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Abstract The debate on the relationship between internationalization and performance is still open and is a hot topic for policymakers, but they ignore the impacts for most of the firms supported. The paper is based on a large database of seven years that considers quantitative-qualitative and control variables. To reduce industry and country heterogeneity we focused on the Italian automotive supply chain. We tested 5 modes of internationalization on firms' profitability so to support the design of policies. Our results are partially in contrast with literature; therefore we identify specific environments where policies, namely for exporting, could be more effective. [ABSTRACT FROM AUTHOR]

Background: To evaluate the analgesic efficacy of continuous erector spinae plane block(c-ESPB) and serratus anterior plane block(c-SAPB) versus the intercostal nerve block (ICNB) in Uniportal-VATS in terms of pain control, drug consumption, and complications. Methods: Ninety-three consecutive patients, undergone one of the three peripheral nerve blocks after Uniportal-VATS, were prospectively enrolled. A 1:1 propensity score matching was used to minimize bias. Results: C-ESPB and c-SAPB groups had no difference in morphine request upon awakening compared to ICNB. A higher VAS-score was recorded in c-ESPB compared to ICNB in the first 12 h after surgery. A significantly lower consumption of paracetamol in II postoperative day (p.o.d.) and tramadol in I and II p.o.d. was recorded in the c-ESPB group compared to the ICNB group. A higher dynamic VAS score was recorded at 24 h and 48 h in the ICNB group compared to the c-SAPB. No difference was found in safety, VAS-score and drug consumption between c-ESPB and c-SAPB at any given time, except for a higher tramadol request in c-SAPB in II p.o.d. Conclusions: C-ESPB and c-SAPB appear to have the same safety and analgesic efficacy when compared between them and to ICNB in Uniportal-VATS approach. C-ESPB showed a delayed onset of analgesic effect and a lower postoperative drug consumption compared to ICNB. [ABSTRACT FROM AUTHOR]

Background A long sought goal in medical genetics has been the replacement of invasive procedures for the detection of chromosomal aneuploidies by isolating and analyzing fetal cells or free fetal DNA from maternal blood, avoiding risk to the fetus. However, a rapid, simple, consistent, and low-cost procedure suitable for routine clinical practice has not yet been achieved. The purpose of this study was to assess the feasibility of predicting fetal aneuploidy by applying our recently established dual-probe FISH protocol to fetal cells isolated and enriched from maternal blood. Methods A total of 172 pregnant women underwent prospective testing for fetal aneuploidy by FISH analysis of fetal cells isolated from maternal blood. Results were compared with the karyotype determined through invasive procedures or at birth. Results Seven of the samples exhibited fetal aneuploidy, which was confirmed by invasive prenatal diagnosis procedures. After enrichment for fetal cells, the frequency of trisomic cells was at least double in samples from aneuploid pregnancies (range 0.38-0.90%) compared to samples from normal pregnancies (≤0.18%). One false negative result was also obtained. Conclusions Noninvasive prenatal aneuploidy screening using fetal cells isolated from maternal blood is feasible and could substantially reduce the need for invasive procedures. [ABSTRACT FROM AUTHOR]

The aim of this paper is to propose an alternative approach for outlining policy responses to stimulate the automotive industry. The scientific community has developed and employed the Delphi method to collect and convey perspectives and impressions, and also define a number of financially viable proposals. The panel of experts takes the view that traditional industrial policy measures denote limited effects to stimulate car demand, in a context of a macro-economic downturn. By contrast, the panel also believe incentives for car demand are important for environmental purposes, for safety and for the diversification of energy sources. The policy measures proposed are fundamental from the viewpoint of overturning path dependencies in the automotive industry which impede the diffusion of alternative vehicles, with respect to business models and consumer attitudes. [ABSTRACT FROM AUTHOR]

Abstract: Supernumerary invdup(15) chromosomes, now also reported as sSMC(15), containing two additional copies of Prader–Willi/Angelman critical region (PWACR) have been associated with distinct clinical phenotype that includes hypotonia, dysmorphisms, developmental delay/mental retardation, autistic behaviour, and epilepsy. We report on a healthy adult male carrying an sSMC(15) with two copies of PWACR in 20–50% of cells from different tissues. Molecular analyses showed the sSMC(15) as resulting from a PWACR-duplicated region spanning 8Mb which is larger than those in the only two other healthy PWACR-duplicated sSMC(15) carriers previously reported. Mosaicism level and mosaic cell line rate variation among different tissues observed in our case support mosaicism in critical tissues as of relevance for sSMC(15) phenotype–genotype correlations. [Copyright &y& Elsevier]

Abstract: The Fmr1 knockout (KO) mouse is characterized by an increased audiogenic seizure (AGS) susceptibility and is considered a good animal model for epilepsy and seizures in the human fragile-X (FRAX) syndrome. Here, we tested the hypothesis that the reintroduction of the FMR1 gene is able to revert the AGS susceptibility characterizing Fmr1 KO mice. To this aim, two groups of Fmr1 KO transgenic mice, which have additional copies of the human FMR1 gene (YAC) or FMR1 cDNA (G6) were used. AGS susceptibility of these mice was examined and compared to that of Fmr1 KO, wild type, and wild-type animals in whom the FMR1gene was also introduced (over-expressed). Mice were tested at different ages because AGS susceptibility is age dependent. The intensity of response was scored and the results were analyzed by means of 2-way analysis of variance to evaluate the effects of age and genetic condition. We found that AGS susceptibility rescue is complete in the G6 mice and partial in YAC mice. Our data indicate that the introduction of the human FMR1 gene in Fmr1 KO mice is able to revert the Fmr1 KO epileptic phenotype. [Copyright &y& Elsevier]

