Effectiveness of a multimodal strategy to reduce external ventricular drain-associated infection: A quasi-experimental study.

BACKGROUND: Infection is a serious complication in neurosurgical patients who undergo external ventricular drain (EVD) insertion. METHODS: We conducted a quasi-experimental study in patients who underwent EVD insertion to evaluate the impact of a multi-modal strategy to reduce the incidence of external ventricular drain associated infections (EVDAIs). The study was divided into 2 periods; (1) the pre-intervention period when techniques for EVD insertion and maintenance were up to the discretion of the neurosurgeons and (2) the post-intervention after implementation of a multi-modal strategy (cefazolin antibiotic prophylaxis, preoperative chlorhexidine showers, application of postoperative chlorhexidine-impregnated dressing, limited manipulation of the EVD, and meticulous EVD management). The primary outcome was the incidence rate of EVDAIs; secondary outcomes included in-hospital mortality rate, the hospital length of stay. RESULTS: In total, 135 patients were included. The incidence rate of EVDAIs was significantly reduced in the post-intervention period (5.6 cases/1,000 EVD-days) compared with the pre-intervention period (18.2 cases/1,000 EVD-days; P=0.026). There were no differences in all secondary outcomes analyzed. This multi-modal strategy was associated with high satisfaction among health care personnel. CONCLUSIONS: Implementation of a multi-modal strategy was associated with a reduction in the incidence of EVDAIs. This was in line with our goal of promoting a new culture of safety despite being in a resource-limited setting.

Taurolidine and Heparin as Catheter Lock Solution for Central Venous Catheters in Hemodialysis.

BACKGROUND: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available. CLINICAL TRIALS: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs. THERAPEUTIC ADVANCE: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment.

Public health surveillance and the data, information, knowledge, intelligence and wisdom paradigm / Vigilancia de salud pública y el paradigma de datos, información, conocimiento, inteligencia y sabiduría / Vigilância em saúde pública e o paradigma de dados, informações, conhecimento, inteligência e sabedoria

[ABSTRACT]. This article points out deficiencies in present-day definitions of public health surveillance, which include data collection, analysis, interpretation and dissemination, but not public health action. Controlling a public health problem of concern requires a public health response that goes beyond information dissemination. It is unde- sirable to have public health divided into data generation processes (public health surveillance) and data use processes (public health response), managed by two separate groups (surveillance experts and policy-makers). It is time to rethink the need to modernize the definition of public health surveillance, inspired by the authors’ enhanced Data, Information, Knowledge, Intelligence and Wisdom model. Our recommendations include expanding the scope of public health surveillance beyond information dissemination to comprise actionable knowledge (intelligence); mandating surveillance experts to assist policy-makers in making evidence-informed decisions; encouraging surveillance experts to become policy-makers; and incorporating public health literacy training – from data to knowledge to wisdom – into the curricula for all public health professionals. Work on modernizing the scope and definition of public health surveillance will be a good starting point.

[RESUMEN]. En este artículo se señalan las deficiencias de las definiciones actuales de la vigilancia de salud pública, que incluyen la recopilación, el análisis, la interpretación y la difusión de los datos, pero no las medidas de salud pública. El control de un problema de salud pública de interés exige una respuesta de salud pública que vaya más allá de la difusión de información. No es deseable que la salud pública esté dividida por un lado en procesos de generación de datos (vigilancia de salud pública) y por otro en procesos de uso de datos (respuesta de salud pública), gestionados por dos grupos diferentes (expertos en vigilancia y responsables de la formulación de políticas). Ha llegado el momento de replantear la necesidad de modernizar la definición de la vigilancia de salud pública tomando como referencia el modelo mejorado de Datos, Información, Cono- cimiento, Inteligencia y Sabiduría de los autores. Entre las recomendaciones que se proponen se encuentran las de ampliar el alcance de la vigilancia de salud pública más allá de la difusión de información para que incluya también el conocimiento aplicable (inteligencia); instar a los expertos en vigilancia a que presten ayuda a los responsables de la formulación de políticas en la toma de decisiones basadas en la evidencia; alentar a los expertos en vigilancia a que se conviertan en responsables de la formulación de políticas; e incorporar la formación en conocimientos básicos de salud pública (desde los datos hasta los conocimientos y la sabiduría) en los planes de estudio de todos los profesionales de la salud pública. Un buen punto de partida será trabajar en la modernización del alcance y la definición de la vigilancia de salud pública.

[RESUMO]. Este artigo aponta deficiências nas definições atuais de vigilância em saúde pública, que incluem coleta, análise, interpretação e disseminação de dados, mas não ações de saúde pública. O controle de um prob- lema preocupante de saúde pública exige uma resposta de saúde pública que vá além da disseminação de informações. A saúde pública não deve ser dividida em processos de geração de dados (vigilância em saúde pública) e processos de uso de dados (resposta de saúde pública) gerenciados por dois grupos distintos (especialistas em vigilância e formuladores de políticas). É hora de repensar a necessidade de modernizar a definição de vigilância em saúde pública, inspirada no modelo aprimorado de Dados, Informações, Con- hecimento, Inteligência e Sabedoria dos autores. Nossas recomendações incluem: expansão do escopo da vigilância em saúde pública para além da disseminação de informações, de modo a abranger conhecimentos acionáveis (inteligência); obrigatoriedade de que os especialistas em vigilância auxiliem os formuladores de políticas na tomada de decisões baseadas em evidências; incentivo para que os especialistas em vigilân- cia se tornem formuladores de políticas; e incorporação de capacitação em letramento em saúde pública (partindo dos dados para o conhecimento e em seguida para a sabedoria) nos currículos de todos os profis- sionais de saúde pública. O trabalho de modernizar o escopo e a definição de vigilância em saúde pública será um bom ponto de partida.

Public health surveillance and the data, information, knowledge, intelligence and wisdom paradigm.

This article points out deficiencies in present-day definitions of public health surveillance, which include data collection, analysis, interpretation and dissemination, but not public health action. Controlling a public health problem of concern requires a public health response that goes beyond information dissemination. It is undesirable to have public health divided into data generation processes (public health surveillance) and data use processes (public health response), managed by two separate groups (surveillance experts and policy-makers). It is time to rethink the need to modernize the definition of public health surveillance, inspired by the authors' enhanced Data, Information, Knowledge, Intelligence and Wisdom model. Our recommendations include expanding the scope of public health surveillance beyond information dissemination to comprise actionable knowledge (intelligence); mandating surveillance experts to assist policy-makers in making evidence-informed decisions; encouraging surveillance experts to become policy-makers; and incorporating public health literacy training - from data to knowledge to wisdom - into the curricula for all public health professionals. Work on modernizing the scope and definition of public health surveillance will be a good starting point.

En este artículo se señalan las deficiencias de las definiciones actuales de la vigilancia de salud pública, que incluyen la recopilación, el análisis, la interpretación y la difusión de los datos, pero no las medidas de salud pública. El control de un problema de salud pública de interés exige una respuesta de salud pública que vaya más allá de la difusión de información. No es deseable que la salud pública esté dividida por un lado en procesos de generación de datos (vigilancia de salud pública) y por otro en procesos de uso de datos (respuesta de salud pública), gestionados por dos grupos diferentes (expertos en vigilancia y responsables de la formulación de políticas). Ha llegado el momento de replantear la necesidad de modernizar la definición de la vigilancia de salud pública tomando como referencia el modelo mejorado de Datos, Información, Conocimiento, Inteligencia y Sabiduría de los autores. Entre las recomendaciones que se proponen se encuentran las de ampliar el alcance de la vigilancia de salud pública más allá de la difusión de información para que incluya también el conocimiento aplicable (inteligencia); instar a los expertos en vigilancia a que presten ayuda a los responsables de la formulación de políticas en la toma de decisiones basadas en la evidencia; alentar a los expertos en vigilancia a que se conviertan en responsables de la formulación de políticas; e incorporar la formación en conocimientos básicos de salud pública (desde los datos hasta los conocimientos y la sabiduría) en los planes de estudio de todos los profesionales de la salud pública. Un buen punto de partida será trabajar en la modernización del alcance y la definición de la vigilancia de salud pública.

