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1.
Ophthalmic Plast Reconstr Surg ; 37(3S): S1-S5, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32932407

RESUMO

PURPOSE: Helicobacter pylori could theoretically induce ocular adnexal lymphoma (OAL) via 2 mechanisms: the first is that of infection within the ocular adnexa and the second is that of infection within the gastric mucosa, leading to the malignant transformation of lymphocytes that migrate to the ocular adnexa, forming a primary "ectopic" cancer. This study investigated if an association exists between gastric H. pylori or ocular adnexal H. pylori and OAL. METHODS: Prospective case-control study including cases with OAL and controls with nonlymphomatous pathologies. Gastric H. pylori infection was assessed via serologic antibody testing. Ocular adnexal infection was assessed via polymerase chain reaction testing for H. pylori and Chlamydia psittaci within ocular adnexal samples. RESULTS: Seventy-two patients were enrolled, of whom 18 had lymphoma and 54 nonlymphomatous pathologies. H. pylori antibodies were present in 5 cases (28%) and 18 controls (33%) (95% CI, 0.24%-2.50%, p = 0.78). All ocular adnexal specimens were negative for H. pylori and C. psittaci infection. The only relevant statistically significant difference between cases and controls was a history of gastric ulcer (95% CI, 1.23%-44.80%, p = 0.03). CONCLUSIONS: In the study's population, infection of gastric mucosa with H. pylori does not appear to influence the development of OAL. Also, H. pylori or C. psittaci infection within the ocular adnexa does not appear to influence the development of OAL. In the study's practice, authors do not recommend antibiotic administration or routine gastroscopy for patients with OAL. The authors do recommend referral of OAL patients with gastric symptoms to a gastroenterologist.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B , Linfoma , Estudos de Casos e Controles , DNA Bacteriano , Mucosa Gástrica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Humanos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Estudos Prospectivos
2.
BMC Public Health ; 19(1): 1683, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842822

RESUMO

BACKGROUND: Migrants represent an increasing proportion of people living with HIV in many developed countries. We aimed to describe the HIV care cascade and baseline genotypic resistance for newly diagnosed asylum seekers referred to the McGill University Health Centre (MUHC) in Montreal, Quebec, Canada. METHODS: We conducted a retrospective cohort study of patients linked to the MUHC from June 1, 2017 to October 31, 2018. We calculated the median time (days; interquartile range (IQR)) from: 1) entry into Canada to immigration medical examination (IME) (i.e. HIV screening); 2) IME to patient notification of diagnosis; 3) notification to linkage to HIV care (defined as a CD4 or viral load (VL) measure); 4) linkage to HIV care to combination antiretroviral therapy (cART) prescription; and 5) cART prescription to viral suppression (defined as a VL < 20 copies/mL). We reviewed baseline genotypes and interpreted mutations using the Stanford University HIV Drug Resistance Database. We calculated the proportion with full resistance to > 1 antiretroviral. RESULTS: Overall, 43% (60/139) of asylum seekers were newly diagnosed in Canada. Among these, 62% were late presenters (CD4 < 350 cells/µl), 22% presented with advanced HIV (CD4 < 200 cells/µl), and 25% with high-level viremia (VL > 100,000 copies/ml). Median time from entry to IME: 27 days [IQR:13;55]; IME to notification: 28 days [IQR:21;49]; notification to linkage: 6 days [IQR:2;19]; linkage to cART prescription: 11 days [IQR:6;17]; and cART to viral suppression: 42 days [IQR:31;88]; 45% were linked to HIV care within 30 days. One-fifth (21%) had baseline resistance to at least one antiretroviral agent; the K103 N/S mutation was the most common mutation. CONCLUSIONS: While the majority of newly diagnosed asylum seekers were late presenters, only 45% were linked to care within 30 days. Once linked, care and viral suppression were rapid. Delays in screening and linkage to care present increased risk for onward transmission, and in the context of 21% baseline resistance, consideration of point-of-care testing and immediate referral at IME screening should be made.


Assuntos
Infecções por HIV/terapia , Refugiados/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Fármacos Anti-HIV/uso terapêutico , Resistência a Medicamentos/genética , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Quebeque , Estudos Retrospectivos
3.
Ecol Lett ; 20(7): 883-891, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28635125

RESUMO

Ageing results from the accumulation of multifactorial damage over time. However, the temporal distribution of this damage remains unknown. In seasonal species, transitions between seasons are critical periods of massive physiological remodelling. We hypothesised that these recurrent peaks of physiological remodelling are costly in terms of survival. We tested whether captive small primates exposed to an experimentally increased frequency of seasonal transitions die sooner than individuals living under natural seasonality. The results show that experiencing one additional season per year increases the mortality hazard by a factor of 3 to 4, whereas the expected number of seasons lived is only slightly impacted by the seasonal rhythm. These results demonstrate that physiological transitions between periods of high and low metabolic activity represent a major mortality risk for seasonal organisms, which has been ignored until now.


Assuntos
Fotoperíodo , Primatas , Envelhecimento , Animais , Mortalidade , Risco , Estações do Ano
4.
J Antimicrob Chemother ; 72(8): 2171-2183, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28472323

RESUMO

Objectives: Viral phylogenetics revealed two patterns of HIV-1 spread among MSM in Quebec. While most HIV-1 strains ( n = 2011) were associated with singleton/small clusters (cluster size 1-4), 30 viral lineages formed large networks (cluster size 20-140), contributing to 42% of diagnoses between 2011 and 2015. Herein, tissue culture selections ascertained if large cluster lineages possessed higher replicative fitness than singleton/small cluster isolates, allowing for viral escape from integrase inhibitors. Methods: Primary HIV-1 isolates from large 20+ cluster ( n = 11) or singleton/small cluster ( n = 6) networks were passaged in vitro in escalating concentrations of dolutegravir, elvitegravir and lamivudine for 24-36 weeks. Sanger and deep sequencing assessed genotypic changes under selective drug pressure. Results: Large cluster HIV-1 isolates selected for resistance to dolutegravir, elvitegravir and lamivudine faster than HIV-1 strains forming small clusters. With dolutegravir, large cluster HIV-1 variants acquired solitary R263K ( n = 7), S153Y ( n = 1) or H51Y ( n = 1) mutations as the dominant quasi-species within 8-12 weeks as compared with small cluster lineages where R263K ( n = 1/6), S153Y (1/6) or WT species (4/6) were observed after 24 weeks. Interestingly, dolutegravir-associated mutations compromised viral replicative fitness, precluding escalations in concentrations beyond 5-10 nM. With elvitegravir, large cluster variants more rapidly acquired first mutations (T66I, A92G, N155H or S147G) by week 8 followed by sequential accumulation of multiple mutations leading to viral escape (>10 µM) by week 24. Conclusions: Further studies are needed to understand virological features of large cluster viruses that may favour their transmissibility, replicative competence and potential to escape selective antiretroviral drug pressure.


Assuntos
Farmacorresistência Viral , Genótipo , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , Mutação , Seleção Genética , Análise por Conglomerados , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Filogenia , Quebeque , Inoculações Seriadas , Cultura de Vírus
5.
Opt Express ; 25(24): 30799-30806, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29221106

RESUMO

We demonstrate the fabrication of a Vernier effect SU8/PMATRIFE polymer optical biosensor with high homogeneous sensitivity using a standard photolithography process. The sensor is based on one micro-resonator embedded on each arm of a Mach-Zehnder interferometer. Measurements are based on the refractive index variation of the optical waveguide superstrate with different concentrations of glucose solutions. The sensitivity of the sensor has been measured as 17558 nm/RIU and the limit of detection has been estimated to 1.1.10-6 RIU.

