HIV-Associated Microbial Translocation May Affect Cytokine Production of CD56bright NK Cells via Stimulation of Monocytes.

The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes' transforming growth factor-ß production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction.

Sex and Gender Considerations in Episodic Migraine.

PURPOSE OF REVIEW: We seek to update readers on recent advances in our understanding of sex and gender in episodic migraine with a two part series. In part 1, we examine migraine epidemiology in the context of sex and gender, differences in symptomatology, and the influence of sex hormones on migraine pathophysiology (including CGRP). In part 2, we focus on practical clinical considerations for sex and gender in episodic migraine by addressing menstrual migraine and the controversial topic of hormone-containing therapies. We make note of data applicable to gender minority populations, when available, and summarize knowledge on gender affirming hormone therapy and migraine management in transgender individuals. Finally, we briefly address health disparities, socioeconomic considerations, and research bias. RECENT FINDINGS: Migraine is known to be more prevalent, frequent, and disabling in women. There are also differences in migraine co-morbidities and symptomatology. For instance, women are likely to experience more migraine associated symptoms such as nausea, photophobia, and phonophobia. Migraine pathophysiology is influenced by sex hormones, e.g., estrogen withdrawal as a known trigger for migraine. Other hormones such as progesterone and testosterone are less well studied. Relationships between CGRP (the target of new acute and preventive migraine treatments) and sex hormones have been established with both animal and human model studies. The natural course of migraine throughout the lifetime suggests a contribution from hormonal changes, from puberty to pregnancy to menopause/post-menopause. Treatment of menstrual migraine and the use of hormone-containing therapies remains controversial. Re-evaluation of the data reveals that stroke risk is an estrogen dose- and aura frequency-dependent phenomenon. There are limited data on episodic migraine in gender minorities. Gender affirming hormone therapy may be associated with a change in migraine and unique risks (including ischemic stroke with high dose estrogen). There are key differences in migraine epidemiology and symptomatology, thought to be driven at least in part by sex hormones which influence migraine pathophysiology and the natural course of migraine throughout the lifetime. More effective and specific treatments for menstrual migraine are needed. A careful examination of the data on estrogen and stroke risk suggests a nuanced approach to the issue of estrogen-containing contraception and hormone replacement therapy is warranted. Our understanding of sex and gender is evolving, with limited but growing research on the relationship between gender affirming therapy and migraine, and treatment considerations for transgender people with migraine.

Development and validation of the Interoceptive States Static Images (ISSI) database.

Internal bodily signals provide an essential function for human survival. Accurate recognition of such signals in the self, known as interoception, supports the maintenance of homeostasis, and is closely related to emotional processing, learning and decision-making, and mental health. While numerous studies have investigated interoception in the self, the recognition of these states in others has not been examined despite its crucial importance for successful social relationships. This paper presents the development and validation of the Interoceptive States Static Images (ISSI), introducing a validated database of 423 visual stimuli for the study of non-affective internal state recognition in others, freely available to other researchers. Actors were photographed expressing various exemplars of both interoceptive states and control actions. The images went through a two-stage validation procedure, the first involving free-labelling and the second using multiple choice labelling and quality rating scales. Five scores were calculated for each stimulus, providing information about the quality and specificity of the depiction, as well as the extent to which labels matched the intended state/action. Results demonstrated that control action stimuli were more recognisable than internal state stimuli. Inter-category variability was found for the internal states, with some states being more recognisable than others. Recommendations for the utilisation of ISSI stimuli are discussed. The stimulus set is freely available to researchers, alongside data concerning recognisability.

Skeletal muscle progenitors are sensitive to collagen architectural features of fibril size and cross linking.

Muscle stem cells (MuSCs) are essential for the robust regenerative capacity of skeletal muscle. However, in fibrotic environments marked by abundant collagen and altered collagen organization, the regenerative capability of MuSCs is diminished. MuSCs are sensitive to their extracellular matrix environment but their response to collagen architecture is largely unknown. The present study aimed to systematically test the effect of underlying collagen structures on MuSC functions. Collagen hydrogels were engineered with varied architectures: collagen concentration, cross linking, fibril size, and fibril alignment, and the changes were validated with second harmonic generation imaging and rheology. Proliferation and differentiation responses of primary mouse MuSCs and immortal myoblasts (C2C12s) were assessed using EdU assays and immunolabeling skeletal muscle myosin expression, respectively. Changing collagen concentration and the corresponding hydrogel stiffness did not have a significant influence on MuSC proliferation or differentiation. However, MuSC differentiation on atelocollagen gels, which do not form mature pyridinoline cross links, was increased compared with the cross-linked control. In addition, MuSCs and C2C12 myoblasts showed greater differentiation on gels with smaller collagen fibrils. Proliferation rates of C2C12 myoblasts were also higher on gels with smaller collagen fibrils, whereas MuSCs did not show a significant difference. Surprisingly, collagen alignment did not have significant effects on muscle progenitor function. This study demonstrates that MuSCs are capable of sensing their underlying extracellular matrix (ECM) structures and enhancing differentiation on substrates with less collagen cross linking or smaller collagen fibrils. Thus, in fibrotic muscle, targeting cross linking and fibril size rather than collagen expression may more effectively support MuSC-based regeneration.

VE/VCO2 slope predicts RV dysfunction and mortality after left ventricular assist device: a fresh look at cardiopulmonary stress testing for prognostication.

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.

Electrocardiographic changes in Takotsubo cardiomyopathy.

Takotsubo Cardiomyopathy (TC) is a syndrome characterized by reversible left ventricular dysfunction in the presence of possible emotional or physical triggers but without evidence of obstructive coronary artery disease. It has become increasingly reported worldwide and is associated with significant morbidity and mortality. TC may present with an array of electrocardiographic (ECG) findings. These ECG findings, if accurately interpreted, can play an important role in the diagnosis and risk stratification of this syndrome. In the last three decades since the disease was first described, multiple diagnostic criteria have been established. The key diagnostic tools for TC include clinical symptomatology, cardiac biomarkers, non-invasive cardiac imaging, and coronary angiography. The ECG findings in TC can be variable, however, some ECG scores have been proposed in association with TC with reasonably good diagnostic sensitivity and specificity. This article aims to provide a succinct review of important electrocardiographic findings associated with TC and its impact on clinical outcomes.

Blend of guar gum and Eudragit shows excellent drug release retarding behavior in sustained release tablets.

The objective of the current study was to compare sustained release behavior of natural and synthetic polymers in matrix tablets of lisinopril and hydrochlorothiazide combination. Guar gum was used as a hydrophilic natural polymer while Eudragit L 100-55 was used as synthetic polymer. Tablets were formulated by direct compression method using different ratios and combinations of both polymers. Various physical tests were performed. After that, in vitro drug release patterns were investigated by performing dissolution in pH 6.8 phosphate buffer. Results indicated that tablets with combination of both guar gum and Eudragit L 100-55 (formulation F10) were having the best drug release retarding behavior. All formulations followed zero order kinetics indicating the drug release was independent of the concentration. Higuchi model revealed drug release by diffusion mechanism while Korsmeyer Peppas model suggested that formulations followed the non-fickian release behavior.

Update on the Diagnosis and Treatment of Idiopathic Intracranial Hypertension.

Advances in ophthalmic diagnostics and results of interventional clinical trials are shifting diagnosis and management of idiopathic intracranial hypertension (IIH) to be more technology- and evidence-based. In this article, the evidence supporting current diagnostic criteria, evaluation, and medical and surgical management of IIH are reviewed.

Current State of Immunotherapy for Treatment of Glioblastoma.

OPINION STATEMENT: At this time, there are no FDA-approved immune therapies for glioblastoma (GBM) despite many unique therapies currently in clinical trials. GBM is a highly immunosuppressive tumor and there are limitations to a safe immune response in the central nervous system. To date, there have been several failures of phase 3 immune therapy clinical trials in GBM. These trials have targeted single components of an antitumor immune response. Learning from these failures, the future of immunotherapy for GBM appears most hopeful for combination of immune therapies to overcome the profound immunosuppression of this disease. Understanding biomarkers for appropriate patient selection as well as tumor progression are necessary for implementation of immunotherapy for GBM.

A Large-Sized Left Main Coronary Artery with Quadfurcation: A Rare Anatomy.

A 63-year-old woman presented to the emergency department with chest pain. She subsequently underwent an evaluation with a diagnostic coronary angiogram that demonstrated a rare coronary anatomy. Instead of its usual bifurcation into two main branches--a left anterior descending and a left circumflex artery--her left main coronary artery quadfurcated into four branches: a left anterior descending artery, a left circumflex artery, and two ramus intermedii arteries. Possible implications of this unusual finding are discussed.

ACR Appropriateness Criteria® Pulmonary Arteriovenous Malformation (PAVM): 2023 Update.

Pulmonary arteriovenous malformations (PAVMs) occur in 30% to 50% of patients with hereditary hemorrhagic telangiectasia. Clinical presentations vary from asymptomatic disease to complications resulting from the right to left shunting of blood through the PAVM such as paradoxical stroke, brain abscesses, hypoxemia, and cardiac failure. Radiology plays an important role both in the diagnosis and treatment of PAVM. Based on different clinical scenarios, the appropriate imaging study has been reviewed and is presented in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Combined surgical and conservative endodontic management of Oehler's type 3b dens invaginatus aided by guided tissue regeneration.

The present case describes the successful healing of a periapical lesion associated with the left maxillary lateral incisor (# 22, Federation Dentaire Internationale) having a type 3b dens invaginatus tooth morphology. The treatment was complicated by the presence of blunderbuss root apex and large periapical lesion (>10 mm) with through and through bone defect (Bucco palatal cortical bone perforation, Von Arx Type 1b). An adolescent boy reported palatal swelling and pus discharge in relation to tooth #22. A thorough clinical and radiographic examination revealed tooth #22 as having a type 3b dens invaginatus with an open apex and a diagnosis of pulp necrosis and acute apical abscess. The case was managed by non-surgical root canal treatment followed by endodontic surgery using principles of guided tissue regeneration. A 5-year recall revealed an asymptomatic functional tooth with complete healing.

Stanford Type A Aortic Dissection in A Patient with Primary Antiphospholipid Syndrome and Coronavirus Disease 2019.

Acute aortic dissection is one of the most lethal diseases, affecting the lining of the aortic wall. We describe a case of Stanford Type A aortic dissection in a patient with underlying primary antiphospholipid syndrome (APS) complicated by coronavirus disease 2019 (COVID-19). APS is characterized by recurrent venous and/or arterial thrombosis, thrombocytopenia, and rarely vascular aneurysms. The hypercoagulable milieu attributable to APS and the prothrombotic state from COVID-19 posed a challenge in achieving optimal postoperative anticoagulation in our patient.

A Case Of Takotsubo Syndrome Precipitated By Diabetic Ketoacidosis.

Takotsubo syndrome (TTS), Takotsubo cardiomyopathy, or stress-induced cardiomyopathy are interchangeable terms characterized by transient left ventricular systolic dysfunction, electrocardiographic changes, and cardiac biomarker elevation similar to acute coronary syndrome (ACS), without the presence of obstructive epicardial coronary artery disease. It predominantly affects postmenopausal females and manifests in the presence of stressful triggers such as severe physical or emotional stress, natural disasters, unexpected death of relatives, acute medical illnesses, etc. TTS was initially considered to be a benign condition however recent studies have shown that it may be associated with complications and mortality similar to ACS. Rare reports of TTS triggered by diabetic ketoacidosis (DKA) have been published. Herein we describe a case of an elderly female with a history of type II diabetes mellitus (DM) who was admitted with DKA and subsequently developed TTS that resolved after treatment of DKA and implementation of heart failure therapies.

Single-cell RNA sequencing identifies a population of human liver-type ILC1s.

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-ß1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

Vestibular Migraine: Cognitive Dysfunction, Mobility, Falls.

OBJECTIVE: Recent evidence has shown that vestibular migraine is strongly associated with cognitive difficulties. However, limited data exist on real-world effects of that dysfunction. The objective of this study is to understand the epidemiology of cognitive dysfunction with vestibular migraine and associated sequelae using National Health Interview Survey data. STUDY DESIGN: Randomized, population-based survey study of US adults. SETTING: We generated a case definition approximating probable vestibular migraine based on Bárány Society criteria and validated that definition in a tertiary care vestibular clinic. PATIENTS: Adult respondents to the 2016 NHIS, which queries a representative sample of the civilian, noninstitutionalized US population. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: We evaluated incidence of self-reported cognitive dysfunction with vestibular migraine and whether individuals were more likely to have impaired mobility, falls, and work absenteeism than those without either condition. RESULTS: Among individuals with vestibular migraine, 40% reported "some" and 12% reported "a lot" of difficulty thinking versus 13% and 2% of those without vestibular migraine, respectively. Vestibular migraine sufferers were more likely to have difficulty thinking or remembering compared with respondents without dizziness (odds ratio, 7.43; 95% confidence interval, 6.06-9.10; p < 0.001) when controlled for age, sex, education, stroke, smoking, heart disease, and diabetes. Individuals with both vestibular migraine and cognitive dysfunction had fivefold increased odds of falls and 10-fold increased odds of mobility issues compared with those without either condition. Furthermore, individuals with both vestibular migraine and cognitive dysfunction missed 12.8 more days of work compared to those without either condition. CONCLUSION: Our findings indicate vestibular migraine is not only associated with cognitive dysfunction, but they are together associated with mobility issues, fall risk, and work absenteeism.