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Morgan Allyn Sendzischew Shane,1 Johannah Ruddy,2 Michael Cline,3 David P Rosenbaum,4 Susan Edelstein,4 Baharak Moshiree5 1Division of Gastroenterology and Digestive Disease, University of Miami, Miami, FL, USA; 2Patient Advocacy, Ardelyx, Inc., Waltham, MA, USA; 3Department of Gastroenterology, Cleveland Clinic, Cleveland, OH, USA; 4Clinical Research, Ardelyx, Inc., Waltham, MA, USA; 5Division of Gastroenterology, Advocate Health Wake Forest Medical University, Charlotte, NC, USACorrespondence: Baharak Moshiree, Advocate Health Wake Forest Medical University, Morehead Medical Plaza, 1025 Morehead Dr, Suite 300, Charlotte, NC, 28204, USA, Email Baha.Moshiree@atriumhealth.orgAbstract: Irritable bowel syndrome (IBS) is a common disorder of the gut–brain axis. IBS with constipation (IBS-C) accounts for approximately one-third of IBS cases and is associated with substantial burden of illness and decreased quality of life. This narrative review provides an overview of the current and upcoming treatment options and disease management for IBS-C from a US perspective and discusses the importance of the relationship between patient and health care provider in diagnosis and treatment. A positive diagnostic strategy for IBS-C is recommended, based on clinical history, physical examination, and minimal laboratory tests. An effective communication strategy between patients and health care professionals is essential to ensure early diagnosis and reduce both health care costs and overall disease burden. Treatment typically begins with lifestyle interventions and nonpharmacologic options, such as dietary interventions, fiber supplements, and osmotic laxatives. In patients with inadequate response to these therapies, 4 currently available therapies (lubiprostone, linaclotide, plecanatide, and tenapanor) approved by the US Food and Drug Administration may relieve IBS-C symptoms. These agents are generally well tolerated and efficacious in improving IBS-C symptoms, including constipation and abdominal pain. In patients with persistent abdominal pain and/or psychological symptoms, brain–gut behavioral therapy or neuromodulator therapy may be beneficial.Keywords: irritable bowel syndrome with predominant constipation, tenapanor, lubiprostone, linaclotide, plecanatide

Brian E Lacy,1 David Rosenbaum,2 Susan Edelstein,2 Kenji Kozuka,2 Laura A Williams,2 David C Kunkel3 1Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA; 2Ardelyx, Inc, Waltham, MA, USA; 3Division of Gastroenterology, University of California San Diego, La Jolla, CA, USACorrespondence: Brian E Lacy, Division of Gastroenterology and Hepatology, Mayo Clinic, Davis Building, 4500 San Pablo Road, Jacksonville, FL, 32224, USA, Tel +1 904-953-6319, Fax +1 904-953-7366, Email lacy.brian@mayo.eduAbstract: Increased intestinal permeability has been identified as one of the many pathophysiological factors associated with the development of irritable bowel syndrome (IBS), a common disorder of gut–brain interaction. The layer of epithelial cells that lines the intestine is permeable to a limited degree, and the amount of paracellular permeability is tightly controlled to enable the absorption of ions, nutrients, and water from the lumen. Increased intestinal permeability to macromolecules can be triggered by a variety of insults, including infections, toxins from food poisoning, or allergens, which in turn cause an inflammatory response and are associated with abdominal pain in patients with IBS. This review article discusses increased intestinal permeability in IBS, focusing on IBS with constipation (IBS-C) through the lens of a patient case with a reported prior diagnosis of “leaky gut syndrome” upon initial contact with a gastrointestinal specialist. We review advantages and disadvantages of several methods of measuring intestinal permeability in patients and discuss when measuring intestinal permeability is appropriate in the therapeutic journey of patients with IBS-C. Furthermore, we discuss a possible mechanism of restoring the intestinal barrier to its healthy state through altering intracellular pH by inhibiting sodium-hydrogen exchanger isoform 3 (NHE3). Tenapanor is a minimally absorbed, small-molecule inhibitor of NHE3 that has been approved by the US Food and Drug Administration for the treatment of IBS-C in adults. Preclinical studies showed that tenapanor may restore the intestinal barrier in IBS-C by affecting the conformation of tight junction proteins via NHE3 inhibition to block the paracellular transport of macromolecules from the intestinal lumen. Testing for increased permeability in patients with IBS-C who experience abdominal pain may help inform the choice of therapeutics and alter patients’ misconceptions about “leaky gut syndrome”.Keywords: tenapanor, abdominal pain, leaky gut, gut permeability, IBS-C, tight junction protein, transepithelial resistance

