Complex N-glycans are important for interspecies transmission of H7 influenza A viruses.

Influenza A viruses (IAVs) can overcome species barriers by adaptation of the receptor-binding site of the hemagglutinin (HA). To initiate infection, HAs bind to glycan receptors with terminal sialic acids, which are either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc); the latter is mainly found in horses and pigs but not in birds and humans. We investigated the influence of previously identified equine NeuGc-adapting mutations (S128T, I130V, A135E, T189A, and K193R) in avian H7 IAVs in vitro and in vivo. We observed that these mutations negatively affected viral replication in chicken cells but not in duck cells and positively affected replication in horse cells. In vivo, the mutations reduced virus virulence and mortality in chickens. Ducks excreted high viral loads longer than chickens, although they appeared clinically healthy. To elucidate why these viruses infected chickens and ducks despite the absence of NeuGc, we re-evaluated the receptor binding of H7 HAs using glycan microarray and flow cytometry studies. This re-evaluation demonstrated that mutated avian H7 HAs also bound to α2,3-linked NeuAc and sialyl-LewisX, which have an additional fucose moiety in their terminal epitope, explaining why infection of ducks and chickens was possible. Interestingly, the α2,3-linked NeuAc and sialyl-LewisX epitopes were only bound when presented on tri-antennary N-glycans, emphasizing the importance of investigating the fine receptor specificities of IAVs. In conclusion, the binding of NeuGc-adapted H7 IAV to tri-antennary N-glycans enables viral replication and shedding by chickens and ducks, potentially facilitating interspecies transmission of equine-adapted H7 IAVs.IMPORTANCEInfluenza A viruses (IAVs) cause millions of deaths and illnesses in birds and mammals each year. The viral surface protein hemagglutinin initiates infection by binding to host cell terminal sialic acids. Hemagglutinin adaptations affect the binding affinity to these sialic acids and the potential host species targeted. While avian and human IAVs tend to bind to N-acetylneuraminic acid (sialic acid), equine H7 viruses prefer binding to N-glycolylneuraminic acid (NeuGc). To better understand the function of NeuGc-specific adaptations in hemagglutinin and to elucidate interspecies transmission potential NeuGc-adapted viruses, we evaluated the effects of NeuGc-specific mutations in avian H7 viruses in chickens and ducks, important economic hosts and reservoir birds, respectively. We also examined the impact on viral replication and found a binding affinity to tri-antennary N-glycans containing different terminal epitopes. These findings are significant as they contribute to the understanding of the role of receptor binding in avian influenza infection.

Series of Protonated Nitrogen Bases with a Weakly Coordinating Counteranion: Observation of the 14N-1H Spin-Spin Coupling.

A distinguished triplet splitting pattern for the 14N-1H couplings in the proton signals of a series of protonated nitrogen bases-aliphatic and aromatic amines, as well as pyridines-with the weakly coordinating tetrakis(pentafluorophenyl)borate anion, [B(C6F5)4]-, is observed for the first time in nonaqueous media at room temperature. The effects of ion pairing, solvent parameters, and correlation between the δH, 1JNH, and pKa values are reported.

A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity.

Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.

GEDEFO-SEFH management of antineoplastic extravasations survey results.

INTRODUCTION: Extravasation is a potentially severe complication of intravenous administration of antineoplastic drugs. The limited data makes it difficult to develop an optimal management scheme. The objective of this study is to describe the clinical practice in the extravasation management of antineoplastic agents in Spanish centers. METHODS: An online survey was distributed to oncology pharmacists using the email distribution list of the Spanish Society of Hospital Pharmacists. Respondents were surveyed on the standard operational protocol (SOP) of extravasation, tissue damage risk classification, and specific measures of extravasation management. RESULTS: A total of 68 surveys were completed. A specific extravasation SOP was available in 82.4% centers. The pharmacist participates in the authorship (100%) and actively collaborates in extravasation management (76.5%). A tissue damage risk classification based on the three categories was mostly adopted (48.2%) and 73.2% applied specific criteria based on concentration and/or extravasated volume. Extravasation management was mainly performed with the application of physical measures and/or antidotes (91.2%). High variability in the choices of pharmacological and/or physical measures recommended is outstanding. CONCLUSION: The results of this study highlight the involvement of Spanish pharmacists in extravasation management, the application of physical measures and/or pharmacological measures as the method of choice in extravasation management, as well as the existing discrepancies in tissue damage risk classification and management recommendations.

