A methodological approach to the classification of dermoscopy images.

In this paper a methodological approach to the classification of pigmented skin lesions in dermoscopy images is presented. First, automatic border detection is performed to separate the lesion from the background skin. Shape features are then extracted from this border. For the extraction of color and texture related features, the image is divided into various clinically significant regions using the Euclidean distance transform. This feature data is fed into an optimization framework, which ranks the features using various feature selection algorithms and determines the optimal feature subset size according to the area under the ROC curve measure obtained from support vector machine classification. The issue of class imbalance is addressed using various sampling strategies, and the classifier generalization error is estimated using Monte Carlo cross validation. Experiments on a set of 564 images yielded a specificity of 92.34% and a sensitivity of 93.33%.     

Elevation of oxidative stress in the aorta of genetically hypertensive mice

Hypertension is an age-dependent disorder. Oxidative stress has been suggested to play a role in aging and age-dependent disorders. The objective of this study is to examine the oxidant and antioxidant status in the aorta of a mouse model with high blood pressure (BPH). Our results showed that the level of malondialdehyde (MDA) in the aorta of BPH mice was approximately 2.6-fold higher than that of the normal blood pressure (BPN) mice, suggesting an increased in vivo oxidative stress in the arterial wall of BPH mice. In addition, the release of hydrogen peroxide (H2O2) from the aorta of BPH mice was significantly faster than that of BPN mice. To determine if the increased H2O2 release is related to a down-regulation of antioxidant enzymes in the arterial wall, we measured the activities of the major antioxidant enzymes in mouse aortas. We observed that the activities of Cu/Zn-superoxide dismutase (SOD) and glutathione peroxidase-1 in BPH mice were similar to BPN mice. On the other hand, the catalase activity in the aorta of BPH mice was significantly reduced while the activities of Mn-SOD and extracellular (EC)-SOD in the aorta of BPH mice were significantly elevated as compared with BPN mice. These results suggest that increase in SOD activity and decrease in catalase activity might be responsible for the increased release of H2O2 in the arterial wall of BPH mice.     

Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin

The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.     

Anti-inflammatory actions of interleukin-13: suppression of tumor necrosis factor-alpha and antigen-induced leukocyte accumulation in the guinea pig lung

The Th2 cytokine interleukin (IL)-13 is believed to play an important role in the development of allergy, although it has also been ascribed anti-inflammatory roles in several experimental models. In this study, we have examined the effects of human recombinant IL-13 on eosinophilic lung inflammation in the guinea pig. IL-13 (1 to 100 ng, given by intratracheal instillation) did not elicit airway eosinophil recruitment. A pronounced accumulation of eosinophils, as well as monocyte/macrophages, was elicited by intratracheal instillation of guinea pig tumor necrosis factor alpha (gpTNF-alpha). Intratracheal administration of IL-13 (1 to 100 ng) given immediately prior to exposure to gpTNF-alpha resulted in a dose-related suppression of eosinophil and monocyte/macrophage accumulation in the airways, as assessed by bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in whole-lung homogenates. IL-13 treatment also reduced BAL fluid (BALF) leukocyte accumulation induced by subsequent aerosol antigen challenge of sensitized guinea pigs. Antigen challenge also resulted in elevated levels of immunoreactive eotaxin and eosinophil-stimulating activity in BALF, although only the latter was reduced significantly by IL-13 instillation prior to challenge. In contrast to the suppressive effects of IL-13, instillation of human recombinant IL-4 (100 ng) alone elicited an increase in BALF monocyte/macrophage numbers, and IL-4 was unable to inhibit gpTNF-alpha-induced leukocyte accumulation. Hence, IL-13 (but not human IL-4) exhibits an anti-inflammatory action in the airways of gpTNF-alpha- or antigen-challenged guinea pigs, by mechanisms that may involve the decreased generation of eosinophil-stimulating activity in the airways.     

Immunomodulatory Effects of Dietary Polyphenols

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.     

Impact of Tibial Tubercle Osteotomy on Final Outcome in Revision Total Knee Arthroplasty: Our Experience and Technique in Pakistan

BackgroudDue to extensive fibrosis during revision surgery, adequate exposure is essential and it can be achieved with several extensile approach options, such as tibial tubercle osteotomy. Information regarding surgical exposure during revision arthroplasty is limited in developing countries, such as Pakistan, due to the lack of adequate data collection and follow-up. Therefore, the purpose of this study was to evaluate the impact of tibial tubercle osteotomy on final outcome of revision total knee arthroplasty (TKA).MethodsA total of 231 revision TKAs were performed between January 2008 and December 2017. Twenty-nine patients underwent tibial tubercle osteotomy for adequate exposure during revision surgery. Of these, 27 patients with complete follow-up were included in our study. Factors examined include age at the time of revision surgery, gender, comorbidities, arthroplasty site (right or left), body mass index (BMI), and primary indications for the tibial tubercle osteotomy during revision TKA. Functional outcome was measured by using Knee Society score (KSS) at 3 months and the final follow-up. All statistical analysis was done using SPSS version 20.0 with a p-value < 0.05 considered significant.ResultsOut of 27 patients, 6 patients (22.2%) were men and 21 patients (77.7%) were women. Right knee revision arthroplasty was performed in 15 patients (55.5%), left knee revision arthroplasty was performed in 12 patients (44.4%), and bilateral revision surgery was performed in only 1 patient (3.7%). The mean BMI was 29.2 kg/m². We used a constrained condylar knee in 20 patients (74%), a rotating hinge knee in 5 patients (18.5%), and mobile bearing tray plus metaphyseal sleeves in 2 patients (7.4%). The KSS was 52.21 ± 4.05 preoperatively, and 79.42 ± 2.2 and 80.12 ± 1.33 at 3 months and 12 months, respectively. Radiological union was achieved in all patients at 3 months. Of 27 patients, only 1 patient (3.7%) had proximal migration of the osteotomy site at 6 months: the patient was asymptomatic and union was also achieved and, therefore, no surgical intervention was performed.ConclusionsTibial tubercle osteotomy during revision TKA can be a safe and reliable technique with superior outcomes and minimal complication rates.     

Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection

To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.     

Auditory brain stem evoked responses (ABRs) in children with delayed speech (DS)—A Diagnostic Problem

The results of analysis of auditory brain- stem evoked responses (ABRS) are reported in 173 patients with delayed speech (DS). The mean age of the patients is 4.6 years (age ranges from 1.4 years to 10 years). The patients were classified into 5 groups based on ABR findings: