Diagnostic yield of exome sequencing in prenatal agenesis of corpus callosum: systematic review and meta-analysis.

OBJECTIVES: To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify the associated genes and variants. METHODS: A systematic search was performed to identify relevant studies published up until June 2022 using four databases: PubMed, SCOPUS, Web of Science and The Cochrane Library. Studies in English reporting on the diagnostic yield of ES following negative CMA in prenatally diagnosed partial or complete ACC were included. Authors of cohort studies were contacted for individual participant data and extended cohorts were provided for two of them. The increase in diagnostic yield with ES for pathogenic/likely pathogenic (P/LP) variants was assessed in all cases of ACC, isolated ACC, ACC with other cranial anomalies and ACC with extracranial anomalies. To identify all reported genetic variants, the systematic review included all ACC cases; however, for the meta-analysis, only studies with ≥ three ACC cases were included. Meta-analysis of proportions was employed using a random-effects model. Quality assessment of the included studies was performed using modified Standards for Reporting of Diagnostic Accuracy criteria. RESULTS: A total of 28 studies, encompassing 288 prenatally diagnosed ACC cases that underwent ES following negative CMA, met the inclusion criteria of the systematic review. We classified 116 genetic variants in 83 genes associated with prenatal ACC with a full phenotypic description. There were 15 studies, encompassing 268 cases, that reported on ≥ three ACC cases and were included in the meta-analysis. Of all the included cases, 43% had a P/LP variant on ES. The highest yield was for ACC with extracranial anomalies (55% (95% CI, 35-73%)), followed by ACC with other cranial anomalies (43% (95% CI, 30-57%)) and isolated ACC (32% (95% CI, 18-51%)). CONCLUSIONS: ES demonstrated an incremental diagnostic yield in cases of prenatally diagnosed ACC following negative CMA. While the greatest diagnostic yield was observed in ACC with extracranial anomalies and ACC with other central nervous system anomalies, ES should also be considered in cases of isolated ACC. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The PHH-1V HIPRA vaccine: a new tool in the vaccination strategy against COVID-19.

OBJECTIVE: Vaccination against SARS-CoV-2 is essential to mitigate the personal, social and global impact of the coronavirus disease (COVID-19) as we move from a pandemic to an endemic phase. Vaccines are now required that offer broad, long-lasting immunological protection from infection in addition to protection from severe illness and hospitalisation. Here we present a review of the evidence base for a new COVID-19 vaccine, PHH-1V (Bimervax®; HIPRA HUMAN HEALTH S.L.U), and the results of an expert consensus. METHODS: The expert committee consisted of Spanish experts in medicine, family medicine, paediatrics, immunology, microbiology, nursing, and veterinary medicine. Consensus was achieved using a 4-phase process consisting of a face-to-face meeting during which the scientific evidence base was reviewed, an online questionnaire to elicit opinions on the value of PHH-1V, a second face-to-face update meeting to discuss the evolution of the epidemiological situation, vaccine programmes and the scientific evidence for PHH-1V and a final face-to-face meeting at which consensus was achieved. RESULTS: The experts agreed that PHH-1V constitutes a valuable novel vaccine for the development of vaccination programmes aimed towards protecting the population from SARS-CoV-2 infection and disease. Consensus was based on evidence of broad-spectrum efficacy against established and emerging SARS-CoV-2 variants, a potent immunological response, and a good safety profile. The physicochemical properties of the PHH-1V formulation facilitate handling and storage appropriate for global uptake. CONCLUSIONS: The physicochemical properties, formulation, immunogenicity and low reactogenic profile of PHH-1V confirm the appropriateness of this new COVID-19 vaccine.

[Efficacy, effectiveness and safety of the adjuvanted influenza vaccine in the population aged 65 or over]. / Eficacia, efectividad y seguridad de la vacuna antigripal adyuvada en población de 65 o más años de edad.

Most of the complications and deaths related to seasonal flu occur in the elderly population (≥65 years) with comorbidities, and the influenza vaccine is the most effective way to prevent them. Immunization is less effective in older adults due to immunosenescence. MF59-adjuvanted vaccines, designed to improve the magnitude, persistence and amplitude of the immune response in elderly people, have been used in clinical practice since 1997 in their trivalent formulation and, since 2020, in their tetravalent formulation. Data from various studies show that these vaccines are not only safe for all age groups, with a reactogenicity profile similar to that of the conventional vaccine, but also that they are especially effective in boosting the immune response in the population aged 65 or over by increasing antibody titers after vaccination and significantly reducing the risk of hospital admission. Adjuvanted vaccines have been shown to provide cross-protection against heterologous strains and to be as effective as the high-dose vaccine in the population aged 65 or over. In this review, the scientific evidence on the efficacy and effectiveness of the MF59-adjuvanted vaccine in real clinical practice in people ≥65 years of age is analyzed through a narrative and descriptive review of the literature with data from clinical trials, observational studies and systematic reviews or meta-analysis.

[Clinical practice guideline for the treatment of spasticity: Consensus and algorithms]. / Guía clínica para el tratamiento de la espasticidad: consenso y algoritmos.

Spasticity is a complex phenomenon of extremely variable clinical expression, a dynamic and evolutionary process that can condition the activity and treatment of the patient. The current recommendation for early treatment aims to avoid progression and complications, and involves an individualized approach based on a wide range of pharmacological and non-pharmacological measures. This guide results from a forum of expert specialists who faced some frequent uncertainties in the assessment process and therapeutic approach of the spastic patient such as the suitability of initiating treatment, considerations for initiating, continuing and ceasing treatment with botulinum toxin, adjuvant treatments, pain or follow-up. The result is one algorithm of decision for the therapeutic approach of spasticity. Both scientific progress and the exchange of clinical experience on which this guide is based, can support decision-making on some areas of gloom that we find in daily practice.

Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.

[Playing-related musculoskeletal disorders in the Valencian Community]. / Dolor musculoesquelético ligado a la interpretación musical en la Comunidad Valenciana.

OBJECTIVES: There is a relationship between routinely playing an instrument and musculoskeletal disorders. The most important of these disorders is pain. Therefore, playing-related musculoskeletal disorders can be established as a specific occupational problem. The Valencian Community is a region with a well-known musical tradition, in which the health impact of playing an instrument has not been sufficiently identified. The aim of this study was to define the frequency of musculoskeletal pain in music students in our environment and to identify its localization according to the instrument played. MATERIALS AND METHOD: This study included music students in the intermediate or advanced levels of the conservatoires of the Valencian Community. The variables were gathered through a health questionnaire completed by the students. To determine pain intensity, we calculated the mean VAS scores and the pain scores of the SRS-22 and CAVIDRA questionnaires, which have been validated for the Spanish population. Segmental pain localization was studied in the different groups of instruments. RESULTS: A total of 268 questionnaires were gathered, of which 222 met the inclusion criteria. Playing-related pain or discomfort was reported by 68% of respondents. The most frequently affected system was the musculoskeletal system. The most frequently-reported playing-related symptoms were pain, muscular tension, spasm and fatigue. CONCLUSIONS: A total of 68% of the musicians in this study reported some type of playing-related pain at some time during their studies. Study of the topography of instrument-related pain provides useful data for the design of prevention strategies.

Atopic dermatitis incidence and risk factors in young adults in Castellon (Spain): A prospective cohort study.

INTRODUCTION: There are few atopic dermatitis (AD) incidence cohort studies in young adults, the etiology of this disease remains obscure, and AD risk factors in adults are not well understood. The objective of this study was to estimate AD ten-year incidence and prevalence in a cohort of adolescent aged 14-16 at inception in Castellon province in Valencia Region, Spain and describe related risk factors. MATERIAL AND METHODS: From 2002 to 2012, a population-based prospective cohort study was carried out. Questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC) were used with an additional questionnaire for related factors completed by participants and their parents, respectively, in 2002. In 2012 the same questionnaires were completed by the participants' through a telephone interview, and incidence and prevalence of AD were estimated. Directed acyclic graphs, Poisson regression and inverse probability weighted regression adjustment were used. RESULTS: The participation rate was 79.5% (1435/1805) with AD lifetime prevalence of 34.9% and AD incidence of 13.5 per 1000 person years. Females presented higher prevalence and incidence than males. After adjustment significant risk factors were being female, history of asthma or allergic rhinitis, family history of AD, history of respiratory infections, history of bronchitis, history of pneumonia, history of sinusitis, and birthplace outside Castellon province. The highest AD population attributable risks were female, 30.3%, and history of respiratory infections 15.3%. Differences with AD childhood risk factors were found. CONCLUSIONS: AD incidence in our cohort was high and several risks factors were related to AD.

