Simultaneous Determination and Stability Studies on Diminazene Diaceturate and Phenazone Using Developed Derivative Spectrophotometric Method

This work presents UV first derivative spectrophotometry as a precise, accurate, and feasible method for simultaneous determination of diminazene diaceturate and phenazone in bulk and dosage forms. The absorbance values of diminazene diaceturate and phenazone aqueous mixture were obtained at 398 nm and 273 nm, respectively. The developed method was proved to be linear over the concentration ranges (2–10) μg/mL and (2.496–12.48) μg/mL for diminazene diaceturate and phenazone, respectively, with good correlation coefficients (not less than 0.997). The detection and quantitation limits were found to be (LOD = 0.63 and 0.48 μg/mL; LOQ = 1.92 and 1.47 μg/mL, resp.). The developed method was employed for stability studies of both drugs under different stress conditions. Diminazene diaceturate was prone to degrade at acidic pH via first-order kinetics. The degradation process was found to be temperature dependent with an activation energy of 7.48 kcal/mole. Photo-stability was also investigated for this drug.

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Parallel Evolutionary Peer-to-Peer Networking in Realistic Environments

In the present paper we first conduct simulations of the parallel evolutionary peer-to-peer (P2P) networking technique (referred to as P-EP2P) that we previously proposed using models of realistic environments to examine if P-EP2P is practical. Environments are here represented by what users have and want in the network, and P-EP2P adapts the P2P network topologies to the present environment in an evolutionary manner. The simulation results show that P-EP2P is hard to adapt the network topologies to some realistic environments. Then, based on the discussions of the results, we propose a strategy for better adaptability of P-EP2P to the realistic environments. The strategy first judges if evolutionary adaptation of the network topologies is likely to occur in the present environment, and if it judges so, it actually tries to achieve evolutionary adaptation of the network topologies. Otherwise, it brings random change to the network topologies. The simulation results indicate that P-EP2P with the proposed strategy can better adapt the network topologies to the realistic environments. The main contribution of the study is to present such a promising way to realize an evolvable network in which the evolution direction is given by users.

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Security Analysis of a Certificateless Signature from Lattices

Tian and Huang proposed a lattice-based CLS scheme based on the hardness of the SIS problem and proved, in the random oracle model, that the scheme is existentially unforgeable against strong adversaries. Their security proof uses the general forking lemma under the assumption that the underlying hash function is a random oracle. We show that the hash function in the scheme is neither one-way nor collision-resistant in the view of a strong Type 1 adversary. We point out flaws in the security arguments and present attack algorithms that are successful in the strong Type 1 adversarial model using the weak properties of the hash function.

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Internet of Things: Architectures, Protocols, and Applications

The Internet of Things (IoT) is defined as a paradigm in which objects equipped with sensors, actuators, and processors communicate with each other to serve a meaningful purpose. In this paper, we survey state-of-the-art methods, protocols, and applications in this new emerging area. This survey paper proposes a novel taxonomy for IoT technologies, highlights some of the most important technologies, and profiles some applications that have the potential to make a striking difference in human life, especially for the differently abled and the elderly. As compared to similar survey papers in the area, this paper is far more comprehensive in its coverage and exhaustively covers most major technologies spanning from sensors to applications.

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Decreased Tissue COX5B Expression and Mitochondrial Dysfunction during Sepsis-Induced Kidney Injury in Rats

Background. Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is the dominant cause of acute kidney injury (AKI), accounting for nearly 50% of episodes of acute renal failure. Signaling cascades and pathways within the kidney are largely unknown and analysis of these molecular mechanisms may enhance knowledge on pathophysiology and possible therapeutic options. Material and Methods. 26 male Wistar rats were assigned to either a sham group (control, ) or sepsis group (; cecal ligature and puncture model, 24 and 48 hours after CLP). Surviving rats () were decapitated at 24 hours (early phase; ) or 48 hours (late phase; ) after CLP and kidneys removed for proteomic analysis. 2D-DIGE and DeCyder 2D software (-test, ) were used for analysis of significantly regulated protein spots. MALDI-TOF in combination with peptide mass fingerprinting (PMF) as well as Western Blot analysis was used for protein identification. Bioinformatic network analyses (STRING, GeneMania, and PCViz) were used to describe protein-protein interactions. Results. 12 spots were identified with significantly altered proteins () in the three analyzed groups. Two spots could not be identified. Four different proteins were found significantly changed among the groups: major urinary protein (MUP5), cytochrome c oxidase subunit B (COX5b), myosin-6 (MYH6), and myosin-7 (MYH7). A significant correlation with the proteins was found for mitochondrial energy production and electron transport. Conclusions. COX5B could be a promising biomarker candidate since a significant association was found during experimental sepsis in the present study. For future research, COX5B should be evaluated as a biomarker in both human urine and serum to identify sepsis.

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Preparation of High Modulus Poly(Ethylene Terephthalate): Influence of Molecular Weight, Extrusion, and Drawing Parameters

Poly(ethylene terephthalate) (PET) which is one of the most commercially important polymers, has for many years been an interesting candidate for the production of high performance fibres and tapes. In current study, we focus on investigating the effects of the various processing variables on the mechanical properties of PET produced by a distinctive process of melt spinning and uniaxial two-stage solid-state drawing (SSD). These processing variables include screw rotation speed during extrusion, fibre take-up speed, molecular weight, draw-ratio, and drawing temperature. As-spun PET production using a single-screw extrusion process was first optimized to induce an optimal polymer microstructure for subsequent drawing processes. It was found that less crystallization which occurred during this process would lead to better drawability, higher draw-ratio, and mechanical properties in the subsequent SSD process. Then the effect of drawing temperature (DT) in uniaxial two-stage SSD process was studied to understand how DT (

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Advances and Prospects in Stem Cells for Cartilage Regeneration

The histological features of cartilage call attention to the fact that cartilage has a little capacity to repair itself owing to the lack of a blood supply, nerves, or lymphangion. Stem cells have emerged as a promising option in the field of cartilage tissue engineering and regenerative medicine and could lead to cartilage repair. Much research has examined cartilage regeneration utilizing stem cells. However, both the potential and the limitations of this procedure remain controversial. This review presents a summary of emerging trends with regard to using stem cells in cartilage tissue engineering and regenerative medicine. In particular, it focuses on the characterization of cartilage stem cells, the chondrogenic differentiation of stem cells, and the various strategies and approaches involving stem cells that have been used in cartilage repair and clinical studies. Based on the research into chondrocyte and stem cell technologies, this review discusses the damage and repair of cartilage and the clinical application of stem cells, with a view to increasing our systematic understanding of the application of stem cells in cartilage regeneration; additionally, several advanced strategies for cartilage repair are discussed.

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An Asymptomatic and Overelongated Styloid Process

Elongation of the styloid process is a rare condition. Only 4% of patients have clinical symptoms where elongated styloid process (ESP) occasionally irritates or disrupts adjacent anatomical structures, which is called Eagle syndrome. This present report was aimed at reporting an asymptomatic ESP with unusual width and length.

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False Positive Findings on I-131 WBS and SPECT/CT in Patients with History of Thyroid Cancer: Case Series

Introduction. Although whole body scan (WBS) with I-131 is a highly sensitive tool for detecting normal thyroid tissue and metastasis of differentiated thyroid cancer (DTC), it is not specific. Additional information, provided by single photon emission computed tomography combined with X-ray computed tomography (SPECT/CT) and by the serum thyroglobulin level, is extremely useful for the interpretation of findings. Case Presentation. We report four cases of false positive WBS in patients with DTC: ovarian uptake corresponding to an endometrioma, scrotal uptake due to a spermatocele, rib-cage uptake due to an old fracture, and hepatic and renal uptake secondary to a granuloma and simple cyst, respectively. Conclusions. Trapping, organification, and storage of iodine are more prominent in thyroid tissue but not specific. Physiologic sodium-iodine symporter expression in other tissues explains some, but not all, of the WBS false positive cases. Other proposed etiologies are accumulation of radioiodine in inflamed organs, metabolism of radiodinated thyroid hormone, presence of radioiodine in body fluids, and contamination. In our cases nonthyroidal pathologies were suspected since the imaging findings were not corroborated by an elevated thyroglobulin level, which is considered a reliable tumor marker for most well-differentiated thyroid cancers. Clinicians should be aware of the potential pitfalls of WBS in DTC to avoid incorrect management.

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Hospitals struggle to integrate physical and mental healthcare, inquiry finds

Hospitals find it difficult to integrate physical and mental healthcare in people with mental health conditions who are admitted with a physical illness, an inquiry has found.1Lesley Regan, chair of...

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UK children have “alarming gap” in health between rich and poor, report finds

Experts in child health have called for a comprehensive strategy to reduce poverty and social inequalities, as a report published this week shows that UK children living in deprived areas have much...

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Boosting Immune Responses Following Fractional-Dose Inactivated Poliovirus Vaccine: A Randomized, Controlled Trial

<span class="paragraphSection"><div class="boxTitle">Background</div>Fractional-dose administration of inactivated poliovirus vaccine (fIPV) could increase IPV affordability and stretch limited supplies. We assessed immune responses following fIPV administered intradermally, compared with full-dose IPV administered intramuscularly, among adults with a history of oral poliovirus vaccine (OPV) receipt.<div class="boxTitle">Methods</div>We conducted a randomized, controlled noninferiority trial in Cuba. fIPV or IPV were administered on days 0 and 28; serum was collected on days 0, 7, 28, and 56 for analysis by a neutralization assay. The primary end point was seroconversion or a ≥4-fold rise in antibody titer. The noninferiority limit was 10%. The secondary end point was safety, assessed by the number and intensity of adverse reactions.<div class="boxTitle">Results</div>A total of 503 of 534 enrolled participants (94.2%) completed all study requirements. Twenty-eight days after the first dose, 94.8%, 98.0%, and 98.0% of fIPV recipients had an immune response to poliovirus types 1, 2, and 3, respectively, compared with 98.1% (<span style="font-style:italic;">P</span> = .06), 98.0% (<span style="font-style:italic;">P</span> = 1.00), and 99.2% (<span style="font-style:italic;">P</span> = .45) in the IPV arm. Noninferiority was achieved on days 7, 28, and 56 for all serotypes. No serious adverse events were reported.<div class="boxTitle">Conclusion</div>fIPV induced similar boosting immune responses, compared with full-dose IPV. This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation.<div class="boxTitle">Clinical Trials Registration</div>ACTRN12615000305527.</span>

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Experimental Therapies for Ebola Virus Disease: What Have We Learned?

<span class="paragraphSection">Ebolaantiviralsimmunotherapeuticsclinical research</span>

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First Newborn Baby to Receive Experimental Therapies Survives Ebola Virus Disease

<span class="paragraphSection"><div class="boxTitle">Abstract</div>A neonate born to an Ebola virus–positive woman was diagnosed with Ebola virus infection on her first day of life. The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734. On day 20, a venous blood specimen tested negative for Ebola virus by quantitative reverse-transcription polymerase chain reaction. The patient was discharged in good health on day 33 of life. Further follow-up consultations showed age-appropriate weight gain and neurodevelopment at the age of 12 months. This patient is the first neonate documented to have survived congenital infection with Ebola virus.</span>

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Transcriptional Categorization of the Etiology of Pneumonia Syndrome in Pediatric Patients in Malaria-Endemic Areas

<span class="paragraphSection"><div class="boxTitle">Background</div>Pediatric acute respiratory distress in tropical settings is very common. Bacterial pneumonia is a major contributor to morbidity and mortality rates and requires adequate diagnosis for correct treatment. A rapid test that could identify bacterial (vs other) infections would have great clinical utility.<div class="boxTitle">Methods and Results</div>We performed RNA (RNA-seq) sequencing and analyzed the transcriptomes of 68 pediatric patients with well-characterized clinical phenotype to identify transcriptional features associated with each disease class. We refined the features to predictive models (support vector machine, elastic net) and validated those models in an independent test set of 37 patients (80%–85% accuracy).<div class="boxTitle">Conclusions</div>We have identified sets of genes that are differentially expressed in pediatric patients with pneumonia syndrome attributable to different infections and requiring different therapeutic interventions. Findings of this study demonstrate that human transcription signatures in infected patients recapitulate the underlying biology and provide models for predicting a bacterial diagnosis to inform treatment.</span>

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Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study

<span class="paragraphSection"><div class="boxTitle">Background</div>Mortality rates remain high for human immunodeficiency virus (HIV)–associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects.<div class="boxTitle">Methods</div>We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates.<div class="boxTitle">Results</div>Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0–24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality.<div class="boxTitle">Conclusions</div>Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality.</span>

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Persistence of Wild-Type Japanese Encephalitis Virus Strains Cross-Neutralization 5 Years After JE-CV Immunization

<span class="paragraphSection"><div class="boxTitle">Background</div>The live-attenuated Japanese encephalitis (JE) vaccine (JE-CV; IMOJEV) induces a protective response in children. A shift in circulating JE virus strains suggests that a genotype shift phenomenon may occur throughout Southeast Asia. We assessed the neutralization of wild-type (WT) JE virus isolates at distal time points after vaccination.<div class="boxTitle">Methods</div>We analyzed serum samples from a subset of 47 children who had received a JE-CV booster after an inactivated JE vaccine primary immunization. We measured antibody titers (50% plaque reduction neutralization test) using a panel of WT JE strains at baseline, then after the booster at 28 days and 6 months in all subjects present at the time points and in a subset at year 5. Three additional recent isolates were tested at year 5.<div class="boxTitle">Results</div>Of 47 subjects, 43 (91.5%) subjects had JE neutralizing antibody titers ≥10 (reciprocal serum dilution) against the homologous strain before JE-CV boost; all were seroprotected up to year 5 after the JE-CV boost. Baseline WT seroprotection ranged between 78.7% and 87.2%; all subjects were seroprotected against the 4 WT strains at 28 days and 6 months; year 5 seroprotection ranged between 95.7% and 97.9%. Similar rates of protection against 3 additional WT isolates were observed at year 5.<div class="boxTitle">Conclusions</div>The long-term immune responses induced after a JE-CV booster dose in toddlers were able to neutralize WT viruses from various genotypes circulating in Southeast Asia and India.<div class="boxTitle">Clinical Trials Registration</div>NCT00621764.</span>

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Monovalent Rotavirus Vaccine Effectiveness and Impact on Rotavirus Hospitalizations in Zanzibar, Tanzania: Data From the First 3 Years After Introduction

<span class="paragraphSection"><div class="boxTitle">Background</div>Low-income settings challenge the level of protection provided by live attenuated oral rotavirus vaccines. Rotarix (RV1) was introduced in the United Republic of Tanzania in early 2013, with 2 doses given at the World Health Organization–recommended schedule of ages 6 and 10 weeks, along with oral poliovirus vaccine.<div class="boxTitle">Methods</div>We performed active surveillance for rotavirus hospitalizations at the largest hospital in Zanzibar, Tanzania, from 2010 through 2015. Using a case–test-negative control design, we estimated the vaccine effectiveness (VE) of 2 RV1 doses in preventing rotavirus hospitalizations.<div class="boxTitle">Results</div>Based on 204 rotavirus case patients and 601 test-negative controls aged 5–23 months, the VE of 2 RV1 doses against hospitalization for rotavirus diarrhea was 57% (95% confidence interval, 14%–78%). VE tended to increase against hospitalizations with higher severity, reaching 69% (95% confidence interval, 15%–88%) against the severity score for the top quarter of case patients. Compared with the prevaccine period, there were estimated reductions of 40%, 46%, and 69% in the number of rotavirus hospitalizations among infants in 2013, 2014, and 2015, respectively, and reductions of 36%, 26%, and 64%, respectively, among children aged <5 years.<div class="boxTitle">Conclusions</div>With data encompassing 3 years before and 3 years after vaccine introduction, our results indicate that successful delivery of RV1 on the current World Health Organization schedule can provide substantial health benefits in a resource-limited setting.</span>

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Human Papillomavirus Prevalence in Unvaccinated Heterosexual Men After a National Female Vaccination Program

<span class="paragraphSection"><div class="boxTitle">Background</div>In Australia, high uptake of the quadrivalent human papillomavirus (4vHPV) vaccine has led to reductions in the prevalence of human papillomavirus (HPV) genotypes 6, 11, 16, and 18 in women and girls aged ≤25 years. We evaluated the impact of the program impact on HPV prevalence in unvaccinated male subjects.<div class="boxTitle">Methods</div>Sexually active heterosexual male subjects aged 16–35 years were recruited in 2014–2016. Participants provided a self-collected penile swab sample for HPV genotyping (Roche Linear Array) and completed a demographic and risk factor questionnaire.<div class="boxTitle">Results</div>The prevalence of 4vHPV genotypes among 511 unvaccinated male subjects was significantly lower in those aged ≤25 than in those aged >25 years: 3.1% (95% confidence interval, 1.5%–5.7%) versus 13.7% (8.9%–20.1%), respectively (<span style="font-style:italic;">P</span> < .001); adjusted prevalence ratio, 0.22 (.09–.51; <span style="font-style:italic;">P</span> < .001). By contrast, the prevalence of high-risk HPV genotypes other than 16 and 18 remained the same across age groups: 16.8% (95% confidence interval, 12.6%–21.9%) in men aged ≤25 years and 17.9% (12.4%–25.0%) in those aged >25 years (<span style="font-style:italic;">P</span> = .76); adjusted prevalence ratio, 0.98, (.57–1.37; <span style="font-style:italic;">P</span> = .58).<div class="boxTitle">Conclusions</div>A 78% lower prevalence of 4vHPV genotypes was observed among younger male subjects. These data suggest that unvaccinated men may have benefited from herd protection as much as women from a female-only HPV vaccination program with high coverage.</span>

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Reduction of Pertussis Inflammatory Pathology by Therapeutic Treatment With Sphingosine-1-Phosphate Receptor Ligands by a Pertussis Toxin-Insensitive Mechanism

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Recent data have demonstrated the potential of sphingosine 1-phosphate (S1P) receptor (S1PR) agonism in the treatment of infectious diseases. A previous study used a murine model of <span style="font-style:italic;">Bordetella pertussis</span> infection to demonstrate that treatment with the S1PR agonist AAL-R reduces pulmonary inflammation during infection. In the current study, we showed that this effect is mediated via the S1PR1 on LysM⁺ (myeloid) cells. Signaling via this receptor results in reduced lung inflammation and cellular recruitment as well as reduced morbidity and mortality in a neonatal mouse model of disease. Despite the fact that S1PRs are pertussis toxin–sensitive G protein-coupled receptors, the effects of AAL-R were pertussis toxin insensitive in our model. Furthermore, our data demonstrate that S1PR agonist administration may be effective at therapeutic time points. These results indicate a role for S1P signaling in <span style="font-style:italic;">B. pertussis</span>–mediated pathology and highlight the possibility of host-targeted therapy for pertussis.</span>

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Interleukin 36α Attenuates Sepsis by Enhancing Antibacterial Functions of Macrophages

<span class="paragraphSection"><div class="boxTitle">Background</div>Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments. The role of interleukin 36α (IL-36α) in host response during sepsis remains unknown.<div class="boxTitle">Methods</div>An experimental sepsis model of cecal ligation and puncture was established to investigate the effects of IL-36α on host response to sepsis.<div class="boxTitle">Results</div>IL-36α production was significantly up-regulated during sepsis. IL-36α treatment reduced the mortality rate in mice with severe sepsis by cecal ligation and puncture. IL-36α–treated mice had more efficient bacterial clearance, inhibited tissue inflammation, improved organ injury, and reduced immune cell apoptosis. The therapeutic implication of these observations was also highlighted by the finding that specific blockade of IL-36α led to an increased mortality rate in mice with nonsevere sepsis. Furthermore, we found that IL-36α enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36α–mediated protection against sepsis.<div class="boxTitle">Conclusions</div>Our results demonstrate that IL-36α plays an important role in the host defense response to sepsis and suggest a potential therapeutic role for IL-36α in sepsis.</span>

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Cross-Reactive and Cross-Neutralizing Activity of Human Mumps Antibodies Against a Novel Mumps Virus From Bats

<span class="paragraphSection"><div class="boxTitle">Abstract</div>To evaluate the antigenic relationship between bat mumps virus (BMV) and the JL5 vaccine strain of mumps virus (MuV^JL5), we rescued a chimeric virus bearing the F and HN glycoproteins of BMV in the background of a recombinant JL5 genome (rMuV^JL5). Cross-reactivity and cross-neutralization between this chimeric recombinant MuV bearing the F and HN glycoproteins of BMV (rMuV^JL5-F/HN^BMV) virus and rMuV^JL5 were demonstrated using hyperimmune mouse serum samples and a curated panel of human serum. All mouse and human serum samples that were able to neutralize rMuV^JL5 infection had cross-neutralizing activity against rMuV^JL5-F/HN^BMV. Our data suggest that persons who have neutralizing antibodies against MuV might be protected from infection by BMV.</span>

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Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

<span class="paragraphSection"><div class="boxTitle">Background</div>Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis.<div class="boxTitle">Methods</div>Phase 2 48-week safety/tolerability study was conducted, comparing 4 regimens: MVC alone, MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. Eligible participants were HIV-uninfected men and transgender women reporting condomless anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days. At each visit, assessments, laboratory testing, and counseling were done. Analyses were intention to treat.<div class="boxTitle">Results</div>Among 406 participants, 84% completed follow-up, 7% stopped early, and 9% were lost to follow-up; 9% discontinued their regimen early. The number discontinuing and the time to discontinuation did not differ among study regimens (<span style="font-style:italic;">P</span> = .60). Rates of grade 3–4 adverse events did not differ among regimens (<span style="font-style:italic;">P</span> = .37). In a randomly selected subset, 77% demonstrated detectable drug concentrations at week 48. Five participants acquired HIV infection (4 MVC alone, 1 MVC + TDF; overall annualized incidence, 1.4% [95% confidence interval, .5%–3.3%], without differences by regimen; <span style="font-style:italic;">P</span> = .32); 2 had undetectable drug concentrations at every visit, 2 had low concentrations at the seroconversion visit, and 1 had variable concentrations.<div class="boxTitle">Conclusions</div>MVC-containing regimens were safe and well tolerated compared with TDF + FTC; this study was not powered for efficacy. Among those acquiring HIV infection, drug concentrations were absent, low, or variable. MVC-containing regimens may warrant further study for pre-exposure prophylaxis.<div class="boxTitle">Clinical Trials Registration</div>NCT01505114.</span>

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Comprehensive Characterization of Cellular Immune Responses Following Ebola Virus Infection

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The West African Ebola virus disease (EVD) outbreak was the largest EVD outbreak in history. However, data on lymphocyte dynamics and the antigen specificity of T cells in Ebola survivors are scarce, and our understanding of EVD pathophysiology is limited. A case of EVD survival in which the patient cleared Ebola virus (EBOV) infection without experimental drugs allowed for the detailed examination of lymphocyte dynamics. We demonstrate the persistence of T-cell activation well beyond viral clearance and detect EBOV-specific T cells. Our study provides significant insights into lymphocyte specificity during the recovery phase of EVD and may inform novel strategies to treat EVD.</span>

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Lymphatic Circulation Disseminates Bartonella Infection Into Bloodstream

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The hallmark of <span style="font-style:italic;">Bartonella</span> infection is long-lasting intraerythrocytic parasitism. However, the process of <span style="font-style:italic;">Bartonella</span> bacteremia is still enigmatic. In the current study, we used <span style="font-style:italic;">Bartonella tribocorum</span> to determine how <span style="font-style:italic;">Bartonella</span> invasion into the bloodstream from dermal inoculation might occur. <span style="font-style:italic;">Bartonella</span> was poorly phagocytized by peritoneal macrophages in vitro. Intracellular <span style="font-style:italic;">Bartonella</span> survived and replicated in macrophages at an early stage of infection. Intracellular <span style="font-style:italic;">Bartonella</span> inhibited spontaneous cell death of macrophages. They also inhibited <span style="font-style:italic;">Salmonella</span>-induced pyroptosis and mildly reduced inflammasome activation through an unidentified mechanism. A rat model confirmed that <span style="font-style:italic;">Bartonella</span> was also inadequately phagocytized in vivo, because numerous free-floating bacilli were observed in lymph collected from thoracic duct drainage as early as 2 hours after inoculation. Lymphatic fluid drainage in the bloodstream significantly reduced the bacterial load in the bloodstream. These findings illustrated a potential route by which <span style="font-style:italic;">Bartonella</span> invade bloodstream from dermal inoculation before they are competent to infect erythrocytes.</span>

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Mortality Rates in Patients With Chronic Hepatitis C and Cirrhosis Compared With the General Population: A Danish Cohort Study

<span class="paragraphSection"><div class="boxTitle">Background</div>Knowledge about mortality rates (MRs) in patients with chronic hepatitis C (CHC) with cirrhosis is limited. This study aimed to estimate all-cause MRs among patients with CHC with or without cirrhosis in Denmark compared with the general population.<div class="boxTitle">Methods</div>Patients registered in the Danish Database for Hepatitis B and C with CHC and a liver fibrosis assessment were eligible for inclusion. Liver fibrosis was assessed by means of liver biopsy, transient elastography, and clinical cirrhosis. Up to 20 sex- and age-matched individuals per patient were identified in the general population. Data were extracted from nationwide registries.<div class="boxTitle">Results</div>A total of 3410 patients with CHC (1014 with cirrhosis), and 67 315 matched individuals were included. Adjusted MR ratios (MRRs) between patients with or without cirrhosis and their comparison cohorts were 5.64 (95% confidence interval [CI], 4.76–6.67) and 1.94 (1.55–2.42), respectively. Cirrhosis among patients was associated with an MRR of 4.03 (95% CI, 3.43–4.72). A cure for CHC was associated with an MRR of 0.64 (95% CI, 0.40–1.01) among cirrhotic patients and 2.33 (1.47–3.67) compared with the general population.<div class="boxTitle">Conclusions</div>MRs were high among patients with CHC with or without cirrhosis compared with the general population. Curing CHC was associated with a reduction in MR among cirrhotic patients, but the MR remained higher than the general population.</span>

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Inflammation, Immune Activation, Immunosenescence, and Hormonal Biomarkers in the Frailty-Related Phenotype of Men With or at Risk for HIV Infection

<span class="paragraphSection"><div class="boxTitle">Background</div>The extent to which inflammation, immune activation/immunosenescence, and hormonal abnormalities are driven by human immunodeficiency virus (HIV) or frailty is not clear.<div class="boxTitle">Methods</div>HIV-infected frail men (n = 155) were matched to nonfrail, HIV-infected (n = 141) and HIV-uninfected (n = 150) men by age, calendar year, and antiretroviral therapy use (HIV-infected men only). Frailty was defined by ≥3 frailty-related phenotype criteria (weight loss, exhaustion, low activity, slowness) at ≥2 visits, or at 1 visit with ≥1 criteria at ≥2 visits. The following measurements were obtained: interleukin 6, high-sensitivity C-reactive protein, soluble receptors for tumor necrosis factor α 1 and 2, the percentages of CD4⁺CD28⁻, CD8⁺CD28⁻, CD4⁺CD38⁺HLA-DR⁺, and CD8⁺CD38⁺HLA-DR⁺ T cells, dehydroepiandrosterone sulfate, free testosterone, homeostatic model assessment of insulin resistance, and insulin-like growth factor 1. Log-linear regressions were adjusted for a priori selected covariates to determine differences by frailty and HIV status.<div class="boxTitle">Results</div>In multivariate analyses adjusted for covariates, frailty was associated among HIV-infected men with higher interleukin 6 and high-sensitivity C-reactive protein and lower free testosterone and dehydroepiandrosterone levels. In contrast, HIV infection but not frailty was associated with significantly greater immune senescence (percentage of CD4⁺CD28⁻ or CD8⁺CD28⁻ T cells) and immune activation (percentages of CD4⁺CD38⁺HLA-DR⁺ and CD8⁺CD38⁺HLA-DR⁺ T cells).<div class="boxTitle">Conclusions</div>Frailty among HIV-infected men was associated with increased inflammation and lower hormone levels, independent of comorbid conditions. Interventions targeting these pathways should be evaluated to determine the impact on prevention or reversal of frailty among HIV-infected men.</span>

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Endoplasmic Reticulum Stress and Chemokine Production in Cystic Fibrosis Airway Cells: Regulation by STAT3 Modulation

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Endoplasmic reticulum (ER) stress has been recognized to play an important role in chronic inflammatory diseases such as cystic fibrosis (CF), and targeting ER stress may be useful for alleviating damaging neutrophilic inflammation in CF airways. Cellular models were used in conjunction with data from a recent CF genome-wide association study (GWAS) meta-analysis to determine modulators of ER stress-mediated inflammation. Surprisingly, cells undergoing ER stress during inflammatory stimulation showed reduced interleukin 8 (IL-8) and CXCL1 secretion (<span style="font-style:italic;">P</span> < .001). Neutralization of CXCL1 and IL-8 reduced neutrophil chemotaxis >50% to supernatants from IL-1β-stimulated CF airway epithelial cells (<span style="font-style:italic;">P</span> < .01). The clinical importance of these chemokines was validated by association of <span style="font-style:italic;">CXCL1</span> and <span style="font-style:italic;">IL8</span> polymorphisms with changes in lung disease severity in patients with CF (n = 6365; <span style="font-style:italic;">IL8, P</span> = .001; <span style="font-style:italic;">CXCL1, P</span> = .001), confirming that targeting these chemokine pathways could help improve lung disease. We determined that production of these chemokines was partially controlled by ER stress in a signal transducer and activator of transcription 3 (STAT3)–dependent manner, whereby ER stress inhibited STAT3 activation. Our findings support a role for CXCL1 and IL-8 in CF lung disease severity and identify STAT3 as a modulating pathway. Targeting these pathways may help improve health outcomes in CF.</span>

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Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever

<span class="paragraphSection"><div class="boxTitle">Abstract</div><span style="font-style:italic;">Shigella sonnei</span> and <span style="font-style:italic;">Salmonella</span> Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated <span style="font-style:italic;">S.</span> Typhi vaccine (Ty21a) by using it as a vector to develop a bivalent oral vaccine to protect against <span style="font-style:italic;">S. sonnei</span> shigellosis and typhoid fever. We recombineered the <span style="font-style:italic;">S. sonnei</span> form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses <span style="font-style:italic;">S. sonnei</span> form I O antigen. To enhance survivability in the acid environment of the stomach, we created an acid-resistant strain, Ty21a-AR-Ss, by inserting <span style="font-style:italic;">Shigella</span> glutaminase–glutamate decarboxylase systems coexpressed with <span style="font-style:italic;">S. sonnei</span> form I O-antigen gene. Mice immunized intranasally with Ty21a-AR-Ss produced antibodies against <span style="font-style:italic;">S. sonnei</span> and <span style="font-style:italic;">S.</span> Typhi, and survived lethal intranasal <span style="font-style:italic;">S. sonnei</span> challenge. This paves the way for proposed good manufacturing practices manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against <span style="font-style:italic;">S. sonnei</span> shigellosis and typhoid fever, as compared with the current Ty21a vaccine.</span>

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The Chemokine CXCL-10 Is a Marker of Infection Stage in Individuals With DNAemia Due to Parvovirus B19

<span class="paragraphSection"><div class="boxTitle">Background</div>Accurate diagnosis of parvovirus B19 (B19V) infection requires the differentiation between acute and past infection, which is especially important when DNAemia due to B19V (hereafter, “B19V DNAemia”) is detected in pregnancy. Here, we explored whether the level of the chemokine CXCL-10, in combination with findings of molecular and serological assays, can discriminate between acute and past B19V infection.<div class="boxTitle">Methods</div>B19V DNA–positive serum samples from 222 immunocompetent individuals were analyzed for (1) viral DNA loads, (2) anti-B19V immunoglobulin M (IgM) and immunoglobulin G (IgG), (3) anti-VP1 IgG avidity, (4) anti-VP-2 epitope type specificity (ETS), and (5) CXCL-10 serum levels.<div class="boxTitle">Results</div>Anti-B19V IgM and IgG, avidity, and ETS assays were used to categorize individuals with B19V DNAemia as having acute or past B19V infection. Acute B19V infection caused a significant increase in the serum concentration of CXCL-10, compared with the concentration at baseline, before infection. Higher CXCL-10 serum levels were furthermore detected in acute B19V infection as compared to past infection. As a marker, CXCL-10 serum levels could discriminate between acute and past B19V infection, with an excellent discriminatory capacity when CXCL-10 and B19V DNA levels were used as combined parameters.<div class="boxTitle">Conclusion</div>Acute B19V infection is associated with increased CXCL-10 production, and measurement of CXCL-10 serum levels thus allows for the staging of B19V infection in individuals with B19V DNAemia.</span>

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Clindamycin Affects Group A Streptococcus Virulence Factors and Improves Clinical Outcome

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Group A <span style="font-style:italic;">Streptococcus</span> (GAS) has acquired an arsenal of virulence factors, promoting life-threatening invasive infections such as necrotizing fasciitis. Current therapeutic regimens for necrotizing fasciitis include surgical debridement and treatment with cell wall–active antibiotics. Addition of clindamycin (CLI) is recommended, although clinical evidence is lacking. Reflecting the current clinical dilemma, an observational study showed that only 63% of the patients with severe invasive GAS infection received CLI. This work thus aimed to address whether CLI improves necrotizing fasciitis outcome by modulating virulence factors of CLI-susceptible and CLI-resistant GAS in vitro and in vivo. Treatment with CLI reduced extracellular DNase Sda1 and streptolysin O (SLO) activity in vivo, whereas subinhibitory CLI concentrations induced expression and activity of SLO, DNase, and <span style="font-style:italic;">Streptococcus pyogenes</span> cell envelope protease in vitro. Our in vivo results suggest that CLI should be administered as soon as possible to patients with necrotizing fasciitis, while our in vitro studies emphasize that a high dosage of CLI is essential.</span>

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Vaseline: Is it safe? - Asianjournal.com

KAGS News

Vaseline: Is it safe? Asianjournal.com ... American Association of Central Cancer Registries (co-author) have shown that “HPV infections cause virtually all cervical cancers, 90 percent of anal cancers, more than 60 percent of certain oropharyngeal cancers (including the base of the tongue ... Nearly Half of Men Have Genital HPV Infection : Hot Issues : Lawyer ...Lawyer Herald all 12 news articles »

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Ylidenemalononitrile Enamine-Coated Media as Fluorescent "Turn-On" Probes for Volatile Primary Amines

Photochem. Photobiol. Sci., 2017, Accepted Manuscript
DOI: 10.1039/C7PP00021A, Communication

Ashley Rose Longstreet, Rebecca R Chandler, Tanmay Banerjee, L. Zane Miller, Kenneth Hanson, D. Tyler McQuade
Two ylidenemalononitrile enamines, adsorbed to various media, undergo a cyclization reaction with primary amine vapors resulting in a fluorometric and colorimetric response. After determining the media with the fastest response...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Epidermodysplasia verruciformis (EV)

Epidermodysplasia verruciformis (EV): a rare genetic condition that leads to susceptibility to infection of the skin by human papillomaviruses (HPVs) and the development of squamous cells carcinomas (a type of cancer) of the skin. Symptoms include flat-to-raised, wart-like bumps and reddish-brown raised plaques on the trunk, hands, upper and lower extremities, and the face. Patients with this condition are typically infected with multiple types of HPV. The genetic defect responsible for epidermodysplasia verruciformis leads to a defective immune response to HPV infection, which leads to the characteristic symptoms. Most cases are inherited in an autosomal recessive manner, which means that both parents must carry a defective copy of the gene for the offspring to develop the condition.

Epidermodysplasia verruciformis has also been referred to as Lewandowsky-Lutz dysplasia, tree-man illness, or tree-man disease.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Treating Early Knee Osteoarthritis with the Atlas® Unicompartmental Knee System in a 26-Year-Old Ex-Professional Basketball Player: A Case Study

Knee osteoarthritis (OA) is a leading cause of disability among adults. Within the affected population, there exists a group of patients who have exhausted conservative treatment options and yet are not ideal candidates for current surgical treatments due to young age, early disease severity, or neutral mechanical knee alignment. For these patients, a new potential treatment option may be considered. We present an interesting case report of a young, ex-professional athlete treated with a minimally invasive load-altering implant (Atlas System) whose young age (26 years), disease status (tibiofemoral kissing lesions), and neutral mechanical limb alignment eliminated all traditional surgical treatment options such as high tibial osteotomy or arthroplasty. At 6 months after surgery, our patient demonstrated positive outcomes improvement in pain, function, and quality of life and had returned to high-impact athletic activity without symptoms. These initial results are promising, and longer follow-up data on the treatment will be necessary.

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A Generalization of the Krätzel Function and Its Applications

In this paper, we introduce new functions as a generalization of the Krätzel function. We investigate recurrence relations, Mellin transform, fractional derivatives, and integral of the function . We show that the function is the solution of differential equations of fractional order.

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Redox and pH Responsive Poly (Amidoamine) Dendrimer-Heparin Conjugates via Disulfide Linkages for Letrozole Delivery

Heparin (Hep) conjugated to poly (amidoamine) dendrimer G3.5 (P) via redox-sensitive disulfide bond (P-SS-Hep) was studied. The redox and pH dual-responsive nanocarriers were prepared by a simple method that minimized many complex steps as previous studies. The functional characterization of G3.5 coated Hep was investigated by the proton nuclear magnetic resonance spectroscopy. The size and formation were characterized by the dynamic light scattering, zeta potential, and transmission electron microscopy. P-SS-Hep was spherical in shape with average diameter about 11 nm loaded with more than 20% letrozole. This drug carrier could not only eliminate toxicity to cells and improve the drugs solubility but also increase biocompatibility of the system under reductive environment of glutathione. In particular, P-SS-Hep could enhance the effectiveness of cancer therapy after removing Hep from the surface. These results demonstrated that the P-SS-Hep conjugates could be a promising candidate as redox and pH responsive nanocarriers for cancer chemotherapy.

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Heat Dissipation of Resonant Absorption in Metal Nanoparticle-Polymer Films Described at Particle Separation Near Resonant Wavelength

Polymer films containing plasmonic nanostructures are of increasing interest for development of responsive energy, sensing, and therapeutic systems. The present work evaluates heat dissipated from power absorbed by resonant gold (Au) nanoparticles (NP) with negligible Rayleigh scattering cross sections randomly dispersed in polydimethylsiloxane (PDMS) films. Finite element analysis (FEA) of heat transport was coordinated with characterization of resonant absorption by Mie theory and coupled dipole approximation (CDA). At AuNP particle separation greater than resonant wavelength, correspondence was observed between measured and CDA-predicted optical absorption and FEA-derived power dissipation. At AuNP particle separation less than resonant wavelength, measured extinction increased relative to predicted values, while FEA-derived power dissipation remained comparable to CDA-predicted power absorption before lagging observed extinguished power at higher AuNP content and resulting particle separation. Effects of isolated particles, for example, scattering, and particle-particle interactions, for example, multiple scattering, aggregation on observed optothermal activity were evaluated. These complementary approaches to distinguish contributions to resonant heat dissipation from isolated particle absorption and interparticle interactions support design and adaptive control of thermoplasmonic materials for a variety of implementations.

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Directional Transport of a Bead Bound to Lamellipodial Surface Is Driven by Actin Polymerization

The force driving the retrograde flow of actin cytoskeleton is important in the cellular activities involving cell movement (e.g., growth cone motility in axon guidance, wound healing, or cancer metastasis). However, relative importance of the forces generated by actin polymerization and myosin II in this process remains elusive. We have investigated the retrograde movement of the poly-D-lysine-coated bead attached with the optical trap to the edge of lamellipodium of Swiss 3T3 fibroblasts. The velocity of the attached bead drastically decreased by submicromolar concentration of cytochalasin D, latrunculin A, or jasplakinolide, indicating the involvement of actin turnover. On the other hand, the velocity decreased only slightly in the presence of 50 μM (−)-blebbistatin and Y-27632. Comparative fluorescence microscopy of the distribution of actin filaments and that of myosin II revealed that the inhibition of actin turnover by cytochalasin D, latrunculin A, or jasplakinolide greatly diminished the actin filament network. On the other hand, inhibition of myosin II activity by (−)-blebbistatin or Y-27632 little affected the actin network but diminished stress fibers. Based on these results, we conclude that the actin polymerization/depolymerization plays the major role in the retrograde movement, while the myosin II activity is involved in the maintenance of the dynamic turnover of actin in lamellipodium.

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Unbalance Compensation of a Full Scale Test Rig Designed for HTR-10GT: A Frequency-Domain Approach Based on Iterative Learning Control

Unbalance vibrations are crucial problems in heavy rotational machinery, especially for the systems with high operation speed, like turbine machinery. For the program of 10 MW High Temperature gas-cooled Reactor with direct Gas-Turbine cycle (HTR-10GT), the rated operation speed of the turbine system is 15000 RPM which is beyond the second bending frequency. In that case, even a small residual mass will lead to large unbalance vibrations. Thus, it is of great significance to study balancing methods for the system. As the turbine rotor is designed to be suspended by active magnetic bearings (AMBs), unbalance compensation could be achieved by adequate control strategies. In the paper, unbalance compensation for the Multi-Input and Multi-Output (MIMO) active magnetic bearing (AMB) system using frequency-domain iterative learning control (ILC) is analyzed. Based on the analysis, an ILC controller for unbalance compensation of the full scale test rig, which is designed for the rotor and AMBs in HTR-10GT, is designed. Simulation results are reported which show the efficiency of the ILC controller for attenuating the unbalance vibration of the full scale test rig. This research can offer valuable design criterion for unbalance compensation of the turbine machinery in HTR-10GT.

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Flexible Job Shop Scheduling Problem Using an Improved Ant Colony Optimization

As an extension of the classical job shop scheduling problem, the flexible job shop scheduling problem (FJSP) plays an important role in real production systems. In FJSP, an operation is allowed to be processed on more than one alternative machine. It has been proven to be a strongly NP-hard problem. Ant colony optimization (ACO) has been proven to be an efficient approach for dealing with FJSP. However, the basic ACO has two main disadvantages including low computational efficiency and local optimum. In order to overcome these two disadvantages, an improved ant colony optimization (IACO) is proposed to optimize the makespan for FJSP. The following aspects are done on our improved ant colony optimization algorithm: select machine rule problems, initialize uniform distributed mechanism for ants, change pheromone’s guiding mechanism, select node method, and update pheromone’s mechanism. An actual production instance and two sets of well-known benchmark instances are tested and comparisons with some other approaches verify the effectiveness of the proposed IACO. The results reveal that our proposed IACO can provide better solution in a reasonable computational time.

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Angular Domain Data-Assisted Channel Estimation for Pilot Decontamination in Massive MIMO

Massive Multiple-Input-Multiple-Output (M-MIMO) system is a promising technology that offers to mobile networks substantial increase in throughput. In Time-Division Duplexing (TDD), the uplink training allows a Base Station (BS) to acquire Channel State Information (CSI) for both uplink reception and downlink transmission. This is essential for M-MIMO systems where downlink training pilots would consume large portion of the bandwidth. In densely populated areas, pilot symbols are reused among neighboring cells. Pilot contamination is the fundamental bottleneck on the performance of M-MIMO systems. Pilot contamination effect in antenna arrays can be mitigated by treating the channel estimation problem in angular domain where channel sparsity can be exploited. In this paper, we introduce a codebook that projects the channel into orthogonal beams and apply Minimum Mean-Squared Error (MMSE) criterion to estimate the channel. We also propose data-aided channel covariance matrix estimation algorithm for angular domain MMSE channel estimator by exploiting properties of linear antenna array. The algorithm is based on simple linear operations and no matrix inversion is involved. Numerical results show that the algorithm performs well in mitigating pilot contamination where the desired channel and other interfering channels span overlapping angle-of-arrivals.

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Manufacturing Data Uncertainties Propagation Method in Burn-Up Problems

A nuclear data-based uncertainty propagation methodology is extended to enable propagation of manufacturing/technological data (TD) uncertainties in a burn-up calculation problem, taking into account correlation terms between Boltzmann and Bateman terms. The methodology is applied to reactivity and power distributions in a Material Testing Reactor benchmark. Due to the inherent statistical behavior of manufacturing tolerances, Monte Carlo sampling method is used for determining output perturbations on integral quantities. A global sensitivity analysis (GSA) is performed for each manufacturing parameter and allows identifying and ranking the influential parameters whose tolerances need to be better controlled. We show that the overall impact of some TD uncertainties, such as uranium enrichment, or fuel plate thickness, on the reactivity is negligible because the different core areas induce compensating effects on the global quantity. However, local quantities, such as power distributions, are strongly impacted by TD uncertainty propagations. For isotopic concentrations, no clear trends appear on the results.

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Comparative Survey of Holding Positions for Reducing Vaccination Pain in Young Infants

Background. Infant holding position may reduce vaccination pain. However, the optimal position for young infants remains controversial. Objectives. To compare the effectiveness of holding infants in the supine position and the effectiveness of holding infants in upright position for relieving acute pain from vaccine injection. Methods. This prospective cohort study enrolled 6–12-week-old healthy infants. We examined infant pain responses by evaluating the following three categories: (1) crying, (2) irritability, and (3) facial expression. Results. In total, 282 infants were enrolled, with 103 and 179 held in the supine and upright positions, respectively. At 30 s after vaccination, the infants in the supine position showed a larger decrease in crying (), irritability (), and pained facial expression () than did those in the upright position. However, there was no significant difference in pain response between two groups at 180 s after intervention. Conclusion. In 2-month-old infants, the supine position may reduce acute pain more effectively than does the upright position. Our findings provide a clinical strategy for relieving vaccination pain in young infants.

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Synchronization and Antisynchronization of -Coupled Complex Permanent Magnet Synchronous Motor Systems with Ring Connection

This paper discusses synchronization and antisynchronization of -coupled complex permanent magnet synchronous motors systems with ring connection. Based on the direct design method and antisymmetric structure, the appropriate controllers are designed to ensure the occurrence of synchronization and antisynchronization in an array of -coupled general complex chaotic systems described by a unified mathematical expression with ring connection. The proposed method is flexible and is suitable both for design and for implementation in practice. Numerical results are plotted to show the rapid convergence of errors to zero and further verify the effectiveness and feasibility of the theoretical scheme.

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Unusual Complication following a Myomectomy: Colic Migration of a Forgotten Abdominal Swab

Surgical sponges are the most common retained foreign bodies following surgery. The morbidity of this condition is illustrated herein with the case of a 36-year-old female patient with a history of myomectomy 5 months before her admission into our unit for enterocutaneous fistula. Although imaging and etiological investigations were made, diagnosis was carried out only by laparotomy. The foreign body found was an abdominal swab that migrated from abdominal cavity to the colon causing several intestinal injuries. The lack of specific clinical signs and the death of the patient raise the necessity of preventing these complications that involve the surgeon liability.

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Use of Molecular Methods for the Rapid Mass Detection of Schistosoma mansoni (Platyhelminthes: Trematoda) in Biomphalaria spp. (Gastropoda: Planorbidae)

The low stringency-polymerase chain reaction (LS-PCR) and loop-mediated isothermal amplification (LAMP) assays were used to detect the presence of S. mansoni DNA in (1) Brazilian intermediate hosts (Biomphalaria glabrata, B. straminea, and B. tenagophila) with patent S. mansoni infections, (2) B. glabrata snails with prepatent S. mansoni infections, (3) various mixtures of infected and noninfected snails; and (4) snails infected with other trematode species. The assays showed high sensitivity and specificity and could detect S. mansoni DNA when one positive snail was included in a pool of 1,000 negative specimens of Biomphalaria. These molecular approaches can provide a low-cost, effective, and rapid method for detecting the presence of S. mansoni in pooled samples of field-collected Biomphalaria. These assays should aid mapping of transmission sites in endemic areas, especially in low prevalence regions and improve schistosomiasis surveillance. It will be a useful tool to monitor low infection rates of snails in areas where control interventions are leading towards the elimination of schistosomiasis.

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Prevalence of Hepatitis C Virus Infection and Its Risk Factors among Patients Attending Rwanda Military Hospital, Rwanda

In Rwanda, the prevalence of viral hepatitis (HCV) is poorly understood. The current study investigated the prevalence and risk factors of HCV infection in Rwanda. A total of 324 patients attending Rwanda Military Hospital were randomly selected and a questionnaire was administered to determine the risk factors. Blood was collected and screened for anti-HCV antibodies and seropositive samples were subjected to polymerase chain reaction method. Hematology abnormalities in the HCV infected patients were also investigated. Anti-HCV antibody and active HCV infection were found in 16.0% and 9.6% of total participants, respectively. Prevalence was highest (28.4%; 19/67) among participants above 55 years and least (2.4%; 3/123) among younger participants (18–35 years). There was a significant () relationship between place of residence and HCV infection with residents of Southern Province having significantly higher prevalence. The hematological abnormalities observed in the HCV infected patients included leukopenia (48.4%; 15/52), neutropenia (6.5%; 2/52), and thrombocytopenia (25.8%; 8/52). The HCV infection was significantly higher in the older population (>55 years) and exposure to injection from traditional practitioners was identified as a significant () risk factor of infection. Further studies to determine the factors causing the high prevalence of HCV in Rwanda are recommended.

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Productivity Analysis of Volume Fractured Vertical Well Model in Tight Oil Reservoirs

This paper presents a semianalytical model to simulate the productivity of a volume fractured vertical well in tight oil reservoirs. In the proposed model, the reservoir is a composite system which contains two regions. The inner region is described as formation with finite conductivity hydraulic fracture network and the flow in fracture is assumed to be linear, while the outer region is simulated by the classical Warren-Root model where radial flow is applied. The transient rate is calculated, and flow patterns and characteristic flowing periods caused by volume fractured vertical well are analyzed. Combining the calculated results with actual production data at the decline stage shows a good fitting performance. Finally, the effects of some sensitive parameters on the type curves are also analyzed extensively. The results demonstrate that the effect of fracture length is more obvious than that of fracture conductivity on improving production in tight oil reservoirs. When the length and conductivity of main fracture are constant, the contribution of stimulated reservoir volume (SRV) to the cumulative oil production is not obvious. When the SRV is constant, the length of fracture should also be increased so as to improve the fracture penetration and well production.

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Evaluation of Decalcification Techniques for Rat Femurs Using HE and Immunohistochemical Staining

Aim. In routine histopathology, decalcification is an essential step for mineralized tissues. The purpose of this study is to evaluate the effects of different decalcification solutions on the morphological and antigenicity preservation in Sprague Dawley (SD) rat femurs. Materials and Methods. Four different decalcification solutions were employed to remove the mineral substances from rat femurs, including 10% neutral buffered EDTA, 3% nitric acid, 5% nitric acid, and 8% hydrochloric acid/formic acid. Shaking and low temperature were used to process the samples. The stainings of hematoxylin-eosin (HE) and immunohistochemical (IHC) were employed to evaluate the bone morphology and antigenicity. Key Findings. Different decalcification solutions may affect the quality of morphology and the staining of paraffin-embedded sections in pathological examinations. Among four decalcifying solutions, 3% nitric acid is the best decalcifying agent for HE staining. 10% neutral buffered EDTA and 5% nitric acid are the preferred decalcifying agents for IHC staining. Significance. The current study investigated the effects of different decalcifying agents on the preservation of the bone structure and antigenicity, which will help to develop suitable protocols for the analyses of the bony tissue.

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Earth Materials and Environmental Applications 2016

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Correlation of Ezrin Expression Pattern and Clinical Outcomes in Ewing Sarcoma

Background. Ezrin is a membrane-cytoskeleton linker protein that has been associated with metastasis and poor outcomes in osteosarcoma and high-grade soft tissue sarcomas. The prognostic value of ezrin expression in Ewing sarcoma is unknown. Methods. The relationship between ezrin expression and outcome was analyzed in a cohort of 53 newly diagnosed Ewing sarcoma patients treated between 2000 and 2011. The intensity and proportion of cells with ezrin immunoreactivity were assessed in diagnostic tumor tissue using a semiquantitative scoring system to yield intensity and positivity scores for each tumor. Results. Ezrin expression was detected in 72% (38/53) of tumor samples. The proportion of patients with metastatic disease was equal in the positive and negative ezrin expression groups. There was no significant difference in the 5-year event-free survival (EFS) between patients with positive versus negative ezrin expression. Patients whose tumor sample showed high ezrin intensity had significantly better 5-year EFS when compared to patients with low/no ezrin intensity (78% versus 55%; ). Conclusions. Ezrin expression can be detected in the majority of Ewing sarcoma tumor samples. Intense ezrin expression may be correlated with a favorable outcome; however further investigation with a larger cohort is needed to validate this finding.

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Adults’ Theory of Infants’ Mind: A Comparison between Parents and Nonparents

This study examined whether there were parental state differences in interpretations of infants’ behaviours as associated with some mental states. Parents, nonparent women, and nonparent men were shown video clips that displayed several infant behaviours (e.g., playing with his/her mother). Then they were given two tasks. In a rating task, participants were asked to rate the likelihood of the filmed infant to have a mental state. On the other hand, in a description task, participants were instructed to explicitly describe the filmed infants’ mental state in an open-ended manner. Importantly, all participants were asked to report the meaning of infants’ behaviour in specific acts from the same set of infants’ behaviours (e.g., the infants saw mother’s face and smiled). The results revealed that parents and nonparent women significantly higher rated that infants were likely to express a mental state in the rating task than nonparent men did. On the other hand, parents were more likely to describe the filmed infants’ mental states in the description task than nonparent women and nonparent men did. Results suggest that parents interpret more meanings from infants’ behaviours compared to nonparents, even when both parents and nonparents equally focused on infants’ behaviours.

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The Risk of Sexually Transmitted Infection and Its Influence on Condom Use among Pregnant Women in the Kintampo North Municipality of Ghana

Sexually transmitted infection (STI) affects the reproductive health of both men and women worldwide. Condoms are important part of the available preventive strategies for STI control. The lack of proper risk-perception continues to impede women’s ability to negotiate condom use with their partners. This paper is the outcome of secondary analysis of data collected in a cross-sectional survey that explored the perception of risk of STI and its influence on condom use among 504 pregnant women attending antenatal clinic at two health facilities in the Kintampo North Municipality. Consecutively, three Focus Group Discussions were conducted among 22 pregnant women which was analyzed using thematic analysis technique. Multivariate logistic regression analysis was used to identify possible predictors of condom use and risk of STI. Respondents mean age was years. 47% of respondents self-identified themselves as high risk for contracting STI, 50% of whom were married. High risk status (OR = 2.1, 95% CI: 1.1–4.4), ability to ask for condoms during sex (OR = 0.3, 95% CI: 0.1–0.73), and partner’s approval of condom use (OR = 0.2, 95% CI: 0.01–0.05) were independent predictors of condom use. Condom use (OR 2.9 (1.5–5.7); ) and marital status (engaged, OR 2.6 (1.5–4.5); ) were independent predictors of risk of STI. Women who self-identified themselves as high risk for STI successfully negotiated condom use with their partners. This is however influenced by partner’s approval and ability to convince partner to use condoms. Self-assessment of STI risk by women and the cooperation of male partners remain critical.

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Epidermolytic Ichthyosis Sine Epidermolysis.

Epidermolytic ichthyosis (EI) is a rare disorder of cornification caused by mutations in KRT1 and KRT10, encoding two suprabasal epidermal keratins. Because of the variable clinical features and severity of the disease, histopathology is often required to correctly direct the molecular analysis. EI is characterized by hyperkeratosis and vacuolar degeneration of the upper epidermis, also known as epidermolytic hyperkeratosis, hence the name of the disease. In the current report, the authors describe members of 2 families presenting with clinical features consistent with EI. The patients were shown to carry classical mutations in KRT1 or KRT10, but did not display epidermolytic changes on histology. These observations underscore the need to remain aware of the limitations of pathological features when considering a diagnosis of EI. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Soluble CD14 acts as a DAMP in human macrophages: origin and involvement in inflammatory cytokine/chemokine production [Research]

The innate immune system is able to detect bacterial LPS through the pattern recognition receptor CD14, which delivers LPS to various TLR signaling complexes that subsequently induce intracellular proinflammatory signaling cascades. In a previous study, we showed the overproduction of the soluble form of CD14 (sCD14) by macrophages from patients with cystic fibrosis (CF). CF is an autosomal recessive disorder that is caused by mutations in the gene that encodes the CFTR protein and is characterized by persistent inflammation. Macrophages play a significant role in the initial stages of this disease due to their inability to act as suppressor cells, leading to chronic inflammation in CF. In this work, we investigated the origin of sCD14 by human macrophages and studied the effect of sCD14 on the production of inflammatory cytokine/chemokine. Our data indicate that sCD14 stimulate proinflammatory cytokine/chemokine production in a manner that is independent of LPS but dependent on the TLR-4/CD14 membrane complex, NF-B, and the inflammasome. Therefore, sCD14, overproduced by CF macrophages, originates primarily from the endocytosis/exocytosis process and should be considered to be a danger-associated molecular pattern. This elucidation of the origin and inflammation-induced mechanisms associated with sCD14 contributes to our understanding of maintained tissue inflammation.—Lévêque, M., Simonin-Le Jeune, K., Jouneau, S., Moulis, S., Desrues, B., Belleguic, C., Brinchault, G., Le Trionnaire, S., Gangneux, J.-P., Dimanche-Boitrel, M.-T., Martin-Chouly, C. Soluble CD14 acts as a DAMP in human macrophages: origin and involvement in inflammatory cytokine/chemokine production.

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Nuclear factor I-C reciprocally regulates adipocyte and osteoblast differentiation via control of canonical Wnt signaling [Research]

Nuclear factor I-C (NFIC) has recently been identified as an important player in osteogenesis and bone homeostasis in vivo. However, the molecular mechanisms involved have yet to be defined. In the current study, Nfic expression was altered in primary marrow stromal cells and established progenitor lines after adipogenic and osteogenic treatment. Overexpression of Nfic in stromal cells ST2, mesenchymal cells C3H10T1/2, and primary marrow stromal cells inhibited adipogenic differentiation, whereas it promoted osteogenic differentiation. Conversely, silencing of endogenous Nfic in the cell lines enhanced adipogenic differentiation, whereas it blocked osteogenic differentiation. Mechanism investigations revealed that Nfic overexpression promoted nuclear translocation of β-catenin and increased nuclear protein levels of β-catenin and transcription factor 7-like 2 (TCF7L2). Promoter studies and the chromatin immunoprecipitation (ChIP) assay revealed that NFIC directly binds to the promoter of low-density lipoprotein receptor-related protein 5 (Lrp5) and thereafter transactivates the promoter. Finally, inactivation of canonical Wnt signaling in ST2 attenuated the inhibition of adipogenic differentiation and stimulation of osteogenic differentiation by NFIC. Our study suggests that NFIC balances adipogenic and osteogenic differentiation from progenitor cells through controlling canonical Wnt signaling and highlights the potential of NFIC as a target for new therapies to control metabolic disorders like osteoporosis and obesity.—Zhou, J., Wang, S., Qi, Q., Yang, X., Zhu, E., Yuan, H., Li, X., Liu, Y., Li, X., Wang, B. Nuclear factor I-C reciprocally regulates adipocyte and osteoblast differentiation via control of canonical Wnt signaling.

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Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits [Research]

Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side-specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.—Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.

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Current applications and limitations of surgical treatments for movement disorders

ABSTRACT

Functional neurosurgery for the treatment of both psychiatric and neurological disorders has been performed regularly since the 1940s. However, misuse in the early days and the appearance of effective medical treatments, such as levodopa and neuroleptic drugs, greatly reduced surgical approaches over several decades. The development of a comprehensive model of basal ganglia pathophysiology in the 1990s facilitated the resurgence of functional neurosurgery, mainly for the treatment of levodopa-related motor complications in Parkinson's disease. This led first to the re-emergence of posteroventral pallidotomy and subsequently to deep brain stimulation. Thirty years on from this turning point, we find ourselves looking at a new scenario. Although deep brain stimulation is accepted worldwide and technical advances continue to improve this therapy, new questions and challenges such as long-term benefits and optimal targeting have emerged. In addition, new nonincisional tools used to perform ablative treatments, such as high-intensity focused ultrasound and gamma-knife, are challenging classical reluctance to therapeutic lesioning, and it remains to be determined how these approaches will fit into the array of movement disorder treatments. This review discusses the current clinical state of the art of functional neurosurgery in the treatment of Parkinson's disease, tremor, and dystonia. © 2017 International Parkinson and Movement Disorder Society

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Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis

ABSTRACT

Background: The thalamus has been a surgical target for the treatment of various movement disorders. Commonly used therapeutic modalities include ablative and nonablative procedures. A major clinical side effect of thalamic surgery is the appearance of speech problems.

Objective: This review summarizes the data on the development of speech problems after thalamic surgery.

Methods: A systematic review and meta-analysis was performed using nine databases, including Medline, Web of Science, and Cochrane Library. We also checked for articles by searching citing and cited articles. We retrieved studies between 1960 and September 2014.

Results: Of a total of 2,320 patients, 19.8% (confidence interval: 14.8–25.9) had speech difficulty after thalamotomy. Speech difficulty occurred in 15% (confidence interval: 9.8–22.2) of those treated with a unilaterally and 40.6% (confidence interval: 29.5–52.8) of those treated bilaterally. Speech impairment was noticed 2- to 3-fold more commonly after left-sided procedures (40.7% vs. 15.2%). Of the 572 patients that underwent DBS, 19.4% (confidence interval: 13.1–27.8) experienced speech difficulty. Subgroup analysis revealed that this complication occurs in 10.2% (confidence interval: 7.4–13.9) of patients treated unilaterally and 34.6% (confidence interval: 21.6–50.4) treated bilaterally. After thalamotomy, the risk was higher in Parkinson's patients compared to patients with essential tremor: 19.8% versus 4.5% in the unilateral group and 42.5% versus 13.9% in the bilateral group. After DBS, this rate was higher in essential tremor patients.

Conclusion: Both lesioning and stimulation thalamic surgery produce adverse effects on speech. Left-sided and bilateral procedures are approximately 3-fold more likely to cause speech difficulty. This effect was higher after thalamotomy compared to DBS. In the thalamotomy group, the risk was higher in Parkinson's patients, whereas in the DBS group it was higher in patients with essential tremor. Understanding the pathophysiology of speech disturbance after thalamic procedures is a priority. © 2017 International Parkinson and Movement Disorder Society

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Issue Information - Table of Contents

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Corrigendum

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Editors' Note: The 200th Anniversary of the Shaking Palsy

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Movement Disorders: Volume 32, Number 1, January 2017

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Issue Information - Masthead

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What Would Dr. James Parkinson Think Today? I. The Role of Functional Neurosurgery for Parkinson's Disease

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Examining the Conditions Under Which Internalized Homophobia Is Associated with Substance Use and Condomless Sex in Young MSM: the Moderating Role of Impulsivity

Abstract

Background

Internalized homophobia (IH) is the internalization of homophobic attitudes by sexual minorities due to social bias. IH has been inconsistently related to substance use and condomless sex for young men who have sex with men (YMSM).

Purpose

We examined negative urgency (the tendency to act impulsively in response to negative emotional experiences), positive urgency (the tendency to act impulsively in response to positive emotional experiences), and sensation seeking as independent moderators of the association of IH with binge drinking, drug use, and condomless anal sex.

Methods

Data were collected from 450 YMSM (mean age = 18.9) over the course of 18 months (baseline, 6-, 12-, and 18-month follow-up).

Results

Hierarchical generalized linear modeling revealed that there was a significant moderation for binge drinking and receptive condomless anal sex, with the association between IH and these risk behaviors increased for those with higher levels of negative urgency and positive urgency.

Conclusions

IH is important to the negative health outcomes of binge drinking and condomless anal sex for individuals high in negative and/or positive urgency, who may act impulsively to avoid subjective negative experiences or in the face of positive emotional experiences. Future research is needed to further establish additional conditions under which IH may be important to understanding risk behaviors in YMSM, which is essential to developing targeted prevention and intervention efforts.

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How Can Implicit and Explicit Attitudes Both Be Changed? Testing Two Interventions to Promote Consumption of Green Vegetables

Abstract

Background

Although correlational studies have demonstrated that implicit and explicit attitudes are both important in predicting eating behavior, few studies targeting food choice have attempted to change both types of attitudes.

Purpose

We tested the impact of (a) an evaluative learning intervention that uses the self to change attitudes (i.e., a Self-Referencing task) and (b) a persuasive communication in modifying implicit and explicit attitudes towards green vegetables and promoting readiness to change. The study targeted individuals who explicitly reported they did not like or only moderately liked green vegetables.

Methods

Participants (N = 273) were randomly allocated to a 2 (self-referencing: present vs. absent) × 2 (persuasive message: present vs. absent) factorial design. The outcomes were implicit and explicit attitudes as well as readiness to increase consumption of green vegetables.

Results

Implicit attitudes increased after repeatedly pairing green vegetable stimuli with the self in the self-referencing task but did not change in response to the persuasive communication. The persuasive message increased explicit attitudes and readiness to change, but did not alter implicit attitudes. A three-way interaction with pre-existing explicit attitudes was also observed. In the absence of a persuasive message, the self-referencing task increased on readiness to change among participants with more negative pre-existing explicit attitudes.

Conclusions

This study is the first to demonstrate that a self-referencing task is effective in changing both implicit attitudes and readiness to change eating behavior. Findings indicate that distinct intervention strategies are needed to change implicit and explicit attitudes towards green vegetables.

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PDF Book Plasticity Of The Auditory System free kagozaki.ru

Capacity for Plasticity in the Adult Owl Auditory System Expanded by . Auditory ... The peripheral auditory system does not have plasticity—even.

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Vaseline: Is it safe? - Asianjournal.com

KAGS News

Vaseline: Is it safe? Asianjournal.com ... North American Association of Central Cancer Registries (co-author) have shown that “HPV infections cause virtually all cervical cancers, 90 percent of anal cancers, more than 60 percent of certain oropharyngeal cancers (including the base of the ... Nearly Half of Men Have Genital HPV InfectionLawyer Herald all 11 news articles »

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Localization of NDR2 to peroxisomes and its role in ciliogenesis [Cell Biology]

Nuclear Dbf2-related (NDR) kinases, comprising NDR1 and NDR2, are serine/threonine kinases that play crucial roles in the control of cell proliferation, apoptosis, and morphogenesis. We recently showed that NDR2, but not NDR1, is involved in primary cilium formation; however, the mechanism underlying their functional difference in ciliogenesis is unknown. To address this issue, we examined their subcellular localization. Despite their close sequence similarity, NDR2 exhibited punctate localization in the cytoplasm, whereas NDR1 was diffusely distributed within the cell. Notably, NDR2 puncta mostly co-localized with the peroxisome marker proteins, catalase and CFP-SKL (cyan fluorescent protein carrying the C-terminal typical peroxisome-targeting signal type-1 (PTS1) sequence, Ser-Lys-Leu). NDR2 contains the PTS1-like sequence, Gly-Lys-Leu, at the C-terminal end, whereas the C-terminal end of NDR1 is Ala-Lys. An NDR2 mutant lacking the C-terminal Leu, NDR2(ΔL), exhibited almost diffuse distribution in cells. Additionally, NDR2, but neither NDR1 nor NDR2(ΔL), bound to the PTS1 receptor Pex5p. Together, these findings indicate that NDR2 localizes to the peroxisome by using the C-terminal GKL sequence. Intriguingly, topology analysis of NDR2 suggests that NDR2 is exposed to the cytosolic surface of the peroxisome. The expression of wild-type NDR2, but not NDR2(ΔL), recovered the suppressive effect of NDR2 knockdown on ciliogenesis. Furthermore, knockdown of peroxisome biogenesis factor genes (PEX1 or PEX3 ) partially suppressed ciliogenesis. These results suggest that the peroxisomal localization of NDR2 is implicated in its function to promote primary cilium formation.

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JCM, Vol. 6, Pages 13: Mechanisms by Which B Cells and Regulatory T Cells Influence Development of Murine Organ-Specific Autoimmune Diseases

Experiments with B cell-deficient (B−/−) mice indicate that a number of autoimmune diseases require B cells in addition to T cells for their development. Using B−/− Non-obese diabetic (NOD) and NOD.H-2h4 mice, we demonstrated that development of spontaneous autoimmune thyroiditis (SAT), Sjogren’s syndrome and diabetes do not develop in B−/− mice, whereas all three diseases develop in B cell-positive wild-type (WT) mice. B cells are required early in life, since reconstitution of adult mice with B cells or autoantibodies did not restore their ability to develop disease. B cells function as important antigen presenting cells (APC) to initiate activation of autoreactive CD4+ effector T cells. If B cells are absent or greatly reduced in number, other APC will present the antigen, such that Treg are preferentially activated and effector T cells are not activated. In these situations, B−/− or B cell-depleted mice develop the autoimmune disease when T regulatory cells (Treg) are transiently depleted. This review focuses on how B cells influence Treg activation and function, and briefly considers factors that influence the effectiveness of B cell depletion for treatment of autoimmune diseases.

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Editorial Board

Publication date: 28 January 2017
Source:Journal of Controlled Release, Volume 246





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Do nanoparticles have a future in dermal drug delivery?

Publication date: 28 January 2017
Source:Journal of Controlled Release, Volume 246
Author(s): Alexa Patzelt, Wing Cheung Mak, Sora Jung, Fanny Knorr, Martina C. Meinke, Heike Richter, Eckart Rühl, Kwan Yee Cheung, Ngo Bich Nga Nathalie Tran, Jürgen Lademann
More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery?Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis.In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC-dextran by passive diffusion due to a concentration gradient via a porous surface. The protease-triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR-triggered controlled release AuNP-doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA.For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified.In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle.

Graphical abstract

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Drug Delivery Research for the Future: Expanding the Nano Horizons and Beyond

Publication date: 28 January 2017
Source:Journal of Controlled Release, Volume 246
Author(s): Samir Mitragotri, Twan Lammers, You Han Bae, Steven Schwendeman, Stefaan De Smedt, Jean-Christophe Leroux, Dan Peer, Ick Chan Kwon, Hideyoshi Harashima, Akihiko Kikuchi, Yu-Kyoung Oh, Vladmir Torchilin, Wim Hennink, Justin Hanes, Kinam Park




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Photothermally triggered on-demand insulin release from reduced graphene oxide modified hydrogels

Publication date: 28 January 2017
Source:Journal of Controlled Release, Volume 246
Author(s): Florina Teodorescu, Yavuz Oz, Gurvan Quéniat, Amar Abderrahmani, Catherine Foulon, Marie Lecoeur, Rana Sanyal, Amitav Sanyal, Rabah Boukherroub, Sabine Szunerits
On-demand delivery of therapeutics plays an essential role in simplifying and improving patient care. The high loading capacity of reduced graphene oxide (rGO) for drugs has made this matrix of particular interest for its hybridization with therapeutics. In this work, we describe the formulation of rGO impregnated poly(ethylene glycol) dimethacrylate based hydrogels (PEGDMA-rGO) and their efficient loading with insulin. Near-infrared (NIR) light induced heating of the PEGDMA-rGO hydrogels allows for highly efficient insulin release. Most importantly, we validate that the NIR irradiation of the hydrogel has no effect on the biological and metabolic activities of the released insulin. The ease of insulin loading/reloading makes this photothermally triggered release strategy of interest for diabetic patients. Additionally, the rGO-based protein releasing platform fabricated here can be expanded towards ‘on demand’ release of various other therapeutically relevant biomolecules.

Graphical abstract

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