α-Tricalcium phosphate cement reinforced with silk fibroin: A high strength biomimetic bone cement with chloride-substituted hydroxyapatite.

In the past decades, bone defects have become an increasing factor in the development of disability in patients, impacting their quality of life. Large bone defects have minor chances to self-repair, requiring surgical intervention. Therefore, α-TCP-based cements are rigorously studied for the development of bone filling and replacement applications due to the possibility of application in minimally invasive procedures. However, α-TCP-based cements do not present adequate mechanical properties for most orthopedic applications. The aim of this study is to develop a biomimetic α-TCP cement reinforced with 0.250-1.000 wt% of silk fibroin using non-dialyzed SF solutions. Samples with SF additions higher than 0.250 wt% presented complete transformation of the α-TCP to a biphasic CDHA/HAp-Cl material, which could enhance the osteoconductivity of the material. Samples reinforced with concentrations of 0.500 wt% SF showed an increase of 450% of the fracture toughness and 182% of the compressive strength of the control sample, even with 31.09% porosity, which demonstrates good coupling between the SF and the CPs. All samples reinforced with SF showed a microstructure with smaller needle-like crystals when compared to the control sample, which possibly contributed to the material's reinforcement. Moreover, the composition of reinforced samples did not affect the cytotoxicity of the CPCs and enhanced the cell viability presented by the CPC without SF addition. Hence, biomimetic CPCs with mechanical reinforcement through the addition of SF were successfully obtained through the developed methodology, with the potential to be further evaluated as a suitable material for bone regeneration.

Adaptive evolution of PB1 from influenza A(H1N1)pdm09 virus towards an enhanced fitness.

PB1 influenza virus retain traces of interspecies transmission and adaptation. Previous phylogenetic analyses highlighted mutations L298I, R386K and I517V in PB1 to have putatively ameliorated the A(H1N1)pdm09 adaptation to the human host. This study aimed to evaluate the reversal of these mutations and infer the role of these residues in the virus overall fitness and adaptation. We generate PB1-mutated viruses introducing I298L, K386R and V517I mutations in PB1 and evaluate their phenotypic impact on viral growth and on antigen yield. We observed a decrease in viral growth accompanied by a reduction in hemagglutination titer and neuraminidase activity, in comparison with wt. Our data indicate that the adaptive evolution occurred in the PB1 leads to an improved overall viral fitness; and such biologic advantaged has the potential to be applied to the optimization of influenza vaccine seed prototypes.

α-TCP-based calcium phosphate cements: A critical review.

Calcium phosphates are promising materials for applications in bone repair and substitution, particularly for their bioactivity and ability to form self-setting cements. Among them, α-tricalcium phosphate (α-TCP) stands out due to its high solubility, its hydration reaction and bioresorbability. The synthesis of α-TCP is particularly complex and the interactions between some of the synthesis parameters are still not completely understood. The variety of methods available to synthesize α-TCP has provided a substantial variance in the properties of α-TCP-based cements and the decision about which method, parameters and starting reagents will be used for the powder's synthesis is determinant of the properties of the resulting material. Therefore, this review paper focuses on α-TCP's synthesis and properties, presenting the synthesis methods currently in use as well as a discussion of how the synthesis parameters and the cement preparation affect the reactivity and mechanical properties of the material, providing a guide for the selection of the most suitable process for each α-TCP application. STATEMENT OF SIGNIFICANCE: α-TCP is a calcium phosphate and it is currently one of the most investigated bioceramics for applications that explore its bioresorbability and the hydration reaction of α-TCP-based cements. Despite the increasing number of publications on the topic, there are still aspects not well understood. This review article aims at contributing to this fascinating subject by offering an update on the state of the art of α-TCP's synthesis methods, while also addressing topics that are not often discussed about this material, such as the preparation of α-TCP-based cements and how its parameters affect the properties of the resulting cements.

Optimization of A(H1N1)pdm09 vaccine seed viruses: The source of PB1 and HA vRNA as a major determinant for antigen yield.

