Significance of plasma B-type natriuretic peptide in hemodialysis patients: blood sample timing and comorbidity burden

Plasma B-type natriuretic peptide (BNP) concentration was evaluated in end-stage renal disease patients to verify if measurements before or after the session could furnish different information. BNP levels in plasma from 52 hemodialysis (HD) patients were measured both before and after the first session of the week. Echocardiographic studies were also performed and patients were followed over a period of 28 months. BNP removal from plasma was influenced by equilibrated Kt/V and patient characteristics. Initial plasma BNP concentration was correlated both with cardiac systolic function (LVEF) and mortality rate, independent of blood sample timing (before or after HD). A relative risk of death of 2.67 was found for plasma BNP levels above 335 pg/mL or 232 pg/mL, before and after HD, respectively. Higher BNP levels were observed in patients with higher burden of comorbidity, as measured by the Charlson Comorbidity Index; however, statistical significance was obtained only for BNP measured before HD. In conclusion, measurement of plasma BNP could give a valuable risk stratification of HD patients while cutting costs, by confining echocardiographic studies only to cases with BNP levels above the established cutoff values.     

Social defeat-induced contextual conditioning differentially imprints behavioral and adrenal reactivity: a time-course study in the rat

The present experiments were based on the rat resident-intruder paradigm and aimed at better understanding the long-term conditioning properties of this social stress model. Intruders were exposed to aggressive conspecifics residents. During 3 daily encounters, intruders were either defeated or threatened by residents, providing the defeated-threatened (DT) and threatened-threatened (TT) groups respectively, or exposed to a novel empty cage (EC). The effect of such exposures was assessed in 3 separate experiments 8, 14, or 21 days following the last session on both behavior and hypothalamus-pituitary-adrenal (HPA) axis parameters. A specific and persistent behavioral conditioning due to social defeat but also to the sole social threat experience was observed as defensive behaviors and anxiety-like behaviors were observed respectively in DT and TT rats, highlighting a lack of habituation for the conditioning properties of this social stressor. On the other hand, at the earlier time points examined a less specific activation of the HPA axis parameters was found, starting to show habituation at day 21 in EC but not in DT or TT rats. These data give further support to the lasting effects of this social stress model, bestowing a special emphasis upon the impact of its psychological component and upon the relevance of its development and maintenance over time.     

Genome analysis linking recent European and African influenza (H5N1) viruses

To better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted.     

Systemic adverse effects and toxicities associated with immunotherapy: A review

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use of immuno-therapeutic agents, it is vital for physicians to acquaint themselves with these adverse effects. The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents. We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems, as well as an extensive discussion of the current recommendations for treatment and clinical trial data. As we continue to see increasing usage of these agents in clinical practice, it is vital for physicians to familiarize themselves with these effects.     

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women

BACKGROUND: Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. OBJECTIVE: The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. DESIGN: Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. RESULTS: Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. CONCLUSIONS: Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.     

Personalized therapeutic strategies in HER2-driven gastric cancer

Gastric Cancer - Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them...     

Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer

ObjectiveThe aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC).MethodsWe enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi-quantitative way, according to a 3-tiered scoring system in absent, focal and substantial.ResultsAmong 524 patients, any positive LVSI was found in 57 patients (10.9%) with focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions (p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment (6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6% in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6% in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate of distant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival (hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI was an independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure (HR=10.6, p=0.006).ConclusionsSubstantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.     

Repeated exposure to alcoholic beer does not induce long-lasting changes in alcohol self-administration and intake in Sardinian alcohol-preferring and Sardinian non-preferring rats

AIMS: Rats avidly consume non-alcoholic beer, and addition of alcohol to non-alcoholic beer may function as a medium to induce intake of large amounts of alcohol in rats. The present study investigated whether Sardinian alcohol-preferring (sP) and Sardinian non-preferring (sNP) rats, initially exposed to non-alcoholic beer, and subsequently to non-alcoholic beer containing increasing concentrations of alcohol, would develop unusually high alcohol self-administration and drinking behaviours: (i) when alcohol was added to non-alcoholic beer, and (2) once beer was withdrawn and a plain alcohol solution was made available. METHODS: In Experiment 1, rats were exposed to operant, 30-min/day self-administration sessions of non-alcoholic beer with increasing concentrations of alcohol [0, 2.5, 5, 7.5, and 10% (v/v)] for a total of 45 days. After a brief 'beer-fading' phase, the rats were exposed to self-administration sessions of a plain 10% (v/v) alcohol solution. In Experiment 2, the rats were exposed to non-alcoholic beer with increasing concentrations of alcohol [0, 2.5, 5, 7.5, and 10% (v/v)] and water under the 2-bottle choice regimen with unlimited access (24 h/day) for a total of 35 days. After a brief 'beer-fading' phase, the rats were exposed to the choice between a plain 10% (v/v) alcohol solution and water. RESULTS: sP and sNP rats did not differ in self-administration (Experiment 1) and intake (Experiment 2) of non-alcoholic beer. In Experiment 1, as alcohol content increased, the amount of self-administered alcohol increased progressively in sP rats (up to 1-1.2 g/kg) and remained stable in sNP rats (approximately 0.65 g/kg). When the plain 10% alcohol solution was available, the amount of self-administered alcohol in sP rats initially dropped, and tended to increase-up to approximately 0.6 g/kg-on continuing exposure. In sNP rats, their lever-pressing behaviour was rapidly extinguished after beer withdrawal. In Experiment 2, as alcohol content was increased, daily alcohol intake increased progressively in sP rats (up to 8-9 g/kg) and averaged approximately 2.4 g/kg in sNP rats. When the plain alcohol solution was available, daily alcohol intake in sP rats was initially low, reaching control values on continuing exposure; conversely, daily alcohol intake was completely suppressed in sNP rats. CONCLUSIONS: These results suggest that exposure to alcoholic beer resulted in unusually high intakes of alcohol in both sP and sNP rats for as long as non-alcoholic beer was added to alcohol; however, these high levels of alcohol self-administration and intake were not maintained once non-alcoholic beer was withdrawn.     

Assessing heteroplasmic load in Leber's hereditary optic neuropathy mutation 3460G->A/MT-ND1 with a real-time PCR quantitative approach

To quantify the amount of the 3460G-->A/ND1 point mutation responsible for Leber's hereditary optic neuropathy, we developed a quantitative real-time polymerase chain reaction method based on the SYBR Green assay and a new approach using the TaqMan assay. Both methods were based on the amplification refractory mutation system, comparing the heteroplasmic load quantified by restriction fragment length polymorphism in 15 Leber's hereditary optic neuropathy family members, with the results obtained using quantitative real-time polymerase chain reaction methods. The comparative evaluation of mitochondrial DNA (mtDNA) heteroplasmy from blood samples showed significant correlation between restriction fragment length polymorphism analysis, real-time SYBR Green assay, and TaqMan assay. We validated the last method by measuring experimental samples composed by a known proportion of cloned plasmids containing either the wild-type or mutant sequence, giving a correlation coefficient of 0.999 (P < 0.0001). The real-time amplification refractory mutation system polymerase chain reaction by TaqMan assay provides a rapid, reliable, sensitive, reproducible, and one-step quantitative method to detect heteroplasmic mutant mtDNA. This method allows the quantitation of a broad range of mutational load (up to 100%, down to 0.01%) on the basis of in vitro calibration, thus rendering the TaqMan assay suitable for the diagnostic analysis of heteroplasmic load in mtDNA-related disorders.