Prashant Singh,1 Gregory S Sayuk,2 David P Rosenbaum,3 Susan Edelstein,3 Kenji Kozuka,3 Lin Chang4 1Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 2Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 3Ardelyx, Inc, Waltham, MA, USA; 4Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USACorrespondence: Prashant Singh, Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA, Tel +1 734 647 9252, Fax +1 734 936 9849, Email singhpr@med.umich.eduBackground: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults.Aim: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal pain.Findings: Abdominal pain is experienced through activation and signaling of nociceptive dorsal root ganglia that innervate the gut. These sensory afferent neurons may become hypersensitized through signaling of transient receptor potential cation channel subfamily V member 1 (TRPV1), resulting in reduced action potential thresholds. TRPV1 signaling is also a key component of the proinflammatory cascade involving mast cell responses to macromolecule exposure following permeation through the intestinal epithelium. Indirect evidence of this pathway is supported by observations of higher pain in association with increased intestinal permeability in patients with IBS. Tenapanor reduces intestinal sodium absorption, leading to increased water retention in the intestinal lumen, thereby improving gastrointestinal motility. In animal models of visceral hypersensitivity, tenapanor normalized visceromotor responses and normalized TRPV1-mediated nociceptive signaling.Conclusion: By improving gastrointestinal motility, decreasing intestinal permeability and inflammation, and normalizing nociception through decreased TRPV1 signaling, tenapanor may reduce visceral hypersensitivity, leading to less abdominal pain in patients with IBS-C. Therapies that have demonstrated effects on visceral hypersensitivity may be the future direction for meaningful abdominal pain relief for patients with IBS-C.Keywords: IBS-C, NHE3, abdominal pain, TRPV1, sodium absorption, intestinal permeability

The COVID-19 public health emergency (PHE) caused significant disruptions in the delivery of care, with in-person visits decreasing and telehealth use increasing. We investigated the impact of these changes on mental health services for Medicaid-enrolled adults and youth in Washington State. Among enrollees with existing mental health conditions, the first year of the PHE was associated with a surge in specialty outpatient mental health visits (13% higher for adults and 7% higher for youth), returning to pre-PHE levels in the second year. Conversely, youth with new mental health needs experienced a decline in specialty outpatient visit rates by ∼15% and 37% in the first and second years of the PHE, respectively. These findings indicate that while mental health service use was maintained or improved for established patients, these patterns did not extend to Medicaid-enrolled youth with new mental health needs, potentially due to barriers such as difficulty in finding providers and establishing new patient-provider relationships remotely. To bridge this gap, there is a need for a multi-faceted approach that includes improving service accessibility, enhancing provider availability, and optimizing initial care encounters, whether in-person or virtual, to better support new patients., Competing Interests: Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials. Author McConnell reports support from multiple grants from NIH, Arnold Ventures, Commonwealth Fund, Robert Wood Johnson Foundation; contracts with states of Washington and Oregon and an honorarium from the Genesis Research Group. Author Edelstein's time was supported by a grant from the National Institute of Mental Health. Author Wolk is supported by NIH grants and reports royalties from a textbook on childhood mental health and consulting fees from Massachusetts General Hospital to support a grant application. She also reports honoraria from Rutgers University Honorarium, Elwyn, Inc, and Behavior Analysis and Therapy Partners, and Participation on an Advisory Board at Penn. Author Lindner's time was supported by grants from NIH and contracts with the states of Oregon and Washington. Author Zhu reports grants from the NIHCM Foundation, AHRQ, NIMH, APA and payment for participation on an Advisory Board (Cambia Medical Policy Physician External Advisory Panel)., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

In contrast with the typical electric currents accelerated under the influence of a Coulombic force, there are only a few condensed matter examples of particles experiencing a force proportional to a constant, external magnetic field. In this Letter, we present a new alternative, based on an isotropic radiation spinning field and the magneto-optical effect, in which a particle is propelled by a magnetic field just like a magnetic monopole will do. This is a purely nonreciprocal effect as the reciprocal equivalent (a chiral dipole), despite presenting a dichroic response, does not experience any force when illuminated by the spinning field. The "magnetic charge" induced by impinging radiation on the magneto-optical dipole is found to depend linearly on the helicity of the field. In addition, this artificial monopole experiences a dichroic permanent optical torque and does not interact with an external electric field.

Because of increased risks of cardiovascular disease and death, patients with hyperphosphatemia receiving maintenance dialysis are advised to limit phosphorus consumption and are prescribed phosphate binders in an effort to better control serum phosphate concentrations. Because of large pill size, pill burden, and tolerability issues, phosphate binder adherence is relatively poor. On ingestion, phosphate is absorbed from the intestine via transcellular or paracellular transport. Data show that inhibiting sodium-hydrogen exchanger 3 modulates paracellular phosphate absorption (the predominant pathway in humans). Tenapanor is a first-in-class, minimally absorbed, phosphate absorption inhibitor that selectively inhibits sodium-hydrogen exchanger 3, with a mechanism distinct from, and complementary to, that of phosphate binders. In phase 3 and postregistrational studies, tenapanor conferred statistically significant and clinically meaningful reductions in serum phosphate in patients receiving maintenance dialysis with hyperphosphatemia. Here, we review the available preclinical and clinical data on the effects of tenapanor on controlling intestinal phosphate absorption., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hospital-acquired resistant infections (HARI) are infections, which develop 48 h or more after admission to a healthcare facility. HARI pose a considerably acute challenge, due to limited treatment options. These infections are associated bacterial biofilms, which act as a physical barrier to diverse external stresses, such as desiccation, antimicrobials and biocides. We assessed the influence of multiple factors on biofilm production by HARI -associated bacteria., Methods: Bacteria were isolated from samples of patients with respiratory HARI who were hospitalized during 2020-2022 in north Israel. Following antibiotic susceptibility testing by disc diffusion or broth microdilution, biofilm formation capacities of resistant bacteria (methicillin-resistant staphylococcus aureus, extended spectrum beta-lactamase-producing Escherichia coli and Klebsiela pneumonia, and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii) was assessed using the crystalline violet staining method. Data regarding season, time to infection, bacterial species, patient age and gender, year, and medical department were collected from the patient medical records., Results: Among the 226 study isolates, K. pneumonia was the most prevalent (35.4%) bacteria, followed by P. aeruginosa (23.5%), and methicillin-resistant staphylococcus aureus (MRSA) (21.7%). A significantly higher rate of HARI was documented in 2022 compared to 2020-2021. The majority of isolates (63.3%) were strong biofilm producers, with K. pneumonia (50.3%) being most dominant, followed by P. aeruginosa (29.4%). Biofilm production strength was significantly affected by seasonality and hospitalization length, with strong biofilm production in autumn and in cases where hospitalization length exceeded 30 days., Conclusion: Biofilm production by HARI bacteria is influenced by bacterial species, season and hospitalization length., (© 2024. The Author(s).)

The pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability, and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in bowel motility and a reduction in IBS-related pain; however, the mechanism by which tenapanor mediates these functions remains unclear. Here, the effects of tenapanor on colonic pain signaling and intestinal permeability were assessed through behavioral, electrophysiological, and cell culture experiments. Intestinal motility studies in rats and humans demonstrated that tenapanor increased luminal sodium and water retention and gastrointestinal transit versus placebo. A significantly reduced visceral motor reflex (VMR) to colonic distension was observed with tenapanor treatment versus vehicle in two rat models of visceral hypersensitivity (neonatal acetic acid sensitization and partial restraint stress; both P < 0.05), returning VMR responses to that of nonsensitized controls. Whole cell voltage patch-clamp recordings of retrogradely labeled colonic dorsal root ganglia (DRG) neurons from sensitized rats found that tenapanor significantly reduced DRG neuron hyperexcitability to capsaicin versus vehicle ( P < 0.05), an effect not mediated by epithelial cell secretions. Tenapanor also attenuated increases in intestinal permeability in human colon monolayer cultures caused by incubation with proinflammatory cytokines ( P < 0.001) or fecal supernatants from patients with IBS-C ( P < 0.005). These results support a model in which tenapanor reduces IBS-related pain by strengthening the intestinal barrier, thereby decreasing permeability to macromolecules and antigens and reducing DRG-mediated pain signaling. NEW & NOTEWORTHY A series of nonclinical experiments support the theory that tenapanor inhibits IBS-C-related pain by strengthening the intestinal barrier. Tenapanor treatment reduced visceral motor responses to nonsensitized levels in two rat models of hypersensitivity and reduced responses to capsaicin in sensitized colonic nociceptive dorsal root ganglia neurons. Intestinal permeability experiments in human colon monolayer cultures found that tenapanor attenuates increases in permeability induced by either inflammatory cytokines or fecal supernatants from patients with IBS-C.

Introduction: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness., Methods: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed., Results: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was -2.66 for tenapanor vs -2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week., Discussion: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Competing Interests: AJL is a consultant for Allergan, Ardelyx, Atmo, Allakos, BioAmerica, AEON, Arena, Takeda, Evoke Pharma, Ironwood Pharmaceuticals, Gemelli, Alkermes, Pfizer, OrthoMed, Vibrant, and has stock with Johnson & Johnson, Bristol Myer Squibb, and Allurion. SE and DPR are employees of Ardelyx, Inc. CR declares no conflict of interest. JDR declares no conflict of interest. WDC is a consultant for Abbvie, Ardelyx, Arena, Baush, Biomerica, Gemelli, Ironwood, Isothrive, Nestle, Progenity, Salix, Takeda, Urovant, and Vibrant, and has stock options with GI on Demand/Gastro Girl, Isothrive, and Modify Health.

Objectives: Non-contrast computed tomography of the brain (NCCTB) is commonly used to detect intracranial pathology but is subject to interpretation errors. Machine learning can augment clinical decision-making and improve NCCTB scan interpretation. This retrospective detection accuracy study assessed the performance of radiologists assisted by a deep learning model and compared the standalone performance of the model with that of unassisted radiologists., Methods: A deep learning model was trained on 212,484 NCCTB scans drawn from a private radiology group in Australia. Scans from inpatient, outpatient, and emergency settings were included. Scan inclusion criteria were age ≥ 18 years and series slice thickness ≤ 1.5 mm. Thirty-two radiologists reviewed 2848 scans with and without the assistance of the deep learning system and rated their confidence in the presence of each finding using a 7-point scale. Differences in AUC and Matthews correlation coefficient (MCC) were calculated using a ground-truth gold standard., Results: The model demonstrated an average area under the receiver operating characteristic curve (AUC) of 0.93 across 144 NCCTB findings and significantly improved radiologist interpretation performance. Assisted and unassisted radiologists demonstrated an average AUC of 0.79 and 0.73 across 22 grouped parent findings and 0.72 and 0.68 across 189 child findings, respectively. When assisted by the model, radiologist AUC was significantly improved for 91 findings (158 findings were non-inferior), and reading time was significantly reduced., Conclusions: The assistance of a comprehensive deep learning model significantly improved radiologist detection accuracy across a wide range of clinical findings and demonstrated the potential to improve NCCTB interpretation., Clinical Relevance Statement: This study evaluated a comprehensive CT brain deep learning model, which performed strongly, improved the performance of radiologists, and reduced interpretation time. The model may reduce errors, improve efficiency, facilitate triage, and better enable the delivery of timely patient care., Key Points: • This study demonstrated that the use of a comprehensive deep learning system assisted radiologists in the detection of a wide range of abnormalities on non-contrast brain computed tomography scans. • The deep learning model demonstrated an average area under the receiver operating characteristic curve of 0.93 across 144 findings and significantly improved radiologist interpretation performance. • The assistance of the comprehensive deep learning model significantly reduced the time required for radiologists to interpret computed tomography scans of the brain., (© 2023. The Author(s).)

Importance: Many states have moved from models that carve out to those that carve in or integrate behavioral health in their Medicaid managed care organizations (MCOs), but little evidence exists about the effect of this change., Objective: To assess the association of the transition to integrated managed care (IMC) in Washington Medicaid with health services use, quality, health-related outcomes, and measures associated with social determinants of health., Design, Setting, and Participants: This cohort study used difference-in-differences analyses of Washington State's 2014 to 2019 staggered rollout of IMC on claims-based measures for enrollees in Washington's Medicaid MCO. It was supplemented with interviews of 24 behavioral health agency leaders, managed care administrators, and individuals who were participating in the IMC transition. The data were analyzed between February 1, 2023, and September 30, 2023., Main Outcomes and Measures: Claims-based measures of utilization (including specialty mental health visits and primary care visits); health-related outcomes (including self-harm events); rates of arrests, employment, and homelessness; and additional quality measures., Results: This cohort study included 1 454 185 individuals ages 13 to 64 years (743 668 female [51.1%]; 14 306 American Indian and Alaska Native [1.0%], 132 804 Asian American and Pacific Islander [9.1%], 112 442 Black [7.7%], 258 389 Hispanic [17.8%], and 810 304 White [55.7%] individuals). Financial integration was not associated with changes in claims-based measures of utilization and quality. Most claims-based measures of outcomes were also unchanged, although enrollees with mild or moderate mental illness experienced a slight decrease in cardiac events (-0.8%; 95% CI, -1.4 to -0.2), while enrollees with serious mental illness experienced small decreases in employment (-1.2%; 95% CI -1.9 to -0.5) and small increases in arrests (0.5%; 95% CI, 0.1 to 1.0). Interviews with key informants suggested that financial integration was perceived as an administrative change and did not have substantial implications for how practices delivered care; behavioral health agencies lacked guidance on how to integrate care in behavioral health settings and struggled with new contracts and regulatory policies that may have inhibited the ability to provide integrated care., Conclusions and Relevance: The results of this cohort study suggest that financial integration at the MCO level was not associated with significant changes in most measures of utilization, quality, outcomes, and social determinants of health. Additional support, including monitoring, training, and funding, may be necessary to drive delivery system changes to improve access, quality, and outcomes.