Este artigo aponta deficiências nas definições atuais de vigilância em saúde pública, que incluem coleta, análise, interpretação e disseminação de dados, mas não ações de saúde pública. O controle de um problema preocupante de saúde pública exige uma resposta de saúde pública que vá além da disseminação de informações. A saúde pública não deve ser dividida em processos de geração de dados (vigilância em saúde pública) e processos de uso de dados (resposta de saúde pública) gerenciados por dois grupos distintos (especialistas em vigilância e formuladores de políticas). É hora de repensar a necessidade de modernizar a definição de vigilância em saúde pública, inspirada no modelo aprimorado de Dados, Informações, Conhecimento, Inteligência e Sabedoria dos autores. Nossas recomendações incluem: expansão do escopo da vigilância em saúde pública para além da disseminação de informações, de modo a abranger conhecimentos acionáveis (inteligência); obrigatoriedade de que os especialistas em vigilância auxiliem os formuladores de políticas na tomada de decisões baseadas em evidências; incentivo para que os especialistas em vigilância se tornem formuladores de políticas; e incorporação de capacitação em letramento em saúde pública (partindo dos dados para o conhecimento e em seguida para a sabedoria) nos currículos de todos os profissionais de saúde pública. O trabalho de modernizar o escopo e a definição de vigilância em saúde pública será um bom ponto de partida.

Microbiota-dependent activation of CD4+ T cells induces CTLA-4 blockade-associated colitis via Fcγ receptors.

Immune checkpoint inhibitors can stimulate antitumor immunity but can also induce toxicities termed immune-related adverse events (irAEs). Colitis is a common and severe irAE that can lead to treatment discontinuation. Mechanistic understanding of gut irAEs has been hampered because robust colitis is not observed in laboratory mice treated with checkpoint inhibitors. We report here that this limitation can be overcome by using mice harboring the microbiota of wild-caught mice, which develop overt colitis following treatment with anti-CTLA-4 antibodies. Intestinal inflammation is driven by unrestrained activation of IFNγ-producing CD4+ T cells and depletion of peripherally induced regulatory T cells through Fcγ receptor signaling. Accordingly, anti-CTLA-4 nanobodies that lack an Fc domain can promote antitumor responses without triggering colitis. This work suggests a strategy for mitigating gut irAEs while preserving antitumor stimulating effects of CTLA-4 blockade.

Richard L. Miller (1945-2023).

Memorializes Richard L. Miller (1945-2023). In the 1990s, Rick began a 24-year tenure at the University of Nebraska at Kearney. As department chair, Rick led the University of Nebraska at Kearney Psychology Department to the system-wide University of Nebraska Outstanding Teaching Department Award. In 2014, Rick moved to Texas A&M University-Kingsville, where he served as department chair. At Texas A&M University-Kingsville, he was recognized for teaching, mentorship, and scholarship, including the A&M Piper Professor Teaching Award. He served in many leadership roles, including the presidencies of the Society for the Teaching of Psychology (APA Division 2) and the Rocky Mountain Psychological Association. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Public health surveillance and the data, information, knowledge, intelligence and wisdom paradigm / Vigilancia de salud pública y el paradigma de datos, información, conocimiento, inteligencia y sabiduría / Vigilância em saúde pública e o paradigma de dados, informações, conhecimento, inteligência e sabedoria

ABSTRACT This article points out deficiencies in present-day definitions of public health surveillance, which include data collection, analysis, interpretation and dissemination, but not public health action. Controlling a public health problem of concern requires a public health response that goes beyond information dissemination. It is undesirable to have public health divided into data generation processes (public health surveillance) and data use processes (public health response), managed by two separate groups (surveillance experts and policy-makers). It is time to rethink the need to modernize the definition of public health surveillance, inspired by the authors' enhanced Data, Information, Knowledge, Intelligence and Wisdom model. Our recommendations include expanding the scope of public health surveillance beyond information dissemination to comprise actionable knowledge (intelligence); mandating surveillance experts to assist policy-makers in making evidence-informed decisions; encouraging surveillance experts to become policy-makers; and incorporating public health literacy training - from data to knowledge to wisdom - into the curricula for all public health professionals. Work on modernizing the scope and definition of public health surveillance will be a good starting point.

RESUMEN En este artículo se señalan las deficiencias de las definiciones actuales de la vigilancia de salud pública, que incluyen la recopilación, el análisis, la interpretación y la difusión de los datos, pero no las medidas de salud pública. El control de un problema de salud pública de interés exige una respuesta de salud pública que vaya más allá de la difusión de información. No es deseable que la salud pública esté dividida por un lado en procesos de generación de datos (vigilancia de salud pública) y por otro en procesos de uso de datos (respuesta de salud pública), gestionados por dos grupos diferentes (expertos en vigilancia y responsables de la formulación de políticas). Ha llegado el momento de replantear la necesidad de modernizar la definición de la vigilancia de salud pública tomando como referencia el modelo mejorado de Datos, Información, Conocimiento, Inteligencia y Sabiduría de los autores. Entre las recomendaciones que se proponen se encuentran las de ampliar el alcance de la vigilancia de salud pública más allá de la difusión de información para que incluya también el conocimiento aplicable (inteligencia); instar a los expertos en vigilancia a que presten ayuda a los responsables de la formulación de políticas en la toma de decisiones basadas en la evidencia; alentar a los expertos en vigilancia a que se conviertan en responsables de la formulación de políticas; e incorporar la formación en conocimientos básicos de salud pública (desde los datos hasta los conocimientos y la sabiduría) en los planes de estudio de todos los profesionales de la salud pública. Un buen punto de partida será trabajar en la modernización del alcance y la definición de la vigilancia de salud pública.

RESUMO Este artigo aponta deficiências nas definições atuais de vigilância em saúde pública, que incluem coleta, análise, interpretação e disseminação de dados, mas não ações de saúde pública. O controle de um problema preocupante de saúde pública exige uma resposta de saúde pública que vá além da disseminação de informações. A saúde pública não deve ser dividida em processos de geração de dados (vigilância em saúde pública) e processos de uso de dados (resposta de saúde pública) gerenciados por dois grupos distintos (especialistas em vigilância e formuladores de políticas). É hora de repensar a necessidade de modernizar a definição de vigilância em saúde pública, inspirada no modelo aprimorado de Dados, Informações, Conhecimento, Inteligência e Sabedoria dos autores. Nossas recomendações incluem: expansão do escopo da vigilância em saúde pública para além da disseminação de informações, de modo a abranger conhecimentos acionáveis (inteligência); obrigatoriedade de que os especialistas em vigilância auxiliem os formuladores de políticas na tomada de decisões baseadas em evidências; incentivo para que os especialistas em vigilância se tornem formuladores de políticas; e incorporação de capacitação em letramento em saúde pública (partindo dos dados para o conhecimento e em seguida para a sabedoria) nos currículos de todos os profissionais de saúde pública. O trabalho de modernizar o escopo e a definição de vigilância em saúde pública será um bom ponto de partida.

Outcomes of a first point of contact speech language therapy clinic for patients requiring vocal cord check pre and post thyroid/parathyroid surgery.

