Familial lung cancer and aggregation of smoking habits: a simulation of the effect of shared environmental factors on the familial risk of cancer.

BACKGROUND: Tobacco smoking is the principal cause of lung cancer. The risk of lung cancer in the offspring of lung cancer patients is about twice higher than the risk in the general population. The present study investigated the contribution of shared smoking habits to the familial clustering of lung cancer. METHODS: We estimated the relative risk of lung cancer attributable to smoking according to the extent to which smokers transmit their smoking habits to the offspring (heritability of smoking), the prevalence of smoking in the general population, and the risk of lung cancer for smokers compared with nonsmokers. FINDINGS: The relative risk of lung cancer for the offspring of lung cancer patients attributable to smoking was 1.19 when published data on smoking practice were modeled (i.e., assuming that the heritability of smoking was 0.5, the smoking prevalence 40%, and the odds ratio of lung cancer for smokers versus nonsmokers was 20). INTERPRETATION: Most familial cases of lung cancer cannot be attributed to shared smoking habits. The example of smoking can be used for other familial cancers, for which no strong environmental risk factors are usually known, to infer the primary role for heritable genes.     

Early increase of plasma soluble VEGFR-2 is associated with clinical benefit from second-line treatment of paclitaxel and ramucirumab in advanced gastric cancer

Ramucirumab plus paclitaxel is considered the standard of care in the second-line treatment of gastric carcinoma (GC). The aim of this study was to evaluate plasma vascular endothelial growth factor-A (VEGF-A), VEGF-D, and circulating soluble VEGF receptor-2 (sVEGFR-2) as possible markers of resistance or response to ramucirumab administered with paclitaxel in pretreated metastatic GC patients. Plasma samples were collected at different time points (on days 1 and 15 of the first 3 cycles, at best radiologic response and at disease progression). VEGF-A, VEGF-D and sVEGFR-2 were analysed by ELISA. Correlations of biomarker baseline levels or dynamic changes with outcome measures were assessed. Progression-free survival (PFS) was the primary endpoint of the study. Forty-one patients were enrolled. VEGF-A and VEGF-D, but not sVEGFR-2, values significantly increased during treatment compared to baseline (P < 0.001). A positive correlation between VEGF-A and sVEGFR-2 at cycle 2 was found (P=0.045). At univariate analysis, higher baseline levels of VEGF-A were associated with worse OS (P=0.015). Early increase of sVEGFR-2 levels after the first treatment cycle was the only factor associated with longer PFS (6.6 vs. 3.6 months, P=0.049) and OS (18.6 vs. 5.2 months, P=0.008). Significance of sVEGFR-2 early increase was retained at multivariate analysis for OS (HR 0.32; 95% CI 0.12-0.91; P=0.032). The reported results confirmed the prognostic role of baseline VEGF-A and, with the limitations of the limited sample size and the lack of a control arm, suggested that the early increase of sVEGFR-2 after 1 cycle of treatment could be a potential predictive biomarker of benefit from second-line ramucirumab plus paclitaxel in GC.     

Filament Transport Control for Enhancing Mechanical Properties of Parts Realised by Fused Filament Fabrication

The fused filament fabrication (FFF) process is widely used for producing prototypes and functional parts for diverse applications. While FFF is particularly attractive due to its cost-effectiveness, on the other hand, the fabricated parts have limitations in terms of large manufacturing time and reduced mechanical properties. The latter is strongly influenced by the fabrication process parameters, which affect the interlayer bonding and the adhesion between consecutive layers. Several works presented in the literature analysed the correlation between mechanical properties and process parameters. It was demonstrated that an increase in the fabrication feed rate causes slippage between filament and the feeding system, which leads to a decrease in the extruded material flow, and thus in part density. This work aims to investigate how the limitation of the slippage phenomenon affects the mechanical properties of parts fabricated using the FFF process. A prototype machine, equipped with a closed-loop control system on filament transport, was used to fabricate samples for tensile tests and dynamical mechanical analysis. Samples fabricated enabling the filament transport control showed an increase both in ultimate tensile strength and elongation at break for those fabricated with disabled control, whilst a decrease in stiffness was observed. In addition, the results showed that the use of a filament transport control system on a FFF machine increases the possibility of fabricating high value-added parts.     

Antibiofilm Efficacy of the Pseudomonas aeruginosa Pbunavirus vB_PaeM-SMS29 Loaded onto Dissolving Polyvinyl Alcohol Microneedles

Resistant bacteria prevail in most chronic skin wounds and other biofilm-related topical skin infections. Bacteriophages (phages) have proven their antimicrobial effectiveness for treating different antibiotic-resistant and multidrug-resistant bacterial infections, but not all phages are effective against biofilms. Phages possessing depolymerases can reach different biofilm layers; however, those that do not have depolymerase activity struggle to penetrate and navigate in the intricate 3D biofilm structure and mainly infect bacteria lodged in the outer biofilm layers. To address this, Pseudomonas aeruginosa phage vB_PaeM-SMS29, a phage with poor antibiofilm properties, was incorporated into polyvinyl alcohol (PVA, Mowiol 4:88) supplemented with 0.1% (v/v) of glycerol, and cast onto two different microneedle arrays varying in geometry. The dissolving microneedles were thoroughly characterized by microscopy, force-displacement, swelling, phage release and stability. Furthermore, 48 h-old biofilms were formed using the colony biofilm procedure (absence of broth), and the antibiofilm efficacy of the phage-loaded microneedles was evaluated by viable cell counts and microscopy and compared to free phages. The phages in microneedles were fairly stable for six months when stored at 4 °C, with minor decreases in phage titers observed. The geometry of the microneedles influenced the penetration and force-displacement characteristics but not the antimicrobial efficacy against biofilms. The two PVA microneedles loaded with phages reduced P. aeruginosa PAO1 biofilms by 2.44 to 2.76 log₁₀ CFU·cm⁻² at 24 h. These values are significantly higher than the result obtained after the treatment with the free phage (1.09 log₁₀ CFU·cm⁻²). Overall, this study shows that the distribution of phages caused by the mechanical disruption of biofilms using dissolving microneedles can be an effective delivery method against topical biofilm-related skin infections.     

