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1.
Trials ; 25(1): 242, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582874

RESUMO

BACKGROUND: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP. METHODS/DESIGN: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05. DISCUSSION: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.


Assuntos
Dor Lombar , Estimulação Elétrica Nervosa Transcutânea , Humanos , Estimulação Elétrica Nervosa Transcutânea/efeitos adversos , Estimulação Elétrica Nervosa Transcutânea/métodos , Dor Lombar/diagnóstico , Dor Lombar/terapia , Estudos Cross-Over , Limiar da Dor , Medição da Dor , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
mBio ; 15(4): e0006924, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38470268

RESUMO

Streptococcus pneumoniae (Spn), a Gram-positive bacterium, is responsible for causing a wide variety of invasive infections. The emergence of multi-drug antibiotic resistance has prompted the search for antimicrobial alternatives. Phage-derived peptidoglycan hydrolases, known as endolysins, are an attractive alternative. In this study, an endolysin active against Spn, designated SP-CHAP, was cloned, produced, purified, biochemically characterized, and evaluated for its antimicrobial properties. Cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains are widely represented in bacteriophage endolysins but have never previously been reported for pneumococcal endolysins. Here, we characterize the first pneumococcal endolysin with a CHAP catalytic domain. SP-CHAP was antimicrobial against all Spn serovars tested, including capsular and capsule-free pneumococci, and it was found to be more active than the most widely studied pneumococcal endolysin, Cpl-1, while not affecting various oral or nasal commensal organisms tested. SP-CHAP was also effective in eradicating Spn biofilms at concentrations as low as 1.56 µg/mL. In addition, a Spn mouse nasopharyngeal colonization model was employed, which showed that SP-CHAP caused a significant reduction in Spn colony-forming units, even more than Cpl-1. These results indicate that SP-CHAP may represent a promising alternative to combating Spn infections. IMPORTANCE: Considering the high rates of pneumococcal resistance reported for several antibiotics, alternatives are urgently needed. In the present study, we report a Streptococcus pneumoniae-targeting endolysin with even greater activity than Cpl-1, the most characterized pneumococcal endolysin to date. We have employed a combination of biochemical and microbiological assays to assess the stability and lytic potential of SP-CHAP and demonstrate its efficacy on pneumococcal biofilms in vitro and in an in vivo mouse model of colonization. Our findings highlight the therapeutic potential of SP-CHAP as an antibiotic alternative to treat Streptococcus pneumoniae infections.


Assuntos
Bacteriófagos , Infecções Pneumocócicas , Animais , Camundongos , Peptídeo Hidrolases , Streptococcus pneumoniae , Cisteína , Histidina , Amidoidrolases , Endopeptidases/genética , Endopeptidases/farmacologia , Endopeptidases/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/microbiologia , Bacteriófagos/genética , Biofilmes
3.
PLoS One ; 19(1): e0297234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38236928

RESUMO

The primary objective of this review was to create a 'trustworthy,' living systematic review and meta-analysis for the application of manual therapy interventions in treating patients with shoulder dysfunction. Included studies were English-language randomized controlled trials published between 1/1/2010 and 8/3/2023, with searches performed in: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, ProQuest Nursing & Allied Health, EBSCO Medline, and PEDro. The population of focus included adults 18 years and older with musculoskeletal impairments related to shoulder dysfunction. Our primary outcomes included pain and region-specific outcome measures. We excluded trials, including participants having shoulder dysfunction resulting from surgery, radicular pain, instability/dislocation, fracture, lymphedema, and radiation. Our screening methodology was based upon a previously published 'trustworthy' systematic review protocol. This included the application of our PICOTS criteria in addition to screening for prospective clinical trial registration and following of prospective intent, as well as assessment of PEDro scores, risk-of-bias ratings, GRADE scoring, and examination of confidence in estimated effects. Twenty-six randomized controlled trials met our PICOTS criteria; however, only 15 of these were registered. Only three were registered prospectively. Two of these did not have discussions and conclusions that aligned with their primary outcome. The remaining single study was found to have a high risk-of-bias, meaning the remainder of the protocol could not be employed and that no randomized controlled trials could undergo further assessment or meta-analysis. The results of this systematic review indicate there are no 'trustworthy' randomized controlled trials examining the effectiveness of manual therapy interventions for the treatment of patients with shoulder dysfunction, as defined by the prospectively established methodology. Therefore, these findings signal that creating a 'trustworthy,' living systematic review on this clinically relevant topic is not yet possible due to a lack of 'trustworthy' randomized controlled trials.