Summary. A patient with refractory anaemia with excess of blasts (RAEB) had a complex karyotype with multiple markers. Spectral karyotyping (SKY) showed rearrangements including three different der(11), containing a very high number of MLL gene copies, shown by fluorescence in situ hybridization (FISH) analysis. Fibre-FISH experiments disclosed the presence of chromatin fibres with multiple MLL copies with a head-to-tail pattern. Apparently, no other region flanking the MLL site was present in the three der(11). MLL amplification was confirmed by the reverse transcription polymerase chain reaction (RT-PCR). The patient died 6 months after diagnosis, supporting the severe prognosis of sole MLL amplification. [ABSTRACT FROM AUTHOR]

This article reports the results of an empirical study on the innovation capabilities of a sample of 25 Italian small-medium car suppliers. The aim of the paper is to highlight the capabilities, the behavioural models and the factors determining innovation: technology transfer, the role of sub-suppliers, the relationships with external research institutes and the obstacles to innovation. Inter-firm differences in the innovation process will be examined using multinomial logit analysis. The homogeneity of the sample allows the testing of some operating strategies that may contribute to more rapid technological change in mature industries such as: diversity, consolidation and co-operation. [ABSTRACT FROM AUTHOR]

Pulmonary metastasectomy (PM) is a well-established treatment that is able to contribute to the cure of oligometastatic cancer. Surgery should adopt the most lung-sparing approach possible to preserve pulmonary function (and, consequently, the quality of life) and to spare the lung for potential additional lung resections. In this framework, laser technology has been introduced in recent decades, but only few experiences combining laser technology with VATS approaches have been reported till now. The main focus of this manuscript is to report our institutional experience in performing lung-sparing laser-assisted PM by uniportal VATS (uniportal laser-assisted VATS: U-LA-VATS). The surgical technique and peri-operative results from our series of patients were herein presented and compared with the pertinent literature. Methods: Between March 2021 and November 2023, among 98 patients who underwent PM, a total of 24 patients (18 men (75%); 6 women (25%); mean age 61.4 years; age range 13–83 years) were treated with laser-assisted PM at our institution. Patients who underwent anatomical resection were excluded for the purpose of the analysis. The U-LA-VATS procedure adopted a modified laser-assisted lung resection technique for performing PM via VATS. Dedicated instruments are used, characterized by a long shape and a curved shape, with distal and proximal articulations. A surgical laser system (Thulium + Diodo OUTPUT 30–10 W, Quanta System S.p.a., Solbiate Olona, Italy) was used, and a 550-μm sterile optical fibre conducted through a specific thoracoscopic handpiece was introduced in the lowest part of the incision. Peri-operative results were analysed in all cohort and compared according to the surgical technique. Moreover, these results were compared with those reported in the literature. Comprehensive research of the literature was conducted on PubMed from 2000 to 2024. A review was performed and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: In 12 cases (50%), thulium laser-assisted resection was performed using uniportal video-assisted thoracic surgery (VATS), and in the other cases (12, 50%), a (mini)thoracotomy access was adopted. In the thoracotomy group, the mean duration of surgery was 95 ± 57.7 min; meanwhile, it was 73.5 ± 35.5 in the uniportal VATS group. At the univariate analysis, this difference resulted to be statistically significant (p value 0.025). We did not observe intra-operative complications or remarkable malfunction of the laser system. We also did not report major complications after surgery; also the air-leak rate was 8.3% and 0% after thoracotomic and VATS procedures, respectively. Surgical margins were free from disease in all cases. Major and minor post-op complication rates were similar in both groups. The mean hospitalization after surgery was 2.9 ± 0.3 days for the uniportal VATS group and 3.7 ± 0.9 days for the thoracotomy group, this difference being statistically significant at the univariate analysis (p value = 0.015). Conclusions: U-LA-VATS is a safe and effective procedure, able to combine a parenchymal sparing exeresis with a mini-invasive approach. This procedure is associated with a shorter hospital stay compared with PM performed by a thoracotomic approach. Compared with the selected works for the review, our series is the only one describing the use of laser resection combined with a uniportal VATS approach. [ABSTRACT FROM AUTHOR]

