Miracle-dz/UniFAR-FTUs huggingface dataset:
Utility of flow cytometry studies in the management of patients with multiple myeloma

Purpose of review Although the input of multiparameter flow cytometry (MFC) into the clinical management of multiple myeloma patients has faced some reluctance, continuously growing evidence supports the utility of MFC in this disease. Recent findings MFC immunophenotyping of bone marrow and peripheral blood plasma cells affords cost-effective assessment of clonality, and provides prognostic information on the risk of progression in smoldering multiple myeloma, and the identification of active multiple myeloma patients with dismal outcome (e.g., high numbers of circulating tumor cells) or long-term survival despite suboptimal responses through the characterization of monoclonal gammopathy of undetermined significance-like phenotypes. Extensive data indicate that minimal residual disease (MRD) monitoring can be used as biomarker to evaluate treatment efficacy and act as surrogate for survival. The time has come to address within clinical trials the exact role of baseline risk factors and MRD monitoring for tailored therapy in multiple myeloma, which implies systematic usage of highly sensitive cost-effective, readily available, and standardized MRD techniques such as MFC. Summary Next-generation MFC should be considered mandatory in the routine evaluation of multiple myeloma patients both at diagnosis and after therapy, and represents an attractive technique to integrate with high-throughput DNA and RNA-seq methods to help in understanding the mechanisms behind dissemination and chemoresistance of multiple myeloma.
Malignant Ectomesenchymoma: Genetic Profile Reflects Rhabdomyosarcomatous Differentiation

Malignant ectomesenchymoma (MEM) represents a heterogeneous group of tumors, most likely originating from pluripotent primitive neural crest cells. In this report, we present an 8-month-old infant boy with an MEM on the left scrotum. Retrospective review of the incision biopsy showed the presence of a few ganglion cells in an otherwise classic embryonal rhabdomyosarcoma (RMS), whereas in the resection specimen after chemotherapy the combined RMS and ganglioneuroma components were very obvious. Cytogenetic analysis of the residual lesion showed an abnormal karyotype, 49, XY, +2, –6, +11, +20, +mar, with a hyperploidy in a subset of cells. By fluorescence in situ hybridization analysis, the marker chromosome was identified as originating from chromosome 6, and the tumor cells were negative for PAX3/PAX7 disrupting translocations specific for alveolar RMS. Gains of chromosomes 2, 11, and 20, found in the current case, are a common finding in embryonal RMS. These gains probably reflect the myogenic differentiation of MEM and support the genetic link between these 2 neoplasms. In addition to the conventional cytogenetics, array comparative genomic hybridization analysis was performed on the primary and residual tumors. The genomic profiles of both specimens were basically the same including the presence of 2 distinctive chromosome 6p21.32-p21.2 and 6p11.2 amplification regions in the primary tumor, which vanished in the postchemotherapy specimen. The pretreatment biopsy exhibited strong expression of HMGA1 and HMGA2 proteins in immunohistochemistry, with the shift toward the loss of expression of both genes in the posttreatment tumoral tissue. This finding supports the oncogenic properties of the HMGA family of proteins and their role in the process of malignant transformation.
Oral-based controlled release formulations using poly(acrylic acid) microgels

Aim: To investigate the release of hydrophobic and hydrophilic substances from tablets containing Pemulen and Carbopol as excipients. Method: The dissolution patterns of a hydrophobic (diazepam) and a hydrophilic active substance (midodrine-HCl) from different tablet formulations containing a nonmodified polyacrylic microgel (Carbopol 981 F) or a hydrophobically modified polyacrylic microgel (Pemulen®) have been studied. Possible differences in dissolution in phosphate buffer (pH 6.8) and in 0.1 M HCl between tablets produced using wet granulation and direct compression were also investigated. Results: Tablets produced by wet granulation had a greater effect on the release of active substance from the tablets. No major differences were observed in the release patterns of the hydrophilic substance midodrine-HCl from wet granulated tablets based on Carbopol and Pemulen. However, the release pattern of the more hydrophobic drug substance, diazepam, differed considerably between the two polymers. Wet granulation gave reproducible release patterns. The release patterns from the polymers differed considerably at pH 6.8 but were similar at low pH. Conclusions: The release of the diazepam from the hydrophobic polymer Pemulen was very slow, and the release was close to zero order.
Polymerization shrinkage and depth of cure of bulk fill flowable composite resins.

OBJECTIVE To evaluate polymerization shrinkage and depth of cure of two bulk fill flowable composites, one nanohybrid composite modified to a flowable consistency, and one standard flowable composite, comparing the scraping method to the Knoop hardness test. METHODS Two bulk fill flowable composites, SureFil SDR flow (SSF) (Dentsply) and Venus Bulk Fill (VBF) (Heraeus Kulzer), one standard flowable, Filtek Supreme Ultra Flowable (FSUF) (3M/ESPE) (control), and one regular bulk composite that can be made flowable, SonicFill (SF) (Kerr), were used in this study. For polymerization shrinkage (PS), ten 2-mm samples were made for each composite and cured for 20 seconds and shrinkage was measured with a Kaman linometer. For hardness, ten specimens of each composite were made in a 10 × 10-mm mold and cured for 20 seconds; the bottom surface was scraped according to ISO 4049 specification, and the remaining thickness was measured with a micrometer. Hardness samples were prepared at 2-, 3-, 4-, and 5-mm thick ×14-mm diameter, cured for 20 seconds, and polished. After 24 hours of dry storage, a Knoop indenter was applied at 100 g load for 11 seconds. Three readings were made on the top and bottom of each specimen and averaged for each surface to calculate a Knoop hardness value and a bottom/top hardness ratio. One-way analysis of variance and Tukey tests were used to determine significant differences between thicknesses and between test methods for each material. RESULTS PS values were 3.43 ± 0.51%, 3.57 ± 0.63%, 4.4 ± 0.79%, and 1.76 ± 0.53% for FSUF, SSF, VBF, and SF, respectively. VBF showed significantly greater shrinkage (4.4 ± 0.79%), followed by FSUF (3.43 ± 0.51%) and SSF (3.57 ± 0.63%), which were similar, and SF (1.76 ± 0.53%), which had significantly less shrinkage (p<0.05). Values for the scraping method for depth of cure were significantly greater for SSF and VBF (>5.0 mm), followed by SF (3.46 ± 0.16 mm) and FSU (2.98 ± 0.22 mm). Knoop top hardness values (KHN) were: VBF 21.55 ± 2.39, FSUF 44.62 ± 1.93, SSF 29.17 ± 0.76, and SF 72.56 ± 2.4 at 2 mm and were not significantly different at 3-, 4-, and 5-mm thick within each material. Ratios for bottom/top values (depth of cure) for 2, 3, 4, and 5 mm were: VBF 0.80 ± 0.1, 0.78 ± 0.03, 0.67 ± 0.10, and 0.59 ± 0.07, respectively; SSF 0.74 ± 0.08, 0.72 ± 0.08, 0.69 ± 0.18, and 0.62 ± 0.08, respectively; SF 0.82 ± 0.05, 0.68 ± 0.05, 0.47 ± 0.04, and 0.21 ± 0.02, respectively; and FSUF 0.56 ± 0.08 at 2 mm and 0.40 ± 0.08 at 3 mm. The bottom/top ratio was . 80 or less at all depths and decreased below 0.70 at 4-mm depth for VBF and SSF, at 3 mm for SF and at 2 mm for FSUF.
Bioaccessibility, bioavailability, and anti-inflammatory effects of anthocyanins from purple root vegetables using mono- and co-culture cell models.

SCOPE Immune-inflammatory signaling and metabolic effects are the main pillars for bioactivity of anthocyanins derived from highly pigmented root vegetables. This study aims to assess the bioaccessibility and bioavailability of purple carrot and potato derived anthocyanins and the molecular mechanisms of their ability to ameliorate cellular inflammation in a mono- and co-culture cell models. METHODS AND RESULTS An in vitro gastrointestinal model was used and demonstrated bioaccessibility of 44.62 and 71.8% for anthocyanins of purple carrot and potato, respectively. These accessible anthocyanins significantly inhibited cellular inflammation in Caco-2 cells. Intact cyanidinglycoside or petunidinglycoside (respectively from carrots and potatoes) were transported across a transmembrane cell model and detected by LC-MS/MS. Computational docking and glucose uptake analyses suggested uptake of anthocyanins was mediated by hexose transporters. Subsequent experiment using an inflamed Caco-2 BBe1/THP-1 co-culture cell model showed these transported anthocyanins inhibited IL-8 and TNF-α secretion,and expression of pro-inflammatory cytokines by blocking NF-κB, and MAPK mediated inflammatory cellular signaling cascades, but with varying degrees due to structural features. CONCLUSION Anthocyanins from purple carrots and potatoes possess a promising anti-inflammatory effect in model gut system. They can be absorbed and act differently but are in general beneficial for inflammation-mediated diseases.
Manipulation of host angioneogenesis

