Group IV Nociceptors Develop Axonal Chemical Sensitivity During Neuritis And Following Treatment Of The Sciatic Nerve With Vinblastine

We have previously shown that nerve inflammation (neuritis) and transient vinblastine application lead to axonal mechanical sensitivity in nociceptors innervating deep structures. We have also shown that these treatments reduce axonal transport, and proposed that this leads to functional accumulation of mechanically sensitive channels in the affected part of the axons. While informing the etiology of mechanically induced pain, axonal mechanical sensitivity does not address the common report of ongoing radiating pain during neuritis, which could be secondary to the provocation of axonal chemical sensitivity. We proposed that neuritis and vinblastine application would induce sensitivities to noxious chemicals, and that the number of chemo-sensitive channels would be increased at the affected site. In adult female rats, nerves were either untreated, or treated with complete Freund’s adjuvant (to induce neuritis) or vinblastine. After 3-7 days, dorsal root teased fiber recordings were taken from Group IV neurons with axons within the sciatic nerve. Sciatic nerves were injected intraneurally with a combination of noxious inflammatory chemicals. While no normal sciatic axons responded to this stimulus, 80% and 38% of axons responded in the neuritis and vinblastine groups, respectively. In separate experiments, sciatic nerves were partially ligated and treated with complete Freund’s adjuvant or vinblastine (with controls), and after 3-5 days were immunolabeled for the histamine 3 receptor. The results supported that both neuritis and vinblastine treatment reduce transport of the histamine 3 receptor. The finding that nociceptor axons can develop ectopic chemical sensitivity is consistent with ongoing radiating pain due to nerve inflammation

Aberrant neuronal activity in a model of work-related upper limb pain and dysfunction

Work-related musculoskeletal disorders associated with intense repetitive tasks are highly prevalent. Painful symptoms associated with such disorders can be attributed to neuropathy. In this study, we characterized the neuronal discharge from the median nerve in rats trained to perform an operant repetitive task. After 3-weeks of the task, rats developed pain behaviors and a decline in grip strength. Ongoing activity developed in 17.7% of slowly conducting neurons at 3-weeks, similar to neuritis. At 12-weeks, an irregular high frequency neuronal discharge was prevalent in >88.4% of slow and fast conducting neurons. At this time point, 8.3% of slow and 21.2% of fast conducting neurons developed a bursting discharge, which, combined with a reduction in fast-conducting neurons with receptive fields (38.4%), is consistent with marked neuropathology. Taken together, we have shown that an operant repetitive task leads to an active and progressive neuropathy that is characterized by marked neuropathology following 12-weeks task that mainly affects fast conducting neurons. Such aberrant neuronal activity may underlie painful symptoms in patients with work-related musculoskeletal disorders

Dorsal Scapular Artery Variations And Relationship To The Brachial Plexus, And A Related Thoracic Outlet Syndrome Case

Knowledge of the relationship of the dorsal scapular artery (DSA) with the brachial plexus is limited. We report a case of a variant DSA path, and revisit DSA origins and underinvestigated relationship with the plexus in cadavers. The DSA was examined in a male patient and 106 cadavers. In the case, we observed an unusual DSA compressing the lower plexus trunk, that resulted in intermittent radiating pain and paresthesia. In the cadavers, the DSA originated most commonly from the subclavian artery (71%), with 35% from the thyrocervical trunk. Nine sides of eight cadavers (seven females) had two DSA branches per side, with one branch from each origin. The most typical DSA path was a subclavian artery origin before passing between upper and middle brachial plexus trunks (40% of DSAs), versus between middle and lower trunks (23%), or inferior (4%) or superior to the plexus (1%). Following a thyrocervical trunk origin, the DSA passed most frequently superior to the plexus (23%), versus between middle and lower trunks (6%) or upper and middle trunks (4%). Bilateral symmetry in origin and path through the brachial plexus was observed in 13 of 35 females (37%) and 6 of 17males (35%), with the most common bilateral finding of a subclavian artery origin and a path between upper and middle trunks (17%). Variability in the relationship between DSA and trunks of the brachial plexus has surgical and clinical implications, such as diagnosis of thoracic outlet syndrome

Minimally Invasive Surgery for the Management of Lung Cancer

Lung cancer is the leading cause of cancer-related death and the most diagnosed cancer. The treatment of Non-Small Cell Lung Cancer (NSCLC) depends on clinical staging. Surgical radical resection is recommended for patients with stage 1 or 2 of disease and represents the treatment of choice. In the last decades, the surgical approach for lung cancer changed moving from an open approach to a minimally invasive approach, represented by Video Assisted Thoracic Surgery (VATS) and Robot-Assisted Thoracic Surgery (RATS). In this chapter, we illustrate the characteristics of lung cancer, the diagnosis, the classification, the staging and the preoperative evaluation. Then we focus on the surgical treatment of lung cancer and on how it has changed during the years. We explain the open approach represented by the traditional posterolateral thoracotomy and by the muscle-sparing thoracotomy. We illustrate VATS approach and evolution: from the hybrid approach to the pure VATS that can be triportal, biportal or even uniportal. Then, we focus on RATS approach, characterized by the use of multiple ports in the same intercostal space and how it evolved toward the uniportal approach. The objective is to combine the advantage of uniportal VATS (lower postoperative pain, enhanced recovery) and RATS (better visualization, more degrees of movements)

Global variation in the beta diversity of lake macrophytes is driven by environmental heterogeneity rather than latitude

Aim: We studied global variation in beta diversity patterns of lake macrophytes using regional data from across the world. Specifically, we examined 1) how beta diversity of aquatic macrophytes is partitioned between species turnover and nestedness within each study region, and 2) which environmental characteristics structure variation in these beta diversity components.  Location: Global  Methods: We used presence-absence data for aquatic macrophytes from 21 regions distributed around the world. We calculated pairwise-site and multiple-site beta diversity among lakes within each region using Sørensen dissimilarity index and partitioned it into turnover and nestedness coefficients. Beta regression was used to correlate the diversity coefficients with regional environmental characteristics. Results: Aquatic macrophytes showed different levels of beta diversity within each of the 21 study regions, with species turnover typically accounting for the majority of beta diversity, especially in high-diversity regions. However, nestedness contributed 30-50% of total variation in macrophyte beta diversity in low-diversity regions. The most important environmental factor explaining the three beta diversity coefficients (total, species turnover and nestedness) was altitudinal range, followed by relative areal extent of freshwater, latitude and water alkalinity range. Main conclusions: Our findings show that global patterns in beta diversity of lake macrophytes are caused by species turnover rather than by nestedness. These patterns in beta diversity were driven by natural environmental heterogeneity, notably variability in altitudinal range (also related to temperature variation) among regions. In addition, a greater range in alkalinity within a region, likely amplified by human activities, was also correlated with increased macrophyte beta diversity. These findings suggest that efforts to conserve aquatic macrophyte diversity should primarily focus on regions with large numbers of lakes that exhibit broad environmental gradients.

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers

Dilation of tracheal stenosis below tracheostomy tube with Dolphin percutaneous tracheostomy kit : Tracheal stenosis treated with Dolphin PDT

We reported a new minimally invasive procedure to treat tracheal stenosis below tracheostomy tube using standard Ciaglia Blue Dolphin kit for percutaneous tracheostomy. Under endoscopic view, the Dolphin kit was inserted through the stoma into the stenosis; the balloon was inflated until a sufficient tracheal diameter was obtained; then, a longer tracheostomy tube was inserted through the stenosis and the distal tip placed near the carina. This procedure was succesfully applied in seven patients

Systematic review of augmented reality in urological interventions:the evidences of an impact on surgical outcomes are yet to come

To perform a systematic literature review on the clinical impact of augmented reality (AR) for urological interventions

Bleeding during Learning Curve of Thoracoscopic Lobectomy: CUSUM Analysis Results

Background The management of intraoperative bleeding during thoracoscopic lobectomy is challenging, especially for non-experienced surgeons. We evaluated intraoperative bleeding in relation to learning curve of thoracoscopic lobectomy, the strategies to face it, the outcomes, and the target case number for gaining the technical proficiency. Methods This was a retrospective single center study including consecutive patients undergoing thoracoscopic lobectomy for lung cancer. Based on cumulative sum analysis, patients were divided into early and late experience groups, and the differences on surgical outcomes, with particular focus on vascular injury, were statistically compared. Results Eight-three patients were evaluated. Cumulative sum charts showed a decreasing of operative time, blood loss, and hospital stay after the 49th, the 43th, and the 39th case, respectively. Early ( n = 49) compared with late experience group ( n = 34) was associated with higher conversion rate ( p = 0.08), longer operative time ( p <0.0001), greater blood loss ( p <0.0001), higher transfusion rate ( p = 0.01), higher postoperative air leak rate ( p = 0.02), longer chest tube stay ( p <0.0001), and hospitalization ( p <0.0001). Six patients (7%) had intraoperative bleeding during early phase of learning curve, successfully treated by thoracoscopy in four cases. Patients with vascular injury ( n = 6) compared with control group ( n = 77) presented a longer operative time ( p = 0.003), greater blood loss ( p = 0.0001), and higher transfusion rate ( p = 0.001); no significant differences were found regarding postoperative morbidity ( p = 0.57), length of chest tube stay ( p = 0.07), and hospitalization ( p = 0.07). Conclusion Technical proficiency was achieved after 50 procedures. All vascular injuries occurred in the early phase of learning curve; they were safely managed, without affecting surgical outcomes