multivariate analysis showed that Killip class 3/4 at hospital arrival was an independent risk factor for hospital mortality (odds ratio 20.4). Patients with more than 5 days of PCPS support period (n = 6), ≥ 4 h to revascularization (n = 6) or maximum CK leakage ≥20,000 IU/dl (n = 3) were not associated with successful PCPS or IABP weaning. The long-term clinical outcomes of patients with LMT disease requiring PCPS is devastating. Rapid cardiopulmonary resuscitation and coronary revascularization and timely insertion of LVAD before the onset of complications might lead to better survival.

Effects of pharmaceuticals and personal care products (PPCPs) on multixenobiotic resistance (MXR) related efflux transporter activity in zebrafish (Danio rerio) embryos.

Certain ATP binding cassette (ABC) transporter proteins, such as zebrafish Abcb4, are efflux pumps acting as a cellular defence against a wide range of different, potentially toxic chemical compounds thus mediating so called multixenobiotic resistance (MXR). Certain chemicals target MXR proteins and, as so called chemosensitisers, inhibit the activity of these proteins thus increasing the toxicity of other chemicals that would normally be effluxed. In this study 14 pharmaceuticals and personal care products (PPCPs) that are being increasingly detected in aquatic systems, were assessed for interference with the MXR system of zebrafish (Danio rerio). Concentration dependent effects of test compounds were recorded with the dye accumulation assay using zebrafish embryos and in ATPase assays with recombinant zebrafish Abcb4. In the dye accumulation assay embryos at 24h post fertilisation (hpf) were exposed to 8µm rhodamine 123 along with test compounds for 2h. The rhodamine 123 tissue levels upon the exposure served as a measure for MXR transporter efflux activity of the embryo (low rhodamine levels - high activity; high levels - low activity). The known ABC protein inhibitors MK571, vinblastine and verapamil served as positive controls. All tested PPCPs affected rhodamine 123 accumulation in embryos. For seven compounds rhodamine tissue levels were either both decreased and increased depending on the compound concentration indicating both stimulation and inhibition of rhodamine 123 efflux by those compounds, only increased (inhibition, six compounds) or only decreased (stimulation, one compound). Recombinant zebrafish Abcb4 was obtained with the baculovirus expression system and PPCPs were tested for stimulation/inhibition of basal transporter ATPase activity and for inhibition of the transporter ATPase activity stimulated with verapamil. Eight of the tested PPCPs showed effects on Abcb4 ATPase activity indicating that their effects in the dye accumulation assay may have indeed resulted from interference with Abcb4-mediated rhodamine 123 efflux. Slight stimulatory effects were found for musk xylene, nerol, isoeugenol, α-amylcinnamaldehyde, α-hexylcinnamaldehyde and simvastatin indicating Abcb4 substrate/competitive inhibitor properties of those compounds. Likewise, decreases of the verapamil-stimulated Abcb4 ATPase activity by diclofenac and fluoxetine may indicate competitive transporter inhibition. Sertraline inhibited the basal and verapamil-stimulated Abcb4 ATPase activities suggesting its property as non-competitive Abcb4 inhibitor. Taken together, our finding that chemically diverse PPCPs interfere with MXR efflux activity of zebrafish indicates that (1) efflux transporters may influence bioaccumulation of many PPCPs in fish and that (2) many PPCPs may act as chemosensitisers. Furthermore, it appears that interference of PPCPs with efflux activity in zebrafish embryos is not only from effects on Abcb4 but also on other efflux transporter subtypes.

Activated clotting time test alone is inadequate to optimize therapeutic heparin dosage adjustment during post-cardiopulmonary resuscitational extracorporeal membrane oxygenation (e-CPR).

BACKGROUND: We conducted an observational study to evaluate the relationship between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) tests, anticipating the possibility that the ACT will become a substitute test for the aPTT in post-CPR extracorporeal membrane oxygenation (e-CPR). PATIENTS AND METHODS: Three hundred and fifteen paired ACT and aPTT samples were derived from 60 in-hospital e-CPR patients and were divided into three groups according to the observed ACT value: low level (ACT < 170 s, Group A), intended target level (ACT 170-210 s Group B) and high level (ACT > 210 s, Group C). The relationship of aPTT in each group was analyzed. RESULTS: The mean ACT and aPTT values were 189.39 ± 48.27 s (IQR, 163-202) and 71.85 ± 45.32 s (IQR, 44.5-81.8), respectively. Although the observed mean ACT value of 189.39 s was similar to the intended mean target value of 190 s (p = 0.823), the observed mean aPTT value (71.85 s) was significantly lower than the predicted mean target value (77.5 s, p = 0.027). Despite the mean ACT values being significantly different in each group (p < 0.0001), the mean aPTT values were not statistically different between Groups A and B (p = 0.317). Of the Group B samples (n = 139), only 31 samples (22.3%) met the optimal therapeutic aPTT range. Pearson's correlation coefficient for Group B showed only a weak correlation between ACT and aPTT (r = 0.177; p = 0.037). CONCLUSIONS: Our study demonstrates that the ACT test alone does not seem to be enough to optimize therapeutic heparin dosage adjustment during e-CPR.

Platelets do not express the oxidized or reduced forms of tissue factor.

BACKGROUND: Expression of tissue factor (TF) antigen and activity in platelets is controversial and dependent upon the laboratory and reagents used. Two forms of TF were described: an oxidized functional form and a reduced nonfunctional form that is converted to the active form through the formation of an allosteric disulfide. This study tests the hypothesis that the discrepancies regarding platelet TF expression are due to differential expression of the two forms. METHODS: Specific reagents that recognize both oxidized and reduced TF were used in flow cytometry of unactivated and activated platelets and western blotting of whole platelet lysates. TF-dependent activity measurements were used to confirm the results. RESULTS: Western blotting analyses of placental TF demonstrated that, in contrast to anti-TF#5, which is directed against the oxidized form of TF, a sheep anti-human TF polyclonal antibody recognizes both the reduced and oxidized forms. Flow cytometric analyses demonstrated that the sheep antibody did not react with the surface of unactivated platelets or platelets activated with thrombin receptor agonist peptide, PAR-1. This observation was confirmed using biotinylated active site-blocked factor (F)VIIa: no binding was observed. Likewise, neither form of TF was detected by western blotting of whole platelet lysates with sheep anti-hTF. Consistent with these observations, no FXa or FIXa generation by FVIIa was detected at the surface of these platelets. Similarly, no TF-related activity was observed in whole blood using thromboelastography. CONCLUSION AND SIGNIFICANCE: Platelets from healthy donors do not express either oxidized (functional) or reduced (nonfunctional) forms of TF.

Phenylmethylsiloxanes in indoor dust from residential area of China: Source, occurrence, bioavailability and exposure assessment.

Phenylmethylsiloxanes, as modified products of dimethylsiloxanes, have been used in personal care products (PCPs) and household appliances, with indoor dust serving as one potential reservoir due to their particle-binding properties. This study measured six isomers of two phenylmethylsiloxanes (P3 and P4) in PCPs (99 %) intakes of phenylmethylsiloxanes for adults, while dust ingestion/adsorption (0.19 ng/d) may play important roles for toddlers/infants with little usage of phenylmethylsiloxanes-containing PCPs. Additionally, total daily intakes of PhMeSi(OH)2 (0.30-0.84 ng/d) via ingestion and dermal absorption of dust were higher than P3 (0.06-0.31 ng/d) and P4 (0.02-0.09 ng/d), suggesting exposure risk of degradation product of phenylmethylsiloxanes deserving attention.

Assessing Quality of Referrals to a Community-Based Chronic Pain Clinic.

Introduction: Because patients with chronic pain are complex, with significant medical and psychiatric comorbidities, referrals to specialty pain clinics are often necessary. The present study explores the quality of information submitted and the profile of referring physicians associated with rejected patient referrals by a community pain clinic. Methods: A retrospective cross-sectional study was conducted on a series of consecutive new patient referrals rejected by a noninterventional community pain clinic (November 2021-June 2022). Data were collected on the reasons for rejected referrals and physicians responsible for these referrals using the public database of the College of Physicians and Surgeons of Ontario. Results: During the study period, 120 new referrals made by 99 physicians (88% primary care providers, or PCPs; male : female ratio 1:1.2; 53% Canadian university graduates) were rejected because of inadequate information (62%) or because they were inappropriate (38%). Only 46% of the rejected referrals were resubmitted within a median of 7 days (range 0-96 days) and accepted. Half of the non-resubmitted referrals could have been accepted if the referring provider had sent in the missing information. Conclusion: A significant number of referrals to our pain clinic (primarily from PCPs) are rejected for mainly avoidable reasons. The process of rejected referrals and resubmissions requires 92 to 126 h of additional staff time/year. Without additional health care resources, our study highlights simple but effective improvements in the referral process that could facilitate patient care, avoid unnecessary delays, and decrease possible sources of patient complaints.

Introduction: Étant donné la complexité des patients atteints de douleur chronique, qui requièrent une prise en charge médicale adaptée et présentent souvent des comorbidités psychiatriques, il est souvent nécessaire de les référer à des cliniques spécialisées en matière de prise en charge de la douleur. Cette étude examine la qualité des informations fournies et le profil des médecins référents associés aux patients référés qui ont été refusés par une clinique communautaire de la douleur.Méthodes: Une étude transversale rétrospective a été menée sur une série de nouvelles références de patients refusées par une clinique communautaire non interventionnelle de la douleur (novembre 2021­ juin 2022). Des données ont été collectées sur les motifs de refus de ces références ainsi que sur les médecins responsables de ces références, en utilisant la base de données publique du Collège des médecins et chirurgiens de l'Ontario.Résultats: Au cours de la période à l'étude, 120 nouvelles références effectuées par 99 médecins (88 % étaient des fournisseurs de soins primaires; le ratio hommes-femmes était de 1:1,2; 53 % étaient des diplômés universitaires canadiens) ont été refusées en raison d'informations insuffisantes (62 %) ou parce qu'elles étaient inappropriées (38 %). Seulement 46 % des références refusées ont été soumises à nouveau dans un délai médian de sept jours (intervalle de 0 à 96 jours) et acceptées. La moitié des références qui n'ont pas été soumises à nouveau auraient pu être acceptées si le fournisseur référent avait envoyé les informations manquantes.Conclusion: De nombreuses références acheminées à notre clinique de la douleur (principalement par des fournisseurs de soins primaires) sont refusées pour des raisons le plus souvent évitables. Le processus de référence et de nouvelle soumission des références refusées nécessite de 92 à 126 heures de temps de personnel supplémentaire/an. Notre étude met en évidence des améliorations simples mais efficaces dans le processus de référencement qui pourraient faciliter les soins aux patients, éviter des retards inutiles et réduire les sources possibles de plaintes des patients, sans nécessiter de ressources supplémentaires en soins de santé.

Perceptions of Multicancer Detection Tests Among Primary Care Physicians and Laypersons: A Qualitative Study.

INTRODUCTION: Multicancer detection tests (MCDs) are blood-based tests designed to detect multiple cancer types. It is currently unclear whether these cancer screening tests improve mortality. To understand awareness of MCDs among providers and patients, as well as explore how they perceive the benefits, harms, and acceptability of MCDs, we have undertaken a focus group study in primary care physicians (PCPs) and laypersons to explore knowledge, attitudes, and expectations of cancer screening using MCDs. METHODS: We conducted six focus groups with 45 PCP participants and 12 focus groups with 80 layperson participants. Participants were identified via a consumer research firm and found eligible following the completion of a screener survey. Moderators used a semi-structured guide containing open-ended questions and prompts to facilitate the discussion. Recordings were transcribed and coded line by line using a codebook developed based on questions and emerging discussion concepts, and emergent themes were identified. RESULTS: Both PCP and layperson participants felt the that benefits of MCDs included ease of use and potential ability to detect cancers early. However, they felt that additional data is needed to overcome some of the concerns related to MCDs. PCP participants expressed concerns related to lack of practice guidelines, cost of diagnostic follow-ups, privacy and insurance issues, fear/anxiety related to confirmation of MCD results, and malpractice liability related to perceived false negative test results. Layperson participants expressed concerns related to costs, insurance coverage, and privacy, as well as anxiety over the confirmation of a positive test result. CONCLUSIONS: There is a major need for more rigorous data regarding MCDs to inform the development of guidelines for use as cancer screening tools.

Single Crystal to Single Crystal Transformation of Porous Materials Based on Zinc Nodes and Mercaptobenzoic Acid.

Porous coordination polymers (PCPs) are an excellent class of porous crystalline materials with tunable properties and intriguing potential applications spanning multiple disciplines. In this work, we report the synthesis and characterization of a PCP (HI-103) based on 4,4'-dithiodibenzoic acid ligand and zinc nitrate with two DMF molecules residing in the porous network. The stability of the porous network was analyzed by heating the compound at 60.0 °C for two days, and the structural analysis revealed a new PCP (HI-104) was formed with one of the DMF molecules, indicating a single-crystal to single-crystal (SCSC) transformation. The solvent molecules were completely removed by extensive drying (HI-103-dry), and the integrity of the porous network was verified by powder X-ray diffraction (PXRD) and thermogravimetric analysis. The reversibility of SCSC transformation was confirmed by treating HI-103-dry with DMF molecules, resulting in HI-103 after five days. The adsorption studies of HI-103-dry with other solvents revealed that SCSC transformation was not observed for DMA and DEA, but some structural changes were observed in the presence of DMSO. The adsorption studies performed in the presence of an equimolar mixture of DMF, DMA, and DMA indicated that HI-103-dry could selectively adsorb DMF molecules from the analogous mixture.