Superior protection against paratuberculosis by a heterologous prime-boost immunization in a murine model.

Vaccination is the best strategy to control Paratuberculosis (PTB), which is a significant disease in cattle and sheep. Previously we showed the humoral and cellular immune response induced by a novel vaccine candidate against PTB based on the Argentinian Mycobacterium avium subspecies paratuberculosis (Map) 6611 strain. To improve 6611 immunogenicity and efficacy, we evaluated this vaccine candidate in mice with two different adjuvants and a heterologous boost with a recombinant modified vaccinia Ankara virus (MVA) expressing the antigen 85A (MVA85A). We observed that boosting with MVA85A did not improve total IgG or specific isotypes in serum induced by one or two doses of 6611 formulated with incomplete Freund's adjuvant (IFA). However, when 6611 was formulated with ISA201 adjuvant, MVA85A boost enhanced the production of IFNγ, Th1/Th17 cytokines (IL-2, TNF, IL-17A) and IL-6, IL-4 and IL-10. Also, this group showed the highest levels of IgG2b and IgG3 isotypes, both important for better protection against Map infection in the murine model. Finally, the heterologous scheme elicited the highest levels of protection after Map challenge (lowest CFU count and liver lesion score). In conclusion, our results encourage further evaluation of 6611 strain + ISA201 prime and MVA85A boost in bovines.

Limited usefulness of the IS6110 touchdown-PCR in blood for tuberculin skin test false-negative cattle with serological response to Mycobacterium bovis.

Ante-mortem diagnosis of bovine tuberculosis (bTB) is based mainly on the tuberculin skin test (TST) and the ɣ-IFN release assay (IGRA). Some infected animals escape screening tests, thus, limit herd sanitation. Previous reports have suggested a predominant pattern of multi-organ lesions attributable to Mycobacterium bovis (the causative agent of bTB) bacteraemia. A case-control study was conducted to investigate blood PCR as an alternative tool for improving ante-mortem detection of TST false-negative bovines. Cases comprised 70 TST false-negative bovines (cases), which were serology positive, and controls included 81 TST positive bovines; all of them confirmed as infected with M. bovis. Detection of the IS6110 target through touchdown blood-PCR (IS6110 TD-PCR) was performed. The positivity of the blood-PCR was 27.2% in the control group. This performance was similar to the 15% obtained among cases (p = 0.134). Most cases identified by the IS6110 TD-PCR exhibited focalized lesions (p = 0.002). Results demonstrated that blood-PCR could detect TST false-negative cattle, even if they are negative for IGRA. Considering that cases exhibited humoral response to M. bovis, further studies conducted in a pre-serological stage could provide evidence about the real contribution of the technique in herds.

Ferromagnetism on an atom-thick & extended 2D metal-organic coordination network.

Ferromagnetism is the collective alignment of atomic spins that retain a net magnetic moment below the Curie temperature, even in the absence of external magnetic fields. Reducing this fundamental property into strictly two-dimensions was proposed in metal-organic coordination networks, but thus far has eluded experimental realization. In this work, we demonstrate that extended, cooperative ferromagnetism is feasible in an atomically thin two-dimensional metal-organic coordination network, despite only ≈ 5% of the monolayer being composed of Fe atoms. The resulting ferromagnetic state exhibits an out-of-plane easy-axis square-like hysteresis loop with large coercive fields over 2 Tesla, significant magnetic anisotropy, and persists up to TC ≈ 35 K. These properties are driven by exchange interactions mainly mediated by the molecular linkers. Our findings resolve a two decade search for ferromagnetism in two-dimensional metal-organic coordination networks.

Impact of Geriatric Consult Evaluations on Hospital Admission Rates for Older Adults.

Introduction: We examined the impact of a geriatric consult program in the emergency department (ED) and an ED observation geriatric care unit (GCU) setting on hospital admission rates for older ED patients. Methods: We performed a retrospective case control study from June 1-August 31, 2019 (pre-program) to September 24, 2019-January 31, 2020 (post-program). Post-program geriatric consults were readily available in the ED and required in the GCU setting. Hospital admission rates (outcome) are reported for patients who received a geriatric consult evaluation (intervention). We analyzed probability of admission using a mixed-effects logistic regression model that included age, gender, recent ED visit, Charlson Comorbidity Index, referral to ED observation, and geriatric consult evaluation as predictor variables. Results: A total of 9,663 geriatric ED encounters occurred, 4,042 pre-program and 5,621 post-program. Overall, ED admission rates for geriatric patients were similar pre- and post-program (44.8% vs 43.9%, P = 0.39). Of 243 geriatric consults, 149 (61.3%) occurred in the GCU. Overall admission rates post-program for patients receiving geriatric intervention were significantly lower compared to pre-program (23.4% vs 44.9%, P < 0.001). Post-program GCU hospital admission rates were significantly lower than pre-program ED observation unit admission rates (14/149, 9.4%, vs 111/477, 23.3%, P < 0.001). In the logistic regression model, admissions post-program were lower when a geriatric consult evaluation occurred (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.41-0.83). Hospital admissions for older ED observation patients were also significantly decreased when a geriatric consult was obtained (GCU vs pre-program ED observation unit; OR 0.27, 95% CI 0.14-0.50). Conclusion: Geriatric consult evaluations were associated with significantly lower rates of hospital admission and persisted when controlled for age, gender, comorbidities, and ED observation unit placement. This model may allow healthcare systems to decrease potentially avoidable hospital admission rates in older ED patients.

Autologous Single Semitendinosus Anatomical Posterolateral Corner Reconstruction With Adjustable-Loop Cortical Suspension Devices.

We present our surgical technique for the reconstruction of the posterolateral corner of the knee. It is a tibia- and fibular-based reconstruction technique. Most of these procedures require the use of 2 tendons (autograft or allograft). In our technique, a single semitendinosus tendon is required, making the procedure more suitable if the surgeon prefers the use of autograft or when there is no access to a tissue bank. This is even more important in the setting of multiligament knee injuries. The most defining feature of this modification is the possibility of achieving the desired graft tension in a progressive and independent way, due to the use of 3 adjustable-loop cortical suspension devices.

Traducción y validez del Literacy of Suicide Scale Short Form en población peruana

La educación sanitaria implica a los profesionales y población general en la alfabetización en salud mental y física para aumentar la búsqueda de ayuda y reducir el estigma. El suicidio es un problema frecuente en población general que afecta a los familiares, red social y profesionales de la salud, siendo necesario una mayor alfabetización sobre las conductas suicidas. El objetivo del estudio fue realizar la traducción al español y validación del Literacy of Suicide Scale Short Form (LOSS-SF) en adultos peruanos de población general. La investigación es de tipo instrumental y participaron 1020 adultos. La traducción inversa se utilizó para la versión en español. Se estimó un modelo Rasch y funcionamiento diferencial del ítem (DIF). En promedio, los participantes tuvieron mayor dificultad con los ítems asociados con los factores de riesgo (26.6% de aciertos) y signos o indicadores del suicidio (26.9% de aciertos), y la menor dificultad con el tratamiento y prevención (57.7% de aciertos). Se evidenció una adecuada validez de contenido (V > .70) y los ítems 11 y 12 tuvieron el mayor parámetro de discriminación. Además, no hubo evidencia de DIF según sexo y el LOSS-SF es más útil en niveles medios y altos del constructo. En conclusión, la versión en español del LOSS-SF presenta fuentes de evidencias de validez basadas en el contenido, estructura interna, confiabilidad e invarianza según sexo. Se recomienda su uso en población general adulta y comparaciones según sexo, siendo útil en programas de prevención y actividades de concientización sobre el suicidio.

Health education involves professionals and the general population on mental and physical health literacy to increase help-seeking and reduce stigma. Suicide is a frequent problem in the general population that affects family members, social network and health professionals, being a need for increased literacy about suicidal behaviors. The objective of the study was make the translation into Spanish and validation of the Literacy of Suicide Scale Short Form in Peruvian adults from the general population. The research was instrumental and 1020 adults participated in the study. Back translation was used for the Spanish version. A Rasch model and differential item functioning (DIF) were estimated. On average, participants had the greatest difficulty with the items associated with risk factors (26.6% correct) and signs or indicators of suicide (26.9% correct), and the least difficulty with treatment and prevention (57.7% correct). There was evidence of adequate content validity (V > .70) and items 11 and 12 had the more discrimination parameter. In addition, there was no evidence of DIF according to sex and the LOSS-SF is more useful at medium and high levels of the construct. In conclusion, the Spanish version of the LOSS-SF presents sources of evidence of validity based on content, internal structure, reliability and invariance by sex. Its use is recommended in the general adult population and comparisons according to sex, being useful in prevention programs and suicide awareness activities.

