Time-Restricted Eating and Bone Health: A Systematic Review with Meta-Analysis.

Time-restricted eating (TRE) has emerged as a dietary strategy that restricts food consumption to a specific time window and is commonly applied to facilitate weight loss. The benefits of TRE on adipose tissue have been evidenced in human trials and animal models; however, its impact on bone tissue remains unclear. To systematically synthesize and examine the evidence on the impact of TRE on bone health (bone mineral content (BMC), bone mineral density (BMD), and bone turnover factors), PubMed, Scopus, Cochrane CENTRAL, and Web of Science databases were systematically explored from inception to 1 October 2023 searching for randomized controlled trials (RCTs) aimed at determining the effects of TRE on bone health in adults (≥18 years). The Cochrane Handbook and the PRISMA recommendations were followed. A total of seven RCTs involving 313 participants (19 to 68 years) were included, with an average length of 10.5 weeks (range: 4 to 24 weeks). Despite the significant weight loss reported in five out of seven studies when compared to the control, our meta-analysis showed no significant difference in BMD (g/cm2) between groups (MD = -0.009, 95% CI: -0.026 to 0.009, p = 0.328; I2 = 0%). BMC and bone turnover markers between TRE interventions and control conditions were not meta-analyzed because of scarcity of studies (less than five). Despite its short-term benefits on cardiometabolic health, TRE did not show detrimental effects on bone health outcomes compared to those in the control group. Nevertheless, caution should be taken when interpreting our results due to the scarcity of RCTs adequately powered to assess changes in bone outcomes.

Effects of physical exercise interventions on balance, postural stability and general mobility in Parkinson's disease: a network meta-analysis.

OBJECTIVE: To assess which type of physical exercise intervention has the most beneficial effects on balance, postural stability and general mobility in patients with Parkinson's disease. These parameters were assessed using the Activities-specific Balance Confidence (ABC) scale, Berg Balance Scale (BBS), Mini-Balance Evaluation Systems Test (MiniBESTest) and Timed Up and Go Test (TUG). DESIGN: Network meta-analysis. METHODS: The PubMed, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched up to August 2022 to identify randomized controlled trials on the effects of physical exercise interventions on balance, postural stability, and general mobility. The network meta-analysis included pairwise and indirect comparisons of results on the ABC scale, BBS, MiniBESTest, and TUG across 8 categories of physical exercise. RESULTS: Eighty-six studies with a total of 4,693 patients were included. For the ABC scale, the indirect comparison showed that the highest effect size was observed for balance vs sensorimotor training without including endurance interventions (0.62; 95% confidence interval (95% CI) 0.06, 1.17). The highest effect sizes for BBS were observed for alternative exercises (1.21; 95% CI 0.62, 1.81), body-weight supported (BWS) interventions (1.31; 95% CI 0.57, 2.05), dance (1.18; 95% CI 0.33, 2.03) and sensorimotor training, including endurance interventions (1.10; 95% CI 0.46, 1.75) vs control groups. Indirect comparisons showed that the highest effect size for the MiniBESTest were observed for balance (0.75; 95% CI 0.46, 1.04) and resistance (0.58; 95% CI 0.10, 1.07) vs control groups. For the TUG, comparisons showed a significant effect size for alternative exercises (-0.54; 95% CI -0.82, -0.26), balance (-0.42; 95% CI -0.75, -0.08), resistance (-0.60; 95% CI -0.89, -0.31), and sensorimotor training including endurance interventions (-0.61; 95% CI -0.95, -0.27) vs control comparisons. CONCLUSION: Balance interventions improve balance, postural stability, and general mobility in people with Parkinson's disease. Moreover, alternative exercises, dance, BWS interventions, resistance, and sensorimotor training, including and not including endurance interventions, are also effective.

Effectiveness of high-intensity interval training on peripheral brain-derived neurotrophic factor in adults: A systematic review and network meta-analysis.

BACKGROUND: High-intensity interval training (HIIT) has emerged as an alternative training method to increase brain-derived neurotrophic factor (BDNF) levels, a crucial molecule involved in plastic brain changes. Its effect compared to moderate-intensity continuous training (MICT) is controversial. We aimed to estimate, and to comparatively evaluate, the acute and chronic effects on peripheral BDNF levels after a HIIT, MICT intervention or a control condition in adults. METHODS: The CINAHL, Cochrane, PubMed, PEDro, Scopus, SPORTDiscus, and Web of Science databases were searched for randomized controlled trials (RCTs) from inception to June 30, 2023. A network meta-analysis was performed to assess the acute and chronic effects of HIIT versus control condition, HIIT versus MICT and MICT versus control condition on BDNF levels. Pooled standardized mean differences (SMDs) and their 95% confidence intervals (95% CIs) were calculated for RCTs using a random-effects model. RESULTS: A total of 22 RCTs were selected for the systematic review, with 656 participants (aged 20.4-79 years, 34.0% females) and 20 were selected for the network meta-analysis. Network SMD estimates were significant for HIIT versus control condition (1.49, 95% CI: 0.61, 2.38) and MICT versus control condition (1.08, 95% CI: 0.04, 2.12) for acutely BDNF increase. However, pairwise comparisons only resulted in a significant effect for HIIT versus control condition. CONCLUSIONS: HIIT is the best training modality for acutely increasing peripheral BDNF levels in adults. HIIT may effectively increase BDNF levels in the long term.

Effect of Vitamin D Supplementation on Fatigue in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre-post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4-41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: -0.18 (95% CI: -0.36 to -0.01; I2 = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.

Effect of different types of exercise on fitness in people with multiple sclerosis: A network meta-analysis.

BACKGROUND: It is assumed that people with multiple sclerosis (MS) who participate in programs of physical exercise improve their physical fitness. OBJECTIVE: The aim of this network meta-analysis (NMA) was to analyze the effect of different types of exercise on muscular fitness and cardiorespiratory fitness (CRF) among people with MS and to determine the best type of exercise according to disease severity. METHODS: MEDLINE, the Physiotherapy Evidence Database, the Cochrane Library, SPORTDiscus, Scopus, and Web of Science were searched from inception to April 2022 to identify randomized controlled trials (RCTs) concerning the effect of physical exercise on fitness in people with MS. We ranked the types of physical exercise by calculating the surface under the cumulative ranking (SUCRA). RESULTS: We included 72 RCTs involving 2543 MS patients in this NMA. A ranking of five types of physical exercise (aerobic, resistance, combined [aerobic and resistance], sensorimotor training, and mind-body exercises) was achieved. Combined and resistance training had the highest effect sizes (0.94, 95% CI 0.47, 1.41, and 0.93, 95% CI 0.57, 1.29, respectively) and the highest SUCRA (86.2% and 87.0%, respectively) for muscular fitness. The highest effect size (0.66, 95% CI 0.34, 0.99) and SUCRA (86.9%) for CRF was for aerobic exercise. CONCLUSIONS: Combined and resistance training seem to be the most effective exercises to improve muscular fitness and aerobic exercise for CRF in people with MS.

Effect of Process Parameters and Postprocessing on Mechanical Properties of Additive Manufacturing Polylactic Acid Obtained by Fused Deposition Modeling.

The aim of this article is to study the influence of some printing parameters and postprocessing on mechanical properties of polylactic acid samples manufactured by fused deposition modeling with a 3D printer. The effects of different building orientations, concentric infill, and postprocessing by annealing were analyzed. In this sense, uniaxial tensile and three-point bending tests were performed to determine the ultimate strength, modulus of elasticity, and elongation at break. Among all printing parameters of interest, the print orientation can be considered one of the most important, being fundamental in the mechanical behavior. Once samples were fabricated, annealing processes were also considered, close to the T g, in order to study the effects on mechanical properties. In the modified print orientation, the average values for the E and the σ TS are 3337.15-3337.92 and 36.42-37.62 MPa, compared with default printing with the E and the σ TS that are 2541.63-2692.34 and 28.81-28.89 MPa, respectively. In the annealed samples, the values for the Ef and the σf are 2337.73 and 63.96 MPa, compared with the reference samples with the Ef and the σf values of 2164.40 and 59.66 MPa, respectively. Hence, the print orientation and postprocessing must be taken into account as important factors for the final properties of the desired product.

