A Novel Whole Tissue Explant Model of Hidradenitis Suppurativa.

Hidradenitis Suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to our relatively limited understanding of HS's pathogenesis, there are currently insufficient treatment options available, and many patients' medical needs are not being met. This is partly due to a scarcity of ex vivo human assays and animal models that accurately recapitulate the disease. To address this deficit, we have developed a whole-tissue explant model of HS to examine its pathogenic mechanisms and the efficacy of potential treatments within intact human tissue. We measured cytokine protein and RNA within whole tissue maintained in an agar-media solution, finding that IL-6 and IL-8 concentrations trended upwards in both HS explants and healthy controls, while IL-17A, IL-1ß, and TNF-α exhibited increases in HS tissue alone. We also show that the explants were responsive to treatment with both dexamethasone and IL-2. Not only do our results show that this model effectively delivers treatments throughout the explants, but they also elucidate which cytokines are related to the explant process regardless of tissue state and which are related to HS tissue specifically, laying the groundwork for future implementations of this model.

Prognostic Molecular and Biological Characteristics of Phyllodes Tumors of the Breast.

Prognosis for some histological variants of a rare breast disease, phyllodes tumors, is evaluated. The prognostic potential of some molecular biological factors significantly correlating with breast cancer prognosis is evaluated on a unique clinical material (244 cases with benign, intermediate, and malignant phyllodes tumors). The development of benign phyllodes tumor relapse directly correlated with the number of G0/1-phase cells and inversely correlated with the number of cells in the G2+M and S phases. The level of steroid hormone receptors in phyllodes tumors cannot serve as a prognostic marker predicting the disease course. The presence of somatic mutations of TP53 gene and loss of heterozygosity of specific intragenic loci in the tumor correlate with the development of disease relapse (p<0.05).

Magnetic field-induced pair density wave state in the cuprate vortex halo.

High magnetic fields suppress cuprate superconductivity to reveal an unusual density wave (DW) state coexisting with unexplained quantum oscillations. Although routinely labeled a charge density wave (CDW), this DW state could actually be an electron-pair density wave (PDW). To search for evidence of a field-induced PDW, we visualized modulations in the density of electronic states N(r) within the halo surrounding Bi2Sr2CaCu2O8 vortex cores. We detected numerous phenomena predicted for a field-induced PDW, including two sets of particle-hole symmetric N(r) modulations with wave vectors QP and 2Q P , with the latter decaying twice as rapidly from the core as the former. These data imply that the primary field-induced state in underdoped superconducting cuprates is a PDW, with approximately eight CuO2 unit-cell periodicity and coexisting with its secondary CDWs.

Occupational exposure and idiopathic pulmonary fibrosis: a multicentre case-control study in Korea.

SETTING: Multicentred hospital-based cases and control subjects in Korea. OBJECTIVE: To evaluate the association between idiopathic pulmonary fibrosis (IPF) and hazardous materials to which people are occupationally exposed. DESIGN: A multicentre, hospital-based, matched case-control study was performed. The ratio of IPF cases to controls was 1:1 (n = 78 in each group). IPF cases and controls were matched in terms of age group, sex and place of residence. Conditional logistic regression analysis was performed. RESULTS: In simple logistic regression analysis, exposure to metal dust and any exposure for >1 year in an occupational setting were significantly associated with IPF (metal dust OR 4.00, 95%CI 1.34-11.97; any exposure OR 3.67, 95%CI 1.02-13.14). After adjustment for environmental and military exposures and smoking history, the OR for metal dust exposure was 4.97 (95%CI 1.36-18.17) in multiple logistic regression analysis. CONCLUSIONS: Metal dust was associated with incident IPF in Seoul and Gyeonggi Provinces in Korea. This information will be used to support a tailored preventive strategy in specific industries or occupations.

Detection of a Cooper-pair density wave in Bi2Sr2CaCu2O8+x.

The quantum condensate of Cooper pairs forming a superconductor was originally conceived as being translationally invariant. In theory, however, pairs can exist with finite momentum Q, thus generating a state with a spatially modulated Cooper-pair density. Such a state has been created in ultracold (6)Li gas but never observed directly in any superconductor. It is now widely hypothesized that the pseudogap phase of the copper oxide superconductors contains such a 'pair density wave' state. Here we report the use of nanometre-resolution scanned Josephson tunnelling microscopy to image Cooper pair tunnelling from a d-wave superconducting microscope tip to the condensate of the superconductor Bi2Sr2CaCu2O8+x. We demonstrate condensate visualization capabilities directly by using the Cooper-pair density variations surrounding zinc impurity atoms and at the Bi2Sr2CaCu2O8+x crystal supermodulation. Then, by using Fourier analysis of scanned Josephson tunnelling images, we discover the direct signature of a Cooper-pair density modulation at wavevectors QP ≈ (0.25, 0)2π/a0 and (0, 0.25)2π/a0 in Bi2Sr2CaCu2O8+x. The amplitude of these modulations is about five per cent of the background condensate density and their form factor exhibits primarily s or s' symmetry. This phenomenology is consistent with Ginzburg-Landau theory when a charge density wave with d-symmetry form factor and wavevector QC = QP coexists with a d-symmetry superconductor; it is also predicted by several contemporary microscopic theories for the pseudogap phase.

