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Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.
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Espasmos Infantis , Criança , Humanos , Lactente , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico , Anticonvulsivantes/uso terapêutico , Ácido Valproico/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Hormônio Adrenocorticotrópico/efeitos adversos , Corticosteroides/uso terapêutico , Resultado do Tratamento , Espasmo/tratamento farmacológico , Espasmo/induzido quimicamente , Espasmo/complicaçõesRESUMO
RCI2/PMP3s are involved in biotic and abiotic stresses and have an influence on the regulation of many genes. RCI2/PMP3 genes, which particularly encode small membrane proteins of the PMP3 family, are involved in abiotic stress responses in plants. In this work, in silico studies were used to investigate RCI2's potential function in stress tolerance and organogenesis. We conducted an extensive study of the RCI2 gene family and revealed 36 RCI2 genes from cotton species that were distributed over 36 chromosomes of the cotton genome. Functional and phylogenetic examination of the RCI2/PMP3 gene family has been studied in Arabidopsis, but in cotton, the RCI2/PMP3 genes have not yet been studied. Phylogenetic and sequencing studies revealed that cotton RCI2s are conserved, with most of them categorized into six distinct clades. A chromosome distribution and localization study indicated that cotton RCI2 genes were distributed unevenly on 36 chromosomes with segmental duplications, suggesting that the cotton RCI2 family is evolutionarily conserved. Many cis-elements related to stress responsiveness, development, and hormone responsiveness were detected in the promoter regions of the cotton RCI2. Moreover, the 36 cotton RCI2s revealed tissue-specific expression patterns in the development of cotton performed by transcriptome analysis. Gene structure analysis indicated that nearly all RCI2 genes have two exons and one intron. All of the cotton RCI2 genes were highly sensitive to drought, abscisic acid, salt, and cold treatments, demonstrating that they may be employed as genetic objects to produce stress-resistant plants.
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Brassica napus and its diploid progenitors (B. rapa and B. oleracea) are suitable for studying the problems associated with polyploidization. As an important anti-stress protein, RCI2 proteins widely exist in various tissues of plants, and are crucial to plant growth, development, and stress response. In this study, the RCI2 gene family was comprehensively identified and analyzed, and 9, 9, and 24 RCI2 genes were identified in B. rapa, B. oleracea, and B. napus, respectively. Phylogenetic analysis showed that all of the identified RCI2 genes were divided into two groups, and further divided into three subgroups. Ka/Ks analysis showed that most of the identified RCI2 genes underwent a purifying selection after the duplication events. Moreover, gene structure analysis showed that the structure of RCI2 genes is largely conserved during polyploidization. The promoters of the RCI2 genes in B. napus contained more cis-acting elements, which were mainly involved in plant development and growth, plant hormone response, and stress responses. Thus, B. napus might have potential advantages in some biological aspects. In addition, the changes of RCI2 genes during polyploidization were also discussed from the aspects of gene number, gene structure, gene relative location, and gene expression, which can provide reference for future polyploidization analysis.
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Brassica napus/genética , Diploide , Genoma de Planta , Família Multigênica , Poliploidia , Sequência de Bases , Cromossomos de Plantas/genética , Éxons/genética , Duplicação Gênica/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Íntrons/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Frações Subcelulares/metabolismo , Sintenia/genéticaRESUMO
BACKGROUND: Jigsaw is a primary care youth mental health service designed to increase access to and utilisation of mental health supports for 12- to 25-year-olds. Effectiveness in community youth mental health services is typically assessed using standardised instruments. The aim of this study was to examine the effectiveness of Jigsaw's brief intervention model of support using an idiographic tool, the goal-based outcome (GBO) measure. The study also aimed to explore the type of goals set by young people engaging with this service. METHOD: The study sample consisted of a secondary dataset of 4839 young people aged 12-25 years (63.5% female, 36.5% male) who engaged with one of Jigsaw's 13 brief intervention services. Overall, 7366 goals set using the GBO were examined. Inductive thematic analysis was conducted to examine the type of goals set by young people, and inferential analyses were used to examine statistical and reliable changes in goal progress. RESULTS: The goals young people set focused on developing coping mechanisms and personal growth and managing interpersonal difficulties. Mean scores for progress towards goals improved significantly from pre- to postintervention. The reliable change index (RCI) indicated that change greater than 2.82 points represents reliable change on the GBO, with 78.6% of young people showing reliable improvement. Demographic characteristics did not impact goal progress. CONCLUSION: These findings suggest Jigsaw's brief intervention model of support is effective in assisting young people reach their goals and that the GBO is a suitable measure for young people attending a community-based youth mental health service.
