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Objective: The characteristics and outcomes of patients undergoing vascular surgery hospitalised and managed in Lombardy are described with a comparison of patients tested positive for COVID-19 (CV19-pos) vs. those tested negative (CV19-neg). Methods: This was a multicentre, retrospective, observational cohort study which involved all vascular surgery services in Lombardy, Northern Italy. Data were retrospectively merged into a combined dataset covering the nine weeks of the Italian COVID-19 pandemic phase 1 (8 March 2020 to 3 May 2020). The primary outcome was freedom from in hospital death, secondary outcomes were re-thrombosis rate after peripheral revascularisation, and freedom from post-operative complication. Results: Among 674 patients managed during the outbreak, 659 (97.8%) were included in the final analysis: 121 (18.4%) were CV19-pos. CV19-pos status was associated with a higher rate of complications (OR 4.5; p < .001, 95% CI 2.64 – 7.84), and a higher rate of re-thrombosis after peripheral arterial revascularisation (OR 2.2; p = .004, 95% CI 1.29 – 3.88). In hospital mortality was higher in CV19-pos patients (24.8% vs. 5.6%; OR 5.4, p < .001;95% CI 2.86 – 8.92). Binary logistic regression analysis identified CV19-pos status (OR 7.6; p < .001, 95% CI 3.75 – 15.28) and age > 80 years (OR 3.2; p = .001, 95% CI 1.61 – 6.57) to be predictors of in hospital death. Conclusion: In this experience of the vascular surgery group of Lombardy, COVID-19 infection was a marker of poor outcomes in terms of mortality and post-operative complications for patients undergoing vascular surgery treatments.

Background Long-standing overt ventriculomegaly in adults is a chronic form of hydrocephalus without a clear pathophysiological description and a consensus about the treatment. We present the results of endoscopic third ventriculostomy (ETV) in a consecutive series with a mean follow-up of 79 ± 23 months, highlighting how the preoperative lumbar infusion test could facilitate understanding the pathophysiology of the disease. Methods We retrospectively collected data regarding clinical assessment, neuroradiological findings, and preoperative lumbar infusion tests in 22 symptomatic patients. Results In the majority of cases, patients reported imbalance and gait disorders, and 8 subjects had headaches. The preoperative lumbar infusion test demonstrated a mean opening pressure of 13.95 ± 2.88 mm Hg, with plateau values ranging from 22 to 39 mm Hg. The resistance to outflow was 11.21 ± 2.00 mm Hg/mL/min. After the procedure, all patients reported improvement or halted progression in their presenting symptoms, whereas no significant reduction was demonstrated in Evans' index. One subject underwent a second ETV procedure after more than 2 years because of the failure of the endoscopic approach. Conclusions A progressive exhaustion of brain compliance plays an important role in explaining the dichotomy between severe ventriculomegaly and mild clinical symptoms in patients with long-standing overt ventriculomegaly in adults. The role of the aqueductal stenosis as a diagnostic criterion might be reconsidered. The preoperative infusion test data support this observation. Preoperative assessment should include not only clinical and neuroradiological evaluation but also the study of cerebrospinal fluid dynamics. ETV should be considered the treatment of choice because of its safety and efficacy. Long-term follow-up is mandatory.

Background: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. Methods: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. Results: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values5) in K-OLPs and nK-OLPs, respectively. The PSQI’s validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. Conclusions: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Significance Cells reside in 3D microenvironments in living tissues; consequently, 3D cultures gained great interest because they better mimic the natural conditions of cells. Self-assembling peptides (SAPs) are synthetic bioabsorbable biomaterials that can provide customized 3D microenvironments regulating cell functionalities and tissue repair. Here we introduce a SAP-hydrogel designed to support human neural stem cell (hNSC) differentiation in 3D serum-free conditions, generating mature and active human neurons in vitro. We also demonstrate its functional neurorigenerative potential in rat spinal cord injuries, peaking when seeded with hNSCs progeny predifferentiated in vitro for 6 weeks. Despite these promising results, this approach should be confirmed in the future with medium-size animal models and with additional and refined behavioral tests before entering a clinical trial., Three-dimensional cell cultures are leading the way to the fabrication of tissue-like constructs useful to developmental biology and pharmaceutical screenings. However, their reproducibility and translational potential have been limited by biomaterial and culture media compositions, as well as cellular sources. We developed a construct comprising synthetic multifunctionalized hydrogels, serum-free media, and densely seeded good manufacturing practice protocol-grade human neural stem cells (hNSC). We tracked hNSC proliferation, differentiation, and maturation into GABAergic, glutamatergic, and cholinergic neurons, showing entangled electrically active neural networks. The neuroregenerative potential of the “engineered tissue” was assessed in spinal cord injuries, where hNSC-derived progenitors and predifferentiated hNSC progeny, embedded in multifunctionalized hydrogels, were implanted. All implants decreased astrogliosis and lowered the immune response, but scaffolds with predifferentiated hNSCs showed higher percentages of neuronal markers, better hNSC engraftment, and improved behavioral recovery. Our hNSC-construct enables the formation of 3D functional neuronal networks in vitro, allowing novel strategies for hNSC therapies in vivo.

