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1.
Indian J Clin Biochem ; 39(1): 124-129, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38223004

RESUMEN

The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian subjects is further enhanced. The present study explored the role of ACE I/D polymorphism, rs4340 as a genetic marker and its association with diabetes. Genomic DNA, isolated from a cohort of 410 urban subjects attending our hospital, was genotyped using polymerase chain reaction followed by electrophoresis. Among the subjects, 84 had type-2 diabetes and 68 had hypertension while 258 were free from these risk factors. Majority (57/84) of diabetic subjects were also suffering from hypertension. Genotype frequencies of ACE I/D polymorphism, of diabetic (84) patients were not different from that of non-diabetic subjects (258). In sharp contrast, we found significant differences, in genotype frequencies of women with diabetes (n = 38) compared to non-diabetic women (70). Diabetic women had significantly higher prevalence of the high risk 'D' allele. Analysis of odds ratio, OR revealed that women with 'D/D' genotype, exhibited threefold risk (OR 3.12, 95% CI 1.21-8.05; p = 0.018) of diabetes, in the recessive model (D/D vs I/I + I/D). Further when we analysed Odds ratio of diabetic women (8) who were free from hypertension, the results revealed even a greater, 6- fold (OR 6.0, 95% CI 1.29-27.96, p = 0.027) risk of diabetes for D/D homozygous women (D/D vs I/I + I/D). These results suggest 'sex-specific' association of ACE 'I/D' polymorphism, with type-2 diabetes, affecting women while there was no influence observed among men. In view of the increased cardiovascular mortality among Indians, data from our pilot study if confirmed in a larger cohort, could add value to our future intervention efforts.

2.
Clin Infect Dis ; 76(9): 1628-1635, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-36571282

RESUMEN

BACKGROUND: We evaluated the prevalence of transmitted drug resistance (TDR) to integrase strand-transfer inhibitors (INSTIs) and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and of clinically relevant resistance (CRR) in newly diagnosed people with human immunodeficiency virus (HIV; PWH) naive to antiretroviral therapy (ART) in Europe. METHODS: MeditRes is a consortium that includes ART-naive PWH newly diagnosed in France, Greece, Italy, Portugal, and Spain during 2018-2021. Reverse transcriptase and INSTI sequences were provided by participating centers. To evaluate the prevalence of surveillance drug resistance mutations (SDRM), we used the calibrated population resistance tools from the Stanford HIV website. To evaluate CRR, defined as any resistance level ≥3, we used the Stanford HIV Drug Resistance Database v.9.1 algorithm. RESULTS: We included 2705 PWH, 72% men, median age of 37 years (interquartile range, 30-48); 43.7% were infected by non-B subtypes. The prevalence of INSTI-SDRMs was 0.30% (T66I, T66A, E92Q, E138T, E138K, Y143R, S147G, R263K; all n=1) and the prevalence of NRTI-SDRMs was 5.77% (M184V: 0.85%; M184I: 0.18%; K65R/N: 0.11%; K70E: 0.07%; L74V/I: 0.18%; any thymidine analog mutations: 4.36%). INSTI-CRR was 2.33% (0.15% dolutegravir/bictegravir, 2.29% raltegravir/elvitegravir) and 1.74% to first-line NRTIs (0.89% tenofovir/tenofovir alafenamide, 1.74% abacavir, 1.07% lamivudine/emtricitabine). CONCLUSIONS: We present the most recent data on TDR to integrase-based first-line regimens in Europe. Given the low prevalence of CRR to second-generation integrase inhibitors and to first-line NRTIs during 2018-2021, it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second-generation integrase inhibitors.


Asunto(s)
Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , VIH-1 , Masculino , Humanos , Adulto , Femenino , Integrasas/genética , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Mutación , Europa (Continente)/epidemiología , VIH-1/genética , Adenina , Farmacorresistencia Viral/genética , Integrasa de VIH/genética , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico
3.
Proc Biol Sci ; 290(2010): 20230957, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37909073

RESUMEN

Recent studies have suggested the presence of moonlight mediated behaviour in avian aerial insectivores, such as swifts. Here, we use the combined analysis of state-of-the-art activity logger data across three swift species, the common, pallid and alpine swifts, to quantify flight height and activity in responses to moonlight-driven crepuscular and nocturnal light conditions. Our results show a significant response in flight heights to moonlight illuminance for common and pallid swifts, i.e. when moon illuminance increased flight height also increased, while a moonlight-driven response is absent in alpine swifts. We show a weak relationship between night-time illuminance-driven responses and twilight ascending behaviour, suggesting a decoupling of both crepuscular and night-time behaviour. We suggest that swifts optimize their flight behaviour to adapt to favourable night-time light conditions, driven by light-responsive and size-dependent vertical insect stratification and weather conditions.


