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1.
Indian J Otolaryngol Head Neck Surg ; 76(4): 3018-3030, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39130301

RESUMO

Nasal surgeries (e.g.: rhinoplasties, septoplasties) and sinus surgeries (e.g.: Functional Endoscopic Sinus Surgeries) are common procedures in Otorhinolaryngology. Tranexamic acid (TXA), an antifibrinolytic drug, has been increasingly utilized to reduce hemorrhage recently. While close in proximity anatomically, the bleeding nature of sinus and nasal surgeries may differ. We present the first meta-analysis that has reviewed both nasal and sinus surgery collectively and compares the two. Pubmed, Embase, Cochrane Library and WoS were searched until April 2023. Outcomes of interest include Boezart Scoring, clotting time, postoperative complications and surgical field quality. 27 Studies were assessed, of which 25 studies were evaluated quantitatively. Of the 27 studies, 15 studies involved Sinus surgery while 12 involved Nasal surgery. The use of tranexamic acid was notably beneficial in the evaluation of blood loss, reduction of operating time, surgical field quality and surgeon satisfaction. TXA has proven to be efficacious in both nasal and sinus surgeries to varying degrees. TXA has more effects in sinus surgeries compared to nasal surgeries in objective markers such as reducing blood loss and operating time, but the converse occurs for subjective markers such as surgeon satisfaction scores. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04579-x.

2.
J Cancer Surviv ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627293

RESUMO

OBJECTIVE: Patient-reported outcome measures (PROM) are frequently adopted to evaluate colorectal cancer (CRC) care, but the use of patient-reported experience measures (PREM) appears to be underdeveloped and not widely validated. This scoping review aims to understand the contexts for deployment of PREMs in CRC care, reliability of measures, gaps in current use of PREMs, and how PREMs are associated with PROMs when deployed together. METHODS: Four scientific databases (PubMed, CINAHL, PsycINFO, Scopus) were systematically searched from January 2011 to December 2023. Observational or interventional studies involving quantitative or mixed methodology with samples consisting CRC patients undergoing screening, treatment, or cancer surveillance and utilizing at least one PREM as an exposure or outcome were included. RESULTS: The initial search resulted in 10,400 records. Only 13 relevant studies (consisting of 17,105 participants) met the eligibility criteria. Utilization of PREMs was heterogenous across our sample and the CRC care continuum, and about half of the studies (53.8%) evaluated the relationship between PREMs and PROMs. PREM usage across the CRC care continuum largely focused on treatment/survivorship. Better care experience was positively associated with improved patient-reported outcomes. CONCLUSIONS: Future work in CRC PREM development should focus on (1) establishing validated measures that aim to either capture disease/treatment-specific granularity or capitalize on applicability across care settings, (2) localizing novel or existing PREMs to consider different cultural contexts in healthcare, and (3) benchmarking associations between PREMs, PROMs, and other outcomes of interest. IMPLICATIONS FOR CANCER SURVIVORS: Individuals progressing through the CRC care continuum often undergo a multitude of procedures from detection and diagnosis to treatment and surveillance. The establishment of validated PREMs specific to CRC would help to benchmark and further improve the quality of care received-which should translate to better patient-reported outcomes-and serve as process indicators for institutions and providers to maintain rigorous health service delivery standard for CRC survivors.

4.
J Clin Med ; 12(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38068537

RESUMO

BACKGROUND: Dry eye disease (DED) is a common chronic condition with increasing prevalence. Standard discriminative visual acuity is not reflective of real-world visual function, as patients can achieve normal acuities by blinking. METHODS: Participants recruited from a tertiary referral eye centre were divided into two groups-Severe DED (with significant, central staining) and Mild DED (absence of such staining). Functional Visual Acuity (FVA) in both groups was assessed using the DryeyeKT mobile application and Impact of Vision Impairment (IVI) questionnaire to assess quality of life (QOL). RESULTS: Among the 78 participants (74.4% women), 30 (38.5%) had Severe DED and 48 (61.5%) Mild DED. In women, Severe DED produced a significantly worse FVA of 0.53 ± 0.20 vs. 0.73 ± 0.30 in the Mild DED group (p = 0.006). FVA decreased with increasing age, showing a significant inverse correlation (r = -0.55). A poorer FVA ≤ 0.6 was seen in older patients (68.2 years ± 7.68) vs. an FVA > 0.6 in younger patients (58.9 years ± 10.7), p < 0.001. When adjusting for age, FVA was still 0.107 lower in the Severe DED group, p = 0.003. There was significant difficulty in performing specific daily activities in the Severe DED group, after adjusting for age, gender and FVA. CONCLUSIONS: FVA is reduced in severe DED and older people. Severe DED significantly impacts certain aspects of QOL. However, no significant relationship was found between FVA and QOL. FVA is not the only reason for the compromise of health-related QOL in severe dry eye.