Antioxidative effects of ethyl 2-(3-(benzo[d]thiazol-2-yl)ureido)acetate against amyloid ß-induced oxidative cell death via NF-κB, GSK-3ß and ß-catenin signaling pathways in cultured cortical neurons.

We have previously shown that 2-(3-(benzo[d]thiazol-2-yl)ureido)acetate (KHG21834) attenuates amyloid beta(Aß)25-35-induced apoptotic death and shows anti-inflammatory activity against Aß25-35-induced microglial activation. However, antioxidative effects of KHG21834 against Aß-induced oxidative stress have not yet been reported. In the present study, we investigated the antioxidative function of KHG21834 in primary cultured cortical neurons, to expand the potential therapeutic efficacy of KHG21834. Pretreatment with KHG21834 protected against Aß-induced neuronal cell death and mitochondrial damage, and significantly restored GSH levels and the activities of catalase, superoxide dismutase, and glutathione peroxidase, and also suppressed the production of reactive oxygen species and protein oxidation. These results imply that KHG21834 may play a role in cellular defense mechanisms against Aß-induced oxidative stress in cultured cortical neurons. Furthermore, KHG21834 significantly attenuated the effects of Aß treatment on levels of NF-κB, ß-catenin, and GSK-3ß proteins in cortical neurons. Taken together, our results suggest that the antioxidant effects of KHG21834 may result at least in part from its ability to regulate the NF-κB, ß-catenin, and GSK-3ß signaling pathways. To our knowledge, this is the first report showing that KHG21834 significantly attenuates Aß25-35-induced oxidative stress in primary cortical neurons, and provides novel insights into KHG21834 as a possible therapeutic agent for the treatment of Aß-mediated neurotoxicity involving oxidative stress.

Spin-transfer torque generated by a topological insulator.

Magnetic devices are a leading contender for the implementation of memory and logic technologies that are non-volatile, that can scale to high density and high speed, and that do not wear out. However, widespread application of magnetic memory and logic devices will require the development of efficient mechanisms for reorienting their magnetization using the least possible current and power. There has been considerable recent progress in this effort; in particular, it has been discovered that spin-orbit interactions in heavy-metal/ferromagnet bilayers can produce strong current-driven torques on the magnetic layer, via the spin Hall effect in the heavy metal or the Rashba-Edelstein effect in the ferromagnet. In the search for materials to provide even more efficient spin-orbit-induced torques, some proposals have suggested topological insulators, which possess a surface state in which the effects of spin-orbit coupling are maximal in the sense that an electron's spin orientation is fixed relative to its propagation direction. Here we report experiments showing that charge current flowing in-plane in a thin film of the topological insulator bismuth selenide (Bi2Se3) at room temperature can indeed exert a strong spin-transfer torque on an adjacent ferromagnetic permalloy (Ni81Fe19) thin film, with a direction consistent with that expected from the topological surface state. We find that the strength of the torque per unit charge current density in Bi2Se3 is greater than for any source of spin-transfer torque measured so far, even for non-ideal topological insulator films in which the surface states coexist with bulk conduction. Our data suggest that topological insulators could enable very efficient electrical manipulation of magnetic materials at room temperature, for memory and logic applications.

Simultaneous transitions in cuprate momentum-space topology and electronic symmetry breaking.

The existence of electronic symmetry breaking in the underdoped cuprates and its disappearance with increased hole density p are now widely reported. However, the relation between this transition and the momentum-space (k-space) electronic structure underpinning the superconductivity has not yet been established. Here, we visualize the Q = 0 (intra-unit-cell) and Q ≠ 0 (density-wave) broken-symmetry states, simultaneously with the coherent k-space topology, for Bi2Sr2CaCu2O(8+δ) samples spanning the phase diagram 0.06 ≤ p ≤ 0.23. We show that the electronic symmetry-breaking tendencies weaken with increasing p and disappear close to a critical doping p(c) = 0.19. Concomitantly, the coherent k-space topology undergoes an abrupt transition, from arcs to closed contours, at the same p(c). These data reveal that the k-space topology transformation in cuprates is linked intimately with the disappearance of the electronic symmetry breaking at a concealed critical point.

Brain MRI measurements at a term-equivalent age and their relationship to neurodevelopmental outcomes.

BACKGROUND AND PURPOSE: An increased prevalence of disabilities is being observed as more preterm infants survive. This study was conducted to evaluate correlations between brain MR imaging measurements taken at a term-equivalent age and neurodevelopmental outcome at 2 years' corrected age among very low-birth-weight infants. MATERIALS AND METHODS: Of the various brain MR imaging measurements obtained at term-equivalent ages, reproducible measurements of the transcerebellar diameter and anteroposterior length of the corpus callosum on sagittal images were compared with neurodevelopmental outcomes evaluated by the Bayley Scales of Infant Development (II) at 2 years' corrected age (mean ± standard deviation, 16.1 ± 6.4 months of age). RESULTS: Ninety infants were enrolled. The mean gestational age at birth was 27 weeks and the mean birth weight was 805.5 g. A short corpus callosal length was associated with a Mental Developmental Index <70 (P = .047) and high-risk or diagnosed cerebral palsy (P = .049). A small transcerebellar diameter was associated with a Psychomotor Developmental Index <70 (P = .003), Mental Developmental Index <70 (P = .004), and major neurologic disability (P = .006). CONCLUSIONS: A small transcerebellar diameter and short corpus callosal length on brain MR imaging at a term-equivalent age are related to adverse neurodevelopmental outcomes at a corrected age of 2 years and could be a useful adjunctive tool for counseling parents about future developmental outcomes.

Protective effect of fetal pulmonary sequestration in two cases of postnatal manifestation of congenital diaphragmatic hernia.

We describe two cases of postnatally diagnosed congenital diaphragmatic hernia (CDH) combined with pulmonary sequestration, both of which were diagnosed as isolated pulmonary sequestration on prenatal ultrasound. In these cases, prenatal ultrasonography demonstrated only a hyperechoic mass on the left lower lung and the diaphragm seemed intact. In each case both lungs showed otherwise normal development throughout pregnancy. Pulmonary sequestration may serve as a 'protector', preventing herniation of abdominal contents into the thoracic cavity. The co-occurrence of CDH may be obscured by a lung mass, especially on the left lower lung, and therefore it is necessary to deliver these infants at a tertiary center and parents should be counseled about the possibility of postnatal CDH.

[Minimally invasive methods for the treatment of the recurrent varicosis].

The experience of 193 cases of recurrent variceal disease (RVD) was summarized. Major reasons of recurrences after surgery were analyzed. Traditional and miniinvasive RVD treatment approaches are listed and its efficacy was thoroughly analyzed. Thus, endovasal laser coagulation and phleboscleroobliteration of insufficient communicant veins were effective in 85% and 65% of RVD, respectively. Possibilities of cryophleboextraction as well as apparate phlebectomy with transillumination were described.

Prevalence of multiple sclerosis in Korea.

OBJECTIVE: The aim of this study was to estimate the prevalence of multiple sclerosis (MS) in Korea through a nationwide survey. METHODS: We estimated the prevalence of MS in Korea using several sources collected between 2000 and 2005: verified cases from 38 major referral hospitals across the nation, the National Health Insurance (NHI) payment request data from NHI Corporation of Korea, and the national mortality dataset from Statistics Korea. We established a network of neurologists from 38 major referral hospitals and performed a nationwide hospital survey for MS cases. The diagnoses of MS were validated according to the McDonald criteria. The diagnostic validity of each hospital was evaluated from hospital survey data to reduce the uncertainty of NHI data and was applied to estimate the prevalence using novel statistical methods. RESULTS: The estimated numbers of MS cases in Korea through 2 different statistical methods which adjust NHI data by the diagnostic validity of each hospital were very similar: 1,681 (95% confidence interval [CI] 1,490-1,902) by the stratification method and 1,640 (95% CI 1,402-1,789) by the linear regression method. The crude MS prevalence was 3.5-3.6 cases per 100,000 individuals. The estimated female-to-male ratio was 1.26. CONCLUSION: This study is the first nationwide survey for the prevalence of MS in Korea utilizing a national database in complementary way. We found an increase in the prevalence of MS that is consistent with reports from neighboring Asian countries.

[Minimally invasive interventions in surgical management of varicose diseases and its relapses].

Over the past several decades, many surgical methods of treatment for varicose disease have been implemented into clinical practice. Nonetheless, an intrinsically too traumatic nature thereof unsatisfactory cosmetic outcomes obtained, long-term postoperative rehabilitation required, and high recurrence rates reported send us in search of minimally invasive but at the same time highly efficient methods of treatment for varicose disease. The present article deals with the experience gained by Russian and foreign authors in and suggesting efficiency of novel minimally invasive technologies used for treatment of both newly diagnosed varicose disease and its relapsing forms. This is followed by analysing different variants of the procedural techniques involved.

Fractional charges on an integer quantum Hall edge.

We propose ways to create and detect fractionally charged excitations in integer quantum Hall edge states. The charge fractionalization occurs due to the Coulomb interaction between electrons propagating on different edge channels. The fractional charge of the solitonlike collective excitations can be observed in time-resolved or frequency-dependent shot noise measurements.

[Outcomes of surgical management of patients with thromboses of the superficial and deep venous system].

Presented herein are the outcomes of examination, surgical management and conservative treatment of 211patients presenting with phlebothromboses of the superficial and deep venous system of the lower limbs. Of these, 119 were treated conservatively and 92 underwent various types of surgical intervention, however those treated conservatively were not included into the final analysis. The diagnosis was verified using ultrasonographic duplex scanning (USDS) of the venous system of the inferior vena cava basin, allowing of assessing the condition of the superficial and deep venous system of the both lower extremities, followed by determining the length of the thrombotic lesion. Based on the findings of USDS, 68 (74%) patients were found to have thrombosis of the superficial veins and 24 (26%) subjects were diagnosed with deep-vein thrombosis. All the patients in order to prevent thromboembolic complications were subjected to active surgical policy. Also studied were methods of surgical management in patients with various-localization thromboses. Based on the obtained findings, it was determined that surgical treatment of patients with thromboses of the superficial and deep venous system of the lower limbs is a justified method to prevent the development of pulmonary thromboembolism.

Expression of VEGF and VEGFR2 in tumors during neoadjuvant therapy of patients with breast cancer.

We revealed a significant positive correlation between the concentrations of tissue VEGF and its receptor VEGFR2 in the primary tumor. The degree and direction of changes in the content of VEGF and VEGFR2 in cytosols of tumors from patients with locally spread breast cancer during the preoperation therapy depended on initial levels of these parameters. We found that the expression of the studied factors depended on the degree of therapeutic pathomorphosis in the tumor tissue.

[Influence of neoadjuvant therapy on VEGFR-2 levels in tumor and blood serum from breast cancer patients].

Degree and trends of changes taking place in the angiogenic factors VEGF and VEGFR-2 were studied in cytosols and blood serum sampled from breast cancer patients in the course of neoadjuvant therapy. Such evidence was evaluated vis-alpha-vis basic indices for clinic-morphological features of the disease. The study included 30 cases of locally-advanced tumors. Our results pointed to an influence produced by preoperative therapy on the levels of angiogenic factors both in tumor and serum. However, trends of development of such parameters are different and independent of therapeutic modality. Correlation was established between VEGF and VEGFR-2 levels in residual tumor, on the one hand, and degree of therapeutic pathomorphosis, on the other.

[Combined therapy of lower limb variceal disease].

Complex surgical and medical therapy was used for 386 patients with lower limb variceal disease 2nd and 3rd form (segmental and disseminated varices with reflux through the superficial and perforant veins) and chronic venous insufficiency stage I (according to the Russian classification). Five main types of surgical interventions were fulfilled: combined phlebectomy, trunk scleroobliteration, short stripping with insufficient perforants ligation, short stripping with excision or damage of variceal influx, and short stripping with trunk scleroobliteration. Besides, vast majority of patients received venotonic drug Phlebodia 600 pre and postoperatively. Miniinvasive and atraumatic interventions were characterized by the decrease of postoperative subcutaneous hematomas, no incidence of n. saphenus damage and lymphorrhea, good cosmetic outcomes due to the absence of additional incisions. The duration of postoperative recovery correlated with intraoperative trauma and Phlebodia 600 administration. In conclusion, combination of complex surgical procedures and venotonic drugs can be widely used for the management of lower limb variceal disease, especially for its uncomplicated forms. While preserving the radicality, these interventions yield favorite esthetical results, reduce the time of postoperative recovery and disability, thus, appear to be cost effective.

Dynamical layer decoupling in a stripe-ordered high-T(c) superconductor.

In the stripe-ordered state of a strongly correlated two-dimensional electronic system, under a set of special circumstances, the superconducting condensate, like the magnetic order, can occur at a nonzero wave vector corresponding to a spatial period double that of the charge order. In this case, the Josephson coupling between near neighbor planes, especially in a crystal with the special structure of La(2-x)Ba(x)CuO(4), vanishes identically. We propose that this is the underlying cause of the dynamical decoupling of the layers recently observed in transport measurements at x = 1/8.

Complicated giant diverticulum of the transverse colon accompanied by right inguinal hernia of the greater omentum.

Giant colonic diverticulum is a very rare entity in colonic diverticular disease and is characterized by a high rate of complications such as perforation, abscess formation and even carcinoma. We report a case of a complicated giant diverticulum of the transverse colon accompanied by a right inguinal hernia of the greater omentum in a 52-year-old man, as demonstrated on CT.