Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-Control Study

Abstract: Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0–9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.

http://ift.tt/2qDmU5n

A Rapidly Growing Facial Mass: Challenge

No abstract available

http://ift.tt/2rBi6L2

Pseudoxanthoma Elasticum-Like Papular Eruption

No abstract available

http://ift.tt/2rBtFlj

Diagnostic Criteria in Intraepithelial Pagetoid Neoplasms: A Histopathologic Study and Evaluation of Select Features in Paget Disease, Bowen Disease, and Melanoma In Situ

Background: Paget disease, Bowen disease, and malignant melanoma in situ are intraepidermal neoplasms, characterized by the presence of pagetoid scatter of atypical cells in the epidermis. This study reviewed the frequency of select histologic criteria to validate their usefulness in the histologic distinction between these entities. Methods: One hundred forty-four specimens with the diagnosis of Bowen disease, 144 specimens with Paget disease (mammary and extramammary), and 144 specimens with malignant melanoma in situ were examined microscopically to define frequencies of select histologic criteria present in each disease. Results: Comparison between mammary Paget and extramammary Paget disease showed no significant differences in the features studied. Crushing of basal keratinocytes, presence of atypical cells in the corneum, and presence of large cells with amphophilic cytoplasm were significantly noted in Paget disease. Transition between the atypical clear cells and surrounding keratinocytes was absent in all cases of melanoma in situ and in 87 (60.4%) cases of Paget disease, but it was significantly associated with Bowen disease (98.6%). Dyskeratotic cells were significantly associated with Bowen disease cases. Conclusion: Our study demonstrated a practical histologic approach to differentiate between intraepidermal pagetoid neoplasms. Careful histologic study of the proposed criteria may reduce reliance on immunohistochemical stains.

http://ift.tt/2rBsPF1

A Pseudoxanthoma Elasticum–Like Papular Eruption: Challenge

No abstract available

http://ift.tt/2rBjVaA

Chronic Localized Fibrosing Leukocytoclastic Vasculitis Associated With Lymphedema, Intralymphatic and Intravascular Lymphocytosis, and Chronic Myelogenous Leukemia: A Case Report of Unilateral Erythema Elevatum Diutinum

Abstract: One of the pathogenic causes of cutaneous inflammatory pseudotumors is chronic localized fibrosing leukocytoclastic vasculitis (CLFLCV), a vasculitic reaction pattern seen in granuloma faciale (GF), a localized vasculitis, and erythema elevatum diutinum (EED), a generalized vasculitis. Patients with myelodysplastic syndromes (MDSs) are at risk for a diverse spectrum of cutaneous neutrophilic dermatoses such as EED. Herein, we report a 74-year-old man who presented with a large ulcerative, fungating tumor affecting the right flexor ankle caused by CLFLCV. During his workup and management, MDS and Philadelphia chromosome-negative chronic myeloid leukemia was diagnosed. Surgical excision of the inflammatory mass promptly triggered tumor recurrence, whereas antineutrophil therapy (dapsone coupled with hydroxyurea, and prednisone) lead to tumor regression. Histopathologic examination revealed an eosinophilic-rich small-vessel neutrophilic vasculitis associated with storiform and angiocentric fibrosis (GF-like). In the regions of fibrosis, dilated lymphatic and vascular spaces were numerous, some of which were congested with small CD3+-positive lymphocytes (intralymphatic and intravascular lymphocytosis). These findings indicate coexisting localized lymphedema. By direct immunofluorescence, IgM and C4d vessel deposits were detected. The pathogenesis of the fibrotic nodules and plaques of CLFLCV is suspected to be due to recurring bouts of immune-complex vasculitis, creating a cycle of vessel damage followed by reparative granulation tissue. Poor lymphatic drainage may be the underlying factor initiating and maintaining recurrent, localized episodes of immune-complex vasculitis and progressive fibrosis. Although his tumor histopathology resembled GF—eosinophilic rich CLFLCV—the clinical context points to a solitary and paraneoplastic case of EED.

http://ift.tt/2rBjUDy

Asymptomatic Annular Plaques in a 67-Year-Old Man: Challenge

No abstract available

http://ift.tt/2rBjT2s

Necrotizing Thrombophlebitis Secondary to Mycobacterium Chelonae in a Hemodialyzed Patient

No abstract available

http://ift.tt/2rBi8SX

Congenital Infantile Fibrosarcoma Associated With a Lipofibromatosis-Like Component: One Train May Be Hiding Another