5.
Cogn Psychol ; 143: 101563, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37141672

RESUMO

Most theories of free recall emphasize the importance of retrieval in explaining temporal and semantic regularities in recall; rehearsal mechanisms are often absent or limit rehearsal to a subset of what was last rehearsed. However, in three experiments using the overt rehearsal method, we show clear evidence that just-presented items act as retrieval cues during encoding (study-phase retrieval) with prior related items rehearsed despite well over a dozen intervening items. Experiment 1 examined free recall of categorized and uncategorized lists of 32 words. In Experiments 2 and 3, we presented categorized lists of 24, 48, and 64 words for free recall or cued recall, with the category exemplars blocked in successive list positions (Experiment 2) or randomized throughout the list (Experiment 3). The probability of rehearsing a prior word was affected by its semantic similarity to the just-presented item, and the frequency and recency of its prior rehearsals. These rehearsal data suggest alternative interpretations to well-known recall phenomena. With randomized designs, the serial position curves were reinterpreted by when words were last rehearsed (which contributed to the list length effects), and semantic clustering and temporal contiguity effects at output were reinterpreted by whether words were co-rehearsed during study. The contrast with the blocked designs suggests that recall is sensitive to the relative (not absolute) recency of targeted list items. We discuss the benefits of incorporating rehearsal machinery into computational models of episodic memory, and suggest that the same retrieval processes that generate the recalls are used to generate the rehearsals.


Assuntos
Memória Episódica , Rememoração Mental , Humanos , Aprendizagem , Semântica , Sinais (Psicologia)
6.
BMJ Case Rep ; 16(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631168

RESUMO

Malignant lymphoma is a rare cause of gastrointestinal intussusception in adults, accounting for less than 1% of all cases of intussusception. This is a case of a South-East Asian woman in her 50s, presenting with intermittent abdominal pain, loose stools and weight loss. CT of the abdomen and pelvis showed an irregular mass causing ileocolic intussusception and she underwent emergency open right hemicolectomy with end ileostomy. Intraoperatively, her bowel was covered with lymphoma nodules, and bulky mesenteric nodules of small bowel and colon were seen. The histology shows mantle cell lymphoma, a rare subtype of B cell non-Hodgkin's lymphoma. She recovered well postoperatively and was started on chemotherapy (Nordic protocol) early.


Assuntos
Neoplasias do Colo , Doenças do Íleo , Intussuscepção , Linfoma de Célula do Manto , Feminino , Humanos , Adulto , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/patologia , Intussuscepção/diagnóstico , Intussuscepção/etiologia , Intussuscepção/cirurgia , Colo Ascendente/patologia , Doenças do Íleo/etiologia , Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia
7.
Hernia ; 27(5): 1299-1306, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36427167