6.
Ophthalmic Plast Reconstr Surg ; 33(1): 57-60, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26866330

RESUMO

PURPOSE: To compare the functional outcome of the polypropylene trapezoid frontalis suspension with the polypropylene modified Crawford frontalis suspension in a large cohort of patients with oculopharyngeal muscular dystrophy. METHODS: Retrospective, nonrandomized comparative case series. Patients with oculopharyngeal muscular dystrophy who underwent bilateral polypropylene frontalis suspension were selected for chart review. Main outcome measures were margin reflex distance, duration of surgery, and ptosis recurrence. RESULTS: Ninety-two patients qualified for chart review; 39 patients underwent the trapezoid sling and 53 patients the modified Crawford sling. There was no difference in preoperative margin reflex distance or levator function between the 2 surgical groups. Postoperative improvement in margin reflex distance was 2.95 ± 1.56 mm in the trapezoid group compared with 2.85 ± 1.65 mm in the modified Crawford group (p = 0.67). Duration of surgery was 40.49 ± 13.33 minutes in the trapezoid group compared with 53.77 ± 16.04 minutes in the modified Crawford group (p < 0.001). Five percent of eyes in the trapezoid group had ptosis recurrence compared with 13% of eyes in the modified Crawford group (p = 0.07). CONCLUSION: Both polypropylene frontalis suspension techniques generated an equivalent increase in margin reflex distance. However, the trapezoid frontalis suspension required less operative time and trended toward a lower rate of ptosis recurrence.


Assuntos
Blefaroplastia/métodos , Blefaroptose/cirurgia , Pálpebras/cirurgia , Distrofia Muscular Oculofaríngea/cirurgia , Músculos Oculomotores/cirurgia , Polipropilenos , Técnicas de Sutura , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Oculofaríngea/fisiopatologia , Duração da Cirurgia , Recidiva , Estudos Retrospectivos
7.
Paediatr Child Health ; 22(3): 130-133, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29479198

RESUMO

INTRODUCTION: Cheerleading has gradually become more popular in Canada and represents an accessible way for youth to be physically active. OBJECTIVE: To determine the differences in the injuries encountered by cheerleaders according to their age, in order to propose safety guidelines that take into account the developmental stages of children. METHOD: Retrospective database review of cheerleading injuries extracted from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) database between 1990 and 2010. The injuries were compared by age group (5 to 11 versus 12 to 19) according to their sex, mechanism of injury and injury severity. RESULTS: Overall, in 20 years, there were 1496 cases of injuries documented secondary to cheerleading (median age 15, 4 (interquartile range [IQR]=2, 2) years); mostly females (1410 [94%]). Of that number, 101 cases were 5 to 11 years old (age group [AG]1), while 1385 were 12 to 19 (AG2). Participants in AG1 were found to have a higher proportion of moderate-to-severe injury (46.5% compared with 28.2% in AG2). The odds ratio of moderate/severe injury for AG1 compared with AG2 was found to be 2.217 (95% CI [1.472; 3.339]). No fatalities were known to have occurred. CONCLUSION: Children's developmental stages affect their ability to participate in sports and the responses of their bodies to impact forces. Our findings concerning cheerleading injuries indicate that younger children (5 to 11 years old) are more likely to suffer moderate-to-severe injuries. Thus, on a local basis, the use of appropriate safety measures including appropriate flooring/safety mats and spotters to catch falling athletes should be mandatory.

8.
Opt Express ; 24(20): 23109-23117, 2016 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-27828376

RESUMO

A selenide integrated platform working in the mid-infrared was designed, fabricated and optically characterized at 7.7 µm. Ge-Sb-Se multilayered structures were deposited by RF magnetron sputtering. Using i-line photolithography and fluorine-based reactive ion etching, ridge waveguides were processed as Y-junction, spiral and S-shape waveguides. Single-mode optical propagation at 7.7 µm was observed by optical near-field imaging and optical propagation losses of 2.5dB/cm are measured. Limits of detection of 14.2 ppm and 1.6 ppm for methane and nitrous oxide, respectively, could be potentially measured by using this platform as an evanescent field sensor. Hence, these technological, experimental and theoretical results represent a first step towards the development of an integrated optical sensor operating in the mid-infrared wavelength range.

9.
J Antimicrob Chemother ; 70(2): 405-11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25281399

RESUMO

OBJECTIVES: Dolutegravir has been recently approved for treatment-naive and -experienced HIV-infected subjects, including integrase inhibitor (INI)-experienced patients. Dolutegravir is a second-generation INI that can overcome many prior raltegravir and elvitegravir failures. Here, we report the evolution of resistance to dolutegravir in a highly treatment-experienced patient harbouring the major N155H mutation consequent to raltegravir treatment failure. METHODS: Genotypic and phenotypic analyses were done on longitudinal samples to determine viral resistance to INIs. Integrase amino acid sequence interactions with raltegravir and dolutegravir were assessed by molecular modelling and docking simulations. RESULTS: Five mutations (A49P, L68FL, T97A, E138K and L234V) were implicated in emergent dolutegravir resistance, with a concomitant severe compromise in viral replicative capacity. Molecular modelling and docking simulations revealed that dolutegravir binding to integrase was affected by these acquired dolutegravir mutations. CONCLUSIONS: Our findings identify a novel mutational pathway involving integrase mutations A49P and L234V, leading to dolutegravir resistance in a patient with the N155H raltegravir mutation.


Assuntos
Evolução Biológica , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Mutação , Substituição de Aminoácidos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Sítios de Ligação , Contagem de Linfócito CD4 , Domínio Catalítico , Genótipo , Infecções por HIV/diagnóstico , Integrase de HIV/química , Integrase de HIV/genética , Inibidores de Integrase de HIV/farmacologia , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Oxazinas , Fenótipo , Piperazinas , Ligação Proteica , Piridonas , Carga Viral
10.
Proc Biol Sci ; 281(1791): 20140830, 2014 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25100693

RESUMO

Classic theories of ageing consider extrinsic mortality (EM) a major factor in shaping longevity and ageing, yet most studies of functional ageing focus on species with low EM. This bias may cause overestimation of the influence of senescent declines in performance over condition-dependent mortality on demographic processes across taxa. To simultaneously investigate the roles of functional senescence (FS) and intrinsic, extrinsic and condition-dependent mortality in a species with a high predation risk in nature, we compared age trajectories of body mass (BM) in wild and captive grey mouse lemurs (Microcebus murinus) using longitudinal data (853 individuals followed through adulthood). We found evidence of non-random mortality in both settings. In captivity, the oldest animals showed senescence in their ability to regain lost BM, whereas no evidence of FS was found in the wild. Overall, captive animals lived longer, but a reversed sex bias in lifespan was observed between wild and captive populations. We suggest that even moderately condition-dependent EM may lead to negligible FS in the wild. While high EM may act to reduce the average lifespan, this evolutionary process may be counteracted by the increased fitness of the long-lived, high-quality individuals.


Assuntos
Envelhecimento , Peso Corporal , Cheirogaleidae/fisiologia , Animais , Feminino , Longevidade , Masculino
11.
Med Sci Educ ; 34(1): 21-23, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38510382

RESUMO

The Canadian Ophthalmology Student Interest Group (COSIG) is the first national medical student-led specialty interest group in Canada. COSIG has run several initiatives aimed at increasing students' opportunities for ophthalmology exposure and learning, including a resident-medical student mentorship program, an annual 6-week introductory course, amongst other events, and webinars.

12.
Can J Infect Dis Med Microbiol ; 24(4): 202-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24489562

RESUMO

HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.


Les tests de détermination du tropisme du VIH-1 jouent un rôle capital dans la détermination de la réponse aux antagonistes des récepteurs du CCR5. Au début, on utilisait des tests phénotypiques, mais leur accès limité a suscité l'élaboration d'autres stratégies. Récemment, le génotypage du tropisme a été validé à l'aide d'une technologie canadienne, dans le cadre d'essais cliniques faisant appel au maraviroc tant chez des patients déjà en traitement que chez des patients naïfs au traitement. Les présentes lignes directrices passent en revue les données probantes en appui à l'utilisation de tests génotypiques et contiennent des recommandations au sujet des tests de détermination du tropisme dans la prise en charge clinique quotidienne.

13.
Can J Ophthalmol ; 58(4): 302-312, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35397233

RESUMO

OBJECTIVE: To evaluate perceptions of blade- versus laser-based blepharoplasty before and after being provided educational information. METHODS: This interventional pre-post study included 145 randomly selected participants (Maisonneuve-Rosemont Hospital, Montreal, Canada, August 2020) who were asked about their perceptions surrounding blepharoplasty. Participants then received information about the techniques before answering final questions. RESULTS: Participants perceived no difference in outcomes for blade (37%) versus laser (40%) blepharoplasty precounselling. This increased to laser blepharoplasty postintervention (56%, p < 0.001) despite being told that there was no difference in outcomes. The higher the level of education among participants, the more likely they were to correctly believe that both techniques had similar outcomes (p = 0.049). Most participants would choose laser blepharoplasty initially (64%), and this percentage increased postintervention (81%, p < 0.001). The preintervention perception of blade blepharoplasty recovery time (20.1 ± 32.6 days) was longer than that for laser blepharoplasty (13.5 ± 32.0 days, p = 0.01) and increased for both techniques postintervention (p < 0.001). Perceived pain was lower for laser blepharoplasty. Postintervention, participants responded that additional costs of ($975 ± $1,091) would justify laser over blade blepharoplasty. CONCLUSION: Elucidating patient perceptions and preferences for blade- versus laser-based blepharoplasty provides surgeons with perspective on how to tailor preoperative counselling. Before and after the intervention, participants had a bias toward choosing laser blepharoplasty. The intervention seems to falsely convince people that laser blepharoplasty leads to better outcomes. Because the doctor's advice can greatly impact patients' decisions, physicians have to be careful not to give false expectations when counselling patients. Inaccurate recall of key educational takeaways suggests that information should be vulgarized and delivered actively to patients.


Assuntos
Blefaroplastia , Cirurgiões , Humanos , Blefaroplastia/métodos , Opinião Pública , Pálpebras/cirurgia , Lasers
14.
Artigo em Inglês | MEDLINE | ID: mdl-36960087

RESUMO

Objectives: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings. Design and setting: This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures. Results: Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases. Conclusion: SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available. Trial registration: clinicaltrials.gov identifier: NCT05411562.

15.
Can Urol Assoc J ; 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37787594

RESUMO

INTRODUCTION: Competency in interpreting genitourinary (GU) imaging is an important skill for urologists; however, no nationally accredited GU imaging curriculum exists for Canadian urology residency training programs. The main objectives of our study were to 1) characterize GU imaging training in Canada; (2) evaluate residents' self-perceived competencies in interpreting GU imaging; (3) explore program directors' (PD) and residents' perceptions regarding the current imaging curriculum and suggestions for future directions. METHODS: From November to December 2022, a survey examining current imaging education in residency, perceived resident imaging knowledge, avenues for improvement in imaging education, and the role of point-of-care ultrasound within urology was distributed to all Canadian urology PDs and residents. RESULTS: All PDs (13/13) and 40% (72/178) of residents completed the survey. Only two programs had a formal GU imaging curriculum. PDs and residents reported trainees were least comfortable interpreting Doppler ultrasound of renal, gonadal, and penile vessels. PDs reported that residents were most comfortable with non-contrast computed tomography (CT) scans (9.5/10), CT urogram (9.3/10), and retrograde pyelography (9.3/10). All but one PD favored increasing imaging training in their program. PDs highlighted the lack of time in the curriculum (n=3) and lack of educators (n=3) as the primary barriers to increasing imaging training in their program. CONCLUSIONS: Most PDs and residents believe there needs to be more imaging training offered at their institution; however, addressing this is challenging due to the limited time in the curriculum and the need for available educators.

16.
J Clin Endocrinol Metab ; 108(12): 3122-3134, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37390454

RESUMO

CONTEXT: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED). OBJECTIVE: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED. DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials. SETTING: Multicenter. PARTICIPANTS: Patients with moderate-to-severe, active TED. INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks. MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial). RESULTS: The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation. CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.


Assuntos
Exoftalmia , Oftalmopatia de Graves , Recém-Nascido , Humanos , Oftalmopatia de Graves/tratamento farmacológico , Qualidade de Vida , Anticorpos Monoclonais/uso terapêutico , Imunoglobulina G/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento
17.
J Infect Dis ; 204(7): 1115-9, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21881127

RESUMO

Phylodynamic analysis and epidemiologic data identified 3 patterns of spread of primary human immunodeficiency virus type 1 infection (PHI) among men who have sex with men (2001-2009): 420 unique PHIs, 102 small clusters (2-4 PHIs per cluster, n = 280), and 46 large clusters (5-31 PHIs per cluster, n = 450). Large clusters disproportionately increased from 25.2% of PHIs in 2005 to 39.1% in 2009 (χ(2) = 33.9, P < .001). Scalar expansion of large clusters over 11 months (interquartile range, 3.5-25.5 months) correlated with cluster membership size (r(2) = 0.174, F = 4.424, P = .047). PHI cohort data revealed variations in social networks and risk behaviors among the 3 groups, suggesting the need for tailored prevention measures.


Assuntos
Infecções por HIV/transmissão , HIV-1/genética , Homossexualidade Masculina , Teorema de Bayes , Análise por Conglomerados , Genes pol , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Humanos , Masculino , Filogeografia , Quebeque/epidemiologia , Assunção de Riscos , Análise de Sequência de DNA , Comportamento Sexual , Apoio Social , Fatores de Tempo
18.
J Med Virol ; 83(5): 751-9, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21360548

RESUMO

We used genotypic and phylogenetic analysis to determine integrase diversity among subtypes, and studied natural polymorphisms and mutations implicated in resistance to integrase inhibitors (INI) in treatment-naïve persons (n = 220) and -experienced individuals (n = 24). Phylogenetics revealed 7 and 10% inter-subtype diversity in the integrase and reverse transcriptase (RT)/protease regions, respectively. Integrase sequencing identified a novel A/B recombinant in which all viruses in a male-sex-male (MSM) transmission cluster (n = 12) appeared to possess subtype B in integrase and subtype A in the remainder of the pol region. Natural variations and signature polymorphisms were observed at codon positions 140, 148, 151, 157, and 160 among HIV subtypes. These variations predicted higher genetic barriers to G140S and G140C in subtypes C, CRF02_AG, and A/CRF01_AE, as well as higher genetic barriers toward acquisition of V151I in subtypes CRF02_AG and A/CRF01_AE. The E157Q and E160Q mutational motif was observed in 35% of INI-naïve patients harboring subtype C infections, indicating intra-subtype variations. Thirteen patients failed raltegravir (RAL)-containing regimens within 8 ± 1 months, in association with the major Q148K/R/H and G140A/S (n = 8/24) or N155H (n = 5/24) mutational pathways. Of note, the remaining patients on RAL regimens for 14 ± 3 months harbored no or only minor integrase mutations/polymorphisms (T66I, T97A, H114P, S119P, A124S, G163R, I203M, R263K). These results demonstrate the importance of understanding subtype variability in the development of resistance to INIs.


Assuntos
Farmacorresistência Viral , Variação Genética , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Substituição de Aminoácidos/genética , Análise por Conglomerados , Evolução Molecular , Integrase de HIV/genética , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Recombinação Genética , Análise de Sequência de DNA
19.
Diagn Microbiol Infect Dis ; 101(4): 115521, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34537474

RESUMO

SARS-CoV-2 whole genome sequencing is a molecular biology tool performed to support many aspects of the response to the pandemic. Freezing of primary clinical nasopharyngeal swabs and shipment to reference laboratories is usually required for sequencing. Cobas PCR Media transport medium facilitates high throughput SARS-CoV-2 RT-PCR analyses on cobas platforms. The manufacturer doesn't recommend freezing this transport medium because of risks of degrading molecular templates and impairing test results. Our objective was to compare the quality and results of SARS-CoV-2 genomic sequencing when performed on fresh or frozen samples in cobas PCR Media. Viral genome sequencing was performed using Oxford Nanopore Technologies MinION platform. Sequencing performance, quality and results did not significantly differ between fresh and frozen samples (n = 10). Freezing of cobas PCR Media does not negatively affect SARS-CoV-2 RNA sequencing results and it is therefore a suitable transport medium for outsourcing sequencing analyses to reference laboratories.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Congelamento , Reação em Cadeia da Polimerase/métodos , SARS-CoV-2/isolamento & purificação , Sequenciamento Completo do Genoma/métodos , COVID-19/virologia , Criopreservação , Genoma Viral , Humanos , Técnicas de Diagnóstico Molecular/métodos , Nasofaringe/virologia , RNA Viral/genética , SARS-CoV-2/genética
20.
Front Public Health ; 9: 670304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414154

RESUMO

Background: Preconception lifestyle interventions appear promising to reduce pregnancy complications, prevent adult cardiometabolic diseases, and prevent childhood obesity. These interventions have almost exclusively been studied in populations of obese infertile women. The development of preconception lifestyle interventions targeting a broader population of overweight and obese women without a history infertility and their partners is needed. Methods: This study is a multicenter open label parallel group randomized controlled trial. Sixty-eight non-infertile women with overweight or obesity in the preconception period and their partners will be recruited from the Sherbrooke and Quebec City regions. The couples will be randomized in a 1:1 ratio to receive the Healthy for my Baby intervention or standard care in the preconception period and pregnancy. Women and their partners will be invited to take part in this lifestyle intervention which includes motivational interviews and daily self-monitoring of lifestyle goals through a mobile phone application. The primary endpoint of this study is the diet quality of women during the preconception period, which will be evaluated using the C-HEI 2007 score at baseline, 2, 4- and 6-months following study enrolment. Women's dietary quality will also be evaluated through the measure of urinary biomarkers of habitual dietary intake at baseline and 2 months in preconception, and 24-26 weeks in pregnancy. Additional indicators of women's lifestyle as well as anthropometric measures will be documented in preconception and pregnancy. For the pregnancy period, the main secondary endpoint is the pattern of gestational weight gain. Pregnancy and neonatal complications will also be evaluated. For partners, diet quality, other lifestyle habits, and anthropometric measures will be documented in the preconception and pregnancy periods. Discussion: This study will evaluate the effectiveness of a low-cost intervention designed to improve diet and other lifestyle characteristics of women in the preconception period who are overweight or obese. If the Healthy for my Baby intervention is efficacious regarding dietary measures, larger trials will be needed to evaluate the impact of this intervention on the rates of pregnancy complications, childhood obesity, and adult cardiometabolic disease. Clinical Trial Registration:clinicaltrials.gov (NCT04242069).


Assuntos
Ganho de Peso na Gestação , Sobrepeso , Adulto , Feminino , Humanos , Estilo de Vida , Masculino , Estudos Multicêntricos como Assunto , Sobrepeso/prevenção & controle , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
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