Vaccination prevents and reduces the severity of influenza virus infections. Continuous evolution of influenza hemagglutinin (HA) and neuraminidase (NA) supports the virus to evade pre-existing immunity, which demands vaccines to be reformulated every year. Incorporation of polymerase basic protein 1 (PB1) viral RNA (vRNA) of the same origin of HA and NA vRNA has been observed in previous pandemic viruses and occasionally reported for influenza A vaccine prototype strains of prior seasons. At this point, it remains to be explored whether this phenomenon translates into an improved growth phenotype. In this work, we showed that the HA vRNA of A(H1N1)pdm09 is generally incorporated with the PB1 vRNA of the same origin, establishing the beneficial effect of the presence of PB1 and the pattern of the PB1-HA co-incorporation in the A(H1N1)pdm09 model. We further investigated the putative interplay between PB1 and antigenic proteins regarding the vRNA composition of the progeny and observed that vRNA segregation does not appear to be mainly determined by protein-protein interactions; while vRNA-vRNA interactions can be suggested as the main driving force. Our data also indicate an increase in the hemagglutination capacity and neuraminidase activity due to incorporation of PB1, HA and NA from A(H1N1)pdm09, in comparison with the recombinant virus incorporating only HA and NA from A(H1N1)pdm09 - which have the potential to improve current limitations regarding antigenicity and immunogenicity of influenza vaccines. Further knowledge of the complex vRNA-vRNA interaction network between PB1 and HA will additionally contribute to improve current vaccine formulation, and to gradually optimize the production of A(H1N1)pdm09 reverse genetics vaccine seed virus towards a higher cost-effectiveness.

Why do patients leave the Pediatric Emergency Department and what happens to them?

BACKGROUND: The dropout rate is an important indicator of the quality of emergency services. The authors intend to evaluate factors that influence abandonments in the Pediatric Emergency Department (PED) and to assess outcome and destination of the highest triage leveled patients. METHODS: Retrospective analysis of the abandonment cases occurring between 2014 and 2016 in a tertiary hospital, including sociodemographic characterization, temporal factors, triage level, referral from other health services, waiting time and patient attendance. The outcome of the highest triage level was also accessed. RESULTS: In the three years analyzed, there were 240171 PED visits, with an abandonment rate of 2.57%. PED abandonment was influenced by higher patient attendance and waiting time, a younger age, and less urgent triage level. Only 1.78% of the urgent or emergent patients (level three or two) abandoned the PED. Of these, 44% sought medical care in the next five days, 41% of which in private institutions, 40% in public hospitals and 19% in primary care. Only 0.81% of those were hospitalized. CONCLUSIONS: The majority of patients who leave the PED do not correspond to urgent cases. Health education awareness campaigns, clinical counseling platforms (online or phone services) and the improved accessibility of primary health care may optimize the usage of health resources. The reinforcement of the teams in times of greater affluence may contribute to decrease the rate of abandonment.

NS1 protein as a novel anti-influenza target: Map-and-mutate antiviral rationale reveals new putative druggable hot spots with an important role on viral replication.

Influenza NS1 is a promising anti-influenza target, considering its conserved and druggable structure, and key function in influenza replication and pathogenesis. Notwithstanding, target identification and validation, strengthened by experimental data, are lacking. Here, we further explored our previously designed structure-based antiviral rationale directed to highly conserved druggable NS1 regions across a broad spectrum of influenza A viruses. We aimed to identify NS1-mutated viruses exhibiting a reduced growth phenotype and/or an altered cell apoptosis profile. We found that NS1 mutations Y171A, K175A (consensus druggable pocket 1), W102A (consensus druggable pocket 3), Q121A and G184P (multiple consensus druggable pockets) - located at hot spots amenable for pharmacological modulation - significantly impaired A(H1N1)pdm09 virus replication, in vitro. This is the first time that NS1-K175A, -W102A, and -Q121A mutations are characterized. Our map-and-mutate strategy provides the basis to establish the NS1 as a promising target using a rationale with a higher resilience to resistance development.

To hit or not to hit: Large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potential.

Influenza NS1 protein is among the most promising novel druggable anti-influenza target, based on its structure; multiple interactions; and global function in influenza replication and pathogenesis. Notwithstanding, drug development guidance based on NS1 structural biology is lacking. Here, we design a promising strategy directed to highly conserved druggable regions as a result of an exhaustive large-scale sequence analysis and structure characterization of NS1 protein across human-infecting influenza A subtypes, over the past 100 years. We have identified 3 druggable pockets and 8 new potential hot spot residues in the NS1 protein, not described before, additionally to other 16 sites previously identified, which represent attractive targets for pharmacological modulation. This study provides a rationale towards structure-function studies of NS1 druggable sites, which have the potential to accelerate the NS1 target validation. This research also contributes to a deeper comprehension and insight into the evolutionary dynamics of influenza A NS1 protein.

Histological and structural evaluation of growth hormone and PLGA incorporation in macroporous scaffold of α-tricalcium phosphate cement.

An in vivo study was conducted to evaluate the effects of the incorporation of fibers of poly(lactic acid-co-glycolic acid, PLGA) and poly(isoprene) blend and recombinant human growth hormone (rhGH) in a macroporous scaffold of α-tricalcium phosphate cement (α-TCP) samples inserted into calvarial defects (8 mm in diameter) of 48 Wistar rats. The samples of α-TCP + PLGA/poly(isoprene) blend fibers were also submitted to a mechanical test of flexural strength. The animals of the different experimental groups [1] α-TCP (n = 6); [2] α-TCP + PLGA/poly(isoprene) blend fibers (n = 6); [3] α-TCP + rhGH, (n = 6) and [4] α-TCP + PLGA/poly(isoprene) blend fibers + rhGH, (n = 6) (the numbers within square brackets identify the experimental groups), after two weeks (subdivision "a") and four weeks (subdivision "b"), were euthanized and the implants removed for histological analysis. There was no statistical difference (p > 0.05) between the samples with and without fibers in the mechanical test. Light microscopy revealed good integration of the material in the host tissue, represented by tissue penetration into the macropores and adequate angiogenesis. In the two-week period, the groups [3a] and [4a] were significantly superior (p < 0.05) to the other groups with regard to angiogenesis and bone neoformation. In the four-week period, the group [3b] was significantly superior (p < 0.05) to the other groups with regard to bone neoformation. We conclude that the macroporous α-TCP scaffold used in this study has low mechanical resistance, is biocompatible and has significantly improved the osteoconductive capacity when rhGH is incorporated into its structure.

Experimental use of new absorbable tracheal stent.

BACKGROUND/PURPOSE: Silicone and metallic stents are not effective in children with tracheobronchial stenosis or tracheomalacia. Herein, we aimed to evaluate the clinical manifestations and histological reaction of rabbit trachea to the presence of a new poly(lactic-co-glycolic acid) with polyisoprene (PLGA/PI) polymer absorbable stent. METHODS: Fourteen adult white rabbits (weight, 3.0-3.5kg) were randomly assigned to three groups: Group I (n=6): PLGA/PI spiral stent; Group II (n=6): PLGA/PI fragment; and Group III (n=2): controls. After a longitudinal incision on three cervical tracheal rings, the stents and fragments were inserted into the trachea and fixed onto the lateral wall with nonabsorbable sutures. RESULTS: The stented group showed significantly more stridor at rest (p=0.0041), agitation (p=0.014), and use of accessory muscles (p=0.0002) and required more emergency endoscopies than the fragment group. Further, it showed significantly more remarkable histological inflammatory damage than the fragment and control groups (p=0.002). CONCLUSIONS: The new PLGA/PI polymeric stent implanted into the trachea of rabbits caused more clinical manifestations and histologically verified inflammatory reaction than the PLGA/PI polymeric fragment. Future studies should be aimed at reducing the stent-wall thickness.

In vitro evaluation of poly (lactic-co-glycolic acid)/polyisoprene fibers for soft tissue engineering.

The polymeric blend of poly (lactic-co-glycolic acid) (PLGA) and polyisoprene (PI) has recently been explored for application as stents for tracheal stenosis and spring for the treatment of craniosynostosis. From the positive results presented in other biomedical applications comes the possibility of investigating the application of this material as scaffold for tissue engineering (TE), acquiring a deeper knowledge about the polymeric blend by exploring a new processing technique while attending to the most fundamental demands of TE scaffolds. PLGA/PI was processed into randomly oriented microfibers through the dripping technique and submitted to physical-chemical and in vitro characterization. The production process of fibers did not show an effect over the polymer's chemical composition, despite the fact that PLGA and PI were observed to be immiscible. Mechanical assays reinforce the suitability of these scaffolds for soft tissue applications. Skeletal muscle cells demonstrated increases in metabolic activity and proliferation to the same levels of the control group. Human dermal fibroblasts didn't show the same behaviour, but presented cell growth with the same development profile as presented in the control group. It is plausible to believe that PLGA/PI fibrous three-dimensional scaffolds are suitable for applications in soft tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2581-2591, 2017.

Effects of dual-task interventions on gait performance of patients with Parkinson's Disease: A systematic review / Efeito da dupla tarefa na marcha em pacientes com doença de parkinson: uma revisão sistemática

OBJECTIVE: Parkinson's disease is characterized by motor and non-motor symptoms that impair patients' gait performance, especially while performing dual/concurrent tasks. These deficits impair patients' daily function, because dual-tasking is a crucial ability in terms of everyday living. The aim of this study was to systematically review the effects of dual task interventions on gait performance of patients with Parkinson's disease. METHOD: Studies were retrieved from MEDLINE/PubMed, LILACS and SciELO. We used the PICOS strategy to determine eligibility criteria. The search strategy included an advanced search on the included databases, using the following search query: "Parkinson's Disease" AND "Double Task" OR "Concurrent Tasks" OR "Gait" AND "Walk". Study selection was carried out by two independent researchers and a third one was called when consensus was needed. RESULTS: A total of 188 articles were identified: 169 articles from Medline/PubMed, 10 articles in SciELO, 8 articles in LILACS and 1 item from manual searches. A total of 56 articles were analyzed regarding the eligibility and exclusion criteria based on full text. A final total of 7 studies were included in the systematic review. CONCLUSION: The different types of dual-task interventions reported (dance, sound stimuli, visual and somatosensory) were associated to improvements in several gait performance indicators of Parkinson's disease patients, including gait speed, stride time and length, cadence and step length. External stimuli seem to play a critical role on specific training effects on dual-task gait performance.

OBJETIVO: A Doença de Parkinson é caracterizada por sintomas motores e não motores que prejudicam a marcha, especialmente durante a realização de tarefas duplas/simultâneas. Estes déficits afetam o funcionamento diário do paciente já que a realização de tarefas duplas é uma habilidade crucial para a vida normal.O objetivo deste estudo foi realizar uma Revisão Sistemática sobre os efeitos das tarefas duplas sobre a marcha em pacientes com Doença de Parkinson. MÉTODOS: Os estudos foram recuperados do MEDLINE/PubMed, SciELO e Lilacs. Adotamos a estratégia PICOS para determinar os critérios de elegibilidade. A estratégia de busca foi realizada utilizando uma pesquisa avançada MEDLINE/PubMed, SciELO e Lilacs com os seguintes termos adotados "Doença de Parkinson", "Dupla Tarefa", "Tarefas Concorrentes", "Marcha" e "Caminhada". Operadores booleanos AND e OR foram utilizados para combinação dos termos. A seleção dos estudos foi realizada por dois pesquisadores independentes que, em caso de desacordo, procuraram um consenso sobre a seleção. RESULTADOS: Foram identificados um total de 188 artigos:169 artigos do PubMed/Medline, 10 artigos no SciELO, 8 artigos no LILACS e 1 artigo em buscas manuais. Após uma seleção inicial, 56 artigos foram analisados pelos critérios de elegibilidade e os critérios de exclusão, sendo que um total de sete estudos foi incluído na revisão sistemática. CONCLUSÃO: De acordo com os estudos analisados nesta revisão, os diferentes tipos de intervenção incluídos (dança, estímulos sonoros, visuais e somato-sensoriais) permitem melhorias em vários indicadores de marcha tais como a velocidade, tempo da passada, cadência e comprimento do passo. A utilização de estímulos externos aparentam desempenhar um papel crítico nos efeitos espeíficos do treinamento na marcha em condições de dupla-tarefa.

Distinct kinetics and pathways of apoptosis in influenza A and B virus infection.

Annual influenza epidemics are associated with high incidence and mortality rates, and are an important cause of work absenteeism and productivity losses. For successful replication, influenza viruses have evolved as to counteract and/or take a part on host defense mechanisms. Manipulation of apoptosis is one of such mechanisms that have been subject of attention, particularly in relation to influenza type A viruses over the past years. However, this knowledge has not been extended to include influenza type B viruses. In this study, MDCK-SIAT1 cells were infected with influenza A and B strains and the kinetics and pathways of apoptosis post infection were studied, through LDH measurements, Hoechst dye staining, caspase activity assays and protein expression analysis. The resulting data points to a difference in induction of apoptosis profiles between influenza A and B strains. While influenza A strain induced apoptosis later in the course of infection and mainly by the intrinsic pathway, influenza B strain induced apoptosis early in infection by both intrinsic and extrinsic pathways. Also, data revealed the IκB/NF-κB pathway as the major contributor for the observed differences. The study of the virus-host interactions, particularly those that could have an impact on viral replication, are essential in both influenza A and B viruses, as they will allow the identification of viral/host targets common to both influenza types, which could affect viral replication. This information may prove useful for vaccine and antiviral research.

Glycerol salicylate-based containing α-tricalcium phosphate as a bioactive root canal sealer.

The use of bioactive materials instead of inert materials to fill the root canal space could be an effective approach to achieve a hermetic seal and stimulate the healing of periapical tissues. The purpose of this study was to develop and characterize an endodontic sealer based on a glycerol salicylate resin and α-tricalcium phosphate (αTCP) at physical and chemical properties. Different sealers were formulated using 70% of a glycerol salicylate resin and 30% of a mixture of calcium hydroxide and αTCP (0, 5, 10, or 15%, in weight). Sealers formulated were characterized based on setting time, in vitro degradation over time, pH, cytotoxicity, and mineral deposition. Sealers presented setting time ranging from 240 to 405 min, and basic pH over 8.21 after 28 days. Higher αTCP concentration leads to sealers with low solubility. Cell viability after 48 h in direct contact with sealers was similar to a commercial sealer used as reference. The 10% and 15% αTCP sealers exhibited a calcium-phosphate layer on the surface after immersion in water and SBF for 7 days. Glycerol salicylate sealers with 10% and 15% α-tricalcium phosphate showed reliable physical-chemical properties and apatite-forming ability.

Influenza A(H1N1)pdm09 resistance and cross-decreased susceptibility to oseltamivir and zanamivir antiviral drugs.

Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.

The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data.

The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and standardized protocols for the experimentation, collection and dissemination of data. Dedicated 'data wranglers' work with each phenotyping center to collate data and perform quality control of data. An automated statistical analysis pipeline has been developed to identify knockout strains with a significant change in the phenotype parameters. Annotation with biomedical ontologies allows biologists and clinicians to easily find mouse strains with phenotypic traits relevant to their research. Data integration with other resources will provide insights into mammalian gene function and human disease. As phenotype data become available for every gene in the mouse, the IMPC web portal will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases.

Evaluation of scaffolds based on α-tricalcium phosphate cements for tissue engineering applications.