Final Phase in the Validation of the Cross-Cultural Adaptation of the Hair-Specific Skindex-29 Questionnaire Into Spanish: Sensitivity to Change and Correlation With the 12-Item Short-Form Health Survey. / Fase final de la validación transcultural al español de la escala Hair Specific Skindex-29: sensibilidad al cambio y correlación con la escala SF-12.

BACKGROUND AND OBJECTIVE: Work has already been done on validating the cross-cultural adaptation of the Hair-Specific Skindex-29 questionnaire (HSS-29) into Spanish. This questionnaire measures the impact of female-pattern hair loss on health-related quality of life (HRQoL). The aim of this study was to complete the validation process by testing the questionnaire's sensitivity to change and assessing its correlation with the generic 12-item Short-Form Health Survey (SF-12). MATERIAL AND METHOD: Patients who started treatment with a nutritional supplement that blocks the activity of 5-alpha-reductase were seen in two visits: a baseline visit and a follow-up visit at 6months. At each visit, hair loss severity was assessed by both investigators and patients via the Sinclair scale, evaluation of hair condition, and administration of HSS-29 and SF-12. RESULTS: In total, 983 women with female-pattern hair loss participated in the study. The mean HSS-29 score decreased from 25.7±18.7 at baseline to 19.3±15.7 at follow-up and significant changes were also observed in the functioning, emotions, and symptoms domains. Changes in overall and subscale HSS-29 scores from baseline to follow-up were all significantly correlated with changes in SF-12 subscale scores. The Pearson correlation coefficients ranged from -0.1 to -0.4 and were all significant at P<.001. CONCLUSIONS: The Spanish version of HSS-29 is sensitive to change, as it detected changes in objective measurements of HRQoL. Correlations between HSS-29 and SF-12 scores were also observed.

SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.

The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma.

PURPOSE: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown.Experimental Design: The patient-derived pilocytic astrocytoma cell culture model, DKFZ-BT66, was used to demonstrate presence of the SASP and analyze its impact on OIS in pilocytic astrocytoma. The model allows for doxycycline-inducible switching between proliferation and OIS. Both states were studied using gene expression profiling (GEP), Western blot, ELISA, and cell viability testing. Primary pilocytic astrocytoma tumors were analyzed by GEP and multiplex assay. RESULTS: SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High IL1B and SASP expression in pilocytic astrocytoma tumors was associated with favorable progression-free survival. CONCLUSIONS: We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted.

Groundwater dynamics in a hydrologically-modified alpine watershed from an ancient managed recharge system (Sierra Nevada National Park, Southern Spain): Insights from hydrogeochemical and isotopic information.

In many of the alpine watersheds of Sierra Nevada (Southern Spain) exists an ancient network of dug canals that collect, transport and facilitate the recharge the snowmelt in the underlying aquifer during the spring season. This practice, known as careos, in the lower part of the watersheds supply drinking water as spring discharge during the dry season. To study how this managed recharge technique modifies the natural response of these basins this work focuses on characterizing the hydrological behavior of one of the sites, the Berchules watershed. The mechanisms for mineralization of groundwater are based on geochemical processes such as evapo-concentration in the soil layer and silicate mineral weathering due to dissolved CO2 originated from both soil biogenic processes and the atmosphere. Groundwater presents a main hydrogeochemical calcium­magnesium-bicarbonate type facies, which is associated to groundwater flowing through the upper weathered silicates and quickly drained through springs located in the uplands and in the intermediate altitude catchment zone. Additionally, in the lower part of the basin some springs discharge mineralized groundwater with a sodium-calcium-bicarbonate composition associated to regional groundwater flow. In natural conditions, this hydrogeological system behaves as a sloping aquifer, occurring recharge between 1400 and 2500 m a.s.l. The springs discharge groundwater with an isotopic content and temperature in coherence with the local rainfall isotopic and thermal atmospheric altitudinal lines. Nevertheless, once the careo recharge begins the affected springs reveal the fingerprint of the concentrated recharge system by blurring the fingerprint of both the isotopic and thermal altitudinal dependence in the springs discharge. This validates the previous conceptual model and supports average recharge values of 141 ±â€¯140 mm/yr and total average water resources of 181 ±â€¯111 mm/yr which include a 40% increase in the study period due to the effect of the acequias de careo.