Assuntos
Manipulações Musculoesqueléticas , Ombro , Humanos , Dor , Estudos Prospectivos , Revisões Sistemáticas como Assunto
4.
J Man Manip Ther ; 32(1): 51-66, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37622723

RESUMO

OBJECTIVES: To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments. DESIGN: SR with meta-analysis. LITERATURE SEARCH: Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro. METHODS: This SR included English-language randomized clinical trials (RCTs) involving manual therapy to treat spinal impairments in adults. The primary outcome was pressure pain thresholds (PPTs). To synthesize RCTs with high confidence in estimated effects using the GRADE, RCTs with questionable prospective, external, and internal validity, and high risk of bias (RoB) were excluded. RESULTS: Following title and abstract screening, 89 full-text RCTs were reviewed. Twenty-two studies included the criteria of interest. Sixteen were not prospectively registered, two contained discussion/conclusions judged to be inconsistent with the registry, and one was rated as having a high RoB. Three studies met the inclusion criteria; heterogeneous interventions and locations for PPT testing prevented synthesis into practice recommendations. The two studies with high confidence in estimated effects had small effect sizes, and one study had confidence intervals that crossed zero for the outcome measures of interest. DISCUSSION: Standardized PPT testing, as a potential measure of centrally mediated pain, could provide clues regarding the mechanisms of manual therapy or help identify/refine research questions. CONCLUSION: High-quality RCTs could not be synthesized into strong conclusions secondary to the dissimilarity in research designs. Future research regarding quantitative sensory testing should develop RCTs with high confidence in estimated effects that can be translated into strong recommendations.


Assuntos
Dor nas Costas , Manipulações Musculoesqueléticas , Cervicalgia , Adulto , Humanos , Viés , Avaliação de Resultados em Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Dor nas Costas/terapia , Cervicalgia/terapia
5.
Microbiol Spectr ; 11(6): e0253823, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37855623

RESUMO

IMPORTANCE: Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can "win" by taking over the host, or the bacteria can "lose" if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that "activate" innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.


Assuntos
Rickettsia , Animais , Rickettsia/fisiologia , Anafilatoxinas , Macrófagos , Proteínas do Sistema Complemento , Proliferação de Células , Mamíferos
7.
J Man Manip Ther ; 31(4): 231-245, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37067434

RESUMO

OBJECTIVES: To establish a 'trustworthy' living systematic review (SR) with a meta-analysis of manual therapy for treating non-radicular cervical impairments. DESIGN: SR with meta-analysis. LITERATURE SEARCH: Articles published between January 2010 and September 2022 were included from: Cochrane Central Register of Controlled Trials (CENTRAL); CINAHL; MEDLINE; PubMed; PEDro, and ProQuest Nursing and Allied Health. METHODS: This SR included English-language randomized clinical trials (RCTs) of manual therapy involving adults used to treat non-radicular cervical impairments. The primary outcomes were pain and region-specific outcome measures. Cervicogenic headaches and whiplash were excluded to improve homogeneity. Two reviewers independently assessed RCTs. The prospective plan was to synthesize results with high confidence in estimated effects using GRADE. RESULTS: Thirty-five RCTs were screened for registration status. Twenty-eight were not registered or registered prospectively. In 5 studies, the discussion and conclusion did not match the registry, or this could not be determined. One study did not meet the external validity criterion, and another was rated as having a high risk of bias. One study met the inclusion and exclusion criteria, so practice recommendations could not be made. The remaining study did not identify any clinically meaningful group differences. DISCUSSION: Only one prospectively registered RCT met this SR's strict, high-quality standards. The single identified paper provides initial high-quality evidence on this topic. CONCLUSION: This SR establishes a foundation of trustworthiness and can be used to generate research agendas to determine the potential clinical utility of manual therapy directed at the cervical spine for non-radicular cervical complaints.