Background: Tenapanor, a first-in-class, minimally systemic inhibitor of intestinal sodium/hydrogen exchanger isoform 3 (NHE3), is approved for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults based on two randomized, placebo-controlled, phase III studies (T3MPO-1 [NCT02621892], T3MPO-2 [NCT02686138]). The open-label T3MPO-3 extension study (NCT02727751) enrolled patients who completed these studies to investigate long-term safety and tolerability of tenapanor., Methods: Patients who completed T3MPO-1 (16 weeks) or T3MPO-2 (26 weeks) were eligible for enrollment in T3MPO-3. Patients in T3MPO-3 received open-label tenapanor 50 mg twice a day for up to an additional 39 (T3MPO-1) or 26 (T3MPO-2) weeks. Treatment-emergent adverse events (TEAEs) were evaluated in the entire T3MPO-3 safety population and in patients who received a total of ≥52 weeks of tenapanor., Key Results: A total of 312 patients were enrolled in T3MPO-3; 90 received ≥52 weeks of tenapanor. TEAEs were reported in 117 (37.5%) patients in the safety population and in 52 (57.8%) patients who received ≥52 weeks of tenapanor. Diarrhea was the most common TEAE, occurring in 10.6% of the safety population and in 11.1% of patients who received ≥52 weeks of tenapanor. Most cases were mild or moderate in severity, with only two severe cases reported in the safety population. No deaths occurred during the T3MPO-3 study., Conclusions: Tenapanor was tolerable over ≥52 weeks of treatment and showed similar safety to that seen in shorter studies. Combined results of the T3MPO studies indicate that tenapanor is a valuable new treatment option for patients with IBS-C., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: To evaluate the impacts of a transition to an "integrated managed care" model, wherein Medicaid managed care organizations moved from a "carve-out" model to a "carve-in" model integrating the financing of behavioral and physical health care., Data Sources/study Setting: Medicaid claims data from Washington State, 2014-2019, supplemented with structured interviews with key stakeholders., Study Design: This mixed-methods study used difference-in-differences models to compare changes in two counties that transitioned to financial integration in 2016 to 10 comparison counties maintaining carve-out models, combined with qualitative analyses of 15 key informant interviews. Quantitative outcomes included binary measures of access to outpatient mental health care, primary care, the emergency department (ED), and inpatient care for mental health conditions., Data Collection: Medicaid claims were collected administratively, and interviews were recorded, transcribed, and analyzed using a thematic analysis approach., Principal Findings: The transition to financially integrated care was initially disruptive for behavioral health providers and was associated with a temporary decline in access to outpatient mental health services among enrollees with serious mental illness (SMI), but there were no statistically significant or sustained differences after the first year. Enrollees with SMI also experienced a slight increase in access to primary care (1.8%, 95% CI 1.0%-2.6%), but no sustained statistically significant changes in the use of ED or inpatient services for mental health care. The transition to financially integrated care had relatively little impact on primary care providers, with few changes for enrollees with mild, moderate, or no mental illness., Conclusions: Financial integration of behavioral and physical health in Medicaid managed care did not appear to drive clinical transformation and was disruptive to behavioral health providers. States moving towards "carve-in" models may need to incorporate support for practice transformation or financial incentives to achieve the benefits of coordinated mental and physical health care., (© 2023 Health Research and Educational Trust.)

Background: Monitoring the effectiveness of COVID-19 vaccines against SARS-CoV-2 infections remains important to inform public health responses. Estimation of vaccine effectiveness (VE) against serological evidence of SARS-CoV-2 infection might provide an alternative measure of the benefit of vaccination against infection., Methods: We estimated mRNA COVID-19 vaccine effectiveness (VE) against development of SARS-CoV-2 anti-nucleocapsid antibodies in March-October 2021, during which the Delta variant became predominant. Participants were enrolled from four participating healthcare systems in the United States, and completed electronic surveys that included vaccination history. Dried blood spot specimens collected on a monthly basis were analyzed for anti-spike antibodies, and, if positive, anti-nucleocapsid antibodies. We used detection of new anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection, and estimated VE by comparing 154 case-participants with new detection of anti-nucleocapsid antibodies to 1,540 seronegative control-participants matched by calendar period. Using conditional logistic regression, we estimated VE ≥ 14 days after the 2nd dose of an mRNA vaccine compared with no receipt of a COVID-19 vaccine dose, adjusting for age group, healthcare worker occupation, urban/suburban/rural residence, healthcare system region, and reported contact with a person testing positive for SARS-CoV-2., Results: Among individuals who completed a primary series, estimated VE against seroconversion from SARS-CoV-2 infection was 88.8% (95% confidence interval [CI], 79.6%-93.9%) after any mRNA vaccine, 87.8% (95% CI, 75.9%-93.8%) after BioNTech vaccine and 91.7% (95% CI, 75.7%-97.2%) after Moderna vaccine. VE was estimated to be lower ≥ 3 months after dose 2 compared with < 3 months after dose 2, and among participants who were older or had underlying health conditions, although confidence intervals overlapped between subgroups., Conclusions: VE estimates generated using infection-induced antibodies were consistent with published estimates from clinical trials and observational studies that used virologic tests to confirm infection during the same period. Our findings support recommendations for eligible adults to remain up to date with COVID-19 vaccination., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Roberto P. Santos has received honoraria and/or travel grants from the American Board of Pediatrics (2020–2025), the American Academy of Pediatrics (2022), and the Mississippi Osteopathic Medicine Association (2022) 2022. Dr. Santos is also site principal investigator/coordinator for a contract awarded to the University of Mississippi Medical Center (UMMC) with Eli Lilly, Janssen Pharmaceutical Companies of Johnson & Johnson, Merck Sharp & Dohme (MSD), and the Health Resources and Services Administration (2020–2021).]., (Published by Elsevier Ltd.)

Progress in sample preparation for scRNA-seq is reported based on RevGel-seq, a reversible-hydrogel technology optimized for samples of fresh cells. Complexes of one cell paired with one barcoded bead are stabilized by a chemical linker and dispersed in a hydrogel in the liquid state. Upon gelation on ice the complexes are immobilized and physically separated without requiring nanowells or droplets. Cell lysis is triggered by detergent diffusion, and RNA molecules are captured on the adjacent barcoded beads for further processing with reverse transcription and preparation for cDNA sequencing. As a proof of concept, analysis of PBMC using RevGel-seq achieves results similar to microfluidic-based technologies when using the same original sample and the same data analysis software. In addition, a clinically relevant application of RevGel-seq is presented for pancreatic islet cells. Furthermore, characterizations carried out on cardiomyocytes demonstrate that the hydrogel technology readily accommodates very large cells. Standard analyses are in the 10,000-input cell range with the current gelation device, in order to satisfy common requirements for single-cell research. A convenient stopping point after two hours has been established by freezing at the cell lysis step, with full preservation of gene expression profiles. Overall, our results show that RevGel-seq represents an accessible and efficient instrument-free alternative, enabling flexibility in terms of experimental design and timing of sample processing, while providing broad coverage of cell types., (© 2023. The Author(s).)

Purpose: Since 2020, a SARS-COV2 epidemic has been raging worldwide. The cycle of the PCR test in which the virus is detected is called cycle threshold (CT). The method of obtaining the sample is not detailed in any published study and is based on general guidelines of the CDC. Our contention is that the manner in which the sample is obtained has a dramatic effect on CT values., Methods: For each person suspected of having Covid-19 who arrives at the emergency room, two swabs are taken in succession, one according to CDC guidelines and the other according to "Ziv" guidelines. The Ziv method sample collection guidelines determine the depth of penetration, the number of rotations of the swab, and their direction. Each double sample was sent for analysis., Results: Analysis of the CT results of the sample to results methods and of the Seegene platform clearly found (p = 0.003 and p = 0.001, respectively) that more rigorous sample collection yielded lower CT values., Conclusion: The method of obtaining the samples had a dramatic effect on CT results. Any publication that includes CT results, and certainly studies that discuss CT kinetics, must describe in detail the method by which the samples were obtained. In places where it is also important to detect the onset of illness (airports, hospitals, schools, etc.), it is important to use the Ziv method to reduce the risk of false negatives., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

In this article we use an exact method to resolve the fields scattered by a spherical magneto-optical particle and calculate the optical forces exerted on it. The resulting force and the contributing components, i.e. magneto-optical gradient force and magneto-optical extinction force, are presented in an analytical form. We also derive analytical expressions for the scattering and extinction cross sections of a magneto-optical particle, expressions which intuitively demonstrate the effect of circular dichroism in magneto-optical scattering and forces. Finally, we demonstrate that the magneto-optical extinction force is the result of circular dichroism in magneto-optical scattering. We show that it is possible to completely cancel the scattering in the forward or in the backward direction, when the incident field is composed of a circularly-polarized reflected beam. Moreover, the directional scattering is interrelated to the direction of the force exerted on the particle.

Objectives: In a post hoc analysis of the VEST III trial, we investigated the effect of the harvesting technique on saphenous vein graft (SVG) patency and disease progression after coronary artery bypass grafting., Methods: Angiographic outcomes were assessed in 183 patients undergoing open (126 patients, 252 SVG) or endoscopic harvesting (57 patients, 114 SVG). Overall SVG patency was assessed by computed tomography angiography at 6 months and by coronary angiography at 2 years. Fitzgibbon patency (FP I, II and III) and intimal hyperplasia (IH) in a patient subset were assessed by coronary angiography and intravascular ultrasound, respectively, at 2 years., Results: Baseline characteristics were similar between patients who underwent open and those who underwent endoscopic harvesting. Open compared with endoscopic harvesting was associated with higher overall SVG patency rates at 6 months (92.9% vs 80.4%, P = 0.04) and 2 years (90.8% vs 73.9%, P = 0.01), improved FP I, II and III rates (65.2% vs 49.2%; 25.3% vs 45.9%, and 9.5% vs 4.9%, respectively; odds ratio 2.81, P = 0.09) and reduced IH area (-31.8%; P = 0.04) and thickness (-28.9%; P = 0.04). External stenting was associated with improved FP I, II and III rates (odds ratio 2.84, P = 0.01), reduced IH area (-19.5%; P < 0.001) and thickness (-25.0%; P < 0.001) in the open-harvest group and reduced IH area (-12.7%; P = 0.01) and thickness (-9.5%; P = 0.21) in the endoscopic-harvest group., Conclusions: A post-hoc analysis of the VEST III trial showed that open harvesting is associated with improved overall SVG patency and reduced IH. External stenting reduces SVG disease progression, particularly with open harvesting., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Brain computed tomography (CTB) scans are widely used to evaluate intracranial pathology. The implementation and adoption of CTB has led to clinical improvements. However, interpretation errors occur and may have substantial morbidity and mortality implications for patients. Deep learning has shown promise for facilitating improved diagnostic accuracy and triage. This research charts the potential of deep learning applied to the analysis of CTB scans. It draws on the experience of practicing clinicians and technologists involved in development and implementation of deep learning-based clinical decision support systems. We consider the past, present and future of the CTB, along with limitations of existing systems as well as untapped beneficial use cases. Implementing deep learning CTB interpretation systems and effectively navigating development and implementation risks can deliver many benefits to clinicians and patients, ultimately improving efficiency and safety in healthcare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study investigated the demographic characteristics, service use patterns, and needs of people who were high users of the homeless services, Cook County Jail, or hospital systems in Chicago, Illinois., Methods: Definitions of "high users" in each system were based on number of stays and days. K-means cluster analysis was performed on the subset of individuals who interacted with all three systems and were high users of at least one system., Results: Cluster analysis was conducted on 1,232 individuals and revealed three profiles. The largest cluster (N=1,059; 86%) consisted of older single individuals exhibiting high rates of disabling conditions and health issues. A second cluster (N=124; 10%) distinguished a particularly vulnerable subgroup with the highest rates of medical and mental health needs. The final, smallest cluster (N=49; 4%) consisted of predominantly younger Black women with children who exhibited the lowest rates of behavioral health issues, but high hospital use.

In this paper we show analytically and numerically the formation of a near-field stable optical binding between two identical plasmonic particles, induced by an incident plane wave. The equilibrium binding distance is controlled by the angle between the polarization plane of the incoming field and the dimer axis, for which we have calculated an explicit formula. We have found that the condition to achieve stable binding depends on the particle's dielectric function and happens near the frequency of the dipole plasmonic resonance. The binding stiffness of this stable attaching interaction is four orders of magnitude larger than the usual far-field optical binding and is formed orthogonal to the propagation direction of the incident beam (transverse binding). The binding distance can be further manipulated considering the magneto-optical effect and an equation relating the desired equilibrium distance with the required external magnetic field is obtained. Finally, the effect induced by the proposed binding method is tested using molecular dynamics simulations. Our study paves the way to achieve complete control of near-field binding forces between plasmonic nanoparticles., (© 2021. The Author(s).)