A educação sanitária envolve profissionais e a população em geral em alfabetização em saúde mental e física para aumentar a procura de ajuda e reduzir o estigma. O suicídio é um problema freqüente na população em geral que afeta membros da família, redes sociais e profissionais de saúde, e há uma necessidade de maior alfabetização sobre os comportamentos suicidas. O objetivo do estudo era traduzir para o espanhol e validar a Literatura de Escala Curta de Suicídio (LOSS-SF) em adultos peruanos da população em geral. A pesquisa foi instrumental e participaram 1020 adultos. A tradução de volta foi utilizada para a versão em espanhol. Foi estimado um modelo Rasch e o funcionamento do item diferencial (DIF). Em média, os participantes tiveram a maior dificuldade com itens associados a fatores de risco (26.6% correto) e sinais ou indicadores de suicídio (26.9% correto), e a menor dificuldade com tratamento e prevenção (57.7% correto). Havia uma validade de conteúdo adequada (V > .70) e os itens 11 e 12 tinham o maior parâmetro de discriminação. Além disso, não havia evidência de DIF por sexo e a LOSS-SF é mais útil em níveis médios e altos da construção. Em conclusão, a versão espanhola da LOSS-SF apresenta fontes de evidência de validade baseada em conteúdo, estrutura interna, confiabilidade e invariância de sexo. É recomendado para uso na população adulta em geral e comparações por sexo, sendo útil em programas de prevenção de suicídios e atividades de conscientização de suicídios.

Agitation Management in the Emergency Department with Physical Restraints: Where Do These Patients End Up?

INTRODUCTION: Agitation is frequently encountered in the emergency department (ED) and can range from psychomotor restlessness to overt aggression and violent behavior. Among all ED patients, 2.6% present with agitation or become agitated during their ED visit. We aimed to determine ED disposition for patients requiring agitation management with physical restraints. METHODS: This was a retrospective cohort of all adult patients who presented to one of 19 EDs in a large integrated healthcare system and received agitation management with physical restraints between January 1, 2018-December 31, 2020. Categorical variables are presented as frequency and percentages, and continuous variables are presented as medians and interquartile range. RESULTS: There were 3,539 patients who had agitation management with physical restraints included in this study. In total 2,076 (58.8%) were admitted to the hospital (95% CI [confidence interval] 0.572-0.605), and of those 81.4% were admitted to a primary medical floor and 18.6% were medically cleared and admitted to a psychiatric unit. Overall, 41.2% were able to be medically cleared and discharged from the ED. Mean age was 40.9 years, 2,140 were male (59.1%), 1,736 were White (50.3%), and 1,527 (43%) were Black. We found 26% had abnormal ethanol, (95% CI 0.245-0.274) and 54.6% had an abnormal toxicology screen (95% CI 0.529-0.562). A significant number were administered a benzodiazepine or antipsychotic in the ED (88.44%) (95% CI 0.874-0.895). CONCLUSION: The majority of patients who had agitation management with physical restraints were admitted to the hospital; of those patients, 81.4% were admitted to a primary medical floor and 18.6% were admitted to a psychiatric unit.

Traducción y validez de la Stigma of Suicide Scale Short Form (SOSS-SF) en población peruana

Introducción: El estigma hacia las personas que mueren por suicidio o presentan conductas suicidas se considera una barrera para la búsqueda de apoyo profesional y porque tiene efectos en el bienestar psicológico, físico y social. La sociedad cumple un rol importante en la prevención y tratamiento del suicidio, siendo un apoyo necesario para las personas. Objetivo: Traducir al español y validar la Stigma of Suicide Scale Short Form en adultos peruanos de la población general. Métodos: Estudio transversal de enfoque cuantitativo e instrumental. Participaron 1013 adultos peruanos que respondieron la Escala de Estigma del Suicidio - Forma corta (SOSS-SF). El método de traducción inversa se utilizó para la versión de inglés al español. Los análisis se realizaron a partir de la teoría clásica de los test y teoría de respuesta al ítem. Resultados: Los participantes estuvieron de acuerdo en que las personas que mueren por suicidio eran solitarias (39,4 %), aisladas (39,3 %), cobardes (35,2 %) e irresponsables (35 %). La estructura de 3 factores fue adecuada, presentó buena confiabilidad (ωbayes > 0,77, H > 0,83) e invarianza según sexo. Además, todos los ítems discriminaron adecuadamente; el ítem 10 fue el más preciso para medir el estigma hacia el suicidio. Conclusiones: La versión en español del SOSS-SF presenta evidencias de validez basadas en el contenido, estructura interna, confiabilidad, invarianza y respuestas del ítem. Se recomienda su uso para la interpretación e inferencia de sus puntuaciones en la evaluación del estigma hacia el suicidio en población general adulta peruana.

Introduction: Stigma towards people who die by suicide or present suicidal behaviors, is considered a barrier for the search professional support and because it has effects on psychological, physical and social well-being. Society complies an important role in suicide prevention and treatment, being a necessary support for individuals. Objective: To translate into Spanish and validate the Stigma of Suicide Scale Short Form in Peruvian adults from the general population. Methods: Cross-sectional study of quantitative and instrumental approach. A total of 1013 Peruvian adults who responded the Suicide Stigma Scale - Short Form (SOSS-SF) participated. The reverse translation method was used for the English to Spanish version. Analyses were performed as from classical test theory and item response theory. Results: Participants agreed that people who die by suicide were lonely (39,4%), isolated (39,3%), cowardly (35,2%), and irresponsible (35%). The 3-factor structure was adequate, presented good reliability (ωbayes > 0,77, H > 0,83) and gender invariance. In addition, all items discriminated adequately, with item 10 being more accurate in measuring suicide stigma. Conclusions: The Spanish version of the SOSS-SF presents sources of evidence of validity based on content, internal structure, reliability, invariance and item responses. Its use is recommended for the interpretation and inference of its scores in the assessment of stigma towards the suicide in the general adult Peruvian population.

Crystal orientation fabric anisotropy causes directional hardening of the Northeast Greenland Ice Stream.

The dynamic mass loss of ice sheets constitutes one of the biggest uncertainties in projections of ice-sheet evolution. One central, understudied aspect of ice flow is how the bulk orientation of the crystal orientation fabric translates to the mechanical anisotropy of ice. Here we show the spatial distribution of the depth-averaged horizontal anisotropy and corresponding directional flow-enhancement factors covering a large area of the Northeast Greenland Ice Stream onset. Our results are based on airborne and ground-based radar surveys, ice-core observations, and numerical ice-flow modelling. They show a strong spatial variability of the horizontal anisotropy and a rapid crystal reorganisation on the order of hundreds of years coinciding with the ice-stream geometry. Compared to isotropic ice, parts of the ice stream are found to be more than one order of magnitude harder for along-flow extension/compression while the shear margins are potentially softened by a factor of two for horizontal-shear deformation.

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial.

BACKGROUND: Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke. METHODS: The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18-80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1-7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6-20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed. FINDINGS: Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9-15), with intra-arterial BMMNC injection done a median of 6 days (4-7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55-7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52-6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72-6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group. INTERPRETATION: Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints. FUNDING: Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.

Bilateral ligation of the anterior trunk of the internal iliac artery in uterine atony secondary to uterine inversion: case report.

Postpartum hemorrhage is one of the leading causes of maternal mortality worldwide. Uterine atony is the main cause, representing up to 90% of cases, and is a risk factor for uterine inversion. Morbidity and mortality occur in 41% of uterine inversion cases, including massive obstetric hemorrhage. Massive obstetric hemorrhage is a medical emergency that puts life and reproductive function at risk, and therefore, its treatment must be timely and immediate. If there is no favorable response with the initial measures, surgical intervention proceeds. When choosing the surgical procedure, priority should be given to the technique with the easiest access and which is the least invasive, the safest, and in which the surgeon has more experience. We present a case report with our technique of bilateral ligation of the anterior trunk of the hypogastric artery, after a uterine compression suture failed, with excellent results and preserved fertility in an adolescent patient. We describe the technique and the result. The response time of the uterus with normal tone was 5 minutes, and postligation bleeding was only 50 mL after the patient had bled 1200 mL without complications; thus, it is an adequate and cost-effective technique. The bilateral ligation of the anterior trunk of the hypogastric artery technique in the case of postpartum hemorrhage is an effective, safe, and fertility-preserving surgical procedure that constitutes an alternative to emergency obstetrical hysterectomy when other, less invasive methods have failed.

Express improvement of acute stroke care accessibility in large regions using a centralized telestroke network.

Introduction: Acute ischemic stroke therapy has improved in recent decades, decreasing the rates of disability and death among stroke patients. Unfortunately, all health care systems have geographical disparities in infrastructure for stroke patients. A centralized telestroke network might be a low-cost strategy to reduce differences in terms of geographical barriers, equitable access, and quality monitoring across different hospitals. Aims: We aimed to quantify changes in stroke patients' geographic access to specialized evaluation by neurologists and to intravenous acute stroke reperfusion treatments following the rapid implementation of a centralized telestroke network in the large region of Andalusia (8.5 million inhabitants). Methods: We conducted an observational study using spatial and analytical methods to examine how a centralized telestroke network influences the quality and accessibility of stroke care for a large region. Results: In the pre-implementation period, 5,005,477 (59.72% of the Andalusian population) had access to specialized stroke care in less than 30 min. After the 5-month process of implementing the telestroke network, 7,832,988 (93.5%) inhabitants had an access time of less than 30 min, bridging the gap in acute stroke care in rural hospitals. Conclusions: A centralized telestroke network may be an efficient tool to reduce the differences in stroke care access and quality monitoring across different hospitals, especially in large regions with low population density.

Spin excitations of individual magnetic dopants in an ionic thin film.

Individual magnetic transition metal dopants in a solid host usually exhibit relatively small spin excitation energies of a few meV. Using scanning tunneling microscopy and inelastic electron tunneling spectroscopy (IETS) techniques, we have observed a high spin excitation energy around 36 meV for an individual Co substitutional dopant in ultrathin NaCl films. In contrast, the Cr dopant in the NaCl film shows much lower spin excitation energy around 2.5 meV. Electronic multiplet calculations combined with first-principles calculations confirm the spin excitation induced IETS, and quantitatively reveal the out-of-plane magnetic anisotropies for both Co and Cr. They also allow reproducing the experimentally observed redshift in the spin excitations of Co dimers and ascribe it to a charge and geometry redistribution.

Análisis de red de la comorbilidad entre síntomas de ansiedad e insomnio en adultos / Network analysis of comorbidity between anxiety symptoms and insomnia in adults

RESUMEN Introducción: La comorbilidad entre los síntomas de ansiedad e insomnio es frecuente y a menudo se entiende porque los síntomas comparten una causa común. La teoría de redes conceptualiza las alteraciones emocionales a nivel de síntomas y es una alternativa contemporánea para comprender la comorbilidad psicopatológica. Objetivo: Explorar la comorbilidad entre los síntomas de ansiedad e insomnio en adultos peruanos. Métodos: La muestra estuvo conformada por 567 adultos (75,1 % mujeres) que respondieron autoinformes de ansiedad e insomnio. Se estimó una red gráfica gaussiana con medidas de centralidad, predictibilidad, estabilidad, precisión y comparación. Para identificar los síntomas que impulsaban la comorbilidad, se analizaron los síntomas puente en la estructura de red. Resultados: Todas las conexiones en la red fueron positivas. Se identificó que los problemas para relajarse y la calidad general del sueño eran los síntomas puente entre la ansiedad y el insomnio. Las puntuaciones más altas en centralidad y predictibilidad para la ansiedad fueron los problemas para relajarse y preocupación, mientas que para el insomnio fue la calidad general del sueño y su duración. La red fue robusta y estable (CS = 0,672). Conclusiones: Los problemas para relajarse y la calidad general del sueño se identificaron como síntomas puente entre la ansiedad y el insomnio. Se necesitan más investigaciones para comprobar si la intervención en aquellos síntomas podría disminuir la comorbilidad entre ambos problemas.

ABSTRACT Introduction: Comorbidity between anxiety and insomnia symptoms is frequent and often it is understood because the symptoms share a common cause. Network theory conceptualizes emotional disorders at symptoms level and is a contemporary alternative for comprehend ​psychopathological comorbidity. Objective: To explore the comorbidity between anxiety and insomnia symptoms in Peruvian adults. Methods: The sample was made up of 567 adults (75,1 % women) who responded to self-reports of anxiety and insomnia. A Gaussian graphical network was estimated with measures of centrality, predictability, stability, precision and comparative. To identify symptoms driving comorbidity, bridge symptoms were analyzed in the network structure. Results: All network connections were positive. Trouble relaxing and general sleep quality were identified as the bridge symptoms between anxiety and insomnia. The highest centrality and predictability scores for anxiety were trouble relaxing and worrying, while for insomnia it was overall sleep quality and sleep duration. The network was robust and stable (CS = 0,672). Conclusions: Trouble relaxing and overall sleep quality were identified as bridge symptoms between anxiety and insomnia. Further research is needed to test whether intervention in those symptoms could decrease comorbidity between both emotional disorders.

Novel Roles of the Nipah Virus Attachment Glycoprotein and Its Mobility in Early and Late Membrane Fusion Steps.

The Paramyxoviridae family comprises important pathogens that include measles (MeV), mumps, parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra virus (HeV). Paramyxoviral entry into cells requires viral-cell membrane fusion, and formation of paramyxoviral pathognomonic syncytia requires cell-cell membrane fusion. Both events are coordinated by intricate interactions between the tetrameric attachment (G/H/HN) and trimeric fusion (F) glycoproteins. We report that receptor binding induces conformational changes in NiV G that expose its stalk domain, which triggers F through a cascade from prefusion to prehairpin intermediate (PHI) to postfusion conformations, executing membrane fusion. To decipher how the NiV G stalk may trigger F, we introduced cysteines along the G stalk to increase tetrameric strength and restrict stalk mobility. While most point mutants displayed near-wild-type levels of cell surface expression and receptor binding, most yielded increased NiV G oligomeric strength, and showed remarkably strong defects in syncytium formation. Furthermore, most of these mutants displayed stronger F/G interactions and significant defects in their ability to trigger F, indicating that NiV G stalk mobility is key to proper F triggering via moderate G/F interactions. Also remarkably, a mutant capable of triggering F and of fusion pore formation yielded little syncytium formation, implicating G or G/F interactions in a late step occurring post fusion pore formation, such as the extensive fusion pore expansion required for syncytium formation. This study uncovers novel mechanisms by which the G stalk and its oligomerization/mobility affect G/F interactions, the triggering of F, and a late fusion pore expansion step-exciting novel findings for paramyxoviral attachment glycoproteins. IMPORTANCE The important Paramyxoviridae family includes measles, mumps, human parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra virus (HeV). The deadly emerging NiV can cause neurologic and respiratory symptoms in humans with a >60% mortality rate. NiV has two surface proteins, the receptor binding protein (G) and fusion (F) glycoproteins. They mediate the required membrane fusion during viral entry into host cells and during syncytium formation, a hallmark of paramyxoviral and NiV infections. We previously discovered that the G stalk domain is important for triggering F (via largely unknown mechanisms) to induce membrane fusion. Here, we uncovered new roles and mechanisms by which the G stalk and its mobility modulate the triggering of F and also unexpectedly affect a very late step in membrane fusion, namely fusion pore expansion. Importantly, these novel findings may extend to other paramyxoviruses, offering new potential targets for therapeutic interventions.

Botfly Parasitism on Two Primates of the Cebidae Family in Peru.

Botflies (Diptera:Oestridae) are a diverse group of insect parasites that affect various vertebrate species. There are previous reports of myiasis affecting wild primates in Central and South America; however, information about botfly parasitism in Peruvian primates is scarce. We present data from two Cebidae primate specimens: a rescued large-headed capuchin monkey (Sapajus macrocephalus) housed at Taricaya Rescue Center, in Tambopata, Peru, and a free-ranging white-fronted capuchin monkey (Cebus albifrons aequatorialis) inhabiting Cerros de Amotape National Park. The first specimen had a larva identified as Dermatobia hominis, whereas Cuterebra baeri larvae infested the second. In both cases we initially identified the parasite species through their morphologic features before confirming the identification with genetic analysis through the cytochrome C oxidase subunit 1 mitochondrial gene sequencing of the larvae. Further field studies on the primate-parasite dynamics are needed to understand the impact of botfly myiasis on primate populations.

Evaluation of a virulent strain of Mycobacterium avium subsp. Paratuberculosis used as a heat-killed vaccine.

Bovine paratuberculosis is one of the most important chronic infectious diseases in livestock. This disease is difficult to control because of its inefficient management (test and cull strategy and inadequate biosecurity). Thus, the development of an effective vaccine is essential. In this study, we evaluated a local virulent strain (6611) of Mycobacterium avium subsp. paratuberculosis as an inactivated vaccine in comparison with the Silirum vaccine in mouse model and cattle. Regarding the mice model, only the groups vaccinated with 6611 showed lower colony forming unit (CFU) counts with a lower lesion score in the liver in comparison to the control group at 6 and 12 weeks post-challenge (wpc). The immune response was predominantly humoral (IgG1), although both vaccinated groups presented a cellular response with IFNγ production as well, but the 6611 group had also significant production of IL-2, IL-6, IL-17a, TNF, and IL-10. In cattle, the 6611 vaccinated group was the only one that maintained significant antibody values at the end of the trial, with significant production of IgG2 and IFNγ. No PPDb reactor was detected in the vaccinated animals, according to the intradermal caudal fold tuberculin test. Our results indicate that the 6611 local strain protected mice from challenge with a virulent strain, by inducing a humoral and cellular immune response. In the bovine, the natural host, the evaluated vaccine also induced humoral and cellular immune responses, with higher levels of CD4 + CD25+ and CD8 + CD25+ T cells populations than the commercial vaccine. Despite the encouraging results obtained in this study, an experimental challenge trial in cattle is mandatory to evaluate the efficacy of our candidate vaccine in the main host.

Evidencias psicométricas del Patient Health Questionnarie-2 para la evaluación de síntomas depresivos en adultos peruanos / Psychometric evidence of the Patient Health Questionnarie-2 for the assessment of depressive symptoms in Peruvian adults

RESUMEN Introducción: los síntomas depresivos constituyen uno de los problemas más frecuentes en población adulta, se presentan en los últimos años como un importante problema de salud pública global. La evidencia empírica sugiere que los síntomas depresivos están relacionados con otros desórdenes emocionales y físicos, por lo que es necesario identificar los probables casos mediante instrumentos de cribado para una intervención temprana. Objetivo: validar el Patient Health Questionnarie-2 en la población adulta peruana. Métodos: el diseño de investigación es instrumental donde participaron 283 adultos peruanos residentes en Lima en el mes de abril del 2021, seleccionados mediante muestreo por bola de nieve y criterios de inclusión. Se evaluó la consistencia interna y mediante el modelamiento de ecuaciones estructurales, se realizó un modelo para la evidencia basada en relación a otras variables. Resultados: la evaluación de la consistencia interna mediante el coeficiente alfa (α = 0,75) y el coeficiente omega (ω = 0,76) fueron aceptables. Asimismo, las puntuaciones derivadas del Patient Health Questionnarie-2 convergieron con la ideación suicida (r = 0,61; p = 0,001) y la ansiedad (r = 0,72; p = 0,001), ambas con tamaños del efecto fuerte. Conclusiones: el Patient Health Questionnarie-2 es un instrumento de cribado confiable para la evaluación de los síntomas depresivos, presenta fuentes de evidencias de validez basadas en relación a otras variables y consistencia interna. Se recomienda su uso en población adulta peruana para la detección de casos como análisis previo a la aplicación de otros instrumentos.