Asunto(s)
Aves , Vuelo Animal , Animales , Vuelo Animal/fisiología , Aves/fisiología , Insectos
4.
J Med Virol ; 95(11): e29205, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37933896

RESUMEN

Norovirus is a major cause of acute diarrheal disease (ADD) outbreaks worldwide. In the present study, we investigated an ADD outbreak caused by norovirus in several municipalities of Santa Catarina state during the summer season, southern Brazil in 2023. As of the 10th epidemiological week of 2023, approximately 87 000 ADD cases were reported, with the capital, Florianópolis, recording the highest number of cases throughout the weeks. By using RT-qPCR and sequencing, we detected 10 different genotypes, from both genogroups (G) I and II. Some rare genotypes were also identified. Additionally, rotavirus and human adenovirus were sporadically detected among the ADD cases. Several features of the outbreak suggest that sewage-contaminated water could played a role in the surge of ADD cases. Storm events in Santa Catarina state that preceded the outbreak likely increased the discharge of contaminated wastewater and stormwater into water bodies, such as rivers and beaches during a high touristic season in the state. Climate change-induced extreme weather events, including intensified rainfall and frequent floods, can disturb healthcare and sanitation systems. Implementing public policies for effective sanitation, particularly during peak times, is crucial to maintain environmental equilibrium and counter marine pollution.


Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Norovirus/genética , Brasil/epidemiología , Brotes de Enfermedades , Genotipo , Agua , Infecciones por Caliciviridae/epidemiología , Heces
5.
Somatosens Mot Res ; : 1-7, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36950966

RESUMEN

PURPOSE/AIM OF THE STUDY: The purpose of this study was to analyse the relationship between digital media use and expressive language skills in the semantic and morphosyntactic domains, of pre-school-aged children (3 years-and-0 months to 5 years-and-11 months). MATERIALS AND METHODS: Verbal oral expression (VOE) tasks of the Pre-school Assessment of Language Test (Teste de Linguagem-Avaliação da Linguagem Pré-Escolar) were administered to 237 pre-school children with no previous identified neurological or developmental conditions associated with language disorders to assess expressive language skills in the semantic and morphosyntactic domains. Parents completed a questionnaire about their children's medical conditions, development (using the milestones of the Survey of Well-being of Young Children and the Pre-school Paediatric Symptom Checklist), and exposure to screens (using ScreenQ). Correlations between VOE and continuous variables such as ScreenQ were computed and a regression model incorporating all variables significantly associated with total language verbal expression was created. RESULTS: ScreenQ revealed a negative and significant correlation with children's verbal oral expression as well as significance in the regression model. Parents' education was the most significant predictor in this regression model. CONCLUSIONS: This study emphasizes the importance of parents establishing limits for digital media use and promote good practices such as co-viewing.

6.
Molecules ; 28(24)2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38138538

RESUMEN

The SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) enzyme opposes the activity of PI3K and therefore is of interest in the treatment of inflammatory disorders. Recent results also indicate that SHIP1 promotes phagolysosomal degradation of lipids by microglia, suggesting that the enzyme may be a target for the treatment of Alzheimer's disease. Therefore, small molecules that increase SHIP1 activity may have benefits in these areas. Recently we discovered a bis-sulfonamide that increases the enzymatic activity of SHIP1. A series of similar SHIP1 activators have been synthesized and evaluated to determine structure-activity relationships and improve in vivo stability. Some new analogs have now been found with improved potency. In addition, both the thiophene and the thiomorpholine in the parent structure can be replaced by groups without a low valent sulfur atom, which provides a way to access activators that are less prone to oxidative degradation.


