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Journal of the American Society For... Jun 2024Data-independent acquisition (DIA) at the shortened data acquisition time is becoming a method of choice for quantitative proteomic applications requiring high...
Data-independent acquisition (DIA) at the shortened data acquisition time is becoming a method of choice for quantitative proteomic applications requiring high throughput analysis of large cohorts of samples. With the advent of the combination of high resolution mass spectrometry with an asymmetric track lossless analyzer, these DIA capabilities were further extended with the recent demonstration of quantitative analyses at the speed of up to hundreds of samples per day. In particular, the proteomic data for the brain samples related to multiple system atrophy disease were acquired using 7 and 28 min chromatography gradients (Guzman et al., ). In this work, we applied the recently introduced DirectMS1 method to reanalysis of these data using only MS1 spectra. Both DirectMS1 and DIA results were matched against long gradient DDA analysis from the earlier study of the same sample cohort. While the quantitation efficiency of DirectMS1 was comparable with DIA on the same data sets, we found an additional five proteins of biological significance relevant to the analyzed tissue samples. Among the findings, DirectMS1 was able to detect decreased caspase activity for Vimentin protein in the multiple system atrophy samples missed by the MS/MS-based quantitation methods. Our study suggests that DirectMS1 can be an efficient MS1-only addition to the analysis of DIA data in high-throughput quantitative proteomic studies.
PubMed: 38938158
DOI: 10.1021/jasms.4c00134 -
Molecular Genetics & Genomic Medicine Jun 2024Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11...
BACKGROUND
Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (MIM *610844).
METHODS
The proband is a 36-year-old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25-years-old). Diagnostic approaches included CGH array, next-generation sequencing, and whole transcriptome sequencing.
RESULTS
CGH array revealed a 180 kb deletion located upstream of SPG11. Sequencing of SPG11 uncovered two rare single nucleotide variants: the novel variant c.3143C>T in exon 17 (in cis with the deletion), and the previously reported pathogenic variant c.6409C>T in exon 34 (in trans). Whole transcriptome sequencing revealed that the variant c.3143C>T caused exon 17 skipping.
CONCLUSION
We report a novel sequence variant in the SPG11 gene resulting in exon 17 skipping, which, along with a nonsense variant, causes Spastic Paraplegia 11 in our proband. In addition, a deletion upstream of SPG11 was identified in the patient, whose implication in the phenotype remains uncertain. Nonetheless, the deletion apparently affects cis-regulatory elements of the gene, suggesting a potential new pathogenic mechanism underlying the disease in a subset of undiagnosed patients. Our findings further support the hypothesis that the origin of thin corpus callosum in patients with SPG11 is of progressive nature.
Topics: Humans; Female; Adult; Spastic Paraplegia, Hereditary; Exons; Proteins; Codon, Nonsense; Corpus Callosum; Sequence Deletion; Phenotype
PubMed: 38938072
DOI: 10.1002/mgg3.2475 -
Journal of Periodontology Jun 2024This randomized controlled trial with two parallel arms and a 1:1 allocation ratio aimed to compare early microvascular healing (primary outcome), surgical times, and...
BACKGROUND
This randomized controlled trial with two parallel arms and a 1:1 allocation ratio aimed to compare early microvascular healing (primary outcome), surgical times, and patient-reported outcomes (PROM) after harvesting palatal epithelialized gingival grafts (EGG), where hemostasis was achieved with sutures and hemostatic sponges (control) or with a sutureless approach (test).
METHODS
From a total of 33 patients, 34 EGG were harvested. Thirty-two were randomized to the test/control group (n = 16) and two were excluded. Early palatal microvascular healing was assessed at 7, 14, and 30 days with laser speckle contrast imaging (LSCI). Postoperative bleeding, pain, discomfort, and analgesic consumption were assessed over 2 weeks with a dedicated questionnaire.
RESULTS
A faster onset and resolution of postharvest hyperemia was observed in the test group where peak blood flow was reached at 7 days. No significant blood flow differences were observed between the groups at any of the evaluated timepoints. The mean surgical time was 13 min shorter in the test (p = 0.00). No significant differences were observed for postoperative bleeding and analgesic consumption at any timepoint.
CONCLUSIONS
The tested approach represents a viable alternative to the standard one, providing no relevant differences in microvascular, clinical, and patient-related results, but with significantly shorter surgical times.
PubMed: 38937873
DOI: 10.1002/JPER.23-0620 -
Health and Quality of Life Outcomes Jun 2024The objective of this study was to examine the psychometric properties of the EQ-5D-Y-3 L, Patient Reported Outcomes Measurement System 25-item version profile v2.0...
OBJECTIVE
The objective of this study was to examine the psychometric properties of the EQ-5D-Y-3 L, Patient Reported Outcomes Measurement System 25-item version profile v2.0 (PROMIS-25), and Pediatric Quality of Life Inventory™ version 4.0 Generic Core Scale (PedsQL 4.0) in Chinese pediatric patients with spinal muscular atrophy (SMA).
METHODS
The data used in this study were obtained via a web-based cross-sectional survey. Parents of pediatric patients with SMA completed the proxy-reported EQ-5D-Y-3 L, PedsQL 4.0, and PROMIS-25 measures. Information about socioeconomic and health status was also obtained. The ceiling and floor effects, factorial structure, convergent validity, and known-group validity of the three measures were assessed.
RESULTS
Three hundred and sixty-three parents of children aged from 5 to 12 completed the questionnaires. Strong floor effects were observed for the physical function components of the PROMIS-25 (41.3%) and PedsQL 4.0 (67.8%). For EQ-5D-Y-3 L, 84.6% of the respondents reported having "a lot of" problems with the dimensions "walking" and "looking after myself." Minimal ceiling or floor effects were observed for the EQ-5D-Y-3 L index value. The confirmatory factor analysis supported a six-factor structure for the PROMIS-25, but did not support a four-factor structure for the PedsQL 4.0. All hypothesized correlations of the dimensions among the three measures were confirmed, with coefficients ranging from 0.28 to 0.68. Analysis of variance showed that EQ-5D-Y-3 L demonstrated better known-group validity than the other two measures in 14 out of 16 comparisons.
CONCLUSIONS
The EQ-5D-Y-3 L showed better discriminant power than the other two measures. The physical health dimensions of all three measures showed the significant floor effects. These findings provide valuable insights into the effectiveness of these measures at capturing and quantifying the impact of SMA on patients' health-related quality of life.
Topics: Humans; Male; Psychometrics; Female; Child; Quality of Life; Cross-Sectional Studies; Surveys and Questionnaires; Child, Preschool; Muscular Atrophy, Spinal; Reproducibility of Results; Patient Reported Outcome Measures; China
PubMed: 38937825
DOI: 10.1186/s12955-024-02264-9 -
BMC Geriatrics Jun 2024The updated World Health Organization 2020 guidelines strongly recommend an optimal physical activity level of 150-300 min/week for older adults. However, few studies...
OBJECTIVES
The updated World Health Organization 2020 guidelines strongly recommend an optimal physical activity level of 150-300 min/week for older adults. However, few studies have examined the relationship between different levels of physical activity and sarcopenia. Therefore, the purpose of this study was to investigate the cross-sectional associations between overall physical activity levels, gender, intensity, and the risk of sarcopenia among older Taiwanese adults.
METHODS
A nationwide cross-sectional telephone survey of older adults (≥ 65 years) was conducted in Taiwan from October 2019 to January 2020. Participants were interviewed to collect self-reported data on their level of physical activity (measured by the Taiwanese version of the IPAQ-SF), sarcopenia risk (measured by the SARC-F questionnaire), and sociodemographics.
RESULTS
A total of 1068 older adults were surveyed. Compared with the optimal physical activity level recommendations in the WHO guidelines and after adjusting for potential confounders and proposing an association independent of sedentary behavior, older adults with insufficient physical activity levels (< 150 min/week) were more likely to have a higher risk of sarcopenia (OR: 3.24; CI: 1.67-6.27), whereas older adults who exceeded physical activity guidelines (> 300 min/week) were more likely to have a lower risk of sarcopenia (OR: 0.39; CI: 0.20-0.78). Maintaining moderate-intensity physical activity is essential for older adults, as physical activity that exceeds the guidelines can significantly lower the risk of sarcopenia; meanwhile, insufficient physical activity can greatly increase it. Also, there seems to be a similar association between sarcopenia risk across different physical activity levels in vigorous-intensity physical activities in older adults. However, due to the small number of sarcopenia-risk participants who met or exceeded vigorous-intensity physical activity levels, further comparisons between different vigorous-intensity physical activity levels did not show significant differences in sarcopenia risk. Additionally, insufficient physical activity was found to be an important risk factor for sarcopenia in both genders, while physical activity that exceeded the guidelines prevented sarcopenia in females.
CONCLUSIONS
The findings of this study highlight the potential dose-response relationship related to physical activity. The 2020 WHO guidelines provide the public with minimum recommendations for physical activity. However, exceeding these recommended levels appears to be more effective in preventing sarcopenia in older adults and may offer even greater health benefits. Future research should further explore whether exceeding these guidelines could result in additional health benefits.
Topics: Humans; Male; Female; Cross-Sectional Studies; Sarcopenia; Aged; Taiwan; Exercise; Aged, 80 and over; Risk Factors
PubMed: 38937702
DOI: 10.1186/s12877-024-05087-x -
BMC Geriatrics Jun 2024No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia.
PURPOSE
No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia.
PATIENTS AND METHODS
We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery.
RESULTS
Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42).
CONCLUSIONS
Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.
Topics: Humans; Sarcopenia; Male; Aged; Female; Postoperative Complications; Aged, 80 and over; Propensity Score; Retrospective Studies; Risk Factors
PubMed: 38937671
DOI: 10.1186/s12877-024-05066-2 -
In Vivo (Athens, Greece) 2024Sarcopenia is a prevalent and clinically significant condition, particularly among older age groups and those with chronic disease. Patients with cancer frequently... (Review)
Review
Sarcopenia is a prevalent and clinically significant condition, particularly among older age groups and those with chronic disease. Patients with cancer frequently suffer from sarcopenia and progressive loss of muscle mass, strength, and function. The complex interplay between cancer and its treatment, including medical therapy, radiotherapy, and surgery, significantly contributes to the onset and worsening of sarcopenia. Cancer induces muscle wasting through inflammatory processes, metabolic alterations, and hormonal imbalance. Moreover, medical and radiation therapies exert direct toxic effects on muscles, contributing to the impairment of physical function. Loss of appetite, malnutrition, and physical inactivity further exacerbate muscle wasting in cancer patients. Imaging techniques are the cornerstones for sarcopenia diagnosis. Magnetic resonance imaging, computed tomography, and dual-energy X-ray absorptiometry provide valuable insights into muscle structure and quality. Although each modality has advantages and limitations, magnetic resonance imaging produces high-resolution images and provides dynamic information about muscle function. Despite these challenges, addressing sarcopenia is essential for optimizing treatment outcomes and improving survival rates in patients with cancer. This review explored the factors contributing to sarcopenia in oncologic patients, emphasizing the importance of early detection and comprehensive management strategies.
Topics: Humans; Sarcopenia; Neoplasms; Muscle, Skeletal; Muscular Atrophy; Magnetic Resonance Imaging
PubMed: 38936901
DOI: 10.21873/invivo.13602 -
Neuromuscular Disorders : NMD May 2024Several studies have shown the efficacy of new disease-modifying therapies in slowing down type II SMA progression using the Hammersmith Functional Motor Scale Expanded...
Several studies have shown the efficacy of new disease-modifying therapies in slowing down type II SMA progression using the Hammersmith Functional Motor Scale Expanded (HFMSE). This research aims to enhance understanding of activity changes across age groups post-nusinersen treatment using shift analysis, compared with untreated individuals. Retrospective data from the, international SMA consortium (iSMAc) dataset were analyzed, assessing individual item changes over 12 months. Shift analysis was used to determine the gain or loss of abilities, defining "gain" as a positive change between scores from 0 to either 1 or 2 and "loss" as a negative change from either 2 or 1 to 0. The cohort included 130 SMA II patients who underwent 12-month assessments from their first nusinersen dose, with age range between 0.6 and 49.6 years. One-third of the entire cohort experienced at least a loss in one activity, while 60% experienced a gain, particularly notable in children aged 2.5 to 5 years and 5 to 13 years. Overall, the study demonstrates a positive impact of nusinersen treatment on SMA II patients, showing a trend of increased activity gains and decreased probability of ability loss across different age groups.
PubMed: 38936290
DOI: 10.1016/j.nmd.2024.05.003 -
Journal of Clinical Neuroscience :... Jun 2024This retrospective study evaluated the outcomes of patients undergoing one-stage resection of VII/VIII schwannomas and hemihypoglossal-facial neurorrhaphy via the...
BACKGROUND
This retrospective study evaluated the outcomes of patients undergoing one-stage resection of VII/VIII schwannomas and hemihypoglossal-facial neurorrhaphy via the translabyrinthine approach (TLA).
METHODS
The study encompassed ten consecutive patients with unilateral hearing loss (six women, four men, mean age: 49.5 ± 12.1 years) who underwent surgery. The cohort included two patients with vestibular schwannomas (VSs), four with facial nerve schwannomas (FNSs) (two originating from the geniculate ganglion of the facial nerve and two from the cerebellopontine angle), one with VS regrowth, and three with residual VSs. Preoperative facial nerve function, assessed using the House-Brackmann (HB) scale, was Grade V in one and Grade VI in nine patients. The mean preoperative duration of facial paralysis was 7.5 ± 6.9 months.
RESULTS
All patients underwent gross total resection. Postoperatively, one patient experienced cerebrospinal fluid leaks, which were successfully managed with lumbar drains and surgical revisions. At follow-up, facial nerve function improved in all patients: HB Grade V to III in one, HB Grade VI to III in one, HB Grade VI to IV in seven, and Grade VI to V in one. No tumor recurrence was observed during the follow-up period (mean duration: 16.6 ± 9.3 months), and no patient had hemilingual atrophy.
CONCLUSION
The TLA for one-stage resection of VII/VIII schwannomas and facial nerve reconstruction is effective in treating both regrowth and residual VSs and FNSs in the cerebellopontine angle or petrosal bone in patients with severe preoperative facial palsy. This technique facilitates simultaneous tumor removal and nerve anastomosis, thereby reducing the need for multiple surgical interventions in patients with hearing loss and compromised facial nerve function.
PubMed: 38935996
DOI: 10.1016/j.jocn.2024.06.010 -
Experimental Physiology Jun 2024Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to...
Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6 ± 2.1 years) underwent 14 days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3 ± 19.2%, interaction: P = 0.0440) and extension (-19.9 ± 15.7%, interaction: P = 0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2 ± 2.4%, interaction: P = 0.466), whereas elbow extensor CSA decreased (-2.9 ± 2.9%, interaction: P = 0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P > 0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P < 0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.
PubMed: 38935545
DOI: 10.1113/EP091782