ABSTRACT Introduction: depressive symptoms constitute one of the most frequent problems in the adult population, presenting itself in recent years as an important global public health problem. Empirical evidence suggests depressive symptoms are related to other emotional and physical disorders, being necessary to identify probable cases by means of screening instruments for an early intervention. Objective: the study was aimed at validating the Patient Health Questionnarie-2 in the Peruvian adult population. Methods: the research design was instrumental, with the participation of 283 Peruvian adults living in Lima on April 2021, chosen by snowball sampling and inclusion criteria. Internal consistency was evaluated and by means of structural equation modeling a model was made for evidence based on relation to other variables. Results: the assessment of internal consistency using the alpha coefficient (α = 0.75) and the omega coefficient (ω = 0.76) were acceptable. Also, scores derived from the Patient Health Questionnarie-2 converged with suicidal ideation (r = 0.61; p = 0.001) and anxiety (r = 0.72; p = 0.001), both with strong effect sizes. Conclusions: the Patient Health Questionnarie-2 is a reliable screening instrument for the assessment of depressive symptoms, presenting sources of evidence of validity in relation to other variables and internal consistency. Its use is recommended in the Peruvian adult population for case detection as an analysis prior to the application of other instruments.

Análisis de redes de las conductas suicidas en adultos peruanos / Network analysis of the suicidal behaviors in Peruvian adults

Introducción: En el estudio de la conducta humana, el suicidio es un problema de salud pública emergente. Dado que la mayoría de las personas que presentan conductas suicidas no lo comunican, es necesario explorar las conductas que son determinantes. Objetivo: Analizar las conductas suicidas mediante el análisis de redes en la población general de adultos peruanos. Métodos: Estudio transversal y de enfoque cuantitativo. Participaron 408 adultos peruanos seleccionados mediante muestreo por conveniencia y criterios de inclusión. Se aplicó un instrumento para evaluar la conducta suicida y se estimó una red de correlación parcial regularizada. Asimismo, se analizaron los índices de centralidad (fuerza e influencia esperada) y la predictibilidad de los nodos. También se evaluó la estabilidad y precisión de la red. Resultados: El modelo de red de conducta suicida estuvo conformado por bordes positivos. Las correlaciones más fuertes surgieron entre pensamientos suicidas e intención de suicidio. El nodo con mayor fuerza e influencia esperada fue considerar quitarse la vida. La predictibilidad promedio fue 42 por cientoy el nodo con mayor predicción fue desear estar muerto. La precisión de la red fue adecuada y su estabilidad también (CS = 0,596). Conclusiones: Los resultados indican que los pensamientos suicidas y la intención de suicidarse son aspectos importantes para comprender las conductas suicidas en población general de adultos peruanos. Por ello, identificar estas conductas mediante los instrumentos de evaluación y entrevista clínica, es una práctica recomendable para la detección de personas en riesgo de conductas suicidas y prevención del suicidio(AU)

Introduction: In the study of human behavior, suicide is an emerging public health problem. Given that the majority of people who present suicidal behavior do not communicate it, it is necessary to explore the behaviors that are decisive. Objective: To analyze the suicidal behaviors by means of the analysis of networks in general population of Peruvian adults. Methods: Cross-sectional study and of quantitative approach. 408 Peruvian adults selected by means of convenience sampling and inclusion criteria participated. An instrument was applied to evaluate suicidal behavior and a regularized partial correlation network was estimated. Likewise, the centrality indices (strength and expected influence) and the predictability of the nodes were analyzed. The stability and precision of the network was also evaluated. Results: The network model of suicidal behavior was made up of positive edges. The strongest correlations emerged between suicidal thoughts and suicide intention. The node with greatest strength and influence expected was considering taking his own life. The average predictability was 42 percent and the node with greatest was prediction was wishing to be dead. The precision of the network was adequate and its stability as well (CS=0,596). Conclusions: The results indicate that suicidal thoughts and the intention to commit suicide are important aspects to understand suicidal behaviors in general population of Peruvian adults. For it, identifying these behaviors be means of the evaluation instruments and clinical interview is a recommended practice for detecting people at risk of suicidal behaviors and suicide prevention(AU)

