Braids with as many full twists as strands realize the braid index

We characterize the fractional Dehn twist coefficient of a braid in terms of a slope of the homogenization of the Upsilon function, where Upsilon is the function-valued concordance homomorphism defined by Ozsv\'ath, Stipsicz, and Szab\'o. We use this characterization to prove that $n$-braids with fractional Dehn twist coefficient larger than $n-1$ realize the braid index of their closure. As a consequence, we are able to prove a conjecture of Malyutin and Netsvetaev stating that $n$-times twisted braids realize the braid index of their closure. We provide examples that address the optimality of our results. The paper ends with an appendix about the homogenization of knot concordance homomorphisms.Comment: 26 pages, 5 figures, comments welcome! V2: Implementation of referee suggestions. Accepted for publication by the Journal of Topolog

Cigarette Smoke-Induced Pulmonary Inflammation Becomes Systemic by Circulating Extracellular Vesicles Containing Wnt5a and Inflammatory Cytokines

Chronic obstructive pulmonary disease (COPD) is a devastating, irreversible pathology affecting millions of people worldwide. Clinical studies show that currently available therapies are insufficient, have no or little effect on elevated comorbidities and on systemic inflammation. To develop alternative therapeutic options, a better understanding of the molecular background of COPD is essential. In the present study, we show that non-canonical and pro-inflammatory Wnt5a is up-regulated by cigarette smoking with parallel up-regulation of pro-inflammatory cytokines in both mouse and human model systems. Wnt5a is not only a pro-inflammatory Wnt ligand but can also inhibit the anti-inflammatory peroxisome proliferator-activated receptor gamma transcription and affect M1/M2 macrophage polarization. Both Wnt5a and pro-inflammatory cytokines can be transported in lipid bilayer sealed extracellular vesicles that reach and deliver their contents to every organ measured in the blood of COPD patients, therefore, demonstrating a potential mechanism for the systemic nature of this crippling disease

Airway stent complications: the role of follow-up bronchoscopy as a surveillance method.

Background: Airway stenting has become an integral part of the therapeutic endoscopic management of obstructive benign and malignant central airway diseases. Despite increased use of airway stents and frequent stent-associated complications, no clear guidelines for surveillance and maintenance exist. This study aim is to elucidate predictive factors associated with development of stent complications, as well as an optimal surveillance period for follow-up bronchoscopy for early detection and possible prevention of stent-associated complications. Methods: Retrospective cohort study of all patients who underwent airway stent placements at our institution from April 2010 to December 2013 for benign and malignant airway diseases. Metallic, silicone (straight, Y stent, T-tube) and hybrid stents were included in the study. Stent complications were analyzed at the time of follow-up bronchoscopy performed four to six weeks after initial stent placement or earlier if patients became symptomatic. Results: The study included 134 patients of which 147 stents were placed. Follow-up bronchoscopy was performed in 94 patients. Symptomatic status at the time of follow-up bronchoscopy was not associated with stent complications [odds ratio (OR) =1.88; 95% CI: 0.79-4.45; P=0.15]. Patient age, sex, indication for stent placement, and stent location, were not associated with development of complications (all P\u3e0.05). Compared to all other stents, hybrid stents were more likely to migrate (OR =6.60; 95% CI: 2.16-20.2; P=0.001) or obstruct by secretions (OR =2.53; 95% CI: 1.10-5.84; P=0.03). There were no complications associated with surveillance bronchoscopy. Conclusions: Surveillance bronchoscopy within 4 to 6 weeks of stent placement may be useful for early detection of complications and their subsequent management, regardless of symptomatic status and indication for stent placement. Prospective multicenter studies are needed to compare optimal surveillance methods and the impact on patient mortality, morbidity and healthcare costs

Alteration in the Wnt microenvironment directly regulates molecular events leading to pulmonary senescence

In the aging lung, the lung capacity decreases even in the absence of diseases. The progenitor cells of the distal lung, the alveolar type II cells (ATII), are essential for the repair of the gas-exchange surface. Surfactant protein production and survival of ATII cells are supported by lipofibroblasts that are peroxisome proliferator-activated receptor gamma (PPARγ)-dependent special cell type of the pulmonary tissue. PPARγ levels are directly regulated by Wnt molecules; therefore, changes in the Wnt microenvironment have close control over maintenance of the distal lung. The pulmonary aging process is associated with airspace enlargement, decrease in the distal epithelial cell compartment and infiltration of inflammatory cells. qRT-PCR analysis of purified epithelial and nonepithelial cells revealed that lipofibroblast differentiation marker parathyroid hormone-related protein receptor (PTHrPR) and PPARγ are reduced and that PPARγ reduction is regulated by Wnt4 via a β-catenin-dependent mechanism. Using a human in vitro 3D lung tissue model, a link was established between increased PPARγ and pro-surfactant protein C (pro-SPC) expression in pulmonary epithelial cells. In the senile lung, both Wnt4 and Wnt5a levels increase and both Wnt-s increase myofibroblast-like differentiation. Alteration of the Wnt microenvironment plays a significant role in pulmonary aging. Diminished lipo- and increased myofibroblast-like differentiation are directly regulated by specific Wnt-s, which process also controls surfactant production and pulmonary repair mechanisms

