Hurleyatkinson2495
Biochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level design specification can be embedded into diverse biomolecular environments, such as cell-free extracts and in vivo milieus. Finally, our software toolbox has a parameter database, which allows users to rapidly prototype large models using very few parameters which can be customized later. By using BioCRNpyler, users ranging from expert modelers to novice script-writers can easily build, manage, and explore sophisticated biochemical models using diverse biochemical implementations, environments, and modeling assumptions.With the advent of high throughput genetic data, there have been attempts to estimate heritability from genome-wide SNP data on a cohort of distantly related individuals using linear mixed model (LMM). Fitting such an LMM in a large scale cohort study, however, is tremendously challenging due to its high dimensional linear algebraic operations. In this paper, we propose a new method named PredLMM approximating the aforementioned LMM motivated by the concepts of genetic coalescence and Gaussian predictive process. PredLMM has substantially better computational complexity than most of the existing LMM based methods and thus, provides a fast alternative for estimating heritability in large scale cohort studies. Theoretically, we show that under a model of genetic coalescence, the limiting form of our approximation is the celebrated predictive process approximation of large Gaussian process likelihoods that has well-established accuracy standards. We illustrate our approach with extensive simulation studies and use it to estimate the heritability of multiple quantitative traits from the UK Biobank cohort.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant condition which phenotype can be extremely variable considering its multisystem involvement, including the central nervous system. Neuromuscular findings are facial and distal extremities muscle weakness, muscle atrophy and myotonia. Standard diagnosis is obtained with molecular testing to detect CTG expansions in the myotonic dystrophy protein of the kinase gene. Brain magnetic resonance imaging typically shows characteristic subcortical white matter (WM) abnormalities located within anterior temporal lobes.
We present a 39-year-old male patient with a progressive external ophthalmoplegia, facial and limb muscle weakness, percussion myotonia and atypical brain magnetic resonance imaging findings, showing confluent brainstem WM lesions, affecting the pons, a rare radiologic feature in this disorder. Genetic testing confirmed the diagnosis for DM1.
This presentation with external ophthalmoplegia and brainstem WM loss in DM1 can show an important correlation with clinical findings and have an important diagnostic and prognostic value.
This presentation with external ophthalmoplegia and brainstem WM loss in DM1 can show an important correlation with clinical findings and have an important diagnostic and prognostic value.
Long-acting injectable antipsychotics (LAIs) have been shown to reduce acute episodes of schizophrenia spectrum disorders (SSDs). However, breakthrough relapses are frequent, possibly because of underdosing in clinical practice. In this framework, the advantages of therapeutic drug monitoring (TDM) may be overlooked. learn more This study explored the association of low steady-state LAI levels with a higher risk of relapse in SSDs, despite the use of a licensed posology.
Forty-eight clinically stable outpatients with SSD underwent LAI-TDM using liquid chromatography-mass spectrometry for routine observational purposes. Baseline anamnestic, pharmacological, and psychometric evaluations compared subjects with "under-range" versus "in-range" LAI serum levels; between-group comparisons for different LAI treatments were also performed. A binary logistic regression explored which baseline factors (age, sex, previous hospitalizations, psychopathology, specific LAI treatment, and underrange serum levels) predicted relapse dvels in real-world practice should prompt adequate monitoring of clinically stable outpatients to identify the early signs of psychopathological deterioration.
Restless legs syndrome (RLS) is a clinical entity characterized by sensory-motor manifestations commonly observed in end-stage renal illness. Evidence suggests that RLS is a multifactorial phenomenon that can be influenced by many critical factors, including genetic predisposition, dietary patterns, and deficiency in some vitamins. Iron metabolism disorders and metabolic derangements have been generally accepted as predisposing elements in RLS. Furthermore, both pharmacological and neuroimaging studies demonstrated dopamine deficiency and dopamine receptors decrease in basal ganglia during RLS.
A literature search was done in three databases (PubMed, Google Scholar, and Cochrane) to identify the pertinent articles discussing the epidemiology, pathogenesis, and management of RLS in hemodialysis patients. RLS can affect the morbidity and mortality of patients treated with dialysis. It also has significant impacts on the quality of life since it can lead to insomnia, increased fatigue, mental health troubles, and other movement problems. Appropriate measures should be considered in this particular population so to prevent and treat RLS. Many drugs and other nonpharmacological methods have been investigated to attenuate the disease's severity. No treatment, however, could offer long-term effects.
Further efforts are still required to improve the understanding of RLS pathogenic trends to find more specific and efficient therapies. A wide range of treatment options is available. However, it can be individualized according to the patients' several factors.
Further efforts are still required to improve the understanding of RLS pathogenic trends to find more specific and efficient therapies. A wide range of treatment options is available. However, it can be individualized according to the patients' several factors.
Patient satisfaction is an important indicator used to monitor quality of care and outcomes after spine surgery.
To examine the complex relationship between preoperative expectations, fulfillment of expectations, postsurgical outcomes, and satisfaction after spine surgery.
In this national study of patients undergoing elective surgery for degenerative spinal conditions from the Canadian Spine Outcomes and Research Network Registry, we used logistic regression to examine the relationships between patient satisfaction with surgery (1-5 scale), preoperative expectation score (0 = none to 100 = highest), fulfillment of expectations, and disability and pain improvement.
Fifty-eight percent of patients were extremely satisfied, and 3% were extremely dissatisfied. Expectations were variable and generally high (mean 79.5 of 100) while 17.3% reported that none of their expectations were met, 49.8% reported that their most important expectation was met, and 32.9% reported that their most important expectation wlly assessing and mitigating the potential discrepancies between patients' preoperative expectations and likely surgical outcomes. The findings are likely relevant across elective surgical populations.
The approach to oculomotor nerve palsies involves the exclusion of compressive, infective, inflammatory, or ischemic lesions. Dural arteriovenous fistulae, including carotid-cavernous fistulae (CCF), are known causes of third nerve palsy. However, diagnosis can sometimes be delayed or missed due to the various clinical presentations. CCF remains a rare but treatable cause of third nerve palsy.
A 63-year-old Chinese female presented to our unit with gradual onset horizontal diplopia. Clinical examination revealed a partial left oculomotor nerve palsy without congestive eye symptoms. A cerebral angiogram revealed a left indirect CCF supplied by the inferolateral trunk of the left internal carotid artery. She underwent successful transvenous embolization. She improved postprocedure and was discharged well on day 10 of her admission. She was reviewed at 2 months follow-up and had recovered completely.
Our case is a classic description of a CCF with posterior drainage into the inferior petrosal sinus. We hope this case and a review of the literature can serve as a reminder to clinicians of the varied presentations of CCF. We believe this case adds value to the clinicians in contributing to their diagnostic process and to our interventional colleagues in highlighting a case with a successful postembolization outcome.
Our case is a classic description of a CCF with posterior drainage into the inferior petrosal sinus. We hope this case and a review of the literature can serve as a reminder to clinicians of the varied presentations of CCF. We believe this case adds value to the clinicians in contributing to their diagnostic process and to our interventional colleagues in highlighting a case with a successful postembolization outcome.
Chronic postsurgical pain (CPSP) is defined by pain intensity and pain-related functional interference. This study included measures of function in a composite score of patient-reported outcomes (PROs) to investigate the incidence of CPSP. Registry data were analyzed for PROs 1 day and 12 months postoperatively. Based on pain intensity and pain-related interference with function, patients were allocated to the groups " CPSPF " (at least moderate pain with interference), " mixed " (milder symptoms), and " no CPSPF ". The incidence of CPSPF was compared with CPSP rates referring to published data. Variables associated with the PRO-12 score (composite PROs at 12 months; numeric rating scale 0-10) were analyzed by linear regression analysis. Of 2319 patients, 8.6%, 32.5%, and 58.9% were allocated to the groups CPSPF , mixed , and no CPSPF , respectively. Exclusion of patients whose pain scores did not increase compared with the preoperative status, resulted in a 3.3% incidence. Of the patients without pre-existsessment of pain and interference resulted in lower CPSP rates than previously reported. Although inclusion of CPSP in the ICD-11 is a welcome step, evaluation of pain characteristics would be helpful in differentiation between CPSPF and continuation of pre-existing chronic pain.
Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-β (TGFβ) signaling pathway. In addition to vascular malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFβ signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined.
Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFβ-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing.