Simple Summary: In cases of advanced lung cancer after neoadjuvant chemotherapy (nCT), the role of uniportal video-assisted thoracoscopic surgery (U-VATS) is still questionable, with concerns about safety, technical feasibility, and oncological completeness. The aim of this retrospective study was to assess the impact of nCT on patients who had undergone U-VATS anatomic lung resections for lung cancer. We compared the short-term outcomes of 60 patients with case-matched counterparts (treated by surgery alone) selected by propensity score analysis, finding that U-VATS after nCT is a feasible approach with a similar rate of cardiopulmonary complications, length of stay, and readmission when compared with the control group. However, it is still a challenging surgery due to the great technical complexity, which is responsible for the higher incidence of conversion. Background: The advantages of video-assisted thoracic surgery (VATS) are well-recognized in several studies. However, in the cases of advanced lung cancer after neoadjuvant chemotherapy (nCT), the role of VATS is still questionable, with concerns about safety, technical feasibility, and oncological completeness. The aim of this study was to assess the impact of nCT on patients who had undergone uniportal VATS (U-VATS) anatomic lung resections for lung cancer, by comparing the short-term outcomes of patients after nCT with case-matched counterparts (treated by surgery alone). Methods: We performed a retrospective, comparative study enrolling 927 patients (nCT: 60; non-nCT:867) who underwent U-VATS anatomic lung resections from 2014 to 2020 in two centers. Data were collected in a shared database with standardized variables' definition. Propensity score matching using 15 baseline preoperative patients' characteristics was performed in order to minimize selection-confounding factors between the two groups, which then were directly compared in terms of perioperative outcomes. Results: After propensity score matching, two groups of 60 patients had been defined. The nCT-group had a higher conversion rate compared to the control group (13.3% vs. 0%, p = 0.003) without an increase in operation time or cardiopulmonary complications. In addition, no differences between the two groups were recorded in terms of prolonged air leaks, length of stay, and readmission. Conclusions: U-VATS after nCT is a feasible approach, showing a similar rate of cardiopulmonary complications and length of stay when compared with the control group. However, it remains a challenging surgery due to its great technical complexity as well as the clinical status of the patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of this study is to emphasize the importance of genetic testing for healthy individuals with a strong family history of hereditary malignancies. A total of 103 healthy subjects with at least two relatives with cancer were enrolled. By NGS analysis of 27 genes, 5% were found to carry a pathogenic variant in a hereditary cancer susceptibility gene. In the era of personalized medicine, genetic testing of healthy subjects in the absence of a living affected collateral is crucially important for early diagnosis, clinical surveillance and surgical choice. Hereditary cancer syndromes caused by germline mutations account for 5–10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network's (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first- or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found, while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status. [ABSTRACT FROM AUTHOR]

Simple Summary: Completion lobectomy (CL) entails the resection of the remaining pulmonary lobe subsequent to wedge resection or segmentectomy. Indications for CL include reoperations for multiple or relapsed lung cancers and metastatic lung tumors, and the prognostic advantage of these procedures has been widely reported. However, ipsilateral surgical treatments, particularly within the same lobe, present challenges due to the development of intrapleural adhesions, rendering reoperation more difficult and time-consuming. VATS has emerged as the gold standard in the surgical treatment of early-stage NSCLC, offering superior postoperative outcomes when compared to thoracotomy. Its efficacy has been well established, even during complex procedures. However, its application in ipsilateral reoperations remains anecdotal, and to the best of our knowledge, no studies have analyzed the safety and efficacy of uniportal-VATS in this setting. This paper aims to evaluate the role of iniportal-VATS in CL long after wedge resection or anatomical segmentectomy in the same lobe. Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07–24.50), p = 0.04). Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy. [ABSTRACT FROM AUTHOR]

The UNC-5 family of netrin receptor genes, predominantly expressed in brain tissues, plays a pivotal role in various neuronal processes. Mutations in genes involved in axon development contribute to a wide spectrum of human diseases, including developmental, neuropsychiatric, and neurodegenerative disorders. The NTN1/DCC signaling pathway, interacting with UNC5C, plays a crucial role in central nervous system axon guidance and has been associated with psychiatric disorders during adolescence in humans. Whole-exome sequencing analysis unveiled two compound heterozygous causative mutations within the UNC5C gene in a patient diagnosed with psychiatric disorders. In silico analysis demonstrated that neither of the observed variants affected the allosteric linkage between UNC5C and NTN1. In fact, these mutations are located within crucial cytoplasmic domains, specifically ZU5 and the region required for the netrin-mediated axon repulsion of neuronal growth cones. These domains play a critical role in forming the supramodular protein structure and directly interact with microtubules, thereby ensuring the functionality of the axon repulsion process. We emphasize that these mutations disrupt the aforementioned processes, thereby associating the UNC5C gene with psychiatric disorders for the first time and expanding the number of genes related to psychiatric disorders. Further research is required to validate the correlation of the UNC5C gene with psychiatric disorders, but we suggest including it in the genetic analysis of patients with psychiatric disorders. [ABSTRACT FROM AUTHOR]

This study aims to define the clinicopathological characteristics and prognosis of non-predominant lepidic invasive adenocarcinoma presenting as Ground Glass Opacity (GGO) nodules. The goal is to assess statistical relationships between histology, tumor size, location, and the incidence of relapse and lymph node dissemination. A retrospective multicenter study was conducted, including patients with GGO observed on CT scans between 2003 and 2021. Anamnestic, radiological, and histological data, as well as SUV values, lymphatic and vascular invasion, pathological stage, resection type, and adjuvant treatment, were analyzed. The primary endpoints were to evaluate prognostic factors for death and recurrence using Cox regression analysis. All 388 patients, including 277 with non-predominant lepidic invasive adenocarcinoma and 161 with lepidic adenocarcinoma, underwent curative anatomical resection. Non-predominant lepidic invasive adenocarcinoma demonstrated a worse prognosis than lepidic adenocarcinoma (p = 0.001). Independent prognostic factors for death and recurrence included lymph node involvement (p = 0.002) and vascular and lymphatic invasion (p < 0.001). In conclusion, non-predominant lepidic invasive adenocarcinoma and lymphatic and vascular invasion are prognostic factors for death and recurrence in GGO patients. Results suggest adjuvant treatment in the case of pN1-N2 disease, emphasizing the necessity of lymphadenectomy (sampling or systematic) for accurate staging and subsequent therapeutic procedures. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to evaluate if the efficacy and safety of chest tube placement are influenced by the level of intercostal space insertion (uniportal VATS vs. biportal VATS) or by the type of drain employed (standard vs. smart coaxial drain). Methods: Data on patients who underwent either uniportal or biportal VATS upper lobectomies with lymphadenectomy were prospectively collected in three European centers. The uniportal VATS group with a 28 Fr standard chest tube (U-VATS standard) was compared with the uniportal VATS group with a 28 Fr smart drain (U-VATS smart), and U-VATS smart was also compared with biportal VATS with a 28 Fr smart drain inserted in the VIII intercostal space (Bi-VATS smart). Results: When comparing the U-VATS standard group with the U-VATS smart, a higher fluid output was recorded in the U-VATS smart (p: 0.004) in the III post-operative day (p.o.) and overall (p: 0.027), with a lower 90-day re-admission in the U-VATS smart (p: 0.04). The Bi-VATS smart group compared to U-VATS smart showed a higher fluid output in the I p.o. (p < 0.001), with no difference in total fluid amount or hospitalization. The Bi-VATS smart recorded a lower incidence (p < 0.001) of residual pleural space or effusion (p: 0.004) at chest X-rays prior to drain removal but a higher level of pain and chronic intercostal neuralgia (p: 0.03). Conclusions: Chest tube insertion through the same incision space in uniportal VATS seems to be safe and effective. Smart drains can improve the fluid output in uniportal VATS, as if the drainage were inserted in a lower space (i.e., biportal VATS), but with less discomfort. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Notably, the incidence of lung cancer among never-smokers, predominantly women, has been rising in recent years. Among the various implicated risk factors, human papilloma virus (HPV) may play a role in the development of NSCLC in a certain subset of patients. The prevalence of high-risk HPV-DNA within human neoplastic lung cells varies across the world; however, the carcinogenetic role of HPV in NSCLC has not been completely understood. Bloodstream could be one of the routes of transmission from infected sites to the lungs, along with oral (through unprotected oral sex) and airborne transmission. Previous studies reported an elevated risk of NSCLC in patients with prior HPV-related tumors, such as cervical, laryngeal, or oropharyngeal cancer, with better prognosis for HPV-positive lung cancers compared to negative forms. On the other hand, 16% of NSCLC patients present circulating HPV-DNA in peripheral blood along with miRNAs expression. Typically, these patients have a poorly differentiated NSCLC, often diagnosed at an advanced stage. However, HPV-positive lung cancers seem to have a better response to target therapies (EGFR) and immune checkpoint inhibitors and show an increased sensitivity to platinum-based treatments. This review summarizes the current evidence regarding the role of HPV in NSCLC development, especially among patients with a history of HPV-related cancers. It also examines the diagnostic and prognostic significance of HPV, investigating new future perspectives to enhance cancer screening, diagnostic protocols, and the development of more targeted therapies tailored to specific cohorts of NSCLC patients with confirmed HPV infection. [ABSTRACT FROM AUTHOR]

Alveolo-pleural fistula remains a serious post-operative complication in lung cancer patients after surgery, which is associated with prolonged hospital stay and higher healthcare costs. The aim of this study is to evaluate the efficacy of a polyglycol acid (PGA)-sheet known as Neoveil in preventing post-operative air-leak in cases of detected intra-operative air-leak after lung resection. Between 11/2021 and 7/2022, a total of 329 non-small cell lung cancer (NSCLC) patients were surgically treated in two institutions. Major lung resections were performed in 251 cases. Among them, 44 patients with significant intra-operative air-leak at surgery were treated by reinforcing staple lines with Neoveil (study group). On the other hand, a historical group (selected by propensity score matched analysis) consisting of 44 lung cancer patients with significant intra-operative air leak treated by methods other than the application of sealant patches were considered as the control group. The presence of prolonged air-leak (primary endpoint), pleural drainage duration, hospital stay, and post-operative complication rates were evaluated. The results showed that prolonged air-leak (>5 days after surgery) was not observed in study group, while this event occurred in four patients (9.1%) in the control group. Additionally, a substantial reduction (despite not statistically significant) in the chest tube removal was noted in the study group with respect to the control group (3.5 vs. 4.5, p = 0.189). In addition, a significant decrease in hospital stay (4 vs. 6 days, p = 0.045) and a reduction in post-operative complications (2 vs. 10, p = 0.015) were observed in the study group when compared with the control group. Therefore, in cases associated with intra-operative air-leak after major lung resection, Neoveil was considered a safer and more effective aerostatic tool and represents a viable option during surgical procedures. [ABSTRACT FROM AUTHOR]