Despite progress over the last decade, opportunistic mold infections continue to be associated with high rates of morbidity and mortality in immunocompromised patients. Given the propensity of molds to invade blood vessels, vasculopathy may be a barrier to effective delivery of antifungal drugs to infected tissue. In a recent study (Ben-Ami R et al. Blood, 2009), we found that A. fumigatus suppresses endothelial cell migration, differentiation and capillary tube formation both in vitro and in an animal model system. This effect is mediated by secreted secondary metabolites such as gliotoxin. Herein, I discuss the potential implications of how invasive molds modulate host angiogenesis in experimental and clinical mold infections. Strategies that employ reversal of vasculopathy, neutralization of metabolites that inhibit endothelial function, exploration of pro-angiogenic factors as diagnostic or prognostic markers affected patients will likely be the focus of future studies. This complex, yet emerging field might add another level of knowledge and therapeutic choices in the management of these devastated infections.
Effects of Timely Antibiotic Administration and Culture Acquisition on the Treatment of Urinary Tact Infection

The purpose of this study was to assess the timeliness of initial antibiotic administration and culture acquisition for Medicare patients discharged with a principal diagnosis of urinary tract infection. The main outcome measurement was reduced length of stay. Data were collected retrospectively from 24,389 randomly selected discharged Medicare patients from September 1, 1994, to August 31,1995. Only 61% of the cases as urinary tract infection had adequate criteria to confirm the diagnosis. Of these cases, antibiotics were administered within 4 hr after presentation in 40.9% patients. Urine cultures within 24 hr of presentation were noted more frequently (94%) than blood cultures (66%). Urine cultures obtained before antibiotic administration were noted more frequently (82%) than were blood cultures (58%). Timely antibiotic administration and the acquisition of urine cultures in the first 24 hr of hospitalization were independently associated with shorter length of stay
Immunologic assessment of regional lymph node histology in relation to survival in head and neck carcinoma

Histologic material from 84 cases of squamous cell carcinoma of head and neck regions was studied by double blind retrospective analysis. Sections of lymph nodes draining the tumors were examined microscopically to assess the morphologic pattern of response. Patients whose lymph nodes demonstrated active immunologic responses in the form of expanded inner cortices or increased numbers of germinal centers had 5‐year survival rates significantly greater than those patients whose regional lymph nodes showed an unstimulated pattern. None of the patients whose lymph nodes showed the depleted pattern survived 5 years. These correlations were independent of the stage or grade of the tumor. Metastases occurred much more frequently in patients having regional nodes showing an unstimulated or depleted pattern than in those whose regional nodes showed evidence of immunologic activity. The data support the concept of a relationship between immunologic activity, progression of neoplasia, and survival. Morphologic assessment of immunologic activity in lymph nodes draining malignant tumors appears to be of significant value in predicting survival.
Management of lower urinary tract infection in women by Slovene GPs.

BACKGROUND Uncomplicated lower urinary tract infection (LUTI) is one of the most common infections treated in general practice. Although nationwide treatment guidelines for LUTI are increasingly available, most European countries, including Slovenia, have not yet set such guidelines. OBJECTIVES Our aim was to describe Slovene GPs' management of uncomplicated LUTIs and to analyse doctor and surgery characteristics that influence this management. METHOD A written case vignette accompanied by open-ended questions regarding doctors' decisions (i.e. investigations and laboratory tests ordered, treatment options, advising sick leave, advice for treatment and follow-up procedures) and questions about doctor and surgery characteristics was sent to a representative sample of Slovene GPs. RESULTS The response rate was 129/171 (75.4%). There were large variations in management of LUTI: 17.8% of GPs ordered various additional laboratory tests; 57% of GPs prescribed trimethoprim/sulfamethoxazole and 37% norfloxacin; 30% of GPs prescribed a drug for 10-14 days; and 53.5% of GPs put the patient on sick leave of 1-10 days duration. Doctors with heavier workloads and those who have to wait for laboratory results for >24 h ordered more additional investigations. CONCLUSIONS Effective strategies for quality improvement are needed, together with practice guidelines. The influence of a heavier workload on management of LUTI and the impact of the accessibility of laboratory tests should be explored in future research.
INTERLEUKIN-22 MODULATES GUT EPITHELIAL AND IMMUNE BARRIER FUNCTIONS FOLLOWING ACUTE ALCOHOL EXPOSURE AND BURN INJURY

ABSTRACT Interleukin-22 (IL-22) maintains gut epithelial integrity and expression of antimicrobial peptides Reg3&bgr; and Reg3&ggr;. Our laboratory has shown that acute alcohol/ethanol (EtOH) exposure before burn injury results in increased gut permeability, intestinal T-cell suppression, and enhanced bacterial translocation. Herein, we determined the effect of combined EtOH intoxication and burn injury on intestinal levels of IL-22 as well as Reg3&bgr; and Reg3&ggr; expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3&bgr; and Reg3&ggr; levels, and bacterial load (e.g., gut bacterial growth) within the intestine after EtOH and burn injury. Male mice, ∼25g, were gavaged with EtOH (2.9 mg/kg) before receiving a ∼12.5% total-body-surface-area, full-thickness burn. Mice were immediately treated with saline control or IL-22 (1 mg/kg) by i.p. injection. One day after injury, there was a significant decrease in intestinal IL-22, Reg3&bgr;, and Reg3&ggr; expression along with an increase in intestinal permeability and gut bacterial load after EtOH combined with burn injury, as compared with sham injury. Treatment with IL-22 normalized Reg3&bgr; and Reg3&ggr; expression and attenuated the increase in intestinal permeability after EtOH and burn injury. Qualitatively, IL-22 treatment reduced the bacterial load in nearly half of mice receiving EtOH combined with burn injury. Our data indicate that IL-22 maintains gut epithelial and immune barrier integrity after EtOH and burn injury; thus, the IL-22/antimicrobial peptide pathway may provide a therapeutic target for the treatment of patients who sustain burn injury under the influence of EtOH.
Influence of Carbohydrate Ingestion on Oxidative Stress and Plasma Antioxidant Potential Following a 3 h Run

Concentrations of reactive oxygen species (ROS) increase during exercise secondary to increased oxygen uptake, xanthine oxidase activity, and immune system activation. Carbohydrate compared to placebo beverage ingestion is associated with an attenuated cortisol and catecholamine response. Catecholamines can undergo autooxidation to form ROS. We hypothesized that during intense exercise, ingestion of carbohydrate compared to placebo would diminish oxidative stress. Sixteen experienced marathoners ran on treadmills for 3 h at ∼70% VO2max on two occasions while receiving carbohydrate or placebo beverages (1 l/h, double-blinded) in a randomized, counterbalanced order. Blood samples were collected before and immediately after exercise, snap frozen in liquid nitrogen, and stored at -80°C until analysis. Plasma samples were analyzed for F2-isoprostanes (FIP) and lipid hydroperoxides (ROOH) as measures for lipid peroxidation, ferric reducing ability of plasma (FRAP) as a measure of plasma antioxidant potential and for cortisol. The pattern of change in cortisol was significantly different between carbohydrate and placebo conditions (P=0.024), with post-exercise levels higher in the placebo condition. Under both carbohydrate and placebo conditions, significant increases in FIP, ROOH, and FRAP were measured, but the pattern of increase was not different (FIP, interaction effect, P=0.472; ROOH, P=0.572; FRAP, P=0.668). Despite an attenuation in the cortisol response, carbohydrate compared to placebo ingestion does not counter the increase in oxidative stress or modulate plasma antioxidant potential in athletes running 3 h at 70% VO2max.
Labour Market Effects of Currency Appreciation: The Case of Switzerland

Recent work on labour market effects of globalization has generated both academic and populist interests. However, this work has focussed exclusively on the manufacturing sector. Moreover, general equilibrium effects of globalization have received little attention. This study contributes to filling both these gaps by examining the general equilibrium effects of external exposure on the labor market in Switzerland. We exploit exogenous exchange rate movements to identify trade-induced shocks across all sectors of the Swiss economy and transpose industry-level exposure to the municipal level, using detailed employment data on the entirety of Swiss firms. We find strong evidence for three channels of employment effects of currency appreciation - negative employment growth induced by increasing export uncompetitiveness and higher import competition, and positive employment growth induced by cheaper availability of foreign inputs. The combined average effect of the three channels on employment is found to be negative in our preferred results, with significant heterogeneity across municipalities.
Which type of conduit to choose for right ventricular outflow tract reconstruction in patients below 1 year of age?†.

OBJECTIVES Reconstruction of the right ventricular outflow tract (RVOT) with a conduit in patients below 1 year of age remains a matter of concern due to limited availability and durability of conduits. We sought to analyse the freedom from conduit exchange in this subgroup of patients by comparing different conduits. METHODS Data of 145 consecutive patients below 1 year of age, requiring a conduit for RVOT reconstruction between 1994 and 2011 were reviewed. The endpoints of the study were defined as: 'conduit exchange for any reason', 'at least moderate conduit stenosis' and 'at least moderate insufficiency'. RESULTS Homografts, bovine jugular vein conduits (Contegra) and porcine-valved Dacron conduits (Hancock) were implanted in 62 (43%), 35 (24%) and 48 (33%) patients, respectively. The mean conduit diameter was 12.9 ± 1.3 mm. A conduit exchange was necessary in 72 patients (55%) at a median time of 5.9 years [1.1-10.8]. The rate of freedom from conduit exchange at 5 years was 69.4 ± 6.6, 59.4 ± 8.7 and 53.8 ± 7.4%, respectively (P = 0.4). The rate of freedom from at least moderate stenosis was 85.4 ± 5.6, 75.1 ± 9.1 69.1 ± 7.9% at 5 years and 59.2 ± 11.1, 35.8 ± 12.0, 49.7 ± 10.1% at 10 years, for homografts, Contegra and Hancock conduits, respectively. The rate of freedom from at least moderate conduit insufficiency was 91.7 ± 4, 74.6 ± 9.1, 86.9 ± 7.4% at 5 years and 64.8 ± 14.1, 44.2 ± 13.7, 52.1 ± 14.2% at 10 years, for homografts, Contegra and Hancock conduits, respectively. Patients with a Contegra conduit developed moderate conduit stenosis or insufficiency faster than patients with a homograft (P = 0.01). Age below 1 month and heterotopic implantation of the conduit emerged as risk factors for conduit exchange in the univariate analysis (P = 0.05, P = 0.02, respectively). There was no significant influence of the conduit type, conduit size, z-score or the body surface area. In the multivariate analysis, heterotopic implantation emerged as the only risk factor for conduit exchange (P = 0.02, hazard ratio = 1.6, 95% confidence interval = 1.0-2.7). CONCLUSIONS Homografts, bovine jugular vein conduits and porcine-valved Dacron conduits exhibit equal durability after implantation in patients below 1 year of age independent of their size. Nonetheless, moderate conduit stenosis or insufficiency develops earlier in patients with a Contegra conduit. Conduit placement in the neonatal period and implantation in a heterotopic position shortens the durability.
A comparative evaluation of the effect of diclofenac sodium with and without per-orally administered methylprednisolone on the sequelae of impacted mandibular third molar removal: A cohort randomized double-blind clinical trial

Aim and Objectives: This study evaluated the efficacy of oral methylprednisolone and diclofenac sodium on post-operative sequelae after third molar surgery. Settings and Design: A randomized double-blind clinical trial was conducted (with institutional and university approval for dissertation) to evaluate the effect of methylprednisolone with diclofenac sodium (group A) as compared with diclofenac sodium and placebo (group B) on three variables: Pain, swelling and trismus, after third molar surgery. Materials and Methods: Thirty consecutive consenting patients for surgical removal of mandibular impacted third molar were randomly placed into two groups of 15 each (groups A and B). Pain, swelling and trismus were observed by visual analog scale, facial measurements and inter-incisal opening. Scores were recorded after 24 and 72 h and on the seventh post-operative day. Results were subjected to the Chi-square test and independent sample t-test (P = 0.05). Results: Mean difference in pain experienced between the two groups was statistically significant at 24 h (P = 0.015) and 72 h (P = 0.001) and on the seventh day (P = 0.005). Difference in inter-incisal distance was insignificant (P = 0.239) pre-operatively, but significant after 24 h (P = 0.014) and 72 h (P = 0.001) and on the seventh post-operative day (P = 0.001). Mean difference in swelling was highly significant after 24 h (P = 0.001) and 72 h (P = 0.0001) and on the seventh post-operative day (P = 0.047). Conclusions: The combination of oral dose of methylprednisolone (a corticosteroid) diclofenac sodium (a non-steroidal anti-inflammatory drug) was found to be more effective than diclofenac sodium alone on the sequelae of surgical removal of impacted mandibular third molar.