Isolated collagenoma in an HIV-positive patient on ART: a case report.

BACKGROUND: Collagenomas are rare connective tissue hamartomas composed of dermal collagen. Patients infected with human immunodeficiency virus (HIV) can present with HIV-related lipodystrophy or lipomas. There are no known associations between HIV and collagenomas. CASE PRESENTATION: Here we describe a case of an isolated collagenoma in an HIV patient on ART. The lesion was a seven by four-centimeter subcutaneous nodule with no epidermal changes located on the occipital scalp. This lesion was excised, and histopathology showed thick and randomly arranged collagen bundles, consistent with a collagenoma. CONCLUSION: This case represents an isolated collagenoma presenting in a patient with HIV. It is unclear whether HIV or ART contributed to the development of this collagenoma. Treatment of collagenomas include surgical excision and intralesional corticosteroids. In addition to lipoma or lipodystrophy, it is important to keep collagenoma in the differential diagnosis in a patient presenting with an isolated large indurated subcutaneous nodule.

Whole Exome Sequencing Identifies PHF14 Mutations in Neurocytoma and Predicts Responsivity to the PDGFR Inhibitor Sunitinib.

Neurocytomas are rare low-grade brain tumors predominantly affecting young adults, but their cellular origin and molecular pathogenesis is largely unknown. We previously reported a sellar neurocytoma that secreted excess arginine vasopressin causing syndrome of inappropriate anti-diuretic hormone (SIADH). Whole exome sequencing in 21 neurocytoma tumor tissues identified somatic mutations in the plant homeodomain finger protein 14 (PHF14) in 3/21 (14%) tumors. Of these mutations, two were missense mutations and 4 caused splicing site losses, resulting in PHF14 dysfunction. Employing shRNA-mediated knockdown and CRISPR/Cas9-based knockout approaches, we demonstrated that loss of PHF14 increased proliferation and colony formation in five different human, mouse and rat mesenchymal and differentiated cell lines. Additionally, we demonstrated that PHF14 depletion resulted in upregulation of platelet derived growth factor receptor-alpha (PDGFRα) mRNA and protein in neuroblastoma SHSY-5Y cells and led to increased sensitivity to treatment with the PDGFR inhibitor Sunitinib. Furthermore, in a neurocytoma primary culture harboring splicing loss PHF14 mutations, overexpression of wild-type PHF14 and sunitinib treatment inhibited cell proliferation. Nude mice, inoculated with PHF14 knockout SHSY-5Y cells developed earlier and larger tumors than control cell-inoculated mice and Sunitinib administration caused greater tumor suppression in mice harboring PHF-14 knockout than control SHSY-5Y cells. Altogether our studies identified mutations of PHF14 in 14% of neurocytomas, demonstrate it can serve as an alternative pathway for certain cancerous behavior, and suggest a potential role for Sunitinib treatment in some patients with residual/recurrent neurocytoma.

Correction to: Water-pipe smoke condensate increases the internalization of Mycobacterium Bovis of type II alveolar epithelial cells (A549).

An amendment to this paper has been published and can be accessed via the original article.

Somatostatin Receptor Ligand Therapy-A Potential Therapy for Neurocytoma.

CONTEXT: Neurocytoma (NC) is a rare, low-grade tumor of the central nervous system, with a 10-year survival rate of 90% and local control rate of 74%. However, 25% of NCs will be atypical, with an elevated Ki-67 labeling index >2%, and will exhibit a more aggressive course, with a high propensity for local recurrence and/or craniospinal dissemination. Although no standard treatment regimen exists for these atypical cases, adjuvant stereotactic or conventional radiotherapy and/or chemotherapy have been typically offered but have yielded inconsistent results. CASE DESCRIPTION: We have described the case of a patient with a vasopressin-secreting atypical NC of the sellar and cavernous sinus region. After subtotal resection via endoscopic transsphenoidal surgery, the residual tumor showed increased fluorodeoxyglucose uptake and high somatostatin receptor (SSTR) expression on a 68Ga-DOTA-TATE positron emission tomography/CT scan. Somatostatin receptor ligand (SRL) therapy with lanreotide (120 mg every 28 days) was initiated. Four years later, the residual tumor was stable with decreased fluorodeoxyglucose tumor uptake. Immunocytochemical SSTR2 and SSTR5 expression >80% was further confirmed in a series of NC tissues. CONCLUSIONS: To the best of our knowledge, we have described the first use of SRL therapy for an atypical NC. Our results support consideration of adjuvant SRL therapy for NC refractory to surgical removal. Our findings further raise the possibility of SSTR-directed peptide receptor radionuclide therapy as NC therapy.

An Introduction to Starting a Biobank.

The purpose of a biobank is to process, organize, and maintain various types of biospecimens that are to be utilized for both clinical and research-based services. There are different types of biobanks, so the goals of the biobank should be delineated at the outset of forming a biobank. The startup of a biobank benefits from accreditation and stringent adherence to standards of practice. Fundamental to these practices is the protection of privacy and informed consent. A budget must be developed, and sources of funding should be obtained to properly equip the designated space and personnel. The appropriate space for freezers and for biospecimen processing should be identified. Information technology is also a critical part of the biobank and effort should be expended to ensure that this aspect is effective and secure. Given the ethical concerns surrounding biospecimens, engagement with the public is also highly valuable.

Domestic and International Shipping of Biospecimens.

The packaging and shipment of biospecimens is a multistep process for which a distinct set of regulations needs to be followed, depending on whether a biospecimen is shipped domestically or internationally and whether the shipment contains hazardous materials. Shipments may be delayed if these regulations are not followed. Once learned, the process is straightforward. Major principles include double or triple packaging, adequate absorbent material, appropriate coolant, accurate labeling, and complete documentation. Training in packaging and shipping is often offered at major biomedical institutions and is a requirement to avoid shipping biohazards.

Budesonide facilitates weaning from mechanical ventilation in difficult-to-wean very severe COPD patients: Association with inflammatory mediators and cells.

INTRODUCTION: Mechanical ventilatory support is life-saving therapy for patients with respiratory failure in intensive care units (ICU) but is linked to ventilator-associated pneumonia and other nosocomial infections. Interventions that improve the efficiency of weaning from mechanical ventilation may improve patient outcomes. OBJECTIVE: To determine whether inhaled budesonide decreases time-to-weaning in COPD stage 4 difficult-to-wean patients and reduces the release of pro-inflammatory cytokines in ICU patients. MATERIALS AND METHODS: We recruited 55 difficult-to-wean COPD patients (Stage 4) within the ICU of the Masih Daneshvari Hospital. Subjects were randomly assigned to receive inhaled budesonide (0.5mg/day) or placebo (normal saline). Dynamic compliance and BAL cytokines were measured. RESULTS: Budesonide significantly reduced the number of days on MV (days-to-weaning=4.6±1.6days) compared to that seen in the control group (7.2±2.7days, p=0.014). Dynamic compliance was significantly improved in the budesonide group on days 3 (p=0.018) and 5 (p=0.011) The levels of CXCL-8 and IL-6 diminished on days 3-5 after start of budesonide (p<0.05). CONCLUSION: In COPD patients on MV, nebulized budesonide was associated with reduced BAL CXCL8 and IL-6 levels and neutrophil numbers as well as an improvement in ventilatory mechanics and facilitated weaning.

An Overview of Tracheal Stenosis Research Trends and Hot Topics.

BACKGROUND: Tracheal stenosis remains a challenge in the thoracic surgery field. Recognizing the hot topics and major concepts in this area would help the health policy makers to determine their own priorities and design the effective research plans. The present study analyzed and mapped the topics and trends of tracheal stenosis studies over time as well as authors' and countries' contributions. MATERIALS AND METHODS: Search results were obtained employing Bibexcel. To determine cold and hot topics, co-occurrence analysis was applied using three international databases 'Web of Science', 'PubMed' and 'Scopus'. Appropriately, different categories in the articles such as keywords, authors, and countries were explored via VOSviewer and NetDraw. Afterward, the trends of research topics were depicted in four time-intervals from 1945 to 2015 by ten co-occurrence terms. RESULTS: The majority of articles were limited to case series and retrospective studies. The studies had been conducted less frequently on prevention, risk factors and incidence determination but extensively on treatment and procedures. Based on the articles indexed in WOS, 45 countries and 8,260 authors have contributed to scientific progress in this field. The highest degree of cooperation occurred between the USA and England with 15 common papers. CONCLUSIONS: Most of the published literature in tracheal stenosis research field was about surgical and non-surgical treatments. Conducting the screening and prevention studies would diminish the burden of this disease on the health system as well as the patients and their families' well-being.

Immunoglobulin Free Light Chains in the Pathogenesis of Lung Disorders.

Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin. These overexpressed FLCs are co-localized to areas of mast cell infiltration. Importantly, FLC expression is associated with basal-like cancers with an aggressive phenotype. Moreover, FLC is expressed in areas of inflammatory cell infiltration and its expression is significantly associated with poor clinical outcome. In addition, serum and bronchoalveolar fluid FLC concentrations are increased in patients with idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) compared to control subjects. In this review, we provide an update on the role of FLC in the pathogenesis of several lung disorders and indicate how this may contribute to new therapeutic opportunities.

