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1.
Curr Pharm Teach Learn ; 16(8): 102091, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38641482

RESUMO

INTRODUCTION: The objective of the study was to assess if improvement of the learner experience could be achieved through the use of instructional design strategies in current Good Manufacturing Practices (cGMP) training. This is a novel application in a topic that is known to be boring but is critical to ensuring patient safety. METHODS: An experimental randomized controlled repeated measures cross-over design was utilized in a sample of pharmacy students to determine the effect of an intervention training strategy (which utilized a mix of strategies including weeding, signaling, use of multimedia, and optimized space and type) on the learner experience (Evaluation, Overall Satisfaction, Perceived Knowledge, and Future Recommendation) compared with a control. RESULTS: The sample of 52 pharmacy students that participated evaluated the intervention training strategy with higher scores than the control, with better overall satisfaction, perceived knowledge, and future recommendation scores than the control training strategy. Thus, an apparent effect which resulted from the use of instructional design strategies was seen for all learner experience variables (p < .01). CONCLUSION: Improvement in the learner experience can be achieved by using instructional design strategies in cGMP training. This indicates that similar results could be obtained in other topics where such techniques have not yet been applied.


Assuntos
Educação em Farmácia , Humanos , Educação em Farmácia/métodos , Educação em Farmácia/normas , Estudos Cross-Over , Estudantes de Farmácia/estatística & dados numéricos , Estudantes de Farmácia/psicologia , Masculino , Feminino , Avaliação Educacional/métodos , Avaliação Educacional/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Currículo/tendências , Currículo/normas
2.
Pflugers Arch ; 475(4): 465-475, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36786845

RESUMO

Older adults exhibit a reduced number and function of CD34 + circulating progenitor cells (CPC), a known risk factor for cardiovascular disease. Exercise promotes the mobilisation of CPCs from bone marrow, so whether ageing per se or physical inactivity in older age reduces CPCs is unknown. Thus, this study examined the effect of age on resting and exercise-induced changes in CPCs in aerobically trained adults and the effect of 8 weeks of sprint interval training (SIT) on resting and exercise-induced CPCs in older adults. Twelve young (22-34 years) and nine older (63-70 years) adults participated in the study. Blood was sampled pre and immediately post a graded exercise test to exhaustion in both groups. Older participants repeated the process after 8 weeks of SIT (3 × 20 s 'all-out' sprints, 2 × a week). Total CPCs (CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were determined by flow cytometry. Older adults exhibited lower basal total CD34+ CPCs (828 ± 314 vs. 1186 ± 272 cells·mL-1, p = 0.0149) and CD34+KDR+ EPCs (177 ± 128 vs. 335 ± 92 cells·mL-1, p = 0.007) than younger adults. The maximal exercise test increased CPCs in young (CD34+: p = 0.004; CD34+KDR+: p = 0.017) and older adults (CD34+: p < 0.001; CD34+KDR+: p = 0.008), without difference between groups (p = 0.211). SIT did not alter resting or exercise-induced changes in CPCs in the older cohort (p > 0.232). This study suggests age per se does not impair exercise-induced CPC counts, but does lower resting CPC counts.


Assuntos
Células Progenitoras Endoteliais , Treinamento Intervalado de Alta Intensidade , Humanos , Idoso , Contagem de Células , Células-Tronco , Envelhecimento
3.
Polymers (Basel) ; 14(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35458292

RESUMO

This research presents a partial biodegradable polymeric blend aimed for large-scale fused deposition modeling (FDM). The literature reports partial biodegradable blends with high contents of fossil fuel-based polymers (>20%) that make them unfriendly to the ecosystem. Furthermore, the reported polymer systems neither present good mechanical strength nor have been investigated in vulnerable environments that results in biodegradation. This research, as a continuity of previous work, presents the stability against biodegradability of a partial biodegradable blend prepared with polylactic acid (PLA) and polypropylene (PP). The blend is designed with intended excess physical interlocking and sufficient chemical grafting, which has only been investigated for thermal and hydrolytic degradation before by the same authors. The research presents, for the first time, ANOVA analysis for the statistical evaluation of endurance against biodegradability. The statistical results are complemented with thermochemical and visual analysis. Fourier transform infrared spectroscopy (FTIR) determines the signs of intermolecular interactions that are further confirmed by differential scanning calorimetry (DSC). The thermochemical interactions observed in FTIR and DSC are validated with thermogravimetric analysis (TGA). Scanning electron microscopy (SEM) is also used as a visual technique to affirm the physical interlocking. It is concluded that the blend exhibits high stability against soil biodegradation in terms of high mechanical strength and high mass retention percentage.