Background: Descending necrotizing mediastinitis (DNM) is a severe, life-threatening complication of oropharyngeal infections with cervical necrotizing fasciitis. In this study, we aimed to identify any possible factors that correlate with favorable outcomes. Methods: We retrospectively analyzed our series of 18 patients who underwent surgical treatment for DNM from a cervical abscess. Gender, age, symptoms, etiopathogenesis, comorbidities, time to surgery from diagnosis, degree of diffusion, identified microorganisms, surgical procedure, days in the intensive care unit, need for tracheostomy, complications, and surgical outcomes were reviewed. Results: The main type of surgery was thoracotomy + cervicotomy in eight cases (50.0%), followed by cervicotomy +VATS in four (22.2%). Seven patients (38.9%) had two or more surgeries; a bilateral operation was necessary for four patients. Evaluating the risk factors associated with post-operative complications, age ≥ 60 years (p:0.031), cervicotomy alone as surgical approach (p = 0.040), and the bilateral approach (p = 0.048) resulted in significance in terms of the univariate analysis; age ≥ 60 years (p = 0.04) and cervical approach (p = 0.05) maintained their significance in terms of the multivariate analysis. Conclusions: The low mortality of our series emphasizes the importance of an extensive and immediate surgical drainage of both the neck and the mediastinum. Mediastinal drainage from cervicotomy seems to be a risk factor for post-operative complications. Minimally invasive surgery on the chest cavity, such as with Uniportal-VATS, could be a good approach above all in elderly patients and all those cases where bilateral access is required. [ABSTRACT FROM AUTHOR]

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association. [ABSTRACT FROM AUTHOR]

From January 1st 2013 to August 31st 2016, 24408 pregnant women received the first trimester Combined test and contingently offered second trimester maternal serum screening to identify those women who would most benefit from invasive prenatal diagnosis (IPD). The screening was based on first trimester cut-offs of ≥1:30 (IPD indicated), 1:31 to 1:899 (second trimester screening indicated) and ≤1:900 (no further action), and a second trimester cut-off of ≥1:250. From January 2014, analysis of fetal cells from peripheral maternal blood was also offered to women with positive screening results. For fetal Down syndrome, the overall detection rate was 96.8% for a false-positive rate of 2.8% resulting in an odds of being affected given a positive result (OAPR) of 1:11, equivalent to a positive predictive value (PPV) of 8.1%. Additional chromosome abnormalities were also identified resulting in an OAPR for any chromosome abnormality of 1:6.6 (PPV 11.9%). For a sub-set of cases with positive contingent test results, FISH analysis of circulating fetal cells in maternal circulation identified 7 abnormal and 39 as normal cases with 100% specificity and 100% sensitivity. We conclude that contingent screening using conventional Combined and second trimester screening tests is effective but can potentially be considerably enhanced through the addition of fetal cell analysis. [ABSTRACT FROM AUTHOR]

We report the first case of an 18p11.32 deletion, detected by array CGH, associated with a drug-resistant form of atypical absence epilepsy, global developmental delay and no signs of holoprosencephaly (HPE). In particular, this region encompasses 19 genes, and none of these genes have been strictly associated with epilepsy. Among these, TGIF1 is expressed in the fetal and adult nervous system, and its deletion has been related to central nervous system diseases. TGIF1 deletions have previously been reported in patients with a comparable phenotype as seen in our case and in children whose neurological signs and symptoms were considerable, but not epileptiform. Mutations and deletions involving the TGIF1 gene have been described in patients with HPE in an autosomal dominant model of inheritance. However, TGIF1 mutations have also been reported in normal individuals and in patients with mental retardation or showing a very mild phenotype, suggesting the characteristic of incomplete penetrance and variable expressivity. Therefore, a TGIF1 deletion may not be always related to HPE, and it may have a link to the development of epilepsy. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A deletion of one of the two copies of the 9-bp tandem repeat sequence (CCCCCTCTA), in the small non-coding/untranslated segment located between the cytochrome oxidase II and lysine tRNA genes of mitochondrial DNA (mtDNA), has previously been used as a polymorphic anthropological marker (MIC9D) for people of Africa and Asia, but it has been rarely reported in Europe. 32 Sicilian patients with syndromic hearing loss, negative for mutations in GJB2 and GJB6 genes, were tested for mtDNA known point mutations associated with syndromic or non-syndromic hearing loss by RFLP and/or direct sequencing. We identified the presence of the MIC9D in homoplasmy in lymphocytes and muscle of three subjects with sensorineural hearing loss and encephalomyopathy, two of these also presented moderate mental retardation. This deletion was absent in 300 Caucasian controls. Although further studies are warranted, our results suggest that the MIC9D polymorphism could have a susceptibility role in Caucasus, such as Sicily population. [ABSTRACT FROM AUTHOR]

Abstract: We report the case of a girl with Cowden syndrome (CS) presenting with unilateral perisylvian dysplasia and with drug resistant focal seizures carrying a novel missense mutation 385G>A (G129R) in the PTEN gene. CS has been rarely reported in association with a cortical malformation or epilepsy. These cases suggest that cortical dysplasia needs to be suspected when a CS patient presents with drug-resistant seizures. [Copyright &y& Elsevier]

Abstract: We report the clinical and molecular investigations in a girl with 46,X,-X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype characterized by mental retardation and facial dysmorphisms in combination with short stature. The structure of the derivative X chromosome was studied using BAC array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene and the presence of the Yq11.1qter chromosome. It is common that females with Xp;Yq translocations present only short stature and are normal in every other aspect. Thus, this would be the first case in which a girl with Xp;Yq translocation presents an unusual phenotype with intermediate male clinical features with Xp;Yq translocations. The risk of developing gonadoblastoma in females with Y chromosome material is also discussed and, to this effect, different explanations related to this apparent variation are also presented. [Copyright &y& Elsevier]

Abstract: We describe the case of a boy with psychomotor delay and dysmorphic features, with a germline 16q22.1 microdeletion identified by array-CGH. The deletion spans 0.24Mb and encompasses three genes (ZFP90, CDH3 and CDH1). The deletion has been demonstrated to be inherited from his mother who was affected by lobular breast cancer (LBC) without any other apparently phenotypic features. We suppose that the microdeletion, in particular ZFP90 which is cerebrally expressed, is causative for the boy''s phenotype. Mental retardation in the affected boy can recognize several mechanisms such as variable expressivity, non-penetrance, multifactorial/polygenic inheritance, recessive inheritance, a second rearrangement event and epigenetics. Furthermore, we suggest that the deletion of the CDH1, a tumor suppressor gene, involved in hereditary diffuse gastric cancer (HDGC) and LBC predisposed the mother to the carcinoma. [Copyright &y& Elsevier]

Extranodal NK/T lymphoma, nasal type, is an uncommon neoplasm that occurs with a higher prevalence among Asian populations and Native American populations of Central and Southern America. In Western countries, this tumor is extremely rare, accounting for less than 1.5% of all non-Hodgkin lymphomas. Cytogenetic analyses have been performed only in a limited number of cases, mainly because of technical problems related to extensive necrosis and the scarcity of clinical samples, and these have shown complex karyotypes with no specific chromosomal translocations. Here, we report the cytogenetic characterization of a clinically aggressive nasal NK/T-cell lymphoma occurring in a 40-year-old Italian male patient, in which the sole chromosome abnormality was a partial trisomy of chromosome 13. [ABSTRACT FROM AUTHOR]

Abstract: We report on an apparently normal 5-month-old boy with a X;Y complex rearrangement identified first on prenatal diagnosis and found on array-CGH to have a 7.6 Mb duplication of Xp22.3 chromosome and a deletion of Yq chromosome, distal to the AZFa locus. Karyotype analysis on amniotic fluid cell cultures revealed a de novo homogenous chromosome marker that we interpreted as an isochromosome Yp. FISH analysis using SRY probe revealed only one signal on the derivative Y chromosome. The final karyotype was interpreted as 46,X,der(Y)t(X;Y)(p22.31;q11.22). Translocation Xp22;Yq11 in male are very rare event and only 4 cases have been published, all showing mental retardation and malformations. Herein we discussed some possible explanation for this apparent phenotypic variability. [Copyright &y& Elsevier]

Background: Stem cells isolated from amniotic fluid are known to be able to differentiate into different cells types, being thus considered as a potential tool for cellular therapy of different human diseases. In the present study, we report a novel single step protocol for the osteoblastic differentiation of human amniotic fluid cells. Results: The described protocol is able to provide osteoblastic cells producing nodules of calcium mineralization within 18 days from withdrawal of amniotic fluid samples. These cells display a complete expression of osteogenic markers (COL1, ONC, OPN, OCN, OPG, BSP, Runx2) within 30 days from withdrawal. In order to test the ability of these cells to proliferate on surfaces commonly used in oral osteointegrated implantology, we carried out cultures onto different test disks, namely smooth copper, machined titanium and Sandblasted and Acid Etching titanium (SLA titanium). Electron microscopy analysis evidenced the best cell growth on this latter surface. Conclusion: The described protocol provides an efficient and time-saving tool for the production of osteogenic cells from amniotic fluid that in the future could be used in oral osteointegrated implantology. [ABSTRACT FROM AUTHOR]

Prenatal diagnosis plays a crucial role in clinical genetics. Non-invasive prenatal diagnosis using fetal cells circulating in maternal peripheral blood has become the goal of prenatal diagnosis, to obtain complete fetal genetic information and avoid risks to mother and fetus. The development of high-efficiency separation technologies is necessary to obtain the scarce fetal cells from the maternal circulation. Over the years, multiple approaches have been applied, including choice of the ideal cell targets, different cell recovering technologies, and refined cell isolation yield procedures. In order to provide a useful tool and to give insights about limitations and advantages of the technologies available today, we review the genetic research on the creation and validation of non-invasive prenatal diagnostic testing protocols based on the rare and labile circulating fetal cells during pregnancy. [ABSTRACT FROM AUTHOR]

Case report A fetus with rhombencephalosynapsis and prenatally diagnosed tetrasomy 9p is reported. Chromosomal analysis from amniocyte culture revealed non-mosaic supernumerary chromosome identified as isochromosome 9p (9p24→q13::q13→p24). Ultrasound scan revealed intrauterine growth retardation, renal anomalies, cardiac anomalies, ventriculomegaly, and agenesis of cerebellar vermis with fusion of the cerebellar hemispheres. Conclusion Although most cases of cerebellar vermis agenesis in tetrasomy 9p are described with cystic malformation such as Dandy-Walker anomaly, our case indicates that this chromosomal disorder should be taken into account in fetuses with the development of cystic and non-cystic malformations of cerebellar vermis and posterior fossa. [ABSTRACT FROM AUTHOR]

Abstract: BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients. [Copyright &y& Elsevier]

Deletions of the SHOX gene (Xp22-Yp11.3) are associated with Leri–Weill dyschondrosteosys (LWD) and idiopathic short stature. It has been estimated that SHOX deletions occur in 1,000–2,000 individuals in the total population, suggesting that this alteration should be investigated in all cases with unexplained short stature. SHOX deletions are currently investigated using fluorescence in situ hybridization (FISH) or molecular analysis of intragenic CA repeats. However, both techniques show some limitations. In the present study, the use of the multiple ligation probe amplification (MLPA) assay for the identification and characterization of SHOX deletions in 15 LWD patients, 3 of which carriers of chromosome abnormalities involving the SHOX gene, is reported. MLPA analysis demonstrated the heterozygous deletion of SHOX in seven patients (46.6%), disclosing the presence of two different proximal breakpoints. In patients with abnormal karyotype, MLPA analysis was able to identify the chromosomal rearrangement, showing, in addition to the SHOX deletions, the gain or loss of other genes mapped on the X and Y chromosomes. Since MLPA analysis can be carried out on a simple buccal swab, avoiding invasive peripheral blood collection, this technique represents a fast, simple and high throughput approach in the screening of SHOX deletions, able to provide more information as compared to FISH and microsatellite analysis. [ABSTRACT FROM AUTHOR]

Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas. [ABSTRACT FROM AUTHOR]

Genetic testing of the cystic fibrosis transmembrane conductance (CFTR) gene is currently performed in couples undergoing assisted reproduction techniques (ART), because of the high prevalence of healthy carriers in the population and the pathogenic relationship with congenital bilateral absence of vas deferens (CBAVD). However, discordant data have been reported concerning the usefulness of this genetic test in couples with no family history of cystic fibrosis (CF). In this study, we report the results of CFTR molecular screening in 1195 couples entering ART. Genetic testing was initially carried out in a single partner of each couple. CFTR mutations were detected in 55 subjects (4.6%), a percentage that overlaps with the one reported in the general population. However, significantly higher frequencies of were found in CBAVD individuals (37.5%) and in males with nonobstructive azoospermia (6.6%). The 5T allele was found in 78 patients (6.5%). This figure was again significantly different in males with nonobstructive-azoospermia (9.9%) and in those with CBAVD (100%). All together, 139 subjects (11.6%) had either a CFTR mutation or the 5T allele. Subsequent molecular analysis of their partners disclosed a CFTR mutation or 5T allele in nine cases (6.5%). However, none of these couples had CFTR alterations in both members, a CFTR mutation being invariably present in one partner and the 5T allele in the other. In order to improve genetic counselling of these couples, the TG-M470V-5T association was analyzed, and a statistically significant relationship between 12TG-V470 and CBAVD was detected.European Journal of Human Genetics (2005) 13, 959–964. doi:10.1038/sj.ejhg.5201437; published online 4 May 2005 [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused in the majority of cases by deletions of the DMD gene and are readily detectable in affected males by multiplex polymerase chain reaction (PCR). However, different approaches must be used for the identification of female carriers, in which deletions are not detectable by PCR, because of the presence of a normal X chromosome. In this study, we used the multiple ligation probe amplification (MLPA) tool for the identification of female carriers of DMD deletions or duplications in 12 families with a single affected male, 10 of which were previously diagnosed as carriers of a DMD rearrangement, and the remaining two as having an unknown disease-causing mutation. In all the investigated affected males, MLPA analysis confirmed the presence of a DMD rearrangement, and in six of them allowed the refinement of the breakpoints. In 12 female relatives of the affected patients, MLPA analysis showed a DMD deletion or duplication, confirming their carrier status. Two of these were the mother and the sister of a patient whose disease-causing mutation was not known. MLPA analysis thus proved to be an useful tool for the analysis of both affected males and females carriers of DMD rearrangements in cases in which the disease-causing mutation in the affected male was not known, providing useful information for the genetic counselling of the family. [ABSTRACT FROM AUTHOR]

Abstract: The male-specific region (MSY) of the Y chromosome contains genes involved mainly in male sex determination and in spermatogenesis. The majority of genes involved in male fertility are localized in multiple copies in the long arm of the Y chromosome, within specific regions defined as “ampliconic regions.” It has been suggested that these genes derived from X-linked or autosomal ancestors during evolution, providing a benefit for male fertility when transposed onto the Y chromosome. So far, the autosomal origin has been demonstrated only for two MSY genes, DAZ and CDY. In the present study we report on the identification within chromosome 8q11.2 of a region homologous to the g amplicon, containing the VCY2 (approved gene symbol BPY2), TTTY4, and TTTY17 genes. A search for ancestor genes within the 8q11.2 region allowed us to identify a gene named BEYLA and to characterize the genomic organization and the expression patterns of this gene. [Copyright &y& Elsevier]