INTRODUCTION: Speech Language Therapy First Point of Contact Clinic (SLT-FPOCC) models can assist assessment of low-risk patient populations referred to ear, nose and throat (ENT) services. To further improve ENT waitlist management and compliance with best-practice care, consideration of other low-risk populations that could be safely managed through this service model is needed. The aims of this paper are to evaluate the clinical and service outcomes of completing vocal cord check (VCC) assessments for patients' pre and post thyroid/parathyroid surgery within an SLT-FPOCC model and examine consumer perceptions. METHODS & PROCEDURES: The service followed existing SLT-FPOCC procedures, with ENT triaging referrals, then SLT completing pre- and postoperative VCC assessment (interview, perceptual assessment, flexible nasendoscopy), with assessment data later reviewed by ENT to diagnose laryngeal pathology. Clinical and service outcomes were collected prospectively. Patients completed an anonymous post-service satisfaction survey. RESULTS: Of the first 100 patients referred for preoperative VCCs, SLT assessment identified 42 with dysphonia and 30 reporting dysphagia, while ENT confirmed 9 with significant preoperative anatomical findings. Eighty-three underwent surgery, with 63 (95 nerves at surgical risk) returning for a postoperative VCC. Postoperative VCC identified three temporary neuropraxias (3.2%) and three unilateral vocal fold paresis (3.2%). Patients were highly satisfied with the service. All 163 pre-/postoperative VCCs were completed with no adverse events. CONCLUSION & IMPLICATIONS: The current data support SLT-FPOCC service expansion to include pre and post thyroid/parathyroid surgery VCC checks, with positive consumer perception. The model supports delivery of best practice management (i.e., pre- and postoperative VCC) for patients receiving surgery for thyroid/parathyroid dysfunction, and associated efficiencies for ENT services. WHAT THIS PAPER ADDS: What is already known Assessment of laryngeal function via flexible nasoendoscopy is recommended best practice for patients pre and postthyroid/parathyroid surgery, as recurrent laryngeal nerve injury is a low incidence (<10%), yet well-recognised risk of these surgeries. Traditionally, general surgeons refer presurgical patients to ear, nose and throat (ENT) for vocal cord check (VCC) assessment. However, with access to specialist outpatient services under increasing pressure, there is growing support for utilisation of other health professionals, such as speech-language therapists working in first point of contact (FPOCC) models, to assist with the administration of pre- and postsurgical assessments of such low-risk populations. What this study adds This work expands on the emerging body of evidence for speech language therapy (SLT) led FPOCC models within ENT outpatient services, providing clinical and service outcomes to support the safety of a new model designed to administer VCCs for patients pre and post thyroid/parathyroid surgery. Adopting a similar model to a prior published SLT-led FPOCC model, the trained SLT completes the pre- and postsurgical VCC including flexible nasoendoscopy and videostroboscopy, with images and clinical information then presented to ENT for diagnosis and management planning. This study also provides the first data on consumer perceptions of this type of service model. Clinical implications of this study Data on 100 consecutive presurgical patients revealed positive service findings, supporting the safety of this model. Nature and incidence of clinical findings pre and post surgery were consistent with previously published studies using traditional models of care (i.e., ENT completing the flexible nasendoscopy). Consumer perception was positive. This model enables delivery of pre-and postsurgical assessments for patients receiving thyroid/parathyroid surgery, consistent with best practice care, and reduces burden on ENT services. In total 163 ENT appointments were avoided with this model, with positive implications for ENT waitlist management.

Functional MRI correlates of emotion regulation in major depressive disorder related to depressive disease load measured over nine years.

Major Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations between enduring depression and brain functioning during regulation of negative and positive emotions using cognitive reappraisal. We used fMRI-data from the longitudinal Netherlands Study of Depression and Anxiety acquired during an emotion regulation task in 77 individuals with MDD. Task-related brain activity was related to disease load, calculated from presence and severity of depression in the preceding nine years. Additionally, we explored task related brain-connectivity. Brain functioning in individuals with MDD was further compared to 35 controls to explore overlap between load-effects and general effects related to MDD history/presence. Disease load was not associated with changes in affect or with brain activity, but with connectivity between areas essential for processing, integrating and regulating emotional information during downregulation of negative emotions. Results did not overlap with general MDD-effects. Instead, MDD was generally associated with lower parietal activity during downregulation of negative emotions. During upregulation of positive emotions, disease load was related to connectivity between limbic regions (although driven by symptomatic state), and connectivity between frontal, insular and thalamic regions was lower in MDD (vs controls). Results suggest that previous depressive load relates to brain connectivity in relevant networks during downregulation of negative emotions. These abnormalities do not overlap with disease-general abnormalities and could foster an incremental vulnerability to recurrence or chronicity of MDD. Therefore, optimizing emotion regulation is a promising therapeutic target for improving long-term MDD course.