4.
Viruses ; 13(9)2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-34578352

RESUMO

Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modify putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 and 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common.


Assuntos
Antígenos Virais/imunologia , Imunoensaio/métodos , Proteínas não Estruturais Virais/imunologia , Zika virus/imunologia , Animais , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Dengue/virologia , Vírus da Dengue/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos , Feminino , Flavivirus , Humanos , Testes Imunológicos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Gravidez , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Vírus do Nilo Ocidental/imunologia , Vírus da Febre Amarela/imunologia , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
5.
J Colloid Interface Sci ; 601: 78-84, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34058554

RESUMO

Iron oxide nanoparticles have been extensively studied for a wide variety of applications. However, there remains a challenge in developing hierarchical magnetic iron oxide nanoparticles as existing synthetic techniques require harsh, toxic chemical conditions and high temperatures or give poorly defined product with weak magnetic properties. In addition, drug loading is limited to post-loading methods such as chemical conjugation or surface adsorption that have poor loading efficiency and are prone to premature drug release. We report a facile biomimetic method for making iron oxide nanoparticle-loaded silica nanocapsules based on a bimodal catalytic peptide surfactant stabilized nanoemulsion template. Iron oxide nanoparticles can be preloaded into the oil phase of the nanoemulsion at tunable concentrations, and the excellent surface activity of the designed bimodal peptide in combination with sufficient electrostatic repulsion promotes the stability of the nanoemulsions. Biosilicification induced by the catalytic peptide module leads to the formation of silica shell nanocapsules containing a magnetic oil core. The bioinspired silica nanocapsules encapsulating iron oxide nanoparticles demonstrate the next-generation of magnetic nanostructures for drug delivery applications.


Assuntos
Nanocápsulas , Sistemas de Liberação de Medicamentos , Compostos Férricos , Dióxido de Silício
6.
Front Neurol ; 11: 439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582003

RESUMO

Background and Purpose: The growth and eventual rupture of intracranial aneurysms may be due to an underlying inflammatory process as evidenced by pathological examination of aneurysm walls. We hypothesize that unruptured aneurysms have an increased inflammatory milieu within their lumen in comparison to the rest of the cerebral arterial vascular system. Methods: Blood was sampled from unruptured aneurysms in patients presenting for aneurysm coil embolization and C3 and C4 complement values from this serum were compared with complement values in the parent artery. Results: Ten patients were enrolled over 32 months with a mean aneurysm size of 9.1 mm. Compared to control samples drawn from peripheral circulation, there were significant decreases of both C3 (p = 0.0003) and C4 (p = 0.0063) levels in aneurysmal blood samples. Conclusions: A state of decreased complement indicative of classic pathway activation was found in all tested aneurysms, thus providing evidence of an ongoing process of complement activation in the blood of live, unruptured aneurysm sacs.

7.
Angew Chem Int Ed Engl ; 58(40): 14357-14364, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364258

RESUMO

A large range of nanoparticles have been developed to encapsulate hydrophobic drugs. However, drug loading is usually less than 10 % or even 1 %. Now, core-shell nanoparticles are fabricated having exceptionally high drug loading up to 65 % (drug weight/the total weight of drug-loaded nanoparticles) and high encapsulation efficiencies (>99 %) based on modular biomolecule templating. Bifunctional amphiphilic peptides are designed to not only stabilize hydrophobic drug nanoparticles but also induce biosilicification at the nanodrug particle surface thus forming drug-core silica-shell nanocomposites. This platform technology is highly versatile for encapsulating various hydrophobic cargos. Furthermore, the high drug loading nanoparticles lead to better in vitro cytotoxic effects and in vivo suppression of tumor growth, highlighting the significance of using high drug-loading nanoparticles.


Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Peptídeos/síntese química , Peptídeos/química , Silício/química , Propriedades de Superfície
8.
Sci Rep ; 8(1): 5939, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29651117

RESUMO

Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient's clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR. The ReLASV rapid diagnostic test (RDT), a lateral flow immunoassay based on paired monoclonal antibodies to the Josiah strain of LASV (lineage IV), performed with 90% sensitivity and 100% specificity. ReLASV immunoassays performed better than the most robust qPCR currently available, which had 82% sensitivity and 95% specificity. The performance characteristics of recombinant antigen-based Lassa virus immunoassays indicate that they can aid in the diagnosis of LASV Infection and inform the clinical management of Lassa fever patients.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/isolamento & purificação , Febre Lassa/diagnóstico , Vírus Lassa/isolamento & purificação , África Ocidental , Anticorpos Antivirais/genética , Antígenos Virais/genética , Humanos , Imunoensaio/métodos , Imunoglobulina M/imunologia , Febre Lassa/imunologia , Febre Lassa/virologia , Vírus Lassa/imunologia , Vírus Lassa/patogenicidade , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Serra Leoa , Estudos de Validação como Assunto
9.
J Infect Dis ; 214(suppl 3): S210-S217, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27587634

RESUMO

BACKGROUND: Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. METHODS: Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance. RESULTS: The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription-polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 105-9.0 × 108 genomes/mL. CONCLUSIONS: The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015.


Assuntos
Antígenos Virais/sangue , Surtos de Doenças , Ebolavirus/imunologia , Doença pelo Vírus Ebola/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Proteínas da Matriz Viral/sangue , África Ocidental/epidemiologia , Animais , Ebolavirus/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Doença pelo Vírus Ebola/virologia , Humanos , Imunoensaio , Limite de Detecção , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
10.
J Infect Dis ; 214(suppl 3): S203-S209, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27521365

RESUMO

BACKGROUND: The 2013-2016 West African Ebola virus disease (EVD) epidemic is the largest recorded. Triage on the basis of clinical signs had limited success, and the time to diagnosis by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) could exceed 5 days. Here we describe the development and field validation of the ReEBOV Antigen Rapid Test (ReEBOV RDT) to aid triage of individuals with suspected EVD. METHODS: Samples from patients with suspected EVD were submitted to Kenema Government Hospital, Sierra Leone, for Lassa fever and EVD screening throughout 2014. Banked residual clinical samples were tested in November 2014 and January 2015 in a blinded field trial to estimate the clinical effectiveness of the ReEBOV RDT, compared with EBOV-specific qRT-PCR. RESULTS: Preliminary ReEBOV RDT performance demonstrated a positive percentage agreement (PPA) of 91.1% (195 of 214 results; 95% confidence interval [CI], 86.5%-94.6%) and a negative percentage agreement (NPA) of 90.2% (175 of 194; 95% CI, 85.1%-94.0%). The final estimates used by the Food and Drug Administration to determine whether to grant emergency use authorization for the test, which excluded a qRT-PCR reference method threshold cutoff, were a PPA of 62.1% (72 of 116 results; 95% CI, 52.6%-70.9%) and a NPA of 96.7% (58 of 60; 95% CI, 88.5%-99.6%), with a diagnostic likelihood of 18.6. A subsequent, independent evaluation by the World Health Organization generated results consistent with the preliminary performance estimates. CONCLUSIONS: The ReEBOV RDT demonstrated the potential to provide clinically effective rapid and accurate point-of-care test results and, thus, to be a powerful tool for increasing triage efficiency.


Assuntos
Antígenos Virais/sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/diagnóstico , Imunoensaio/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Ebolavirus/genética , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/virologia , Hospitais , Humanos , RNA Viral/sangue , Kit de Reagentes para Diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Serra Leoa
11.
Nat Commun ; 7: 11544, 2016 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-27161536

RESUMO

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vírus Lassa/imunologia , Especificidade de Anticorpos , Antígenos Virais/química , Antígenos Virais/genética , Antígenos Virais/imunologia , Arenavirus/imunologia , Reações Cruzadas , Mapeamento de Epitopos , Epitopos/química , Epitopos/genética , Epitopos/imunologia , Humanos , Febre Lassa/imunologia , Febre Lassa/prevenção & controle , Vírus Lassa/genética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Deleção de Sequência , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
12.
J Infect Dis ; 212 Suppl 2: S359-67, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26232440

RESUMO

BACKGROUND: Throughout the 2014-2015 Ebola outbreak in West Africa, major gaps were exposed in the availability of validated rapid diagnostic platforms, protective vaccines, and effective therapeutic agents. These gaps potentiated the development of prototype rapid lateral flow immunodiagnostic (LFI) assays that are true point-of-contact platforms, for the detection of active Ebola infections in small blood samples. METHODS: Recombinant Ebola and Marburg virus matrix VP40 and glycoprotein (GP) antigens were used to derive a panel of monoclonal and polyclonal antibodies. Antibodies were tested using a multivariate approach to identify antibody-antigen combinations suitable for enzyme-linked immunosorbent assay (ELISA) and LFI assay development. RESULTS: Polyclonal antibodies generated in goats were superior reagents for capture and detection of recombinant VP40 in test sample matrices. These antibodies were optimized for use in antigen-capture ELISA and LFI assay platforms. Prototype immunoglobulin M (IgM)/immunoglobulin G (IgG) ELISAs were similarly developed that specifically detect Ebola virus-specific antibodies in the serum of experimentally infected nonhuman primates and in blood samples obtained from patients with Ebola from Sierra Leone. CONCLUSIONS: The prototype recombinant Ebola LFI assays developed in these studies have sensitivities that are useful for clinical diagnosis of acute ebolavirus infections. The antigen-capture and IgM/IgG ELISAs provide additional confirmatory assay platforms for detecting VP40 and other ebolavirus-specific immunoglobulins.


Assuntos
Antígenos Virais/imunologia , Filoviridae/imunologia , Imunoensaio/métodos , África Ocidental , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Ebolavirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Doença do Vírus de Marburg/sangue , Doença do Vírus de Marburg/imunologia , Doença do Vírus de Marburg/virologia , Marburgvirus/imunologia , Serra Leoa
13.
Viral Immunol ; 28(1): 19-31, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25531344

RESUMO

Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction-based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak.


Assuntos
Surtos de Doenças , Febres Hemorrágicas Virais/epidemiologia , Febres Hemorrágicas Virais/etiologia , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , DNA de Protozoário/sangue , Ensaio de Imunoadsorção Enzimática , Febres Hemorrágicas Virais/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Reação em Cadeia da Polimerase , RNA Viral/sangue , Estudos Retrospectivos , Estudos Soroepidemiológicos , Serra Leoa/epidemiologia
14.
PLoS Negl Trop Dis ; 8(3): e2748, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24651047

RESUMO

BACKGROUND: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. CONCLUSIONS/SIGNIFICANCE: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.


Assuntos
Febre Lassa/epidemiologia , Vírus Lassa/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Criança , Pré-Escolar , Feminino , Humanos , Imunoensaio , Incidência , Lactente , Febre Lassa/diagnóstico , Febre Lassa/tratamento farmacológico , Febre Lassa/mortalidade , Masculino , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Ribavirina/uso terapêutico , Estações do Ano , Serra Leoa/epidemiologia , Análise de Sobrevida , Adulto Jovem
15.
Am Surg ; 76(7): 703-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20698374

RESUMO

Single-incision laparoscopic surgical procedures are being developed with the goal of improving cosmesis, reducing postoperative pain, and increasing patient satisfaction. We performed this study to evaluate our initial experience with single-incision laparoscopic cholecystectomy. We used an infraumbilical incision with two upper low-profile 5-mm ports and one lower standard 5-mm port and either a standard 30 degrees Storz laparoscope or an Olympus deflectable tip laparoscope. All patients were followed postoperatively to evaluate the feasibility and outcomes of the procedure. A total of 60 gallbladders were successfully removed by this method (95.2% success rate). Three cases were converted to standard laparoscopic cholecystectomy (4.8% conversion rate) with no conversion to open cholecystectomy. There were no major complications (bile duct injury, liver injury, bowel injury, biliary leak). Median operative time was 51 +/- 21 minutes. Diagnoses included cholelithiasis (55%), biliary dyskinesia (32%), biliary colic (13%), and one case of gangrenous cholecystitis. Median patient age was 47 years with a strong female predominance (87%). Our initial experience demonstrates that single-incision laparoscopic cholecystectomy is effective and safe. We are confident that single-incision laparoscopic cholecystectomy is a viable alternative to standard laparoscopic cholecystectomy.


Assuntos
Colecistectomia Laparoscópica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
16.
Arthritis Res Ther ; 9(5): R86, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17822528

RESUMO

The objectives of the present study were to evaluate the presence of antipolymer antibody (APA) seropositivity in 285 Italian patients affected by primary fibromyalgia (FM) and to verify whether APA levels correlate with disease severity and with cytokine levels.APA levels were determined on serum samples by an indirect ELISA kit that detects IgG APA. Cytokines (IL-1, IL-6, IL-8, IL-10 and TNFalpha) were measured by ELISA in plasma. The impact of FM on the quality of life was estimated using the Fibromyalgia Impact Questionnaire, while pain severity was evaluated using a visual analogic scale. Patients were also characterized by the presence of tiredness, stiffness, nonrestorative sleep, anxiety, depression, tension headache, irritable bowel syndrome, temporomandibular dysfunction and Raynaud's phenomena. Using a cut-off value of 30 U, APA-positive values were detected in 60 FM patients (21.05%) and in 15 healthy control individuals (15.00%) without significant differences among their levels or the percentage of seropositivity. FM patients with moderate and severe symptoms had slightly higher APA levels with respect to patients with mild symptoms. APA-seropositive patients exhibited significant correlations between APA levels and the Fibromyalgia Impact Questionnaire estimate (P = 0.042), tiredness (P = 0.003) and IL-1 levels (P = 0.0072). In conclusion, APA cannot be considered a marker of disease in Italian FM patients. The presence of APA, however, might permit the identification of a subset of FM patients with more severe symptoms and of patients who may respond differently to different therapeutic strategies.


Assuntos
Anticorpos/sangue , Fibromialgia/sangue , Polímeros , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Citocinas/sangue , Feminino , Fibromialgia/diagnóstico , Fibromialgia/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade
18.
Virus Res ; 120(1-2): 146-55, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16616792

RESUMO

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause of an atypical pneumonia that affected Asia, North America and Europe in 2002-2003. The viral spike (S) glycoprotein is responsible for mediating receptor binding and membrane fusion. Recent studies have proposed that the carboxyl terminal portion (S2 subunit) of the S protein is a class I viral fusion protein. The Wimley and White interfacial hydrophobicity scale was used to identify regions within the CoV S2 subunit that may preferentially associate with lipid membranes with the premise that peptides analogous to these regions may function as inhibitors of viral infectivity. Five regions of high interfacial hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine hepatitis virus (MHV) were identified. Peptides analogous to regions of the N-terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV plaque formation by 40-70% at concentrations of 15-30 microM. Interestingly, peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque formation by >80% at similar concentrations. The observed effects were dose-dependent (IC50 values of 2-4 microM) and not a result of peptide-mediated cell cytotoxicity. The antiviral activity of the CoV peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions.


