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Journal of Orofacial Orthopedics =... Mar 2023This prospective study was designed to assess whether patients with skeletal deformities show characteristic masseter inhibitory reflex (MIR) and blink reflex (BR)...
OBJECTIVES
This prospective study was designed to assess whether patients with skeletal deformities show characteristic masseter inhibitory reflex (MIR) and blink reflex (BR) patterns. A secondary aim was to investigate whether these reflexes change following bilateral sagittal split osteotomy (BSSO).
MATERIALS AND METHODS
Fourteen consecutive patients who underwent single-jaw BSSO and 14 class I subjects who constituted the control group were enrolled into the study. MIR and BR, obtained by the stimulation of supraorbital (SBR) and mental nerves (MBR), were electrophysiologically recorded. Sensory impairment in the mental nerve distribution was clinically tested. Three evaluation periods were specified as immediately before (T0), 1 month (T1) and 6 months (T2) after surgery.
RESULTS
MIR early silent period duration was significantly shorter in the patients at T0 (p < 0.001). Sensory deficits developed on 23 sides after BSSO, of which, 17 recovered after 6 months. At T1, MBR was inelicitable bilaterally in 3 patients and unilaterally in 2 patients. These responses were still unrecordable bilaterally in 1 patient, and unilaterally in 4 patients at T2. MIR were unrecordable on 18 sides at T1 and recovered on 11 sides at T2. There were no parallels between the clinical sensory deficits and the abnormal results of the reflexes.
CONCLUSIONS
Shorter MIR in patients with dentofacial abnormalities may be a reflection of an adapted trigeminal reflex mechanism. Although MBR and MIR abnormalities do not develop parallel to the clinical sensory deficits, their course might provide insights into the disturbed trigeminal reflex pathways.
Topics: Humans; Brain Stem; Mandible; Mandibular Nerve; Osteotomy; Prospective Studies; Reflex; Dentofacial Deformities
PubMed: 34570255
DOI: 10.1007/s00056-021-00350-x -
The Journal of Physical Chemistry. A Jan 2023Heat-bath configuration interaction (HCI) is a deterministic method that approaches the full CI limit at greatly reduced computational cost. In this work, computational...
Heat-bath configuration interaction (HCI) is a deterministic method that approaches the full CI limit at greatly reduced computational cost. In this work, computational improvements to the HCI algorithm are introduced targeting speed, parallel efficiency, and memory requirements. The new implementation introduces a hash function to distribute determinants and takes advantage of MPI and OpenMP for parallelism allowing for a (22e,168o) active space to be studied, which explicitly includes 2.39 × 10 variational determinants and 8.95 × 10 perturbative determinants. Benchmarks show up to 86% parallel efficiency of the perturbative step on 32 nodes (4096 cores) and a total efficiency of 74%. The new HCI implementation is benchmarked for accuracy against prior results and applied to study the triplet-quintet gap in the challenging [FeO(NH)] complex.
Topics: Hot Temperature; Algorithms
PubMed: 36580361
DOI: 10.1021/acs.jpca.2c07949 -
Menopause (New York, N.Y.) May 2024The increasing attention to the management of perimenopausal and postmenopausal women parallels the growth of the aging population. Although hormone therapy is commonly... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The increasing attention to the management of perimenopausal and postmenopausal women parallels the growth of the aging population. Although hormone therapy is commonly used to alleviate menopausal symptoms, it carries a potential risk of cancer. Recently, mind-body exercises have emerged as innovative approaches for improving menopausal symptoms and bone health. However, research findings have needed to be more consistent, highlighting the significance of this study's systematic review of mind-body exercise effects on perimenopausal and postmenopausal women.
OBJECTIVE
This study aims to evaluate the impact of mind-body exercises, including tai chi, yoga, Pilates, qigong, baduanjin, and mindfulness-based stress reduction, on bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women.
EVIDENCE REVIEW
Four electronic databases-PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science-were systematically searched from inception until July 2023. The search focused exclusively on randomized controlled trials to examine the impact of mind-body exercise interventions on perimenopausal and postmenopausal women. The methodological quality of the included studies was evaluated using the Cochrane Bias Risk Assessment tool.
FINDINGS
A total of 11 randomized controlled trials, comprising 1,005 participants, were included in the analysis. Traditional meta-analysis indicated that mind-body exercise significantly enhanced bone mineral density in perimenopausal and postmenopausal women compared with control groups, with a standardized mean difference (SMD) of 0.41 (95% CI, 0.17 to 0.66; P = 0.001, I2 = 7%). In addition, significant improvements were observed in sleep quality (SMD, -0.48; 95% CI, -0.78 to -0.17; P = 0.002, I2 = 76%), anxiety reduction (SMD, -0.80; 95% CI, -1.23 to -0.38; P = 0.0002, I2 = 84%), depressive mood (SMD, -0.80; 95% CI, -1.17 to -0.44; P < 0.0001, I2 = 79%), and fatigue (SMD, -0.67; 95% CI, -0.97 to -0.37; P < 0.0001, I2 = 0%).
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis demonstrate that mind-body exercise positively influences bone mineral density, sleep quality, anxiety, depression, and fatigue among perimenopausal and postmenopausal women.
Topics: Humans; Female; Perimenopause; Postmenopause; Bone Density; Mind-Body Therapies; Middle Aged; Depression; Sleep Quality; Randomized Controlled Trials as Topic; Anxiety; Fatigue; Exercise; Tai Ji; Yoga
PubMed: 38669625
DOI: 10.1097/GME.0000000000002336 -
Human Molecular Genetics Oct 2022Linkage disequilibrium and the incomplete regulatory annotation of the noncoding genome complicates the identification of functional noncoding genetic variants and their...
Linkage disequilibrium and the incomplete regulatory annotation of the noncoding genome complicates the identification of functional noncoding genetic variants and their causal association with disease. Current computational methods for variant prioritization have limited predictive value, necessitating the application of highly parallelized experimental assays to efficiently identify functional noncoding variation. Here, we summarize two distinct approaches, massively parallel reporter assays and CRISPR-based pooled screens and describe their flexible implementation to characterize human noncoding genetic variation at unprecedented scale. Each approach provides unique advantages and limitations, highlighting the importance of multimodal methodological integration. These multiplexed assays of variant effects are undoubtedly poised to play a key role in the experimental characterization of noncoding genetic risk, informing our understanding of the underlying mechanisms of disease-associated loci and the development of more robust predictive classification algorithms.
Topics: Humans; Genome; Genomics; Linkage Disequilibrium; Algorithms; Genome-Wide Association Study
PubMed: 36057282
DOI: 10.1093/hmg/ddac194 -
Methods in Molecular Biology (Clifton,... 2020The increase in the human lifespan has not been paralleled by an increase in healthy life. With the increase in the proportion of the aged population, there has been a... (Review)
Review
The increase in the human lifespan has not been paralleled by an increase in healthy life. With the increase in the proportion of the aged population, there has been a natural increase in the prevalence of age-related disorders, such as Alzheimer's disease, type 2 diabetes mellitus, frailty, and various other disorders. A continuous rise in these conditions could lead to a widespread medical and social burden. There are now considerable efforts underway to address these deficits in preclinical and clinical studies, which include the use of better study cohorts, longitudinal designs, improved translation of data from preclinical models, multi-omics profiling, identification of new biomarker candidates and refinement of computational tools and databases containing relevant information. Such efforts will support future interdisciplinary studies and help to identify potential new targets that are amenable to therapeutic approaches such as pharmacological interventions to increase the human healthspan in parallel with the lifespan.
Topics: Aging; Alzheimer Disease; Animals; Biomarkers; Diabetes Mellitus, Type 2; Drug Delivery Systems; Frailty; Humans; Longevity; Pharmaceutical Preparations
PubMed: 32219738
DOI: 10.1007/978-1-0716-0471-7_1 -
Frontiers in Systems Neuroscience 2021Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels... (Review)
Review
Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels of excitation to cortical neurons, synapses adjust to maintain excitatory-inhibitory (EI) balance. In this review, we summarize research on this EI homeostasis in the neocortex, using stroke as our case study, and in particular the loss of excitation to distant cortical regions after focal lesions. Widespread changes following a localized lesion, a phenomenon known as diaschisis, are not only related to excitability, but also observed with respect to functional connectivity. Here, we highlight the main findings regarding the evolution of excitability and functional cortical networks during the process of post-stroke recovery, and how both are related to functional recovery. We show that cortical reorganization at a global scale can be explained from the perspective of EI homeostasis. Indeed, recovery of functional networks is paralleled by increases in excitability across the cortex. These adaptive changes likely result from plasticity mechanisms such as synaptic scaling and are linked to EI homeostasis, providing a possible target for future therapeutic strategies in the process of rehabilitation. In addition, we address the difficulty of simultaneously studying these multiscale processes by presenting recent advances in large-scale modeling of the human cortex in the contexts of stroke and EI homeostasis, suggesting computational modeling as a powerful tool to tie the meso- and macro-scale processes of recovery in stroke patients.
PubMed: 35082606
DOI: 10.3389/fnsys.2021.806544 -
The Journal of Hand Surgery Aug 2019Randomized controlled trials (RCTs) are the gold standard for comparing clinical interventions. Statistical significance as reported via a P value has been used to... (Review)
Review
PURPOSE
Randomized controlled trials (RCTs) are the gold standard for comparing clinical interventions. Statistical significance as reported via a P value has been used to determine if a difference between clinical interventions exists in an RCT. However, P values do not clearly convey information about the robustness of a study's conclusions. An emerging metric, called the fragility index (the number of subjects who would need to change outcome category to raise the P value above the .05 threshold), is an indirect measure of how likely a repeat of the trial would reach the same conclusions. This study addressed the fragility of RCTs using dichotomous outcomes in hand surgery.
METHODS
Using systematic searching of the MEDLINE database, we identified hand surgery RCTs published in 11 high-impact journals published in the last decade (2007-2017). Studies were identified that involved 2 parallel arms, allocated patients to treatment and control in a 1:1 ratio, and reported statistical significance for a dichotomous variable. The fragility index was calculated using Fisher's exact test, using previously published methods.
RESULTS
Five hand surgery RCTs were identified for inclusion reporting a range of fragility indices from 0 to 26. Two of the trials (40%) had a fragility index of 2 or less. Two of the trials (40%) reported that the number of patients lost to follow-up exceeded the fragility index, meaning that results of the patients lost to follow-up could theoretically completely reverse the study conclusions.
CONCLUSIONS
The range of fragility indices reported in the recent hand surgery literature is consistent with previous reporting within orthopedic surgery.
CLINICAL RELEVANCE
The fragility index is a useful metric to analyze the robustness of the study conclusions that should complement other methods of critical evaluation including the P value or effect sizes. Our results emphasize the need for future efforts to strengthen the robustness of RCT conclusions.
Topics: Hand; Humans; Orthopedic Procedures; Randomized Controlled Trials as Topic; Research Design; Sample Size
PubMed: 30420197
DOI: 10.1016/j.jhsa.2018.10.005 -
Chimia Apr 2023RNA splicing, the removal of introns and ligation of exons, is a crucial process during mRNA maturation. Group II introns are large ribozymes that self-catalyze their...
RNA splicing, the removal of introns and ligation of exons, is a crucial process during mRNA maturation. Group II introns are large ribozymes that self-catalyze their splicing, as well as their transposition. They are living fossils of spliceosomal introns and eukaryotic retroelements. The yeast mitochondrial Sc.ai5γ is the first identified and best-studied self-splicing group II intron. A combination of biochemical, biophysical, and computational tools enables studying its catalytic properties, structure, and dynamics, while also serving to develop new therapeutic and biotechnological tools. We survey the history of group II intron studies paralleling the trends in RNA methodology with Sc.ai5γ in the spotlight.
Topics: Introns; Biophysics; Biotechnology; Catalysis; Mitochondria
PubMed: 38047803
DOI: 10.2533/chimia.2023.235 -
Molecular Biology and Evolution Sep 2021Population genetic theory predicts that small effective population sizes (Ne) and restricted gene flow limit the potential for local adaptation. In particular, the...
Population genetic theory predicts that small effective population sizes (Ne) and restricted gene flow limit the potential for local adaptation. In particular, the probability of evolving similar phenotypes based on shared genetic mechanisms (i.e., parallel evolution), is expected to be reduced. We tested these predictions in a comparative genomic study of two ecologically similar and geographically codistributed stickleback species (viz. Gasterosteus aculeatus and Pungitius pungitius). We found that P. pungitius harbors less genetic diversity and exhibits higher levels of genetic differentiation and isolation-by-distance than G. aculeatus. Conversely, G. aculeatus exhibits a stronger degree of genetic parallelism across freshwater populations than P. pungitius: 2,996 versus 379 single nucleotide polymorphisms located within 26 versus 9 genomic regions show evidence of selection in multiple freshwater populations of G. aculeatus and P. pungitius, respectively. Most regions involved in parallel evolution in G. aculeatus showed increased levels of divergence, suggestive of selection on ancient haplotypes. In contrast, haplotypes involved in freshwater adaptation in P. pungitius were younger. In accordance with theory, the results suggest that connectivity and genetic drift play crucial roles in determining the levels and geographic distribution of standing genetic variation, providing evidence that population subdivision limits local adaptation and therefore also the likelihood of parallel evolution.
Topics: Animals; Fresh Water; Gene Flow; Genetic Drift; Genome; Smegmamorpha
PubMed: 33956140
DOI: 10.1093/molbev/msab144 -
JMIR Research Protocols May 2023Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing...
BACKGROUND
Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD.
OBJECTIVE
Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness.
METHODS
Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods.
RESULTS
Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal.
CONCLUSIONS
The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/39223.
PubMed: 37166948
DOI: 10.2196/39223