RESUMO

PURPOSE: Value driven outcome (VDO) initiative is a value-based, patient-focused tool which utilizes a clinical outcome-based approach to optimize value of care based on clinically relevant quality indicators and costs required to achieve the care. In this study, we evaluate the impact of a VDO initiative on groin hernia repair, a commonly performed elective surgery in our hospital. METHODS: A VDO initiative was implemented in 2019 to encourage elective inguinal hernia repair to be performed at a day surgery setting. A comparison of outcomes was made between hernia surgeries performed in 2019 with those in 2020 and 2021. Pre-defined criteria were used to select patients that can be operated at a day surgery setting. Patients' expectations were addressed preoperatively about day surgery procedure and postoperative recovery. Day surgery bundles were used to standardize pre- and post-surgery protocols. Pain control was optimized using a specialized local anesthesia regime. RESULTS: A total of 263 laparoscopic hernia surgeries were performed between May 2019 and December 2021. After implementation of VDO initiative, the percentage of patients discharged within 24 h increased from 78% in year 2019 to 97% in year 2020 and 99% in year 2021. Conversion rate for day surgery to short stay decreased from 9% in year 2019 to 1% in year 2020 and 2% in year 2021. In 2019 to 2021, there were no 30-day readmission, no hernia recurrence in 90 days, no conversion to open surgery. CONCLUSION: VDO initiative is a promising tool to deliver better value-based care for patients undergoing endo-laparoscopic inguinal hernia repair.


Assuntos
Hérnia Inguinal , Laparoscopia , Humanos , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Virilha/cirurgia , Laparoscopia/métodos , Manejo da Dor
8.
Asian J Surg ; 46(2): 712-717, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35842388

RESUMO

PURPOSE: The ideal surgical treatment of small ventral hernias (defect less than 4 cm) is still debatable. In our study, we sought to compare the outcomes of open versus laparoscopic intraperitoneal on-lay mesh (IPOM) repair in small ventral hernias. METHODS: Patients with a single ventral hernia defect of less than 4 cm undergoing surgical mesh repair between January 2016 and September 2018 were prospectively registered for this study. The minimum follow-up duration was 12 months. Patient demographics, operative findings and regular post-operative follow-up details including recurrence rates and complications were recorded and analysed. RESULTS: 41 patients underwent laparoscopic IPOM repair and 47 patients underwent open IPOM repair. The mean age for both groups is similar with no significant difference. The mean hernia defect size for the laparoscopic group is 2.8 cm (±0.8) whereas the mean hernia defect size for the open repair group is 2.1 cm (±0.4). The mean surgery duration for open IPOM repair was significantly shorter (59 min (±17) vs 74 min (±26); p = 0.001). There was no significant difference in the incidence of seroma formation and surgical site infections post-operatively. There was also no significant difference in both groups in terms of chronic pain and recurrence at 1-year follow-up. CONCLUSION: Open IPOM repair for small ventral hernias may be superior to laparoscopic IPOM repair due to the shorter operative duration, single incision, and no additional risk of port-site hernias. There was no difference in chronic pain, wound infection and recurrence rate between the two groups.


Assuntos
Dor Crônica , Hérnia Ventral , Laparoscopia , Humanos , Telas Cirúrgicas , Dor Crônica/cirurgia , Hérnia Ventral/cirurgia , Infecção da Ferida Cirúrgica , Herniorrafia , Recidiva
9.
Front Digit Health ; 3: 639827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34713111

RESUMO

The COVID-19 pandemic has created a huge burden on the healthcare industry worldwide. Pressures to increase the isolation healthcare facility to cope with the growing number of patients led to an exploration of the use of wearables for vital signs monitoring among stable COVID-19 patients. Vital signs wearables were chosen for use in our facility with the purpose of reducing patient contact and preserving personal protective equipment. The process of deciding on the wearable solution as well as the implementation of the solution brought much insight to the team. This paper presents an overview of factors to consider in implementing a vital signs wearable solution. This includes considerations before deciding on whether or not to use a wearable device, followed by key criteria of the solution to assess. With the use of wearables rising in popularity, this serves as a guide for others who may want to implement it in their institutions.