Non-adherence to medication regimens among older African-American adults.

BACKGROUND: Despite concerns about racial differences on adherence to prescribed medication rigimens among older adults, current information about nonadherence among underserved elderly African Americans with co-morbidities is limited. This study examines the association between adherence to drug regimens and an array of medication-related factors, including polypharmacy, medication regimen complexity, use of Potentially Inappropriate Medications (PIM), and knowledge about the therapeutic purpose and instructions of medication use. METHODS: Four-hundred African Americans, aged 65 years and older, were recruited from South Los Angeles. Structured, face-to-face interviews and visual inspection of participants' medications were conducted. From the medication container labels, information including strength of the drug, expiration date, instructions, and special warnings were recorded. The Medication Regimen Complexity Index (MRCI) was measured to quantify multiple features of drug regimen complexity. The Beers Criteria was used to measure the PIM use. RESULTS: Participants reported taking an average of 5.7 prescription drugs. Over 56% could not identify the purpose of at least one of their medications. Only two-thirds knew dosage regimen of their medications. Thirty-five percent of participants indicated that they purposely had skipped taking at least one of their medications within last three days. Only 8% of participants admitted that they forgot to take their medications. The results of multivariate analysis showed that co-payment for drugs, memory deficits, MRCI, and medication-related knowledge were all associated with adherence to dosage regimen of medications. Participants with a higher level of knowledge about therapeutic purpose and knowledge about dosage regimen of their medications were seven times (CI: 4.2-10.8) more likely to adhere to frequency and dose of medications. Participants with a low complexity index were two times (CI: 1.1-3.9) more likely to adhere to the dosage regimen of their medications, compared with participants with high drug regimen complexity index. CONCLUSIONS: While other studies have documented that non-adherence remains an important issue among older adults, our study shows that for underserved elderly African Americans, these issues are particularly striking. A periodic comprehensive assessment of all medications that they use remains a critical initial step to identify medication related issues. Assessment of their disease and medication related knowledge (e.g., therapeutic purposes, side-effects, special instructions, etc.) and their ability to follow complicated medication regimens and modification of their drug regimens requires inter-professional collaboration.

Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats.

BACKGROUND: Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. METHODS: As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. RESULTS: A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. CONCLUSIONS: In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to exhaustively independently validate a commercial genomic profiling assay, examination of a few markers provides some reassurance of its robustness. While potential targeted drugs are recommended based on genetic alterations, to date most targeted therapies have failed in glioblasomas so the usefulness of such recommendations will increase with development of novel and efficacious drugs.

Polypharmacy among Underserved Older African American Adults.

The purpose of the present study was to examine correlates of polypharmacy among underserved community-dwelling older African American adults. Methods. This study recruited 400 underserved older African Americans adults living in South Los Angeles. The structured face-to-face interviews collected data on participants' characteristics and elicited data pertaining to the type, frequency, dosage, and indications of all medications used by participants. Results. Seventy-five and thirty percent of participants take at least five and ten medications per day, respectively. Thirty-eight percent of participants received prescription medications from at least three providers. Inappropriate drug use occurred among seventy percent of the participants. Multivariate analysis showed that number of providers was the strongest correlate of polypharmacy. Moreover, data show that gender, comorbidity, and potentially inappropriate medication use are other major correlates of polypharmacy. Conclusions. This study shows a high rate of polypharmacy and potentially inappropriate medication use among underserved older African American adults. We documented strong associations between polypharmacy and use of potentially inappropriate medications, comorbidities, and having multiple providers. Polypharmacy and potentially inappropriate medications may be attributed to poor coordination and management of medications among providers and pharmacists. There is an urgent need to develop innovative and effective strategies to reduce inappropriate polypharmacy and potentially inappropriate medication in underserved elderly minority populations.

Bovis Bacillus Calmette-Guerin (BCG) infection induces exosomal miRNA release by human macrophages.