Assuntos
Hemaglutininas Virais/química , Glicoproteínas de Membrana/química , Peptídeos/farmacologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Proteínas do Envelope Viral/química , Sequência de Aminoácidos , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Hemaglutininas/química , Dados de Sequência Molecular , Vírus da Hepatite Murina/química , Peptídeos/síntese química , Peptídeos/genética , Subunidades Proteicas/síntese química , Subunidades Proteicas/genética , Subunidades Proteicas/farmacologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/crescimento & desenvolvimento , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , Glicoproteína da Espícula de Coronavírus , Ensaio de Placa Viral , Virulência/efeitos dos fármacos
19.
Dis Colon Rectum ; 49(2): 197-204, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16328607

RESUMO

INTRODUCTION: Laparoscopic procedures converted to open approaches have been associated with higher complication rates than laparoscopic and open cholecystectomy and appendectomy. Laparoscopic colorectal resections have relatively high conversion rates compared with other laparoscopic procedures. This study was designed to evaluate outcomes of conversions compared with laparoscopic and open colorectal resections. METHODS: We reviewed 498 consecutive colorectal resections performed between 1995 and 2002. Procedures were divided into laparoscopic colorectal resections, open colorectal resections, or conversions. Demographics, underlying disease, type of procedure performed, and operative outcomes were compared between groups. RESULTS: Of the 238 laparoscopic procedures performed, 182 were completed laparoscopically and 56 (23 percent) required conversion; 260 were performed open. Conversions were associated with greater blood loss (200 (range, 50-750) vs. 100 (range, 30-900) ml), longer time to first bowel movement (82 (range, 40-504) vs. 72 (range, 12-420) hr), and longer length of stay (6 (range, 2-67) vs.. 5 (range, 2-62) days) than the laparoscopic colorectal resections group. There was no difference in operative time, transfusion requirements, intraoperative and postoperative complications, or mortality between conversions and laparoscopic colorectal resections. Conversions resulted in fewer patients requiring transfusions (4 vs. 14 percent), shorter time to first bowel movement (82 (range, 40-504) vs. 93 (range, 24-240) hr), and shorter length of stay (6 (range, 2-67) vs. 7 (range, 2-180) days) than in the open colorectal resections group. There were no differences in complications or mortality between the conversion group and the open colorectal resections group. CONCLUSIONS: Laparoscopic colorectal resections has a relatively high conversion rate; however, the converted cases have outcomes similar to open colorectal resections. In fact, the converted group required fewer blood transfusions than the open group. Experience and good judgment are fundamental for timely conversion of a laparoscopic procedure to open to decrease complication rates. Despite a high conversion rate, surgeons should consider laparoscopic colorectal resections, because even when necessary, conversion does not result in poorer outcomes than laparoscopic colorectal resections or open colorectal resections.


Assuntos
Colectomia , Doenças do Colo/cirurgia , Laparoscopia , Complicações Pós-Operatórias , Doenças Retais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Microsc Res Tech ; 68(3-4): 209-21, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16276510

RESUMO

Sequences highly similar (>95%) to the mouse mammary tumor virus (MMTV) env gene have been amplified from human DNA samples, including DNA samples from patients with breast cancer (BC) and persons who did not have BC. The sequences from human DNA were distinct from the MMTV sequences used as controls in these PCR reactions, indicating that these results are not simply due to contamination. In addition to both, mouse and human-related sequences were also amplified from some monkey and cat genomic DNA samples. These products were shown to be distinct from, but highly related to, the MMTV env gene, whereas, testing of other sources (lambda phage, snake, cockroach, sea urchin, chicken, or dog) demonstrated no specific amplification. A sequence 90% similar to the MMTV group antigen gene (gag) was amplified from cat DNA. These results indicate that DNA from vertebrate species other than rodents, including some but not all humans, monkeys, and cats, can contain sequences closely related to MMTV.


Assuntos
Neoplasias da Mama/virologia , DNA Viral/análise , Genes env , Vírus do Tumor Mamário do Camundongo/genética , Animais , Sequência de Bases , Gatos , DNA de Neoplasias/análise , Feminino , Humanos , Macaca mulatta , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
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