Physical Exercise Interventions on Quality of Life in Parkinson Disease: A Network Meta-analysis.

BACKGROUND AND PURPOSE: Physical exercise is considered an effective intervention for maintaining or improving quality of life (QoL) in patients with Parkinson disease (PD), but there is no evidence showing which type of physical exercise intervention has more positive effects. This systematic review and meta-analysis aimed to synthesize the evidence regarding the effectiveness of exercise interventions on improving QoL in patients with PD, comparing different types of exercise interventions. METHODS: A literature search was conducted through January 2022. The methodological quality of the trials was assessed using the Cochrane risk of bias tool RoB2. For the meta-analysis, physical exercise interventions were classified into 5 training categories: resistance, endurance, alternative exercises, dance, and sensorimotor interventions. A standard meta-analysis and network meta-analysis were carried out to evaluate the efficacy of the different types of physical exercise interventions. RESULTS: The search retrieved 2451 studies, 48 of which were included in this network meta-analysis with a total of 2977 patients with PD. The indirect effects of the network meta-analysis showed positive results for alternative exercises (-0.46; 95% confidence interval [CI]: -0.76, -0.16), dance (-0.63; 95% CI: -1.08, -0.17), and sensorimotor interventions (-0.23; 95% CI: -0.40, -0.07) versus control comparisons. DISCUSSION AND CONCLUSIONS: More research is needed to determine the types of physical exercise interventions that are most beneficial and for which conditions of the disease they have the most positive effects.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A398 ).

Inhibition of Nogo-A rescues synaptic plasticity and associativity in APP/PS1 animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive decline. Synaptic impairment is one of the first events to occur in the progression of this disease. Synaptic plasticity and cellular association of various plastic events have been shown to be affected in AD models. Nogo-A, a well-known axonal growth inhibitor with a recently discovered role as a plasticity suppressor, and its main receptor Nogo-66 receptor 1 (NGR1) have been found to be overexpressed in the hippocampus of Alzheimer's patients. However, the role of Nogo-A and its receptor in the pathology of AD is still widely unknown. In this work we set out to investigate whether Nogo-A is working as a plasticity suppressor in AD. Our results show that inhibition of the Nogo-A pathway via the Nogo-R antibody in an Alzheimer's mouse model, APP/PS1, leads to the restoration of both synaptic plasticity and associativity in a protein synthesis and NMDR-dependent manner. We also show that inhibition of the p75NTR pathway, which is strongly associated with NGR1, restores synaptic plasticity as well. Mechanistically, we propose that the restoration of synaptic plasticity in APP/PS1 via inhibition of the Nogo-A pathway is due to the modulation of the RhoA-ROCK2 pathway and increase in plasticity related proteins. Our study identifies Nogo-A as a plasticity suppressor in AD models hence targeting Nogo-A could be a promising strategy to understanding AD pathology.

Comparative Effectiveness of Manual Therapy Interventions on Pain and Pressure Pain Threshold in Patients With Myofascial Trigger Points: A Network Meta-analysis.

OBJECTIVES: Myofascial trigger points (MTPs) are one of the most important causes of musculoskeletal pain. Evidence has suggested a positive effect of manual therapy in the treatment of MTPs. However, a comprehensive review comparing the effect of different manual therapy techniques are lacking. Thus, we conducted a network meta-analysis of randomized controlled trials to determine the type of manual therapy technique that has the greatest positive influence in patients with MTPs. MATERIALS AND METHODS: PubMed, Web of Science, Cochrane Library, and Scopus databases were searched to identify direct and indirect evidence comparing the effectiveness of different types of manual therapy interventions on pain intensity and pressure pain threshold (PPT) in patients with MTPs. Risk of bias was assessed using the Cochrane RoB2 tool. A pairwise meta-analysis for direct and indirect comparisons between intervention and control/nonintervention groups was carried out. RESULTS: A total of 37 studies were eligible for analysis. Combined interventions had the highest effect size for pain (-1.40; 95% CI, -2.34, -0.47), and the highest probability to be the best intervention and the highest Surface Under the Cumulative Ranking (64.7% and 87.9%, respectively). Afferent reduction techniques, understood as the interventions aimed to restore muscle spindles helping to dictate sarcomere length and tone in MTPs, had the highest effect size for PPT (0.93; 95% CI, 0.47, 1.39), and the highest probability to be the best intervention and the highest Surface Under the Cumulative Ranking (34.7% and 71.2%, respectively). The results were consistent in sensitivity analyses, with minimal inconsistencies between direct and indirect results. DISCUSSION: Manual therapy interventions should be considered an effective strategy for pain and PPT in patients with MTPs. The results suggest that among the different manual therapy modalities, combined and afferent reduction techniques are the most effective for pain and PPT, respectively.