Inventario de Frecuencia de Ideación Suicida: evidencias psicométricas en adultos peruanos / Frequency of Suicidal Ideation Inventory: Psychometric evidence in Peruvian adults / Inventário de Frequência de Ideação Suicida: evidências psicométricas em adultos peruanos

RESUMEN Introducción: Estudios recientes indican la prevalencia de ideación suicida en la población general. En el Perú, el aumento de suicidios consumados y la falta de instrumentos de evaluación basados en evidencias, es un problema a considerar. La evaluación de la ideación suicida es esencial para la prevención del suicidio y es recomendable contar con instrumentos confiables para la interpretación e inferencias fundadas de las puntuaciones obtenidas. Objetivo: Analizar las propiedades psicométricas del Inventario de Frecuencia de Ideación Suicida (IFIS) en población general adulta peruana. Método: Diseño de investigación instrumental y transversal, donde participaron 376 adultos peruanos. Se analizó la evidencia basada en el contenido, estructura interna, confiabilidad, invarianza de medición según sexo y edad, y evidencia en la relación con otras variables. Resultados: El IFIS es una medida unidimensional (CFI=0,99, RMSEA=0,03 [IC del 90 %: 0,00-0,08], SRMR=0,03, WRMR= 0,37), con adecuada confiabilidad (ω=0,80 y H= 0,91) e invarianza según sexo y edad (ΔCFI< 0,010; ΔSRMR<0,030). Asimismo, las puntuaciones del IFIS se correlacionaron con la depresión (r=0,67; p=0,001), presentando un tamaño del efecto fuerte. Los revisores expertos consideraron todos los ítems relevantes. Conclusiones: El IFIS es un instrumento unidimensional con aceptables valores de confiabilidad y diferentes fuentes de evidencias de validez. Por lo tanto, se recomienda utilizar el IFIS como herramienta adicional para la evaluación de la ideación suicida en población general adulta peruana.

ABSTRACT Introduction: Updated research reveals permanence of suicidal ideation in the Peruvian population. In Peru the significant increases of completed suicides and the lack of evidence-based assessment instruments are problem to be considered. The assessment of suicidal ideation is essential for suicide prevention and it is advisable to have confidence instruments for the correct interpretation and informed inferences of the scores obtained. Objective: To assess the psychometric properties of the Frequency of Suicidal Ideation Inventory (FSII) in the Peruvian adult population. Method: An instrumental and cross-sectional research was designed, involving in it 376 Peruvian adults. Content-based evidence, internal structure, confidence, not invariant measurement according sex and age, and evidence of the relationship among other variables. Results: FSII is a unidimensional measurement (CFI=0.99, RMSEA=0,03 [90% confidence interval (CI): 0.00 to 0.08], SRMR=0.03, WRMR=0.37), with an adequate confidence (ω=0.80 and H= 0.91) and invariant measurement according sex and age (ΔCFI<0.010; ΔSRMR<0.030). At the same time, the FSII scores were correlated with depression stages (r=0.67; p=0.001) presenting a strong effect size. The expert reviewers considered all items as relevant. Conclusions: The FSII is a unidimensional tool with an adequate confidence values and different sources which can provide valid evidence. Therefore, it is recommended to use the FSII as an additional tool for the assessment of suicidal ideation in the general Peruvian adult population.

RESUMO Introdução: Estudos recentes indicam a prevalência de ideação suicida na população em geral. No Peru, o aumento de suicídios consumados e a falta de instrumentos de avaliação baseados em evidências é um problema a ser considerado. A avaliação da ideação suicida é essencial para a prevenção do suicídio e é aconselhável contar com instrumentos confiáveis para a interpretação e inferências fundamentadas dos escores obtidos. Objetivo: Analisar as propriedades psicométricas do Inventário de Frequência de Ideação Suicida (IFIS) na população adulta peruana em geral. Método: Desenho de pesquisa instrumental e transversal, onde participaram 376 adultos peruanos. Foram analisadas as evidências baseadas no conteúdo, estrutura interna, confiabilidade, invariância das medidas segundo sexo e idade e evidências em relação às demais variáveis. Resultados: IFIS é uma medida unidimensional (CFI=0,99, RMSEA=0,03 [90% CI: 0,00-0,08], SRMR=0,03, WRMR=0,37), com confiabilidade adequada (ω=0,80 e H=0,91) e invariância de acordo com sexo e idade (ΔCFI<0,010; ΔSRMR<0,030). Da mesma forma, os escores do IFIS se correlacionaram com a depressão (r=0,67; p=0,001), apresentando um forte tamanho de efeito. Os revisores especialistas consideraram todos os itens relevantes. Conclusões: O IFIS é um instrumento unidimensional com valores de confiabilidade aceitáveis e diferentes fontes de evidências de validade. Portanto, é recomendado o uso do IFIS como uma ferramenta adicional para a avaliação da ideação suicida na população adulta peruana em geral.