User-Centered Design of a Preference-Driven Patient Activation Tool for Optimizing Depression Treatment in Integrated Primary Care Settings (The Transform DepCare Study).

BACKGROUND: Few patient engagement tools incorporate the complex patient experiences, contexts, and workflows that limit depression treatment implementation. OBJECTIVE: Describe a user-centered design (UCD) process for operationalizing a preference-driven patient activation tool. DESIGN: Informed by UCD and behavior change/implementation science principles, we designed a preference-driven patient activation prototype for engaging patients in depression treatment. We conducted three usability cycles using different recruitment/implementation approaches: near live/live testing in primary care waiting rooms (V1-2) and lab-based think aloud testing (V3) oversampling older, low-literacy, and Spanish-speaking patients in the community and via EHR algorithms. We elicited clinician and "heuristic" expert input. MAIN MEASURES: We administered the system usability scale (SUS) all three cycles and pre-post V3, the patient activation measure, decisional conflict scale, and depression treatment barriers. We employed descriptive statistics and thematically analyzed observer notes and transcripts for usability constructs. RESULTS: Overall, 43 patients, 3 clinicians, and 5 heuristic (a usability engineering method for identifying usability problems) experts participated. Among patients, 41.9% were ≥ 65 years old, 79.1% female, 23.3% Black, 62.8% Hispanic, and 55.8% Spanish-speaking and 46.5% had ≤ high school education. We described V1-3 usability (67.2, 77.3, 81.8), treatment seeking (92.3%, 87.5%, 92.9%), likelihood/comfort discussing with clinician (76.9%, 87.5%, 100.0%), and pre vs. post decisional conflict (23.7 vs. 15.2), treatment awareness (71.4% vs. 92.9%), interest in antidepressants (7.1% vs. 14.3%), and patient activation (66.8 vs. 70.9), with fewer barriers pertaining to cost/insurance, access/coordination, and self-efficacy/stigma/treatment efficacy. Key themes included digital literacy, understandability, high acceptability for aesthetics, high usefulness of patient/clinician videos, and workflow limitations. We adapted manual entry/visibility/content; added patient activation and a personalized algorithm; and proposed flexible, care manager delivery leveraging clinic screening protocols. DISCUSSION: We provide an example of leveraging UCD to design/adapt a real-world, patient experience and workflow-aligned patient activation tool in diverse populations.

Cardiac-Specific Deletion of Scn8a Mitigates Dravet Syndrome-Associated Sudden Death in Adults.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a fatal complication experienced by otherwise healthy epilepsy patients. Dravet syndrome (DS) is an inherited epileptic disorder resulting from loss of function of the voltage-gated sodium channel, NaV 1.1, and is associated with particularly high SUDEP risk. Evidence is mounting that NaVs abundant in the brain also occur in the heart, suggesting that the very molecular mechanisms underlying epilepsy could also precipitate cardiac arrhythmias and sudden death. Despite marked reduction of NaV 1.1 functional expression in DS, pathogenic late sodium current (INa,L) is paradoxically increased in DS hearts. However, the mechanisms by which DS directly impacts the heart to promote sudden death remain unclear. OBJECTIVES: In this study, the authors sought to provide evidence implicating remodeling of Na+ - and Ca2+ -handling machinery, including NaV 1.6 and Na+/Ca2+exchanger (NCX) within transverse (T)-tubules in DS-associated arrhythmias. METHODS: The authors undertook scanning ion conductance microscopy (SICM)-guided patch clamp, super-resolution microscopy, confocal Ca2+ imaging, and in vivo electrocardiography studies in Scn1a haploinsufficient murine model of DS. RESULTS: DS promotes INa,L in T-tubular nanodomains, but not in other subcellular regions. Consistent with increased NaV activity in these regions, super-resolution microscopy revealed increased NaV 1.6 density near Ca2+release channels, the ryanodine receptors (RyR2) and NCX in DS relative to WT hearts. The resulting INa,L in these regions promoted aberrant Ca2+ release, leading to ventricular arrhythmias in vivo. Cardiac-specific deletion of NaV 1.6 protects adult DS mice from increased T-tubular late NaV activity and the resulting arrhythmias, as well as sudden death. CONCLUSIONS: These data demonstrate that NaV 1.6 undergoes remodeling within T-tubules of adult DS hearts serving as a substrate for Ca2+ -mediated cardiac arrhythmias and may be a druggable target for the prevention of SUDEP in adult DS subjects.

Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.

BACKGROUND: Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little is known regarding how infection can acutely induce an arrhythmogenic substrate before significant immune responses. Adenovirus is a leading cause of myocarditis, but due to species specificity, models of infection are lacking, and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse adenovirus type-3 was previously reported as cardiotropic, yet it has not been utilized to understand the mechanisms of cardiac infection and pathology. METHODS: We have developed mouse adenovirus type-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart before an appreciable immune response or gross cardiomyopathy. RESULTS: Optical mapping of infected hearts exposes decreases in conduction velocity concomitant with increased Cx43Ser368 phosphorylation, a residue known to regulate gap junction function. Hearts from animals harboring a phospho-null mutation at Cx43Ser368 are protected against mouse adenovirus type-3-induced conduction velocity slowing. Additional to gap junction alterations, patch clamping of mouse adenovirus type-3-infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreased IK1 and IKs current density. Turning to human systems, we find human adenovirus type-5 increases phosphorylation of Cx43Ser368 and disrupts synchrony in human induced pluripotent stem cell-derived cardiomyocytes, indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. CONCLUSIONS: Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.

Realizing the price of academic freedom.

Since 2010, the number of life science doctoral graduates opting into academic postdoctoral employment has steadily declined. In recent years, this decline has made routine headlines in academic news cycles, and faculty members, universities, and funding bodies alike have begun to take notice. In November 2022, the National Institutes of Health (NIH) convened a special interest group to address the problems in postdoctoral recruitment and retention. In response, the American Physiological Society Science Policy Committee highlighted several key issues in postdoctoral training and working conditions and offered the NIH solutions to consider. There are known issues that affect postdoctoral recruitment and retention efforts: low wages relative to other employment sectors, a heavy workload, and poor job prospects to name a few. Unfortunately, these concerns are frequently dismissed as "the price of doing business in academia," and postdoctoral scholars are promised that if they overcome the trials and tribulations of this training period, the reward at the end, a career with academic freedom to pursue your own interests, justifies the means. However, academic freedom cannot and should not be used as the band-aid in a system where most of us will never actually experience academic freedom. Instead, we should systematically embrace solutions that improve the personal and professional health of early career researchers in all levels of training and independence if the goal is to truly shore up the academic workforce.

Genome sequencing and detection of Philippine SARS-CoV-2 infections with viruses classified under the B.1.1.7 lineage

We report the sequencing and detection of 39 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage (UK variant) in the Philippines.

Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines

The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.35 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.

ANALYSIS OF SARS-COV-2 GENOME SEQUENCES FROM THE PHILIPPINES: GENETIC SURVEILLANCE AND TRANSMISSION DYNAMICS

The spread of the corona virus around the world has spurred travel restrictions and community lockdowns to manage the transmission of infection. In the Philippines, with a large population of overseas Filipino contract workers (OFWs), as well as foreign workers in the local online gaming industry and visitors from nearby countries, the first reported cases were from a Chinese couple visiting the country in mid-January 2020. Three months on, by mid-March, the COVID-19 cases in the Philippines had reached its first 100, before it exploded to the present 178,022 cases (as of August 20, 2020). Here, we report a genomic survey of six (6) whole genomes of the SARS-CoV-2 virus collected from COVID-19 patients seen at the Philippine General Hospital, the major referral hospital for COVID-19 cases in Metro Manila at about the time the Philippines had over a hundred cases. Analysis of commonly observed variants did not reveal a clear pattern of the virus evolving towards a more infectious and severe strain. When combined with other available viral sequences from the Philippines and from GISAID, phylogenomic analysis reveal that the sequenced Philippine isolates can be classified into three primary groups based on collection dates and possible infection sources: (1) January samples collected in the early phases of the pandemic that are closely associated with isolates from Wuhan, China; (2) March samples that are mainly linked to the M/V Diamond Princess Cruise Ship outbreak; and (3) June samples that clustered with European isolates, one of which already harbor the globally prevalent D614G mutation which initially circulated in Europe. The presence of community-acquired viral transmission amidst compulsory and strict quarantine protocols, particularly for repatriated Filipino workers, highlights the need for a refinement of the quarantine, testing, and tracing strategies currently being implemented to adapt to the current pandemic situation.

