Postural loads during walking after an imbalance of occlusion created with unilateral cotton rolls

<p>Abstract</p> <p>Background</p> <p>It was showed that stomatognathic functions correlate with alterations in locomotion, that are detectable through the analysis of loading during walking. For example, subjects with symptoms of Temporomandibular disorders (TMDs) showed a significant higher load pressure on the two feet, respect to health subjects, when cotton rolls were inserted. This previous study appeared to suggest that the alteration of postural loads associated to a particular alteration of stomatognathic condition (in this case, the cotton rolls inserted between the two dental arches) is detectable only in TMD's subjects, while it resulted not detectable in health subjects, because in that study, health subjects did not show any significant alteration of postural loads related to the different stomatognathic tested conditions. In other words, in that previous study, in the group of health subjects, no significant difference in postural loads was observed among the different test conditions; while TMD subjects showed a significant higher load pressure on the two feet when cotton rolls were inserted, respect to all the other tested conditions. Thus, the aim of this study was to better investigate these correlations in health subjects without TMD's symptoms, testing other different intra-oral conditions, and to verifywhether an experimentally induced imbalance of occlusion, obtained putting an unilateral cotton roll, could cause an alteration of postural loading on feet during walking.</p> <p>Findings</p> <p>In a sample of thirty Caucasian adult females (mean age 28.5 ± 4.5), asymptomatic for TMDs, when a cotton roll was positioned on the left or the right sides of dental arches, so causing a lateral shift of the mandible, the percentage of loading and the loading surface of the ipsi-lateral foot, left or right, were found to be significantly lower than in habitual occlusion (p < 0.05). Males were not included because of their different postural attitude respect to females. Further studies in a sample of males will be presented.</p> <p>Conclusions</p> <p>This study showed that in health subjects without TMD's symptoms, an experimentally induced imbalance of the occlusion, obtained through an unilateral cotton roll, is associated to detectable alterations in the distribution of loading on feet surface, during walking.</p

Dynamic Characteristics of a Non-symmetric Tilting Pad Journal Bearing

Because tilting-pad journal bearings are more stable and efficient than conventional bearings, they have been commonly applied to many rotating machinery applications. Most of the studies about steady state and dynamic characteristics of tilting-pad journal bearings are usually evaluated by means of thermo hydrodynamic models assuming nominal dimensions for the bearing. However machining errors could lead to actual bearing geometry and dimensions different from the nominal ones. In particular for tilting-pad journal bearing the asymmetry of the bearing geometry is the principal cause of unexpected behavior. In this paper a theoretical analysis on dynamic characteristics of a five-pad tilting-pad journal bearing is investigated with non-nominal geometry, that is, different thickness for each pad. The dynamic coefficients of a five-pad tilting-pad journal bearing with a nominal diameter of 100 mm, length-to-diameter ratio (L/D) of 0.7 are evaluated versus rotor rotational speed, load direction and static load. Then, the analytical results of the non-nominal bearing are compared to those of a bearing having nominal (i.e. ideal) geometry

Cascaded two-photon nonlinearity in a one-dimensional waveguide with multiple two-level emitters

We propose and theoretically investigate a model to realize cascaded optical nonlinearity with few atoms and photons in one-dimension (1D). The optical nonlinearity in our system is mediated by resonant interactions of photons with two-level emitters, such as atoms or quantum dots in a 1D photonic waveguide. Multi-photon transmission in the waveguide is nonreciprocal when the emitters have different transition energies. Our theory provides a clear physical understanding of the origin of nonreciprocity in the presence of cascaded nonlinearity. We show how various two-photon nonlinear effects including spatial attraction and repulsion between photons, background fluorescence can be tuned by changing the number of emitters and the coupling between emitters (controlled by the separation).Comment: 6 pages, 4 figure

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

A Phase I Dose Escalation Trial of Gemcitabine with Radiotherapy for Breast Cancer in the Treatment of Unresectable Chest Wall Recurrences

