On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier.

Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism. Accumulation of Th17 cells at the gingiva was driven in response to the physiological barrier damage that occurs during mastication. Physiological mechanical damage, via induction of interleukin 6 (IL-6) from epithelial cells, tailored effector T cell function, promoting increases in gingival Th17 cell numbers. These data highlight that diverse tissue-specific mechanisms govern education of Th17 cell responses and demonstrate that mechanical damage helps define the immune tone of this important oral barrier.

Longitudinal multi-omics of host-microbe dynamics in prediabetes.

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.

Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.

Changes to physical activity behavior during the COVID-19 pandemic and their associated factors: a cross sectional survey of Mexican women.

BACKGROUND: On March 24, 2020, the Mexican Government established social distancing measures to address the outbreak of the COVID-19 pandemic. The resulting home confinement affected daily lifestyle habits such as eating, sleeping, and physical activity (PA). The objectives of this study were to determine changes in PA behaviors among Mexican women due to the COVID-19 pandemic and to assess potential factors associated with these changes. METHODS: This was a cross-sectional study based on an anonymous online questionnaire developed by the Task Force on Physical Activity for Persons with Disabilities (PAPD) within the International Society of Physical and Rehabilitation Medicine (ISPRM). Descriptive, quantitative statistics were used for data analysis. A Chi-squared (χ²) test was used to explore associations between dependent and independent variables. RESULTS: A total of 1882 surveys were completed. Among the respondents, 53.3% declared that their PA was reduced during the pandemic, 26.6% reported similar PA behavior, and 20.1% declared that their PA had increased during the pandemic. Lower PA behavior during the pandemic was associated with lower education levels, stricter pandemic constraints, obesity, and lower self-perceived functioning levels. A statistically significant association between poorer self-perceived mental health and decreased PA behaviors was also found. Respondents who were younger, self-perceived as unimpaired, not overweight, and whose income was not impacted by COVID-19 were associated with higher levels of reported physical and mental health. CONCLUSIONS: The study results identify disparities experienced in PA behavior during the COVID-19 pandemic among Mexican women and highlights the need for social support for PA participation.

Physical activity, quality of life and parenting stress in children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) are less physically active than their typically developing peers. The effects of decreased physical activity on children's quality of life (QOL) or caregiver's lives are not well understood. This study aimed to investigate the association between physical activity, QOL, and parenting stress in children with CP. METHODS: A prospective cross-sectional study was done in children with CP. Daily physical activity was measured over 7 days using an accelerometer (ActiGraph™). Caregivers completed the Child Health Questionnaire - Parent Form 50 and Parenting Stress Index - Short Form. Multiple regression analysis was used. RESULTS: In total, data from 65 children with Gross Motor Function Classification System (GMFCS) levels I-V, aged 4-13 years, were analyzed. Non-ambulatory (GMFCS IV-V) children had significantly lower activity counts and moderate to vigorous physical activity (MVPA) in comparison with ambulatory (GMFCS I-II) and marginally ambulatory (GMFCS III) children. The ambulatory group had better physical QOL than the non-ambulatory group. Caregivers of the non-ambulatory or marginally ambulatory children with CP reported higher parenting stress levels than those of the ambulatory group. Time spent in MVPA and activity counts were positively associated with physical QOL in children with CP. Low activity counts and low amounts of MVPA of children with CP were significant predictors of high parenting stress. CONCLUSIONS: Physical activity in children with CP is associated with children's QOL and parenting stress. These results suggest that clinicians should conduct physical activity assessment and counseling to promote physical activity.