Evaluation and management of blunt traumatic aortic injury: a practice management guideline from the Eastern Association for the Surgery of Trauma

BACKGROUND: Blunt traumatic aortic injury (BTAI) is the second most common cause of death in trauma patients. Eighty percent of patients with BTAI will die before reaching a trauma center. The issues of how to diagnose, treat, and manage BTAI were first addressed by the Eastern Association for the Surgery of Trauma (EAST) in the practice management guidelines on this topic published in 2000. Since that time, there have been advances in the management of BTAI. As a result, the EAST guidelines committee decided to develop updated guidelines for this topic using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework recently adopted by EAST. METHODS: A systematic review of the MEDLINE database using PubMed was performed. The search retrieved English language articles regarding BTAI from 1998 to 2013. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included imaging to diagnose BTAI, type of operative repair, and timing of operative repair. RESULTS: Sixty articles were identified. Of these, 51 articles were selected to construct the guidelines. CONCLUSION: There have been changes in practice since the publication of the previous guidelines in 2000. Computed tomography of the chest with intravenous contrast is strongly recommended to diagnose clinically significant BTAI. Endovascular repair is strongly recommended for patients without contraindications. Delayed repair of BTAI is suggested, with the stipulation that effective blood pressure control must be used in these patients.(AU)

HIV infection seroprevalence and risk factor study among pregnant women attending the Antenatal Clinic at the University Hospital of the West Indies, Kingston, Jamaica

The objectives of this study were to determine the seroprevalence and risk factors for Human Immunodeficiency Virus (HIV) infection among the antenatal clinic population at the University Hospital of the West Indies (UHWI). Pregnant mothers (4186) attending antenatal clinic at the UHWI were screened for HIV infection between September, 1998, and October, 2000. Tests were performed with the use of Abbott enzyme immunoassay (EIA) kits for the detection of antibodies to HIV 1 and 2. Demographic characteristics and risk factor assessments were performed using a questionnaire for all positive cases and four randomly selected negative controls matched by age to each positive case. Twenty-one women were found to be HIV positive. Nineteen of these women were not previously aware that they were HIV-positive. The seroprevalence of HIV infection among antenatal mothers was 0.5. The mean age of cases was 29.3 +/- 4.6 years. There was no significant difference between cases and controls with regards to parity, socio-economic status and educational achievement. Women residing in urban Kingston and St Andrew (Odds ratio (OR) 5, 95 confidence interval (CI) 1.4, 18), as well as those with a higher number of lifetime sexual partners (OR 1.42, 95 CI 1.13, 1.79) and those with previous sexually transmitted diseases (OR 3.4, 95 CI 1.1, 10.6) were at greater risk for HIV infection. In contrast, women who commenced coitus at a later age were at less risk of becoming infected (OR 0.79, 95 CI 0.6, 0.97). This study demonstrates a low seroprevalence of HIV in the UHWI antenatal population compared to the reported seroprevalence of 2-8 in pregnant women in Latin America and the Caribbean. The results from this study emphasize the continuing need for voluntary HIV testing and HIV/AIDS educational campaign for this vulnerable group.

Respuesta inmunológica de linfocitos T frente a diferentes fracciones antigénicas de mycobacterium bovis en poliartritis crónica juvenil / T lymphocyte immunological response to different antigenic fractions of mycobacterium bovis in juvenile chronic polyarthritis

Background: The possible relationship of stress or heat-shock proteins (hsp) with the pathogenesis of autoimmune disease has been intensely studied recently. In adult rheumatoid arthritis, a bacterial hsp (65 kDa hsp from Mycobacterium tuberculosis or bovis) would have a cross reactivity with a hsp of ARTICULAR cartilage. Aim: To assess the cellular immune response to the 65 kA hsp from M Bovis in children. Patients and methods: The proliferative response of peripheral mononuclear cells of 20 children with juvenile chronic polyarthritis and 20 healthy controls, against the 65 kDa hsp and other antigenic fractions from M bovis, was studied. Results: Patients with juvenile chronic polyarthritis had a intense reaction against 65 kDa fraction and a second fraction located between 32.5 and 27.5 kDa. Patients with a prolonged evolution of the disease (more than five years), reacted preferentially to an antigenic segment located between 32.5 and 27.5 kDa and those with a shorter evolution did so with an antigen of 27.5-18.5 kDa. Conclusions: These results support the hypothesis that 65 kDa hsp from M bovis is involved in the pathogenesis of chronic juvenile polyarthritis and suggest that patients with short or prolonged evolutions of the disease would react to different antigenic fractions

Utilidad clínica de multitest en la evaluación de inmunidad celular / Usefulness of multitest in the assessment of cell immunity

The aim of this work was to assess cellular immunity using the Multitest CMI and relate its results with lymphocyte counts and lymphocyte subpopulations determined using monoclonal antibodies against CD4 and CD8 and fluorescence microscopy. We studied 51 patients (31 males), 20 infected with HIV, 18 with recurring infections, 5 with cancer, 2 with tuberculosis and 6 with miscellaneous diagnoses. According to Multitest results, patients were classified as normal, hypoergic or anergic. Twenty five percent of patients were normal, 65 percent hypoergic and 10 percent anergic. Eighty percent of anergic patients were infected with HIV. No differences in total lymphocyte count were observed between the 3 groups. CD4 lymphocyte count was lower in anergic patients when compared with the other groups. All patients with CD4 counts below 200 cells/mmü were anergic. It is cincluded that Multitest CMI is useful for the assessment of cellular immunity and complements the determination of lymphocyte subpopulations

Amplificación de un segmento del gen BCG en el hombre / Segment amplification of the BCG gen in man

Estudios recientes en animales de experimentación han identificado la participación de un gen, denominado BCG, en la inmunidad innata frente a la infección por mycobacterium tuberculosis. En el hombre se desconoce aún su existencia, sin mebargo, hay antecedentes que apoyan la presencia de un gen homólogo en el cromosoma 2q. El objetivo de nuestro estudio fue confirmar en animales de experimentación, la presencia de este gen, y buscar una secuencia homóloga a nivel humano. Se estudiaron los DNA de 2 cepas de ratones resistentes, 2 susceptibles a la infección tuberculosa y los DNA de 10 niños sanos y 10 tuberculosos por medio de la técnica de reacción de polimerasa en cadena con oligonecleótidos específicos. Los resultados permitieron comprobar la presencia de este gen en ratones con la amplificación del segmento de DNA esperado. En el hombre se obtuvo la amplificación de un segmento de DNA, con un tamaño molecular diferente al del ratón. Estos hallazgos sugieren la existencia del gen BCG en humanos, el que presentaría diferencias importantes a nivel molecular con el descrito en animales de experimentación

Determinación de receptores de haptoglobina y proteína C reactiva en linfocitos de pacientes con patología autoinmune e infecciosa / Determination of haptoglobin and C reactive protein receptors in lymphocytes of patients with autoimmune and infectious diseases

En la actualidad, se desconoce el rol del aumento de proteína C recativa (PCR) y haptoglobina (Hp) en la respuesta de fase aguda. Algunos autores han postulado la posibilidad que estas proteínas intervengan en la regulación del sistema inmune. Nuestro estudio estuvo orientado a demostrar la presencia de receptores para Hp y PCR en linfocitos procedentes de niños sanos y niños con patología infecciosa y autoinmune. Para este efecto, se obtuvieron células mononucleares de 48 niños (24 sanos, 14 con infecciones demostradas y 10 con enfermedades autoinmune), se incubaron por 72 horas a 37 grados Celsius y 5 por ciento de CO2, con estímulo de fitohemaglutinina (PHA) y con diferentes concentraciones de PCR y Hp en el medio. Se separaron las subpoblaciones CD4 y CD8 mediante anticuerpos monoclonales unidos a partículas magnéticas y se analizó la presencia de receptores a distintos tiempos (0, 24, 48 y 72 horas) mediante una técnica de inmunofluorescencia indirecta

Inmunodeficiencias primarias en el área occidente de Santiago: estudio de 6 casos (1981-1994) / Primary immunodeficiencies in western metropolitan area at Santiago: study of 6 cases (1981-1994)

Se analiza una casuística de 6 pacientes con inmunodeficiencias primarias, estudiados entre 1981 y 1994 y que cumplen con los criterios establecidos por la OMS en 1991. Se plantean las siguientes conclusiones: 1. Las inmunodeficiencias primarias específicas más frecuentes fueron las predominantemente de anticuerpos 2. Las infecciones recurrentes fueron el pilar del diagnóstico clínico. Estas fueron causadas por bacterias encapsuladas y afectaron de preferencia la piel y los sistemas respiratorio y digestivo 3. A todo paciente con score de Haeney mayor o igual a 25, independiente de su edad y especialmente si no tiene causa reconocible de inmunodeficiencia secundaria, debería evaluarse inmunológicamente 4. En las inmunodeficiencias humorales los exámenes más útiles fueron la electroforesis de proteínas séricas y la cuantificación de inmunoglobulinas, mientras que en las celulares lo fue el Multitest

Deficiencia selectiva de inmunoglobulina A (IgA) / Selective IgA deficiency

Un niño de 9 años con deficiencia selectiva de inmunoglobulina A (IgA) que fue pesquisado al realizar un estudio sobre valores normales de inmunoglobulinas séricas en niños chilenos sanos del área metropolitana de salud Occidente. Las concentraciones séricas de IgA de este paciente fueron de 0 mg/dl en muestras repetidas. No se encontraron antecedentes familiares, evidencia de enfermedad, ni alteraciones de laboratorio asociadas