Efficacy of Different Types of Physical Activity Interventions on Exercise Capacity in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Network Meta-Analysis.

AIM: A network meta-analysis (NMA) was performed to determine the effects on the exercise capacity, measured by the 6 MWT, of patients with COPD of (i) different physical activity interventions and (ii) supervised or unsupervised programs. METHODS: A literature search was carried out from inception to April 2022. Randomized controlled trials of the effectiveness of physical activity on exercise capacity in patients with COPD were included. The risk of bias was assessed using the Cochrane Risk of Bias (RoB 2.0) tool, and the Grading of Recommendations, Assessment, Development, and Evaluation tool (GRADE) was used to assess the quality of the evidence. A pairwise meta-analysis for direct and indirect effects was carried out. RESULTS: A total of 41 studies were included in this NMA. The highest effects were for urban training pulmonary rehabilitation (PR) programs (ES, 1.50; 95% CI: 0.46 and 2.55) versus the control group. For supervised and unsupervised PR and home-based PR programs, the highest effects were found for supervised PR (ES, 0.85; 95% CI: 0.46 to 1.23) versus the control group. CONCLUSIONS: PR implemented with urban circuit training should be considered the most effective strategy to improve exercise capacity in patients with COPD. Supervision of the programs improves exercise capacity.

Glucose derived carbon nanosphere (CSP) conjugated TTK21, an activator of the histone acetyltransferases CBP/p300, ameliorates amyloid-beta 1-42 induced deficits in plasticity and associativity in hippocampal CA1 pyramidal neurons.

The master epigenetic regulator lysine acetyltransferase (KAT) p300/CBP plays a pivotal role in neuroplasticity and cognitive functions. Recent evidence has shown that in several neurodegenerative diseases, including Alzheimer's disease (AD), the expression level and function of p300/CBP are severely compromised, leading to altered gene expression causing pathological conditions. Here, we show that p300/CBP activation by a small-molecule TTK21, conjugated to carbon nanosphere (CSP) ameliorates Aß-impaired long-term potentiation (LTP) induced by high-frequency stimulation, theta burst stimulation, and synaptic tagging/capture (STC). This functional rescue was correlated with CSP-TTK21-induced changes in transcription and translation. Mechanistically, we observed that the expression of a large number of synaptic plasticity- and memory-related genes was rescued, presumably by the restoration of p300/CBP mediated acetylation. Collectively, these results suggest that small-molecule activators of p300/CBP could be a potential therapeutic molecule for neurodegenerative diseases like AD.

Accuracy of the Most Common Provocation Tests for Diagnosing Carpal Tunnel Syndrome: A Systematic Review With Meta-analysis.