Asunto(s)
Monoéster Fosfórico Hidrolasas , Monoéster Fosfórico Hidrolasas/metabolismo
7.
J Cell Sci ; 133(5)2020 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-31780579

RESUMEN

We show here that both SHIP1 (Inpp5d) and its paralog SHIP2 (Inppl1) are expressed at protein level in microglia. To examine whether targeting of SHIP paralogs might influence microglial physiology and function, we tested the capacity of SHIP1-selective, SHIP2-selective and pan-SHIP1/2 inhibitors for their ability to impact on microglia proliferation, lysosomal compartment size and phagocytic function. We find that highly potent pan-SHIP1/2 inhibitors can significantly increase lysosomal compartment size, and phagocytosis of dead neurons and amyloid beta (Aß)1-42 by microglia in vitro We show that one of the more-potent and water-soluble pan-SHIP1/2 inhibitors, K161, can penetrate the blood-brain barrier. Consistent with this, K161 increases the capacity of CNS-resident microglia to phagocytose Aß and apoptotic neurons following systemic administration. These findings provide the first demonstration that small molecule modulation of microglia function in vivo is feasible, and suggest that dual inhibition of the SHIP1 and 2 paralogs can provide a novel means to enhance basal microglial homeostatic functions for therapeutic purposes in Alzheimer's disease and, possibly, other types of dementia where increased microglial function could be beneficial.


Asunto(s)
Enfermedad de Alzheimer , Microglía , Péptidos beta-Amiloides , Homeostasis , Humanos , Fagocitosis
8.
Org Biomol Chem ; 20(19): 4016-4020, 2022 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-35506893

RESUMEN

AQX-1125 is an indane based SHIP1 agonist that has been evaluated in the clinic for the treatment of bladder pain syndrome/interstitial cystitis. To support our own studies on SHIP1 agonists as potential treatments for IBD and Crohn's disease, a new synthetic route to the SHIP1 agonist AQX-1125 has been developed. This sequence utilizes a hydroxy-acid intermediate which allows for ready differentiation of the C6 and C7 positions. The role of the C17 alkene in the biological activity of the system is also investigated, and this functional group is not required for SHIP1 agonist activity. While AQX-1125 shows SHIP1 agonist activity in enzyme assays, it does not show activity in cell based assays similar to other SHIP1 agonists, which limits the utility of this molecule.


Asunto(s)
Ciclohexanoles , Monoéster Fosfórico Hidrolasas , Indanos
9.
Acta Paediatr ; 111(10): 1950-1955, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35648466

RESUMEN

AIM: Digital media use is prevalent among children and linked to potential developmental and health risks, but validated measures of children's digital media use are lacking. The aim of this study was to validate the Portuguese version of the ScreenQ with three distinct children's age groups. METHODS: Parents of children living in Portugal completed an online survey including the 16-item version of the ScreenQ and items related to home activities and digital media use. A combination of classical and modern theory (Rasch) methods was used for analysis. RESULTS: A total of 549 mothers and 51 fathers of 325 girls and 322 boys from 6 months to 9 years and 11 months old responded to the survey. Point-measure correlations were all positive and endorsement of item values were within acceptable ranges. Cronbach's coefficient α was acceptable for a new measure, and test-retest reliability was high. Statistically significant correlations were found between ScreenQ total scores and relevant demographic, play-related, parenting and digital media use items. CONCLUSION: The Portuguese version of the ScreenQ exhibited sound psychometric properties, including internal consistency and concurrent validity referenced to external items. Higher ScreenQ scores were correlated with higher digital media multitasking, lower parent-child interaction, and higher concerns regarding child's learning and behaviour.


Asunto(s)
Internet , Preescolar , Femenino , Humanos , Lactante , Masculino , Portugal , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
10.
Molecules ; 27(23)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36500543

RESUMEN

Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Monoéster Fosfórico Hidrolasas/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo , Fosforilación , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Línea Celular
11.
J Immunol ; 195(9): 4466-4478, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-26416276

RESUMEN

Dectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through a hemITAM motif and couples sensing of pathogens such as fungi to induction of innate responses. Dectin-1 engagement triggers a plethora of activating events, but little is known about the modulation of such pathways. Trying to define a more precise picture of early Dectin-1 signaling, we explored the interactome of the intracellular tail of the receptor in mouse dendritic cells. We found unexpected binding of SHIP-1 phosphatase to the phosphorylated hemITAM. SHIP-1 colocalized with Dectin-1 during phagocytosis of zymosan in a hemITAM-dependent fashion. Moreover, endogenous SHIP-1 relocated to live or heat-killed Candida albicans-containing phagosomes in a Dectin-1-dependent manner in GM-CSF-derived bone marrow cells (GM-BM). However, SHIP-1 absence in GM-BM did not affect activation of MAPK or production of cytokines and readouts dependent on NF-κB and NFAT. Notably, ROS production was enhanced in SHIP-1-deficient GM-BM treated with heat-killed C. albicans, live C. albicans, or the specific Dectin-1 agonists curdlan or whole glucan particles. This increased oxidative burst was dependent on Dectin-1, Syk, PI3K, phosphoinositide-dependent protein kinase 1, and NADPH oxidase. GM-BM from CD11c∆SHIP-1 mice also showed increased killing activity against live C. albicans that was dependent on Dectin-1, Syk, and NADPH oxidase. These results illustrate the complexity of myeloid C-type lectin receptor signaling, and how an activating hemITAM can also couple to intracellular inositol phosphatases to modulate selected functional responses and tightly regulate processes such as ROS production that could be deleterious to the host.