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Objetivos , Serviços de Saúde Mental , Adolescente , Feminino , Humanos , Masculino , Saúde Mental , Avaliação de Resultados em Cuidados de Saúde , Atenção Primária à SaúdeRESUMO
PURPOSE: To compare the binding and agonistic activity of Acthar® Gel and synthetic melanocortin receptor (MCR) agonists and examine how the activity of select agonists affects the in vivo production of corticosterone. MATERIALS AND METHODS: In vitro binding was determined using concentration-dependent displacement of the ligand [125I]Nle4, D-Phe7-α-melanocyte-stimulating hormone (α-MSH) on cells expressing MC1R, MC3R, MC4R, or MC5R. Functional activity was determined using a time-resolved fluorescence cyclic adenosine monophosphate (cAMP) assay in cells expressing MC1R, MC2R, MC3R, MC4R, or MC5R. In vivo corticosterone analyses were performed by measuring plasma corticosterone levels in Sprague Dawley rats. RESULTS: Acthar Gel and synthetic MCR agonists exhibited the highest binding at MC1R, lowest binding at MC5R, and moderate binding at MC3R and MC4R. Acthar Gel stimulated the production of cAMP in all 5 MCR-expressing cell lines, with MC2R displaying the lowest level of full agonist activity, 3-, 6.6-, and 10-fold lower than MC1R, MC3R, and MC4R, respectively. Acthar Gel was a partial agonist at MC5R. The synthetic MCR agonists induced full activity at all 5 MCRs, with the exception of α-MSH having no activity at MC2R. Acthar Gel treatment had less of an impact on in vivo production of corticosterone compared with synthetic ACTH1-24 depot. CONCLUSIONS: Acthar Gel bound to and activated each MCR tested in this study, with partial agonist activity at MC5R and the lowest level of full agonist activity at MC2R, which distinguished it from synthetic MCR agonists. The minimal activity of Acthar Gel at MC2R corresponded to lower endogenous corticosteroid production.
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Hormônio Adrenocorticotrópico/metabolismo , Corticosterona/metabolismo , Receptores de Melanocortina/metabolismo , alfa-MSH/metabolismo , Animais , Ligantes , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Melanocortina/agonistas , Receptores de Melanocortina/classificaçãoRESUMO
A radiation combined injury is defined as an injury that occurs in the setting of irradiation, such as those expected after a nuclear accident, radiation dispersal device release (a 'dirty bomb'), or a nuclear weapon detonation. There is much research on irradiation-associated burns and their healing, but there is less known about other injuries sustained in the context of irradiation. Animal models are limited in their correlations to clinical situations but can support research on specific questions about injuries and their healing. Mouse models of irradiation with skin or bone wounds are validated as highly reproducible and quantitative. They show dose-dependent impairment of wound healing, with later recovery. Irradiation-induced delay of bone wound healing was mitigated to different extents by single doses of gramicidin S-nitroxide JP4-039, a plasmid expressing manganese superoxide dismutase, amifostine/WR2721, or the bifunctional sulfoxide MMS-350. These models should be useful for research on mechanisms of radiation dermal and osseous damage and for further development of new radioprotectors. They also provide information of potential relevance to the effects of clinical radiation therapies.
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Lesões por Radiação , Roedores , Animais , Modelos Animais de Doenças , Camundongos , Pele , CicatrizaçãoRESUMO
OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by proximal muscle weakness. H. P. Acthar gel [repository corticotropin injection (RCI)] is a formulation of adrenocorticotropic hormone and has been approved by Food and Drug Administration for use in IIM; however, literature is limited. In this study, we report longitudinal follow-up of myositis patients treated with RCI. METHODS: Patients with refractory IIM who were enrolled in the prospective, open-label RCI trial were included in this study. The post-trial follow-up period was 6 months with assessments every 2 months, which included myositis core set measures including extra-muscular global, muscle and patient global disease activities, HAQ, and manual muscle testing. RESULTS: Two patients were lost to follow-up after finalization of the trial, and the remaining eight patients were enrolled in the follow-up study. One patient remained on RCI after the trial. In the follow-up period, four of eight patients had flare at on average 4.1 months after the RCI trial. Among the patients who flared, three required an increase in prednisone. One patient was restarted on RCI at 5.5 months, but had minimal improvement after 3 months. Four patients who remained stable continued to satisfy criteria for the definition of improvement through the 6-month follow-up. However, none showed any further improvement in the primary or secondary efficacy outcomes after the initial RCI trial. CONCLUSION: To our knowledge, this is the first study reporting the follow-up results of patients treated with standard dose and duration of Acthar. We believe that our study will provide the basis for the development of future randomized RCI trials in IIM.
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Hormônio Adrenocorticotrópico/administração & dosagem , Miosite/tratamento farmacológico , Hormônio Adrenocorticotrópico/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Feminino , Seguimentos , Géis , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prednisona/administração & dosagem , Estudos Prospectivos , Exacerbação dos SintomasRESUMO
OBJECTIVE: To investigate the disparity in dental caries between native and migrant children in Shanghai, China. METHODS: Between 2013 and 2015, a random cluster sample of native and migrant children aged 5, 9, 12 and 15 years was collected from each district in Shanghai. Oral examination was performed following the World Health Organization (WHO) method, and findings were reported as decayed-missing-filled teeth of primary dentition (dmft) and permanent dentition (DMFT). RESULTS: A total of 10 150 children were examined, and 33.6% of them were migrants. Migrant children had a higher prevalence of deciduous caries than native children (the 5-year-old age group, 67.8% vs 63.0%, P = 0.024; the 9-year-old age group, 75.9% vs 66.1%, P < 0.001), and higher dmft values were found in migrant children. But with respect to permanent teeth, no statistical differences were found between the two groups in caries prevalence or DMFT. After controlling for potential confounders by logistic regression, migrant children showed a higher risk of deciduous caries (odds ratio 1.42, 95% confidence interval 1.25-1.61, P < 0.001) but not of permanent caries. Migrant children exhibited relatively lower deciduous Restorative Care Index (RCI). However, 9- and 15-year-old migrant children had a higher permanent RCI than their native counterparts. CONCLUSIONS: Dental caries prevalence in migrant children was higher in the deciduous teeth but not in the permanent teeth compared to that in their native counterparts. School-based dental public health services may contribute to reducing the disparity in dental health status between migrant and native children.
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Cárie Dentária , Migrantes , Adolescente , Criança , Pré-Escolar , China , Estudos Transversais , Índice CPO , Humanos , PrevalênciaRESUMO
Rare cold-inducible 2 (RCI2) proteins are small hydrophobic proteins that are known to be localized in cellular membranes. The function of RCI2 proteins has been reported to be associated with low-temperature, salt, and drought stress tolerances as a membrane potential regulator; however, the specific functions are still unknown. The PIP2 (plasma membrane intrinsic protein 2) aquaporins are proteins that transport water and small solutes into the cell. The expression and activity of PIP2 proteins, like RCI2, are also related to salt- and drought-stress tolerance. In this study, we identified novel protein interactions between RCI2 and PIP2; 1, including protein accumulation changes in the bioenergy crop Camelina sativa L. under various NaCl stress conditions. Accumulation of both CsRCI2E and CsRCI2F proteins increased with NaCl stress; however, to differing levels depending on the NaCl stress intensity. A co-immunoprecipitation test revealed interaction between CsRCI2E-CsPIP2 and CsRCI2F-CsPIP2. Moreover, co-expression of the four CsRCI2 proteins with CsPIP2; 1 in Xenopus laevis oocytes reduced water transport activity. Furthermore, the abundance of CsPIP2; 1 protein was decreased under CsRCI2E and CsRCI2F co-expression. These results suggest that NaCl-induced expression of CsRCI2E and CsRCI2F contributes to the regulation of CsPIP2; 1.
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Aquaporinas/metabolismo , Brassicaceae/fisiologia , Proteínas de Plantas/metabolismo , Estresse Salino , Água/metabolismo , Animais , Secas , Mapas de Interação de Proteínas , Cloreto de Sódio/metabolismo , XenopusRESUMO
BACKGROUND: Members of the Early Salt Induced 3 (Esi3/RCI2/PMP3) gene family in plants have been shown to be induced in response to both biotic and abiotic stresses and to enhance stress tolerance in both transgenic plants and Saccharomyces cerevisiae. Esi3 was first identified as a salt stress induced gene in the salt tolerant wild wheat grass, Lophopyrum elongatum, and subsequently homologous genes in many other species were found to be members of the gene family. These include Arabidopsis thaliana and Oryza sativa where they are referred to as Rare Cold Inducible 2 (RCI2), and Zea mays where they are referred to as Plasma Membrane Protein 3 (PMP3). This study characterizes the Esi3 family members in Triticum aestivum and explores the tissue specific expression patterns of the gene family members as well as their response to a variety of environmental stresses. RESULTS: The Esi3 gene family was found to have a total of 29 family members comprised of ten paralogous groups in the hexaploid T. aestivum. Each paralogous group contains three homeologous copies, one in each of the A, B and D genomes with the exception of Esi3-2 which is missing the B copy. The genes of the Esi3 gene family were also identified in four other monocot species, Aegilops tauschii, Hordeum vulgare, Secale cereale and Sorghum bicolor, and were confirmed or corrected for Brachypodium distachyon, Oryza sativa and Zea mays, as well as the dicot Arabidopsis thaliana. Gene expression of the Esi3s was analyzed using tissue-specific, abiotic and biotic stress RNA-Seq 454 sequence libraries and Affymetrix microarray data for T. aestivum. CONCLUSIONS: Members of nearly all paralogous groups of the Esi3 genes in T. aestivum have altered gene expression in response to abiotic or biotic stress conditions. In addition, there are modest differences in gene expression among homeologous members of the gene family. This suggests that the Esi3 gene family plays an important role in the plants response to the stresses presented in this study. The Esi3-9 in T. aestivum has a unique N terminal extension placing it into Group III, a new group for the Esi3/RCI2/PMP3 gene family.
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Genes de Plantas , Família Multigênica , Triticum/genética , Secas , Fusarium/fisiologia , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Especificidade de Órgãos/genética , Estresse Fisiológico/genética , TemperaturaRESUMO
The objectives of the current study were to examine cognitive decline in relation to psychological wellbeing, HIV disease and treatment characteristics and baseline variables over a one-year period of time in a group of HIV-infected patients on long term cART with undetectable viral load in comparison to a HIV-negative control group. Eighty-two of 95 patients and 43 of 55 controls who completed a baseline assessment for the Art-NeCo study underwent a follow-up neuropsychological assessment. A repeated-measure general linear model analysis was performed to compare the performance at follow-up in comparison to baseline between the patients and controls. Reliable change indices were computed as a measure of significant change in cognitive function. Compared to controls, patients overall performed worse on the domain speed of information processing. In the patient group a worse performance at follow-up was present for the verbal fluency domain compared to the controls, in the absence of a baseline group difference. For the executive function domain, no group differences were found at follow-up, but the patients performed worse than the controls at baseline. We found that cognitive decline was related to more frequent use of recreational drugs and a somewhat heightened level of irritability and more somatic complaints at baseline. However, the decliners did not differ from the non-decliners on any of the HIV-related variables.
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Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Função Executiva/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adulto , Cognição , Disfunção Cognitiva , Feminino , Seguimentos , Infecções por HIV/virologia , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida , Carga ViralRESUMO
West Nile virus (WNV) circulation dynamics in the context of the urban environment is not yet elucidated. In this perspective, three groups of eight rock pigeons (Columbia livia) were inoculated with three WNV lineage 1 strains isolated in Italy between 2009 and 2012. The pigeons did not develop any clinical signs consistent with WNV acute infection. All animals seroconverted and shed virus up to 15 days post-infection by the oral or cloacal routes. In all infected groups viraemia lasted for 4 days post-infection. No WNV-specific gross or histological lesions were found in infected birds compared to control birds and immunohistochemistry remained constantly negative from all tissues. The reservoir competence index was also assessed and it ranged between 0·11 and 0·14. This study demonstrates that pigeons are competent reservoir hosts for Italian WNV lineage 1 circulating strains thus potentially posing a risk to the public health system.
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Doenças das Aves/virologia , Columbidae , Reservatórios de Doenças/veterinária , Viremia/veterinária , Febre do Nilo Ocidental/veterinária , Vírus do Nilo Ocidental/fisiologia , Animais , Reservatórios de Doenças/virologia , Itália , Viremia/virologia , Febre do Nilo Ocidental/virologiaRESUMO
Approaches based on continuous indicators (the size of the pre-to-post-test change; effect size or ΔT) and on categorical indicators (Percentage Improvement and the Jacobson-Truax approach to Clinical Significance) are evaluated to determine which has the best methodological and statistical characteristics, and optimal performance, in comparing outcomes of treatment providers. Performance is compared in two datasets from providers using the Brief Symptom Inventory or the Outcome Questionnaire. Concordance of methods and their suitability to rank providers is assessed. Outcome indicators tend to converge and lead to a similar ranking of institutes within each dataset. Statistically and conceptually, continuous outcome indicators are superior to categorical outcomes as change scores have more statistical power and allow for a ranking of providers at first glance. However, the Jacobson-Truax approach can complement the change score approach as it presents outcome information in a clinically meaningful manner. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONERS MESSAGES: When comparing various indicators or treatment outcome, statistical considerations designate continuous outcomes, such as the effect size of the pre-post change (effect size or ΔT) as the optimal choice. Expressing outcome in proportions of recovered, changed, unchanged or deteriorated patients has supplementary value, as it is more easily interpreted and appreciated by clinicians, managerial staff and, last but not the least, by patients. If categorical outcomes are used with small datasets, true differences in institutional performance may get obscured due to diminished power to detect differences. With sufficient data, outcome according to continuous and categorical indicators converge and lead to similar rankings of institutes' performance.
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Benchmarking/métodos , Transtornos Mentais/terapia , Psicologia Clínica/normas , Psicoterapia/normas , Projetos de Pesquisa , Adulto , Feminino , Humanos , Masculino , Países Baixos , Psicologia Clínica/métodos , Psicoterapia/métodos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The quantitative viral outgrowth assay (QVOA) provides a precise minimal estimate of the reservoir of resting CD4(+) T-cell infection (resting cell infection [RCI]). However, the variability of RCI over time during antiretroviral therapy (ART), relevant to assess potential effects of latency-reversing agents or other interventions, has not been fully described. We performed QVOA on resting CD4(+) T cells obtained via leukapheresis from 37 human immunodeficiency virus (HIV)-infected patients receiving stable suppressive ART for a period of 6 years. Patients who started ART during acute (n = 17) or chronic (n = 20) HIV infection were studied once HIV RNA levels were <50 copies/mL for ≥ 6 months. Using random effects analysis of 160 RCI measurements, we found that RCI declined significantly over time (P < .001), with an estimated mean half-life of 3.6 years (95% confidence interval, 2.3-8.1 years), remarkably consistent with findings of prior studies. There was no evidence of more rapid decay in acute versus chronic HIV infection (P = .99) for patients suppressed ≥ 6 months. RCI was reliably estimated with longitudinal measurements generally showing < 2-fold variation from the previous measure. When QVOA is performed in this format, RCI decreases of >6-fold were rare. We suggest that a 6-fold decline is a relevant threshold to reliably identify effects of antilatency interventions on RCI.
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HIV-1/isolamento & purificação , HIV-1/fisiologia , Latência Viral/efeitos dos fármacos , Doença Aguda , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/virologia , Doença Crônica , Estudos de Avaliação como Assunto , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Viremia/tratamento farmacológico , Adulto JovemRESUMO
Radar coincidence imaging (RCI) is a high-resolution staring imaging technique without the limitation of relative motion between target and radar. The sparsity-driven approaches are commonly used in RCI, while the prior knowledge of imaging models needs to be known accurately. However, as one of the major model errors, the gain-phase error exists generally, and may cause inaccuracies of the model and defocus the image. In the present report, the sparse auto-calibration method is proposed to compensate the gain-phase error in RCI. The method can determine the gain-phase error as part of the imaging process. It uses an iterative algorithm, which cycles through steps of target reconstruction and gain-phase error estimation, where orthogonal matching pursuit (OMP) and Newton's method are used, respectively. Simulation results show that the proposed method can improve the imaging quality significantly and estimate the gain-phase error accurately.
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To critically evaluate the effects of manual therapy (MT) on pain and functional improvement in patients with rotator cuff injury (RCI), a systematic review of all randomized controlled trials (RCTs) on MT for RCI was conducted in the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, Physiotherapy Evidence Database, Chinese National Knowledge Infrastructure, Wan-fang Data, Chinese Scientific Journal Database, and Chinese Biomedical Literature database from inception to March 28, 2023. A total of 1,110 participants from 24 eligible RCTs were included in the analysis. Compared with placebo, MT could not effectively relieve pain [standardized mean difference (SMD)=-0.25; 95% CI: -0.51 to 0.01; P=0.06], although its impact on functional improvement appears limited (SMD=0.20; 95% CI: -0.09 to 0.49; P=0.18). Combining MT with exercise had significant advantages over exercise alone, as combined therapy contributed to both pain reduction (SMD=0.36; 95% CI: 0.08 to 0.64; P=0.01) and functional enhancement (SMD=0.32; 95% CI: 0.11 to 0.52; P=0.002). Furthermore, MT combined with multimodal physiotherapy showed additional benefits in pain reduction (mean difference=1.57; 95% CI: 0.18 to 2.96; P=0.03) and functional improvement (SMD=0.77; 95% CI: 0.43 to 1.12; P<0.0001) compared with multimodal physiotherapy alone. These findings highlight the superior pain alleviation and functional improvement provided by MT when combined with exercise or physiotherapy. Consequently, MT has emerged as a pivotal component of therapeutic intervention for RCI.
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BACKGROUND: To evaluate the therapeutic effects of topical RCI001 (RCI) and compare its efficacy with that of 1% prednisolone acetate (PDE) and 5% Lifitegrast in a modified mixed dry eye disease (DED) model. METHODS: The environmental DED model was induced in BALB/c mice in a dry chamber with scopolamine. The eyes of the mice were treated topically with phosphate buffered saline (PBS), PDE, Lifitegrast or RCI twice daily for 1 week. Ocular surface staining (OSS), tear secretion, inflammatory cytokines in the ocular surface and lacrimal gland, and immunofluorescence staining in the conjunctiva and cornea(CC) were assessed. RESULTS: The RCI group demonstrated better improvement of OSS and tear secretion than the PBS group (OSS, PBS: 13.0 ± 1.6, RCI: 9.4 ± 3.0; tear secretion, PBS: 5.0 ± 0.4 mm, RCI: 7.0 ± 0.3 mm, each P < 0.001) and better clinical efficacy than PDE and Lifitegrast groups on Day 7 (improvement rate of OSS, RCI: 32.45%, Lifitegrast: 13.13%, PDE: 12.25%). The RCI group resulted in significantly lower expression of oxidative stress markers in the CC than the PBS group (4-HNE, NOX2, and NOX4 in the conjunctiva; NOX2 in the cornea, each P < 0.05). However, the PDE and Lifitegrast groups did not show significant differences compared with the PBS group. There were no significant differences of inflammatory cytokines in the ocular surface and lacrimal gland between all groups. CONCLUSION: Topical RCI001 showed excellent therapeutic effects in environmental DED models by stimulating tear secretion, modulating oxidative stress and improving corneal epithelial healing compared to 1% PDE and 5% Lifitegrast.
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Our objective was to establish normative data and reliable change indices (RCI) for the Montreal Cognitive Assessment's auditory items (MoCA-22). 4,935 cognitively unimpaired participants were administered the MoCA during an in-person visit to an Alzheimer's Disease Research Center (Mage = 67.9, Meducation = 16.2, 65.8% women, 75.9% non-Hispanic-White), with 2,319 unimpaired participants returning for follow-up. Normative values and cutoffs were developed using demographic predictions from ordinary and quantile regression. Test-retest reliability was calculated using Spearman and intraclass correlations. RCI values were calculated using Chelune and colleagues' (1993) formula. Education, age, and sex were all statistically related to MoCA-22 scores, with education having the strongest relationship. Notably, these relationships were not consistent across MoCA-22 quantiles, with education becoming more important and sex becoming less important for predicting low scores. These models were integrated into a calculator for deriving normative scores for an individual case. Furthermore, there was adequate-to-good test-retest reliability (ϱ = 0.56 95% CI [.54, .59]; ICC = 0.75, 95% CI [.73, .77]) and changes of at least 2-3 points are necessary to identify reliable change at 1-3-year follow-up. These findings add to the literature regarding utility of the MoCA-22 in the cognitive screening of older adults.
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OBJECTIVE: To evaluate neurocognitive test results and symptom reporting after sports-related concussion in a group of female cheerleaders. STUDY DESIGN: Junior and senior high school female cheerleaders (n = 138) underwent preparticipation baseline testing and repeated the ImPACT (Immediate Postconcussion Assessment and Cognitive Testing) evaluation within 7 days of concussive injury (range, 0-7 days; mean, 3.9 days). Postinjury neurocognitive and symptom scores were compared with preinjury (baseline) scores. "Abnormal" test performance was determined statistically using Reliable Change Index scores and self-reported symptoms. Main outcome variables included the composite scores indices from the ImPACT test, as well as symptoms reported by participants. Preinjury baseline and postinjury test results were compared using MANOVA. RESULTS: As a group, cheerleaders with concussion evaluated within 7 days of injury performed poorly on the ImPACT test battery relative to their own baseline (F = 6.5; P = .00). In addition, 61% of the cheerleaders with concussions reported an increase in symptoms compared with baseline. The groups did not differ significantly by position on the squad (F = 0.37; P = .96). Of the group of cheerleaders who did not report increased symptoms at the time of postinjury evaluation, 37% had at least 1 abnormal ImPACT composite score result, suggesting some residual cognitive decline compared with baseline. CONCLUSION: The diagnosis and management of concussion in cheerleaders should not consist solely of self-reported symptoms. Neurocognitive test results represent an important component of the evaluation process and may identify athletes with residual neurocognitive deficits who report being clinically asymptomatic.