Effects of three personal resources interventions on employees' burnout.

Personal resources are related to positive psychological states that can translate into lower burnout among employees. However, although these personal resources can be promoted through ad hoc interventions, there are few studies that analyze this type of interventions in workers. The aim of this study was to assess the effectiveness of three interventions on personal resources on reducing employees' burnout. To this end, it was hypothesized that a positive psychological capital intervention (PsyCap), a job crafting intervention and a combined intervention would have a positive impact on burnout levels. This research used a quasi-experimental, longitudinal, pretest-posttest design, with repeated measures and a waiting list control group. Study participants (N = 144) were all workers divided into three interventions and a control group. A noteworthy aspect of the study design is that the intervention was implemented as a voluntary online training activity. This study showed that personal resources interventions were effective in reducing burnout among employees. The PsyCap intervention and the combined intervention showed the greatest efficacy. Contrary to expectations, the combined intervention did not show significantly greater efficacy than the other two experimental groups. The study concludes with a discussion of its limitations and practical implications for future personal resources intervention studies.

Interarytenoid injection outcomes in pediatric feeding disorders.

Objectives: Type 1 laryngeal clefts (LC1) and deep interarytenoid grooves contribute to pediatric feeding disorders. Management of these defects remains heterogeneous among surgeons and interarytenoid injection augmentation (IIA) is not always offered as a treatment option. This study evaluated IIA outcomes among a pediatric patient cohort comprised mostly of those with deep interarytenoid grooves. Methods: A single-institution retrospective chart review featured children under the age of 5 years presenting for aspiration, dysphagia, or choking. Over the period of 7 years (January 2014-October 2021), 39 met inclusion criteria and had sufficient follow-up data. Descriptive statistics and subgroup analyses were performed. Results: Of the 39 included patients, 76.92% had clinical improvement post-injection, with the mean time to follow-up being 47 days. Within the deep interarytenoid groove group, improvement rates were 82.76%. Bronchoscopy findings revealed 29 (74.36%) patients with a DIG, 3 (7.69%) with LC1, 3 (7.69%) with no anatomic abnormality, and 4 (10.26%) with vocal cord paralysis. There were no adverse events. There were no associations with the outcomes based on subgroup analysis and logistic regression. Conclusions: IIA is an effective and safe treatment for pediatric feeding disorders. No covariates were associated with symptom improvement. Within the deep interarytenoid groove diagnosis subgroup, IIA effectively improved symptoms. Further investigations are needed to explore predictors of success with IIA in this population. Level of Evidence: VI.

Prácticas de autocuidado en el adulto mayor con Diabetes Mellitus Tipo II / Self-care prectices in the elderly with Diabetes Mellitus II

Objetivo: Describir la vivencia del cuidado y el autocuidado en el adulto mayor diagnosticado de diabetes mellitus II. Material y método: Estudio cualitativo fenomenológico de enfoque explicativo-interpretativo. Se persigue entender las vivencias ante los autocuidados en personas diabéticas mayores de 65 años. Se lleva a término en el CAP Les Planes de Sant Joan Despí, Barcelona (España). Se realizó un muestreo opinático, no probabilístico intencionado y razonado. La muestra final se compuso de 13 participantes. Para la recogida de datos se utilizó la entrevista semiestructurada e individual. Las entrevistas se llevaron a cabo entre junio del 2019 y diciembre del 2020. Se realizó un análisis temático siendo concomitante a la recogida de estos. Resultados: El diagnóstico de diabetes supone para la persona el conocimiento sobre la pérdida de su salud, de la vivencia de este momento dependerá la forma en que afrontará la enfermedad. La mayoría de los pacientes de este estudio afirman no haber recibido ningún tipo de información sobre los cuidados a realizar respecto a la dieta, el ejercicio físico o el cuidado de los pies, aunque sí que recuerdan el tratamiento farmacológico. Conclusiones: El cuidado de enfermería en las personas con Diabetes Mellitus tipo II debe incluir la consideración de los aspectos físicos, tecnológicos, económicos y educativos de la persona cuidada, adaptando la planificación de los cuidados a cada una de ellas, según dichos factores. (AU)