OBJECTIVE: To estimate the screening performances of the most important provocation tests for diagnosing carpal tunnel syndrome (CTS). DESIGN: Diagnostic test accuracy systematic review with meta-analysis. LITERATURE SEARCH: We systematically searched the MEDLINE, Scopus, Web of Science, and Cochrane databases from inception to November 2020. STUDY SELECTION CRITERIA: Observational studies comparing the accuracies of the Durkan test (DT), the hand elevation test (HET), the Phalen test (PT), the Tinel test (TT), and the upper-limb neurodynamic test specific to the median nerve (ULNT1) with electrodiagnosis for screening for CTS. DATA SYNTHESIS: Random-effects models for the diagnostic odds ratio (dOR) values computed by Moses' constant for a linear model and 95% confidence intervals (CIs) were used to calculate the accuracy of these tests. Hierarchical summary receiver operating characteristic curve analyses were used to summarize the overall test performance. RESULTS: Thirty-seven studies were included in the meta-analysis, with a total sample of 2662 wrists for DT, 864 wrists for HET, 6361 wrists for PT, 6094 wrists for TT, and 571 wrists for ULNT1. The pooled dORs for screening for CTS were 15.84 (95% CI: 3.78, 66.38) for DT, 128.63 (95% CI: 40.64, 407.12) for HET, 7.23 (95% CI: 4.06, 12.86) for PT, 5.31 (95% CI: 3.49, 8.09) for TT, and 1.78 (95% CI: 0.61, 5.19) for ULNT1. CONCLUSION: HET has the best clinical performance for detecting CTS and should be considered the first screening test of choice during the physical examination. The most common tests (DT, PT, and TT) have good accuracies for screening for CTS. J Orthop Sports Phys Ther 2022;52(8):522-531. Epub: 19 June 2022. doi:10.2519/jospt.2022.10828.

The type of exercise most beneficial for quality of life in people with multiple sclerosis: A network meta-analysis.

BACKGROUND: There is overwhelming evidence regarding the beneficial effects of exercise on the management of symptoms, functionality and health-related quality of life (HRQoL) of people with multiple sclerosis (MS). However, few analyze have compared different types of exercise. OBJECTIVE: The aim of this network meta-analysis (NMA) was to assess which type of physical exercise has the greatest positive effect on HRQoL in people with MS. METHODS: MEDLINE, Cochrane Library, Embase, Web of Science, Physiotherapy Evidence Database and SPORTDiscus databases were searched from inception to June 2021 to identify randomized controlled trials (RCTs) examining the effect of physical exercise on HRQoL in people with MS. The NMA included pairwise and indirect comparisons. We ranked the effect of interventions calculating the surface under the cumulative ranking (SUCRA). RESULTS: We included 45 RCTs in this NMA (2428 participants; 76% women; mean age 45 years). Five types of physical exercises were ranked. Sensorimotor training had the highest effect size (0.87, 95% confidence interval [CI] 0.60; 1.15) and the highest SUCRA (87%) for total HRQoL. The highest effect size and SUCRA for physical and mental HRQoL were for aerobic exercise (0.85, 95% CI 0.28; 1.42) (89%) and mind-body exercises (0.54, 95% CI 0.03; 1.06) (89%). Sensorimotor training was the best exercise for mild disease and aerobic exercise for severe disease for total HRQoL. CONCLUSIONS: Sensorimotor training seems the most effective exercise to improve HRQoL and aerobic and mind-body exercises to improve physical and mental HRQoL, respectively.

Effect of Manual Therapy Interventions on Range of Motion Among Individuals with Myofascial Trigger Points: A Systematic Review and Meta-Analysis.

OBJECTIVE: Patients with myofascial trigger points (MTPs) frequently manifest restricted range of motion (ROM) during physical evaluation. Multiple manual therapy interventions have been developed for the treatment of MTPs, but their effect on ROM has not been clarified through a systematic review and meta-analysis. Thus, this systematic review aimed to assess the effect of manual therapy interventions on ROM among individuals with MTPs. METHODS: A systematic search was conducted in PubMed, Web of Science, Cochrane, Scopus, and Clinical Trials.gov. Articles analyzing the effect of manual therapy interventions on ROM were included. The risk of bias was assessed with the Cochrane Risk of Bias (RoB) 2 tool. The DerSimonian-Laird method was used to compute the pooled effect size (ES) and its 95% confidence interval (95% CI) for ROM. RESULTS: A total of 13 randomized controlled trials were included in this systematic review and meta-analysis. The pooled ES for ROM was 0.52 (95% CI: 0.42-0.63). The pooled ES for ROM evaluated in centimeters was 0.36 (95% CI: 0.14-0.59), and the pooled ES for ROM evaluated in degrees was 0.57 (95% CI: 0.47-0.68). CONCLUSION: Manual therapy interventions may be an effective approach for improving ROM among individuals with MTPs.

What emotions do physical therapy students feel during their first visit to the dissection room?

Dissections are a fundamental practical methodology for teaching human anatomy. However, this experience can be stressful, generating anxiety situations among students. This study tries to understand the attitudes, reactions, fears and anxiety state among students earning a physiotherapy degree when facing their first prosection. A cross-sectional before-and-after study was carried out with students who were provided with an anonymous "ad hoc" questionnaire and the State-Trait Anxiety Inventory (STAI).The values obtained from the total STAI questionnaire remained stable and unchanged during the prosection (p>0.05). The levels of trait anxiety (TA) and state anxiety (SA) remained stable except in female students, who showed higher TA and SA scores, with a significance of p<0.05 before and after the prosection. Although 100% of the students were satisfied with the dissection practices, the experience can provoke stressful responses and should be addressed using coping mechanisms, especially among female students.

Effect of Exercise on Fatigue in Multiple Sclerosis: A Network Meta-analysis Comparing Different Types of Exercise.

OBJECTIVE: A network meta-analysis (NMA) of current evidence was conducted to determine if physical exercise has a positive influence on multiple sclerosis (MS) fatigue and type of exercise with the largest effect on fatigue also according to disease severity. DATA SOURCES: MEDLINE, Embase, SPORTDiscus, Physiotherapy Evidence Database, Cochrane Library, and Web of Science. The search strategy combined relevant terms related to (1) MS; (2) clinical trials; (3) exercise; and (4) fatigue from inception to February 2021. STUDY SELECTION: Randomized controlled trials concerning the effectiveness of different types of exercise on total and physical fatigue in people with MS were included. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated with the Cochrane Risk of Bias tool (RoB 2.0), and the Grading of Recommendations, Assessment, Development, and Evaluation tool was used to evaluate the quality of the evidence. DATA SYNTHESIS: A total of 58 studies were examined. Data were pooled using a random-effects model. A ranking of 7 and 8 different exercise interventions for physical and total fatigue scores, respectively, was achieved. The highest effects for pairwise comparisons were for combined exercise and resistance training vs control (ranging between -0.74 and -1.24). In the NMA, combined exercise (-1.51; 95% confidence interval [CI], -2.01 to -1.01) and resistance training (-1.15; 95% CI, -1.81 to -0.49) compared with the control group achieved the highest effects for physical and total fatigue, respectively. CONCLUSIONS: Exercise should be considered an effective fatigue management strategy. Among the different exercise modalities, combined exercise is the most effective exercise modality for improving both physical and total fatigue. Resistance training is also an effective exercise for total fatigue among people diagnosed with MS.

Sex-specific accelerated decay in time/activity-dependent plasticity and associative memory in an animal model of Alzheimer's disease.

Clinical studies have shown that female brains are more predisposed to neurodegenerative diseases such as Alzheimer's disease (AD), but the cellular and molecular mechanisms behind this disparity remain unknown. In several mouse models of AD, synaptic plasticity dysfunction is an early event and appears before significant accumulation of amyloid plaques and neuronal degeneration. However, it is unclear whether sexual dimorphism at the synaptic level contributes to the higher risk and prevalence of AD in females. Our studies on APP/PS1 (APPSwe/PS1dE9) mouse model show that AD impacts hippocampal long-term plasticity in a sex-specific manner. Long-term potentiation (LTP) induced by strong tetanic stimulation (STET), theta burst stimulation (TBS) and population spike timing-dependent plasticity (pSTDP) show a faster decay in AD females compared with age-matched AD males. In addition, behavioural tagging (BT), a model of associative memory, is specifically impaired in AD females with a faster decay in memory compared with males. Together with the plasticity and behavioural data, we also observed an upregulation of neuroinflammatory markers, along with downregulation of transcripts that regulate cellular processes associated with synaptic plasticity and memory in females. Immunohistochemistry of AD brains confirms that female APP/PS1 mice carry a higher amyloid plaque burden and have enhanced microglial activation compared with male APP/PS1 mice. Their presence in the diseased mice also suggests a link between the impairment of LTP and the upregulation of the inflammatory response. Overall, our data show that synaptic plasticity and associative memory impairments are more prominent in females and this might account for the faster progression of AD in females.

Selective estrogen receptor modulators (SERMs) affect cholesterol homeostasis through the master regulators SREBP and LXR.

Selective estrogen receptor modulators (SERMs) are nonsteroidal drugs that display an estrogen-agonist or estrogen-antagonist effect depending on the tissue targeted. SERMs have attracted great clinical interest for the treatment of several pathologies, most notably breast cancer and osteoporosis. There is strong evidence that SERMs secondarily affect cholesterol metabolism, although the mechanism has not been fully elucidated. In this study, we analysed the effect of the SERMs tamoxifen, raloxifene, and toremifene on the expression of lipid metabolism genes by microarrays and quantitative PCR in different cell types, and ascertained the main mechanisms involved. The three SERMs increased the expression of sterol regulatory element-binding protein (SREBP) target genes, especially those targeted by SREBP-2. In consonance, SERMs increased SREBP-2 processing. These effects were associated to the interference with intracellular LDL-derived cholesterol trafficking. When the cells were exposed to LDL, but not to cholesterol/methyl-cyclodextrin complexes, the SERM-induced increases in gene expression were synergistic with those induced by lovastatin. Furthermore, the SERMs reduced the stimulation of the transcriptional activity of the liver X receptor (LXR) by exogenous cholesterol. However, their impact on the expression of the LXR canonical target ABCA1 in the presence of LDL was cell-type dependent. These actions of SERMs were independent of estrogen receptors. We conclude that, by inhibiting the intracellular trafficking of LDL-derived cholesterol, SERMs promote the activation of SREBP-2 and prevent the activation of LXR, two master regulators of cellular cholesterol metabolism. This study highlights the impact of SERMs on lipid homeostasis regulation beyond their actions as estrogen receptor modulators.

Body Weight Support Gait Training for Patients With Parkinson Disease: A Systematic Review and Meta-analyses.

OBJECTIVE: To determine the effectiveness of body weight support (BWS) gait training to improve the clinical severity, gait, and balance in patients with Parkinson disease (PD). DATA SOURCES: A literature search was conducted until July 2020 in MEDLINE, Physiotherapy Evidence Database, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. STUDY SELECTION: Randomized controlled trials that aimed at determining the effectiveness of physical activity interventions with BWS during gait training in patients with PD. DATA EXTRACTION: The methodological quality of randomized controlled trials was assessed using the Cochrane risk of bias tool (RoB 2.0). Effect size (ES) and 95% confidence intervals [CIs] were calculated for the Unified Parkinson Disease Rating Scale (UPDRS), the UPDRS section III, the 6-minute walk test (6MWT), gait parameters (ie, velocity, cadence, stride length), and the Berg Balance Scale (BBS). DATA SYNTHESIS: Twelve studies were included in the systematic review. The pooled ES for the effect of BWS on total UPDRS was -0.35 (95% CI, -0.57 to -0.12; I2=1.9%, P=.418), whereas for UPDRS III it was -0.35 (95% CI, -0.68 to -0.01; I2=66.4 %, P<.001). Furthermore, the pooled ES for 6MWT was 0.56 (95% CI, -0.07 to 1.18; I2=77.1%, P=.002), for gait velocity was 0.37 (95% CI, -0.10 to 0.84); I2=78.9%, P<.001), for cadence was 0.03 (95% CI, -0.25 to 0.30; I2=0.0%, P=.930), for stride length was 1.00 (95% CI, 0.23 to 1.78; I2=79.5%, P=.001), and for BBS was 0.65 (95% CI, 0.30, 0.99; I2=51.8%, P=.042). CONCLUSIONS: Interventions with BWS could improve the general and motor clinical severity of patients with PD, as well as other parameters such as stride length and balance. However, the effect does not appear to be statistically significant in improving gait parameters such as velocity, cadence, and distance.

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services.

BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.