CHRONIC INFLAMMATION AND END-DIALYSIS OVERWEIGHT. A 36 MONTH PROSPECTIVE OBSERVATIONAL STUDY

Introduction and Aims: Attaining dry body weight is paramount in dialysis practice, but this goal is not always reached.We hypothesized that the amount of end-dialysis overweight (edOW), could be associated to increased chronic inflammation and mortality. Aim of the study: to evaluate the effect of edOWon serum C-reattive protein (hsCRP) concentrations and on survival in a cohort of 182 prevalent HD patients ( pts) followed for 36 months. Methods: In 182 pts (117 men, age 65±12 years, vintage 48 months; range 6-336), edOWwas present in 98/182 (54%) pts. Mean value was 0.4±0.2 Kg (range: 0.1-1.4). In the 98 pts with edOW(Group 1) and in the other 84 (Group 2) we evaluated: Ultrafiltration rate(UFR), hsCRPdry body weight (dBW), Kt/V, protein catabolic rate (PCRn), interdialytic weight gain (IDWG), mean arterial pressure (MAP). Unpaired Student’s t test was employed to compare groups, linear regression analysis to test correlations, log-rank test and Kaplan-Meier curves to evaluate survival. Results: Mean UFR was 11.7±2.8 ml/Kg/hour, dBW 64±12 Kg, hsCRP 6.6 (0.2-36) mg/L, Kt/V 1.27±0.09, PCRn 1.06±0.10 g/Kg/day, IDWG 2.8±0.4 Kg, MAP 97±6.5 mmHg. edOWand hsCRP were directly and significantly correlated (r= 0.67; p<0.0001). Comparison between pts with (Group 1) and without (Group 2) edOW showed significant differences in: UFR (12.7±2.6 vs 10.9±2.6 ml/Kg/hour; p< 0.0001), hsCRP (13.0±8.1 vs 5.2±5.3 mg/L; p< 0.0001), and PCRn (1.03±0.09 vs 1.08±0.10 g/Kg/day; p<0.004). 98 pts (54%) died during follow-up for cardiovascular complications in 69% of cases. Survival curves showed significantly greater mortality in Group 1 vs Group 2 in relation to the amount of edOW, and hsCRP (p<0.0001). Conclusions: edOWand chronic inflammation are directly correlated in HD pts, and both are associated to a greater long-term risk of mortality

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: a nested study within a randomized placebo controlled trial

The effect of levothyroxine (LT4) therapy for subclinical hypothyroidism (SHypo) on appendicular bone geometry and volumetric density has so far not been studied. In a nested study within the randomized, placebo-controlled Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) trial, we assessed the effect of LT4 therapy on bone geometry as measured by peripheral quantitative computed tomography (pQCT). In the TRUST trial, community-dwelling adults aged ≥65 years with SHypo were randomized to LT4 with dose titration vs. placebo with mock titration. We analyzed data from participants enrolled at the TRUST site in Bern, Switzerland who had bone pQCT measured at baseline and at 1 to 2 years follow-up. The primary outcomes were the annual percentage changes of radius and tibia epi- and diaphysis bone geometry (total and cortical cross-sectional area (CSA) and cortical thickness), and of volumetric bone mineral density (bone mineral content (BMC) and total, trabecular and cortical volumetric bone mineral density (vBMD)). We performed linear regression of the annual percentage changes adjusted for sex, LT4 dose at randomization and muscle cross-sectional area. The 98 included participants had a mean age of 73.9 (±SD 5.4) years, 45.9% were women, and 12% had osteoporosis. They were randomized to placebo (n = 48) or LT4 (n = 50). Annual changes in BMC and vBMD were similar between placebo and LT4-treated groups, without significant difference in bone geometry or volumetric bone mineral density changes, neither at the diaphysis, nor at the epiphysis. For example, in the placebo group, epiphyseal BMC (radius) decreased by a mean 0.2% per year, with a similar decrease of 0.5% per year in the LT4 group (between-group difference in %ΔBMC 0.3, 95% CI -0.70 to 1.21, p = 0.91). Compared to placebo, LT4 therapy for an average 14 months had no significant effect on bone mass, bone geometry and volumetric density in older adults with subclinical hypothyroidism. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov numbers NCT01660126 (TRUST Thyroid trial) and NCT02491008 (Skeletal outcomes)

Examples of non-minimal open books with high fractional Dehn twist coefficient

For a fixed surface S, one can ask if there are conditions on open books with pages S that imply maximality of the Euler characteristic of S among all pages of open books encoding the same 3-manifold (or at least imply maximality among those open books that encode the same 3-manifold and support the same contact structure). In this short note we propose an explicit variant of this question with a condition that involves the amount of twisting of the monodromy and the topological type of S, and we construct examples of open books for 3-manifolds that support our choice of condition. In particular, our examples show that the condition on twisting necessarily depends on the topological type of S. We find these examples of open books as the double branched covers of families of closed braids studied by Malyutin and Netsvetaev