Immunoactivating Peptide P4 Augments Alveolar Macrophage Phagocytosis in Two Diverse Human Populations

New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniaeex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells.     

The HMG-CoA reductase inhibitor simvastatin overcomes cell adhesion-mediated drug resistance in multiple myeloma by geranylgeranylation of Rho protein and activation of Rho kinase

Primary drug resistance is a major problem in multiple myeloma, an incurable disease of the bone marrow. Cell adhesion-mediated drug resistance (CAM-DR) causes strong primary resistance. By coculturing multiple myeloma cells with bone marrow stromal cells (BMSCs), we observed a CAM-DR of about 50% to melphalan, treosulfan, doxorubicin, dexamethasone, and bortezomib, which was not reversed by secreted soluble factors. Targeting the adhesion molecules lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) by monoclonal antibodies or by the LFA-1 inhibitor LFA703 reduced CAM-DR significantly. Only statins such as simvastatin and lovastatin, however, were able to completely restore chemosensitivity. All these effects were not mediated by deadhesion or reduced secretion of interleukin 6. Targeting geranylgeranyl transferase (GGTase) and Rho kinase by specific inhibitors (GGTI-298 and Y-27632), but not inhibition of farnesyl transferase (FTase) by FTI-277, showed similar reduction of CAM-DR. Addition of geranylgeranyl pyrophosphate (GG-PP), but not of farnesyl pyrophosphate (F-PP), was able to inhibit simvastatin-induced CAM-DR reversal. Our data suggest that the 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA)/GG-PP/Rho/Rho-kinase pathway mediates CAM-DR and that targeting this pathway may improve the efficacy of antimyeloma therapies by reduction of CAM-DR.     

Delayed diagnosis of tuberculous arthritis

Monoarticular tuberculosis (TB) affecting the knee is rare in all forms of TB (0.1-0.3%). We present the case of a patient with tuberculous arthritis in whom the diagnosis was belated due to a lack of familiarity with the disease; here, we emphasize the difficulties associated with the diagnosing joint TB. A 20-year-old man was referred to our department due to swelling of the right knee and the presence of persistent, mild pain for 4 years. The lack of systemic evidence of this disease, the indolent course of disease, and the presence of non-specific symptoms renders early recognition of this disease difficult. Furthermore, in cases in which a diagnosis cannot be reached simply by culturing the synovial fluid, synovial biopsy cultures should be considered in the diagnostic process, due to the high rate of positivity of such cultures. The diagnosis and treatment of articular TB are both urgent matters; surgical debridement and strict adherence to antituberculous chemotherapy tend to yield a satisfactory functional outcome.     

Reliability and Validity of the Turkish Version of the Abiloco-Kids

ABILOCO-Kids is a scale that assesses the walking ability of children with Cerebral Palsy (CP) from the viewpoint of parental perception. The aim of this study was to translate the ABILOCO-Kids scale into Turkish and to establish its reliability and validity in children with CP. Turkish children were recruited in this study. ABILOCO-Kids is a scale developed by Caty and et al. This scale assess the walking ability of children with CP focusing on the activity domain of the International Classification of Functioning, Disability and Health (ICF). The ABILOCO-Kids scale was translated from English into Turkish using the forward-backward-forward method. The motor functions of the 63 children participating in the study were evaluated by the Gross Motor Function Classification System (GMFCS) and the Gross Motor Function Measurement-88 (GMFM-88). The ABILOCO-Kids scale was repeated in 30 children after one week to establish test-retest reliability. While internal and external construct validity were investigated using Rasch analysis and Spearman correlation coefficient, respectively; reliability was evaluated in terms of internal consistency by Cronbach’s alpha and Person Separation Index (PSI). All items of the ABILOCO-Kids were found to fit the Rasch Model (chi-square 14.35 (df?=?20), p?=?0.813). The internal construct validity was good, overall mean item fit residual was ?0.109 (SD: 0.719) and mean person fit residual was ?0.215 (SD: 0.817). The reliability was good with Cronbach’s Alpha of 0.98 and PSI of 0.99. When the test-retest was examined via Differential Item Functioning (DIF) by time, none of the items showed DIF. Spearman correlation coefficients of the ABILOCO-Kids scale in relation to the GMFM and GMFCS were r?=?0.824, p?<?0.001; r?=??0.788, p?<?0.001 respectively. The Turkish version of the ABILOCO-Kids scale is a valid, reliable and unidimensional scale for children with CP. This scale will allow the differences in the locomotion of children with CP to be evaluated from the perspective of the family.     

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.     

Acromegaly is associated with a distinct oral and gut microbiota

Pituitary - Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. Oral and fecal...     

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging‑derived texture features

Purpose

Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas.

Methods

The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy.

Results

A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types.

Conclusions

Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.

     

Inhibition of inducible nitric oxide synthase reduces bacterial translocation in a rat model of acute pancreatitis

INTRODUCTION: Translocation of bacteria from the gut into pancreatic necrosis is an important factor in the development of septic complications and mortality in acute pancreatitis. S-methylisothiourea (SMT) is an inducible nitric oxide synthase inhibitor that has been shown to decrease bacteria] translocation in sepsis and thermal injury. AIM: To investigate whether SMT could affect bacterial translocation in acute necrotizing pancreatitis. METHODOLOGY: Forty-five Sprague-Dawley rats were studied. Acute pancreatitis was induced in Group I and Group II by injection of taurocholate and trypsin into the common biliopancreatic duct. Group III underwent laparotomy with the manipulation (but not cannulation) of the pancreas and received saline injection. Group I rats received normal saline as a placebo, and Group II rats received SMT after surgery for 2 days. At 48 hours, blood was drawn for serum amylase determinations. Bacterial translocation to mesenteric lymph nodes and distant sites (pancreas, liver, and peritoneum) were examined. A point scoring system of histologic features was used to evaluate the severity of pancreatitis. RESULTS: Plasma amylase levels and pancreatic histologic score were significantly reduced in Group II rats given SMT compared with those in Group I rats given saline (p < 0.01, p < 0.05, respectively). All Group I rats had bacterial translocation to mesenteric lymph nodes compared with 7 of 12 rats in Group II (p < 0.05). There was no difference in bacterial translocation to distant organs between the two groups, although rates tended to be lower in Group II compared with Group I (p > 0.05). Bacterial counts in the pancreas were significantly reduced in Group II rats compared with those in Group I rats (p < 0.05). CONCLUSION: Treatment with SMT appears to have ameliorated the course of acute pancreatitis; however, mortality was not affected.     

Is There a Role for On-Site Evaluation of Thyroid Fine Needle Aspiration to Reduce the Nondiagnostic Rate?

The use of immediate on-site evaluation of fine-needle aspiration biopsy (FNAB) specimens can determine the adequacy of specimens and provides a specific preliminary diagnosis. In this prospective study, we evaluated the impact of on-site assessment of thyroid FNAB performed under ultrasound guidance. Totally, 204 (170 female, 34 male) patients (102 on site, 102 control group) were included. The patients were randomized on site and regular cytologic examination groups. Quick May-Grünwald Giemsa stain was used for on-site examination and FNA was continued until adequate aspirate for optimal cytological examination. Two (2.0 %) of the 102 patients evaluated with on-site examination had a nondiagnostic result. However, 16 (15.7 %) of the 102 patients examined by regular cytologic examination method, had nondiagnostic result. The difference between these two groups was statistically significant (p?<?0.0001). The major cause of a nondiagnostic thyroid FNAB specimen is the failure to aspirate a sufficient number of cells necessary for diagnosis cystic lesions. Immediate on-site evaluation can significantly decrease the nondiagnostic rate of thyroid FNAB specimens.