Biosecurity and Management Strategies for Economically Important Exotic Tephritid Fruit Fly Species in Australia.

Exotic tephritid incursions are of high concern to Australia's biosecurity and its horticultural industries. It is vital that Australia remains ready to respond to incursions as they arise, as an incursion of tephritid fruit fly species will result in significant economic losses. In this review, we compared Australian incursion management strategies for fruit flies with global management strategies and identified possible areas where improvements could be made in an Australian context. Overall, Australia has a good understanding of the main tephritid threats, of which Bactrocera species from across the Torres Strait (northern Australia) are of most concern. Effective tools for tephritid detection and early warning surveillance at points of entry are in place at ports and in horticultural areas Australia-wide and provide the basis for initiating biosecurity responses in the event of an incursion. Area-wide control measures used in successful eradication attempts globally are available for use in Australia. However, a specific tephritid emergency response plan identifying suitable response measures and control options for species of concern is not yet available. We have identified that Australia has the policies and management tools available to respond to an exotic tephritid incursion, but the speed at which this could be accomplished would be greatly improved by the development of species-specific emergency response plans.

Understanding and predicting future relapse in depression from resting state functional connectivity and self-referential processing.

BACKGROUND: The recurrent nature of Major Depressive Disorder (MDD) asks for a better understanding of mechanisms underlying relapse. Previously, self-referential processing abnormalities have been linked to vulnerability for relapse. We investigated whether abnormalities in self-referential cognitions and functioning of associated brain-networks persist upon remission and predict relapse. METHODS: Remitted recurrent MDD patients (n = 48) and never-depressed controls (n = 23) underwent resting-state fMRI scanning at baseline and were additionally assessed for their implicit depressed self-associations and ruminative behaviour. A template-based dual regression approach was used to investigate between-group differences in default mode, cingulo-opercular and frontoparietal network resting-state functional connectivity (RSFC). Additional prediction of relapse status at 18-month follow-up was investigated within patients using both regression analyses and machine learning classifiers. RESULTS: Remitted patients showed higher rumination, but no implicit depressed self-associations or RSFC abnormalities were observed between patients and controls. Nevertheless, relapse was related to i) baseline RSFC between the ventral default mode network and the precuneus, dorsomedial frontal gyrus, and inferior occipital lobe, ii) implicit self-associations, and iii) uncontrollability of ruminative thinking, when controlled for depressive symptomatology. Moreover, preliminary machine learning classifiers demonstrated that RSFC within the investigated networks predicted relapse on an individual basis. CONCLUSIONS: Remitted MDD patients seem to be commonly characterized by abnormal rumination, but not by implicit self-associations or abnormalities in relevant brain networks. Nevertheless, relapse was predicted by self-related cognitions and default mode RSFC during remission, suggesting that variations in self-relevant processing play a role in the complex dynamics associated with the vulnerability to developing recurrent depressive episodes. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, August 18, 2015, trial number NL53205.042.15.

Dynamical interactions reconfigure the gradient of cortical timescales.

The functional organization of the brain is usually presented with a back-to-front gradient of timescales, reflecting regional specialization with sensory areas (back) processing information faster than associative areas (front), which perform information integration. However, cognitive processes require not only local information processing but also coordinated activity across regions. Using magnetoencephalography recordings, we find that the functional connectivity at the edge level (between two regions) is also characterized by a back-to-front gradient of timescales following that of the regional gradient. Unexpectedly, we demonstrate a reverse front-to-back gradient when nonlocal interactions are prominent. Thus, the timescales are dynamic and can switch between back-to-front and front-to-back patterns.

