Effectiveness of trigger point manual treatment on the frequency, intensity, and duration of attacks in primary headaches: A systematic review and meta-analysis of randomized controlled trials

Background: A variety of interventions has been proposed for symptomatology relief in primary headaches. Among these, manual trigger points (TrPs) treatment gains popularity, but its effects have not been investigated yet. Objective: The aim was to establish the effectiveness of manual TrP compared to minimal active or no active interventions in terms of frequency, intensity, and duration of attacks in adult people with primary headaches. Methods: We searched MEDLINE, COCHRANE, Web Of Science, and PEDro databases up to November 2017 for randomized controlled trials (RCTs). Two independent reviewers appraised the risk-of-bias (RoB) and the grading of recommendations, assessment, development, and evaluation (GRADE) to evaluate the overall quality of evidence. Results: Seven RCTs that compared manual treatment vs minimal active intervention were included: 5 focused on tension-type headache (TTH) and 2 on Migraine (MH); 3 out of 7 RCTs had high RoB. Combined TTH and MH results show statistically significant reduction for all outcomes after treatment compared to controls, but the level of evidence was very low. Subgroup analysis showed a statistically significant reduction in attack frequency (no. of attacks per month) after treatment in TTH (MD -3.50; 95% CI from -4.91 to -2.09; 4 RCTs) and in MH (MD -1.92; 95% CI from -3.03 to -0.80; 2 RCTs). Pain intensity (0-100 scale) was reduced in TTH (MD -12.83; 95% CI from -19.49 to -6.17; 4 RCTs) and in MH (MD -13.60; 95% CI from -19.54 to -7.66; 2RCTs). Duration of attacks (hours) was reduced in TTH (MD -0.51; 95% CI from -0.97 to -0.04; 2 RCTs) and in MH (MD -10.68; 95% CI from -14.41 to -6.95; 1 RCT). Conclusion: Manual TrPs treatment of head and neck muscles may reduce frequency, intensity, and duration of attacks in TTH and MH, but the quality of evidence according to GRADE approach was very low for the presence of few studies, high RoB, and imprecision of results

VKORC1 and CYP2C9 polymorphisms related to adverse events in case-control cohort of anticoagulated patients

Vitamin K antagonists (VKAs) are highly effective but have a narrow therapeutic index and require routine monitoring of the INR. The primary aim of pharmacogenetics (PGx) is to optimize patient care, achieving drug treatments that are personalized according to the genetic profile of each patient. The best-characterized genes involved in VKA PGx involve pharmacokinetics (VKORC1) and pharmacodynamics (CYP2C9) of VKA metabolism. The role of these genes in clinical outcomes (bleeding and thrombosis) during oral anticoagulant (OAC) therapy is controversial. The aim of the present study was to evaluate any potential association between genotype VKORC1 and CYP2C9 and adverse events (hemorrhagic and/or thrombotic), during initiation and long-term VKA treatment, in Caucasian patients. Furthermore, we aimed to determine if the concomitant prescription of other selected drugs affected the association between genotype and adverse events.We performed a retrospective, matched case-control study to determine associations between multiple gene variants, drug intake, and any major adverse effects in anticoagulated patients, monitored in 2 Italian anticoagulation clinics.Our results show that anticoagulated patients have a high risk of adverse events if they are carriers of 1 or more genetic polymorphisms in the VKORC1 (rs9923231) and CYP2C9 (rs1799853 and rs1057910) genes.Information on CYP2C9 and VKORC1 variants may be useful to identify individualized oral anticoagulant treatment for each patient, improve management and quality of VKA anticoagulation control, and monitor drug surveillance in pharmacovigilance programs

The EPFL Logic Synthesis Libraries

We present a collection of modular open source C++ libraries for the development of logic synthesis applications. These libraries can be used to develop applications for the design of classical and emerging technologies, as well as for the implementation of quantum compilers. All libraries are well documented and well tested. Furthermore, being header-only, the libraries can be readily used as core components in complex logic synthesis systems.Comment: 11 pages, originally accepted at Int'l Workshop on Logic & Synthesis 2018, extended for Workshop on Open-Source EDA Technology 201

Logic Synthesis for Established and Emerging Computing

Logic synthesis is an enabling technology to realize integrated computing systems, and it entails solving computationally intractable problems through a plurality of heuristic techniques. A recent push toward further formalization of synthesis problems has shown to be very useful toward both attempting to solve some logic problems exactly--which is computationally possible for instances of limited size today--as well as creating new and more powerful heuristics based on problem decomposition. Moreover, technological advances including nanodevices, optical computing, and quantum and quantum cellular computing require new and specific synthesis flows to assess feasibility and scalability. This review highlights recent progress in logic synthesis and optimization, describing models, data structures, and algorithms, with specific emphasis on both design quality and emerging technologies. Example applications and results of novel techniques to established and emerging technologies are reported

Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence:

Chronic rhinosinusitis with nasal polyps is a multifactorial disease of the nasal and paranasal sinus mucosa and it includes, as comorbidities, anatomic and morphologic alterations, allergic rhinitis, and immunologic diseases. We investigated matrix metalloproteinases (MMP-2, MMP-7, and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) concentration in different etiopathogenetical groups of patients with nasal polyposis (NP) in relation to recurrence after sinonasal surgery. The study group consisted of 45 patients with NP (those with allergic rhinitis, nonallergic rhinitis and asthma or nonallergic rhinitis, and obstruction of osteomeatal complex [OMC]) who underwent endonasal sinus surgery. We also collected 10 patients who underwent septoplasty as control. Immunohistochemistry of nasal mucosa fragments, Western blotting, and polymerase chain reaction analysis showed increased MMPs levels (MMP-9 more than MMP-2 and MMP-7) and decreased tissue inhibitors of MMPs levels (TIMP-1 less than TIMP-2), in patients with chronic rhinosinusitis with nasal polyps compared with control group, in particular in patients with nonallergic rhinitis and asthma compared to those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC. We observed a higher risk of recurrence in patients with nonallergic rhinitis and asthma than in those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC after 36 months from surgery. In this research, we evaluated pathogenesis of NP related to MMPs and their inhibitors concentrations in polypoid tissue

Exact Synthesis for Logic Synthesis Applications with Complex Constraints

Exact synthesis is the problem of finding logic networks that represent given Boolean functions and respect given constraints. With exact synthesis it is possible to find optimum networks, e.g., in size or depth; consequently, it primarily finds application in logic optimization. However, exact synthesis is also very helpful in logic synthesis applications necessitating complex constraints that are present in the hardware primitives or the logic representations for which the synthesis has to be performed. Conventional heuristic logic synthesis algorithms are not considering such constraints. They still can be employed to optimize networks, but they cannot guarantee that optimized networks meets all requirements. Being faced with a logic synthesis application that seeks for low-depth majority-based networks with limited fan-out for small functions, we demonstrate how state-of-the-art exact synthesis algorithms can be adapted and used to find logic networks that match these constraints. To emphasize the need for exact synthesis, we also demonstrate how conventional logic synthesis either fails to find constraint-satisfying logic networks or yields networks of inferior quality

Mapping Monotone Boolean Functions into Majority

We consider the problem of decomposing monotone Boolean functions into majority-of-three operations, with a particular focus on decomposing the majority-n function. When targeting monotone Boolean functions, Shannon's expansion can be expressed by a single majority-of-three operation. We exploit this property to transform binary decision diagrams (BDDs) for monotone functions into majority-inverter graphs (MIGs), using a simple one-to-one mapping. This process highlights desirable properties for further majority graph optimization, e.g., symmetries between the inputs of primitive operations, which are not apparent from BDDs. Although our construction yields a quadratic upper bound on the number of majority-3 operations required to realize majority-n, for small n the concrete values are much smaller compared to those obtained from previous constructions which have linear and quasi-linear asymptotic upper bounds. Further, we demonstrate that minimum size MIGs, for the monotone functions majority-5 and majority-7, can be obtained applying a small number of algebraic transformations to the BDD

Inversion Minimization in Majority-Inverter Graphs

In this paper, we present new optimization techniques for the recently introduced Majority-Inverter Graph (MIG). Our optimizations exploit intrinsic algebraic properties of MIGs and aim at rewriting the complemented edges of the graph without changing its shape. Two exact algorithms are proposed to minimize the number of complemented edges in the graph. The former is a dynamic programming method for trees; the latter finds the exact solution with a minimum number of inversions using Boolean satisfiability (SAT). We also describe a heuristic rule based algorithm to minimize complemented edges using local transformations. Experimental results for the exact algorithm to fanout-free regions show an average reduction of 12.8% on the EPFL benchmark suite. Applying the heuristic method on the same instances leads to a total improvement of 60.2%

Data Supporting the Roles of BAP1, Sting, and IFN-β in ISGF3 Activation in ccRCC

The data presented in this article are companion materials to our manuscript titled BAP1 maintains HIF-dependent interferon beta induction to suppress tumor growth in clear cell renal cell carcinoma (Langbein et al., 2022), where we investigated the downstream effects of BAP1 (BRCA1-associated protein 1) expression in clear cell renal cell carcinoma (ccRCC) cell lines and mouse xenograft models. In the manuscript, we showed that BAP1 upregulates STING (stimulator of interferon genes) expression and activity in ccRCC cells, leading to IFN-β transcription and activation of interferon stimulated gene factor 3 (ISGF3), the transcription factor that mediates the effects of type I interferons (IFNs). Here, we suppressed additional components of the type I IFN pathway, including IRF9 (a component of ISGF3), IFNAR1 (the type I IFN receptor), and STING (a stimulator of IFN production) by shRNA to investigate their involvement in BAP1-mediated upregulation of ISGF3 activity. We also inhibited extracellular IFN-β via neutralizing antibody treatment in BAP1-expressing cells to ascertain the role of the secreted cytokine in this pathway. ISGF3 activity was assessed by western blot analysis and qPCR measurement of its transcriptional targets. To examine the relevance of our observations in another model system, we characterized primary kidney cells from WT and Bap1 fl/fl mice by cytokeratin 8 immunohistochemistry and examined the effect of Bap1 knockout on Sting protein expression. Finally, we treated mice bearing BAP1 knockdown xenografted tumors with diABZI, a STING agonist, and measured immune cell recruitment via CD45 immunohistochemistry. These data can serve as a starting point for further investigation on the roles of BAP1 and other tumor suppressor genes in interferon pathway regulation