Objective: To describe the experience of care and self-care in the elderly diagnosed with diabetes mellitus II Material and method: Qualitative phenomenological study with an explanatory-interpretive approach. The aim is to understand the experiences of self-care in diabetic people over 65 years of age. It takes place at the CAP Les Planes de Sant Joan Despí, Barcelona (Spain). An opinionated, non-probabilistic intentional and reasoned sampling was carried out. The final sample consisted of 13 participants. For data collection, the semi-structured and individual interview was used. The interviews were carried out between June 2019 and December 2020. A thematic analysis was carried out, concomitant with the collection of these. Results: Diagnosis of diabetes supposes for the person the knowledge about the loss of his health, the experience of this moment will depend on the way in which he will face the disease. Most of the patients in this study claim not to have received any type of information about the care to be taken regarding diet, physical exercise or foot care, although they do remember the pharmacological treatment Conclusions: Nursing care in people with type II Diabetes Mellitus should include the consideration of the physical, technological, economic and educational aspects of the person cared for, adapting the care planning to each one of them, according to these factors. (AU)

Postpartum family planning uptake in Uganda: findings from the lot quality assurance sampling survey.

BACKGROUND: The initiation and use of family planning (FP) services within the first 12 months following childbirth, postpartum family planning (PPFP), promotes safe motherhood by reducing unintended pregnancies and ensuring appropriate pregnancy spacing. However, there is a paucity of information on PPFP uptake from community surveys. This study aimed to quantify the reported use of PPFP and identify predictors and barriers to PPFP uptake from a large community survey. METHODS: We analysed data collected from the 2021 Lot Quality Assurance Sampling (LQAS) survey, a cross-sectional community and household survey that covered 68 districts in Uganda. The survey uses small sample sizes to designate health or administrative geographical areas which are assessed to determine whether they achieved the pre-determined target for defined indicators of interest. We abstracted and analysed data collected from mothers of children aged 12 months or younger on reproductive health and FP. PPFP use was defined as the reported use of modern FP by the mother or their partner. Associations were measured using Pearson's chi-square test at 5% significance. Multivariate logistic regression was performed for variables that were significantly associated with PPFP use to identify the predictors of PPFP. RESULTS: Overall, 8103 mothers of children aged less than 12 years were included in the analysis; the majority of mothers, 55.8% (4521/8103) were above 24 years while 11.7% (950/8103) were 19 years and under. 98% (7942/8103) of the mothers attended at least one antenatal care (ANC) visit and 86.3% (6997/8103) delivered at a health facility. Only 10% (814/8103) of mothers who participated in the survey reported PPFP use at the time of the survey. Reporting of PPFP use was 5 times higher among mothers of children aged 7-12 months (AOR 4.9; 95%CI 4.1-5.8), 50% higher among mothers with secondary education (AOR 1.5; 95%CI 1.0-2.3), 80% higher among breastfeeding mothers (AOR 1.8; 95%CI 1.3-2.4) and 30% lower among those that didn't receive a health worker visit within 3 months preceding the survey (AOR 0.7; 95% CI 0.5-0.8). Among 4.6% (372/8103) who stated a reason for non-use of PPFP, the most cited reasons for not using were breastfeeding 43% (161/372), fear of side effects 26.9% (100/372), respondent/partner opposition 17.6% (48/372) and infrequent sex 12.1% (48/372). CONCLUSION: The analysis showed a low proportion of PPFP uptake among mothers of children under 12 years. Possible barriers included child age, education, a health worker visit, and side effects and perceived benefits of possibly improperly implementing lactation amenorrhea method. Integration of social, community and health services could provide a more holistic approach to improving PPFP uptake.

Assessing Use, Usefulness, and Application of the High Impact Practices in Family Planning Briefs and Strategic Planning Guides.

BACKGROUND: In global health, persistent barriers and challenges to bridging the gap between research and practice remain critical to address in most health areas. The High Impact Practices (HIPs) briefs and strategic planning guides aim to bridge the know-do gap in family planning (FP) by facilitating research utilization and knowledge sharing and also providing a summary of experiential knowledge from experts. The purpose of this qualitative study was to assess the use, usefulness, and application of these 2 knowledge products developed by the HIP Partnership for decision-makers and implementers in low- and middle-income countries (LMICs). METHODS: This research used in-depth interviews with FP stakeholders from various LMICs to assess the use, usefulness, and application of 2 HIP products for FP decision-makers and implementers. The analysis was shaped by an adapted logic model framework to assess HIP product reach, engagement, usefulness, learning, and action. RESULTS: We interviewed 35 FP professionals from January to March 2021. Participants reported that HIP products have a wide reach, have garnered positive engagement, and were useful. Participants generally liked the current format of the HIP products and reported using them to inform program design, guide discussions with partners, enhance personal knowledge, support advocacy work, and strengthen the guidance they provide to colleagues in the field. The participants shared important feedback to improve the development and dissemination of HIP products, particularly a need to enhance local access and use. CONCLUSION: The study highlighted the importance of knowledge products, such as the HIP briefs and strategic planning guides, to make evidence and experiential knowledge accessible to a wide audience. These can be valuable tools for policymakers and program implementers to ensure public health practices are evidence-based and integrate experiential knowledge.

Drivers of intra-seasonal δ13 C signal in tree-rings of Pinus sylvestris as indicated by compound-specific and laser ablation isotope analysis.

Carbon isotope composition of tree-ring (δ13 CRing ) is a commonly used proxy for environmental change and ecophysiology. δ13 CRing reconstructions are based on a solid knowledge of isotope fractionations during formation of primary photosynthates (δ13 CP ), such as sucrose. However, δ13 CRing is not merely a record of δ13 CP . Isotope fractionation processes, which are not yet fully understood, modify δ13 CP during sucrose transport. We traced, how the environmental intra-seasonal δ13 CP signal changes from leaves to phloem, tree-ring and roots, for 7 year old Pinus sylvestris, using δ13 C analysis of individual carbohydrates, δ13 CRing laser ablation, leaf gas exchange and enzyme activity measurements. The intra-seasonal δ13 CP dynamics was clearly reflected by δ13 CRing , suggesting negligible impact of reserve use on δ13 CRing . However, δ13 CP became increasingly 13 C-enriched during down-stem transport, probably due to post-photosynthetic fractionations such as sink organ catabolism. In contrast, δ13 C of water-soluble carbohydrates, analysed for the same extracts, did not reflect the same isotope dynamics and fractionations as δ13 CP , but recorded intra-seasonal δ13 CP variability. The impact of environmental signals on δ13 CRing , and the 0.5 and 1.7‰ depletion in photosynthates compared ring organic matter and tree-ring cellulose, respectively, are useful pieces of information for studies exploiting δ13 CRing .

Teledermatology Evaluation and Feedback Systems: A Tool for Improving Care.