Circulating magnesium as a potential risk stratification tool for sudden cardiac death: a systematic review.

BACKGROUND: Sudden cardiac death (SCD) is one of the main causes of cardiovascular mortality and accounts for 15-20% of deaths worldwide. The current stratification strategy using depressed left ventricular ejection fraction is insufficient to stratify the risk of SCD, especially in the general population. In recent years, there has been increasing evidence showing the antiarrhythmic properties of magnesium. In this systematic review, the authors aim to determine circulating magnesium as a potential risk stratification tool for SCD. METHODS: This systematic review was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was conducted in July 2021 with sources from Google Scholar, PubMed, Science Direct, EBSCO Medline, and ProQuest. RESULTS: A total of six studies were included in this review. Three studies conducted in the general population consistently showed lower risk of SCD in populations with high circulating magnesium. There was no association between circulating magnesium level and risk of SCD in intensive cardiac care unit (ICCU) patients, whilst the results were conflicting in congestive heart failure (CHF) patients. CONCLUSION: High circulating magnesium might have the potential to be utilized as a risk stratification tool for SCD, especially in the general population. However, further study is needed to support this evidence.

Identification of small-molecule protein-protein interaction inhibitors for NKG2D.

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ+, and CD8+ T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

Undiagnosed sub-valvular aortic stenosis with an associated Ventricular Septal Defect (VSD) presenting late in a multi-parous woman.

BACKGROUND: Sub-valvular aortic stenosis is a rare disorder that has a prevalence of 6.5% of all adult congenital heart diseases. The hemodynamic changes that occur in pregnancy with the resultant increase in cardiac output may not well be tolerated by a pregnant woman with sub-valvular aortic stenosis. CASE PRESENTATION: We report the case of a 34-year-old para 7 (6 alive + 1 dead) who has been experiencing intermittent episodes of easy fatigability on moderate exertion since childhood and had survived 6 prior pregnancies. During her last pregnancy, she started experiencing chest pain, palpitations, dyspnea, orthopnea, and pre-syncope at 36 weeks and had a caesarean section at 37 weeks on account of fetal distress. The post-delivery cardiac evaluation showed severe sub-valvular Aortic stenosis and a ventricular septal defect. CONCLUSION: Sub-valvular Aortic stenosis may progress slowly in adults and may be tolerated during pregnancy. Despite the rare presentation and contraindication of pregnancy in such a patient, she extraordinarily survived the pregnancy with a healthy baby. Routine cardiovascular assessment during prenatal, ante-natal and post-natal care is highly advocated particularly so in resource-poor settings.

Paracingulate Sulcus Length and Cortical Thickness in Schizophrenia Patients With and Without a Lifetime History of Auditory Hallucinations.

BACKGROUND: It has been theorized that hallucinations, a common symptom of schizophrenia, are caused by failures in reality monitoring. The paracingulate sulcus (PCS) has been implicated as a brain structure supporting reality monitoring with the absence or shorter length of PCS associated with an occurrence of hallucinations in schizophrenia. The absence or shorter length of PCS has been associated with an occurrence of hallucinations. There are inconsistent findings in the literature regarding the role of the asymmetry of this structure for hallucinations. Here, we investigated the length of the PCS and cortical thickness of surrounding structures in patients with a lifetime history of auditory verbal hallucinations (AVH). DESIGN: Seventy-seven patients and twenty-eight healthy controls (HC) underwent an anatomical MRI scan. PCS length and cortical thickness were estimated using Mango brain visualization and FreeSurfer, respectively. Patients with AVH (n = 45) and patients without AVH were compared (n = 32) to the controls. RESULTS: PCS length significantly differed between HC and patient groups (F(2,102) = 3.57, P = .032) in the left but not in the right sulcus. We found significantly longer PCS between HC and AVH group but no difference between patient groups. Similarly, we found significant thinning of cortical structures including structures surrounding anterior parts of PCS between HC and patients either in general or per group, but no significant differences were observed between patient groups. CONCLUSIONS: PCS length in the left hemisphere is shorter in schizophrenia patients with hallucinations as compared to HC subjects. The patient group without hallucinations was in between those 2 groups. Cortical thickness of neighboring areas of PCS is diminished in patient groups relative to the healthy comparison subjects. The role of lateralization and functional involvement of the PCS region in processes underlying hallucinations, such as reality monitoring, needs further clarification.