Growth of cells in 3-D porous scaffolds has gained importance in the field of tissue engineering. The scaffolds guide cellular growth, synthesize extracellular matrix and other biological molecules, and make the formation of tissues and functional organs easier. The aim of this study is to use α-tricalcium phosphate cement in order to obtain new types of scaffolds with the aid of paraffin spheres as pore generators. The porosity of the scaffolds produced with paraffin spheres was analyzed and compared to the literature, and the study of scaffold permeability using the Forchheimer equation allowed the analysis of pore interconnectivity. In vitro tests showed the behavior of scaffolds in solutions of simulated body fluid, and viability and cell proliferation were also evaluated. The results show the potential use of the materials developed for scaffolds for use in tissue engineering applications.

Clinical and imaging features in a patient with hemifacial hyperplasia.

Hemifacial hyperplasia is a developmental disorder characterized by marked unilateral facial asymmetry. It involves the hard and soft tissues of the face. The cause is unknown, although several predisposing factors have been described. A case report of an 8-year-old boy with hemifacial hyperplasia is presented to highlight the clinical and imaging findings.

Characterization of bone repair in rat femur after treatment with calcium phosphate cement and autogenous bone graft.

BACKGROUND: In this study, the biocompatibility, stability and osteotransductivity of a new cement based on alpha-tricalcium phosphate (alpha-TCP) were investigated in a bone repair model using a rat model. METHODS: The potential of alpha-TCP on bone repair was compared to autogenous bone grafting, and unfilled cavities were used as negative control. Surgical cavities were prepared and designated as test (T), implanted with alpha-TCP blocks; negative control (C - ), unfilled; and positive control (C + ), implanted with autogenous bone graft. Results were analyzed on postoperative days three, seven, 14, 21 and 60. RESULTS: The histological analyses showed the following results. Postoperative day three: presence of inflammatory infiltrate, erythrocytes and proliferating fibroblasts in T, C - and C + samples. Day seven: extensive bone neoformation in groups T and C + , and beginning of alpha-TCP resorption by phagocytic cells. Days 14 and 21: osteoblastic activity in the three types of cavities. Day 60: In all samples, neoformed bone similar to surrounding bone. Moderate interruption on the ostectomized cortical bone. CONCLUSIONS: Bone neoformation is seen seven days after implantation of alpha-TCP and autogenous bone. Comparison of C - with T and C + samples showed that repair is faster in implanted cavities; on day 60, control groups presented almost complete bone repair. Alpha-TCP cement presents biocompatibility and osteotransductivity, besides stability, but 60 days after surgery the cavities were not closed.

Antiviral drug profile of seasonal influenza viruses circulating in Portugal from 2004/2005 to 2008/2009 winter seasons.

A research project on antiviral drug resistance of influenza viruses circulating in Portugal has been carried out since 2007. Here, the first results obtained regarding the evaluation of susceptibility to amantadine and oseltamivir are presented. Information about antiviral prescription and exposure was available through the National Influenza Surveillance Programme. Amantadine susceptibility was evaluated by pyrosequencing for known resistance markers on 178 influenza A strains from 2004/2005 to 2006/2007. Susceptibility to oseltamivir was evaluated by 50% inhibitory concentration determination on 340 virus strains from 2004/2005 to 2008/2009, 134 of which were further analyzed by sequencing of the neuraminidase gene. This study revealed that influenza antiviral drugs were rarely prescribed at national level. Resistance to amantadine was observed on only A(H3N2) strain isolated during 2005/2006 and on 38 (74.5%) of the 51 A(H3N2) strains from 2006/2007, all carrying the mutation S31N in their M2 sequence. Oseltamivir resistance was observed in 6 (20.7%) of the 29 A(H1N1) strains from 2007/2008 and in all strains from 2008/2009, which exhibited extremely high IC(50) values and carrying the mutation H275Y in their neuraminidase sequence. The national data generated and analyzed in this study may contribute to increase the knowledge on influenza antiviral drug resistance which is a problem of global concern.