Abstract: Congenital infantile fibrosarcoma (CIFS) is a soft tissue sarcoma of infants mainly involving lower extremities and usually developing during the first year of life. At another end of the spectrum of pediatric fibroblastic lesions, lipofibromatosis is a rare benign infiltrative soft tissue tumor that affects children. The authors report in this study a particular presentation with a CIFS surrounded by lipofibromatosis-like areas. The presence of a surrounding benign tumor confused and delayed CIFS diagnosis.

http://ift.tt/2rBLqki

A Rapidly Growing Facial Mass: Answer

No abstract available

http://ift.tt/2qDmTyl

Isofraxidin inhibited proliferation and induced apoptosis via blockage of Akt pathway in human colorectal cancer cells

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Peng Shen, Hong-Gang Wang, Miao-Miao Li, Qian-Yun Ma, Chuan-Wen Zhou, Feng Pan, Rui Xie
BackgroundIsofraxidin (IF), a natural coumarin compound, has been reported to possess anti-cancer activity in human liver cancer. However, whether IF is involved in the regulation of colorectal cancer tumorigenesis and development has been not well elucidated.MethodsThe cell proliferation were assessed by Cell Counting Kit-8 (CCK-8) and colony formation test, respectively. The transwell assays were conducted to estimate cell migration and invasion abilities. Further, cell apoptosis was evaluated by confocal microscopy analysis, flow cytometry detection and TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Western blot were performed to detect the expression of related protein.ResultsHerein, the result indicated that IF remarkably bated cell proliferation in human colorectal cancer cells HT-29 and SW-480 in a dose- and time-dependent manner. In addition, IF treatment showed obvious inhibitory activity to cell colony formation in HT-29 and SW-480 cells. Confocal microscopy analysis and flow cytometry detection revealed that IF dramatically induced cell apoptosis in HT-29 and SW-480 cells compared with the control. And IF markedly decreased the expression of anti-apoptotic protein bcl-2, whereas the expression of pro-apoptotic proteins, including caspase-3, caspase-9 and bax, notably increased in HT-29 and SW-480 cells. Besides, IF blocked Akt pathway via inhibition expression of p-Akt. Furthermore, MK2206, an Akt inhibitor, could inhibit cell colony formation and induced apoptosis. This effect is even more obvious in the presence of MK2206 and IF compared to that of either agent alone.ConclusionsTogether, the present study reports a novel use of IF in mitigating human colorectal cancer proliferation and inducing apoptosis via blockage of Akt pathway.



http://ift.tt/2rAEyEX

Simvastatin ameliorate memory deficits and inflammation in clinical and mouse model of Alzheimer’s disease via modulating the expression of miR-106b

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BackgroundAlzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored.MethodsFirst, we tested the effect of simvastatin on AD in clinical research. The fasting venous blood was collected in order to evaluate the levels of interleukin-6 (IL-6), interleukine-1 beta (IL-1β), antichymotrypsin (ACT) and human tumor necrosis factor α (TNF-α), which were measured with the enzyme-linked immunosorbent assay (ELISA) kits. Amyloid-β (Aβ), amyloid-β precursor protein (APP) and β-site APP-cleaving enzyme 1(BACE1) were tested by western blotting. Second, we used an APPswe/PS1E9 (APP/PS1) double transgenic mice to evaluate the amelioration ability of simvastatin against the memory impairment in vivo. Spatial learning and memory of mice were investigated by the Morris water maze test (MWM). The mRNA of inflammatory cytokines were measured using real-time PCR. Third, the phospho-proteome profile of SH-SY5Y human neuroblastoma cells treated with simvastatin was used to investigate the possible mechanisms.ResultsThe results showed that simvastatin ameliorated the memory deficits both in clinical AD patients and animal model of AD. Simvastatin could reduce the mRNA expression of inflammatory cytokines and mediators, suppress the apoptosis of neural stem cells and improve the survival rate of neurons. Moreover, long non-coding RNA (lnc RNA) n336694 and miR-106b was overexpressed in APP/PS1 mice brain tissues, the relationship between lnc RNA n336694 and miR-106b was explored using the method of Target Scan bioinformatics predictions, the results revealed that miR-106b might be a potential target of lnc RNA n336694. Furthermore, miR-106b mediated apoptosis in SH-SY5Y cell and simvastatin could suppressed this process.ConclusionOur results suggested that simvastatin could be of benefit in preventing the progression of AD and expected to be potentially used as a lead drug for further anti-AD treatment.



http://ift.tt/2r1zoou

ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Hatem M. Abuohashish, Mohammed M. Ahmed, Dina Sabry, Mahmoud M. Khattab, Salim S. Al-Rejaie
The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg⁻¹ d⁻¹), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg⁻¹min⁻¹ for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca²⁺ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases.



http://ift.tt/2rASUVw

Anti-inflammatory and antioxidant effect of cerium dioxide nanoparticles immobilized on the surface of silica nanoparticles in rat experimental pneumonia

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Z. Serebrovska, R.J. Swanson, V. Portnichenko, A. Shysh, S. Pavlovich, L. Tumanovska, A. Dorovskych, V. Lysenko, V. Tertykh, Y. Bolbukh, V. Dosenko
A massage with the potent counter-inflammatory material, cerium dioxide nanoparticles, is promising and the antioxidant properties of CeO2 are considered the main, if not the only, mechanism of this action. Nevertheless, the elimination of ceria nano-particles from the organism is very slow and there is a strong concern for toxic effect of ceria due to its accumulation. To overcome this problem, we engineered a combined material in which cerium nanoparticles were immobilized on the surface of silica nanoparticles (CeO2 NP), which is shown to be easily removed from an organism and could be used as carriers for nano-ceria. In our study particle size was 220±5nm, Zeta-potential −4.5mV (in water), surface charge density −17.22μC/cm² (at pH 7).Thirty-six male Wistar rats, 5 months old and 250–290g were divided into four groups: 1) control; 2) CeO2 NP treatment; 3) experimental pneumonia (i/p LPS injection, 1mg/kg); and 4) experimental pneumonia treated with CeO2 NP (4 times during the study in dosage of 0.6mg/kg with an orogastric catheter). Gas exchange and pulmonary ventilation were measured four times: 0, 1, 3 and 24h after LPS injection in both untreated and CeO2 NP-treated animals. The mRNA of TNF-α, Il-6, and CxCL2 were determined by RT-PCR. ROS-generation in blood plasma and lung tissue homogenates were measured by means of lucigenin- and luminol-enhanced chemiluminescence.Endotoxemia in the acute phase was associated with: (1) pathological changes in lung morphology; (2) increase of ROS generation; (3) enhanced expression of CxCL2; and (4) a gradual decrease of VO2 and VE. CeO2 NP treatment of intact animals did not make any changes in all studied parameters except for a significant augmentation of VO2 and VE. CeO2 NP treatment of rats with pneumonia created positive changes in diminishing lung tissue injury, decreasing ROS generation in blood and lung tissue and decreasing pro-inflammatory cytokine expression (TNF-α, Il-6 and CxCL2). Oxygen consumption in this group was increased compared to the LPS pneumonia group.In our study we have shown anti-inflammatory and antioxidant effects of CeO2 NP. In addition, this paper is the first to report that CeO2 NP stimulates oxygen consumption in both healthy rats, and rats with pneumonia. We propose the key in understanding the mechanisms behind the phenomena lies in the property of CeO2 NP to scavenge ROS and the influence of this potent antioxidant on mitochondrial function. The study of biodistribution and elimination of СеО2NP is the purpose of our ongoing study.



http://ift.tt/2r1G8Ta

Stimuli-directed self-organized chiral superstructures for adaptive windows enabled by mesogen-functionalized graphene

Publication date: Available online 18 May 2017
Source:Materials Today
Author(s): Ling Wang, Hari Krishna Bisoyi, Zhigang Zheng, Karla G. Gutierrez-Cuevas, Gautam Singh, Satyendra Kumar, Timothy J. Bunning, Quan Li
Harnessing the distinct characteristics of nanomaterials integrated into host matrices to enable multi-responsive, multi-functional and adapting capabilities of the resulting materials and systems is a thriving research frontier in contemporary nanoscience. Herein, we have judiciously designed and synthesized a mesogen-functionalized graphene (MFG) to facilitate homogeneous dispersion and compatibility with our newly developed liquid crystal (LC) medium. We then demonstrate the concept of an adaptive window system that can autonomously change the optical transparency in response to external multiple stimuli by the fabrication of polymer-stabilized MFG-containing liquid crystalline films with self-organized chiral superstructures. The light transmittance of films could be expediently modulated through the reversible phase transition between the chiral smectic A (SmA*) and the chiral nematic (N*) phases either by environmental temperature change or shining infrared radiation, where the transparent state is furnished by the homeotropic SmA* phase whilst the opaque state results from the focal conic configuration of the N* phase. Importantly, when desired, the opaque state of the devices could be facilely switched into a transparent state by applying an electric field. The research disclosed here provides a convenient and versatile method to dynamically control over the light transmittance through the windows with adaptive behavior in response to multiple environmental cues such as surrounding temperature and infrared exposure from solar radiations, which holds great potential in architectural and automotive applications with intelligent adaptability and energy efficiency.