Asunto(s)
Secuencias de Aminoácidos/inmunología , Candida albicans/inmunología , Células Dendríticas/inmunología , Lectinas Tipo C/inmunología , Monoéster Fosfórico Hidrolasas/inmunología , Especies Reactivas de Oxígeno/inmunología , Secuencias de Aminoácidos/genética , Secuencia de Aminoácidos , Animales , Western Blotting , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/microbiología , Candida albicans/fisiología , Células Dendríticas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Interacciones Huésped-Patógeno/inmunología , Inositol Polifosfato 5-Fosfatasas , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Ratones Noqueados , Microscopía Confocal , Datos de Secuencia Molecular , FN-kappa B/inmunología , FN-kappa B/metabolismo , Factores de Transcripción NFATC/inmunología , Factores de Transcripción NFATC/metabolismo , Fagocitosis/inmunología , Fagosomas/inmunología , Fagosomas/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Unión Proteica/inmunología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/inmunología
12.
Surg Innov ; 24(6): 598-604, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28871872

RESUMEN

BACKGROUND: Usually laparoscopy is performed by means of a 2-dimensional (2D) image system and multiport approach. To overcome the lack of depth perception, new 3-dimensional (3D) systems are arising with the added advantage of providing stereoscopic vision. To further reduce surgery-related trauma, there are new minimally invasive surgical techniques being developed, such as LESS (laparoendoscopic single-site) surgery. The aim of this study was to compare 2D and 3D laparoscopic systems in LESS surgical procedures. MATERIALS AND METHODS: All participants were selected from different levels of experience in laparoscopic surgery-10 novices, 7 intermediates, and 10 experts were included. None of the participants had had previous experience in LESS surgery. Participants were chosen randomly to begin their experience with either the 2D or 3D laparoscopic system. The exercise consisted of performing an ex vivo pork cholecystectomy through a SILS port with the assistance of a fixed distance laparoscope. Errors, time, and participants' preference were recorded. Statistical analysis of time and errors between groups was conducted with a Student's t test (using independent samples) and the Mann-Whitney test. RESULTS: In all 3 groups, the average time with the 2D system was significantly reduced after having used the 3D system ( P < .05). In the postexercise questionnaire, two thirds of participants showed a preference for using the 3D system. CONCLUSION: This study suggests that the 3D system may improve the learning curve and that learning from the 3D system is transferable to the 2D environment. Additionally, the majority of participants prefer 3D equipment.


Asunto(s)
Competencia Clínica , Imagenología Tridimensional , Laparoscopía , Hígado/cirugía , Cirugía Asistida por Computador , Animales , Percepción de Profundidad , Laparoscopios , Curva de Aprendizaje , Hígado/diagnóstico por imagen , Modelos Animales , Porcinos
13.
J Virol ; 88(20): 11748-59, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25078698

RESUMEN

Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses. Importance: Most DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid protein (VP1) of porcine parvovirus. The major protein (VP2) nuclear localization was shown to depend on a complex structural motif. This motif can be used as a strategy by the virus to avoid transport of incorrectly folded proteins and to selectively import assembled trimers into the nucleus. Structural nuclear localization motifs can also be important for nuclear proteins without a classic basic amino acid stretch, including multimeric cellular proteins.


Asunto(s)
Cápside/metabolismo , Señales de Localización Nuclear , Parvovirus Porcino/metabolismo , Secuencia de Aminoácidos , Animales , Cápside/química , Línea Celular , Datos de Secuencia Molecular , Mutagénesis , Transporte de Proteínas , Homología de Secuencia de Aminoácido , Porcinos
14.
Bioorg Med Chem Lett ; 25(22): 5344-8, 2015 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-26453006

RESUMEN

Recently, inhibition of the SH2-containing inositol 5'-phosphatase 1 (SHIP1) has become an attractive strategy for facilitating engraftment of MHC-I mismatched bone marrow grafts, increasing the number of adult stem cells in vivo, and inducing mobilization of hematopoietic stem cells. Utilizing high-throughput screening, two quinoline small molecules (NSC13480 and NSC305787) that inhibit SHIP1 enzymatic activity were discovered. New syntheses of these inhibitors have been developed which verified the relative stereochemistry of these structures. Utilizing this synthetic route, some analogs of these quinolines have been prepared and tested for their ability to inhibit SHIP. These structure activity studies determined that an amine tethered to the quinoline core is required for SHIP inhibition. SHIP inhibition may explain the antitumor effects of similar quinoline amino alcohols and provides an impetus for further synthetic studies in this class of compounds.


Asunto(s)
Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Inositol Polifosfato 5-Fosfatasas/antagonistas & inhibidores , Quinolinas/química , Quinolinas/farmacología , Dominios Homologos src , Adamantano/análogos & derivados , Activación Enzimática/efectos de los fármacos , Estructura Molecular
15.
Mem Inst Oswaldo Cruz ; 110(1): 101-5, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25742269

RESUMEN

The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future.


Asunto(s)
Antivirales/uso terapéutico , Farmacorresistencia Viral/genética , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , Mutación , Oseltamivir/uso terapéutico , Adulto , Brasil , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Gripe Humana/tratamiento farmacológico , Tasa de Mutación , Líquido del Lavado Nasal/virología , Neuraminidasa/genética , Filogenia , Filogeografía , ARN Viral/aislamiento & purificación
16.
J Gen Virol ; 95(Pt 4): 910-921, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24347493

RESUMEN

Porcine parvovirus (PPV) is a small DNA virus with restricted coding capacity. The 5 kb genome expresses three major non-structural proteins (NS1, NS2 and SAT), and two structural proteins (VP1 and VP2). These few viral proteins are pleiotropic and interact with cellular components throughout viral replication. In this regard, very few cell lines have been shown to replicate the virus efficiently. Cell lines were established from a primary culture of bovine cells that allowed allotropic variants of PPV to be distinguished. Three cell lines were differentially sensitive to infection by two prototype PPV strains, NADL-2 and Kresse. In the first cell line (D10), infection was restricted early in the infectious cycle and was not productive. Infection of the second cell line (G11) was 1000 times less efficient with the NADL-2 strain compared with porcine cells, while production of infectious virus of the Kresse strain was barely detectable. Restriction points in these cells were the initial generation of DNA replication intermediates and NS1 production. Infection with chimeras between NADL-2 and Kresse showed that residues outside the previously described allotropic determinant were also partially responsible for the restriction to Kresse replication in G11 cells. F4 cells were permissive to both strains, although genome replication and infectious virus production were lower than in the porcine cells used for comparison. These results highlight the dependent nature of parvovirus tropism on host factors and suggest that cells from a non-host origin can fully support a productive infection by both strains.


Asunto(s)
ADN Viral/metabolismo , Expresión Génica , Parvovirus Porcino/fisiología , Proteínas no Estructurales Virales/biosíntesis , Tropismo Viral , Replicación Viral , Animales , Bovinos , Línea Celular , ADN Viral/genética , Porcinos
17.
Behav Sci (Basel) ; 14(5)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38785887

RESUMEN

Phonological processing skills, such as phonological awareness, are known predictors of reading acquisition in alphabetic languages with varying degrees of orthographic complexity. However, the role of multi-letter-sound knowledge, an important foundation for early reading development, in supporting reading fluency development remains to be determined. This study examined whether two core foundational skills, phonemic awareness and grapheme sounding, have a predictive role in reading fluency development in an intermediate-depth orthography. The participants were 62 children learning to read in European Portuguese, and they were longitudinally assessed on phonemic awareness, complex grapheme sounding, and reading fluency (decoding, word, and text) from Grade 2 to Grade 3. The results showed that grapheme sounding predicted reading fluency development controlled for nonverbal intelligence and vocabulary, short-term verbal memory, and phonemic awareness. Grapheme sounding plays a prominent role in predicting reading fluency outcomes, whereas phonemic awareness (both accuracy and time per correct item) did not contribute to any of the three types of reading fluency. The fact that grapheme-sounding predicted reading fluency is likely due to complex grapheme-phoneme correspondences being required to achieve proficient reading. These findings provide insights into the cognitive processes underlying reading development in intermediate-depth orthographies and have implications for early literacy instruction.

