Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

PURPOSE OF REVIEW: Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges. RECENT FINDINGS: Low SES presents barriers to effective pain care, while gender differences and the prevalence of chronic pain in aging adults emphasize the need for tailored approaches. The association between chronic pain and physical comorbidities like cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus reveals shared risk factors and further highlights the importance of integrated treatment strategies. Chronic pain and mental health are intricately linked through biochemical mechanisms, profoundly affecting overall quality of life. This review explores pharmacologic treatment for chronic pain, particularly opioid analgesia, with attention to the risk of substance misuse and the ongoing opioid epidemic. We discuss the potential role of medical cannabis as an alternative treatment with a nuanced perspective on its impact on opioid use. Addressing the totality and complexity of pain states is crucial to individualizing chronic pain management. With different types of pain having different underlying mechanisms, considerations should be made when approaching their treatment. Moreover, the synergistic relationship that pain states can have with other comorbidities further complicates chronic pain conditions.

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet+ subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c+CD80+ cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.

Social media for learning: A qualitative exploration of the factors that impact clinical learners' attitudes and intentions.

BACKGROUND: Social media has created a revolution in learning and teaching. This study set out to provide a theory-informed exploration of the factors influencing medical students' perspectives of learning with social media using the theory of planned behaviour (TPB) as a framework. METHODS: The study collected data using semi-structured interviews from seven third year medical students at an undergraduate Australian medical school, who were in their first clinical year. The data were analysed inductively and deductively using TPB. RESULTS: Three themes emerged relating to the factors that influence medical students' attitudes and intentions regarding using social media for learning: (1) Social media aligns with the needs and preferences of the contemporary learner; (2) rise of medical professionals on social media during the COVID-19 pandemic; and (3) being an informed user of social media for learning. Participants had largely positive views and attitudes towards social media as a learning tool especially for preclinical content due to its capacity for multimodal information delivery and evolving social norms. However, this positivity was tempered by the challenges they faced in determining quality of resources, linking their learning to clinical medicine and accessing specialist content. CONCLUSION: Social media can play a significant role in medical students' learning. However, its potential as an educational tool can be enhanced by widening access to resources, and implementing strategies that help students increase their evaluative judgement skills to make informed decisions regarding the quality of social media resources and to translate their social media-mediated learning into clinical practice.

Epilepsy surgery perceptions among general neurologists and epilepsy specialists: A survey.

OBJECTIVE: Surgical intervention for drug-resistant epilepsy (DRE) is a safe and efficacious evidence-based treatment. Yet, neurologists have historically revealed hesitance in referring patients for surgical evaluations. The present study surveyed general neurologists and epilepsy specialists to assess their views and process in referring patients for specialized epilepsy care and epilepsy surgery. METHODS: A 14-item survey assessing epilepsy referrals and views of epilepsy surgery was distributed to all neurologists currently practicing in a large national integrated health system using REDCap. Responses were qualitatively analyzed and differences between general neurologists and epileptologists were assessed using chi-squared tests. RESULTS: In total, 100 responses were received from 67 general neurologists and 33 epileptologists with several similarities and differences emerging between the two groups. Both groups endorsed surgery and neuromodulation as treatment options in DRE, felt that seizure frequency rather than duration was relevant in considering epilepsy surgery, and indicated patient preference as the largest barrier limiting epilepsy surgery. General neurologists were more likely to require ≥ 3 ASMs to fail to diagnose DRE compared to epileptologists (45% vs. 15%, p < 0.01) who more often required ≥ 2 ASMs to fail. Epileptologists were also more likely than neurologists to try a new ASM (75.8% vs. 53.7%, p < 0.05) or optimize the current ASM (75.8% vs. 49.3%, p < 0.05) in DRE. General neurologists were more likely to consider epilepsy surgery to be less efficacious (p = 0.001) or less safe (p < 0.05). SIGNIFICANCE: Overall, neurologists appear to have generally positive opinions of epilepsy surgery, which is a change from prior literature and represents a changing landscape of views toward this intervention. Furthermore, epileptologists and general neurologists endorsed more similarities than differences in their opinions of surgery and steps to referral, which is another encouraging finding. Those gaps that remain between epileptologists and general neurologists, particularly in standards of ASM prescription, may be addressed by more consistent education about DRE and streamlining of surgical referral procedures.

Heritable changes in chromatin contacts linked to transgenerational obesity.

Burgeoning evidence demonstrates that effects of environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations1,2. This phenomenon remains controversial because underlying mechanisms have not been identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology. Here, we used an established murine model of male-specific transgenerational obesity to show that exposure to the obesogen tributyltin (TBT) elicited heritable changes in chromatin interactions (CIs) in primordial germ cells (PGCs). New CIs were formed within the Ide gene encoding Insulin Degrading Enzyme in the directly exposed PGCs, then stably maintained in PGCs of the subsequent (unexposed) two generations. Concomitantly, Ide mRNA expression was decreased in livers of male descendants from the exposed dams. These males were hyperinsulinemic and hyperglycemic, phenocopying Ide-deficient mice that are predisposed to adult-onset, diet-induced obesity. Creation of new CIs in PGCs, suppression of hepatic Ide mRNA, increased fat mass, hyperinsulinemia and hyperglycemia were male-specific. Our results provide a plausible molecular mechanism underlying transmission of the transgenerational predisposition to obesity caused by gestational exposure to an environmental obesogen. They also provide an entry point for future studies aimed at understanding how environmental exposures alter chromatin structure to influence physiology across multiple generations in mammals.

Veno-venous Extracorporeal Membrane Oxygenation: Anesthetic Considerations in Clinical Practice.

Context: After the COVID-19 pandemic, multiple reviews have documented the success of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients who experience hypoxemia but have normal contractility may be switched to veno-venous-ECMO (VV-ECMO). Purpose: In this review, we present three protocols for anesthesiologists. Firstly, transesophageal echocardiography (TEE) aids in cannulation and weaning off inotropes and fluids. Our main objective is to assist in patient selection for the Avalon Elite single catheter, which is inserted into the right internal jugular vein and terminates in the right atrium. Secondly, we propose appropriate anticoagulant doses. We outline day-to-day monitoring protocols to prevent heparin-induced thrombocytopenia (HIT) or resistance. Once the effects of neuromuscular paralysis subside, sedation should be reduced. Therefore, we describe techniques that may prevent delirium from progressing into permanent cognitive decline. Methods: We conducted a PubMed search using the keywords VV-ECMO, TEE, Avalon Elite (Maquet, Germany), and quetiapine. We combined these findings with interviews conducted with nurses and anesthesiologists from two academic ECMO centers, focusing on anticoagulation and sedation. Results: Our qualitative evidence synthesis reveals how TEE confirms cannulation while avoiding right atrial rupture or low flows. Additionally, we discovered that typically, after initial heparinization, activated partial thromboplastin time (PTT) is drawn every 1 to 2 hours or every 6 to 8 hours once stable. Daily thromboelastograms, along with platelet counts and antithrombin III levels, may detect HIT or resistance, respectively. These side effects can be prevented by discontinuing heparin on day two and initiating argatroban at a dose of 1 µg/kg/min while maintaining PTT between 61 - 80 seconds. The argatroban dose is adjusted by 10 - 20% if PTT is between 40 - 60 or 80 - 90 seconds. Perfusionists assist in establishing protocols following manufacturer guidelines. Lastly, we describe the replacement of narcotics and benzodiazepines with dexmedetomidine at a dose of 0.5 to 1 µg/kg/hour, limited by bradycardia, and the use of quetiapine starting at 25 mg per day and gradually increasing up to 200 mg twice a day, limited by prolonged QT interval. Conclusions: The limitation of this review is that it necessarily covers a broad range of ECMO decisions faced by an anesthesiologist. However, its main advantage lies in the identification of straightforward argatroban protocols through interviews, as well as the discovery, via PubMed, of the usefulness of TEE in determining cannula position and contractility estimates for transitioning from VA-ECMO to VV-ECMO. Additionally, we emphasize the benefits in terms of morbidity and mortality of a seldom-discussed sedation supplement, quetiapine, to dexmedetomidine.

Neuromodulators for Skin.

Neurotoxins are the most popular nonsurgical aesthetic procedure for men and women of all ages. Five botulinum toxin A (BoNTA) products represent the current palette of available BoNTA for cosmetic use. Off-label uses of BoNTA continue to expand and are now used for skin rejuvenation, to treat various skin disorders, and in facial nerve paralysis. Dermal and subdermal injections of dilute BoNTA has grown in popularity and been shown to improve skin texture and quality. Common targets for chemodenervation in facial nerve synkinesis are ipsilateral orbicularis oculi, mentalis, depressor anguli oris, buccinator, corrugator muscles, and the ipsilateral and/or contralateral frontalis.

An Open-label Pilot Study of NicoBloc as a Novel Smoking Cessation Intervention.

INTRODUCTION: NicoBloc is a viscous fluid applied to the cigarette filter designed to block tar and nicotine. This novel and understudied smoking cessation device presents a nonpharmacological means for smokers to gradually reduce nicotine and tar content while continuing to smoke their preferred brand of cigarette. This pilot study aimed to assess the feasibility, acceptability, and initial efficacy of NicoBloc as compared with nicotine replacement therapy (nicotine lozenge). METHODS: A community sample of predominately Black smokers (N = 45; 66.7% Black) were randomized to receive NicoBloc or nicotine lozenge. Both groups engaged in 4 weeks of smoking cessation therapy followed by 2 months of independent usage with monthly check-ins to assess medication adherence. The intervention lasted 12 weeks, and the study concluded with a 1-month postintervention follow-up visit (week 16). RESULTS: NicoBloc was comparable with nicotine lozenge in smoking reduction, feasibility, symptom adverse effects, and reported acceptability at week 16. Participants in the lozenge group endorsed higher treatment satisfaction ratings during the intervention and lower cigarette dependence. Adherence to NicoBloc was superior throughout the study. CONCLUSION: NicoBloc was feasible and acceptable to community smokers. NicoBloc presents a unique, nonpharmacological intervention. Future research is needed to examine whether this intervention may be most effective in subpopulations where pharmacological approaches are restricted or in combination with established pharmacological methods such as nicotine replacement therapy.

Association between maternity care practitioner type and postpartum depression screening.

BACKGROUND: Postpartum depression (PPD) is increasingly common in the United States and poses a significant threat to maternal and neonatal health. Universal screening for postpartum depression is recommended by numerous organizations, including the American College of Obstetricians and Gynecologists, but is not achieved in practice. METHODS: A cross-sectional, weighted, state-representative study of California residents who gave birth in 2016 using the Listening to Mothers in California 2018 data set. Primary exposure was type of maternity care professional providing care during pregnancy, and the primary outcome was PPD screening. The secondary exposure was self-reported depression or anxiety during pregnancy, and the secondary outcome was attending a postpartum office visit. Bivariate analyses were conducted using Rao-Scott chi-square tests, and multivariate analyses were conducted using logistic regression. RESULTS: Compared to participants cared for by obstetricians, participants cared for by midwives had 2.6 times the odds of reporting being screened for PPD after controlling for covariates (95% CI = 1.5, 4.4). Receiving care from any other practitioner type compared with an obstetrician was not associated with a different rate of postpartum depression screening. Reporting depression or anxiety during pregnancy was associated with 0.7 times the odds (95% CI = 0.5, 1.0) of returning for postpartum care after controlling for covariates. CONCLUSIONS: Being cared for by a midwife during pregnancy increases the likelihood of being screened for postpartum depression. In addition, even perfectly implemented universal screening will miss a vulnerable sector of the population that is at high risk for postpartum depression and is less likely to return for postpartum care.

The role of nurses in inpatient geriatric rehabilitation units: A scoping review.

AIMS: (1) To review and synthesize research on the contributions of nurses to rehabilitation in inpatient geriatric rehabilitation units (GRUs), and (2) to compare these reported contributions to the domains of international rehabilitation nursing competency models. The roles and contributions of nurses (e.g. Registered Practical Nurses, Registered Nurses and Licensed Practical Nurses) in GRUs are non-specific, undervalued, undocumented and unrecognized as part of the formal Canadian rehabilitation process. DESIGN: Arksey and O'Malley's methodological framework for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used. METHODS: Six databases were searched for relevant literature: MEDLINE, PsychINFO, CINAHL, EMBASE, SCOPUS and Nursing and Allied Health. English articles were included if they examined nursing roles or contributions to inpatient geriatric rehabilitation. Integrated synthesis was used to combine the qualitative and quantitative data, and thematic analysis was used for coding. Three sets of international competency models were amalgamated to explore how different nurse roles in geriatric rehabilitation were portrayed in the included literature. RESULTS: Eight studies published between 1991 and 2020 were included in the review. Five main geriatric rehabilitation nursing roles were generated from synthesis of the domains of international rehabilitation nursing competency models: conserver, supporter, interpreter, coach and advocate. CONCLUSIONS: Nurses working in inpatient geriatric rehabilitation are recognized more for their role in conserving the body than their roles in supporting, interpreting, coaching and advocacy. Interprofessional team members appear to be less sure of the nurses' role in the rehabilitation unit. Nurses themselves do not acknowledge the unique rehabilitation aspects of care for older adults. Enhancing formal education, or adding continuing education courses, to facilitate role clarity for nurses in geriatric rehabilitation could improve nurses' and interprofessional healthcare team members' understandings of the possible contributions of nurses working in rehabilitation settings.

The Role and Contributions of Nurses in Stroke Rehabilitation Units: An Integrative Review.

Nurses' contributions to stroke rehabilitation have been viewed as pivotal, but therapeutically nonspecific. This integrative review synthesized empirical literature on the roles and contributions of nurses to inpatient stroke rehabilitation to answer three research questions: (a) What specific skills or tasks have been identified as the roles and contributions of nurses to inpatient stroke rehabilitation? (b) How do nurses perform these skills/tasks to support and promote inpatient stroke rehabilitation and recovery? and (c) What factors have been identified to impact nurses' working conditions on inpatient stroke rehabilitation units? A systematic search of multiple electronic databases retrieved seven studies which provided significant context and examples to these questions. What nurses do in practice included, for example, maximizing patients' independence in performing daily activities, preventing harm, and preserving integrity. How nurses perform their therapeutic roles included teaching, coaching, coordination, management, advocacy, collaboration. Factors that impact nurses' working conditions consisted of time, resources, and knowledge. This review demonstrates our current understanding of nurses' contributions to inpatient stroke rehabilitation, highlights their significant role, identifies current barriers/challenges of implementing stroke nursing care, and suggests ways of documenting and measuring nurses' contributions.

Case report: Immune profiling links neutrophil and plasmablast dysregulation to microvascular damage in post-COVID-19 Multisystem Inflammatory Syndrome in Adults (MIS-A).

Despite surviving a SARS-CoV-2 infection, some individuals experience an intense post-infectious Multisystem Inflammatory Syndrome (MIS) of uncertain etiology. Children with this syndrome (MIS-C) can experience a Kawasaki-like disease, but mechanisms in adults (MIS-A) are not clearly defined. Here we utilize a deep phenotyping approach to examine immunologic responses in an individual with MIS-A. Results are contextualized to healthy, convalescent, and acute COVID-19 patients. The findings reveal systemic inflammatory changes involving novel neutrophil and B-cell subsets, autoantibodies, complement, and hypercoagulability that are linked to systemic vascular dysfunction. This deep patient profiling generates new mechanistic insight into this rare clinical entity and provides potential insight into other post-infectious syndromes.

Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE.

Resident-tissue macrophages (RTMs) arise from embryonic precursors1,2, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15-/- mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E2 production. A compromised AM compartment resulted in increased susceptibility to acute lung injury induced by lipopolysaccharide and to pulmonary infections with influenza A virus or SARS-CoV-2. Our results highlight the complexity of prenatal RTM programming and reveal their dependency on in trans eicosanoid production by neutrophils for lifelong self-renewal.

Parkin coregulates glutathione metabolism in adult mammalian brain.

We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis. To further examine the protective effects of parkin in an oxidative stress model, we first combined the loss of prkn with Sod2 haploinsufficiency in mice. Although adult prkn-/-//Sod2± animals did not develop dopamine cell loss in the S. nigra, they had more reactive oxidative species and a higher concentration of carbonylated proteins in the brain; bi-genic mice also showed a trend for more nitrotyrosinated proteins. Because these redox changes were seen in the cytosol rather than mitochondria, we next explored the thiol network in the context of PRKN expression. We detected a parkin deficiency-associated increase in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in murine brain, PRKN-linked human cortex and several cell models. This shift resulted from enhanced recycling of GSSG back to GSH via upregulated glutathione reductase activity; it also correlated with altered activities of redox-sensitive enzymes in mitochondria isolated from mouse brain (e.g., aconitase-2; creatine kinase). Intriguingly, human parkin itself showed glutathione-recycling activity in vitro and in cells: For each GSSG dipeptide encountered, parkin regenerated one GSH molecule and was S-glutathionylated by the other (GSSG + P-SH [Formula: see text] GSH + P-S-SG), including at cysteines 59, 95 and 377. Moreover, parkin's S-glutathionylation was reversible by glutaredoxin activity. In summary, we found that PRKN gene expression contributes to the network of available thiols in the cell, including by parkin's participation in glutathione recycling, which involves a reversible, posttranslational modification at select cysteines. Further, parkin's impact on redox homeostasis in the cytosol can affect enzyme activities elsewhere, such as in mitochondria. We posit that antioxidant functions of parkin may explain many of its previously described, protective effects in vertebrates and invertebrates that are unrelated to E3 ligase activity.

Neighborhood Socioeconomic Status and Women's Mental Health: A Longitudinal Study of Hurricane Katrina Survivors, 2005-2015.

There is limited knowledge on the relationship between neighborhood factors and mental health among displaced disaster survivors, particularly among women. Hurricane Katrina (Katrina) was the largest internal displacement in the United States (U.S.), which presented itself as a natural experiment. We examined the association between neighborhood socioeconomic status (SES) and mental health among women up to 10 years following Katrina (N = 394). We also investigated whether this association was modified by move status, comparing women who were permanently displaced to those who had returned to their pre-Katrina residence. We used hierarchical linear models to measure this association, using data from the American Community Survey and the Gulf Coast Child and Family Health study. Neighborhood SES was created as an index which represented social and economic characteristics of participants' neighborhoods. Mental health was measured using mental component summary (MCS) scores. Increased neighborhood SES was positively associated with mental health after controlling for age, race/ethnicity, economic positioning, time, and move status (19.6, 95% Confidence Interval: 5.8, 33.7). Neighborhood SES and mental health was also modified by move status. These findings underscore the need to better understand the impacts of socioeconomic conditions and health outcomes among women affected by natural disasters.

Helminth Infection-Induced Increase in Virtual Memory CD8 T Cells Is Transient, Driven by IL-15, and Absent in Aged Mice.

CD8 virtual memory T (TVM) cells are Ag-naive CD8 T cells that have undergone partial differentiation in response to common γ-chain cytokines, particularly IL-15 and IL-4. TVM cells from young individuals are highly proliferative in response to TCR and cytokine stimulation but, with age, they lose TCR-mediated proliferative capacity and exhibit hallmarks of senescence. Helminth infection can drive an increase in TVM cells, which is associated with improved pathogen clearance during subsequent infectious challenge in young mice. Given the cytokine-dependent profile of TVM cells and their age-associated dysfunction, we traced proliferative and functional changes in TVM cells, compared with true naive CD8 T cells, after helminth infection of young and aged C57BL/6 mice. We show that IL-15 is essential for the helminth-induced increase in TVM cells, which is driven only by proliferation of existing TVM cells, with negligible contribution from true naive cell differentiation. Additionally, TVM cells showed the greatest proliferation in response to helminth infection and IL-15 compared with other CD8 T cells. Furthermore, TVM cells from aged mice did not undergo expansion after helminth infection due to both TVM cell-intrinsic and -extrinsic changes associated with aging.

Routine screening of emergency admissions at risk of chronic hepatitis (SEARCH) identifies and links hepatitis B cases to care.

BACKGROUND AND AIMS: Significant barriers exist with hepatitis B (HBV) case detection and effective linkage to care (LTC). The emergency department (ED) is a unique healthcare interaction where hepatitis screening and LTC could be achieved. We examined the efficacy and utility of automated ED HBV screening for Overseas Born (OB) patients. METHODS: A novel-automated hepatitis screening service "SEARCH" (Screening Emergency Admissions at Risk of Chronic Hepatitis) was piloted at a metropolitan hospital. A retrospective and comparative analysis of hepatitis testing during the SEARCH pilot compared to a period of routine testing was conducted. RESULTS: During the SEARCH pilot, 4778 OB patients were tested for HBV (86% of eligible patient presentations), compared with 1.9% of eligible patients during a control period of clinician-initiated testing. SEARCH detected 108 (2.3%) hepatitis B surface antigen positive patients including 20 (19%) in whom the diagnosis was new. Among 88 patients with known HBV, 57% were receiving medical care, 33% had become lost to follow-up and 10% had never received HBV care. Overall, 30/88 (34%) patients with known HBV were receiving complete guideline-based care prior to re-engagement via SEARCH. Following SEARCH, LTC was successful achieved in 48/58 (83%) unlinked patients and 19 patients were commenced on anti-viral therapy. New diagnoses of cirrhosis and hepatocellular carcinoma were made in five and one patient(s) respectively. CONCLUSIONS: Automated ED screening of OB patients is effective in HBV diagnosis, re-diagnosis and LTC. Prior to SEARCH, the majority of patients were not receiving guideline-based care.

Bromocriptine and Colesevelam Hydrochloride: Novel Therapies for Type II Diabetes Mellitus.

The increasing prevalence of type II diabetes mellitus (T2DM) is a worldwide healthcare concern. Over the years, our understanding of T2DM has grown considerably in uncovering the pathophysiology of the disease and, in turn, understanding how improved treatment methods can be used to slow disease progression. Some long-term complications that are responsible for most T2DM mortalities include cardiovascular disease, neurological decline, and renal failure. In treating T2DM, it is important that not only glycemic control be obtained but also control of associated complications. Bromocriptine and colesevelam hydrochloride have both been approved by the Food and Drug Administration (FDA) to treat T2DM but are not readily used in practice. These medications are known to treat glycemic dysregulation via unconventional mechanisms, which might contribute to their potential to provide protection against common diabetic complications such as cardiovascular disease. In order to ensure that these overlooked medications become more readily used, it is vital that more research be performed to further elucidate their efficacy in a clinical setting. Future studies should continue to provide clinicians a better understanding of the role these medications have on the treatment of T2DM such as their ability to be used in combination with other commonly used T2DM medications or as monotherapies.

A B1a-natural IgG-neutrophil axis is impaired in viral- and steroid-associated aspergillosis.

The lung naturally resists Aspergillus fumigatus (Af) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis-severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use-in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes, Af-binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed Af from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.