[Monoclonal spread of multi-drug resistant CTX-M-15-producing Klebsiella pneumoniae. Impact of measures to control the outbreak]. / Diseminación monoclonal de Klebsiella pneumoniae productora de CTX-M-15 multirresistente. Impacto de las medidas para controlar el brote.

OBJECTIVE: To describe an outbreak of multi-drug resistant extended-spectrum ß-lactamases-producing Klebsiella pneumoniae (MDR-ESBL-KPN) and the impact of measures for its control. METHODS: We reviewed the patients´ clinical records with MDR-ESBL-KPN isolation during 2013-2016 with resistance to fluoroquinolones, aminoglycosides, fosfomycin, and nitrofurantoin; susceptible to imipenem, meropenem, colistin, and tigecycline and variable to ertapenem and cotrimoxazole (Vitek-2). The genetic relationship between 35 isolates was established by PFGE and MLST. Control measures were put in place in January 2016. RESULTS: We detected 269 patients colonized and/or infected by KPN-ESBL-MDR with a common resistance phenotype; the strains studied carried the blaCTX-M-15 gene and formed a single cluster belonging to ST11. The outbreak was detected at the end of 2015, although it began in 2013 in an elderly center. The acquisition source of the strains was: 6% community-acquired, 37% hospital-acquired (76% in internal medicine) and 57% related to long health care facilities (78% of hospitalizations in the last year). Ninety-four percent of patients had at least one underlying disease, 90% received antibiotics previously and 49% had some invasive devices. After the introduction of control measures, the incidence of cases in the quarter was reduced from 29 to 15. CONCLUSIONS: We detected a monoclonal outbreak of MDR-CTX-M-15-KPN in 2015, with predominance of health-care associated cases. The success in the rapid spread of the outbreak was due to the delay in its detection and to the fact that most of the patients had previously received antibiotics. The control measures reduced the number of isolates by 50%.

[Results of the implementation of an Antimicrobial Stewardship Program in the "Gerencia de Atención Integrada" of Alcazar de San Juan (Castilla La Mancha)]. / Resultados de la implantación de un Programa de Optimización de Antimicrobianos en la Gerencia de Atención Integrada de Alcázar de San Juan (Castilla La Mancha).

OBJECTIVE: Our aim was to evaluate the efficiency of an ASP after its implementation in 2016 in a Spanish hospital quality system. METHODS: Efficiency of the ASP was measured by process and outcome indicators at the level of the patient's quality of life, antimicrobial consumption and percentage of resistance to them during the 2016-2017 period. In 2017, the failures mode and effects analysis (FMEA) methodology was applied. An annual satisfaction survey was conducted. RESULTS: The clinical indicators were within the threshold of acceptability, as well as the empirical prescription of antimicrobials, the consumption of antibiotics (reduction of 77 DDD in the first semester of 2016 to 26 in the second semester of 2017) and the renal (gentamicin) and neurological (carbapenems) toxicity. The FMEA identified as a main risk the lack of adequacy of the empirical treatment once the antibiogram was obtained; thus, a corrective action was taken in 2017. Regarding the microbiological indicators, the incidence of multi-drug resistant and carbapenemase-producing enterobacteria, and that of methicillin-resistant Staphylococcus aureus, were reduced. Eighty-three percent of the counselling activities carried out were accepted. The surveys revealed a good acceptance and spread of the program, the need for protocols and training in the use of antibiotics. CONCLUSIONS: The implementation of the ASP in the quality system was efficient. The consumption of antibiotics and the adverse effects derived from their use were reduced, improving the quality of life of patients, and reducing health costs.

Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ±âŸ38.4 mg/dL; week 48: 171.0 ±âŸ35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ±âŸ1.2; week 48: 4.0 ±âŸ1.2), HDL (baseline: 49.1 ±âŸ12.0 mg/dL; week 48: 49.2 ±âŸ45.8 mg/dL), LDL (baseline: 119.2 ±âŸ30.2 mg/dL; week 48: 114.2 ±âŸ110.7 mg/dL), and triglycerides (baseline: 136.6 ±âŸ86.8 mg/dL; week 48: 113.4 ±âŸ67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ±âŸ48.8 mg/dL; week 48: 173.4 ±âŸ36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ±âŸ1.6; week 48: 4.0 ±âŸ1.2), HDL (baseline: 46.4 ±âŸ12.5 mg/dL; week 48: 52.1 ±âŸ54.4 mg/dL), LDL (baseline: 127.0 ±âŸ36.3 mg/dL; week 48: 111.4 ±âŸ35.8 mg/dL), and triglycerides (baseline: 167.6 ±âŸ107.7 mg/dL; week 48: 122.7 ±âŸ72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.

Waning protection of influenza vaccination during four influenza seasons, 2011/2012 to 2014/2015.

BACKGROUND: Concerns have been raised about intraseasonal waning of the protection conferred by influenza vaccination. METHODS: During four influenza seasons, we consecutively recruited individuals aged 18years or older who had received seasonal influenza vaccine and were subsequently admitted to the hospital for influenza infection, asassessed by reverse transcription polymerase chain reaction. We estimated the adjusted odds ratio (aOR) of influenza infection by date of vaccination, defined by tertiles, as early, intermediate or late vaccination. We used a test-negative approach with early vaccination as reference to estimate the aOR of hospital admission with influenza among late vaccinees. We conducted sensitivity analyses by means of conditional logistic regression, Cox proportional hazards regression, and using days between vaccination and hospital admission rather than vaccination date. RESULTS: Among 3615 admitted vaccinees, 822 (23%) were positive for influenza. We observed a lower risk of influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.68 (95% CI: 0.47-1.00) and 0.69 (95% CI: 0.50-0.95). We found no differences in the risk of admission with influenza among late versus early vaccinees in the 2012/2013A(H1N1)pdm09-dominant or 2013/2014B/Yamagata lineage-dominant seasons: aOR=1.18 (95% CI: 0.58-2.41) and 0.98 (95% CI: 0.56-1.72). When we restricted our analysis to individuals aged 65years or older, we found a statistically significant lower risk of admission with influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.61 (95% CI: 0.41-0.91) and 0.69 (95% CI: 0.49-0.96). We observed 39% (95% CI: 9-59%) and 31% (95% CI: 5-50%) waning of vaccine effectiveness among participants aged 65years or older during the two A(H3N2)-dominant seasons. Similar results were obtained in the sensitivity analyses. CONCLUSION: Waning of vaccine protection was observed among individuals aged 65years old or over in two A(H3N2)-dominant influenza seasons.

Mixed-Substituent Cyclophosphazenes with Calamitic and Polycatenar Mesogens.

A synthetic strategy has been developed to prepare liquid crystalline cyclotriphosphazenes that have two different types of mesogenic units linked to the same phosphorus atom. Hexachlorocyclotriphosphazene, N3P3Cl6, was reacted with 3 mol of the calamitic unit 4-cyano-4'-hydroxybiphenyl to give a mixture of compounds in which the nongem-trans-trisubstituted derivative N3P3Cl3(OC6H4C6H4{CN}-p)3 was the major product. The substitution of all three chlorine atoms in this nongeminal compound gave rise to the hydroxyl-functional phosphazenes, nongem-trans-N3P3(OC6H4C6H4{CN}-p)3(OC6H4{OH}-p)3 or nongem-trans-N3P3(OC6H4C6H4{CH3}-p)3(OC6H4{OH}-p)3, from which the second mesogenic unit, a polycatenar one, was introduced. The chemical structure of the resulting materials, deduced from spectroscopic and MALDI-TOF techniques, was in accordance with monodisperse, fully functionalized cyclotriphosphazenes. Mesomorphism is highly dependent on the terminal group of the calamitic units, and liquid crystal phases were only detected on the cyano-derivatives. The calamitic or columnar nature of the mesophase depends on the number of alkyl chains of the polycatenar moieties.