18.
Cureus ; 16(2): e54286, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38500923

RESUMEN

Phytophotodermatitis is a dermatological reaction caused by exposure to certain plants, which becomes activated upon subsequent exposure to sunlight. This can frequently result in a rash. Typically, supportive treatment is recommended. In this report, we describe the case of phytophotodermatitis in a 57-year-old man who experienced a painful rash with streaked lesions following the pruning of a fig tree during the summer. The patient, with no significant medical history, presented to the emergency department in July with a painful, streaked rash on both forearms. The lesions appeared overnight, predominantly on areas of skin exposed while sleeping. The patient denied contact with potential irritants and had not engaged in recent travel or altered his usual habits. Laboratory tests, including complete blood count and markers of inflammation, showed no abnormalities. A thorough patient history revealed recent fig tree pruning, a task usually undertaken in winter. The diagnosis of phytophotodermatitis was made based on the characteristic skin lesions and the patient's history of exposure to fig tree sap. Treatment with antihistamines led to improvement in symptoms, and the patient was discharged with a week-long course of antihistamines and advice to avoid sunlight and contact with fig trees. This case underscores the importance of a detailed medical history, especially in the context of dermatological lesions, to accurately diagnose and treat conditions like phytophotodermatitis.

19.
Healthcare (Basel) ; 12(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38610165

RESUMEN

The transition to college is a period of higher risk of the development of eating disorders, with nutrition/dietetics students representing a group of particular vulnerability. Hence, it is interesting to assess eating disorders, taking into consideration potential sources of bias, including social desirability. Our aims were to compare the risk of eating disorders between students of nutrition/dietetics and those attending other courses and to study potential social desirability biases. A total of 799 higher education students (81.7% females) aged 18 to 27 years old completed a questionnaire assessing the risk of eating disorders (EAT-26) and social desirability (composite version of the Marlowe-Crowne Social Desirability Scale). The proportion of students with a high risk of eating disorders was higher among females (14.5% vs. 8.2%, p = 0.044). Nutrition/dietetics students did not differ from those attending other courses regarding the risk of eating disorders. The social desirability bias when assessing the risk of eating disorders was overall low (EAT-26 total score: r = -0.080, p = 0.024). Social desirability correlated negatively with the Diet (r = -0.129, p < 0.001) and Bulimia and food preoccupation subscales (r = -0.180, p < 0.001) and positively with Oral self-control (r = 0.139, p < 0.001).

20.
Viruses ; 16(4)2024 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-38675962

RESUMEN

BACKGROUND: The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission. OBJECTIVE: We investigated the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) among HIV-1 patients in Portugal. METHODS: Data were obtained from 1050 HIV-1 patient samples submitted for HIV drug resistance (HIVDR) testing from January 2022 to June 2023. Evaluation of DRM affecting viral susceptibility to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was performed using an NGS technology, the Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay. RESULTS: About 71% of patients were ART naïve and 29% were experienced. Overall, 20% presented with any DRM. The prevalence of TDR and ADR was 12.6% and 41.1%, respectively. M184V, T215S, and M41L mutations for NRTI, K103N for NNRTI, and M46I/L for PIs were frequent in naïve and treated patients. E138K and R263K mutations against INSTIs were more frequent in naïve than treated patients. TDR and ADR to INSTIs were 0.3% and 7%, respectively. Patients aged 50 or over (OR: 1.81, p = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, p = 0.050), HIV-1 subtype G (OR: 1.78, p = 0.010), and with CD4 < 200 cells/mm3 (OR: 1.70, p = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, p = 0.003) with a viral load between 4.1 to 5.0 Log10 (OR: 0.55, p = 0.003) or greater than 5.0 Log10 (OR: 0.52, p < 0.001), had lower chances of presenting with DRMs. CONCLUSIONS: We present the first evidence on TDR and ADR to INSTI regimens in followed up patients presenting for healthcare in Portugal. We observed low levels of TDR to INSTIs among ART-naïve and moderate levels in ART-exposed patients. Regimens containing PIs could be an alternative second line in patients with intermediate or high-level drug resistance, especially against second-generation INSTIs (dolutegravir, bictegravir, and cabotegravir).


Asunto(s)
Fármacos Anti-VIH , Farmacorresistencia Viral , Infecciones por VIH , VIH-1 , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Humanos , VIH-1/genética , VIH-1/efectos de los fármacos , Portugal/epidemiología , Infecciones por VIH/virología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Farmacorresistencia Viral/genética , Masculino , Femenino , Persona de Mediana Edad , Adulto , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Genotipo , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto Joven , Anciano
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