10.
Mem Cognit ; 47(4): 658-682, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30617748

RESUMO

According to the Atkinson and Shiffrin (1968) model, control processes in the short-term memory store determine the selection of different storage, search, and retrieval strategies. Although rehearsal is the most studied short-term control process, it is necessary to specify the different retrieval strategies available for participants to use in searching for and outputting from short-term or immediate memory, as well as the degree to which participants can flexibly select different retrieval strategies for recalling rehearsed and unrehearsed materials. In three experiments we examined retrieval strategies in tests of immediate free recall (Exp. 1), immediate serial recall (ISR; Exp. 2), and a variant of ISR that we call ISR-free (Exp. 3). In each experiment, participants were presented with very short lists of four, five, or six words and were instructed to recall one, two, three, or all of the items from each list. Neither the list length nor the number of to-be-recalled items was known in advance. The serial position of the first item recalled in all three tasks depended on the number of to-be-recalled items. When only one or two items were to be recalled, participants tended to initiate recall with the final or penultimate list item, respectively; when participants were required to recall as many list items as possible, they tended to initiate recall with the first list item. These findings show that different retrieval strategies exist for rapidly searching for different numbers of items from immediate memory, and they confirm that participants have some control over their output order, as measured by the first items recalled.


Assuntos
Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Aprendizagem Seriada/fisiologia , Adulto , Humanos , Adulto Jovem
11.
Cell Rep ; 25(12): 3252-3261.e4, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30566854

RESUMO

Heat shock factors (Hsfs) are transcription factors that regulate responses to heat shock and other environmental stimuli. Four heat shock factors (Hsf1-4) have been characterized from vertebrates to date. In addition to stress response, they also play important roles in development and gametogenesis. Here, we study the fifth member of heat shock factor family, Hsf5, using zebrafish as a model organism. Mutant hsf5-/- males, generated by CRISPR/Cas9 technique, were infertile with drastically reduced sperm count, increased sperm head size, and abnormal tail architecture, whereas females remained fertile. We show that Hsf5 is required for progression through meiotic prophase 1 during spermatogenesis as suggested by the accumulation of cells in the leptotene and zygotene-pachytene stages and increased apoptosis in post-meiotic cells. hsf5-/- mutants show gonadal misregulation of a substantial number of genes with roles in cell cycle, apoptosis, protein modifications, and signal transduction, indicating an important role of Hsf5 in early stages of spermatogenesis.


Assuntos
Fatores de Transcrição de Choque Térmico/metabolismo , Espermatogênese , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologia , Animais , Apoptose , Feminino , Fertilidade , Fatores de Transcrição de Choque Térmico/genética , Masculino , Meiose , Mutação/genética , Caracteres Sexuais , Espermatócitos/citologia , Espermatócitos/metabolismo , Espermatócitos/ultraestrutura , Espermatozoides/citologia , Espermatozoides/ultraestrutura , Testículo/citologia , Testículo/ultraestrutura , Transcriptoma/genética , Proteínas de Peixe-Zebra/genética
12.
J Exp Psychol Learn Mem Cogn ; 43(12): 1909-1933, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28557502

RESUMO

In 2 experiments, participants were presented with lists of between 2 and 12 words for either immediate free recall (IFR) or immediate serial recall (ISR). Auditory recall advantages at the end of the list (modality effects) and visual recall advantages early in the list (inverse modality effects) were observed in both tasks and the extent and magnitude of these effects were dependent upon list length. Both tasks displayed modality effects with short lists that were large in magnitude but limited to the final serial position, consistent with those observed in the typically short lists used in ISR, and both tasks displayed modality effects with longer lists that were small in magnitude and more extended across multiple end-of-list positions, consistent with those observed in the typically longer lists used in IFR. Inverse modality effects were also observed in both tasks at early list positions on longer lengths. Presentation modality did not affect where recall was initiated, but modality effects were greatest on trials where participants initiated recall with the first item. We argue for a unified account of IFR and ISR. We also assume that the presentation modality affects the encoding of all list items, and that modality effects emerge due to the greater resistance of auditory items to output interference. (PsycINFO Database Record


Assuntos
Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Aprendizagem Seriada/fisiologia , Estimulação Acústica , Adolescente , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa , Fatores de Tempo , Vocabulário , Adulto Jovem
13.
PLoS One ; 12(3): e0172675, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28273167