Assuntos
Vértebras Cervicais , Manipulações Musculoesqueléticas , Humanos , Pescoço , Dor
8.
Arch Physiother ; 13(1): 8, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024951

RESUMO

Trustworthy, preprocessed sources of evidence, such as systematic reviews and clinical practice guidelines, are crucial for practicing clinicians. Confidence in estimated effects is related to how different the outcome data were between the two groups. Factors including the effect size, variability of the effect, research integrity, research methods, and selected outcome measures impact confidence in the estimated effect. The current evidence suggests that post-randomization biases cannot be ruled out with a high degree of certainty in published research, limiting the utility of preprocessed sources for clinicians. Research should be prospectively registered to improve this situation, and fidelity with prospective intent should be verified to minimize biases and strengthen confidence in estimated effects. Otherwise, discussions related to preprocessed literature, including P-values, point estimates of effect, confidence intervals, post-randomization biases, external and internal validity measures, and the confidence in estimated effects required to translate research into practice confidently, are all moot points.

9.
J Man Manip Ther ; 31(3): 184-197, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35942578

RESUMO

INTRODUCTION: It is unknown if verified prospective registration of systematic reviews (SRs) and the randomized clinical trials (RCTs) that they use affect an SR's methodological quality on A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). METHODS: Data originated from interventional SRs published in International Society of Physiotherapy Journals Editors (ISPJE) member journals, indexed in MEDLINE, between 1 January 2018 and 18 August 2021. Blinded reviewers identified the SRs and extracted the data for the variables of interest for the SRs and the RCTs. RESULTS: Two of 14 ISPJE member journals required prospective SR registration. Twenty SRs were identified, and 169 unique, retrievable RCTs were included within those SRs. One (5.0%) of the 20 SRs and 15 of the 169 (8.9%) RCTs were prospectively registered and published consistent with this intent. Nineteen (95.0%) of the 20 identified SRs was categorized as 'critically low' on the AMSTAR 2. DISCUSSION: SRs and the RCTs identified within them were infrequently prospectively registered, prospectively verifiable, or prospectively verified based on the established research record. CONCLUSIONS: Ensuring that SRs and RCTs have fidelity with the research record from conception to publication may help rule out low-value interventions, decrease variability in physical therapy practice, and solidify evidence-based physical therapy practice.


Assuntos
Medicina Baseada em Evidências , Revisões Sistemáticas como Assunto
10.
J Man Manip Ther ; 31(2): 72-83, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35607259

RESUMO

OBJECTIVES: Examine: (1) whether variability in dry needling (DN) dosage affects pain outcomes, (2) if effect sizes are clinically important, and (3) how adverse events (AE) were documented and whether DN safety was determined. METHODS: Nine databases were searched for randomized controlled trials (RCTs) investigating DN in symptomatic musculoskeletal disorders. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Included RCTs met PEDro criteria #1 and scored > 7/10. Data extraction included DN dosage, pain outcome measures, dichotomous AE reporting (yes/no), and AE categorization. Clinically meaningful differences were determined using the minimum clinically important difference (MCID) for pain outcomes . RESULTS: Out of 22 identified RCTs, 11 demonstrated significant between-group differences exceeding the MCID, suggesting a clinically meaningful change in pain outcomes. Nine documented whether AE occurred. Only five provided AEs details and four cited a standard means to report AE. DISCUSSION: There was inconsistency in reporting DN dosing parameters and AE. We could not determine if DN dosing affects outcomes, whether DN consistently produces clinically meaningful changes, or establish optimal dosage. Without more detailed reporting, replication of methods in future investigations is severely limited. A standardized method is lacking to report, classify, and provide context to AE from DN. Without more detailed AE reporting in clinical trials investigating DN efficacy, a more thorough appraisal of relative risk, severity, and frequency was not possible. Based on these inconsistencies, adopting a standardized checklist for reporting DN dosage and AE may improve internal and external validity and the generalizability of results.