Perceived Physical and Mental Health and Healthy Eating Habits During the COVID-19 Pandemic in Korea.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted the lives of people around the world since 2020. This study aims to reveal perceived impact of the coronavirus pandemic on physical and mental health and eating behaviors among people with disabilities and without disabilities in South Korea, as compared to other countries. METHODS: A secondary analysis of a prospective cross-sectional study which was conducted with a web-based global survey. RESULTS: Among the 3,550 responses from 65 countries, 2,621 responses with nation information were set as full data, 189 for South Korea and 2,432 for other countries. In Korea, there was no significant difference in healthy lifestyle behaviors between people with and without disabilities before the COVID-19 pandemic. Perceived physical and mental health and changes in eating habits during the COVID-19 pandemic showed no significant difference between people with and without disabilities in Korea. There were significant differences in physical health and dietary habits, but no differences in its effect on mental health between people living in Korea and other countries in both people with and without disabilities groups. In other words, more than 60% of people in all groups (disability vs. non-disability, Korea vs. non-Korea) reported worse mental health than before the COVID-19 pandemic. CONCLUSION: In Korea and other countries, mental health showed a tendency to deteriorate regardless of the presence or absence of disability during the COVID-19 pandemic. In terms of healthy eating habits, Koreans were relatively less affected than people from other countries.

Gut commensals, dysbiosis, and immune response imbalance in the pathogenesis of multiple sclerosis.

Intestinal microbiota alterations have been found to be directly related to a wide range of disease states in humans, including multiple sclerosis (MS). The etiology of MS is highly debated and subsequently, there is no cure. Research dedicated to MS and its murine model, experimental autoimmune encephalomyelitis (EAE), have found that dysbiosis of the gut microbiota may play a role in the disease state and severity. In this review, we discuss the characteristic dysbiosis in MS, the role commensal-derived ligands may have in the pathogenesis of the disease, and the possibility of targeting the microbiota as a future therapy.

Microbial signatures of health, gingivitis, and periodontitis.

The subgingival crevice harbors diverse microbial communities. Shifts in the composition of these communities occur with the development of gingivitis and periodontitis, which are considered as successive stages of periodontal health deterioration. It is not clear, however, to what extent health- and gingivitis-associated microbiota are protective, or whether these communities facilitate the successive growth of periodontitis-associated taxa. To further our understanding of the dynamics of the microbial stimuli that trigger disruptions in periodontal homeostasis, we reviewed the available literature with the aim of defining specific microbial signatures associated with different stages of periodontal dysbiosis. Although several studies have evaluated the subgingival communities present in different periodontal conditions, we found limited evidence for the direct comparison of communities in health, gingivitis, and periodontitis. Therefore, we aimed to better define subgingival microbiome shifts by merging and reanalyzing, using unified bioinformatic processing strategies, publicly available 16S ribosomal RNA gene amplicon datasets of periodontal health, gingivitis, and periodontitis. Despite inherent methodological differences across studies, distinct community structures were found for health, gingivitis, and periodontitis, demonstrating the specific associations between gingival tissue status and the subgingival microbiome. Consistent with the concept that periodontal dysbiosis is the result of a process of microbial succession without replacement, more species were detected in disease than in health. However, gingivitis-associated communities were more diverse than those from subjects with periodontitis, suggesting that certain species ultimately become dominant as dysbiosis progresses. We identified the bacterial species associated with each periodontal condition and prevalent species that do not change in abundance from one state to another (core species), and we also outlined species co-occurrence patterns via network analysis. Most periodontitis-associated species were rarely detected in health but were frequently detected, albeit in low abundance, in gingivitis, which suggests that gingivitis and periodontitis are a continuum. Overall, we provide a framework of subgingival microbiome shifts, which can be used to generate hypotheses with respect to community assembly processes and the emergence of periodontal dysbiosis.

Integrity of the Inferior Cerebellar Peduncle Correlates with Ambulatory Function after Hemorrhagic Stroke.

OBJECTIVES: Cerebro-cerebellar connectivity plays a critical role in motor recovery after stroke; however, the underlying mechanism of walking recovery is unclear. The dorsal spinocerebellar pathway has been suggested as a biomarker of poststroke ambulatory function. We aimed to explore the association between ambulatory function and the dorsal spinocerebellar pathway's integrity after intracerebral hemorrhage (ICH). MATERIALS AND METHODS: Twenty-seven patients with ICH who were admitted for inpatient rehabilitation during the subacute phase of stroke and 27 age-matched healthy controls were included retrospectively. Ambulatory function was assessed using the Berg Balance Scale and Mobility score. We measured the fractional anisotropy (FA) values of the corticospinal tract (CST) and inferior cerebellar peduncle (ICP) as the final route of the dorsal spinocerebellar pathway. The FA laterality indices, representing the degree of degeneration, were calculated. A Spearman correlation analysis and multivariate linear regression models were used to determine the associations between the FA laterality indices and ambulatory function. RESULTS: An FA reduction was found in both the ipsilesional CST and contralesional ICP of the patients. The ICP FA laterality index exhibited a moderate correlation with ambulatory function (Berg Balance Scale, ρBBS=0.589; Mobility score, ρMS=0.619). On dividing the patient group into the moderate (mRS 3, 4) and severe disability (mRS 5) groups, a stronger correlation was found (ρBBS=0.777, ρMS=0.856, moderate disability; ρBBS=0.732, ρMS=0.797, severe disability). The ICP FA laterality index and age were independently associated with the Mobility score (R2=0.525). CONCLUSIONS: ICP degeneration occurs after ICH, and its degree is associated with ambulatory function after ICH.

Could DOAC Be a Better Choice Than Warfarin in Low Compliance Patients with Fontan Procedure?

Background and Objectives: After the Fontan procedure, thromboembolic events need to be prevented. We present a young patient with a history of Fontan procedure and poor adherence to warfarin who developed systemic thromboembolism. He was changed to maintenance dabigatran, which is one of the available direct oral anticoagulants (DOACs). Case presentation: A 20-year-old man was diagnosed with cerebral infarct, pulmonary thromboembolism (PTE), and renal infarcts. He was prescribed warfarin to prevent thromboembolic events after the Fontan procedure. Based on his poor adherence to warfarin, we decided to change the anticoagulant therapy from warfarin to dabigatran 150 mg bid. One month later, his pulmonary thromboembolism regressed. Conclusion: Our case report showed a young adult with low compliance to warfarin who developed cerebral, pulmonary, and renal thromboembolic events. Thus, in our opinion, the change from warfarin to a DOAC was necessary for further prevention and treatment of PTE. A change from warfarin to a DOAC should be considered in patients with poor compliance who are at high risk of thromboembolic events, for example, after the Fontan procedure.

The Long-Term Functional Effect of Thrombectomy on Patients with Middle Cerebral Artery Occlusion Who Exhibit Moderate to Severe Disability.

Background and Objectives: Endovascular thrombectomy (EVT is an emerging gold standard treatment for acute cerebral infarction and may allow functional improvement after subacute cerebral infarction. However, the long-term functional benefits of EVT in patients with moderate to severe disability remain unclear. We investigated the effects of EVT on the activities of daily living (ADL), handicap, gait, and eating in patients with middle cerebral artery (MCA) occlusion who exhibited moderate to severe disability (score of 3-5 on the modified Rankin scale (mRS)) due to stroke, up to six months after onset. Materials and Methods: This retrospective longitudinal case-control study assessed 45 patients with MCA occlusion who exhibited moderate to severe disability (mRS score ≥ 3): 15 underwent EVT and 30 served as controls. Clinical assessments were conducted at two weeks (12-16 days), four weeks (26-30 days), and six months (180-210 days) after stroke onset. Functional assessments comprised the Korean version of the modified Barthel index (MBI), mRS, functional ambulation category (FAC), and dysphagia outcome severity scale (DOSS) to assess disability, handicap, gait, and eating. Results: The MBI, mRS, FAC, and DOSS scores all improved significantly (all p < 0.05) in the EVT group, compared to the controls. Conclusions: EVT has favorable effects on performing routine ADL, the handicap itself, walking, and eating. Therefore, EVT is recommended for patients with acute MCA occlusion, including those with severe disability at the initial assessment.

Body composition of school-aged children with disabilities.

