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Hypertension is a leading risk factor for cardiovascular disease among patients living with HIV (PLWH). Understanding the predictors and patterns of antihypertensive medication prescription and blood pressure (BP) control among PLWH with hypertension (HTN) is important to improve the primary prevention efforts for this high-risk population. We sought to assess important patient-level correlates (eg, race) and inter-facility variations in antihypertension medication prescriptions and BP control among Veterans living with HIV (VLWH) and HTN. We studied VLWH with a diagnosis of HTN who received care in the Veterans Health Administration (VHA) from January 2018 to December 2019. We evaluated HTN treatment and blood pressure control across demographic variables, including race, and by medical comorbidities. Data were also compared among VHA facilities. Predictors of HTN treatment and control were assessed in 2-level hierarchical multivariate logistic regression models to estimate odds ratios (ORs). The VHA facility random-effects parameters from the hierarchical models were used to calculate the median odds ratios to characterize the variation across the different VHA facilities. A total of 17,468 VLWH with HTN (mean age 61 years, 97% male, 54% Black, 40% White) who received care within the VHA facilities in 2018-2019 were included. 73% were prescribed antihypertension medications with higher prescription rates among Black vs White patients (75% vs 71%) and higher prescription rates among patients with a history of cardiovascular disease, diabetes, and kidney disease (>80%), and those receiving antiretroviral therapy and with controlled HIV viral load (∼75%). Only 27% of VLWH with HTN had optimal BP control of systolic BP <130 mmHg and diastolic BP <80 mmHg, with a lower rate of control among Black vs White patients (24% v. 31%). In multivariate regression, Black patients had a higher likelihood of HTN medication prescription (OR 1.32, 95% CI: 1.22-1.42) but were less likely to have optimal BP control (OR 0.82; 0.76-0.88). Important positive correlates of antihypertensive prescription and optimal BP control included: number of outpatient visits in prior year, and histories of diabetes, coronary artery disease, and heart failure. There was about 10% variability in both antihypertensive prescription and BP control patterns between VHA facilities for patients with similar characteristics. There was increased inter-facility variation in antihypertensive prescription among those with a history of heart failure and those not receiving antiretroviral therapy. In a retrospective analysis of large VHA data, we found that VLWH with HTN have suboptimal antihypertensive medication prescription and BP control. Black VLWH had higher HTN medication prescription rates but lower optimal BP control. [ABSTRACT FROM AUTHOR]

Neuromodulation holds great promise for the treatment of drug-resistant epilepsy. This article reviews the most common types of neuromodulation as well as potential future applications of preclinical techniques such as optogenetics. This review serves as a reference for treating neurologists on the latest science behind such treatment approaches. This narrative review briefly describes the preclinical and clinical history of each technique, with a special emphasis on, wherever possible, strong clinical evidence and any available data from pediatric populations. A detailed literature review was performed for each method of neuromodulation. Since the concept of electrical stimulation as a treatment for neurologic conditions emerged in the early 19th century, neuromodulatory techniques using direct or induced electrical currents have been developed to reduce seizure frequency and duration in patients with drug-resistant epilepsy. This article reviews the applications, clinical guidelines, outcomes, and proposed mechanisms of available approaches, including vagus nerve stimulation, responsive neurostimulation, deep brain stimulation, and transcranial stimulation. Although promising outcomes have been achieved in adults and children with drug-resistant epilepsy, heterogeneity among epilepsy types and etiologies, optimization of stimulation parameters, and a lack of direct comparisons between neuromodulatory approaches are challenges that have yet to be overcome. Neuromodulation is a rapidly evolving field in clinical neuroscience that has treatment implications in a variety of clinical arenas, with epilepsy among the most important of those. It offers the promise of delivering effective treatment for drug-resistant epilepsy, with potentially fewer side effects than standard surgical approaches. © 2020 Elsevier HS Journals, Inc. [ABSTRACT FROM AUTHOR]

To report the five-year follow up results of a prior prospective clinical trial (NCT01212562) on immunocryosurgery for the treatment of non-superficial basal cell carcinoma (BCC) ≤20 mm in diameter. Immunocryosurgery consists of five weeks daily 5% imiquimod cream and a cryosurgery session on day fourteen. This combination cleared 95 ± 2% of BCCs at the eighteen month follow up. Herein, we present the results of the five year follow-up or per last available information of the aforementioned cohort. The primary study outcome was treatment failure (non-complete response or relapse); failure rates were calculated per intention to treat and per protocol. Data for at least five years after initial treatment were available for 55% of the patients (53.4% of per protocol treated tumors) as actualized up to 31th July 2016. Age at recruitment was the only significant predictor of follow-up availability. Nine treatment failures were documented after one immunocryosurgery cycle. The five-year tumor free rate after one immunocryosurgery cycle was 91.4 ± 2.8% and 87.7 ± 3.1% according to per protocol and per intention to treat analysis, respectively. Sex, tumor size or high-risk anatomical localization within the 'H-area' of the face did not affect treatment outcome. With repeat immunocryosurgery cycles only 3 sites were not tumor free at last follow up (effectiveness: 97.1 ± 1.6% per protocol or 93.2 ± 2.3% per intention to treat analysis). Immunocryosurgery is an effective, minimally invasive treatment alternative to surgical modalities for most BCC ≤20 mm in diameter, including those in high risk localizations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Automatic detection of multiple actinic keratoses in sun affected skin areas. • Evaluation of cutaneous cancerization fields using cross-polarized clinical photography. • Superpixel-based detection system, using an end-to-end hybrid convolutional neural network classifier. • Convolutional neural network optimal configuration using support vector machines. Areas of cutaneous field cancerization (CFC) occur in sun-damaged skin and are prone to skin cancer development. Actinic keratosis (AK) is the pathognomonic lesion of CFC. Therefore, the reliable and non-invasive AK burden assessment is essential to assist clinicians in delivering patient-tailored therapeutic interventions and support the objective evaluation of emerging therapeutic modalities. Herein, we introduce a system for automated AK detection in CFC areas. For the differentiation of AK from healthy skin areas and co-localized benign growths (Seborrheic Keratosis/Lentigo Solaris; SK/LS), cross-polarized digital photographs of afflicted skin surfaces were taken, and a convolutional neural network (AKCNN) whose convolution part was optimally transferred from a pre-trained VGG16 was implemented. For the detection of multifocal AK in wide skin regions, superpixels were employed to generate region patches for the subsequent evaluation. AKCNN was implemented and evaluated in 19739, 43067, and 12,205 image patches of AK, SK/LS, and healthy skin, respectively, originating from 46 patients. AKCNN performance was assessed in two ways: (a) patch classification using the macro averaged F1 score and (b) AK burden evaluation in broad skin areas using an adapted region-based F1 (a F 1) score. Using raw clinical images, AKCNN exhibited a macro F1 of 0.78 at patch level and a region-based a F 1 of 0.81, with good tolerance against image scaling. The proposed system efficiently uses cross-polarized clinical photography to assess the AK burden within the CFC. [ABSTRACT FROM AUTHOR]

Introduction: Solar cheilosis (SC), a common precancer of the lower lip with a high potential to progress to invasive squamous cell carcinoma, presents with characteristic morphological vermillion-skin border alterations, like the border retraction.Aim: To determine robust macro-morphological descriptors of the vermillion border from non-standardized digital photographs and to exploit a probabilistic model for SC recognition in real clinical environments.Methods: Lip borders of 150 individuals (75 SC patients, 75 non-SC controls) were quantified on the basis of the extent of vermillion retraction and the degree of border irregularity employing fractal features and type-P Fourier descriptors. Eight lip border quantifiers were evaluated in terms of their reliability and reproducibility. The probabilistic 'diagnostic' model was implemented using the relevance vector machine (RVM) algorithm.Results: Picture acquisition contributes substantially to overall variability of lip border images; however, for the different lip descriptors 33% to 65% of border morphological variability is due to differences among individuals. Different camera operators or the use of cameras with different specifications did not affect significantly the extracted lip features. The proposed RVM probabilistic model yielded a high sensitivity and specificity of 94.6% and 96%, respectively.Conclusion: We explored the use of digital photography within the clinical routine setting to validate a probabilistic model for the assessment of lip conditions like SC. The proposed method opens new perspectives toward a cost effective, non-invasive monitoring of SC to support large scale epidemiological and interventional studies in different clinical environments. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Accurate lip contour identification is demanding since variations in color, form and surface texture, even in normal lips, introduce artifacts in non-adapted segmentation algorithms. Herein, a method for vermilion border detection and quantification in healthy and diseased lower lips is presented. Aim: To quantify the morphological irregularities of lower lip border, to validate its discriminative power in solar cheilosis diagnosis and to provide supportive tools toward, cost effective, non invasive, disease monitoring. Materials: Segmentation algorithm for lower lip border was based on spatial fuzzy c-means clustering algorithm with adaptive selection of fuzzy exponent m. Lip features measuring morphological lip border deviations were estimated. The method of lip border extraction and quantitative description was evaluated in a gold standard set of 25 young volunteers without onset of lip diseases. Quantitative descriptors were evaluated in terms of correct classification rates in differentiating 30 healthy control cases from 41 patients with solar cheilosis and were further applied to quantify the therapeutic outcome after immunocryosurgery in eight patients with solar cheilosis. Results: Adaptive estimation of fuzzy exponent m substantially boosted the segmentation quality in gold standard cases yielding quite smooth lip contours and uniformly low values of lip irregularity features. Discriminant analysis highlighted the distance between the extracted and modeled vermilion border as a feature with excellent diagnostic accuracy (sensitivity and specificity 98% and 93% respectively). Results on patients with solar cheilosis followed up after treatment with immunocryosurgery showed that proposed quantitative lip marker was able to trace the improvement of disease after treatment. Conclusion: Correct lip border recognition is the prerequisite for extracting essential morphological descriptors from lips with epithelial diseases like solar cheilosis. In this paper we presented an efficient method for the automatic identification and quantitative description of lower lip vermilion border morphology in health and disease using digital photography and image analysis techniques. [Copyright &y& Elsevier]

Abstract: Focal cortical dysplasias are among the most common causes of intractable epilepsy in children. As the neuropathology of these conditions has been better clarified, the nomenclature has undergone numerous revisions. Their recognition has grown with the use of neuroimaging, and recent advances in imaging technology will further improve detection. Clinical, electroencephalographic, and imaging findings are often diagnostic, so it is imperative for the clinician to recognize the characteristic patterns. Treatment for developmental and behavioral disability remains largely symptomatic, and epilepsy medications are often ineffective. Epilepsy surgery, however, can be successful in selected patients. The basic science underlying the development of focal cortical dysplasias may lead to novel therapeutic approaches in the future. [Copyright &y& Elsevier]

Abstract: The implication of the yeast genus Malassezia in skin diseases has been characterized by controversy, since the first description of the fungal nature of pityriasis versicolor in 1846 by Eichstedt. This is underscored by the existence of Malassezia yeasts as commensal but also by their implication in diseases with distinct absence of inflammation despite the heavy fungal load (pityriasis versicolor) or with characteristic inflammation (eg, seborrheic dermatitis, atopic dermatitis, folliculitis, or psoriasis). The description of 14 Malassezia species and subsequent worldwide epidemiologic studies did not reveal pathogenic species but rather disease—associated subtypes within species. Emerging evidence demonstrates that the interaction of Malassezia yeasts with the skin is multifaceted and entails constituents of the fungal wall (melanin, lipid cover), enzymes (lipases, phospholipases), and metabolic products (indoles), as well as the cellular components of the epidermis (keratinocytes, dendritic cells, and melanocytes). Understanding the complexity of their interactions will highlight the controversies on the clinical presentation of Malassezia-associated diseases and unravel the complexity of skin homeostatic mechanisms. [Copyright &y& Elsevier]

Abstract: Psoriasis is a genetically determined, almost worldwide-distributed inflammatory skin disease with overall higher prevalence among people of northern European ancestry. Since enhanced innate immunity is an important feature of the pathophysiology of this disease, it has been proposed that differences in the prevalence of psoriasis in different populations mainly result from differences in natural selection for gene polymorphisms associated with more vigorous immunity against infectious agents. However the infectious agent(s) that could have acted upon human population as selection pressure for psoriasis is still obscure. Based on the remarkable clinical observation that psoriasis and leprosy are almost mutually exclusive, a fact that is further supported by divergent HLA patterns in patients with psoriasis and leprosy we propose that “resisting leprosy” may have been the evolutionary advantage that favoured the expansion of some psoriasis-associated genotypes especially in the progenitors of modern Europeans. Moreover, we suggest that the spreading out of a certain genetic resistance trait may offer a supplementary explanation for the better understanding of the relatively rapid decline of leprosy in the late medieval epoch in Europe. Both genetic and paleoepidemiologic methods could be employed in order to challenge the present hypothesis. [Copyright &y& Elsevier]

Abstract: Malassezia yeasts are found on the skin of all humans and many warm-blooded animals. In vitro they have the ability to synthesize potent ligands (indolo[3,2-b]carbazole, malassezin and indirubin) of the aryl-hydrocarbon receptor (AhR; synonym: dioxin receptor) when the sweat contained l-tryptophan is used as the single nitrogen source. The production of these AhR-ligands has been associated with pathogenic strains of a certain Malassezia species (Malassezia furfur) but recent evidence shows that this property is widely distributed in almost all currently known Malassezia species. AhR is associated with carcinogenesis and the potential connection of these ubiquitous skin symbionts, and putative pathogens, with skin neoplasia should be evaluated mainly focusing on mechanisms related to the distinctive ability of the yeast to produce potent AhR ligands. Hypothesis: Synthesis of available pertinent data show a possible link between Malassezia produced AhR ligands and skin carcinogenesis, particularly of basal cell carcinoma (BCC). BCCs are almost exclusively observed in animal species colonized by Malassezia. In humans and animals there is overlapping in the skin regions colonized by this yeast and affected by BCC. The potent AhR ligands synthesized by pathogenic Malassezia strains could contribute to tumor promotion by: modification of the UV radiation carcinogenesis, alterations in the salvage/survival of initiated tumor cells, inhibition of cell senescence, interaction with vitamin D metabolism, promotion of immune tolerance and finally pro-carcinogenic modulation of cell cycle progression and apoptosis. [Copyright &y& Elsevier]

Abstract: We have studied the properties of the pixel updating coefficients in the 2D ordered subsets expectation maximization (OSEM) algorithm for iterative image reconstruction in positron emission tomography, in order to address the problem of image quality degradation—a known property of the technique after a number of iterations. The behavior of the updating coefficients has been extensively analyzed on synthetic coincidence data, using the necessary software tools. The experiments showed that the statistical properties of these coefficients can be correlated with the quality of the reconstructed images as a function of the activity distribution in the source and the number of subsets used. Considering the fact that these properties can be quantified during the reconstruction process of data from real scans where the activity distribution in the source is unknown the results of this study might be useful for the development of a stopping criterion for the OSEM algorithm. [ABSTRACT FROM AUTHOR]

Amyoplasia is the most common subtype of arthrogryposis multiplex congenita. Children exhibit congenital muscle aplasia or hypoplasia, resulting in symmetric limb contractures that occur in a characteristic pattern. A high incidence of midforehead capillary hemangiomas, micrognathia, and minor genital anomalies also occurs with this disorder. The etiology and specific site of injury in amyoplasia remain unclear. Previous muscle biopsy and electrophysiologic studies could not differentiate between neurogenic or myogenic causes. We describe five children with amyoplasia. Four children demonstrated electrophysiologic features consistent with motor neuronopathy. A careful segmental needle electromyography study revealed variable involvement at different myotomes. We hypothesize that the anterior horn cell may represent the site of disease in a subset of children with amyoplasia. [Copyright &y& Elsevier]

Abstract: An empirical stopping criterion for the 2D-maximum-likelihood expectation–maximization (MLEM) iterative image reconstruction algorithm in positron emission tomography (PET) has been proposed. We have applied the MLEM algorithm on Monte Carlo generated noise-free projection data and studied the properties of the pixel updating coefficients (PUC) in the reconstructed images. Appropriate fitting lead to an analytical expression for the parameterization of the minimum value in the PUC vector for all non-zero pixels for a given number of detected counts, which can be employed as basis for the stopping criterion proposed. These results have been validated with simulated data from real PET images. [Copyright &y& Elsevier]

Malassezia yeasts are connected with seborrheic dermatitis (SD) whereas M. furfur pathogenicity is associated with the production of bioactive indoles. In this study, the production of indoles by M. furfur isolates from healthy and diseased skin was compared, the respective HPLC patterns were analyzed, and substances that are preferentially synthesized by strains isolated from SD lesions were isolated and characterized. Malassezin, pityriacitrin, indole-3-carbaldehyde, and indolo[3,2-b]carbazole (ICZ) were isolated by HPLC from extracts of M. furfur grown in L-tryptophan agar, and identified by nuclear magnetic resonance and mass spectroscopy. Of these, ICZ, a potent ligand of the aryl hydrocarbon receptor (AhR), is described for the first time to our knowledge as a M. furfur metabolite. HPLC-photodiode array detection analysis of strain extracts from 7 healthy subjects and 10 SD patients showed that M. furfur isolates from only SD patients consistently produce malassezin and ICZ. This discriminatory production of AhR agonists provides initial evidence for a previously unreported mechanism triggering development of SD and indicates that the variable pathogenicity patterns recorded for M. furfur-associated SD conditions may be attributed to selective production (P<0.001) of measurable bioactive indoles.Journal of Investigative Dermatology (2008) 128, 1620–1625; doi:10.1038/sj.jid.5701252; published online 24 January 2008 [ABSTRACT FROM AUTHOR]

Background Context: In patients with osteoporosis, changes in spinal alignment after a vertebral compression fracture (VCF) are believed to increase the risk of fracture of the adjacent vertebrae. The alterations in spinal biomechanics as a result of osteoporotic VCF and the effects of deformity correction on the loads in the adjacent vertebral bodies are not fully understood. Purpose: To measure 1) the effect of thoracic VCFs on kyphosis (geometric alignment) and the shift of the physiologic compressive load path (loading alignment), 2) the effect of fracture reduction by balloon (bone tamp) inflation in restoring normal geometric and loading alignment and 3) the effect of spinal extension alone on fracture reduction and restoration of normal geometric and loading alignment. Study Design/setting: A biomechanical study using six fresh human thoracic specimens, each consisting of three adjacent vertebrae with all soft tissues and bony structures intact. Methods: In order to reliably create fracture, cancellous bone in the middle vertebral body was disrupted by inflation of bone tamps. After removal of the bone tamps, the specimen was compressed using bilateral loading cables until a fracture was observed with anterior vertebral body height loss of >/=25%. Fracture reduction was performed under a compressive preload of 250 N first under the application of extension moments, and then using inflatable bone tamps. The vertebral body heights, kyphotic deformity of the fractured vertebra and adjacent segments and location of compressive load (cable) path in the fractured and adjacent vertebral bodies were measured on video-fluoroscopic images. Results: The VCF caused anterior wall height loss of 37+/-15%, middle-height loss of 34+/-16%, segmental kyphosis increase of 14+/-7.0 degrees and vertebral kyphosis increase of 13+/-5.5 degrees (p<.05). The compressive load path shifted anteriorly by about 20% of anteroposterior end plate width in the fractured and adjacent vertebrae (p=.008). Bone tamp inflation restored the anterior wall height to 91+/-8.9%, middle-height to 91+/-14% and segmental kyphosis to within 5.6+/-5.9 degrees of prefracture values. The compressive load path returned posteriorly relative to the postfracture location in all three vertebrae (p=.004): the load path remained anterior to the prefracture location by about 9% to 11% of the anteroposterior end plate width. With application of extension moment (6.3+/-2.2 Nm) until segmental kyphosis and compressive load path were fully restored, anterior vertebral body heights were improved to 85+/-8.6% of prefracture values. However, the middle vertebral body height was not restored and vertebral kyphotic deformity remained significantly larger than the prefracture values (p<.05). Conclusions: The anterior shift of the compressive load path in vertebral bodies adjacent to VCF can induce additional flexion moments on these vertebrae. This eccentric loading may contribute to the increased risk of new fractures in osteoporotic vertebrae adjacent to an uncorrected VCF deformity. Bone tamp inflation under a physiologic preload significantly reduced the VCF deformity (anterior and middle vertebral body heights, segmental and vertebral kyphosis) and returned the compressive load path posteriorly, approaching the prefracture alignment. Application of extension moments also was effective in restoring the prefracture geometric and loading alignment of adjacent segments, but the middle height of the fractured vertebra and vertebral kyphotic deformity were not restored with spinal extension alone. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a multifactorial, pervasive neurodevelopmental disorder defined by the core symptoms of significant impairment in social interaction and communication as well as restricted, repetitive patterns of behavior. In addition to these core behaviors, persons with ASD frequently have associated noncore behavioral disturbance (ie, self-injury, aggression), as well as several medical comorbidities. Currently, no effective treatment exists for the core symptoms of ASD. This review reports the available preclinical and clinical data regarding the use of cannabis and cannabidiol in the treatment of core symptoms, noncore symptoms and comorbidities associated with ASD. Additionally, we describe our clinical experience working with children and young adults with ASD who have used cannabis or cannabidiol. At present, preclinical and clinical data suggest a potential for therapeutic benefit among some persons with ASD and that it is overall well tolerated. Further research is required to better identify patients who may benefit from treatment without adverse effects. [ABSTRACT FROM AUTHOR]

The mathematics of single photon emission computed tomography (SPECT) involve the inversion of a certain integral, namely the attenuated Radon transform. This integral is stored in the form of the so-called attenuated sinogram. By modifying the original formulation introduced by one of the authors in 2006, we have presented a slightly different formulation of the Inverse Attenuated Radon Transform (IART), which we refer to as attenuated Spline Reconstruction Technique (aSRT). The purpose of this study is to evaluate aSRT using simulated SPECT/CT phantoms and compare it with the industry standard, filtered backprojection (FBP). We have rederived the analytic formula of the IART, which involves the Hilbert transform of the attenuation correction coefficient as well as of two functions of the attenuated sinogram. For the numerical implementation of these Hilbert transforms we have employed an approximation of custom-made third degree piecewise polynomials, namely cubic splines. Relevant sinograms were generated in STIR (Software for Tomographic Imaging Reconstruction) and were acquired for 30, 60, 120, 180, and 360 projections over 360 degrees. Comparisons with FBP were evaluated using contrast and bias. Our numerical tests suggest that the new technique can efficiently produce accurate reconstructions for real phantoms. aSRT provides an alternative to FBP, which incorporates the attenuation correction within the algorithm itself. G.A. Kastis acknowledges the financial support of the "Alexander S. Onassis Public Benefit Foundation" under grant No. R ZL 001-0. Furthermore, this work was partially supported by the research program "Inverse Problems and Medical Imaging" (200/842) of the Research Committee of the Academy of Athens. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor demonstrating a polymerase chain reaction conformation polymorphism based system for detecting and screening of Malassezia sympodialis sequence coding. Focus on the Mal allergen involved in atopic dermatitis; Preparation of genomic DNA; Generation of the amplicon by only the M. sympodialis template DNA; Revelation of the lack of functional proteins due to the absence of PCR products.

Objective Demoralization, a state of lowered morale and poor coping, has a prevalence of 13–18% among patients with advanced cancer. We surveyed clinicians' perspectives of the utility of “with demoralization” as a diagnostic specifier for adjustment and depressive disorders. Method Using comparative clinical vignettes in a field survey, clinicians from a range of disciplines were asked their perception of the utility of diagnosis and treatment options. Response frequencies were compared using Cochran's Q and McNemar's tests, with sensitivity and specificity rated against expert rankings of diagnosis. Analysis of variance and paired t -tests examined significant differences in ratings of utility. Results Vignettes were assessed by 280 clinicians; 77% supported utility of the category ‘adjustment disorder with demoralization’ compared to 33% supporting ‘adjustment disorder with anxiety’ (McNemar test, p < 0.001), while 83% supported the utility of ‘with demoralization’ for major depressive episode, matching 83% perceiving utility for ‘with melancholia.’ Sensitivity and specificity ratings were 77% and 94% for adjustment disorder with demoralization and 83% and 91% for major depression with demoralization. Conclusion Clinicians perceived the specifier ‘with demoralization’ to deepen diagnostic understanding, treatment choice, and ability to communicate with clinicians and patients, particularly for the category of adjustment disorder with demoralization. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor related to an article, which was previously published in the December 2004 issue of the "Journal of Investigative Dermatology."

Objective This study was aimed at the development of a DNA-based procedure directly applicable to pathological skin scales and at the assessment of its value in rapid laboratory confirmation and identification of each of the seven Malassezia species. These lipophilic basidiomycetous yeasts in predisposed individuals are involved in pityriasis versicolor, seborrheic dermatitis, blepharitis, folliculitis, atopic dermatitis and fungemia. Standard identification procedures to species level are available, but so far no system for direct detection and characterization of Malassezia species in clinical specimens is available. Methods Malassezia DNA was extracted from pathological skin scales by a modified hexadecyltrimethylammonium bromide (CTAB) method and amplified by single and nested polymerase chain reaction (PCR), assays using the general fungal ITS 1/4 and 3/4 primers for amplification of sequences from the Malassezia major ribosomal DNA complex. Restriction fragment length polymorphism (RFLP) analysis of PCR products was used in subsequent species identification. DNA extracted from culture-positive skin scales was also tested by PCR and the RFLP patterns obtained were analyzed. Results A total of 36 isolates were tested. Distinct pure culture and skin-scale ITS 3/4 Hinf I and Alu I restriction patterns differentially identified M. furfur , M. globosa , M. restricta , M. sympodialis , M. pachydermatis , M. obtusa and M. slooffiae . Malassezia DNA was extracted from pathological skin scales and RFLP identified solitary and multiple Malassezia species in the same specimen. Molecular identification was confirmed by cultures and biochemical tests. Concurrent detection and identification of Candida and Yarrowia species was also feasible from skin scales. Conclusion The proposed method, described for the first time, could provide a sensitive and rapid detection and identification system for Malassezia species, which may be applied to epidemiological surveys and... [ABSTRACT FROM AUTHOR]

Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10- to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients' extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin- and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Lumbar fusion has been associated with inconsistent clinical outcomes and significant complications. Posterior dynamic devices have been developed to stabilize painful diseased lumbar motion segments while avoiding fusion. The Device for Intervertebral Assisted Motion (DIAM) is a silicone interspinous process “bumper” that is being clinically implanted for varied indications. Purpose: We analyzed the effects of the DIAM device on the biomechanical response of the lumbar spine in flexion-extension, lateral bending, and axial rotation after partial facetectomy and discectomy; the clinical situations in which its use might be considered. Study design/setting: A biomechanical study was performed using whole lumbar spine specimens (L1–sacrum). Surgical interventions were simulated at the L4–L5 level, and motions were measured at the operated and adjacent segments. Patient sample: Six fresh human lumbar spine specimens were used. Methods: The lumbar spines were subjected to moments in flexion-extension (±6 Nm), lateral bending (±5 Nm), and axial rotation (±4 Nm). The specimens were tested under the following conditions: 1) intact; 2) after unilateral hemifacetectomy at L4–L5; 3) #2 and discectomy; and 4) #3 with DIAM. The angular motion values at the operated and adjacent segments were analyzed using analysis of variance and multiple comparisons with Bonferroni correction. Results: Unilateral hemifacetectomy did not increase angular motion. Subsequent discectomy increased L4–L5 angular motion (degrees) from 9.2±1.6 to 11.7±2.0 in flexion-extension (p=.01), from 6.7±1.1 to 8.5±1.5 in lateral bending (p=.01), and from 2.6±0.7 to 3.8±0.8 in axial rotation (p=.00). Insertion of the DIAM device after discectomy restored the angular motion to below the level of the intact segment in flexion-extension (6.7±0.7 vs. 9.2±1.6, p=.02). In lateral bending, DIAM reduced the increased motion induced by discectomy (7.8±1.0 vs. 8.5±1.5, p<.05), but not to the intact level (7.8±1.0 vs. 6.7±1.1, p=.05). DIAM insertion did not reduce the increased axial rotation induced by discectomy, and the axial rotation remained larger than the intact value (4.1±0.6 vs. 2.6±0.7, p=.00). Conclusions: The DIAM device is effective in stabilizing the unstable segment, reducing the increased segmental flexion-extension and lateral bending motions observed after discectomy. In flexion-extension the DIAM restored postdiscectomy motion to below the intact values (p<.05). Interestingly, the DIAM device did not reduce the increased axial rotation motion observed after discectomy. These biomechanical effects must be considered when evaluating the clinical applications of the DIAM. [Copyright &y& Elsevier]

Abstract: The blood–brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood–brain barrier. Hypoxic–ischemic damage to the blood–brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood–brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood–brain barrier function in the fetus. Blood–brain barrier function was quantified with the blood-to-brain transfer constant (Ki ) and tight junction proteins by Western immunoblot in fetal sheep at 127days of gestation without ischemia, and 4, 24, or 48h after ischemia. The largest increase in Ki (P <0.05) was 4h after ischemia. Occludin and claudin-5 expressions decreased at 4h, but returned toward control levels 24 and 48h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood–brain barrier function after ischemia. We conclude that impaired blood–brain barrier function is an important component of hypoxic–ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki ) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4h after ischemia and blood–brain barrier function improves early after injury because the blood–brain barrier is less permeable 24 and 48 than 4h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood–brain barrier permeability after ischemia. [Copyright &y& Elsevier]

Netherton syndrome (NS) is a severe skin disease caused by loss-of-function mutations in SPINK5 (serine protease inhibitor Kazal-type 5) encoding the serine protease inhibitor LEKTI (lympho-epithelial Kazal type-related inhibitor). Here, we disclose new SPINK5 defects in 12 patients, who presented a clinical triad suggestive of NS with variations in inter- and intra-familial disease expression. We identified a new and frequent synonymous mutation c.891C>T (p.Cys297Cys) in exon 11 of the 12 NS patients. This mutation disrupts an exonic splicing enhancer sequence and causes out-of-frame skipping of exon 11. Haplotype analysis indicates that this mutation is a founder mutation in Greece. Two other new deep intronic mutations, c.283-12T>A in intron 4 and c.1820+53G>A in intron 19, induced partial intronic sequence retention. A new nonsense c.2557C>T (p.Arg853X) mutation was also identified. All mutations led to a premature termination codon resulting in no detectable LEKTI on skin sections. Two patients with deep intronic mutations showed residual LEKTI fragments in cultured keratinocytes. These fragments retained some functional activity, and could therefore, together with other determinants, contribute to modulate the disease phenotype. This new founder mutation, the most frequent mutation described in European populations so far, and these unusual intronic mutations, widen the clinical and molecular spectrum of NS and offer new diagnostic perspectives for NS patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Methods: Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Results: Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. Conclusions: The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis. [Copyright &y& Elsevier]

Abstract: Background context: Total disc replacement (TDR) has been recommended to reduce pain of presumed discogenic origin while preserving spinal motion. The floating core of Charité TDR is professed to allow the replication of the kinematics of a healthy disc under physiologic loads. While segmental motion after Charité TDR has been measured, little is known about the effects of a physiologic compressive preload on vertebral motion and the motion of prosthesis components after TDR. Purpose: (1) Does Charité TDR allow restoration of normal load-displacement behavior of a lumbar motion segment under physiologic loads? (2) How do the prosthesis components move relative to each other under physiologic loads when implanted in a lumbar motion segment? Study design: A biomechanical study using human lumbar spines (L1-sacrum). Methods: Five lumbar spines (age: 52±9.3) were used. Specimens were tested under flexion (8 Nm) and extension (6 Nm) moments with compressive follower preloads of 0 N and 400 N in the following sequence: (i) intact, (ii) Charité TDR at L5-S1, (iii) simulated healed fusion at L5-S1 with Charité TDR at L4-L5. Segmental motion was measured optoelectronically. Motions between prosthesis end plates and core were visually assessed using sequential digital video-fluoroscopy over the full range of motion. Here we report on kinematics of 10 Charité TDRs: 5 at L5-S1 and 5 at L4-L5. Results: Charité TDR increased the flexion-extension range of motion of lumbar segments (p<.05). At 400 N preload, the range of motion increased from intact values of 6.8±4.4 to 10.0±2.4 degrees at L5-S1 and from 7.0±2.6 to 10.8±2.9 degrees at L4-L5. Charité TDR increased segmental lordosis by 8.1±6.9 degrees at L5-S1 (p<.05) and 5.4±3.5 degrees at L4-L5 (p<.05). Four patterns of prosthesis component motion were noted: (1) angular motion only between the upper end plate and core, with little or no visual evidence of core translation (9 of 10 TDRs at 0 N preload and 5 of 10 TDRs at 400 N preload); (2) lift-off of upper prosthesis end plate from core or of core from lower end plate (observed in extension in 9 of 10 TDRs under 0 N preload only); (3) core entrapment, resulting in a locked core over a portion of the range of motion (observed in extension in 8 of 10 TDRs under 400 N preload); (4) angular motion between both the upper and lower end plates and core, with visual evidence of core translation (1 of 10 TDRs at 0 N preload, 5 of 10 TDRs at 400 N preload). The pattern of load-displacement curves was substantially changed under a physiologic preload in 8 of 10 TDRs; instead of a relatively gradual change in angle with changing moment application as seen for an intact segment, the TDR displayed regions of both relatively small and relatively large angular changes with gradual moment application. Conclusions: Charité TDR restored near normal quantity of flexion-extension range of motion under a constant physiologic preload; however, the quality of segmental motion differed from the intact case over the flexion-extension range. Whereas some TDRs showed visual evidence of core translation, the predominant angular motion within the prosthesis occurred between the upper end plate and the polyethylene core. Likely factors affecting the function of the Charité TDR include implant placement and orientation, intraoperative change in lordosis, and magnitude of physiologic compressive preload. Further work is needed to assess the effects of the prosthesis motion patterns identified in the study on the load sharing at the implanted level and polyethylene core wear. [Copyright &y& Elsevier]