Assuntos
Agulhamento Seco , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor , Modalidades de Fisioterapia , Padrões de Referência
11.
J Man Manip Ther ; 31(4): 220-230, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36082787

RESUMO

BACKGROUND: Preprocessed research resources are believed to be highly 'trustworthy' when translating research to clinical practice. However, the overall 'trustworthiness' is unknown if this evidence contains randomized clinical trials (RCTs) where prospective has not been/cannot be verified, has low confidence in estimated effects, and if they are not up to date. OBJECTIVES: This protocol will be used to create a baseline benchmark for a series of trustworthy living systematic reviews (SRs) regarding manual therapy interventions. METHODS: Data will originate from RCTs related to manual therapy neuromusculoskeletal interventions, indexed in 6 search engines in English from 1 January 2010, to the present. Two blinded reviewers will identify the RCTs and extract data using Covidence. The data will be synthesized based on consensus and analyzed using the Cochrane collaboration's Review Manager. EXPECTED OUTCOMES: It is expected that there will be a shortage of RCTs with at least a moderate confidence in estimated effects that will allow for strong practice recommendations. DISCUSSION: Identifying evidence that can be translated into strong practice recommendations is essential to identify beneficial and harmful interventions, decrease practice variability, and identify neuromusculoskeletal manual therapy interventions that require further disciplined methodological focus.


Assuntos
Manipulações Musculoesqueléticas , Metanálise como Assunto , Revisões Sistemáticas como Assunto
12.
Braz J Phys Ther ; 26(4): 100428, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35849892

RESUMO

BACKGROUND: Physical therapists obtain information from a variety of sources. The sources may influence their believability and use in clinical practice. OBJECTIVES: In this hypothesis-based study, we queried physical therapists (PTs) on the believability of evidence across six musculoskeletal treatment domains and analyzed variables that predicted the strength of beliefs. METHODS: This international survey included six different language portals and used a snowball dispensation strategy. PTs who were credentialed, licensed, or who practiced in the field, were queried on the believability of six treatment domains (i.e., exercise, manual therapy, psychologically-informed practice, sports/occupational performance, thermal/electrical agents, and pain science/patient education) and potential predictors of believability (i.e., social media use, years of practice, time and access to literature, specialization, confidence in reviewing literature and attributions of the researcher). RESULTS: In total, 1098 PTs from 36 countries completed the survey. PTs had strong beliefs in what they read or hear about exercise, sports/occupational performance, pain science/patient education, and psychologically-informed interventions. There was only moderate believability regarding manual therapy treatment and weak believability associated with thermal/electrical agents. Multiple linear regression analyses revealed that the most robust predictor to outcome relationships included time and access to literature and believability of pain science/patient education, years of clinical practice and believability of psychologically informed practice, and believability of thermal/electrical agents. CONCLUSION: An important takeaway from this study is that believability was influenced by several factors (primarily by years of practice, attributions of the researcher, and time and access to literature) and appeared to vary across treatment domains.