BACKGROUND: Children with disabilities are more likely to have problems related to growth and development than typically developing children. This study aimed to compare the growth and body composition indices of children with disabilities with those of typically developing children. METHODS: Students from two elementary schools and one special school were recruited. Height, bodyweight, fat mass, fat-free mass, skeletal muscle mass, and percentage body fat (PBF) were measured. Raw data and proportions of classifications (under, within, and over range) according to the reference value were analyzed. RESULTS: In total, 355 typically developing children, and 73 children with disabilities participated. Fat-free mass was significantly lower in students with disabilities than in typically developing students (32.14 ± 5.82 versus 28.71 ± 5.92, P < 0.05). Compared with typically developing students, students with disabilities showed tendencies of lower ranges of body mass index (BMI) and fat mass index (FMI). The proportion of under, within, or over ranges of FFMI (fat-free mass index) was significantly different between the two groups. Among the factors, age, gender, and disability, disability significantly influenced FFMI in school-aged children. The proportion of three ranges of BMI, PBF, FMI were significantly different among the age groups in students with disabilities (P = 0.006, P = 0.0001, and P = 0.001, respectively). Younger children had significantly greater proportions of under range in BMI, PBF, and FMI. CONCLUSIONS: Disability significantly affects FFMI, which represents muscle mass. Therefore, it is crucial to make efforts to increase physical activity and to improve nutrition in rehabilitative intervention strategies.

Effects of Age on Long-Term Functional Recovery in Patients with Stroke.

Background and objectives: Age might be a determinant that limits functional recovery in patients with stroke. Here, we investigated the effect of age on functional recovery within 30 months after stroke onset. Materials and Methods: This retrospective longitudinal study enrolled 111 patients with first-ever stroke. Functional recovery was assessed at 2 weeks and at 1, 6, and 30 months after stroke onset using the modified Barthel Index (MBI), modified Rankin Score (mRS), functional ambulation category (FAC), muscle strength, and Mini-Mental State Examination (MMSE). A generalized estimating equation analysis was performed. Results: With the MBI, function improved until 6 months after stroke onset in patients aged <70 years and until 1 month after stroke onset in patients ≥70 years. At 30 months after stroke, there was no significant change of MBI in patients aged <70 years, whereas there was a significant decline in older patients. With the mRS and FAC, function improved until 30 months after stroke onset in patients aged <70 years and until 1 month after stroke onset in older patients. Motor deficit, assessed using the Medical Research Council (MRC), improved significantly until 6 months after stroke onset in patients aged <70 years. There was a significant improvement in cognition (assessed using the MMSE) until 6 months after stroke onset in patients aged <70 years and until 1 month after stroke onset in older patients. Conclusions: Long-term functional recovery occurred for up to 30 months after stroke. Patients aged ≥70 years showed functional decline between 6 and 30 months after onset. These findings could be useful when measuring functional recovery after stroke.

Degeneration of the Inferior Cerebellar Peduncle After Middle Cerebral Artery Stroke: Another Perspective on Crossed Cerebellar Diaschisis.

Background and Purpose- Deafferentation of the cortico-ponto-cerebellar pathway has been proposed as a key mechanism of crossed cerebellar diaschisis. Although the cerebellum receives afferent stimuli from both cortico-ponto-cerebellar and spinocerebellar pathways, evidence on whether spinocerebellar deafferentation contributes to a hypofunctional cerebellum is lacking. Therefore, we aimed to determine whether changes in the spinocerebellar pathway occur after middle cerebral artery stroke. Methods- Twenty-three patients admitted to our inpatient rehabilitation facility and 23 age-matched healthy controls were retrospectively enrolled. Patients' functional ambulation category was determined and the Medical Research Council muscle scale test of the lower limb muscles was performed at admission and discharge. The fractional anisotropy (FA) values of the corticospinal tract and the inferior cerebellar peduncle (ICP), as the final route of the dorsal spinocerebellar pathway, were compared between the groups. The FA laterality indices of the ICP and corticospinal tract were calculated as follows: (FAaffected-FAunaffected)/(FAaffected+FAunaffected). Pearson correlation analysis and multivariate linear regression models were used to determine the associations between the FA laterality indices and ambulatory function. Results- The FAs of the corticospinal tract and ICP were lower in the patient group than in the control group. The FA laterality index of the corticospinal tract was not correlated with the functional ambulation category or Medical Research Council muscle scale score at admission or discharge. The FA laterality index of the ICP at the pontomedullary junction was positively correlated with the functional ambulation category and Medical Research Council muscle scale scores of all hemiplegic lower limb muscles at admission and discharge. The FA laterality index of the ICP at the pontomedullary junction was independently associated with the functional ambulation category according to the multivariate regression models. Conclusions- ICP degeneration occurs in the subacute and early chronic phase of middle cerebral artery stroke. The lower FA laterality index of the ICP was indicative of poorer ambulatory and lower limb function.