RESUMO

Staphyloccus aureus is a major human pathogen leading frequently to sepsis and soft tissue infections with abscesses. Multiple virulence factors including several immune modulating molecules contribute to its survival in the host. When S. aureus invades the human body, one of the first line defenses is the complement system, which opsonizes the bacteria with C3b and attract neutrophils by release of chemotactic peptides. Neutrophils express Complement receptor-1 [CR1, CD35) that interacts with the C3b-opsonized particles and thereby plays an important role in pathogen recognition by phagocytic cells. In this study we observed that a fraction of S. aureus culture supernatant prevented binding of C3b to neutrophils. This fraction consisted of S. aureus leukocidins and Efb. The C-terminus of Efb is known to bind C3b and shares significant sequence homology to the extracellular complement binding protein [Ecb). Here we show that S. aureus Ecb displays various mechanisms to block bacterial recognition by neutrophils. The presence of Ecb blocked direct interaction between soluble CR1 and C3b and reduced the cofactor activity of CR1 in proteolytic inactivation of C3b. Furthermore, Ecb could dose-dependently prevent recognition of C3b by cell-bound CR1 that lead to impaired phagocytosis of NHS-opsonized S. aureus. Phagocytosis was furthermore reduced in the presence of soluble CR1 [sCR1). These data indicate that the staphylococcal protein Ecb prevents recognition of C3b opsonized bacteria by neutrophil CR1 leading to impaired killing by phagocytosis and thereby contribute to immune evasion of S. aureus.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas Opsonizantes/imunologia , Receptores de Complemento 3b/metabolismo , Staphylococcus aureus/imunologia , Staphylococcus aureus/metabolismo , Fatores de Virulência/metabolismo , Complemento C3b/imunologia , Complemento C3b/metabolismo , Eritrócitos/imunologia , Eritrócitos/metabolismo , Humanos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose/imunologia , Ligação Proteica
14.
J Exp Psychol Learn Mem Cogn ; 42(8): 1282-92, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26844583

RESUMO

When participants are asked to recall a short list of words in any order that they like, they tend to initiate recall with the first list item and proceed in forward order, even when this is not a task requirement. The current research examined whether this tendency might be influenced by varying the number of items that are to be recalled. In 3 experiments, participants were presented with short lists of between 4 and 6 words and instructed to recall 1, 2, 3, or all of the items from the lists. Data were collected using immediate free recall (IFR, Experiment 1), immediate serial recall (ISR, Experiment 2), and a variant of ISR that we call ISR-free (Experiment 3), in which participants had to recall words in their correct serial positions but were free to output the words in any order. For all 3 tasks, the tendency to begin recall with the first list item occurred only when participants were required to recall as many items from the list as they could. When participants were asked to recall only 1 or 2 items, they tended to initiate recall with end-of-list items. It is argued that these findings show for the first time a manipulation that eliminates the initial tendency to recall in forward order, provide some support for recency-based accounts of IFR and help explain differences between single-response and multiple-response immediate memory tasks. (PsycINFO Database Record


Assuntos
Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Aprendizagem Seriada/fisiologia , Vocabulário , Análise de Variância , Sinais (Psicologia) , Feminino , Humanos , Masculino , Probabilidade , Estudantes , Universidades
15.
J Virol ; 87(14): 8213-26, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23698290

RESUMO

Genomic variation and related evolutionary dynamics of human respiratory syncytial virus (RSV), a common causative agent of severe lower respiratory tract infections, may affect its transmission behavior. RSV evolutionary patterns are likely to be influenced by a precarious interplay between selection favoring variants with higher replicative fitness and variants that evade host immune responses. Studying RSV genetic variation can reveal both the genes and the individual codons within these genes that are most crucial for RSV survival. In this study, we conducted genetic diversity and evolutionary rate analyses on 36 RSV subgroup B (RSV-B) whole-genome sequences. The attachment protein, G, was the most variable protein; accordingly, the G gene had a higher substitution rate than other RSV-B genes. Overall, less genetic variability was found among the available RSV-B genome sequences than among RSV-A genome sequences in a comparable sample. The mean substitution rates of the two subgroups were, however, similar (for subgroup A, 6.47 × 10(-4) substitutions/site/year [95% credible interval {CI 95%}, 5.56 × 10(-4) to 7.38 × 10(-4)]; for subgroup B, 7.76 × 10(-4) substitutions/site/year [CI 95%, 6.89 × 10(-4) to 8.58 × 10(-4)]), with the time to their most recent common ancestors (TMRCAs) being much lower for RSV-B (19 years) than for RSV-A (46.8 years). The more recent RSV-B TMRCA is apparently the result of a genetic bottleneck that, over longer time scales, is still compatible with neutral population dynamics. Whereas the immunogenic G protein seems to require high substitution rates to ensure immune evasion, strong purifying selection in conserved proteins such as the fusion protein and nucleocapsid protein is likely essential to preserve RSV viability.


Assuntos
Evolução Molecular , Variação Genética/genética , Genômica/métodos , Filogenia , Vírus Sincicial Respiratório Humano/genética , Sequência de Aminoácidos , Sequência de Bases , Teorema de Bayes , Evasão da Resposta Imune/genética , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , Dinâmica Populacional , Seleção Genética , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie , Replicação Viral/genética
16.
J Exp Psychol Learn Mem Cogn ; 39(2): 317-47, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22774850

RESUMO

Participants tend to initiate immediate free recall (IFR) of short lists of words with the very first word on the list. Three experiments examined whether rehearsal is necessary for this recent finding. In Experiment 1, participants were presented with lists of between 2 and 12 words for IFR at a fast, medium, or slow rate, with and without articulatory suppression (AS). The tendency to initiate output with the first item for short lists (a) did not change greatly when presentation rate was increased from a medium to a fast rate under normal conditions, (b) was reduced but not eliminated by AS, and (c) was maintained at slower rates when rehearsal was allowed but decreased at slower rates when rehearsal was prevented. In Experiment 2, the overt rehearsal methodology was used, and the tendency to initiate output with the first item for short lists was present even in the absence of overt rehearsal. Experiment 3 re-examined IFR under normal encoding conditions and replicated the main findings from the normal encoding conditions of Experiment 1 while using the presentation rates and list lengths of Experiment 2. We argue that rehearsal is not strictly necessary for the tendency to initiate recall with the first item under normal conditions, but rehearsal nevertheless contributes to this effect at slower rates.


Assuntos
Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Prática Psicológica , Aprendizagem Seriada/fisiologia , Análise de Variância , Feminino , Seguimentos , Humanos , Inibição Psicológica , Masculino , Probabilidade , Psicolinguística , Fatores de Tempo , Vocabulário
17.
PLoS One ; 7(12): e51439, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23236501

RESUMO

Human respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host's immune response in a way that stimulates pathogenesis. Yet, the interplay between RSV-evoked immune responses and epidemic behavior, and how this affects the genomic evolutionary dynamics of the virus, remains poorly understood. Here, we present a comprehensive collection of 33 novel RSV subgroup A genomes from strains sampled over the last decade, and provide the first measurement of RSV-A genomic diversity through time in a phylodynamic framework. In addition, we map amino acid substitutions per protein to determine mutational hotspots in specific domains. Using Bayesian genealogical inference, we estimated the genomic evolutionary rate to be 6.47 × 10(-4) (credible interval: 5.56 × 10(-4), 7.38 × 10(-4)) substitutions/site/year, considerably slower than previous estimates based on G gene sequences only. The G gene is however marked by elevated substitution rates compared to other RSV genes, which can be attributed to relaxed selective constraints. In line with this, site-specific selection analyses identify the G gene as the major target of diversifying selection. Importantly, statistical analysis demonstrates that the immune driven positive selection does not leave a measurable imprint on the genome phylogeny, implying that RSV lineage replacement mainly follows nonselective epidemiological processes. The roughly 50 years of RSV-A genomic evolution are characterized by a constant population size through time and general co-circulation of lineages over many epidemic seasons - a conclusion that might be taken into account when developing future therapeutic and preventive strategies.


Assuntos
Evolução Molecular , Variação Genética/genética , Genoma Viral/genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/genética , Seleção Genética , Substituição de Aminoácidos/genética , Sequência de Bases , Teorema de Bayes , Bélgica/epidemiologia , Pré-Escolar , Primers do DNA/genética , Genômica/métodos , Humanos , Lactente , Recém-Nascido , Modelos Genéticos , Dados de Sequência Molecular , Taxa de Mutação , Países Baixos/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Vírus Respiratório Sincicial/virologia , Análise de Sequência de DNA , Proteínas do Envelope Viral/genética
18.
Exp Hematol ; 39(3): 384-90, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21168468

RESUMO

OBJECTIVE: We previously reported that inhibition or loss of CD26 (DPPIV/dipeptidylpeptidase IV) results in a defect in normal mobilization of hematopoietic stem and progenitor cells induced by granulocyte-colony stimulating factor (G-CSF). This suggests that CD26 is a necessary component of the mobilization pathway. Our goal in this study was to determine whether mobilization can be induced by the CXCR4 antagonist AMD3100 in mice lacking CD26 (CD26(-/-)). MATERIALS AND METHODS: Ten week old CD26(-/-) and C57BL/6 mice received a subcutaneous injection of AMD3100. One hour post-injection the mice were euthanized and peripheral blood and bone marrow were collected and evaluated. RESULTS: AMD3100 mobilizes hematopoietic progenitors into the peripheral blood of CD26(-/-) and mice. CONCLUSIONS: Our finding that AMD3100 rapidly mobilizes hematopoietic progenitor cells from the bone marrow into the periphery in CD26-deficient transgenic mice that otherwise exhibit a mobilization defect in response to G-CSF suggests that: (1) CD26 is downstream of G-CSF but upstream of the CXCL12-CXCR4 axis and (2) AMD3100 can be used as a single agent to mobilize hematopoietic stem and progenitor cells in normal donors or patients that have an intrinsic defect in their response to G-CSF treatment. Stem cell transplants are often the only curative treatment in some cancer patients. The ability to perform the transplantation and its success is dependent on the ability to mobilize adequate numbers of hematopoietic progenitor cells. The use of AMD3100 as a single agent would give patients or donors an additional option for a successful stem cell transplant.


Assuntos
Fármacos Anti-HIV/farmacologia , Quimiocina CXCL12/metabolismo , Dipeptidil Peptidase 4 , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Compostos Heterocíclicos/farmacologia , Receptores CXCR4/metabolismo , Animais , Benzilaminas , Quimiocina CXCL12/genética , Ciclamos , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Camundongos , Camundongos Knockout , Receptores CXCR4/genética
19.
J Exp Psychol Learn Mem Cogn ; 36(5): 1207-41, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20804293

RESUMO

In 4 experiments, participants were presented with lists of between 1 and 15 words for tests of immediate memory. For all tasks, participants tended to initiate recall with the first word on the list for short lists. As the list length was increased, so there was a decreased tendency to start with the first list item; and, when free to do so, participants showed an increased tendency to start with one of the last 4 list items. In all tasks, the start position strongly influenced the shape of the resultant serial position curves: When recall started at Serial Position 1, elevated recall of early list items was observed; when recall started toward the end of the list, there were extended recency effects. These results occurred under immediate free recall (IFR) and different variants of immediate serial recall (ISR) and reconstruction of order (RoO) tasks. We argue that these findings have implications for the relationship between IFR and ISR and between rehearsal and recall.


Assuntos
Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Aprendizagem Seriada/fisiologia , Adulto , Análise de Variância , Sinais (Psicologia) , Humanos , Fatores de Tempo , Vocabulário
20.
Ann Acad Med Singap ; 38(9): 817-20, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19816642

RESUMO

The dual energy CT (DECT) technology has been recently employed in the form of two X-ray sources of different energies to enhance the contrast between adjacent structures. Its use in the cardiac arena has been widely highlighted due to the higher temporal resolution. However, it may also be used in the craniocervical and peripheral vasculature for better differentiation between contrast-enhanced vascular lumina and calcified plaques, in the characterisation of ureteric stones, and in the evaluation of hepatic lesions. The objective of this paper is to revisit DECT physics, review the literature and discuss its use in CT neuroangiography with case illustrations from our institution, and impact on dose savings.


Assuntos
Angiografia Cerebral , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Constrição Patológica/diagnóstico , Humanos , Interpretação de Imagem Assistida por Computador , Aneurisma Intracraniano/diagnóstico , Doses de Radiação , Literatura de Revisão como Assunto
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