Increased reversal and oscillatory shear stress cause smooth muscle contraction-dependent changes in sheep aortic dynamics: role in aortic balloon pump circulatory support

Aims: The intra‐aortic balloon pumping (IABP) changes pressure and increases the aorta shear stress reversal (SS_R) and oscillatory (SS_O) components. Hence, IABP‐dependent changes in aortic biomechanics would be expected, because of vascular smooth muscle (VSM) tone (i.e. flow‐induced endothelium‐dependent response, related to SS_R and SS_O variations) and/or pressure changes. To characterize: (i) the IABP effects on the aortic and global (systemic circulation) biomechanics, analysing their dependence on pressure and VSM basic tone changes and (ii) the relation between the SS_R and SS_O and the aortic biomechanical changes associated with the VSM tone variations. Methods: Aortic flow, pressure and diameter were measured in eight sheep during basal, augmented and assisted beats (1 : 1 and 1 : 2 IABP modalities). Calculations: (i) aortic effective and isobaric elasticity, viscosity, circumferential stress, pulse wave velocity, shear stress and buffer and conduit functions, (ii) peripheral resistance, global compliance, reflection coefficient and wave propagation times and (iii) the relation between SS_R and SS_O and biomechanical changes associated with variations in the aortic VSM tone. Results: Augmented and assisted beats showed: global VSM relaxation pattern (reduced peripheral resistance and reflection coefficient; increased propagation times) and local VSM contraction pattern (increased viscosity; reduced diameter, elasticity and circumferential stress), associated with SS_R and SS_O, levels and changes. The vascular changes reduced the ventricle afterload determinants, increased the vascular buffer performance and kept the conduit capability. Conclusion: In addition to pressure‐dependent changes, IABP determined biomechanical changes related to variations in the VSM tone. The increased SS_R and SS_O were associated with the aortic VSM contraction pattern and biomechanical changes.     

Synthesis and Optical Properties of a Copolymer of Tetrafluoro‐ and Dialkoxy‐Substituted Poly(p‐phenylenevinylene) with a High Percentage of Fluorinated Units

A copolymer of 2,3,5,6‐tetrafluoro‐1,4‐phenylenevinylene and 2,5‐dioctyloxy‐1,4‐phenylenevinylene [co(TFPV‐DOPV)], containing more than 60% of tetrafluorophenylenevinylene monomeric units, was synthesized by the Stille cross‐coupling reaction. Its linear and nonlinear optical properties were investigated. Linear absorption and photoluminescence measurements performed on thin films and solution indicate interchain migration upon excitation. The Z‐scan technique was used to evaluate the third‐order nonlinear susceptibility at λ = 1064 nm. A very high refractive nonlinearity (n₂ = (?10 ± 2) × 10^?12 cm² · W^?1) was measured with a value one order of magnitude larger than that of the corresponding dialkoxy‐substituted homopolymer.

     

Diaphragmatic sulci and portal fissures

Diaphragmatic sulci in the superior surface of the liver were found in 40% of cases at autopsy. All sulci were located in the right lobe and in 47% they were multiple. In order to evaluate possible predisposing factors for these accessory sulci, their topography and characteristics were observed in unfixed livers; moreover, intravenous injections of radio‐opaque resins were performed in the portal and hepatic veins (HVs). After formalin fixation, the livers underwent CT and MR scans and a three‐dimensional (3D) elaboration of the images was performed. Radiological examination revealed a correspondence between the topography of the sulci and the course of the right and middle HVs and their main tributaries in 67%. The corrosion casts showed the location of the sulci at the level of the boundaries between the ramifications of the terminal branches of the portal triad, where the HVs are located, in 73%. These findings suggest that, rather than the action of ‘special’ or hypertrophied muscle bundles, the pressure exerted by the diaphragm as a whole may be responsible for the production of sulci at the level of weak zones, represented by the portal fissures, where the watershed superficial hepatic parenchyma, owing to the absence of all but the smallest vascular branches, exhibits a lower resistance to external pressure.     

Epidemiological relationships between Aeromonas strains isolated from symptomatic children and household environments as determined by ribotyping

Ribotyping was used to study the epidemiology of Aeromonasassociated gastro-enteritis in young children. Ribotyping patterns of 29 Aeromonasstrains (16 Aeromonas caviae, 8 Aeromonas hydrophila, 3 Aeromonas eucrenophila, 1 Aeromonas veronii, and 1 Aeromonas encheleia) isolated from primary stool cultures of sick children were compared using the GelCompare software with patterns of 104 strains (39 Aeromonas eucrenophila, 29 Aeromonas caviae, 11 Aeromonas encheleia, 10 Aeromonas hydrophila, 6 Aeromonas bestiarum, 3 Aeromonas veronii, 3 Aeromonas popoffiiand 3 Aeromonas media) isolated from their household environment in order to investigate the route of transmission of these bacteria. Fifteen strains (47%) isolated from stool cultures of patients showed the same riboprofile as strains found in contacts or environment. In particular, three strains isolated from patients shared the same riboprofile with strains found in their domestic environment. The wide diffusion of potentially pathogenic Aeromonasstrains in our household samples, and the high rate of asymptomatic carriers among family members, suggested that predisposing factors of the host could make children prone to an Aeromonas-related intestinal disease.     

Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey

BackgroundSeveral studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn.ObjectiveWe investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders.MethodsThe nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics.ResultsOut of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19–like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked.ConclusionsCurrent smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04471701","term_id":"NCT04471701"}}NCT04471701; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT04471701","term_id":"NCT04471701"}}NCT04471701     

Intestinal antispasmodic effects of Helichrysum italicum (Roth) Don ssp. italicum and chemical identification of the active ingredients

Ethnopharmacological relevance

In the Mediterranean Area, the flowers of Helichrysum italicum ssp. italicum are a traditional remedy for the treatment of intestinal complaints and are used as herbal tea for curing digestive, stomachic and intestinal diseases. In order to find scientific evidence for the traditional utilization of this plant, the effect of an ethanolic extract of Helichrysum italicum was investigated by using in vivo and in vitro experimental models. Then, through bioassay-guided fractionation procedures, active component(s) were identified.

Material and methods

Contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with acetylcholine and barium chloride; motility in vivo was evaluated by measuring upper gastrointestinal transit, both in control mice and in mice with experimental intestinal inflammation induced by croton oil. Chromatographic separation techniques such as HPLC and silica gel columns have yielded the active principles of Helichrysum italicum.

Results

We found that the ethanolic extract of Helichrysum italicum ssp. italicum flowers elicited antispasmodic actions in the isolated mouse ileum and inhibited transit preferentially in the inflamed gut. A bioassay guided fractionation of the extract yielded the known compounds 12-acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2).

Conclusion

Present study supported the traditional use of Helichrysum italicum ssp. italicum flowers for intestinal complaints and through bioassay-guided fractionation procedures from the crude extract we showed that 12-acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2) acted in a synergistic way to produce an intestinal antispasmodic effect.     

5-fluorouracil plus folinic acid with or without ifosfamide in advanced colorectal cancer: a phase II randomized trial

AIM: This phase II trial evaluated the biomodulation of 5-fluorouracil (5-FU) plus folinic acid (FA) with or without ifosfamide (IFO) in chemotherapy-naive patients with colorectal cancer. PATIENTS AND METHODS: Forty-eight patients were randomized to receive: FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750 mg/m2 iv bolus days 1 to 3), arm A; or FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750 mg/m2 iv bolus days 1 to 3) plus IFO (2,000 mg/m2 in 1000 mL 5% dextrose in a 2-hr infusion, days 1 to 3), arm B. Mesna was added during and after IFO to prevent hemorrhagic cystitis. Treatment was repeated every 21 days in both arms. RESULTS: Forty-five patients were assessable for response: in arm A, 5 patients achieved a partial response (overall response, 25%), and in arm B, 2 patients achieved a complete and 1 a partial response (overall response, 12%). Time to failure was 3.5 months (range, 1-38) in patients treated with 5-FU plus FA, and 3 months (range, 1-21) in patients treated with the IFO combination. The median survival time was 13.5 months (range, 1-49 months) in arm A and 16 months (range, 1-43 months) in arm B. Diarrhea, stomatitis and vomiting were the most common nonhematologic toxicities in both arms. The most notable hematologic toxicity was leukopenia; 15% and 20% of patients experienced grade 4 in arm A and arm B, respectively. CONCLUSIONS: IFO does not increase the activity of the 5-FU plus FA combination in advanced colorectal cancer.     

Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours

Objective: A combination regimen of temozolomide (TMZ) and pegylated liposomal doxorubicin has been evaluated in the treatment of brain metastases from solid tumours. Study design: Nineteen consecutive patients (pts) have been enrolled in a prospective phase II trial and treated with TMZ 200 mg/m² (days 1–5) and pegylated liposomal doxorubicin 35 mg/m² (day 1) every 28 days. The study was prospectively projected according to the Simon’s two-stage optimal design. Results: Major toxicities have been grade III neutropenia and thrombocytopenia in one patient (pt) and grade III erythrodisesthesia in two pts. Three pts achieved a complete response (CR) and four a partial response (PR), for an overall response rate of 36.8% (95% CI: 19.1–59.2), which exceeded the target activity in the study design. A significant improvement in quality of life was demonstrated by FACT-G analysis. The median Progression Free Survival (PFS) was 5.5 (95% CI: 2.7–8.2) months while the median Overall Survival (OS) was 10.0 months (95% CI: 6.3–13.7). Conclusions: The TMZ/pegylated liposomal doxorubicin regimen was well tolerated with an encouraging activity in brain metastases from solid tumours.     

Current and future therapeutic approaches for the treatment of small cell lung cancer

Introduction: Small-cell lung cancer (SCLC) is a very aggressive disease characterized by a high response rate to first-line chemotherapy, but most patients relapse within 1 year with disappointing results to second-line treatments. Chemotherapy has reached a plateau of effectiveness and new therapeutic strategies are needed to change the natural history of SCLC.

Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC.

Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results. To date, no targeted drugs have been approved for clinical practice but several novel agents are in an advanced stage of clinical development in SCLC.