Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery

Purpose:This study aimed to non-invasively test the hypothesis that(a) short-term lower limb unloading would induce changes in the neural control of force production(based on motor units(MUs) properties) in the vastus lateralis muscle and(b) possible changes are reversed by active recovery(AR).Methods:Ten young males underwent 10 days of unilateral lower limb suspension(ULLS) followed by 21 days of AR.During ULLS,participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position(15°-20°) and with the contralateral foot raised by an elevated shoe.The AR was based on resistance exercise(leg press and leg extension) and executed at 70% of each participant’s 1repetition maximum,3 times/week.Maximal voluntary isometric contraction(MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline,after ULLS,and after AR.MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%,25%,and 50% of the current MVC,and individual MUs were tracked across the 3 data collection points.Results:We identified 1428 unique MUs,and 270 of them(18.9%) were accurately tracked.After ULLS,MVC decreased by 29.77%,MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities(with changes between the 2 variables strongly correlated),while discharge rate was reduced at 10% and 25% but not at 50% MVC.Impaired MVC and MUs properties fully recovered to baseline levels after AR.Similar changes were observed in the pool of total as well as tracked MUs.Conclusion:Our novel results demonstrate,non-invasively,that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs,suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold.However,after 21 days of AR,the impaired MUs properties were fully restored to baseline levels,highlighting the plasticity of the components involved in neural control.

Role of the adipocyte immune brain axis in Parkinson's disease:friend or foe?

The classical role of adipocytokines is a negative feedback mechanism,providing information about bodily energy reserves to the brain,and thus controlling satiety and food intake (Campfield et al.,1995).Adipose tissue forms the largest endocrine organ of the body.After the initial description of leptin and its receptor,LEPR/OBR,with its main active isoform OBRb,there was an initial hope for a drugable pathway to counteract the increasing burden of overweight/adiposity,metabolic syndrome,and related disorders (Figure1).

Methane Concentration Influence on Combustion in a Rapid Compression Machine under DFICE Relevant Conditions

In this experimental work,an optically accessible rapid compression machine is used to study the ignition and combustion process under engine relevant operation conditions for five different air-natural gas equivalence ratios(λ)ignited with either 12.2 mg or 6.7 mg of pilot diesel injected at 1,600 bar.Initial temperature of the ambient mixture,walls and injector was 333 K.Additionally,for the short(6.7 mg)diesel injection,the variation in the ID(ignition delay)for two higher ambient temperatures(343 K and 353 K)was measured.Pressure and piston displacement are recorded while two high-speed cameras simultaneously capture signals in the visible range spectrum and at 305 nm wavelength for OH^(*)chemiluminescence respectively.ID is measured both from OH^(*)and pressure rise.From the recorded data,the heat release ratio is estimated and compared with the visual signals.This gives an insight of the temporal and spatial evolution of the flame,as well as a qualitative perception of the transition from spray ignition into a premixed flame in the ambient fuel-air mixture.It was found that increasing the methane concertation delays the ignition,reduces the natural flame luminosity and enhances the OH^(*)chemiluminescence signal.

First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.

CT上股部肌肉和脂肪组织的三维分布与急性髋部骨折的关系

目的通过CT评估股上部软组织成分,评价髋部骨折的决定因素。材料与方法在对前瞻性收集数据的回顾性分析中,对55名女性对照者[平均年龄(73.1±9.3)岁]的CT结果与40例女性急性髋部骨折病人[平均年龄(80.2±11.0)岁]的CT结果进行比较。测定了软组织的87种特征。

Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer

The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated with multiple processes involved in tumor growth and metastasis.Compared with mTORC1,much less is known about mTORC2 in cancer,mainly because of the unavailability of a selective inhibitor.However,existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so far.It is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth,cell survival,metabolism,and cytoskeletal organization.It is not only implicated in tumor progression,metastasis,and the tumor microenvironment but also in resistance to therapy.Rictor,the central subunit of mTORC2,was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad prognosis.Moreover,AKT,the main downstream regulator of mTORC2/Rictor,is one of the most highly activated proteins in cancer.Primary and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment,emphasizing the need for further therapeutic options.This review,therefore,summarizes the role of mTORC2/Rictor in cancer,with special focus on primary liver cancer but also on liver metastases.

An approach to controlling the fluorescence of graphene quantum dots: From surface oxidation to fluorescent mechanism

We report a facile method of synthesizing graphene quantum dots（GQDs） with tunable emission. The as-prepared GQDs each with a uniform lateral dimension of ca. 6 nm have fine solubility and high stability. The photoluminescence mechanism is further investigated based on the surfacestructure and the photoluminescence behaviors. Based on our discussion, the green fluorescence emission can be attributed to the oxygen functional groups, which could possess broad emission bands within the π –π ＊ gap. This work is helpful to explain the vague fluorescent mechanism of GQDs, and the reported synthetic method is useful to prepare GQDs with controllable fluorescent colors.

