Safety and efficacy of superior calyceal access versus inferior calyceal access for pelvic and/or lower calyceal renal calculi- a prospective observational comparative study.

OBJECTIVE: To compare efficacy and safety between superior calyceal access and inferior calyceal access for pelvic and/or lower calyceal renal stones. METHODS: Consecutive patients presenting with Pelvic and/or inferior calyceal renal calculi were allocated to the superior calyceal access (group 1) or inferior calyceal access (group 2) treatment arm. Allocation of treatment access was based on the surgeon's preference. Variables studied included stone free rate, operating time, intraoperative and postoperative complications. Statistical analysis was executed using SPSS, Version 16.0. The statistical significance was evaluated at 5% level of significance (p value < 0.05). RESULTS: Between July 2018 and February 2019, 63 patients were included in each group. The percutaneous inserted guidewire entered the ureter in 92% in group1 and 74.6% in group 2 (p = 0.034). Stone fragments migrated to the middle calyx in 3.2% in group1 and 9.5% in group 2 (p = 0.033). A second puncture was required in one patient in group 1 and in 5 patients in group 2 (p = 0.04). The operative duration (minutes) was 13.46 ± 1.09 in the group 1 while 16.58 ± 1.44 in the group 2 (p = 0.002). Thoracic complications (hydropneumothorax) occurred to 2 patients in superior calyceal access group managed with intercostal tube drainage (p = 0.243).Post operatively blood transfusion was required in two patients in group 2 (p = 0.169). Angioembolization was done in one patient among the inferior calyceal access approach (p = 0.683). Complete stone clearance assessed at 3 months was 96.8% in group 1 and 85.7% in group 2 (p = 0.046). CONCLUSIONS: Superior calyceal access is a safe and most efficacious in terms of achieving complete stone clearance rate with reduced operative time, minimal blood loss, less need for a second puncture and auxiliary procedures at minimal complications. STUDY REGISTRATION: Clinical trials registry - INDIA; CTRI/2018/07/014,687.

Chiral Phase Transition Temperature in (2+1)-Flavor QCD.

We present a lattice-QCD-based determination of the chiral phase transition temperature in QCD with two degenerate, massless quarks and a physical strange quark mass using lattice QCD calculations with the highly improved staggered quarks action. We propose and calculate two novel estimators for the chiral transition temperature for several values of the light quark masses, corresponding to Goldstone pion masses in the range of 58 MeV≲m_{π}≲163 MeV. The chiral phase transition temperature is determined by extrapolating to vanishing pion mass using universal scaling analysis. Finite-volume effects are controlled by extrapolating to the thermodynamic limit using spatial lattice extents in the range of 2.8-4.5 times the inverse of the pion mass. Continuum extrapolations are carried out by using three different values of the lattice cutoff, corresponding to lattices with temporal extents N_{τ}=6, 8, and 12. After thermodynamic, continuum, and chiral extrapolations, we find the chiral phase transition temperature T_{c}^{0}=132_{-6}^{+3} MeV.

Additional strange hadrons from QCD thermodynamics and strangeness freezeout in heavy ion collisions.

We compare lattice QCD results for appropriate combinations of net strangeness fluctuations and their correlations with net baryon number fluctuations with predictions from two hadron resonance gas (HRG) models having different strange hadron content. The conventionally used HRG model based on experimentally established strange hadrons fails to describe the lattice QCD results in the hadronic phase close to the QCD crossover. Supplementing the conventional HRG with additional, experimentally uncharted strange hadrons predicted by quark model calculations and observed in lattice QCD spectrum calculations leads to good descriptions of strange hadron thermodynamics below the QCD crossover. We show that the thermodynamic presence of these additional states gets imprinted in the yields of the ground-state strange hadrons leading to a systematic 5-8 MeV decrease of the chemical freeze-out temperatures of ground-state strange baryons.

Strangeness at high temperatures: from hadrons to quarks.

Appropriate combinations of up to fourth order cumulants of net strangeness fluctuations and their correlations with net baryon number and electric charge fluctuations, obtained from lattice QCD calculations, have been used to probe the strangeness carrying degrees of freedom at high temperatures. For temperatures up to the chiral crossover, separate contributions of strange mesons and baryons can be well described by an uncorrelated gas of hadrons. Such a description breaks down in the chiral crossover region, suggesting that the deconfinement of strangeness takes place at the chiral crossover. On the other hand, the strangeness carrying degrees of freedom inside the quark gluon plasma can be described by a weakly interacting gas of quarks only for temperatures larger than twice the chiral crossover temperature. In the intermediate temperature window, these observables show considerably richer structures, indicative of the strongly interacting nature of the quark gluon plasma.

Intraoperative evaluation of the resected bone margin in mandibular cancers using a trephine drill and frozen section analysis.

The objective of this study was to evaluate the accuracy and feasibility of intraoperative frozen section analysis of samples harvested with a trephine drill from the bone resection margins to identify malignancy. Thirty-five patients who were diagnosed with locally advanced oral squamous cell carcinoma involving the mandible were included in this study. After tumour resection, bone samples were collected from the resection margin of the specimen using a trephine drill. Sampling yielded a cylindrical specimen of bony tissue that included both cortical and cancellous areas. A second sample was obtained from the area where bone invasion was evident; this was used as a positive control. Frozen section analysis was performed intraoperatively to check for malignancy. The sensitivity of this technique was found to be 81.8%, with specificity of 87.5%, a positive predictive value of 75%, negative predictive value of 91.3%, and accuracy of 85.7% when compared to standard histopathology as the gold standard. In conclusion, the evaluation of bone margins using the trephine drill technique and frozen section analysis proved to be fast and reliable.

Freeze-out conditions in heavy ion collisions from QCD thermodynamics.

We present a determination of freeze-out conditions in heavy ion collisions based on ratios of cumulants of net electric charge fluctuations. These ratios can reliably be calculated in lattice QCD for a wide range of chemical potential values by using a next-to-leading order Taylor series expansion around the limit of vanishing baryon, electric charge and strangeness chemical potentials. From a computation of up to fourth order cumulants and charge correlations we first determine the strangeness and electric charge chemical potentials that characterize freeze-out conditions in a heavy ion collision and confirm that in the temperature range 150 MeV ≤ T ≤ 170 MeV the hadron resonance gas model provides good approximations for these parameters that agree with QCD calculations on the 5%-15% level. We then show that a comparison of lattice QCD results for ratios of up to third order cumulants of electric charge fluctuations with experimental results allows us to extract the freeze-out baryon chemical potential and the freeze-out temperature.

Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy.

Intravenous immunoglobulin (IVIG) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors. For more than 20 years, IVIG has been used in the treatment of a wide range of primary and secondary immunodeficiencies. IVIG now represents a standard therapeutic option for most antibody deficiencies. Routinely, IVIG is used in patients with X-linked agammaglobulinaemia (XLA), common variable immunodeficiency (CVID), X-linked hyper-IgM, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and selective IgG class deficiency. In addition, IVIG is used extensively in the treatment of a wide variety of autoimmune disorders. IVIG is administered at distinct doses in the two clinical settings: whereas immunodeficient patients are treated with replacement levels of IVIG, patients with autoimmune and inflammatory diseases are administered with very high doses of IVIG. Several lines of experimental evidence gathered in the recent years suggest that the therapeutic beneficial effect of IVIG in immunodeficiencies reflects an active role for IVIG, rather than a mere passive transfer of antibodies.

Neoadjuvant denosumab: its role and results in operable cases of giant cell tumour of bone.

AIMS: The aims of this study were to evaluate the efficacy of preoperative denosumab in achieving prospectively decided intention of therapy in operable giant cell tumour of bone (GCTB) patients, and to document local recurrence-free survival (LRFS). PATIENTS AND METHODS: A total of 44 patients received preoperative denosumab: 22 to facilitate curettage, 16 to facilitate resection, and six with intent of converting resection to curettage. There were 26 male and 18 female patients. The mean age was 27 years (13 to 47). RESULTS: The mean number of denosumab treatments was five (2 to 7) per patient. In 42 of 44 patients (95%), denosumab helped to achieve prospectively decided intention. A total of 41 patients were available for follow-up at a mean follow-up of 34 months (24 to 48). There were 12 local recurrences (29%), in 11 patients (11/25, 44%) who had curettage and in one patient (1/16, 6%) who had resection. The mean time to local recurrence was 16 months (8 to 25). The LRFS was 76% at two years: 94% for cases with resection and 64% for cases with curettage (p = 0.013). CONCLUSION: Although local control rates are unlikely to improve with use of preoperative denosumab, a short preoperative course of denosumab can facilitate surgery in certain cases of operable GCTB, with a high risk of local recurrence making curettage or resection technically easier. It may also help in converting a lesion requiring resection to a lesion that could possibly be treated with curettage.