Background: Migraine is a major cause of disability, which affects many areas of life, including productivity at work. Measuring absenteeism and presenteeism resulting from migraine with the use of appropriate tools is essential for better understanding the impact of this disease. Objective: The aim of the present study was to assess the work impact of migraine using the Brazilian Portuguese version of Work Productivity and Activity Impairment (WPAI) questionnaire. Methods: This survey was carried out with the aid of a smartphone app (Dr Cefaleia for Doctors) containing the questionnaires: ID-Migraine, Headache Impact Test (HIT-6), and WPAI. The data were collected during a headache awareness event. Correlations were assessed between migraine impact (HIT-6) with WPAI parameters: a) work time missed (absenteeism), b) impairment at work (presenteeism), c) overall work productivity loss (absenteeism+presenteeism), and d) activity impairment outside work. Results: Overall, 305 subjects with headache were interviewed and 167 were classified as having migraine. No significant differences in migraine impact according to sex (p=0.8) and modality of work were registered (p=0.8). Females had significantly higher absenteeism score (p

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann–Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13–0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

BACKGROUND: To highlight clinical practice among referral (Hub, HH) or satellite (Spoke, SH) hospitals Vascular Surgery Units (VSUs) in Lombardy, during the COVID-19 pandemic "phase 1" period (March 8 - May 3, 2020). METHODS: The Vascular Surgery Group of Regione Lombardia Register, a real-word, multicenter, retrospective register was interrogated. All patients admitted with vascular disease were included. Patients' data on demographics, COVID-19 positivity, comorbidities and outcomes were extrapolated. Two cohorts were obtained: patients admitted to HH or SH. Primary endpoint was 30- day mortality rate. Secondary outcomes were 30-day complications and amputation (in case of peripheral artery disease [PAD]) rates. Univariate and multivariate analysis were used to compare HH and SH groups and predictors of poor outcomes. RESULTS: During the study period, 659 vascular patients in 4 HH and 27 SH were analyzed. Among these, 321 (48.7%) were admitted to a HH. No difference in COVID-19 positive patients was described (21.7% in HH vs 15.9% in SH; p=.058). After 30 days from intervention, HH and SH experienced similar mortality and no-intervention-related complication rate (12.1% vs 10.0%; p=.427 and 10.3% vs 8.3%; p=.377, respectively). Conversely, in HH postoperative complications were higher (23.4% vs 16.9%, p=.038) and amputations in patients treated for PAD were lower (10.8% vs 26.8%; p

Background: A new propylene glycol (PG)-free 5% minoxidil (Mnx) lotion has been recently commercialized. Aim of this study was to evaluate the acceptability/tolerability and clinical efficacy of 3-month application of this new PG-free Mnx lotion and the penetration of the active compound in a reconstructed human epidermis (RHE/Episkin) model in comparison with a PG Mnx 5% lotion. Methods: Thirty subjects of both sex with a diagnosis of AGA were enrolled in the trial. Cosmetic acceptability and clinical efficacy were evaluated after 4, 8 and 12 weeks of treatment. Global tolerability was evaluated at week 12. Cosmetic acceptability evaluation was assessed using a 7-item questionnaire using a 10-point scale score. Global Tolerability was evaluated with a 4-grade scale. Clinical efficacy was evaluated with a 5-grade scale. Skin absorption of PG-free Mnx was evaluated and compared with a PG Mnx solution using the Episkin model. Results: All subjects concluded the study. The 7-item questionnaire mean values were always

CHRNA7, encoding the neuronal alpha7 nicotinic acetylcholine receptor (a7nAChR), is highly expressed in the brain, particularly in the hippocampus. It is situated in the 15q13.3 chromosome region, frequently associated with a Copy Number Variation (CNV), which causes its duplication or deletion. The clinical significance of CHRNA7 duplications is unknown so far, but there are several research data suggesting that they may be pathogenic, with reduced penetrance. We have produced an iPS cell line from a single healthy donor's fibroblasts carrying a 15q13.3 CNV, including CHRNA7 in order to study the exact role of this CNV during the neurodevelopment.

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by developmental delay, behavioural problems and circadian rhythm dysregulation. About 90% of SMS cases are due to a 17p11.2 deletion containing retinoic acid induced1 (RAI1) gene, 10% are due to heterozygous mutations affecting RAI1 coding region. Little is known about RAI1 role.

High sodium and low potassium intakes are associated with increased levels of blood pressure and risk of cardiovascular diseases. Assessment of habitual dietary habits are helpful to evaluate their intake and adherence to healthy dietary recommendations. In this study, we determined sodium and potassium food-specific content and intake in a Northern Italy community, focusing on the role and contribution of adherence to Mediterranean diet patterns. We collected a total of 908 food samples and measured sodium and potassium content using inductively coupled plasma mass spectrometry. Using a validated semi-quantitative food frequency questionnaire, we assessed habitual dietary intake of 719 adult individuals of the Emilia-Romagna region. We then estimated sodium and potassium daily intake for each food based on their relative contribution to the overall diet, and their link to Mediterranean diet patterns. The estimated mean sodium intake was 2.15 g/day, while potassium mean intake was 3.37 g/day. The foods contributing most to sodium intake were cereals (33.2%), meat products (24.5%, especially processed meat), and dairy products (13.6%), and for potassium they were meat (17.1%, especially red and white meat), fresh fruits (15.7%), and vegetables (15.1%). Adherence to a Mediterranean diet had little influence on sodium intake, whereas potassium intake was greatly increased in subjects with higher scores, resulting in a lower sodium/potassium ratio. Although we may have underestimated dietary sodium intake by not including discretionary salt use and there may be some degree of exposure misclassification as a result of changes in food sodium content and dietary habits over time, our study provides an overview of the contribution of a wide range of foods to the sodium and potassium intake in a Northern Italy community and of the impact of a Mediterranean diet on intake. The mean sodium intake was above the dietary recommendations for adults of 1.5–2 g/day, whilst potassium intake was only slightly lower than the recommended 3.5 g/day. Our findings suggest that higher adherence to Mediterranean diet patterns has limited effect on restricting sodium intake, but may facilitate a higher potassium intake, thereby aiding the achievement of healthy dietary recommendations.

Summary Background Malnutrition is a common finding in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients, and there is some evidence that malnutrition might negatively affect the transplant outcomes. Method We performed a retrospective study with 148 patients aged 18–75 years, who underwent alloHSCT between 2011 and 2017. Patients were classified according to the body mass index (BMI) and the Subjective Global Assessment (SGA). The SGA was assessed on the day of hospitalization for the transplant, and classifies patients into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). Results The SGA classified 49 (33%) patients as well-nourished, 54 (37%) as moderately malnourished, and 45 (30%) as severely malnourished. SGA-C was also associated with severe acute graft versus host disease (aGVHD) with a cumulative incidence (CI) of 31% vs. a CI of 14% for combined well-nourished or moderately malnourished group (SGA-A or –B, P = 0.017). In multivariate analysis, SGA-C compared to SGA-A or –B, remained as an independent risk factor for aGVHD (hazard ratio - HR 1.68, 95% confidence interval - 95% CI 1.02–2.74), and nonrelapse mortality (NRM - HR 3.63, 95% CI 1.76–7.46), worse progression free survival (HR 2.12, 95% CI 1.25–3.60), and worse overall survival (HR 3.27, 95% CI 1.90–5.64). Conclusion Malnutrition increases the risk of aGVHD and NRM and has a negative impact on survival.

Melanoma is an immunogenic neoplasm infiltrated by T cells, although these adaptive T cells usually fail to eradicate the tumor. Plasmacytoid dendritic cells (PDCs) are potent regulators of the adaptive immune response and can eliminate melanoma cells via TLR-mediated effector functions. The PDC compartment is maintained by progressively restricted bone marrow progenitors. Terminally differentiated PDCs exit the bone marrow into the circulation, then home to lymph nodes and inflamed peripheral tissues. Infiltration by PDCs is documented in various cancers. However, their role within the melanoma immune contexture is not completely known. We found that in locoregional primary cutaneous melanoma (PCM), PDC infiltration was heterogeneous, occurred early, and was recurrently localized at the invasive margin, the site where PDCs interact with CD8+ T cells. A reduced PDC density was coupled with an increased Breslow thickness and somatic mutations at the NRAS p.Q61 codon. Compared with what was seen in PCM, high numbers of PDCs were found in regional lymph nodes, as also identified by in silico analysis. In contrast, in metastatic melanoma patients, PDCs were mostly absent in the tumor tissues and were significantly reduced in the circulation, particularly in the advanced M1c group. Exposure of circulating PDCs to melanoma cell supernatant (SN-mel) depleted of extracellular vesicles resulted in significant PDC death. SN-mel exposure also resulted in a defect of PDC differentiation from CD34+ progenitors. These findings indicate that soluble components released by melanoma cells support the collapse of the PDC compartment, with clinical implications for refining TLR agonist–based trials.

This study compared children's and mothers' digital media use and mothers' mental health in two samples: one accessed before (Group 1; N = 257; M = 33.18 years; SD = 4.79) and the other accessed during (Group 2; N = 256; M = 33.51 years; SD = 4.96) the COVID-19 pandemic in Brazil. Mothers of children up to 3 years old (Group 1: M = 17.95 months, SD = 9.85; Group 2: M = 16.48 months, SD = 10.15) answered an online survey. Bivariate analysis, factorial ANOVA tests, and multiple linear regression were performed. Results suggest that mothers' and children's media use duration was higher during the pandemic only among children over 12 months. Mothers' media use duration (β = .18) and mothers' intention to offer media (β = .23) contributed to the explanation of children's media use duration (F(4, 474) = 16.81; p .001; REste estudio comparó el uso de los medios digitales por parte de los niños y las madres con la salud mental de las madres en dos grupos muestra: uno al cual se tuvo acceso antes (Grupo 1: N = 257; M = 33.18 años; SD = 4.79) y el otro al cual se tuvo acceso durante (Grupo 2; N = 256; M = 33.51 años; SD = 4.96) la pandemia del COVID-19 en Brasil. Las madres de niños de hasta tres años (Grupo 1: M = 17.95 meses, SD = 9.85; Grupo 2: M = 16.48 meses, SD = 10.15) respondieron una encuesta electrónica. Los análisis bivariados los exámenes factoriales ANOVA, así como múltiples regresiones lineales se llevaron a cabo. Los resultados indican que la duración de uso de los medios por parte de las madres y los niños fue más alta durante la pandemia sólo entre niños de más de 12 meses. La duración de uso de los medios por parte de las madres (β = 0.18) y la intención de las madres de ofrecer los medios (β = 0.23) contribuyeron a explicar la duración de uso de los medios por parte de los niños (F(4,474) = 16,81; p.001; RCette étude a comparé l'utilisation des médias numériques des enfants et des mères et la santé mentale des mères chez deux échantillons: l'un accédé avant la pandémie du Covid-19 (Groupe 1; N = 257; M = 33,18 ans; SD = 4,79) et l'autre accédé durant la pandémie du covid-19 (Groupe 2; N = 256; M = 33,51 ans; SD = 4,96) au Brésil. Les mères d'enfants jusqu’à l’âge de trois ans (Groupe 1: M = 17,95 mois, SD = 9,85; Groupe 2: M = 16,48 mois, SD = 10,15) ont répondu à un questionnaire en ligne. Une analyse à deux variables, des tests ANOVA factoriels, et une régression linéaire multiple ont été faits. Les résultats suggèrent que la durée de l'utilisation média des mères et des enfants a été plus élevée durant la pandémie uniquement pour les enfants de plus de 12 mois. La durée de l'utilisation média des mères (β = 0,18) et l'intention des mères à offrir le média (β = 0,23) a contribué à l'explication de la durée de l'utilisation média des enfants (F(4, 474) = 16,81; p,001; RDie Nutzung digitaler Medien durch Säuglinge und Kleinkinder und die psychische Gesundheit der Mütter: Eine vergleichende Studie vor und während der COVID-19-Pandemie In dieser Studie wurden die Nutzung digitaler Medien durch Kinder und Mütter und die mütterliche psychische Gesundheit in zwei Stichproben verglichen: eine wurde vor (Gruppe 1; N = 257; M = 33,18 Jahre; SD = 4,79) und die andere während (Gruppe 2; N = 256; M = 33,51 Jahre; SD = 4,96) der COVID-19-Pandemie in Brasilien erhoben. Mütter von Kindern im Alter von bis zu drei Jahren (Gruppe 1: M = 17,95 Monate, SD = 9,85; Gruppe 2: M = 16,48 Monate, SD = 10,15) bearbeiteten eine Online-Umfrage. Es wurden bivariate Analysen, faktorielle ANOVA-Tests und multiple lineare Regressionen durchgeführt. Die Ergebnisse deuten darauf hin, dass die Dauer der Mediennutzung von Müttern und Kindern während der Pandemie nur bei Kindern über 12 Monaten höher war. Die Mediennutzungsdauer der Mütter (β = 0,18) und die Absicht der Mütter, Medien anzubieten (β = 0,23), trugen zur Erklärung der Mediennutzungsdauer der Kinder bei (F(4, 474) = 16,81; p.001; R乳児と幼児のデジタルメディアの使用と母親の精神保健:COVID-19パンデミック 以前とパンデミック中との比較研究 この研究では、子どもと母親のデジタルメディアの使用と母親の精神保健を2つのサンプルで比較した。サンプルは、いずれもブラジルで、一つはcovid-19パンデミック以前のアクセスのグループ1;N = 257;M = 33.18歳、SD = 4.79、もう一方はパンデミック中のアクセスのグループ 2;N = 256;M = 33.51歳、SD = 4.96であった。3歳以下の子どもの母親(グループ1:M = 17.95ヶ月、SD = 9.85;グループ2:M = 16.48ヶ月、SD = 10.15)がオンライン調査に回答した。二変量解析、要因分散分析テスト、および多重線形回帰を行った。その結果、パンデミックの間に母親と子どものメディアの使用利用時間が長くなったのは、生後12ヶ月以上の子どもでのみであると示唆された。母親のメディア使用時間(β = 0.18)と母親のメディアを提供する意図(β = 0.23)は、子どものメディア使用時間(F(4,474) = 16.81;p.001;R这项研究比较了两个样本中儿童和母亲使用数字媒体的情况以及母亲的心理健康状况:一个 (第一组; N = 257; M = 33.18岁; SD = 4.79) 是在巴西COVID-19大流行之前获得的, 另一个 (第二组; N = 256; M = 33.51岁; SD = 4.96) 是在COVID-19大流行期间获得的。三岁以下儿童的母亲 (第一组:M = 17.95个月, SD = 9.85;第二组:M = 16.48个月, SD = 10.15) 回答了一项在线调查。对数据进行了双变量分析、因子方差分析和多元线性回归分析。结果表明, 仅在12个月以上的儿童中, 母亲和儿童在大流行期间使用媒体的时间更长。母亲的媒体使用时长 (β = 0.18) , 以及母亲提供媒体的意图 (β = 0.23) 有助于解释儿童的媒体使用时长 (F(4, 474) = 16.81; p.001; Rاستخدام الأطفال والرضع للوسائط الالكترونية والصحة النفسية للأمهات: دراسة مقارنة قبل وأثناء وباء كوفيد-19 قارنت هذه الدراسة استخدام الوسائط الرقمية للأطفال والأمهات والصحة النفسية للأمهات في عينتين من البرازيل: مجموعة تم الوصول إليها قبل الجائحة (مجموعة 1 - العدد 257 ومتوسط عمر 33.18 بانحراف معياري 4.79) والمجموعة الثانية خلال الجائحة (المجموعة 2 ؛ العدد 256 ومتوسط عمر 33.51 بانحراف معياري 4.96(. أجابت أمهات الأطفال حتى سن ثلاث سنوات من المجموعتين (مجموعة 1: متوسط عمر 17.95 - مجموعة 2: متوسط عمر 16.48) على استبيان عبر الإنترنت. وتم إجراء تحليل ثنائي المتغير واختبارات التباين العاملي والانحدار الخطي المتعدد. تشير النتائج إلى أن مدة استخدام الأمهات والأطفال لوسائل الإعلام كانت أعلى أثناء الجائحة فقط بين الأطفال فوق 12 شهرًا. ساهمت مدة استخدام الوسائط للأمهات(β = 0.18) ونية الأمهات في تقديم الوسائط(β = 0.23) في تفسير مدة استخدام الأطفال لهذه الوسائط (R