Introducing Cinematic Rendering: A Novel Technique for Post-Processing Medical Imaging Data

Since the 1980s, various techniques have been used in the field of medicine for the post-processing of medical imaging data from computed tomography (CT) and magnetic resonance (MR). They include multiplanar reformations (MPR), maximum intensity projection (MIP) and Volume Rendering (VR). This paper presents the prototype of a new means of post-processing radiological examinations such as CT and MR, a technique that, for the first time, provides photorealistic visualizations of the human body. This new procedure was inspired by the quality of images achieved by animation software such as programs used in the entertainment industry, particularly to produce animated films. Thus, the name: Cinematic Rendering. It is already foreseeable that this new method of depiction will quickly be incorporated into the set of instruments employed in socalled virtual anatomy (teaching anatomy through the use of radiological depictions of the human body via X-ray, CT and MR in addition to the use of computer animation programs designed especially for human anatomy). Its potential for medical applications will have to be evaluated by future scientific investigations.

Effects of immune cells on mesenchymal stem cells during fracture healing

In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.

Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases

Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma(CRC) and inflammatory bowel diseases(IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong antiangiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.

Jejunitis and brown bowel syndrome with multifocal carcinogenesis of the small bowel

This is the first report describing a case where prolonged,severe malabsorption from brown bowel syndrome progressed to multifocally spread small bowel adenocarcinoma. This case involves a female patient who was initially diagnosed with chronic jejunitis associated with primary diffuse lymphangiectasia at the age of 26 years. The course of the disease was clinically,endoscopically,and histologically followed for 21 years until her death at the age 47 due to multifocal,metastasizing adenocarcinoma of the small bowel. Multiple lipofuscin deposits(so-called brown bowel syndrome) and severe jejunitis were observed microscopically,and sections of the small bowel showed dense lymphoplasmacytic infiltration of the lamina propria as well as blocked lymphatic vessels. After several decades,multifocal nests of adenocarcinoma cells and extensive,flat,neoplastic mucosal proliferations were found only in the small bowel,along with a loss of the mismatch repair protein MLH1 as a long-term consequence of chronic jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis colon carcinoma syndrome. This article demonstrates for the first time multifocal carcinogenesis in the small bowel in a malabsorption syndrome in an enteritis-dysplasia-carcinoma sequence.

LIMITATIONS OF CANCER MARGIN DELINEATION BY MEANS OF AUTOFLUORESCENCE IMAGING UNDER CONDITIONS OF LASER SURGERY

Limitations of cancer margin delineation and surgical guidance by means of autofluorescence imaging under conditions of laser ablation were investigated and preliminary results are presented.PinPoint^(TM)(Novadaq Technologies Inc.,Canada)was used to capture digital images and Er:YAG laser(2.94μm,Glissando,WaveLight^(TM),Germany)was exploited to cause laser ablation on both normal and cancer sites of the specimen.It was shown that changes of the autofluorescence image after ablation extend beyond the actual sizes of the ablation loci.The tumor tissue after the laser ablation starts to emit fluorescent light within the green wavelength band(490-550nm)similar to normal tissue stating that the current technology of in-process tissue classification fails.However,when the autofluorescence was collected in the red range(600-750nm),then the abnormal/normal contrast was reduced,but still present even after the laser ablation.The present study highlights the importance of finding a proper technology for surgical navigation of cancer removal under conditions of high power effects in biological tissues.

Histone deacetylases in hearing loss: Current perspectives for therapy

Hearing loss is one of the most frequent health issues in industrialized countries. The pathogenesis and molecular mechanisms of hearing loss are still unclear. Histone deacetylases(HDACs) are emerging as key enzymes in many physiological processes, including chromatin remodeling,regulation of transcription, DNA repair, metabolism, genome stability and protein secretion. Recent studies indicated that HDACs are associated with the development and progression of hearing loss. Dysfunction of HDACs could promote the oxidative stress and aging in the inner ear. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of hearing loss has never been so pressing. In this review, we will summarize the reported literatures for HDACs in hearing loss and discuss how HDAC family members show different performances for the possibility of process of diseases development. The possibility of pharmacological intervention on hearing loss opens a novel path in the treatment of hearing loss.

REAL-TIME OPTICAL MONITORING OF CAPILLARY GRID SPATIAL PATTERN IN EPITHELIUM BY SPATIALLY RESOLVED DIFFUSE REFLECTANCE PROBE

We developed a novel method for real-time monitoring of alteration of the local epithelium vessel/capillary and blood oxygenation spatial pattern in epithelium exploiting a compact fibre sensor system based on spatially and spectrally resolved diffuse reflectance.The method is based on collection of spatially resolved diffuse reflectance Re(λ)by fiber sensors.The spatial resolution is provided as a dependence of Re(λ)on a set of distancesρbetween the source and detector(attenuation curve).It is expected that the new method can reasonably extract the minor spatial deviations of oxygenation and local blood volume fraction-parameters,directly related to the local vessel density and capillary spatial patterns in the epithelium.Light scattering in visible range is naturally taken into account in the proposed method.

Feet injuries in rock climbers

While injuries of the upper extremity are widely discussed in rock climbers, reports about the lower extremity are rare. Nevertheless almost 50 percent of acute injuries involve the leg and feet. Acute injuries are either caused by ground falls or rock hit trauma during a fall. Most frequently strains, contusions and fractures of the calcaneus and talus. More rare injuries, as e.g., osteochondral lesions of the talus demand a highly specialized care and case presentations with combined iliac crest graft and matrix associated autologous chondrocyte transplantation are given in this review. The chronic use of tight climbing shoes leads to overstrain injuries also. As the tight fit of the shoes changes the biomechanics of the foot an increased stress load is applied to the fore-foot. Thus chronic conditions as subungual hematoma, callosity and pain resolve. Also a high incidence of hallux valgus and hallux rigidus is described.

Solution-processed tandem organic solar cells

Organic solar cells(OSCs)show great potential in non-grid energy supply due to its unique properties including light-weight,flexibility,semi-transparency,design flexibility,low cost and so on.Thanks to researchers'tremendous efforts in materials development and device engineering,the power con-version efficiency(PCE)for single-junction OSCs(SJ-OSCs)has exceeded 18%[1,2].

MICROENDOSCOPIC SPECTRAL IMAGING AS A TOOL FOR SMALL DUCTUAL DIAGNOSTICS:PRELIMINARY EXPERIENCE

A technical feasibility of autofluorescence ductoscopy in breast milk ducts as blood vessels phantoms has been assessed as successful.Malignant tumor can be clearly identified through the milk ducts.We also present the operation principle as well as the preliminary experimental results of a new type of microsize multicorefiber that enables imaging through blood vessel phantoms.Imaging of a manipulated microwire through a drilled phantom is presented.

Restoration of function after cortical lesion: does it require an internal template?

The brain controls virtually all body functions, both internally and in interaction with the external environment. As the basic body anatomy of all vertebrates has a bilateral symmetry, structures and functions of vertebrate brains are also organized according to this fundamental anatomical principle to meet all sensory, motor, and internal requirements of body control. Consequently, particular parts or functions of the body are controlled by particular brain structures.

Rotating Lepton Model of Pions and Kaons: Mechanics at fm Distances

The present article is a continuation of a recently published paper [1] in which we have modeled the composition and structure of neutrons and other hadrons using the Rotating Lepton Model (RLM) which is a Bohr type model employing the relativistic gravitational attraction between three ultrafast rotating neutrinos as the centripetal force. The RLM accounts for special relativity and also for the De Broglie equation of quantum mechanics. In this way this force was shown to reach the value of the Strong Force while the values of the masses of the rotating relativistic neutrinos reach those of quarks. Masses computed for twelve hadrons and bosons are in very close (~2%) agreement with the experimental values. Here we use the same RLM approach to describe the composition and structure and to compute the masses of Pions and Kaons which are important zero spin mesons. Contrary to hadrons and bosons which have been found via the RLM to comprise the heaviest neutrino eigenmass m3, in the case of mesons the intermediate neutrino mass eigenstate m2 is found to play the dominant role. This can explain why the lowest masses of mesons are generally smaller than those of hadrons and bosons. Thus in the case of Pions it is found that they comprise three rotating m2 mass eigenstate neutrinos and the computed mass of 136.6 MeV/c2 is in good agreement with the experimental value of 134.977 MeV/c2. The Kaon structure is found to consist of six m2 mass eigenstate neutrinos arranged in two parallel pion-type rotating triads. The computed Kaon mass differs less that 2% from the experimental K± and K°values of 493.677 MeV/c2 and 497.648 MeV/c2 respectively. This, in conjunction with the experimentally observed decay products of the Kaons, provides strong support for the proposed K structure.

Acquired Gerbode Defect Secondary to Severe Bicuspid Aortic Valve Endocarditis

An annular aortic abscess is a fatal complication of infective endocarditis. Echocardiography is the initial imaging modality to confirm the diagnosis in suspected infective endocarditis. Here, we present a case of a bicuspid aortic valve infective endocarditis caused by Staphylococcus aureus and complicated with annular aortic abscess resulting in acquired Gerbode defect (type II) with tricuspid valve vegetation which was undiagnosed preoperatively. The intraoperative transoesophageal echocardiography yields a new finding prior to the surgical incision, which impacted the clinical decision-making and increased the burden of the procedure.