Large parathyroid adenomas: Potential mechanisms to reconcile adenoma size and disease phenotype.

Parathyroid adenomas weighing more than 3.5 g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants accounting for no more than 1.5% of all parathyroid adenomas. Large parathyroid adenomas are often associated with more severe form of the disease, including osteitis fibrosa cystica (OFC) and share many biochemical, histological, and molecular features of both benign and malignant parathyroid neoplasms, and are considered a distinct clinical entity. However, the pathogenesis of oversized parathyroid adenomas and the often-associated skeletal phenotype remains unclear. We present 5 cases of primary hyperparathyroidism (PHPT) with OFC, an uncommon manifestation of contemporary PHPT, associated with larger parathyroid adenomas, seen in the Bone and Mineral Disorders Clinic of the Henry Ford Health in the last 30 years to illustrate the critical role of vitamin D nutrition in the pathogenesis of both the OFC and adenoma size. The estimated prevalence of OFC was very low 0.2%, 5 of the >3000 surgically confirmed cases of PHPT seen during this time. The mean ± SD values were: age: 36.8 ± 22.1 years (4 of the 5 <36years), serum calcium 11.6 ± 1.1 mg/dl, alkaline phosphatase 799 ± 487 IU/L, PTH 1440 ± 477 pg/ml, 25-hydroxyvitamin D 13.0 ± 8.9 ng/ml, 1,25-dihyroxyvitamin D 26.5 ± 13.7 pg/ml, urine calcium 562 ± 274 mg/day, and parathyroid adenoma weight 4.53 ± 2.2 g. Parathyroidectomy led to the resolution of both the biochemical indices and OFC in each patient without recurrence over >10 years of follow-up. Because OFC is a very rare in the West, but very common areas of endemic vitamin D deficiency, we also examined the relationship between vitamin D nutrition, as assessed by serum 25-hydroxyvitamin D level, and parathyroid adenoma weight as well as prevalence of OFC in two large secularly diverse cohorts of patients with PHPT (Detroit, USA and Chandigarh, India). Based on this relationship and the relative prevalence of OFC in these two large cohorts, we propose that vitamin D nutrition (and perhaps calcium nutrition) best explains both the adenoma size and prevalence of OFC.

Evaluation of health service outcomes for an audiology first point of contact retrocochlear clinic: a 6-year retrospective cohort study.

OBJECTIVE: Although existing studies of audiology first point of contact clinics which screen for retrocochlear pathology have demonstrated positive clinical outcomes, they have provided limited information regarding service impacts. Thus, this study aimed to evaluate both the clinical and health service outcomes of an audiology first point of contact (FPOC) clinic for adults referred to ENT services with suspected retrocochlear pathology. DESIGN: Retrospective cohort study. STUDY SAMPLE: All 1123 patients referred to the clinic over a 6-year period (2013-2019). RESULTS: Most (73.7%) of the 1123 patients referred to the Retrocochlear Clinic were managed and discharged by the audiologist and did not require ENT appointment. Almost half (43.1%) were directly referred for MRI imaging, of which 4 (1.1%) were diagnosed with Vestibular Schwannoma. Waiting times for first appointments significantly (p < 0.001) reduced from a median of 748 days to 63.5 days over the 6-year period. Attendance rates also significantly (p < 0.001) improved over this time (from 52.2% to 90%). There were no adverse events reported. Of those discharged without attending an ENT appointment, 1.8% were rereferred to ENT within 12 months of discharge. CONCLUSIONS: This audiology FPOC Retrocochlear Clinic was shown to be a safe and effective alternative service model.