Chile is a country where teledermatology has been growing exponentially since the implementation of a single national asynchronous teledermatology platform for the public system in December 2018. To ensure the quality of care in teledermatology systems, it is crucial to evaluate the fulfillment of basic specifiers such as ICD-Diagnosis, therapeutic suggestions, and diagnostic suggestions, among others. This article aims to evaluate the teledermatology system of the Chilean public health service by analyzing 243 randomly extracted consultations, representative of the 20,716 electronic consultations performed during 2020. Compliance with basic specifiers is evaluated. From these, fulfillment of core teledermatology functions, such as diagnostic and therapeutic suggestions, is observed in most consultations. There are statistically significant relationships between the patient's destination (primary health center [PHC] or face-to-face referral), pharmacological prescription, coverage of the drug prescribed by the public system, and the education received by the consulting physician. If the consultation is resolved in the PHC, there is a higher chance for pharmacological prescription, prescribing mostly drugs that are covered by the government. This is less likely to occur when patients are referred for face-to-face evaluation. A targeted evaluation of education, pharmacological prescriptions, and their applicability is key to improving the quality of teledermatology systems.

Autocuidado de los pies en personas con diabetes tipo 2. Un estudio cualitativo / "Self-care of the feet in people with type 2 diabetes. A qualitative study"

Objetivo: Entender las vivencias de los adultos mayores de 65 años con diabetes mellitus tipo 2 respecto al autocuidado de los pies. Método: Estudio cualitativo fenomenológico de enfoque descriptivo. Se lleva a término en las dependencias del Centro de Atención Primaria de Les Planes de Sant Joan Despí, Barcelona, perteneciente al Instituto Catalán de la Salud. Para la recogida de datos se utilizó una entrevista semiestructurada e individual, con un guion de aspectos básicos a explorar, no cerrado y centrado en los objetivos de la investigación. Las entrevistas se llevaron a cabo entre junio del 2019 y diciembre del 2020. Se realizó un análisis temático siendo concomitante a la recogida de estos. Resultados: Una muestra final de 13 personas (4 hombres y 9 mujeres) participaron en el estudio. La adherencia a las recomendaciones del autocuidado del pie diabético es irregular. Los participantes explican conductas de riesgo a pesar de saber que pueden suponer una lesión para unos pies considerados previamente de alto riesgo. La valoración del podólogo supone un coste económico que no pueden permitirse algunas personas. Conclusiones: La enfermera ha de hacer un seguimiento exhaustivo de cómo las personas con diabetes cuidan sus pies, insistiendo en las recomendaciones preventivas no solo en la revisión anual, sino cada vez que la persona acude a la consulta de seguimiento de la diabetes. Es necesaria una comunicación efectiva enfermera-podólogo para mejorar la prevención y el seguimiento de las personas con riesgo de sufrir pie diabético.(AU)

Objective: To understand the experiences of adults over 65 years of age with type 2 diabetes mellitus, regarding foot self-care. Method: Qualitative phenomenological study with a descriptive approach. It is carried out in the facilities of the Primary Care Center of Les Planes de Sant Joan Despí, Barcelona, belonging to the Catalan Institute of Health. For the data collection, a semi-structured and individual interview was used, with a script of basic aspects to be explored, not closed and focused on the objectives of the research. The interviews were carried out between June 2019 and December 2020. A thematic analysis was carried out concomitantly with the collection of these. Results: A final sample of 13 persons (4 men and 9 women) participated in the study. Adherence to diabetic foot self-care recommendations is irregular. Participants explain risky behaviors despite knowing that they can cause injury to feet previously considered high risk. The evaluation of the podiatrist supposes an economic cost that some people cannot afford. Conclusions. The nurse has to do an exhaustive follow-up of how persons with diabetes take care of her feet, insisting on preventive recommendations not only in the annual review but every time the person attends the diabetes follow-up consultation. Effective nurse-podiatrist communication is needed to improve prevention and follow-up of people at risk of diabetic foot disease.

N-Acetylcistein for thrombotic thrombocytopenic purpura: an observational case series study.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. N-Acetylcysteine (NAC) rapidly degrades ultra-large von Willebrand factor multimers by disrupting the disulfide bonds. We report a series of twelve consecutive patients diagnosed with acquired TTP successfully treated with high-dose NAC (150 mg/kg/day) in combination with plasma exchange and steroids. Eight patients also received rituximab. Two patients presented refractory TTP. All patients achieved a quick clinical response in a median time of 5.5 days after starting NAC and are alive after a median follow-up of 29 months. The treatment was feasible and well tolerated. These data provide further evidence of the potential benefit and safety of adding NAC to the standard of care.

Validación de la utilidad de la guía farmacológica Ostomecum en formato de software de aplicación / Validation of the utility of the OSTOMECUM pharmacological guidelines in application software format

Objetivo: evaluar el perfil farmacoterapéutico del paciente con ileostomía y validar el uso de una aplicación móvil en las plataformas iOS y Android de carácter universal, gratuito y funcional dirigida a la comunidad de enfermeras expertas en ostomía y probar esta aplicación tanto por médicos como por enfermeras.Método: veinte especialistas en ostomía (10 médicos y 10 enfermeras) respondieron de forma anónima a un cuestionario de prescripción. Se preguntaron un total de 576 ítems en dos fases. La primera fase se llevó a cabo utilizando fuentes tradicionales de consulta y la segunda empleando la app Ostomecum. Se comparó la velocidad (proporción de preguntas respondidas en el tiempo dado) y la precisión (proporción de respuestas correctas) a la hora de contestar las preguntas. También se investigaron diferencias en la evaluación entre diferentes escenarios de práctica de la Enfermería. La comparación se realizó mediante la prueba pareada de Wilcoxon.Resultados: el porcentaje de preguntas respondidas pasó de 36% en la primera ronda con fuentes tradicionales (43% médicos, 30% enfermeras) a 99% en la segunda ronda usando el software de la aplicación (99% médicos, 99% enfermeras). La precisión de las respuestas aumentó del 22% (26% médicos, 18% enfermeras) al 94% (93% médicos, 95% enfermeras). Las diferencias entre médicos y enfermeras en la primera ronda(p< ,0001) se igualaron al emplear Ostomecum (p= ,7882). El nivel de certeza con la respuesta también cambió del 12% (20% médicos, 4% enfermeras) al 60% con la aplicación móvil (70% médicos, 50% enfermeras) (p< ,0001 total y ambos grupos). En cuanto al entorno laboral, la proporción de aciertos aumentó por igual tanto en el ámbito de Enfermería de consultorio como hospitalario (p< 0,0001 en cada uno).Conclusión: el estomaterapeuta con frecuencia es consultado en los cuidados del paciente ostomizado...(AU)

Objectives: to assess the pharmacotherapeutic profile of the patient with ileostomy and to validate the use of a universal, free and functional mobile application in the IOS and Android platforms, targeted to the community of ostomy-expert nurses, and to try this application both by doctors and by nurses.Method: twenty ostomy specialists (10 doctors and 10 nurses) answered anonymously a prescription questionnaire. In total, 576 items were asked in two stages. The first stage was conducted using traditional sources of reference, and the second one using the OSTOMECUM application. There was a comparison in speed (proportion of questions answered within the given time) and accuracy (proportion of correct answers) at the time of answering the questions. There was also research into the differences in assessment among different settings of Nursing practice. The comparison was conducted through the paired samples Wilcoxon test.Results: the proportion of answered questions went from 36% in the first round using traditional sources (43% for doctors, 30% for nurses) to 99% in the second round using the application software (99% for doctors, 99% for nurses). The accuracy in answers increased from 22% (16% for doctors, 18% for nurses) to 94% (93% for doctors, 95% for nurses). Differences between doctors and nurses in the first round(p< .0001) were equalled when using OSTOMECUM (p= .7882). The level of certainty with the answer also changed from 12% (20% for doctors, 4% for nurses) to 60% with the mobile application (70% for doctors, 50% for nurses) (p< .0001 total and both groups). In terms of work setting, the proportion of right answers increased equally both in the outpatient and the hospital Nursing settings (p< 0.0001 in each one).Conclusion: the stomal therapist is frequently consulted about care for ostomized patients. The OSTOMECUM application is a useful tool for reviewing medication and reconsidering the adequacy of a treatment prescribed to ostomized...(AU)

SARS-CoV-2 Spike N-Terminal Domain Engages 9-O-Acetylated α2-8-Linked Sialic Acids.

SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor binding domain (RBD) and an N-terminal domain (NTD). The NTD of other coronaviruses includes a glycan binding cleft. However, for the SARS-CoV-2 NTD, protein-glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of variants of concern (VoC) show antigenic pressure, which can be an indication of NTD-mediated receptor binding. Trimeric NTD proteins of SARS-CoV-2, alpha, beta, delta, and omicron did not reveal a receptor binding capability. Unexpectedly, the SARS-CoV-2 beta subvariant strain (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9-O-acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity toward 9-O-acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domain, which was quickly selected against. These results indicate that SARS-CoV-2 can probe additional evolutionary space, allowing binding to glycan receptors on the surface of target cells.

Self-care of the feet in people with type 2 diabetes. A qualitative study.

OBJECTIVE: To understand the experiences of adults over 65 years of age with type 2 diabetes mellitus, regarding foot self-care. METHOD: Qualitative phenomenological study with a descriptive approach. It is carried out in the facilities of the Primary Care Center of Les Planes de Sant Joan Despí, Barcelona, belonging to the Catalan Institute of Health. For the data collection, a semi-structured and individual interview was used, with a script of basic aspects to be explored, not closed and focused on the objectives of the research. The interviews were carried out between June 2019 and December 2020. A thematic analysis was carried out concomitantly with the collection of these. RESULTS: A final sample of 13 persons (4 men and 9 women) participated in the study. Adherence to diabetic foot self-care recommendations is irregular. Participants explain risky behaviours despite knowing that they can cause injury to feet previously considered high risk. The evaluation of the podiatrist supposes an economic cost that some people cannot afford. CONCLUSIONS: The nurse has to do an exhaustive follow-up of how persons with diabetes take care of her feet, insisting on preventive recommendations not only in the annual review but every time the person attends the diabetes follow-up consultation. Effective nurse-podiatrist communication is needed to improve prevention and follow-up of people at risk of diabetic foot disease.

Community Mobilization is Associated with HIV Testing Behaviors and Their Psychosocial Antecedents Among Zambian Adults: Results from a Population-Based Study.

Community mobilization (CM) is a vital yet under-explored avenue for increasing HIV testing in generalized HIV epidemic settings. Using multi-stage cluster sampling, a population-based sample of 3535 Zambian adults (mean age: 28 years, 50% women) were recruited from 14 districts to complete a household survey. Exploratory factor analysis (EFA) was used to re-validate a 23-item, 5-factor CM scale. Multivariable logistic and Poisson regression were then used to identify associations of CM with HIV testing behaviors and their psychosocial antecedents. A 21-item, 3-factor ("Leadership", "Collective Action Capacity", and "Social Cohesion") CM solution emerged from EFA (Cronbach's α 0.88). Among men and in rural settings, higher CM was significantly (p < 0.05) associated with elevated odds of HIV testing and more past-year HIV testing discussion sources, controlling for socio-demographics and sexual behaviors. Results underscore the importance of prioritizing CM to cultivate more favorable environments for HIV testing uptake, especially for men and rural residents.

UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial.

