De novo engineering of reticular connective tissue in vivo by silk fibroin nonwoven materials

Biologically tolerated biomaterials are the focus of intense research. In this work, we examined the biocompatibility of three-dimensional (3D) nonwovens of sericin-deprived, Bombyx mori silk fibroin (SF) in beta-sheet form implanted into the subcutaneous tissue of C57BL6 mice, using sham-operated mice as controls. Both groups of mice similarly healed with no residual problem. Macroarray analysis showed that an early (day 3) transient expression of macrophage migration inhibitory factor (MIF) mRNA, but not of the mRNAs encoding for 22 additional proinflammatory cytokines, occurred solely at SF-grafted places, where no remarkable infiltration of macrophages or lymphocytes subsequently happened. Even an enduring moderate increase in total cytokeratins without epidermal hyperkeratosis and a transient (days 10-15) upsurge of vimentin occurred exclusively at SF-grafted sites, whose content of collagen type-I, after a delayed (day 15) rise, ultimately fell considerably under that proper of sham-operated places. By day 180, the interstices amid and surfaces of the SF chords, which had not been appreciably biodegraded, were crammed with a newly produced tissue histologically akin to a vascularized reticular connective tissue, while some macrophages but no lymphocytic infiltrates or fibrous capsules occurred in the adjoining tissues. Therefore, SF nonwovens may be excellent candidates for clinical applications since they both enjoy a long-lasting biocompatibility, inducing a quite mild foreign body response, but no fibrosis, and efficiently guide reticular connective tissue engineering.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

A Cross-Country Network Analysis of Adolescent Resilience

PurposeIn situations of adversity, young people draw on individual, relational, and contextual (community and cultural) resources to foster their resilience. Recent literature defines resilience as a capacity that is underpinned by a network of interrelated resources. Although empirical studies show evidence of the value of a network approach, little is known regarding how different country contexts influence which resources are most critical within a resource network and how resources interact for adolescent resilience.MethodsNetwork analysis was conducted with data from studies that had used the Child and Youth Resilience Measure. Regularized partial correlation networks of 17 resources were estimated for 14 countries (Botswana, Canada, China, Colombia, Equatorial Guinea, India, Indonesia, Italy, Jordan, New Zealand, the Philippines, Romania, South Africa, and Syrian refugees living in Jordan). The sample size was 18,914 (mean age = 15.70 years, 48.8% female).ResultsWe observed mostly positive associations between the resources of interest. The salience and strength of associations between resources varied by country. The most central resource across countries was having supportive caregivers during stressful times because this resource had the most and strongest positive associations with other resources.ConclusionsThis study gives first empirical evidence from multiple countries that an interplay of social–ecological resources (such as individual skills, peer, caregiver and community support, and educational aspirations and opportunities) matter for adolescent resilience. Across countries, caregiver support appears to be most central for adolescent resilience. Future resilience interventions might apply this network approach to identify important, contextually relevant resources that likely foster additional resources.     

The utility of in-bore multiparametric magnetic resonance-guided biopsy in men with negative multiparametric magnetic resonance-ultrasound software-based fusion targeted biopsy

ObjectivesTo evaluate the utility of in-bore multiparametric magnetic resonance-guided biopsy of the prostate (IB) in patients with visible lesion/s and previous negative software-based multiparametric magnetic resonance imaging/ultrasonography fusion-targeted biopsy of the prostate (FTB).Patients and methodsWe retrospectively analysed prospectively maintained database including consecutive men undergoing IB from March 2013 to October 2017 in 2 European centres expert in this procedure. We selected men with the following criteria: No previous treatment for prostate cancer (CaP), multiparametric magnetic resonance imaging (mpMRI) lesion(s) PIRADS score ≥ 3, FTB showing no clinically significant cancer (csCaP), and subsequent IB. Patient's characteristics, mpMRI findings, biopsy technique, and histopathological results were extracted. The primary outcome was to determine the detection rate of csCaP, defined as any Gleason pattern ≥ 4. A multivariable analysis was performed to identify predictors of positive findings at IB.ResultsFifty-three men were included. Median age was 68 years (interquartile range [IQR] 64–68), median Prostate-Specific Antigen (PSA) was 7.6 ng/ml (IQR 5.2–10.9), and median prostate volume was 59 ml (IQR 44–84). Fifty-six lesions with PIRADS score 3 in 9 cases (16%), 4 in 30 cases (54%), and 5 in 17 cases (30%) were detected. FTB was performed in all cases using a transrectal approach with 3 different platforms (Toshiba, Koelis, and Artemis). Median time between FTB and IB was 3 months (IQR 1–7). A median of 2 cores per lesion were collected with IB (IQR 2–3). No cancer, clinically insignificant and clinically significant cancer were found in 33 (59%), 9 (16%), and 14 (25%) targeted lesions, respectively. Median maximum cancer core length and maximum positive percentage were 9 mm (3–13) and 55% (21%–80%). The only predictor of csCaP on IB was prostate volume (P = 0.026) with an ideal cut-off at 70 ml.ConclusionOne in 4 patients with previous negative FTB, IB was able to detect csCaP. According to this study, IB would be of particularly useful in patients with large glands.     

Esophageal adenocarcinoma after sleeve gastrectomy: actual or potential threat? Italian series and literature review

BackgroundSleeve gastrectomy (SG) leads to esophageal mucosal damage in an elevated percentage of cases, configuring a clinical condition of Barrett’s esophagus (BE) in a proportion as high as 15–18.8%. BE may rarely evolve into esophageal adenocarcinoma (EAC).ObjectivesTo raise awareness of BE as a precancerous lesion which may progress toward malignancy after this popular bariatric procedure.SettingBariatric referral centers, Italy.MethodsAll patients referred to our bariatric center who developed an EAC after SG between 2012 and 2019 were reviewed and consecutively included in this study. The available scientific literature regarding this complication is additionally reviewed.ResultsThe 3 male patients comprised in this case series underwent laparoscopic SG between 2012 and 2015 in different bariatric referral centers. Age and body mass index at baseline ranged from 21–54 years and 43.1–75.6 kg/m², respectively. All patients were lost to follow-up early after surgery (3.7 ± 1.4 months), and were diagnosed with EAC at a mean of 27.3 ± 7.6 months after SG. The 4 reported cases in the scientific literature developed an EAC at a mean of 32.5 ± 23 months from SG. Overall, a diagnosis of EAC was made approximately 30.3 ± 17.1 months postoperatively, which seems relatively and worryingly early after surgery.ConclusionAlthough the rate and probability of progression from BE to EAC is still not well defined, assuming that the rising popularity and execution of SG leads to a growth in the BE incidence, then the preoperative identification and stratification of cancer risk factors in this subset of patients is strongly encouraged. Clinical and endoscopic follow-ups are essential to allow for prevention and early diagnosis and for epidemiologic data collection purposes.     

Proline-rich tyrosine kinase Pyk2 regulates deep vein thrombosis

Deep vein thrombosis results from the cooperative action of leukocytes, platelets, and endothelial cells. The proline-rich tyrosine kinase Pyk2 regulates platelet activation and supports arterial thrombosis. In this study, we combined pharmacological and genetic approaches to unravel the role of Pyk2 in venous thrombosis. We found that mice lacking Pyk2 almost completely failed to develop deep venous thrombi upon partial ligation of the inferior vena cava. Pyk2-deficient platelets displayed impaired exposure of phosphatidylserine and tissue factor expression by endothelial cells and monocytes was completely prevented by inhibition of Pyk2. In human umbilical vein endothelial cells (HUVEC), inhibition of Pyk2 hampered IL-1β-induced expression of VCAM and P-selectin, and von Willebrand factor release. Pyk2-deficient platelets showed defective adhesion on von Willebrand factor and reduced ability to bind activated HUVEC under flow. Moreover, inhibition of Pyk2 in HUVEC strongly reduced platelet adhesion. Similarly, Pyk2-deficient neutrophils were unable to efficiently roll and adhere to immobilized endothelial cells under venous flow conditions. Moreover, platelets and neutrophils from Pyk2-knockout mice showed defective ability to form heterogeneous aggregates upon stimulation, while platelet monocyte interaction occurred normally. Consequently, platelet neutrophil aggregates, abundant in blood of wild-type mice upon inferior vena cava ligation, were virtually undetectable in Pyk2-knockout mice. Finally, we found that expression of Pyk2 was required for NETosis induced by activated platelets. Altogether our results demonstrate a critical role of Pyk2 in the regulation of the coordinated thromboinflammatory responses of endothelial cells, leukocytes and platelets leading to venous thrombosis. Pyk2 may represent a novel promising target in the treatment of deep vein thrombosis.     

Depressive symptoms in amnesic mild cognitive impairment: an FDG-PET/CT study

IntroductionThe detection in mild cognitive impairment (MCI) of metabolic alterations suggestive of depression and/or of evolution to dementia.MethodsSixty-nine MCI patients underwent clinical and imaging evaluation including position emission tomography/computed tomography with fluorodeoxy-glucose (FDG-PET/CT).ResultsThe metabolism mean values in parietal, temporal and pre-cuneus areas were lower in subjects who evolved to dementia, and in frontal and in anterior cingulate areas in depressed subjects. Abnormal metabolism values were higher in the frontal and parietal lobes, and in the precuneus in subjects who evolved to dementia independently from depression.ConclusionsIn MCI FDG-PET/CT abnormality patterns suggest the presence of depression or the evolution to dementia.     

Probiotics Administration in Cystic Fibrosis: What Is the Evidence?

In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary.