Live Cell Imaging of Bone Marrow Stromal Cells on Nano-pitted and Polished Titanium Surfaces: A Micro-Incubator in vitro Approach

Current orthopedic implants are not conducive for optimal integration of the biomaterial with newly-formed tissue (osseointegration) inside a patient’s body. In this study, medical-rade Ti-6Al-4V was used as a substrate due to its biocompatibility and ability to facilitate cellular adhesion and proliferation. Live cell imaging was conducted on bone marrow stromal cells, genetically modified to express the green fluorescent protein (GFP), from the 24-96 hours growth period, with the first 24 hours of growth being held inside a lab-scale incubator. Periodic images were recorded on nanopitted anodized and polished Ti-6Al-4V substrates to study how substratestiffness influences adhesion and proliferation. Collected images were analyzed for mitosis, adhesion, and filopodia-stretchability using ImageJ, an image processing program. Images were enhanced in order to perform cell counts at 24, 48, 72, and 96 hours of growth. Continuous recordings were produced to account for the number of mitosis occurrences and cellular migration on each of the substrates. Based on the conducted experiments, it appears that polished Ti-6Al-4V has a higher cell adherence than “nanopitted” anodized surface and an improved rate of proliferation which may be because the cells once adhered on the nano-pitted surface have less ability to detach in-order to undergo mitosis.https://engagedscholarship.csuohio.edu/u_poster_2014/1004/thumbnail.jp

A Prospective Study of Etiology of Childhood Acute Bacterial Meningitis, Turkey

Vaccines to prevent bacterial meningitis in this region must provide reliable protection against serogroup W-135

Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo

IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Mutations in STAT3 and IL12RB1 impair the development of human IL-17 producing T cells

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Inborn Errors of Immunity and Coronovirus Pandemic

Inborn errors of immunity (IEI) are a heterogeneous group of diseases, typically characterized by recurrent ve severe infections, autoimmunity, autoinflammatory, allergic diseases and cancer. Since their immune response to pathogens are impaired, they have high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has spread more than 180 countries. It is reported that two groups of people were prone to life-threatening coronavirus disease 2019 (COVID-19): aged (>65 years of age) and people with comorbidities such as hypertension, cardiovascular diseases, chronic lung, renal and liver diseases, diabetes mellitus, obesity, including immunodeficiencies. The aim of this paper is to present information about the new coronavirus, modes of transmission, clinical findings, diagnostic procedures, treatment modalities of COVID-19 to the physicians who is caring patients with primary immunodeficiency. Patients with primary immunodeficiencies, must exclusively rely on hygiene and protective measures to combat SARS-CoV-2, since vaccines or effective antiviral treatments against COVID-19 are still not available

Clinical Manifestations and Diagnosis of Extrapulmonary Tuberculosis in Children

Objective:Tuberculosis (TB) is an important public health problem both in developing and developed countries due to migration with increasing incidence despite control strategies. Various clinical manifestations of extrapulmonary tuberculosis (EPTB) cause delay in diagnosis and treatment. In the present study, we aimed to evaluate the clinical and laboratory findings of extrapulmonary tuberculosis in childhood

Bladder Wall Telangiectasia in a Patient with Ataxia-Telangiectasia and How to Manage?

Ataxia-telangiectasia (A-T) is a rare neurodegenerative, inherited disease causing severe morbidity. Oculocutaneous telangiectasias are almost constant findings among the affected cases as telangiectasia is considered the main clinical finding for diagnosis. Vascular abnormalities in organs have been reported infrequently but bladder wall telangiectasias are extremely rare. We aimed to report recurrent hemorrhage from bladder wall telangiectasia in a 9-year-old boy with A-T who had received intravenous cyclophosphamide for non-Hodgkin's lymphoma. Since A-T patients are known to be more susceptible to chemical agents, we suggested that possibly cyclophosphamide was the drug which induced bladder wall injury in this patient