The purpose of this study was to determine the maximum tolerated dose (MTD) of gemcitabine when given concurrently with standard radiotherapy for the treatment of chest wall recurrences, and to compare actuarial rates of local-regional control with those achieved in historical controls. Patients with unresectable chest wall recurrences were enrolled in a phase I trial of concurrent gemcitabine and radiotherapy. Gemcitabine was increased at 150 mg/m 2 /week increments, starting at 300 mg/m 2 /week. Radiotherapy was delivered to the chest wall and regional nodes to a total of 60 to 70 Gy in 2 Gy daily fractions. Treatment toxicity was assessed and a comparison of treatment outcome was performed between study patients and historical groups treated with either radiotherapy alone or excision followed by radiotherapy. The dose-limiting toxicities of neutropenia and thrombocytopenia occurred at the second planned dose of 450 mg/m 2 /week after accrual of only six patients, resulting in a MTD of 300 mg/m 2 /week. Myelosuppression and skin desquamation were commonly observed. Actuarial rates of local-regional control were 100%, 50%, and 90% at 2 years for the gemcitabine with radiotherapy, radiotherapy alone, and excision followed by radiotherapy groups, respectively ( p  = 0.105). The difference among the Kaplan–Meier curves for overall local-regional control was statistically significant at p  = 0.007 in favor of combined gemcitabine and radiotherapy. The MTD of gemcitabine is 300 mg/m 2 /week when gemcitabine is delivered concurrently with radiotherapy for unresectable chest wall failures. This novel approach suggests excellent local-regional control when compared to historical controls. A phase II trial is warranted. Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75565/1/j.1075-122X.2004.21305.x.pd

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Cocoa flavanols adjuvant to an oral nutritional supplement acutely enhances nutritive flow in skeletal muscle without altering leg glucose uptake kinetics in older adults

This is the final version. Available on open access from MDPI via the DOI in this record. Data Availability Statement: The data presented in this study are available on request from the corresponding authors.Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.Abbott NutritionMedical Research Council (MRC)National Institute for Health Research (NIHR

Gemcitabine twice weekly as a radiosensitiser for the treatment of brain metastases in patients with carcinoma: a phase I study

Conventional treatment for brain metastases (BM) is whole-brain radiotherapy (WBRT). Efficacy is poor. It might be increased by a potent radiosensitiser such as gemcitabine which is believed to cross the disrupted blood–brain barrier. Primary objective of this study was to determine the maximum tolerated dose (MTD) of twice weekly gemcitabine given concurrently with WBRT. Patients with BM from carcinoma were included. The dose of WBRT was 30 Gys (10 daily fractions). Gemcitabine was given 2–4 h prior to WBRT on days 1 and 8 for the first cohort of patients and then on days 1, 4, 8 and 11. Starting dose was 25 mg m−2, escalated by 12.5 mg m−2 increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 haematological or grade ⩾3 nonhaematological toxicity. A total of 25 patients were included; 74% had a PS 1 (ECOG). In all, 23 had non-small-cell lung cancer, six colorectal, four breast, two renal cell and one oesophageal carcinoma. A total of 92% had concurrent extracranial disease. Six had single BM, 13 had two or three BM and six multiple. Up to 50 mg m−2 (level 4) no DLT was observed. At 62.5 mg m−2, one out of six patients developed DLT (thrombocytopenia-bleeding). The next dose level (75 mg m−2) was abandoned after grade 4 bone marrow toxicity (fatal neutropenic sepsis) was seen in one out of two patients. So that the dose of 50 mg m−2 will be taken forward for further study

Randomized Controlled Trial of Fish Oil and Montelukast and Their Combination on Airway Inflammation and Hyperpnea-Induced Bronchoconstriction

Both fish oil and montelukast have been shown to reduce the severity of exercise-induced bronchoconstriction (EIB). The purpose of this study was to compare the effects of fish oil and montelukast, alone and in combination, on airway inflammation and bronchoconstriction induced by eucapnic voluntary hyperpnea (EVH) in asthmatics. In this model of EIB, twenty asthmatic subjects with documented hyperpnea-induced bronchoconstriction (HIB) entered a randomized double-blind trial. All subjects entered on their usual diet (pre-treatment, n = 20) and then were randomly assigned to receive either one active 10 mg montelukast tablet and 10 placebo fish oil capsules (n = 10) or one placebo montelukast tablet and 10 active fish oil capsules totaling 3.2 g EPA and 2.0 g DHA (n = 10) taken daily for 3-wk. Thereafter, all subjects (combination treatment; n = 20) underwent another 3-wk treatment period consisting of a 10 mg active montelukast tablet or 10 active fish oil capsules taken daily. While HIB was significantly inhibited (p0.017) between treatment groups; percent fall in forced expiratory volume in 1-sec was −18.4±2.1%, −9.3±2.8%, −11.6±2.8% and −10.8±1.7% on usual diet (pre-treatment), fish oil, montelukast and combination treatment respectively. All three treatments were associated with a significant reduction (p0.017) in these biomarkers between treatments. While fish oil and montelukast are both effective in attenuating airway inflammation and HIB, combining fish oil with montelukast did not confer a greater protective effect than either intervention alone. Fish oil supplementation should be considered as an alternative treatment for EIB

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome