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Abstract Shannon entropy is a core concept in machine learning and information theory, particularly in decision tree modeling. To date, no studies have extensively and quantitatively applied Shannon entropy in a systematic way to quantify the entropy of clinical situations using diagnostic variables (true and false positives and negatives, respectively). Decision tree representations of medical decision-making tools can be generated using diagnostic variables found in literature and entropy removal can be calculated for these tools. This concept of clinical entropy removal has significant potential for further use to bring forth healthcare innovation, such as quantifying the impact of clinical guidelines and value of care and applications to Emergency Medicine scenarios where diagnostic accuracy in a limited time window is paramount. This analysis was done for 623 diagnostic tools and provided unique insights into their utility. For studies that provided detailed data on medical decision-making algorithms, bootstrapped datasets were generated from source data to perform comprehensive machine learning analysis on these algorithms and their constituent steps, which revealed a novel and thorough evaluation of medical diagnostic algorithms.

Introdução: O artigo apresenta informações referentes aos impactos iniciais da pandemia pela COVID-19 no sistema de saúde brasileiro, a partir do diagnóstico do 1º caso, em fevereiro de 2020. São abordados especialmente impactos económicos e relacionados ao diagnóstico laboratorial.

Posterior shoulder tightness (PST) is a common impairment implicated in the etiology of shoulder pain. Individuals participating in athletics have a predilection for PST, thus interventions to mitigate such tightness should be incorporated into training programs. This column presents exercises to address PST applicable to the asymptomatic and injured population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Randomized trials in selected patient populations have demonstrated dramatic reductions in the incidence of in-stent restenosis (ISR) following implantation of paclitaxel-eluting (PE) coronary stents compared with bare metal stents in native coronary disease. The clinical outcome following implantation of PE stents for saphenous vein graft (SVG) stenosis is largely unknown. AIM: To assess the safety and efficacy of PE coronary stents for the treatment of SVG stenosis in an unselected population. METHODS: All patients who received PE stents for the treatment of SVG disease from May 1, 2003, to May 1, 2005, were entered into a prospectively collected database. Fifty-five patients were identified with 69 lesions. In-hospital and late major adverse cardiac events (MACE) including death, myocardial infarction (MI), and target lesion revascularization (TLR) were recorded as well as the rate of target vessel revascularization (TVR). RESULTS: Mean follow-up was 13 months with 54 of the 55 patients contacted. The number of stents implanted was 1.12 +/- 0.37 per lesion and 1.38 +/- 0.59 per patient. Clinically significant procedural MACE was 0%. The late MACE rate was 9% with a 2% clinically driven TLR, a 4% coronary artery bypass graft (CABG), and a 4% TVR rate. There were four deaths, two cardiac and two noncardiac. CONCLUSION: PE stents appear safe and effective in the treatment of SVG disease at a mean follow-up time of 13 months. Randomized studies are needed to further delineate the optimal management of this high-risk group. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the frequency and timing of complications at our institution when surgery was performed within two months of coronary stent placement.Background: The optimal delay following coronary stent placement prior to non-cardiac surgery is unknown.Methods: We analyzed the Mayo Clinic Percutaneous Coronary Intervention and Surgical databases between 1990 and 2000 and identified 207 patients who underwent surgery in the two months following successful coronary stent placement.Results: Eight patients (4.0%) died or suffered a myocardial infarction or stent thrombosis. All 8 patients were among the 168 patients (4.8%, 95% confidence interval [CI] 2.1 to 9.2) undergoing surgery six weeks after stent placement; the frequency of these events ranged from 3.8% to 7.1% per week during each of the six weeks. No events occurred in the 39 patients undergoing surgery seven to nine weeks after stent placement (0%, 95% CI 0.0 to 9.0).Conclusions: These data suggest that, whenever possible, non-cardiac surgery should be delayed six weeks after stent placement, by which time stents are generally endothelialized, and a course of antiplatelet therapy to prevent stent thrombosis has been completed. [ABSTRACT FROM AUTHOR]

Introduction:Efficient laboratory services are the basis of modern health systems. Scientific innovations have contributed to substantial improvements in the laboratory environment, but errors still persist. These errors are classified as pre-analytical, analytical and post-analytical, according to the time of occurrence.Objective:To evaluate the frequency of pre-analytical errors in the clinical laboratory service of a military hospital.Methods:A total of 329,582 tests were performed in the clinical laboratory of Hospital Naval Marcílio Dias (HNMD) from August to October 2012, and pre-analytical errors were documented.Results:The most frequent cause of the observed pre-analytical errors was hemolysis (27.54%), followed by samples not received (25.43%) and insufficient sample volume (18.49%). The samples from the Integrated Home Care Service (SIAD) showed the highest frequency of errors (3.38%), followed by those from the inpatient (0.76%) and the outpatient departments (0.21%).Conclusion:Our study demonstrates the importance of managing laboratory pre-analytical quality in order to ensure service excellence.

Systematic review.

JUSTIFICATIVA E OBJETIVOS: O número de pacientes alérgicos ao látex vem aumentando significativamente. É essencial reconhecê-los para preve nir e aplicar o tratamento adequado. O objetivo do estudo foi avaliar a prevalência de alergia ao látex em pacientes com mielomeningocele. MATERIAIS E MÉTODOS: Foram avaliados, retrospectivamente, os prontuários médicos de pacientes com diagnóstico de mielomeningocele no período de janeiro de 2002 a dezembro de 2007. Os pacientes foram agrupados em alérgicos e não alérgicos. A comparação dos grupos em relação ao gênero foi feita pelo teste do Qui-quadrado, pelo teste t de Student em relação à idade, e o teste de Mann-Whitney para comparação entre os grupos em relação as manifestações clínicas de alergia, número de procedimentos sob anestesia, de internações hospitalares e de cateterizações vesicais. RESULTADOS: O número médio de procedimentos sob anestesia foi de 7 no grupo com alergia e 4 no grupo sem alergia, sendo esta diferença estatisticamente significante (p = 0,028). O número médio de internações hospitalares foi de 4,5 no grupo com alergia e 3,4 no grupo sem alergia e a média de cateterização vesical foi 24,5 nos alérgicos e 21,7 nos não alérgicos. CONCLUSÕES: Os pacientes portadores de mielomeningocele submetidos a múltiplos procedimentos sob anestesia apresentam alto risco de desenvolvimento de sinais clínicos de alergia ao látex. Há necessidade de que pacientes com diagnóstico de mielomeningocele sejam submetidos exclusivamente a procedimentos latex-free, evitando o alto risco de sensibilização e suas complicações. Testes específicos para avaliação da sensibilização, marcadores genéticos e relação látex-fruta poderão contribuir para melhor entendimento dos fatores de risco relacionados à alergia ao látex e formas de prevenção

A Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) lançou, em seu 44º Congresso Brasileiro de Patologia Clínica e Medicina Laboratorial, uma série de recomendações para minimizar os erros na fase pré-analítica, sendo este texto uma delas. Além do crescimento do mercado de testes moleculares, é frequente a percepção errônea de que esses testes são menos sujeitos a erros. Enfatizamos, neste documento, que certos cuidados na fase pré-analítica são extremamente importantes para garantir a confiabilidade de testes moleculares.The Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML) launched a series of recommendations on how to minimize errors on the pre-analytical testing phase during the 44th Brazilian Congress of Clinical Pathology and Laboratory Medicine. This is one of them. The molecular diagnostics market is growing fast and many people believe these tests are less error-prone. In this study we highlight that proper care during the pre-analytical phase is extremely important in order to ensure the reliability of molecular diagnostic tests.

Abstract In Tanzania, the first cases of schistosomiasis were reported in the early 19th century. Since then, various studies have reported prevalences of up to 100% in some areas. However, for many years, there have been no sustainable control programmes and systematic data from observational and control studies are very limited in the public domain. To cover that gap, the present article reviews the epidemiology, malacology, morbidity, and the milestones the country has made in efforts to control schistosomiasis and discusses future control approaches. The available evidence indicates that, both urinary and intestinal schistosomiasis are still highly endemic in Tanzania and cause significant morbidity.Mass drug administration using praziquantel, currently used as a key intervention measure, has not been successful in decreasing prevalence of infection. There is therefore an urgent need to revise the current approach for the successful control of the disease. Clearly, these need to be integrated control measures.

Abstract Background It is now well established that nearly 20% of human cancers are caused by infectious agents, and the list of human oncogenic pathogens will grow in the future for a variety of cancer types. Whole tumor transcriptome and genome sequencing by next-generation sequencing technologies presents an unparalleled opportunity for pathogen detection and discovery in human tissues but requires development of new genome-wide bioinformatics tools. Results Here we present CaPSID (Computational Pathogen Sequence IDentification), a comprehensive bioinformatics platform for identifying, querying and visualizing both exogenous and endogenous pathogen nucleotide sequences in tumor genomes and transcriptomes. CaPSID includes a scalable, high performance database for data storage and a web application that integrates the genome browser JBrowse. CaPSID also provides useful metrics for sequence analysis of pre-aligned BAM files, such as gene and genome coverage, and is optimized to run efficiently on multiprocessor computers with low memory usage. Conclusions To demonstrate the usefulness and efficiency of CaPSID, we carried out a comprehensive analysis of both a simulated dataset and transcriptome samples from ovarian cancer. CaPSID correctly identified all of the human and pathogen sequences in the simulated dataset, while in the ovarian dataset CaPSID’s predictions were successfully validated in vitro.

Abstract Background Amongst school-aged children living in malaria endemic areas, chronic morbidity and exacerbation of morbidity associated with other infections are often not coincident with the presence or levels of Plasmodium parasitaemia, but may result from long-term exposure to the parasite. Studies of hepatosplenomegaly associated with Schistosoma mansoni infection and exposure to Plasmodium infection indicate that differences that occur over 1–2 km in levels of Plasmodium transmission are related to the degree of exacerbation of hepatosplenomegaly and that Plasmodium falciparum schizont antigen (Pfs)-IgG3 levels may be a marker for the differing levels of exposure. Methods To investigate the validity of Pfs-IgG3 measurements as a tool to assess these comparative exposure levels on a microgeographical scale, cross-sectional community surveys were conducted over a 10 × 6 km study site in Makueni District, Kenya, during low and high malaria transmission seasons. During both high and low malaria transmission seasons, thick blood smears were examined microscopically and circulating Pfs-IgG3 levels measured from dried blood spot elute. GIS techniques were used to map prevalence of parasitaemia and Pfs-IgG3 levels. Results Microgeographical variations in prevalence of parasitaemia were observed during the high but not the low transmission season. Pfs-IgG3 levels were stable between high and low transmission seasons, but increased with age throughout childhood before reaching a plateau in adults. Adjusting Pfs-IgG3 levels of school-aged children for age prior to mapping resulted in spatial patterns that reflected the microgeographical variations observed for high season prevalence of parasitaemia, however, Pfs-IgG3 levels of adults did not. The distances over which age-adjusted Pfs-IgG3 of school-aged children fluctuated were comparable with those distances over which chronic morbidity has previous been shown to vary. Conclusion Age-adjusted Pfs-IgG3 levels of school-aged children are stable and when mapped can provide a tool sensitive enough to detect microgeographical variations in malaria exposure, that would be useful for studying the aetiology of morbidities associated with long-term exposure and co-infections.

OBJETIVO: Introduzir e familiarizar em nosso meio o uso do teste de químio-sensibilidade MTT avaliando a ação de agentes quimioterápicos sobre células tumorais de 30 doentes com câncer gástrico avançado. Correlacionar os resultados do teste MTT com os aspectos clínicos, anátomo-patológicos e estádio utlizando a mesma metodologia do estudo realizado em pacientes japoneses na Universidade de Keio, Japão. MÉTODO: Foi realizado o teste MTT em tumores de 30 pacientes com diagnóstico de adenocarcinoma gástrico, submetidos ao tratamento cirúrgico no Departamento de Cirurgia da Faculdade de Ciências Médicas da Santa Casa de São Paulo. Foram estudados in vitro os seguintes agentes quimioterápicos: mitomicina C, doxorrubicina, cisplatina e 5-fluorouracil. RESULTADOS: Os índices de atividade sobre células tumorais foram: 16,6% para a mitomicina C, 10,0% para a doxorrubicina, 6,6% para a cisplatina e 6,6% para o 5-fluorouracil. Os resultados do teste MTT não tiveram correlação com a idade, sexo, aspectos microscópicos e estádio (p0,05). CONCLUSÕES: A ação dos agentes quimioterápicos estudados sobre células tumorais do câncer gástrico foi baixa. Os resultados da ação dos quimioterápicos in vitro não apresentou correlação estatística com a idade, sexo, aspectos microscópicos e estádio destes doentes. Utilizando a mesma metodologia, tanto em nosso meio como em pacientes japoneses, a quimio-sensibilidade se mostrou baixa em ambos os estudos, podendo-se deduzir também que os resultados da químiosensibilidade independe da etnia. Com o surgimento de novos agentes quimioterápicos, a expectativa é grande para melhores resultados na prática clínica. Com a utilização e difusão do teste MTT em nosso meio, poder-se-á criar protocolos e estudos multicêntricos para selecionar os quimioterápicos a serem utlizados.

ABSTRACT Background: Laboratory medicine is an important part of the health care system and directly contributes to preventive actions, diagnostics, treatment, and management of diseases. The level and quality of laboratory resources utilization have been frequently questioned. A dissemination of conflicting data regarding the amount of laboratory tests not accessed by the requesting doctors or by the patients themselves is observed, although very often the sources and methodologies used to access these numbers are not properly clarified. Objective: The objective of this study was to obtain data on access to tests results performed in Brazilian private clinical analysis laboratories using the laboratory information system developed by SHIFT Consultoria e Sistemas (Consulting and Systems). Methods: The information was extracted from 81 laboratories, responsible for the performance of 93,240,651 tests, collected from 7,067,087 patients. Results: The total number of tests not accessed, considering all the regions, was 5,071,454, corresponding to a proportion of 5.4%. Due to the potential risks of adverse events or impacts on diagnostic and treatment management, including the economic impacts due to prolonged hospitalization time, the 17.9% proportion which was found to correspond to “not accessed” tests showing “abnormal” results. It is of particular concern, mainly if we observe that from these, 2.5% were related to “abnormal” test results processed by laboratories working in hospital units. Conclusion: Due to the relevance of the theme, Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML), will keep encouraging the monitoring and utilization of adequate laboratory resources, in order to enable sustainable health care systems.

Introduction: Both the quadratus lumborum block (QLB) and the pericapsular nerve group (PENG) block provide effective postoperative analgesia after hip surgery while minimizing the impact on motor function. This study aimed to compare QLB and PENG in patients undergoing primary total hip arthroplasty (THA)., Methods: This superiority trial randomized patients scheduled for elective THA to receive a lateral QLB or a PENG with a lateral femoral cutaneous nerve (LFC) block for postoperative analgesia. Perioperative analgesic protocols were standardized. The primary outcome was postoperative cumulative opioid consumption measured over time up to 72 hours. Secondary outcomes included postoperative pain scores in the first 72 hours, time to ambulation, length of stay, and patient-reported functional outcome measures (Hip disability and Osteoarthritis Outcome Score for Joint Replacement and Patient-Reported Outcome Measures Information System-10 scores)., Results: This trial consented and randomized 106 subjects and 101 were included in the analysis: PENG (n=50), QLB (n=51). Mean (95% CI) opioid consumption in intravenous morphine milligram equivalents differed at 36 hours (mean difference (95% CI), 18.0 (0.80, 35.1); p = 0.040), 48 hours (23.0 (5.20, 40.8); p=0.011), 60 hours (28.0 (9.24, 46.7); p=0.004), and 72 hours (33.0 (13.0, 53.0); p=0.001). There were no significant differences between treatment arms in average resting pain score, time to ambulation, rate of same-day discharge, length of stay, or patient-reported functional outcomes., Conclusion: While both lateral QLB and PENG block+LFC block are effective analgesic methods for patients undergoing THA, patients receiving lateral QLB had decreased cumulative opioid consumption from 36 to 72 hours postoperative and lower pain scores with movement compared with patients receiving PENG+LFC blocks., Trial Registration Number: NCT05710107., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The quadratus lumborum block (QLB) and the pericapsular nerve group (PENG) block both provide effective postoperative analgesia after hip surgery while minimizing impact on motor function. This study aimed to compare QLB and PENG in patients undergoing primary total hip arthroplasty., Methods: This superiority trial randomized patients scheduled for elective total hip arthroplasty to receive a lateral QLB or PENG with lateral femoral cutaneous nerve blocks for postoperative analgesia. Perioperative analgesic protocols were standardized. The primary outcome was postoperative cumulative opioid consumption at 72 hours. Secondary outcome was postoperative pain scores. Additional outcomes of interest included time to first ambulation, length of stay, patient reported outcome measures, and opioid-related side effects., Results: This trial consented and randomized 106 subjects and 101 were included in analysis: PENG (n=50), QLB (n=51). Mean (95% CI) opioid consumption (IV MME) in the first 72 hours did not differ between PENG [109.6 (93.6, 125.6)] and QL [92.3 (76.6, 107.9)] groups (p=0.129) There were no significant differences between treatment arms in average pain score, time to ambulation, distance ambulated, rate of same day discharge, or hospital length of stay. There were also no differences in patient reported outcomes using HOOS-JR and PROMIS-10 scores., Conclusion: Patients undergoing primary THA receiving preoperative PENG vs QLB had similar opioid consumption, pain scores, time to ambulation, and hospital length of stay. Both QL and PENG blocks are analgesic options in patients undergoing primary THA., Clinical Trials Registration: NCT05710107; www.ClinicalTrial.gov IRB Protocol ID: Pro00124880., Key Message: Pericapsular nerve group (PENG) block may provide analgesia after hip arthroplasty and improve early functional recovery. This study evaluated postoperative opioid consumption in patients randomized to PENG or lateral quadratus lumborum block (QLB).Opioid consumption, pain scores, motor recovery, and functional outcome measures did not differ in patients randomized to PENG vs lateral QLB.PENG and lateral QLBs are analgesic options following total hip arthroplasty with similar rates of same day discharge.

Nonopioid analgesics serve to improve analgesia and limit side effects and risks of perioperative opioids. N-acetylcysteine (NAC), the primary treatment of acetaminophen toxicity, may have perioperative indications, including analgesia. NAC impacts glutathione synthesis, oxidant scavenging, glutamate receptor modulation and neuroinflammation. Potential perioperative benefits include arrhythmia prevention after cardiac surgery, decreased contrast-induced nephropathy, improved post-transplant liver function and superior pulmonary outcomes with general anesthesia. NAC may improve perioperative analgesia, with some studies displaying a reduction in postoperative opioid use. NAC is generally well tolerated with an established safety profile. NAC administration may predispose to gastrointestinal effects, while parenteral administration may carry a risk of anaphylactoid reactions, including bronchospasm. Larger randomized trials may clarify the impact of NAC on perioperative analgesic outcomes.

Aim: N-acetylcysteine (NAC) decreases inflammation and could augment perioperative analgesia. Materials & methods: This prospective pilot trial examined postoperative opioid consumption at 12 h following intraoperative NAC. In phase I, 20 adults scheduled for posterior spine surgery were randomized to NAC (0, 50, 100 and 150 mg/kg) to determine the optimal dose. In phase II, 30 patients were randomized to placebo or NAC (150 mg/kg). Opioid consumption, pain ratings and time to opioid rescue were recorded. Results: Postoperative opioid consumption was reduced in the NAC group 19.3% at 12 h and 20% at 18 and 36 h. Opioid consumption was reduced 22-24% in the NAC group at all times after adjusting for intraoperative opioid administration. NAC subjects reported lower pain scores relative to placebo. Conclusion: Subjects randomized to NAC consumed less postoperative opioids and reported less pain versus placebo. Larger randomized controlled trials are needed to further evaluate NAC for analgesia. Clinical Trial Registration : NCT04562597 (ClinicalTrials.gov).

Glucagon-like peptide 1 (GLP-1) receptor agonists have surged in popularity for the treatment of both diabetes mellitus and obesity. While GLP-1 reduces proximal gastrointestinal motility and delays gastric emptying, the impact of these medications on adequate fasting before surgery is not clear. We present 2 cases of particulate gastric contents after following appropriate presurgical fasting in diabetic patients taking GLP-1 receptor agonists and review current literature regarding perioperative implications of these drugs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

The National Heart, Lung, and Blood Institute-funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best predict a diagnosis of myeloid malignancy and among those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a positive predictive value (PPV) of 0.84 and negative predictive value (NPV) of 0.8 with an area under the receiver operating characteristic curve (AUROC) of 0.85 when classifying patients as having myeloid vs no myeloid malignancy based on variant allele frequencies (VAFs) in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as having MDS vs non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard)., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Aim: Anesthesia for cardiac surgery has evolved toward fast-track recovery strategies incorporating non opioid analgesics and regional anesthesia. Materials & methods: This retrospective cohort study compared opioid consumption, pain scores and length of stay in patients who underwent cardiac surgery via median sternotomy and did or did not receive preoperative parasternal intercostal plane block catheters with postoperative ropivacaine infusions. Results: Postoperative opioid consumption and postoperative pain scores did not differ. Blocks were associated with decreased intraoperative opioids and reduced length of stay in the intensive care unit and hospital. Conclusion: Parasternal intercostal plane block catheters were not associated with decreased postoperative opioid consumption or pain scores, but were associated with reduced intraoperative opioids and length of stay.

Laser micro-irradiation across the nucleus rapidly generates localized chromatin-associated DNA lesions permitting analysis of repair protein recruitment in living cells. Recruitment of three fluorescently-tagged base excision repair factors [DNA polymerase β (pol β), XRCC1 and PARP1], known to interact with one another, was compared in gene-deleted mouse embryonic fibroblasts and in those expressing the endogenous factor. A low energy micro-irradiation (LEMI) forming direct single-strand breaks and a moderate energy (MEMI) protocol that additionally creates oxidized bases were compared. Quantitative characterization of repair factor recruitment and sensitivity to clinical PARP inhibitors (PARPi) was dependent on the micro-irradiation protocol. PARP1 recruitment was biphasic and generally occurred prior to pol β and XRCC1. After LEMI, but not after MEMI, pol β and XRCC1 recruitment was abolished by the PARPi veliparib. Consistent with this, pol β and XRCC1 recruitment following LEMI was considerably slower in PARP1-deficient cells. Surprisingly, the recruitment half-times and amplitudes for pol β were less affected by PARPi than were XRCC1 after MEMI suggesting there is a XRCC1-independent component for pol β recruitment. After LEMI, but not MEMI, pol β dissociation was more rapid than that of XRCC1. Unexpectedly, PARP1 dissociation was slowed in the absence of XRCC1 as well with a PARPi after LEMI but not MEMI, suggesting that XRCC1 facilitates PARP1 dissociation from specific DNA lesions. XRCC1-deficient cells showed pronounced hypersensitivity to the PARPi talazoparib correlating with its known cytotoxic PARP1 trapping activity. In contrast to DNA methylating agents, PARPi only minimally sensitized pol β and XRCC1-deficient cells to oxidative DNA damage suggesting differential binding of PARP1 to alternate repair intermediates. In summary, pol β, XRCC1, and PARP1 display recruitment kinetics that exhibit correlated and unique properties that depend on the DNA lesion and PARP activity revealing that there are multiple avenues utilized in the repair of chromatin-associated DNA., Competing Interests: Declaration of Competing interest The authors declare there is no conflict of interest. There was no financial or non-financial assistance provided by a third party for the reported work. There are no patents or copyrights relevant to this work., (Published by Elsevier B.V.)

Background: Anaesthesia providers often work at a variety of perioperative and procedural locations. However, the layout of anaesthesia supplies and equipment is often inconsistent from operating theatre to operating theatre. This lack of standardisation may create delays in identification and retrieval of supplies. The primary goal of this study was to compare the duration of time required by anaesthesia providers to identify and retrieve a list of anaesthesia supplies prior to and after standardisation of the location for anaesthesia supplies., Methods: In this observational simulation study, a pre-set list of ten items that may be rapidly needed when caring for patients was created. Volunteer anaesthesia providers were then timed retrieving these in two different operating theatres before and after anaesthesia cart standardisation. Cumulative time to retrieve all items was recorded in seconds. Participants were evaluated regarding mean time to compete the task before and after supply standardisation. Paired t-test were used to assess mean time to retrieve the ten items both before and after standardisation and between the two operating theatre locations. Providers were also evaluated on their familiarity with the operating theatre location, and this was assessed by chi-square tests of homogeneity. Multivariable generalised linear modelling was used to evaluate the impact of covariables on the change in time., Results: Data from 18 anaesthesia providers was collected. Mean (95% confidence interval) time in seconds to retrieve items was decreased by 45% after supply standardisation (105.3 [88.6, 121.9 vs 57.1 [50.8, 63.5]; p < 0.001) with a mean (95% confidence interval) reduction of 48.1 seconds (30.6, 65.6; p < 0.001). Providers who worked primarily at that location also had faster times to complete the task. In a multivariable regression model that considered both the provider's familiarity with the location and the simulation attempt (Operating theatre 1 or Operating theatre 2), the mean time to retrieve all items remained reduced by 48.1 seconds (95% confidence interval: 31.9-64.4) after supply standardisation (p < 0.001)., Conclusion: Standardisation of the location for anaesthesia supplies decreased the time for on-demand item retrieval. Retrieval times were most improved after standardisation for providers in an unfamiliar area. Supply standardisation of anaesthesia carts across perioperative and procedural sites could result in more timely interventions in patient care and efficiency.

Background: Electrical storm can be challenging to treat, requiring a multidisciplinary team to coordinate medical management and invasive procedures. As the stellate ganglion provides efferent sympathetic outflow to the myocardium, stellate ganglion blocks (SGB) can be used to combat ventricular arrhythmias that arise from sympathetic overactivity. Data are scarce regarding SGB catheters as a treatment for electrical storm. We reviewed our use of SGB catheters for refractory electrical storm using our pathway collaboratively developed by critical care, cardiology, and regional anesthesia teams., Methods: We conducted a retrospective cohort study of patients who underwent an SGB for electrical storm between January 2020 and April 2022 in our cardiovascular intensive care unit. The primary outcome was the sustained cessation of electrical storm for 24 hours., Results: Upon chart review, 27 patients were identified and 11 met inclusion criteria. Cessation of electrical storm for 24 hours was achieved in 90% (n=10) of patients after left SGB. Similarly, 90% (n=10) had no documented episodes of ventricular arrhythmias requiring intervention within 6 hours after SGB., Conclusions: SGBs can interrupt or treat electrical storm. SGB catheters allow for prolonged arrhythmia cessation without repeated blocks and decrease the risk of repeat episodes of ventricular arrhythmias., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The double-strand break (DSB) repair pathway called microhomology-mediated end-joining (MMEJ) is thought to be dependent on DNA polymerase theta (Polθ) and occur independently of nonhomologous end-joining (NHEJ) factors. An unresolved question is whether MMEJ is facilitated by a single Polθ-mediated end-joining pathway or consists of additional undiscovered pathways. We find that human X-family Polλ, which functions in NHEJ, additionally exhibits robust MMEJ activity like Polθ. Polλ promotes MMEJ in mammalian cells independently of essential NHEJ factors LIG4/XRCC4 and Polθ, which reveals a distinct Polλ-dependent MMEJ mechanism. X-ray crystallography employing in situ photo-induced DSB formation captured Polλ in the act of stabilizing a microhomology-mediated DNA synapse with incoming nucleotide at 2.0 Å resolution and reveals how Polλ performs replication across a DNA synapse joined by minimal base-pairing. Last, we find that Polλ is semisynthetic lethal with BRCA1 and BRCA2. Together, these studies indicate Polλ MMEJ as a distinct DSB repair mechanism., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Pregnancy is a critical time to provide access to substance use treatment; this is especially true among incarcerated populations, who are known to be at particularly high risk of poor health outcomes. In this integrated literature review, we (1) report what is known about the prevalence of substance use among incarcerated pregnant and postpartum populations; (2) describe substance use treatment programs and current care practices of pregnant and postpartum populations in carceral settings; and (3) explore recommendations and strategies for increasing access to substance use treatment for incarcerated pregnant and postpartum populations. A comprehensive search of seven electronic databases yielded in the retrieval of 139 articles that were assessed for inclusion. Of the retrieved articles, 33 articles met criteria for inclusion in this review. A review of the literature revealed that the understanding of substance use prevalence among pregnant incarcerated women is limited. We also found that treatment of substance use disorders among pregnant and postpartum populations is not routinely available, enhanced perinatal services are sorely needed, and substance use treatment programs are feasible with the help of community partnerships. More research is required to understand current substance use treatment initiatives and outcomes for pregnant women in prison. In addition, strategies for integrating evidence-based, substance use treatment in carceral settings is also needed. Future directions are discussed.

RNA is modified by hundreds of chemical reactions and folds into innumerable shapes. However, the regulatory role of RNA sequence and structure and how dysregulation leads to diseases remain largely unknown. Here, we uncovered a mechanism where RNA abasic sites in R-loops regulate transcription by pausing RNA polymerase II. We found an enhancer RNA, AANCR, that regulates the transcription and expression of apolipoprotein E (APOE). In some human cells such as fibroblasts, AANCR is folded into an R-loop and modified by N-glycosidic cleavage; in this form, AANCR is a partially transcribed nonfunctional enhancer and APOE is not expressed. In contrast, in other cell types including hepatocytes and under stress, AANCR does not form a stable R-loop as its sequence is not modified, so it is transcribed into a full-length enhancer that promotes APOE expression. DNA sequence variants in AANCR are associated significantly with APOE expression and Alzheimer's Disease, thus AANCR is a modifier of Alzheimer's Disease. Besides AANCR, thousands of noncoding RNAs are regulated by abasic sites in R-loops. Together our data reveal the essentiality of the folding and modification of RNA in cellular regulation and demonstrate that dysregulation underlies common complex diseases such as Alzheimer's disease., (Published by Oxford University Press on behalf of Nucleic Acids Research 2022.)

Purpose: The purpose of this study was to examine enhanced perinatal support programs for pregnant and postpartum people in six state prisons, describe the service components offered by each program, and discuss similarities and differences of services offered between programs., Methods: In-depth, semi-structured interviews were conducted with each program's site lead(s) in order to collect information regarding each program's historical context, conception, and key aspects of the implementation of service components offered at each site., Results: Program components fell into five broad categories: group-based education and support, one-on-one support, labor and birth support, lactation facilitation and support, and other support services. Results highlight similarities and differences within and across programs and common themes that govern program success., Conclusions: This study provides an initial understanding of the variation in enhanced perinatal programming in six state prisons and offers insights for other states interested in establishing these types of programs. These programs implemented individual components piecemeal to fit site-specific context and needs, instead of adopting the entirety of another program model. Programs' success was largely dependent upon collaboration between program facilitators and partnering prison sites.

Introduction: Effective analgesia after total hip arthroplasty must minimize pain and optimize early ambulation. Lumbar plexus blocks (LPBs) provide analgesia but may cause motor weakness. Quadratus lumborum blocks (QLBs) may provide analgesia with preserved motor strength., Methods: This trial randomized subjects scheduled for elective hip arthroplasty to receive an LPB or lateral QLB for postoperative analgesia. The primary outcome was opioid consumption at 12-hour postoperative. Non-inferiority of lateral QLBs compared with LPBs was conducted using a one-sided two-sample t-test. Secondary outcomes included pain scores, cumulative opioid consumption, quadriceps strength, time to ambulation, and distance ambulated. Differences in pain scores and opioid consumption over time between groups were evaluated using a linear mixed model., Results: The trial consented and randomized 111 subjects and 103 completed the study: LPB (n=50) and lateral QLB (n=53). Mean (95% CI) cumulative opioid consumption (mg) at 12-hour postoperative was not found to be non-inferior in the lateral QLB (15.9 (12.7 to 19.2)) vs the LPB (12.7 (10.2 to 15.1)) group (p=0.625). Pain scores in postoperative anesthetic care unit (PACU) and 24-hour postoperative did not differ. The maximum distance ambulated did not differ, but lateral QLB patients were 2.4 times more likely to ambulate in the first 12 hours (p=0.024) and had significantly greater quadriceps strength in PACU (p<0.001)., Discussion: Although we were unable to demonstrate non-inferiority for opioid consumption at 12-hour postoperative, strength and mobilization were improved in lateral QLB subjects., Trial Registration Number: NCT04402437., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

DNA repair in the context of chromatin is poorly understood. Biochemical studies using nucleosome core particles, the fundamental repeating unit of chromatin, show most DNA repair enzymes remove DNA damage at reduced rates as compared to free DNA. The molecular details on how base excision repair (BER) enzymes recognize and remove DNA damage in nucleosomes have not been elucidated. However, biochemical BER data of nucleosomal substrates suggest the nucleosome presents different structural barriers dependent on the location of the DNA lesion and the enzyme. This indicates the mechanisms employed by these enzymes to remove DNA damage in free DNA may be different than those employed in nucleosomes. Given that the majority of genomic DNA is assembled into nucleosomes, structural information of these complexes is needed. To date, the scientific community lacks detailed protocols to perform technically feasible structural studies of these complexes. Here, we provide two methods to prepare a complex of two genetically fused BER enzymes (Polymerase β and AP Endonuclease1) bound to a single-nucleotide gap near the entry-exit of the nucleosome for cryo-electron microscopy (cryo-EM) structural determination. Both methods of sample preparation are compatible for vitrifying quality grids via plunge freezing. This protocol can be used as a starting point to prepare other nucleosomal complexes with different BER factors, pioneer transcription factors, and chromatin-modifying enzymes.