BACKGROUND: The prognosis for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia remains poor. UCART19, an allogeneic genome-edited anti-CD19 chimeric antigen receptor (CAR) T-cell product derived from healthy donors and available for immediate clinical use, offers a potential therapeutic option for such patients. The CALM trial is a first-in-human study evaluating the safety and antileukaemic activity of UCART19 in adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. METHODS: This phase 1, open-label study was conducted at eight centres across France, the UK, the USA, and Japan. Adult patients aged 16-70 years with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukaemia who had morphological relapse or a minimal residual disease level of at least 1 × 10-3 and had exhausted standard treatment options were enrolled in the study, which comprised a dose-escalation phase of up to three UCART19 doses followed by a safety expansion phase. Patients underwent lymphodepletion with fludarabine (30 mg/m2 per day intravenously for 3 days) and cyclophosphamide (500 mg/m2 per day intravenously for 3 days) with or without alemtuzumab (1 mg/kg or 40 mg or 60 mg over 5 days) and received UCART19 doses of 6 × 106, 6-8 × 107, or 1·8-2·4 × 108 total CAR T cells intravenously, followed by safety evaluation and disease response assessments. The primary endpoint was incidence and severity of adverse events. Secondary endpoints were the overall response rate, duration of response, relapse-free survival, progression-free survival, and overall survival. This trial is registered with ClinicalTrials.gov (NCT02746952) and is complete. FINDINGS: Between Aug 1, 2016, and June 30, 2020, 25 patients were enrolled in the study and treated with UCART19. Median duration of follow-up was 12·8 months (IQR 2·8-24·8). Median age was 37 years (IQR 28-45). 14 (56%) patients were male and 11 (44%) female. 17 (68%) patients were White, two (8%) Black, two (8%) Asian, and four (16%) from other racial or ethnic groups. Three patients developed dose-limiting toxicities (one at each dose level); one had grade 4 cytokine release syndrome and two had grade 4 prolonged cytopenias. Grade 3 or higher cytokine release syndrome was reported in six (24%) patients and grade 3 or higher neurological toxicity in one (4%) patient. Grade 3 or higher infections occurred in seven (28%) patients, and grade 4 prolonged cytopenia in four (16%) patients. Two (8%) patients developed grade 1 acute cutaneous graft-versus-host disease. 14 patients died, nine from progressive disease and five from infections or other complications, of which four were considered to be related to UCART19 or lymphodepletion, or both. After a median of follow-up of 12·8 months (IQR 2·8-24·8), overall response rate was 48% (95% CI 28-69; 12 of 25 patients), duration of response and median relapse-free survival were 7·4 months (95% CI 1·8 to not calculable), progression-free survival was 2·1 months (95% CI 1·2-2·8), and overall survival was 13·4 months (95% CI 4·8-23·0). INTERPRETATION: UCART19 had a manageable safety profile, and showed evidence of antileukaemic activity in heavily pretreated adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. This study shows that allogeneic off-the-shelf CAR T cells can be used safely to treat patients with relapsed B-cell acute lymphoblastic leukaemia. FUNDING: Servier.

The SARS-CoV-2 spike N-terminal domain engages 9- O -acetylated α2-8-linked sialic acids.

SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor-binding domain (RBD) and an N-terminal domain (NTD). The NTD of other coronaviruses includes a glycan-binding cleft. However, for the SARS-CoV-2 NTD protein-glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of Variants of Concern (VoC) shows antigenic pressure, which can be an indication of NTD-mediated receptor binding. Trimeric NTD proteins of SARS-CoV-2, Alpha, Beta, Delta, and Omicron did not reveal a receptor binding capability. Unexpectedly, the SARS-CoV-2 Beta subvariant strain (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9- O -acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The Beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity towards 9- O -acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domain, which was quickly selected against. These results indicate that SARS-CoV-2 can probe additional evolutionary space, allowing binding to glycan receptors on the surface of target cells. Synopsis: Coronaviruses utilize their N-terminal domain (NTD) for initial reversible low-affinity interaction to (sialylated) glycans. This initial low-affinity/high-avidity engagement enables viral surfing on the target membrane, potentially followed by a stronger secondary receptor interaction. Several coronaviruses, such as HKU1 and OC43, possess a hemagglutinin-esterase for viral release after sialic acid interaction, thus allowing viral dissemination. Other coronaviruses, such as MERS-CoV, do not possess a hemagglutinin-esterase, but interact reversibly to sialic acids allowing for viral surfing and dissemination. The early 501Y.V2-1 subvariant of the Beta SARS-CoV-2 Variant of Concern has attained a receptor-binding functionality towards 9- O -acetylated sialic acid using its NTD. This binding functionality was selected against rapidly, most likely due to poor dissemination. Ablation of sialic acid binding in more recent SARS-CoV-2 Variants of Concern suggests a fine balance of sialic acid interaction of SARS-CoV-2 is required for infection and/or transmission.