The lung microbiome, vitamin D, and the tuberculous granuloma: A balance triangle.

Mycobacterium tuberculosis (Mtb) has the extraordinary ability to persist for decades within granulomas in the human host. These histopathological structures involved in both protection and pathogenesis, are subject to various influences from the host systemically and through micro-niche environments. Despite the fact that vitamin D (VD) has a key role in macrophage activation and mycobacterial clearance in the early stages of Mtb infection, the overall role of VD in granuloma maintenance or functionality has been scarcely studied. VD deficiency has long time been known to influence on gut microbiota composition, and recent studies have shown that it can also impact on respiratory microbiome. The human microbiota plays an important role in pathogen colonization resistance, and it has been proposed to play a potential role in TB pathogenesis. In this article, we have reviewed current knowledge on the interaction between VD, the lung microbiome and TB, and propose mechanisms by which the tuberculous granuloma's outcome could be modulated by these two factors. The determinants of the final fate of lung granulomas are still unclear, and deciphering the underlying drivers of Mtb infection outcome within those structures is of critical importance.

The effect of white matter integrity on functional outcome in central pontine demyelination.

[Purpose] Central pontine demyelination is a common osmotic demyelination syndrome. Typically, central pontine demyelination shows high signal intensity with demyelination in the mid-pons. Despite severe imaging findings, patients usually recover. This study investigated the integrity of the corticospinal tract (CST) and corticoreticular pathway (CRP) in patients at 12 months after the onset of central pontine demyelination. [Participants and Methods] This retrospective cross-sectional observational study assessed two patients with central pontine demyelination, who were ultimately able to walk without using an aid or orthosis and to use both hands but with mild residual symptoms. All participants underwent diffusion tensor imaging (DTI) at 12 months after onset. [Results] Both patients had mild ataxia at 12 months after onset. The integrity of the CST was restored in both cases, while the integrity of the CRP recovered partially. [Conclusion] The integrity of the CST and CRP at 12 months after the onset of central pontine demyelination was similar in both cases as well as the recovery status of the hand function and ambulation. These results may be useful in planning therapy for patients with central pontine demyelination.

Modification of Cerebellar Afferent Pathway in the Subacute Phase of Stroke.

BACKGROUND: This study aims to identify the relationship between corticopontocerebellar tract (CPCT) and corticospinal tract (CST) integrity as well as motor function after stroke. MATERIALS AND METHODS: A total of 33 patients with stroke (18 left, 15 right hemispheric lesions) who underwent diffusion tensor imaging within 2 months of stroke onset and 17 age- and sex-matched healthy controls were retrospectively enrolled. Tract volume and the asymmetry index based on tract volume (AITV) of the CST and CPCT were used to identify structural changes in individual tracts and the correlation between those tracts. Motor function was assessed using the Medical Research Council (MRC) muscle scale, manual function test (MFT), functional ambulation category, and modified Barthel index. RESULTS: The volume of the affected CPCT was lower, and that of the unaffected CPCT was higher than the volumes in the control group (P < .001, P = .001, respectively). The CPCT AITV showed a strong positive correlation with the CST AITV in patients with either left or right hemispheric lesions (rs = .779, P < .001; rs = .732, P = .003, respectively). The CPCT AITV negatively correlated with the MRC muscle scale of the shoulder, wrist, and ankle muscles (r = -.490, -.490, -.416; P = .004, .004, .016, respectively). A higher unaffected CPCT volume was indicative of less affected upper extremity function, as assessed by MFT (rs = -.546, P = .029). CONCLUSIONS: Modification of the CPCT depended on CST integrity and was associated with the severity of hemiplegia and hemiplegic upper extremity function. The CPCT may complement the role of the CST and help to predict the motor function.

Microbiome Changes during Tuberculosis and Antituberculous Therapy.

The critical role of commensal microbiota in the human body has been increasingly recognized, and our understanding of its implications in human health and disease has expanded rapidly. The lower respiratory tract contains diverse communities of microbes known as lung microbiota, which are present in healthy individuals and in individuals with respiratory diseases. The dysbiosis of the airway microbiota in pulmonary tuberculosis (TB) may play a role in the pathophysiological processes associated with TB disease. Recent studies of the lung microbiome have pointed out changes in lung microbial communities associated with TB and other lung diseases and have also begun to elucidate the profound effects that antituberculous drug therapy can have on the human lung microbiome composition. In this review, the potential role of the human microbiome in TB pathogenesis and the changes in the human microbiome with Mycobacterium tuberculosis infection and TB therapy are presented and discussed.

Factors Influencing the Gross Motor Outcome of Intensive Therapy in Children with Cerebral Palsy and Developmental Delay.

The study was designed to identify factors influencing the short term effect of intensive therapy on gross motor function in children with cerebral palsy or developmental delay. Retrospectively, total Gross Motor Function Measure-88 (GMFM-88) scores measured during the first and last weeks of intensive therapy were analyzed (n = 103). Good and poor responder groups were defined as those in the top and bottom 25% in terms of score difference, respectively. The GMFM-88 score increased to 4.67 ± 3.93 after 8 weeks of intensive therapy (P < 0.001). Gross Motor Function Classification System (GMFCS) level (I-II vs. IV-V; odds ratio [OR] = 7.763, 95% confidence interval [CI] = 2.177-27.682, P = 0.002) was a significant factor in a good response to therapy. Age (≥ 36 months; OR = 2.737, 95% CI = 1.003-7.471, P = 0.049) and GMFCS level (I-II vs. IV-V; OR = 0.189, 95% CI = 0.057-0.630, P = 0.007; and III vs. IV-V; OR = 0.095, 95% CI = 0.011-0.785, P = 0.029) were significantly associated with a poor response. GMFCS level is the most important prognostic factor for the effect of intensive therapy on gross motor function. In addition, age ≥ 36 months, is associated with a poor outcome.

The efficacy of 308-nm excimer laser/light (EL) and topical agent combination therapy versus EL monotherapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials (RCTs).

BACKGROUND: Combination therapies of excimer laser/light (EL) and various topical agents are widely used in the treatment of vitiligo. OBJECTIVE: We sought to compare the efficacy of EL and topical agent combination therapy versus EL monotherapy for vitiligo. METHODS: Manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, and Cochrane library (from inception through December 15, 2014) were conducted to identify randomized controlled trials that assessed the efficacy of EL alone or in combination with topical agents for vitiligo. The primary outcome was treatment success (≥75% repigmentation), and the secondary outcome was treatment failure (<25% repigmentation); meta-analyses were performed when possible. RESULTS: We analyzed 8 randomized controlled trials comprising a total of 425 patches/patients. The combination of EL and topical calcineurin inhibitors (4 studies: relative risk 1.93, 95% confidence interval 1.28-2.91; number needed to treat 4.5, 95% confidence interval 2.9-10) was superior to EL monotherapy for vitiligo. There was insufficient evidence to support beneficial effects of topical vitamin-D3 analogs (3 studies) and corticosteroids (1 study). LIMITATIONS: These findings are based on small numbers of randomized controlled trials and heterogeneities among included studies are another limitation. CONCLUSION: Topical calcineurin inhibitors in conjunction with EL are more effective compared with EL monotherapy.