Modeling and analysis of an ankle-foot orthosis (AFO) using multibody methodologies

Biomechanics is the scientific domain which deals with the study of biological systems, such as the human body, using physical concepts and mechanical engineering methodologies. It allows the development of new medical devices and provides a quantitative analysis of the subject being studied. In the present work, the effect of an ankle foot orthosis (AFO) was studied on a healthy male subject. For this purpose, a biomechanical multibody 2D- model was developed in code MOBILE. The model was made of 9 rigid bodies connected by 9 frictionless hinged joints. Three additional degrees-of- freedom (DOFs) were added so the model can move freely in the plane. Kinematic data acquired in a gait lab were used as time functions to drive the joints and a foot model was designed based on three Hunt-Crossley’s spheres-plane contact model. The measured ankle kinematics was successfully reproduced using forward dynamics principles, for the stance phase period. In a first approach, barefoot kinematics was reproduced to define the foot model properties by adjusting manually the foot parameters and fitting the ankle angle. The ankle moment obtained in the gait lab was used to power the ankle joint. Then, the ankle-foot orthosis was added as a linear torsional spring element acting at the ankle joint and the moment powering the ankle joint was diminished. A manual optimization process was performed in order to fit the ankle ankle and it was concluded that the AFO reduces the muscle moment developed at the ankle in 15% and it can be simulated as a spring with k = 50 N.m/rad.Fundação para a Ciência e a Tecnologia (FCT

Seasonal variation of hip fractures in patients with Benign Paroxysmal Positional Vertigo

Introduction: Seasonal variation of benign paroxysmal positional vertigo (BPPV) presentation has been reported, with higher rates of presentation in months associated with times of lower serum vitamin D levels. The purpose of this study was to examine the association between the timing of hip fracture in patients with BPPV. Methods: A retrospective review (2013 to 2019) of adult patients was performed at a tertiary care academic center to identify patients with hip fracture due to ground level fall (ICD-10 code S72) and a previously established diagnosis of vestibular disorder (ICD-10 codes H81-83, A88.1, and R42). Included patients were matched by age and sex to control for patients who had hip fracture without a vestibular diagnosis. Patient charts were reviewed, and demographic and clinical data were extracted related to hip fracture and prior vestibular diagnosis. Groups were subdivided based on whether patients had a hip fracture from January to June versus July to December. Fisher’s exact test was used to evaluate for a difference in seasonal variation between groups. Results: There were 201 patients with vestibular disorders of whom 27 patients carried the diagnosis of BPPV, with a mean age of 80.4 years. The rates of hip fracture among patients with BPPV was higher in the period extending from January to June (63.0%) versus July to December (37.0%), [odds ratio 1.59, 95% CI 0.66-4.00]. The rate of hip fracture was not significantly different between these time periods for the control group (51.7% versus 48.3%) or the vestibular group (53.2% versus 46.8%). Conclusion: These results offer preliminary evidence that, in addition to an increased presentation for BPPV during months associated with decreased serum vitamin D, injuries due to BPPV may be increased as well. The present study is limited by the statistical power afforded by the small number of patients with BPPV and hip fracture that were identified

The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor interacting protein (RIP) lcinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-gamma in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases

The impact of gender ideologies on men's and women's desire for a traditional or non-traditional partner

Two studies examine preferences for a long-term partner who conforms to traditional or non- traditional gender roles. The studies both demonstrate a link between benevolent sexism and preference for a traditional partner. However, Study 1 also demonstrates a strong preference among women for a non-traditional partner. We measured ambivalent sexist ideologies before introducing participants to either a stereotypically traditional or stereotypically non-traditional character of the opposite sex. In Study 1, women high in benevolence toward men reported a preference for a traditional man when compared to women low in benevolence toward men. We found no such link for hostility toward men. Study 2 showed that men high in benevolent sexism preferred a traditional woman more than men low in benevolent sexism. Again, this was not the case for hostile sexism. The studies provide evidence using both the Ambivalence Toward Men Inventory and the Ambivalent Sexism Inventory and demonstrate a relationship between benevolent ideology and partner choice that adds to a literature on partner preference which has to date been focused on preference dimensions of attractiveness and resources

Measurement of the proton and deuteron structure functions, F2p and F2d, and of the ratio sigma(L)/sigma(T)

The muon-proton and muon-deuteron inclusive deep inelastic scattering cross sections were measured in the kinematic range 0.002 < x < 0.60 and 0.5 < Q2 < 75 GeV2 at incident muon energies of 90, 120, 200 and 280 GeV. These results are based on the full data set collected by the New Muon Collaboration, including the data taken with a small angle trigger. The extracted values of the structure functions F2p and F2d are in good agreement with those from other experiments. The data cover a sufficient range of y to allow the determination of the ratio of the longitudinally to transversely polarised virtual photon absorption cross sections, R= sigma(L)/sigma(T), for 0.002 < x < 0.12 . The values of R are compatible with a perturbative QCD prediction; they agree with earlier measurements and extend to smaller x.Comment: In this replacement the erroneously quoted R values in tables 3-6 for x>0.12, and R1990 values in tables 5-6 for all x, have been corrected, and the cross sections in tables 3-4 have been adapted. Everything else, including the structure functions F2, remained unchanged. 22 pages, LateX, including figures, with two .sty files, and three separate f2tab.tex files for the F2-tables. Accepted for publication in Nucl.Phys.B 199

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis

DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b–/– lymphomas, but not in Dnmt3b–/– pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b–/– lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies

Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

BACKGROUND: Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. METHODS: A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m(2)), L-FA (200 mg/m(2)) and 5-FU bolus (400 mg/m(2)) on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m(2)). One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. RESULTS: The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4 CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. CONCLUSIONS: The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant protocols