A copper chelate selectively triggers apoptosis in myeloid-derived suppressor cells in a drug-resistant tumor model and enhances antitumor immune response

Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of immunosuppressive network are present in the tumor microenvironment suppress antitumor immunity by subverting Th1 response in tumor site and considered as a great obstacle for advancement of different cancer immunotherapeutic protocols. Till date, various pharmacological approaches have been explored to modulate the suppressive functions of MDSCs in vivo. The present study describes our endeavor to explore a possibility of eradicating MDSCs by the application of a copper chelate, namely copper N-(2-hydroxy acetophenone) glycinate (CuNG), previously found to be a potential immunomodulator that can elicit antitumorogenic Th1 response in doxorubicin-resistant EAC (EAC/Dox) bearing mice. Herein, we demonstrated that CuNG treatment could reduce Gr-1+CD11b+ MDSC accumulation in ascitic fluid and spleen of EAC/Dox tumor model. Furthermore, we found that CuNG mediated reduction in MDSCs is associated with induction of Th1 response and reduction in Treg cells. Moreover, we observed that CuNG could deplete MDSCs by inducing Fas-FasL mediated apoptotic cell death where death receptor Fas expression is enhanced in MDSCs and FasL is provided by activated T cells. However, MDSC expansion from bone marrow cells and their differentiation was not affected by CuNG. Altogether, these findings suggest that the immunomodulatory property of CuNG is attributed to, at least in part, by its selective cytotoxic action on MDSCs. So, this preclinical study unveils a new mechanism of regulating MDSC levels in drug-resistant cancer model and holds promise of translating the findings into clinical settings.     

Influence of Zeolite Coating on the Corrosion Resistance of AZ91D Magnesium Alloy

The protective performance of zeolite coating on AZ91D magnesium alloy was evaluated using potentiodynamic polarisation and electrochemical impedance spectroscopy (EIS) in 0.1 M sodium chloride solution (NaCl). Electrical equivalent circuit (EEC) was developed based upon hypothetical corrosion mechanisms and simulated to correspond to the experimental data. The morphology and the chemical nature of the coating were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. Post corrosion morphologies of the zeolite coated and the uncoated AZ91D alloy were investigated using SEM. The corrosion resistance of the zeolite coated specimen was at least one order of magnitude higher than the uncoated specimen.     

Association of pulse pressure,pulse pressure index,and ambulatory arterial stiffness index with kidney function in a cross‐sectional pediatric chronic kidney disease cohort from the CKiD study

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end‐stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1‐16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non‐immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non‐immunological group. There were no significant differences with iohexol‐based glomerular filtration rate (iGFR), LVMI, PPi, or high‐sensitivity C‐reactive protein (hs‐CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non‐immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.     

Reduced hippocampal brain-derived neurotrophic factor (BDNF) in neonatal rats after prenatal exposure to propylthiouracil (PTU)

Thyroid hormone is critical for central nervous system development. Fetal hypothyroidism leads to reduced cognitive performance in offspring as well as other effects on neural development in both humans and experimental animals. The nature of these impairments suggests that thyroid hormone may exert its effects via dysregulation of the neurotrophin brain-derived neurotrophic factor (BDNF), which is critical to normal development of the central nervous system and has been implicated in neurodevelopmental disorders. The only evidence of BDNF dysregulation in early development, however, comes from experimental models in which severe prenatal hypothyroidism occurred. By contrast, milder prenatal hypothyroidism has been shown to alter BDNF levels and BDNF-dependent functions only much later in life. We hypothesized that mild experimental prenatal hypothyroidism might lead to dysregulation of BDNF in the early postnatal period. BDNF levels were measured by ELISA at 3 or 7 d after birth in different regions of the brains of rats exposed to propylthiouracil (PTU) in the drinking water. The dose of PTU that was used induced mild maternal thyroid hormone insufficiency. Pups, but not the parents, exhibited alterations in tissue BDNF levels. Hippocampal BDNF levels were reduced at both d 3 and 7, but no significant reductions were observed in either the cerebellum or brain stem. Unexpectedly, more males than females were born to PTU-treated dams, suggesting an effect of PTU on sex determination. These results support the hypothesis that reduced hippocampal BDNF levels during early development may contribute to the adverse neurodevelopmental effects of mild thyroid hormone insufficiency during pregnancy.     

Cytodiagnosis of cutaneous histoplasmosis in HIV positive patient initially presenting with multiple umbilicated disseminated skin nodules

Histoplasmosis is usually an opportunistic fungal infection in patients with defective cell mediated immunity, and has been considered as one of the acquired immunodeficiency syndrome (AIDS) defining illness. However, cutaneous involvement in human immunodeficiency virus (HIV) positive patients is less common, and very rarely can be the initial presenting symptom for the diagnosis of AIDS. We present here an unusual case of multiple diffuse cutaneous nodular lesions predominantly in face, trunk, and upper extremities diagnosed initially on aspiration cytology as histoplasmosis. Subsequent serological test revealed positivity for HIV 1 and 2, along with a low CD4 count and low CD4:CD3 ratio. The cytomorphological features were further corroborated by histology and histochemical stains. Hence, cutaneous histoplasmosis can cause multiple wide spread nodular or umbilicated lesions in AIDS patients as the initial presentation. Fine needle aspiration cytology (FNAC) is a rapid, cost effective tool for diagnosis of the fungi from such lesions and initiating work up for immunocompromised states including AIDS. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

What contributes to self‐rated oral health among community‐dwelling older adults? Findings from the ElderSmile program

Objectives: As part of ongoing efforts by the Columbia University College of Dental Medicine to devise community‐based models of health promotion and care for local residents, we sought to answer the following query: “What contributes to self‐rated oral health among community‐dwelling older adults?” Methods: The present study is cross sectional in design and centrally concerned with baseline data collected during community‐based screenings of adults aged 50 years and older who agreed to participate in the ElderSmile program in northern Manhattan, New York City. The primary outcome measure of interest is self‐rated oral health, which was assessed as follows: “Overall, how would you rate the health of your teeth and gums – excellent, good, fair, or poor?” Results: More than a quarter (28.5 percent) of ElderSmile participants aged 50 years and older reported that their oral health was poor. After adjustment for age (in years), place of birth, educational level, and dental insurance status in a logistic regression model, recent visits to the dentist (within the past year versus more than a year ago) contributed to better self‐rated oral health and non‐Hispanic Black race/ethnicity, dentate (versus edentulous) status, tooth decay as measured by decayed missing filled teeth, and severe periodontal inflammation contributed to worse self‐rated oral health in this population. Conclusions: Recent dental care contributed to better self‐rated oral health among community‐dwelling older adults living in northern Manhattan. Significant gradients were evident in the caries experience and periodontal inflammation of dentate adults by self‐rated oral health, suggesting that untreated oral disease contributes to poor self‐rated oral health.     

CT‐guided aspiration cytology of advanced silicosis and confirmation of the deposited zeolite nano particles through X ray diffraction: A novel approach

Silicosis is a common occupational lung disease, resulting in fibrotic nodular lesions in the upper lobes of the lung parenchyma. Most of the pneumoconioses are diagnosed on the basis of relevant history and clinico‐radiological correlation. Image‐guided aspiration cytology appears to be poorly yielding and is not usually considered as a diagnostic modality. However, silicosis may sometimes offer a diagnostic challenge because of its radiological resemblance and clinical overlap with pulmonary tuberculosis and neoplastic lesions. We present a unique situation where image‐guided fine needle aspiration cytology (FNAC) has been advised on the basis of nodular upper lobe opacities. The cytology smears revealed hypocellular granular material, while phase contrast and polarized light microscopy highlighted crystalline particles. History of silica dust exposure long back was available after the cytological evaluation, suggesting the diagnosis of pulmonary silicosis. X ray diffraction (XRD) crystallography was also possible on cytology smears, confirming zeolite nano particles of size as small as 40 ? 50 nm as the concerned agent for the first time. Cytological evaluation by phase contrast and polarized light microscopy may be useful for the confirmation of silicosis, supplemented by clinical history and radiological evaluation. XRD on smears may help in determination of chemical nature and particle size. Diagn. Cytopathol. 2016;44:246–249. © 2015 Wiley Periodicals, Inc.