BACKGROUND: Tuberculosis (TB) remains a significant global health concern and its diagnosis is challenging due to the limitations in the specificity and sensitivity of the current diagnostic tests. Exosomes are bioactive 30-100 nm vesicles produced by most cell types and are found in almost all human body fluids. Exosomal microRNAs (miRNAs) can transfer biological information between cells and tissues and may act as potential biomarkers in many diseases. In this pilot study, we assessed the miRNA profile of exosomes released from human monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). METHODS: Human monocytes were obtained from the peripheral blood of three healthy subjects and driven to a monocyte-derived macrophage (MDM) phenotype using standard protocols. MDMs were infected with BCG or left uninfected as control. 72 h post-infection, exosomes were collected from the cell culture medium, RNA was isolated and RNA-seq performed. The raw reads were filtered to eliminate adaptor and primer sequences and the sequences were run against the mature human miRNA sequences available in miRBase. MicroRNAs were identified using an E value <0.01. miRNA network analysis was performed using the DIANA miRNA tool, miRDB and functional KEGG pathway analysis. RESULTS: Infection of MDMs with BCG leads to the release of several exosomal miRNAs. These included miR-1224, -1293, -425, -4467, -4732, -484, -5094, -6848-6849, -4488 and -96 all of which were predicted to target metabolism and energy production-related pathways. CONCLUSIONS: This study provides evidence for the release of specific exosomal miRNAs from BCG-infected MDMs. These exosomal miRNAs reflect host-pathogen interaction and subversion of host metabolic processes following infection.

Water-pipe smoke condensate increases the internalization of Mycobacterium Bovis of type II alveolar epithelial cells (A549).

BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection. Here, we studied the effects of water-pipe condense (WPC) on the internalization of Mycobacterium Bovis BCG by macropinocytosis in the alveolar epithelial cell line A549. METHODS: A549 cells were exposed to WPC (4 mg/ml) for 24, 48, 72 and 96 h. Cell viability was studied using the methyl thiazolyldipenyl-tetrazolium bromide (MTT) reduction assay and proliferation by bromodeoxyUridine (BrdU) incorporation. Cells were exposed to FITC-Dextran (1 mg/ml) (as a control) and FITC-BCG (MOI = 10) for 20 min at 37 °C before cells were collected and the uptake of BCG-FITC determined by flow cytometry. Similar experiments were performed at 4 °C as a control. The Rho-associated protein kinase (ROCK) inhibitor Y-27632 (1 µM) was used to assess the mechanism by which WPC enhanced BCG uptake. RESULTS: WPC (4 mg/ml) increased the uptake of BCG-FITC after 72 (1.3 ± 0.1 fold, p < 0.05) and 96 (1.4 ± 0.05 fold, p < 0.05) hours. No effect on BCG-FITC uptake was observed at 24 or 48 h. WPC also significantly increased the uptake of FITC-Dextran (2.9 ± 0.3 fold, p < 0.05) after 24 h. WPC significantly decreased cell viability after 24 (84 ± 2%, p < 0.05), 48 (78±, 3%, p < 0.05), 72 (64 ± 2%, p < 0.05) and 96 h (45 ± 2%, p < 0.05). Y-27632 completely attenuated the increased uptake of BCG by WPC. Cell proliferation showed a decreasing trend in a time-dependent manner with WPC exposure. CONCLUSION: WPC exposure increased epithelial cell endocytosis activity and death as well as enhancing their capacity for macropinocytosis. Our in vitro data indicates possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacterium.

Incidence, survival, pathology, and genetics of adult Latino Americans with glioblastoma.

Latino Americans are a rapidly growing ethnic group in the United States but studies of glioblastoma in this population are limited. We have evaluated characteristics of 21,184 glioblastoma patients from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. This SEER data from 2001 to 2011 draws from 28% of the U.S. POPULATION: Latinos have a lower incidence of GBM and present slightly younger than non-Latino Whites. Cubans present at an older age than other Latino sub-populations. Latinos have a higher incidence of giant cell glioblastoma than non-Latino Whites while the incidence of gliosarcoma is similar. Despite lower rates of radiation therapy and greater rates of sub-total resection than non-Latino Whites, Latinos have better 1 and 5 year survival rates. SEER does not record chemotherapy data. Survivals of Latino sub-populations are similar with each other. Age, extent of resection, and the use of radiation therapy are associated with improved survival but none of these variables are sufficient in a multivariate analysis to explain the improved survival of Latinos relative to non-Latino Whites. As molecular data is not available in SEER records, we studied the MGMT and IDH status of 571 patients from a UCLA database. MGMT methylation and IDH1 mutation rates are not statistically significantly different between non-Latino Whites and Latinos. For UCLA patients with available information, chemotherapy and radiation rates are similar for non-Latino White and Latino patients, but the latter have lower rates of gross total resection and present at a younger age.

The role of pattern recognition receptors in lung sarcoidosis.

Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs). Due to the similar clinical and histopathological picture of sarcoidosis and tuberculosis, Mycobacterium tuberculosis antigens such early secreted antigen (ESAT-6), heat shock proteins (Mtb-HSP), catalase-peroxidase (katG) enzyme and superoxide dismutase A peptide (sodA) have been often considered as factors in the etiopathogenesis of sarcoidosis. Potential non-TB-associated PAMPs include lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria, peptidoglycan, lipoteichoic acid, bacterial DNA, viral DNA/RNA, chitin, flagellin, leucine-rich repeats (LRR), mannans in the yeast cell wall, and microbial HSPs. Furthermore, exogenous non-organic antigens such as metals, silica, pigments with/without aluminum in tattoos, pesticides, and pollen have been evoked as potential causes of sarcoidosis. Exposure of the airways to diverse infectious and non-infectious agents may be important in the pathogenesis of sarcoidosis. The current review provides and update on the role of PPRs and DAMPs in the pathogenesis of sarcoidsis.

Pattern recognitions receptors in immunodeficiency disorders.

Pattern recognition receptors (PRRs) recognize common microbial or host-derived macromolecules and have important roles in early activation and response of the immune system. Initiation of the innate immune response starts with the recognition of microbial structures called pathogen associated molecular patterns (PAMPs). Recognition of PAMPs is performed by germline-encoded receptors expressed mainly on immune cells termed pattern recognition receptors (PRRs). Several classes of pattern recognition receptors (PRRs) are involved in the pathogenesis of diseases, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins in the human immune system. Defects in interleukin-1 receptor-associated kinase-4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor-κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are associated with susceptibility to herpes simplex virus type 1 encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell defects enhance defective responses of B cells to shared TLR agonists. Altered TLR responses to TLR2 and 4 agonists are seen in chronic granulomatous disease (CGD) and X-linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome (HIES), and for most TLRs in adenosine deaminase deficiency. In this review we provide the reader with an update on the role of TLRs and downstream signaling pathways in PID disorders.

The frequency and importance of chest pain in midterm follow up of transcatheter closure of interatrial septal defect.

Introduction: We evaluated chest pain alongside other midterm subjective and objective complications of the transcatheter closure of atrial septal defects (ASDs) and patent foramen ovales (PFOs) with various closure devices. Methods: This cross-sectional study, performed from March 2010 to October 2015 in Rajaie Cardiovascular, Medical, and Research Center, evaluated 313 patients (mean age = 29.12 ± 10 years, 32.9% male) for probable complications associated with the transcatheter occlusion of secundum ASDs (n = 289, mean age = 30.5 ± 11.4 years, 28% male) or PFOs (n = 24, mean age = 42.8 ± 10.2 years). ASD closure was performed under sedation and transesophageal echocardiography (TEE) guidance. Duration of follow-up was 12 ± 3 months (mean follow-up = 11.52 months). Results: Among the subjective complications, chest pain was the most frequent complaint during the follow-up period and although it was common (7.3%), a clear cardiac etiology was rare. Thirteen (4.2%) patients reported palpitation during the follow-up period, and 4 had documented arrhythmias-including atrial flutter, atrial fibrillation, and 2:1 atrioventricular block. Migraine with or without aura occurred in 1.6% of the patients. Objective complications comprising tamponade, device embolization, and thrombus formation occurred in 6 (1.9%) patients. There was no procedure-related mortality in our patients. Conclusion: Transcatheter closure of PFOs and secundum-type ASDs in our adult patients using ASD septal occluders was associated with a high degree of success, minimal procedural subjective and objective complication rates, and excellent short- and midterm results. Although chest pain was common after the first month following ASD closure, there was no cardiac death or aortic erosion in 11.52 months follow up.

Critical role of Toll-like receptors in pathophysiology of allergic asthma.

Allergic asthma is an airway disease, characterized by reversible bronchoconstriction, chronic inflammation of the airway, and thickness of smooth muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2-adaptive immune response, in which innate immunity plays a key role. Recently TLRs have received more and more attention as they are central to orchestrate the innate immune responses. TLRs are localized as integral membrane or intracellular glycoproteins with those on the cell surface sensing microbial antigens and the ones, localized in intracellular vesicles, sensing microbial nucleic acid species. Having recognized microbial antigens, TLRs conduct the immune response towards a pro- or anti-allergy response. As a double-edged sword, they could initiate either harmful or helpful responses by the immune system in case of allergic asthma. In the current review, we will describe the role of TLRs and their signaling pathways in allergic asthma.

Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.

BACKGROUND: While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. METHODS: We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study. RESULTS: Inflammation related signaling pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures. Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8, and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men. In addition, several genes relevant to brain function (KMO, DDIT4, VEGFA, IGF1R, IGF2R, and FGD4) showed differential activation between sexes. Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms. CONCLUSIONS: These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.