Graphical abstract

http://ift.tt/2rB8ocu

Are we a step closer to 3D printed carbon nanotube composites?

Publication date: Available online 18 May 2017
Source:Materials Today
Author(s): Laurie Winkless




http://ift.tt/2rAOu10

Effect of Valgus Knee Alignment on Gait Biomechanics in Healthy Women

Publication date: Available online 19 May 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Matthew C. Hoch, Joshua T. Weinhandl
The purpose of this study was to compare lower extremity kinematics and kinetics between women with greater or lesser degrees of valgus knee alignment during gait. Nine women with greater valgus knee alignment (11.9±1.6^o) were compared to nine women with lesser valgus knee alignment (6.6±2.4^o). Participants completed a biomechanical assessment of overground walking for the right limb. Dependent variables included sagittal and frontal plane joint angles and moments for the hip, knee, and ankle at peak vertical ground reaction force, along with knee abduction angular impulse. Sagittal and frontal plane excursions for the hip, knee, and ankle were calculated from heel strike to the peak angle for each variable. The greater valgus alignment group demonstrated lower knee abduction moment (p=0.007), lower knee adduction angle (p<0.001), and greater ankle inversion moment (p=0.034) at peak vertical ground reaction force, as well as lower knee abduction angular impulse (p=0.007), and knee adduction ROM (p=0.026). No other group differences were identified for any kinematic or kinetic variables (p>0.05). Less knee adduction angle and excursion coupled with lower knee abduction moment and angular impulse in women with greater knee valgus indicates these individuals may be experiencing biomechanics which promote lateral tibiofemoral joint loading.



http://ift.tt/2pUABhe

Finite element method simulating temperature distribution in skin induced by 980-nm pulsed laser based on pain stimulation

Abstract

For predicting the temperature distribution within skin tissue in 980-nm laser-evoked potentials (LEPs) experiments, a five-layer finite element model (FEM-5) was constructed based on Pennes bio-heat conduction equation and the Lambert-Beer law. The prediction results of the FEM-5 model were verified by ex vivo pig skin and in vivo rat experiments. Thirty ex vivo pig skin samples were used to verify the temperature distribution predicted by the model. The output energy of the laser was 1.8, 3, and 4.4 J. The laser spot radius was 1 mm. The experiment time was 30 s. The laser stimulated the surface of the ex vivo pig skin beginning at 10 s and lasted for 40 ms. A thermocouple thermometer was used to measure the temperature of the surface and internal layers of the ex vivo pig skin, and the sampling frequency was set to 60 Hz. For the in vivo experiments, nine adult male Wistar rats weighing 180 ± 10 g were used to verify the prediction results of the model by tail-flick latency. The output energy of the laser was 1.4 and 2.08 J. The pulsed width was 40 ms. The laser spot radius was 1 mm. The Pearson product-moment correlation and Kruskal-Wallis test were used to analyze the correlation and the difference of data. The results of all experiments showed that the measured and predicted data had no significant difference (P > 0.05) and good correlation (r > 0.9). The safe laser output energy range (1.8–3 J) was also predicted. Using the FEM-5 model prediction, the effective pain depth could be accurately controlled, and the nociceptors could be selectively activated. The FEM-5 model can be extended to guide experimental research and clinical applications for humans.

http://ift.tt/2qzGIWC

Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF- Mutated Melanoma

Abstract

Background

Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis.

Objective

We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients.

Patients and Methods

Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman^® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences.

Results

At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04–6.56; p = 0.04).

Conclusions

This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.

http://ift.tt/2rlWQMV

Editorial Board and Contents

Publication date: June 2017
Source:Trends in Cell Biology, Volume 27, Issue 6





http://ift.tt/2qCAQMI