Objective: To evaluate the accuracy of a new subcutaneous glucose sensor (Glucoday; A. Menarini Diagnostics) compared with venous blood glucose measurement in type 1 and type 2 diabetic patients.Research Design: A multicenter study was performed in 70 diabetic patients. A microdialysis fiber was inserted subcutaneously into the periumbelical region and perfused with a buffer solution. Glucose concentrations in the dialysate were then measured every 3 min by the glucose sensor over a 24-h period, during which nine venous blood samples were also collected throughout the day.Results: Both the insertion of the fiber and the wearing of the device were well tolerated by the patients. Subcutaneous glucose levels were well correlated with venous glucose measurements (r = 0.9, P < 0.001) over a wide range (40-400 mg/dl) for up to 24 h, with a single-point calibration. An analysis of 381 data pairs showed a linear relationship between the GlucoDay and serial venous blood glucose levels, and 97% of the data fell in the A and B regions of the error grid analysis. Percentage bias between the GlucoDay and the blood venous levels was -2.0% in the hypoglycemic range (<70 mg/dl), 6.9% in the euglycemic range (70-180 mg/dl), and 11.2% in the hyperglycemic range (>180 mg/dl).Conclusions: The GlucoDay system demonstrated high reliability and reported values that closely agreed with venous blood glucose measurements. The system was well tolerated and thus constitutes a relatively easy method to monitor glucose excursions in diabetic patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic started in China in early December 2019, and quickly spread around the world. The epidemic gradually started in Italy at the end of February 2020, and by May 31, 2020, 232,664 cases and 33,340 deaths were confirmed. As a result of this pandemic, the Italian Ministerial Decree issued on March 11, 2020, enforced lockdown; therefore, many social, recreational, and cultural centers remained closed for months. In Apulia (southern Italy), all non-urgent hospital activities were suspended, and some wards were closed, with a consequent reduction in the use of the water network and the formation of stagnant water. This situation could enhance the risk of exposure of people to waterborne diseases, including legionellosis. The purpose of this study was to monitor the microbiological quality of the water network (coliforms, E. coli , Enterococci, P. aeruginosa, and Legionella) in three wards (A, B and C) of a large COVID-19 regional hospital, closed for three months due to the COVID-19 emergency. Our study revealed that all three wards' water network showed higher contamination by Legionella pneumophila sg 1 and sg 6 at T1 (after lockdown) compared to the period before the lockdown (T0). In particular, ward A at T1 showed a median value = 5600 CFU/L (range 0–91,000 CFU/L) vs T0, median value = 75 CFU/L (range 0–5000 CFU/L) (p-value = 0.014); ward B at T1 showed a median value = 200 CFU/L (range 0–4200 CFU/L) vs T0, median value = 0 CFU/L (range 0–300 CFU/L) (p-value = 0.016) and ward C at T1 showed a median value = 175 CFU/L (range 0–22,000 CFU/L) vs T0, median value = 0 CFU/L (range 0–340 CFU/L) (p-value < 0.001). In addition, a statistically significant difference was detected in ward B between the number of positive water samples at T0 vs T1 for L. pneumophila sg 1 and sg 6 (24% vs 80% p-value < 0.001) and for coliforms (0% vs 64% p-value < 0.001). Moreover, a median value of coliform load resulted 3 CFU/100 ml (range 0–14 CFU/100 ml) at T1, showing a statistically significant increase versus T0 (0 CFU/100 ml) (p-value < 0.001). Our results highlight the need to implement a water safety plan that includes staff training and a more rigorous environmental microbiological surveillance in all hospitals before occupying a closed ward for a longer than one week, according to national and international guidelines. • Microbiological quality of the water network in a COVID-19 hospital was monitored. • The water network showed high contamination by L. pneumophila. • Coliforms and P.aeruginosa were detected in temporarily closed units. [ABSTRACT FROM AUTHOR]

Composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) is rare and not fully characterized from a genetic and clinicopathological point of view. We report a composite lymphoma (CL) in which a G1-2 FL was associated with an in situ mantle cell neoplasia (ISMCN) and a mantle zone growth pattern (MZGP) MCL, followed-up for six years after the first diagnosis, until the exitus of the patient. We performed a comprehensive immunohistochemical study and a detailed cytogenetic analysis, including conventional karyotyping, SKY FISH, FISH on metaphases and interphasic separated nuclei, and FISH on histological sections. The study was completed by the review of the 13 published composite FL and MCL. Our results show that this entity generally behaves like an indolent lymphoma, with the outcome of patients driven by the progression of the FL component. The MCL component generally does not evolve in an aggressive disease. Indeed, half of the cases present exclusively ISMCN. In our case, mantle cell neoplasia at diagnosis was represented by ISMCN and MZGP MCL and it was characterized by a simple karyotype, with t(11;14) as the sole cytogenetic abnormality. This cytogenetic aspect well correlates with the indolent behavior of the mantle cell component. Conversely, the complex karyotype of the FL component was associated with disseminated disease that influenced patient's outcome. Finally, we suggest that not only ISMCN, but also isolated MZGP MCL, may be considered as lesions with low potential of transformation in an aggressive MCL. [ABSTRACT FROM AUTHOR]

The C677T polymorphism of the MTHFR gene has been associated to maternal risk of Down syndrome, due to the detection of an higher prevalence of the T allele among mothers of children with trisomy 21, compared to control mothers. In order to confirm this association, we studied the presence of the C677T in 64 mothers of Down syndrome children and 112 controls from central Italy. An higher incidence of the mutant T allele in controls (48.2%) than in Down syndrome children mothers (44%) was detected. These results do not support the presence of an increased risk of Down syndrome in mothers carriers of the T allele in the Italian population. [ABSTRACT FROM AUTHOR]

A 40-year-old woman presented in her second pregnancy, naturally conceived. Maternal serum screening and ultrasound examination raised concerns regarding aneuploidy. After genetic counselling an amniocentesis was performed, showing a 69,XXX karyotype. Here we report a case of digynic triploidy, which resulted from fertilization of a diploid ovum by a single sperm. [ABSTRACT FROM AUTHOR]

The article presents information on a phase 1 pilot clinical trial of microencapsulated pancreatic islet allograft into 10 nonimmunsuppressed patients with type 1 diabetes, under permission and surveillance by the Italian Ministry of Health. Research design and methods are given. Results and conclusions are discussed.