Stress-induced changes in sleep and associated neuronal activity in rat hippocampus and amygdala.

Stress increases vulnerability to anxiety and depression. We have investigated the effect of acute immobilization stress in amygdalohippocampal circuits by measuring the electroencephalogram (EEG) in male Wistar rats during rapid eye movement (REM) sleep. Electrodes were implanted stereotaxically in the hippocampus (CA1 and CA3 subregions of the hippocampus) and the amygdala (lateral nucleus). Prior to the stress, two baseline recordings were taken. Twenty-four hours later rats were exposed once to acute immobilization stress (AIS) session for 2 h. After the release and on subsequent days, electrophysiological changes that occurred due to stress during REM sleep were analyzed by comparing them with baseline measurements. Our results suggest that acute immobilization stress induced significant increase in REM sleep in the first 24 h after the exposure. In addition to changes in the sleep patterns, we have observed increased theta oscillations in CA1 area of the hippocampus with decreased coherence at theta range (4-8 Hz) between hippocampus and amygdala. These results suggest that single exposure to aversive experience such as immobilization stress can lead to dynamic changes in neuronal activities with altered sleep morphology. The results obtained in the present study are comparable to those seen in human patients suffering from panic, and anxiety due to posttraumatic stress disorder (PTSD).

Transcriptomic analysis of hepatocellular carcinoma reveals molecular features of disease progression and tumor immune biology.

Hepatocellular carcinoma (HCC) develops in the context of chronic inflammatory liver disease and has an extremely poor prognosis. An immunosuppressive tumor microenvironment may contribute to therapeutic failure in metastatic HCC. Here, we identified unique molecular signatures pertaining to HCC disease progression and tumor immunity by analyzing genome-wide RNA-Seq data derived from HCC patient tumors and non-tumor cirrhotic tissues. Unsupervised clustering of gene expression data revealed a gradual suppression of local tumor immunity that coincided with disease progression, indicating an increasingly immunosuppressive tumor environment during HCC disease advancement. IHC examination of the spatial distribution of CD8+ T cells in tumors revealed distinct intra- and peri-tumoral subsets. Differential gene expression analysis revealed an 85-gene signature that was significantly upregulated in the peri-tumoral CD8+ T cell-excluded tumors. Notably, this signature was highly enriched with components of underlying extracellular matrix, fibrosis, and epithelial-mesenchymal transition (EMT). Further analysis condensed this signature to a core set of 23 genes that are associated with CD8+ T cell localization, and were prospectively validated in an independent cohort of HCC specimens. These findings suggest a potential association between elevated fibrosis, possibly modulated by TGF-ß, PDGFR, SHH or Notch pathway, and the T cell-excluded immune phenotype. Indeed, targeting fibrosis using a TGF-ß neutralizing antibody in the STAM™ model of murine HCC, we found that ameliorating the fibrotic environment could facilitate redistribution of CD8+ lymphocytes into tumors. Our results provide a strong rationale for utilizing immunotherapies in HCC earlier during treatment, potentially in combination with anti-fibrotic therapies.

Obstetric interventions and maternal morbidity among women who experience severe postpartum hemorrhage during cesarean delivery.

BACKGROUND: Compared to vaginal delivery, women undergoing cesarean delivery are at increased risk of postpartum hemorrhage. Management approaches may differ between those undergoing prelabor cesarean delivery compared to intrapartum cesarean delivery. We examined surgical interventions, blood component use, and maternal outcomes among those experiencing severe postpartum hemorrhage within the two distinct cesarean delivery cohorts. METHODS: We performed secondary analyses of data from two cohorts who underwent prelabor cesarean delivery or intrapartum cesarean delivery at a tertiary obstetric center in the United States between 2002 and 2012. Severe postpartum hemorrhage was classified as an estimated blood loss ≥1500mL or receipt of a red blood cell transfusion up to 48h post-cesarean delivery. We examined blood component use, medical and surgical interventions and maternal outcomes. RESULTS: The prelabor cohort comprised 269 women and the intrapartum cohort comprised 278 women. In the prelabor cohort, one third of women received red blood cells intraoperatively or postoperatively, respectively. In the intrapartum cohort, 18% women received red blood cells intraoperatively vs. 44% postoperatively (P<0.001). In the prelabor and intrapartum cohorts, methylergonovine was the most common second-line uterotonic (33% and 43%, respectively). Women undergoing prelabor cesarean delivery had the highest rates of morbidity, with 18% requiring hysterectomy and 16% requiring intensive care admission. CONCLUSION: Our findings provide a snapshot of contemporary transfusion and surgical practices for severe postpartum hemorrhage management during cesarean delivery. To determine optimal transfusion and management practices in this setting, large pragmatic studies are needed.

Iron addiction: a novel therapeutic target in ovarian cancer.

Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependence on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). We show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.

Inhibition of estrone sulfatase and proliferation of human breast cancer cells by nonsteroidal (p-O-sulfamoyl)-N-alkanoyl tyramines.

Estrogen levels in breast tumors of postmenopausal women are as much as 10 times higher than estrogen levels in plasma, presumably due to in situ formation of estrogen. The major source of estrogen in breast cancer cells may be the conversion of estrone sulfate to estrone by the enzyme estrone sulfatase. Thus, inhibitors of estrone sulfatase have potential for the treatment of estrogen-dependent breast cancers. Several steroidal agents have been developed that are potent estrone sulfatase inhibitors, most notably estrone-3-O-sulfamate. However, these compounds may be metabolized to forms that have undesired actions, including estrogenicity. To avoid the problems associated with a potentially active steroid nucleus, we designed and synthesized a series of (p-O-sulfamoyl)-N-alkanoyl tyramines as nonsteroidal estrone sulfatase inhibitors. These nine compounds differ in the length of their alkanoyl chains. We tested the ability of the (p-O-sulfamoyl)-N-alkanoyl tyramines to inhibit: (a) estrone sulfatase activity in intact cultures of human breast cancer cells (MDA-MB-231); and (b) the growth of estrogen-dependent human breast cancer cells (MCF-7). All of the test compounds (1 microM) inhibited the estrone sulfatase activity of intact MDA-MB-231 cells; however, compounds with a longer alkanoyl chain were more effective than those with a shorter chain. Dose-response analysis indicated an IC50 of 350 nM for (p-O-sulfamoyl)-N-tetradecanoyl tyramine for the inhibition of MDA-MB-231 estrone sulfatase activity. The inhibition of MDA-MB-231 cell estrone sulfatase activity by this compound was found to be irreversible. Cell proliferation assays involved the treatment of estrogen-deprived MCF-7 cells with test compounds (10 microM) in the presence of estrone sulfate (1 microM) as the only source of estrogen. All compounds inhibited cell proliferation to some extent, but the longer-chain analogues again were more effective. Dose-response analysis indicated an IC50 of 38 nM for (p-O-sulfamoyl)-N-tetradecanoyl tyramine for the inhibition of MCF-7 cell proliferation. Our data indicate the utility of (p-O-sulfamoyl)-N-alkanoyl tyramines for the inhibition of breast cancer cell estrone sulfatase activity. Furthermore, our data support the concept that nonsteroidal estrone sulfatase inhibitors may be useful as therapeutic agents for estrogen-dependent breast cancers.

Identification of tumor markers in models of human colorectal cancer using a 19,200-element complementary DNA microarray.

Metastasis represents a crucial transition in disease development and progression and has a profound impact on survival for a wide variety of cancers. Cell line models of metastasis have played an important role in developing our understanding of the metastatic process. We used a 19,200-element human cDNA microarray to profile transcription in three paired cell-line models of colorectal tumor metastasis. By correlating expression patterns across these cell lines, we have identified 176 genes that appear to be differentially expressed (greater than 2-fold) in all highly metastatic cell lines relative to their reference. An analysis of these genes reiterates much of our understanding of the metastatic process and suggests additional genes, many of previously uncharacterized function, that may be causatively involved in, or at least prognostic of, metastasis. Northern analysis of a limited number of these genes validates the observed pattern of expression and suggests that further investigation and functional characterization of the identified genes is warranted.

Microbial contamination of "in use" bar soap in dental clinics.

Bar soap from 18 different dental clinics were investigated for microbial contamination, while it was "in-use". Of the 32 samples obtained from the bar soap, 100% yielded positive culture. A total of 8 different genera of organisms were isolated. Each bar soap was found to harbor 2-5 different genera of micro organisms. Heavily used soap had more micro organisms compared to less used soap. The microbial load of the "in-use" bar soap constituted a mixed flora of gram positive, gram negative, aerobes, anaerobes, and fungi. The results indicate that the bar soap under "in-use" condition is a reservoir of microorganisms and handwashing with such a soap may lead to spread of infection.

Simulations to Predict Clinical Trial Outcome of Bevacizumab Plus Chemotherapy vs. Chemotherapy Alone in Patients With First-Line Gastric Cancer and Elevated Plasma VEGF-A.

To simulate clinical trials to assess overall survival (OS) benefit of bevacizumab in combination with chemotherapy in selected patients with gastric cancer (GC), a modeling framework linking OS with tumor growth inhibition (TGI) metrics and baseline patient characteristics was developed. Various TGI metrics were estimated using TGI models and data from two phase III studies comparing bevacizumab plus chemotherapy vs. chemotherapy as first-line therapy in 976 GC patients. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, Eastern Cooperative Oncology Group (ECOG) score, albumin level, and Asian ethnicity were significant covariates in the final OS model. The model correctly predicted a decreased hazard ratio favorable to bevacizumab in patients with high baseline plasma VEGF-A above the median of 113.4 ng/L. Based on trial simulations, in trials enrolling patients with elevated baseline plasma VEGF-A (500 patients per arm), the expected hazard ratio was 0.82 (95% prediction interval: 0.70-0.95), independent of ethnicity.

Influence of non-thermal TiCl4/Ar+O2 plasma-assisted TiOx based coatings on the surface of polypropylene (PP) films for the tailoring of surface properties and cytocompatibility.

The superior bulk properties (corrosion resistance, high strength to weight ratio, relatively low cost and easy processing) of hydrocarbon based polymers such as polypropylene (PP) have contributed significantly to the development of new biomedical applications such as artificial organs and cell scaffolds. However, low cell affinity is one of the main draw backs for PP due to its poor surface properties. In tissue engineering, physico-chemical surface properties such as hydrophilicity, polar functional groups, surface charge and morphology play a crucial role to enrich the cell proliferation and adhesion. In this present investigation TiOx based biocompatible coatings were developed on the surface of PP films via DC excited glow discharge plasma, using TiCl4/Ar+O2 gas mixture as a precursor. Various TiOx-based coatings are deposited on the surface of PP films as a function of discharge power. The changes in hydrophilicity of the TiOx/PP film surfaces were studied using contact angle analysis and surface energy calculations by Fowke's approximation. X-ray photo-electron spectroscopy (XPS) was used to investigate the surface chemical composition of TiOx/PP films. The surface morphology of the obtained TiOx/PP films was investigated by scanning electron and transmission electron microscopy (SEM &TEM). Moreover, the surface topography of the material was analyzed by atomic force microscopy (AFM). The cytocompatibility of the TiOx/PP films was investigated via in vitro analysis (cell viability, adhesion and cytotoxicity) using NIH3T3 (mouse embryonic fibroblast) cells. Furthermore the antibacterial activities of TiOx/PP films were also evaluated against two distinct bacterial models namely Gram positive Staphylococcus aureus (S.aureus) and Gram negative Escherichia coli DH5α. (E.coli) bacteria. XPS results clearly indicate the successful incorporation of TiOx and oxygen containing polar functional groups on the surface of plasma treated PP films. Moreover the surface of modified PP films exhibited nano structured morphology, as confirmed by SEM, TEM and AFM. The physico-chemical changes have improved the hydrophilicity of the PP films. The in-vitro analysis clearly confirms that the TiOx coated PP films performs as good as the standard tissue culture plates and also are unlikely to impact the bacterial cell viability.

A concise guide to cDNA microarray analysis.

Microarray expression analysis has become one of the most widely used functional genomics tools. Efficient application of this technique requires the development of robust and reproducible protocols. We have optimized all aspects of the process, including PCR amplification of target cDNA clones, microarray printing, probe labeling and hybridization, and have developed strategies for data normalization and analysis.