Assuntos
Fisioterapeutas , Exercício Físico , Humanos , Dor , Inquéritos e Questionários
13.
Front Physiol ; 13: 890848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586720

RESUMO

Fast growth rate in broiler chickens comes with welfare concerns and the contribution of growth rate to pathogen resistance and sickness behavior is relatively unknown. The objective of this study was to evaluate physiological and behavioral responses of conventional (CONV) and slow-growing (SG) male broilers challenged with Salmonella Typhimurium. CONV (n = 156) and SG (n = 156) chicks were raised in a pen with wood litter shavings until day 7 of age, when birds were transferred to 24 isolators (n = 11 chicks/isolator). On day 14 of age, half of the birds (n = 12 isolators) were challenged with S. Typhimurium (ST) and the other half (n = 12 isolators) received a control (C). On days 7, 13, 17, 21, and 24, body weight was recorded, and blood, jejunum and ileum sections were collected from 2 birds/isolator (n = 48 birds/sampling) to measure plasma IgA and IgG and intestinal histomorphology, respectively. On days 12, 16, 21, and 23, video was recorded to evaluate bird postures (sitting, standing, or locomoting) and behaviors (eating, drinking, preening, stretching, sham foraging, allopreening, and aggression). CONV birds were 70 g heavier (p = 0.03) on day 21 and 140 g heavier (p = 0.007) on day 24 than SG. On day 7, CONV jejunum villus height and crypt depth were 22 and 7 µm greater (p ≤ 0.001), respectively, than SG. On day 24, ST ileum villus height was 95 µm shorter (p = 0.009) than C. IgA increased after day 17 for all birds and at day 21, CONV IgA was greater (p = 0.01) than SG. Although SG IgG was 344 µg/ml greater (p = 0.05) than CONV on day 7, CONV IgG increased with age (p < 0.0001) to greater (p ≤ 0.03) concentrations than SG on day 21 and day 24 by 689 µg/ml and 1,474 µg/ml, respectively, while SG IgG remained at similar concentrations after day 13. Generally, a greater proportion of birds sham foraged as they aged (p < 0.0001). A greater proportion of CONV tended to sit (p = 0.09) and fewer locomoted (p < 0.0001) than SG as they aged. The results illustrate conventional and slow-growing broilers differ in their behavior, immunity, and response to Salmonella.

14.
J Man Manip Ther ; 30(5): 292-299, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35188881

RESUMO

OBJECTIVES: To determine if there are any statistically significant associations between: 1) randomized clinical trials (RCTs) investigating physical therapy musculoskeletal interventions, 2) journal impact factor (JIF), 3) frequency of RCT citation, 4) whether prospective intent was identifiable, and 5) the Physiotherapy Evidence Database (PEDro) scores. METHODS: MEDLINE indexed RCTs addressing musculoskeletal interventions published between January 2016 and July 2020 in physical therapy journals were included. Two blinded reviewers identified the RCTs and extracted the variables of interest. RESULTS: With a familywise alpha adjustment, there was no statistically significant correlation between JIF and number of citations (rho = 0.187; p = 0.0280). Statistically significant weak positive correlations were identified between the JIF and prospectively registered RCTs (rho = 0.240; p = 0.0046), JIF and PEDro scores (rho = 0.250; p = 0.0031), and PEDro scores and prospectively registered RCTs (rho = 0.335; p < 0.0001). CONCLUSION: The findings of this study suggest that JIF and PEDro scores may not be accurate measures of RCT quality. Failing to ensure that published RCTs followed their prospective intent and using bibliometrics that fail to accurately measure what they propose appears to create untrustworthy preprocessed resources for practicing physical therapists during the evidence-based practice process. LEVEL OF EVIDENCE: 1a.


Assuntos
Bibliometria , Fator de Impacto de Revistas , Bases de Dados Factuais , Exame Físico , Modalidades de Fisioterapia
15.
Artigo em Inglês | MEDLINE | ID: mdl-34950570

RESUMO

Functional resonance magnetic imaging (fMRI) allows for identification of eloquent cortex in pre-treatment planning. Previous studies have shown a correlation among lesion to activation distance (LAD) measures and morbidity and mortality. This study investigates the relationship between LAD, well-established language centers (Wernicke's and Broca's), and language performance measures. We included a sample population of brain tumor patients that received language fMRI (verbal fluency and sentence verification) for pre-treatment assessment (n = 51). LAD to the nearest language area was measured and divided into groups ≤ 10 mm and > 10 mm. Verbal fluency scores were compared between these groups. Additionally, patients were divided into similar groups based on LAD to either Broca's or Wernicke's areas, and the verbal fluency scores and sentence verification accuracy (n = 29) were subsequently compared between groups. Brain tumor patients with LAD ≤ 10 mm to either language area had significantly lower verbal fluency scores (p = 0.028). The difference in verbal fluency scores between groups with LAD ≤ 10 mm and > 10 mm to Wernicke's area trends toward significance (p = 0.067). The sentence verification accuracy was significantly lower in patients with LAD ≤ 10 mm to either language area (p = 0.039). These findings suggest that there exists a significant relationship between LAD to language centers and measures; greater language deficits are seen when LAD ≤ 10 mm.

16.
Mol Microbiol ; 116(6): 1476-1488, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34725868

RESUMO

Pathogenic Rickettsia are obligate intracellular bacteria and the etiologic agents of many life-threatening infectious diseases. Due to the serious nature of these infections, it is imperative to both identify the responsive immune sensory pathways and understand the associated immune mechanisms that restrict Rickettsia proliferation. Previous studies have demonstrated that the mammalian complement system is both activated during Rickettsia infection and contributes to the immune response to infection. To further define this component of the mammalian anti-Rickettsia immune response, we sought to identify the mechanism(s) of complement activation during Rickettsia infection. We have employed a series of in vitro and in vivo models of infection to investigate the role of the classical complement activation pathway during Rickettsia infection. Depletion or elimination of complement activity demonstrates that both C1q and pre-existing IgM contribute to complement activation; thus implicating the classical complement system in Rickettsia-mediated complement activation. Elimination of the classical complement pathway from mice increases susceptibility to R. australis infection with both increased bacterial loads in multiple tissues and decreased immune activation markers. This study highlights the role of the classical complement pathway in immunity against Rickettsia and implicates resident Rickettsia-responsive IgM in the response to infection.


Assuntos
Anticorpos Antibacterianos/imunologia , Complemento C1q/imunologia , Imunoglobulina M/imunologia , Infecções por Rickettsia/imunologia , Rickettsia/imunologia , Animais , Via Clássica do Complemento , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Rickettsia/genética , Infecções por Rickettsia/microbiologia
17.
J Orthop Sports Phys Ther ; 51(11): 542-550, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34546817

RESUMO

OBJECTIVES: To determine the prevalence of prospective clinical trial registration and postrandomization bias in published musculoskeletal physical therapy randomized clinical trials (RCTs). DESIGN: A methods review. LITERATURE SEARCH: Articles indexed in MEDLINE and published between January 2016 and July 2020 were included. STUDY SELECTION CRITERIA: Two independent blinded reviewers identified the RCTs using Covidence. We included RCTs related to musculoskeletal interventions that were published in International Society of Physiotherapy Journal Editors member journals. DATA SYNTHESIS: Data were extracted independently for the variables of interest from the identified RCTs by 2 blinded reviewers. The data were presented descriptively or in frequency tables. RESULTS: One hundred thirty-eight RCTs were identified. One third of RCTs were consistent with their prospectively registered intent (49/138); consistency with prospectively registered intent could not be determined for two thirds (89/138) of the RCTs. Four RCTs (8%)reported inconsistent results with the primary aims and 7 (14%) with the outcomes from the prospective clinical trial registry, despite high methodological quality (Physiotherapy Evidence Database [PEDro] scale score). Differences between prospectively registered and non-prospectively registered RCTs for PEDro scale scores had a medium effect size (r = 0.30). Two of 15 journals followed their clinical trial registration policy 100% of the time; in 1 journal, the published RCTs were consistent with the clinical trial registration. CONCLUSION: Postrandomization bias in musculoskeletal physical therapy RCTs could not be ruled out, due to the lack of prospective clinical trial registration and detailed data analysis plans. J Orthop Sports Phys Ther 2021;51(11):542-550. Epub 21 Sep 2021. doi:10.2519/jospt.2021.10491.


Assuntos
Publicações Periódicas como Assunto , Viés , Humanos , Modalidades de Fisioterapia , Prevalência , Sistema de Registros , Relatório de Pesquisa
18.
Physiother Res Int ; 26(3): e1914, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34028940

RESUMO

OBJECTIVES: The objectives of this study were the following: (1) to determine if there was a difference in outcomes between immediate responders to glenohumeral mobilizations at the initial evaluation, 2-week, 4-week, and 6-month follow-up as compared to those that do not respond in participants with subacromial pain syndrome; (2) to see if there were statistically significant differences in outcomes within these groups between these time frames of interest, and (3) to see if symptom response at the initial evaluation was predictive of a favorable recovery. METHODS: This was a prospective, single-group observational design. Clinicians pragmatically identified positive responders as improving at least two points on the Numeric Pain Rating Scale and/or a 20° improvement in shoulder active range of motion (AROM) following shoulder mobilization at the initial evaluation. Data were collected for the subjective and objective variables of interest at the initial evaluation, 2-week, 4-week, and 6-month follow-up. RESULTS: The prevalence of responders at the initial evaluation was 99 (81.8%). There were no statistically significant between-group differences for the variables of interest except for the Global Rating of Change (GRoC; f = 2.79, p = 0.006). The shoulder abduction AROM between-group difference exceeded the minimal detectable change at 4 weeks. The pair-wise comparison showed statistically significant differences for the outcomes of interest at each time point except for the GRoC between 4 weeks and 6 months. There was a statistically significant correlation between responders at the initial evaluation and shoulder abduction AROM at the 4-week follow-up (rpb (112) = 0.27, p = 0.004). CONCLUSION: Individuals with SAPS may benefit from shoulder mobilization independent of their within-session response to shoulder mobilization at the initial evaluation. Future research should seek to differentiate if these improvements are related to the within-session positive treatment response at the initial evaluation in individuals who are randomized to receive shoulder mobilization or not.


Assuntos
Síndrome de Colisão do Ombro , Estudos de Coortes , Humanos , Estudos Prospectivos , Amplitude de Movimento Articular , Dor de Ombro/terapia
20.
Braz J Phys Ther ; 25(4): 407-414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33371952

RESUMO

BACKGROUND: There is considerable overlap between pain referral patterns from the lumbar disc, lumbar facets, the sacroiliac joint (SIJ), and the hip. Additionally, sciatic like symptoms may originate from the lumbar spine or secondary to extra-spinal sources such as deep gluteal syndrome (GPS). Given that there are several overlapping potential anatomic sources of symptoms that may be synchronous in patients who have low back pain (LBP), it may not be realistic that a linear deductive approach can be used to establish a diagnosis and direct treatment in this group of patients. OBJECTIVE: The objective of this theoretical clinical reasoning model is to provide a framework to help clinicians integrate linear and non-linear clinical reasoning approaches to minimize clinical reasoning errors related to logically fallacious thinking and cognitive biases. METHODS: This masterclass proposes a hypothesis-driven and probabilistic approach that uses clinical reasoning for managing LBP that seeks to eliminate the challenges related to using any single diagnostic paradigm. CONCLUSIONS: This model integrates the why (mechanism of primary symptoms), where (location of the primary driver of symptoms), and how (impact of mechanical input and how it may or may not modulate the patient's primary complaint). The integration of these components individually, in serial, or simultaneously may help to develop clinical reasoning through reflection on and in action. A better understanding of what these concepts are and how they are related through the proposed model may help to improve the clinical conversation, academic application of clinical reasoning, and clinical outcomes.


Assuntos
Dor Lombar , Articulação Sacroilíaca , Raciocínio Clínico , Humanos , Região Lombossacral
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