Results of the national survey of borderline ovarian tumors in Spain

MATERIAL AND METHODS: Retrospective multi-center analysis of women diagnosed with borderline ovarian tumor and treated between January 1990 and December 1997. A national survey was conducted, in which 457 patients from 27 centers corresponding to ten of Spain's autonomous communities were analyzed. RESULTS: Four hundred fifty-seven women with borderline ovarian tumor were analyzed. The mean age of patients was 45.5+/-16.9 years. Of these, 390 patients (85.3%) were at stage I, 8 (1.8%) were at stage II and 36 (7.9%) at stage III. A bilateral tumor was observed in 63 women (13.8%). The mean tumor size was 14.2 cm and in 88 cases (19.3%) the tumor was on the surface of the ovary. Microinvasion was observed in 25 (5.5%) cases, and 29 women (6.3%) showed a micropapillary pattern. Study of the factors related to the appearance of peritoneal implants revealed positive tumor markers (OR 15.02: 1.9-32.9) and a tumor on the ovarian surface (OR 8.0: 1.8-127) to be independent risk factors. With respect to recurrence, the presence of peritoneal implants at the time of initial surgery (OR 3.4: 1.1-10.4) and signs of microinvasion in the anatomicopathological study (OR 5.5: 1.5-17.8) were found to be independent risk factors. The overall survival rate in our series was 97% with a mean follow-up of 88.3 months. The survival rate by stage was 97% for stage I, 100% for stage II and 97% for stage III. CONCLUSIONS: Although borderline ovarian tumors have an excellent prognosis, they are not exempt from a risk of recurrence. Characterization of patients with borderline ovarian tumor is essential in order to prevent their evolution. Likewise, the taking on board of risk factors will enable more selective treatments to be offered in each case.     

3D Printed Customized Facemask for Maxillary Protraction in the Early Treatment of a Class III Malocclusion: Proof-of-Concept Clinical Case

In order to improve fit and comfort, a maxillary protraction facemask customized to the patient’s anatomy was produced by means of 3D face scanning, digital design and additive manufacturing. An 8-year-old patient in need of early treatment for the Class III malocclusion received a rapid palatal expander and a Petit-type facemask, whose components were digitally designed on a 3D scan of the patient’s face. For face scanning, the iPad Pro 2018 tablet (Apple, Cupertino, CA, USA) with the Bellus3D DentalPro application (Bellus3D, Campbell, CA, USA) was used. Facemask components were modelled with 3D Blender software. The rests were 3D printed in BioMed Clear biocompatible resin (Formlabs, Somerville, MA, USA), and the bar in stainless steel. For greater comfort, the internal surface of the rests was lined with a polymer gel pad (Silipos, Niagara Falls, NY, USA). The manufacturing procedure of the customized facemask is patented. The patient wore the facemask at night for a period of 9 months. The patient’s experience was evaluated with a questionnaire at 1 week, 3, 6, and 10 months of treatment. The customized facemask was well accepted by the patient and obtained the expected treatment outcome. Furthermore, 3D face scanning, 3D modelling and 3D printing allow for the manufacturing of customized facemasks with improved fit and comfort, favoring patient compliance and treatment success.     

Very Low Alcohol Consumption Is Associated with Lower Prevalence of Cirrhosis and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients.     

Apathy and impulsiveness in Parkinson disease: Two faces of the same coin?

Apathy and impulsiveness are 2 common non-motor symptoms in Parkinson disease that could occur in different periods or simultaneously. Apathy and impulsiveness could be interpreted as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, in which, impulsivity, is a result of a hyperdopaminergic state, whereas apathy is viewed as a hypodopaminergic. The study aimed to investigate the presence of impulsiveness and other neuropsychiatric symptoms in Parkinson disease patients with apathy symptoms.Eighty-one patients with Parkinson disease were enrolled in this retrospective study. All subjects were evaluated by the Italian version of the Dimensional Apathy Scale and the Barratt Impulsiveness Scale-version 11, to assess, respectively, apathy and impulsiveness; they were divided into 2 groups (apathy and no apathy). All patients were administered also with questionnaires assessing depressive and anxious symptoms.Statistical analyses showed relevant results. In no-apathy group, education was a significant predictor on impulsiveness (attentional and motor) and apathy (executive and emotional); depression was a significant predictor on planning impulsivity and apathy.This study aimed to consider the importance of apathy and impulsivity in Parkinson disease. Although these are considered as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, these can also occur separately. Moreover, several variables could represent important predictors of apathy and impulsiveness, such as depression. Future investigations should deepen the role of other demographics and psychological variables.