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

Objectives: To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain. Methods: In this case–control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann–Whitney U test and hierarchical multiple linear regression analysis, were used. Results: Poor sleep quality (PSQI≥5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p&nbsp

Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.

The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine 2019;8:887–897

It is believed that the approximate estimation of large sets and the exact quantification of small sets (subitizing) are supported by two different systems, the Approximate Number System (ANS) and Object Tracking System (OTS), respectively. It is a current matter of debate whether they are both impaired in developmental dyscalculia (DD), a specific learning disability in symbolic number processing and calculation. Here we tackled this question by asking 32 DD children and 32 controls to perform a series of tasks on visually presented sets, including exact enumeration of small sets as well as comparison of large, uncountable sets. In children with DD, we found poor sensitivity in processing large numerosities, but we failed to find impairments in the exact enumeration of sets within the subitizing range. We also observed deficits in visual short-term memory skills in children with dyscalculia that, however, did not account for their low ANS acuity. Taken together, these results point to a dissociation between quantification skills in dyscalculia, they highlight a link between DD and low ANS acuity and provide support for the notion that DD is a multifaceted disability that covers multiple cognitive skills.

Different approaches with different clinical outcomes have been found in treating capillary hemangioma (CH), venous lake (VL), or venous malformations (VM) of the lips. This retrospective study aims to assess scar quality, recurrence rate, and patient satisfaction after different surgeries with different laser wavelengths. A total of 143 patients with CH or VM were included. Nd:YAG laser was used for 47 patients, diode 980 nm laser was used for 32 patients (treatments by transmucosal photo-thermo-coagulation), Er,Cr:YSSG laser was used for 12 patients (treatments by excision), and CO2 laser was used for 52 patients (treatments by photo-vaporization). The Manchester scar scale was used by practitioners to assess the scar quality. The recurrence rate and patients&rsquo, satisfaction were noted at different follow-ups during 12 months. Our retrospective study showed that laser-assisted aesthetic treatment of vascular lesions (CH, VL, and VM) of the lips can be considered effective regardless of the wavelength used (Er,Cr:YSGG, CO2, Nd:YAG, and diode 980 nm) or the treatment procedure (transmucosal photo-thermo-coagulation, photo-vaporization, and surgical excision). There was no significant difference in patient and practitioner satisfaction with aesthetic outcome at 6 months follow-up. Furthermore, the treatments of lip vascular lesions performed using Er,Cr:YSGG and CO2 lasers did not show any recurrence during the 12 months of follow-up, while recurrence rates of 11% &plusmn, 1.4% and 8% &plusmn, 0.9% were seen in the diode and Nd:YAG groups, respectively.

Background Colorectal cancer (CRC) harboring BRAFV600E mutation exhibits low response to conventional therapy and poorest prognosis. Due to the emerging correlation between gut microbiota and CRC carcinogenesis, we investigated in serrated BRAFV600E cases the existence of a peculiar fecal microbial fingerprint and specific bacterial markers, which might represent a tool for the development of more effective clinical strategies. Methods By injecting human CRC stem-like cells isolated from BRAFV600E patients in immunocompromised mice, we described a new xenogeneic model of this subtype of CRC. By performing bacterial 16S rRNA sequencing, the fecal microbiota profile was then investigated either in CRC-carrying mice or in a cohort of human CRC subjects. The microbial communities’ functional profile was also predicted. Data were compared with Mann-Whitney U, Welch’s t-test for unequal variances and Kruskal-Wallis test with Benjamini–Hochberg false discovery rate (FDR) correction, extracted as potential BRAF class biomarkers and selected as model features. The obtained mean test prediction scores were subjected to Receiver Operating characteristic (ROC) analysis. To discriminate the BRAF status, a Random Forest classifier (RF) was employed. Results A specific microbial signature distinctive for BRAF status emerged, being the BRAF-mutated cases closer to healthy controls than BRAF wild-type counterpart. In agreement, a considerable score of correlation was also pointed out between bacteria abundance from BRAF-mutated cases and the level of markers distinctive of BRAFV600E pathway, including those involved in inflammation, innate immune response and epithelial-mesenchymal transition. We provide evidence that two candidate bacterial markers, Prevotella enoeca and Ruthenibacterium lactatiformans, more abundant in BRAFV600E and BRAF wild-type subjects respectively, emerged as single factors with the best performance in distinguishing BRAF status (AUROC = 0.72 and 0.74, respectively, 95% confidence interval). Furthermore, the combination of the 10 differentially represented microorganisms between the two groups improved performance in discriminating serrated CRC driven by BRAF mutation from BRAF wild-type CRC cases (AUROC = 0.85, 95% confidence interval, 0.69–1.01). Conclusion Overall, our results suggest that BRAFV600E mutation itself drives a distinctive gut microbiota signature and provide predictive CRC-associated bacterial biomarkers able to discriminate BRAF status in CRC patients and, thus, useful to devise non-invasive patient-selective diagnostic strategies and patient-tailored optimized therapies. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-020-01801-w.

Objective: To estimate the incidence of congenital syphilis and temporal trends of the reported cases of the disease in the state of Santa Catarina between 2007 and 2017. Methods: Observational study with retrospective cohort design, with secondary data from the Injury of Notification Information System (SINAN). Linear trend test and geoprocessing were performed to verify the behavior of the cases in the period. Results: There were 2,898 reported cases of congenital syphilis in the period, with an average of 2.9 per 1,000 live births in the period. There was an exponential increase of 0.9 percentage points per year, considered statistically significant (p

Objective The bell-bottom technique is a widely used technique to treat aortoiliac aneurysms with preservation of the hypogastric arteries. The published data are scarce with conflicting results regarding the evolution. The aim of this study was to compare the outcomes of patients submitted to endovascular abdominal aortic aneurysm repair with standard technique (S-EVAR) versus bell-bottom technique. Methods This retrospective cohort study compared the outcomes of standard endovascular aneurysm repair (Results Two hundred and three patients were treated with bell-bottom technique ( n = 84, mean age 72.2 ± 8.9) and S-EVAR ( n = 119, mean age 72.7 ± 8.4). The overall 30-day mortality was 1.9%, with no significant difference between groups. There was higher prevalence of coronary heart disease in the bell-bottom technique group compared to the S-EVAR group (41.6% vs. 18.4%, p Conclusions This study shows lower freedom from type IB endoleak in the bell-bottom group compared to the standard repair group. There is no significant difference in reoperation rate and 30-day mortality.

Background and aim Lead is a highly toxic heavy metal released into the environment after natural and anthropogenic activities. Excluding populations in occupations where there is possible lead contamination, food is the major source of human exposure. In this study, we determined lead contamination in food and beverages consumed in a Northern Italy community and performed a health risk assessment. Methods: We collected a total of 908 food samples and measured lead levels using inductively coupled plasma mass spectrometry. Using a validated food frequency questionnaire, we assessed the dietary habits and estimated daily lead dietary intakes in a sample of 719 adult individuals. We performed risk assessment using a benchmark dose and margin of exposure approach, based on exposure levels for both adverse effect of systolic blood pressure and chronic kidney disease. Results: Foods with the highest lead levels include non-chocolate confectionery (48.7 µg/kg), leafy (39.0 µg/kg) and other vegetables (42.2 µg/kg), and crustaceans and molluscs (39.0 µg/kg). The estimated mean lead intake was 0.155 µg/kg bw-day in all subjects, with little lower intakes in men (0.151 µg/kg bw-day) compared to women (0.157 µg/kg bw-day). Top food contributors were vegetables, cereals, and beverages, particularly wine. In relation to risk assessment, the estimated dietary intake was lower than levels associated with cardiovascular risk and nephrotoxicity. Conclusions: Our study provides an updated assessment of lead food contamination and dietary exposure in a Northern Italian community. The margin of exposure risk assessment approach suggests that risk of detrimental effects due to dietary lead intake is low in the investigated population. Nonetheless, these exposure levels for adverse effects are not reference health standards, and no safety threshold value can be established for lead. As a consequence, other and more subtle adverse effects may still occur in vulnerable and occupationally exposed individuals, particularly in relation to the nervous system.

INTRODUCTION Different osteotomy techniques have been proposed in order to improve postoperative course of impacted third molar extraction. The aim is to evaluate the possible advantages achieved with erbium yttrium-aluminum-garnet (Er:YAG) laser osteotomy compared with traditional burs. MATERIALS AND METHODS Seventy-six extractions were randomly classified into 2 groups according to osteotomy instrument: group 1 (G1)-Er:YAG laser: 35 patients; group 2 (G2)-traditional bur: 41 patients. Intraoperative parameters: total time, stitches number, and patient compliance. Postoperative: pain, health-related quality of life (HR-QoL), need for analgesics, edema, trismus, intra- and extraoral hematoma, and postoperative complications. RESULTS Mean time for G1 resulted 1069.4 seconds; for G2 1913.5 seconds (P

The aim of this study was to examine the impact of contextual factors on relative locomotor and metabolic power distances during professional female soccer matches. Twenty-eight players (forwards, n = 4; midfielders, n = 12; defenders, n = 12) that competed in a 90-min home and away match (regular season only). The generalised estimating equations (GEE) was used to evaluate relative locomotor and metabolic power distances for three contextual factors: location (home vs. away), type of turf (natural vs. artificial), and match outcome (win, loss and draw). No differences were observed for home vs. away matches. Moderate-intensity running (20.0 ± 1.0 m min−1 and 16.4 ± 0.9 m min−1), high-intensity running (8.6 ± 0.4 m min−1 and 7.3 ± 0.4 m min−1) and high-metabolic power (16.3 ± 0.5 m min−1 and 14.4 ± 0.5 m min−1) distances were elevated on artificial turf compared to natural grass, respectively. Relative sprint distance was greater during losses compared with draws (4.3 ± 0.4 m min−1 and 3.4 ± 0.3 m...

Background Cavernous malformations (CMs) are congenital malformations and may be located anywhere in the brain. We present a series of CMs located close to or inside of the motor-sensory cortex or corticospinal tract (CST) with clinical onset due to hemorrhage or mass effect. In such cases, surgery becomes an acceptable option. Objective To evaluate the role of diffusion tensor imaging (DTI), functional-magnetic-resonance imaging (fMRI), intraoperative neurophysiological monitoring, neuronavigation, and brain-mapping and the clinical results of surgical treatment of CMs in this critical location. Methods The study included 54 patients harboring 22 cortical and 32 deep locations. This series was distinct because in group I, where the DTI was not obtained, and in the group II, where this evaluation was performed. Results The postoperative permanent morbidity rate was 4% in the historical group for the deeper CMs, and there was no morbidity in the second group. DTI and fMRI permitted us to estimate the distance between the CMs and both the cortical activation cluster and the pyramidal tract. These data, in addition to intraoperative mapping and monitoring, made it necessary for us to perform a partial resection in 2 cases in the second series. Conclusion CMs are congenital lesions and CST fibers can run directly on their surface. Integration of fMRI and DTI data with intraoperative functional monitoring and direct cortical and subcortical mapping are mandatory to accomplish an optimal resection, tailoring the best surgical approach to the acceptable morbidity. A subtotal resection could be considered an option for deep locations.

// Alessio D’Alessio 1 , Gabriella Proietti 1 , Gina Lama 1 , Filippo Biamonte 1 , Libero Lauriola 2 , Umberto Moscato 3 , Angelo Vescovi 4 , Annunziato Mangiola 5 , Cristiana Angelucci 1 , Gigliola Sica 1 1 Institute of Histology and Embryology, “A. Gemelli” Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy 2 Institute of Pathology, “A. Gemelli” Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy 3 Institute of Public Health, Hygiene Division,“A. Gemelli” Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy 4 IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy 5 Institute of Neurosurgery, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy Correspondence to: Alessio D’Alessio, email: alessio.dalessio@unicatt.it Keywords: angiogenesis, glioblastoma, peritumoral tissue, cancer stem cells, hypoxia Received: April 22, 2016 Accepted: September 25, 2016 Published: October 01, 2016 ABSTRACT The formation of new blood vessels represents a crucial event under both physiological and pathological circumstances. In this study, we evaluated by immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR the expression of HIF1α, HIF2α, VEGF, VEGFR1 and VEGFR2 in surgical glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50 patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro . Immunohistochemistry demonstrated the expression of angiogenesis markers in both GBM and peritumoral tissue. In addition, in vitro tube formation assay indicated that both GCSCs and PCSCs stimulate EC proliferation as well as tube-like vessel formation. An increased migration aptitude was mainly observed when ECs were cultured in the presence of GCSCs rather than in the presence of PCSCs. These findings suggest that relevant neoangiogenetic events may occur in GBM. In particular, VEGF/VEGFR co-expression in PCSCs leads to hypothesize the involvement of an autocrine signaling. Moreover, our results suggest that both GCSCs and PCSCs own the skill of activating the “angiogenic switch” and the capability of modulating EC behavior, indicating that both cell types are either responsive to angiogenic stimuli or able to trigger angiogenic response. Together with our previous findings, this study adds a further piece to the challenging puzzle of the characterization of peritumoral tissue and of the definition of its real role in GBM pathophysiology.

In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples). Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.

Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1-6 ANN NEUROL 2019;85:296-301.

Juvenile Onset Huntington's Disease (JOHD) is a rare variant of HD withage of onset ≤20 years, accounting for 3–10% of all HD patients. The rarity occurrence of JOHD cases, who severely progress towards mental and physical disability with atypical clinical manifestations compared to classical HD, are responsible of general lack of knowledge about this variant. We obtained a fully reprogrammed iPS cell line from fibroblasts of a JOHD patient carrying 65 CAG repeats and age at onset at age 15. At the biopsy time, the patient showed an advanced stage after 10 years of disease.

Background Invasive tests measuring resistance to cerebral spinal fluid (CSF) outflow and the effect of temporary drainage of CSF are used to select candidates affected by idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. Neither test, however, completely excludes patients from treatment. Perfusion and diffusion magnetic resonance imaging (MRI) are non-invasive techniques that might be of value in selecting patients for surgical treatment and understanding brain changes in iNPH patients. The aim of this study was to understand the role of perfusion and diffusion MRI in selecting candidates for shunt surgery and to investigate the relationship between cerebral perfusion and possible microstructural changes in brain tissue before and after invasive tests, and after ventricular-peritoneal (VP) shunt implantation, to better clarify pathophysiological mechanisms underlying iNPH. Methods Twenty-three consecutive patients with probable iNPH were included in this study. Patients underwent a clinical and neuroradiological evaluation before and after invasive tests, and after surgery. Only patients who showed a positive result in at least one of the invasive tests were submitted for VP shunt implantation. Perfusion and diffusion magnetic resonance imaging (MRI) was performed before and after invasive tests and after shunt surgery. Results Thirteen patients underwent surgery and all showed clinical improvement after VP shunt implantation and a significant increase in perfusion in both periventricular white matter (PVWM) and basal ganglia (BG) regions. The 10 patients that did not have surgery showed after invasive tests, a significant reduction in perfusion in both PVWM and BG regions. Comparing the changes in perfusion with those of diffusion in positive patients we found a significant positive correlation in BG and a significant inverse correlation in PVWM area. Conclusions Perfusion MRI is a non-invasive technique that could be useful together with invasive tests in selecting patients for surgical treatment. Furthermore, the relationship between perfusion and diffusion data could better clarify pathophysiological mechanisms underlying iNPH. In PVWM area we suggest that interstitial edema could reduce microvascular blood flow and interfere with the blood supply to these regions. In BG regions we suggest that a chronic hypoxic insult caused by blood hypo-perfusion produces a chronic cytotoxic edema. Both in PVWM and in BG regions, pathophysiological mechanisms could be modified after VP-shunt implantation.

Background: Oral leukoplakia (OL) is the most typical potentially malignant disorder of the oral mucosa. We aimed to evaluate the clinical outcome of oral leukoplakia treated with several types of lasers and with the use of quantic molecular resonance (QMR) lancet, in terms of recurrence rate. Material and Methods: Eighty-seven previously untreated OL (52 occurring in females and 35 in males, mean age of 59.4 ± 13.9 years) were consecutively submitted to surgical treatment at University Hospital of Parma, Italy, and Hospital de Valongo, Portugal, (1999 to 2012). Interventions were subclassified into 5 groups according to the instrument used for the surgical removal of OL (cold blade – 17; Nd:YAG 1064nm laser – 14; Er:YAG 2940nm laser - 33; CO2 10600nm laser – 15; and QMR scalpel – 8). The mean follow-up period after treatment was 21.6 months (range 1-151 months). The outcome of treatment was scored through the same clinical protocol in the two participating units. Statistical analysis were carried by univariate analysis using chi-square test (or Pearson´s test when appropriate). Results: Recurrences were observed in 24 cases of OL (27.6%). Malignant transformation occurred in one patient (1.1%) after a period of 35 months. Statistical comparison of the 5 surgical treatment modalities showed no differences in clinical outcomes nor in the recurrence rate of OL. However, when Er:YAG laser group was compared with traditional scalpel, a significantly better outcome in cases treated with Er:YAG laser (P = 0.015) was highlighted. Conclusions: Our results suggests that Er:YAG laser could be a promising option for the treatment of OL. Key words:Oral leukoplakia; Potentially malignant disorders; Er:YAG Laser; CO2 Laser; Nd:YAG Laser; Quantic molecular resonance scalpel; malignant transformation rate.

Introduction Polycythemia vera (PV) is a disorder characterized by clonal proliferation of myeloid cells and increased red blood cell mass. Recently, the revised 2016 WHO classification of myeloid neoplasms decreased the threshold levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new proposed cutoffs have remarkable overlap with the normal reference values reported and the clinical impact of these new cutoffs has not been widely assessed in the general population. Methods We retrospectively examined 248 839 patients with presumptively normal complete blood cell results, consecutively obtained in an outpatient setting. Results The proportion of men with Hb >165 g/L was 5.99%, Hct>49% was 2.4%, and Hb >165 g/dL or Hct>49% was 6.48%, while the proportion of women with Hb >160 g/L was 0.22%, Hct>48% was 0.11%, and Hb >160 g/L or Hct>48% was 0.28%. Conclusion The isolated use of the proposed Hb/Hct levels as a definer of polycythemia may lead to a substantial increase in unnecessary diagnostic tests. In cases with borderline levels of hemoglobin, the diagnostic workup of PV should only be indicated in the presence of clinical and/or laboratorial features associated with MPN.

Auto-fluorescence (AF) of healthy bone tissue has recently been described. Loss of AF (LAF) has, on the contrary, been reported in necrotic bone. Further, the use of LAF as a possible guidance to distinguish viable from necrotic bone during surgical treatment of osteonecrosis has been proposed. The aim of this study is to detail 8 patients of medication-related osteonecrosis of the jaws treated through an AF-guided surgical resection. The authors also provide the histopathologic description of hypo-fluorescent and hyper-fluorescent bone in each patient. After removal of necrotic bone block, Er:YAG laser was used for vaporizing further necrotic bone, up to the detection of strongly hyper-fluorescent bone. Samples of hyper-fluorescent bone were collected around areas of necrosis. Histopathologic evaluation revealed viable bone tissue in all hyper-fluorescent specimens. On the basis of these data, AF-guided surgical resection could be effective in highlighting surgical margins of necrotic bone tissue and it might have some utility in a range of applications of bone surgery.

[Background] Salmonella enterica subsp. diarizonae (IIIb) is frequently isolated from the environment, cold-blooded reptiles, sheep and humans; however only a few studies describe the isolation of this subspecies from invasive human infections. The factors contributing to this unusual behavior are currently unknown., [Results] We report here the genome features of two diarizonae strains, SBO13 and SBO27, isolated from endocervical tissue collected post-abortion and from cerebrospinal fluid of a newborn child, respectively, in the city of Santa Cruz, Bolivia. Although isolated six years apart, SBO27 in 2008 and SBO13 in 2014, both strains belong to the same sequence type 1256 (ST1256) and show a high degree of genome conservation sharing more than 99% of their genes, including the conservation of a ~ 10 kb plasmid. A prominent feature of the two genomes is the presence of 24 genomic islands (GIs), in addition to 10 complete Salmonella pathogenicity islands (SPI) and fragments of SPI-7, a pathogenicity island first reported in the human-adapted serovar Typhi. Some of the GIs identified in SBO13 and SBO27 harbor genes putatively encoding auto-transporters involved in adhesion, lipopolysaccharide modifying enzymes, putative toxins, pili-related proteins, efflux pumps, and several putative membrane cation transport related-genes, among others. These two Bolivian isolates also share genes encoding the type-III secretion system effector proteins SseK2, SseK3 and SlrP with other diarizonae sequence types (ST) mainly-associated with infections in humans. The sseK2, sseK3 and slrP genes were either absent or showing frameshift mutations in a significant proportion of genomes from environmental diarizonae isolates., [Conclusions] The comparative genomic study of two diarizonae strains isolated in Bolivia from human patients uncovered the presence of many genes putatively related to virulence. The statistically-significant acquisition of a unique combination of these functions by diarizonae strains isolated from humans may have impacted the ability of these isolates to successfully infect the human host., This work was supported by grants 215RT-0493 from Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (CYTED), BIO2016–77639-P (AEI/FEDER, UE) and PCIN-2016-082, from Spanish Ministry of Economy and Competitiveness and European Regional Development Funds (FEDER), awarded to FGdP; and, grants DGAPA IN213516, CONACyT 239659 and FC-2015-2/950, awarded to JLP. PV gratefully acknowledges funding grants DGAPA-PAPIIT IN211814 and IN206318 and CONACyT FC-2015-2/879. Other supporting grants were from Comisión Sectorial de Investigación Científica (CSIC), Universidad de la República (Proyecto Grupos I + D 2014), awarded to LB. CS was supported by CONACyT FC-2015-2/879., We acknowledge support of the publication fee by the CSIC Open Access Support Initiative through its Unit of Information Resources for Research (URICI)

Aluminum and tin are ubiquitous in the environment. In normal biological systems, however, they are present only in trace amounts and have no recognized biological functions in humans. High exposure to these metals can result in adverse health effects such as neurodegenerative diseases. In non-occupationally exposed subjects, diet is the primary source of exposure. In this study, we aimed at estimating dietary aluminum and tin intake in an Italian adult population. We measured aluminum and tin concentrations through inductively-coupled plasma mass spectrometry in 908 food samples. We also estimated dietary intake of these two metals, by using a validated semi-quantitative food-frequency questionnaire administered to 719 subjects (319 men and 400 women) recruited from the general population of the Emilia Romagna region, Northern Italy. We found the highest aluminum levels in legumes, sweets, and cereals, while the highest tin levels were in sweets, meat and seafood. The estimated median daily dietary intake of aluminum was 4.1 mg/day (Interquartile range – IQR: 3.3–5.2), with a major contribution from beverages (28.6%), cereals (16.9%), and leafy vegetables (15.2%). As for tin, we estimated a median intake of 66.8 μg/day (IQR: 46.7–93.7), with a major contribution from vegetables (mainly tomatoes) (24.9%), fruit (15.5%), aged cheese (12.2%), and processed meat (10.4%). This study provides an updated estimate of the dietary intake of aluminum and tin in a Northern-Italy adult population, based on data from a validated food-frequency questionnaire. The intake determined for this population does not exceed the established thresholds of tolerable intake.

Background To evaluate the use of retrograde endovascular internal iliac artery preservation (REIIAP) technique for treating aortoiliac aneurysms. Methods We reviewed our database for all patients with aortoiliac aneurysms who underwent REIIAP technique between April 2004 and April 2014. Patients underwent implantation of an Apollo aortomonoiliac (Nano Endoluminal, Florianopolis, Brazil), contralateral implantation of a Viabahn stent graft (Gore Medical, Flagstaff, AZ) positioned from the external iliac artery into the internal iliac arteries as a bridging stent and femorofemoral bypass. The outcomes that we evaluated included technical success, operative mortality and morbidity, endoleak, aneurysm diameter, bridging stent occlusion, and reintervention during follow-up. Results A total of 21 patients (19 men, mean age 73 ± 2.3 years) were identified. Technical success was achieved in all cases, and none of the patients died during the follow-up (mean follow-up 52 ± 38.5 months). Type IB endoleak was diagnosed in 2 patients, bridging stent occlusion was diagnosed in 1 patient, and reintervention was required for 2 patients. Diameter regression was observed in the aorta ( P = 0.15), left common iliac artery ( P = 0.37), and right common iliac artery ( P = 1.22). Conclusions This study demonstrates the feasibility of the REIIAP technique presenting high success rate and similar complication rates compared with other therapeutic options during follow-up. These results demonstrated that it is a useful option for selected patients with aortoiliac aneurysms unfit for other techniques.

This observational case study examined the association of inter- and intraday energy intake and exercise energy expenditure with bone health, menstrual status and hematological factors in a female triathlete. The study spanned 7 months whereby energy intake and exercise energy expenditure were monitored three times (13 d); 16 blood samples were taken, urinary hormones were assessed for 3 months, and bone mineral density was measured twice. Energy availability tended to be sustained below 30 kcal/kg FFM/d and intraday energy intake patterns were often “back-loaded” with approximately 46% of energy consumed after 6 p.m. Most triiodothyronine values were low (1.1–1.2nmol/L) and supportive of reduced energy availability. The athlete had suppressed estradiol (105.1 ± 71.7pmol/L) and progesterone (1.79 ±1.19nmol/L) concentrations as well as urinary sex-steroid metabolites during the entire monitoring period. Lumbar spine (L1-L4) bone mineral density was low (age-matched Z-score −1.4 to −1.5). Despite these health related maladies the athlete was able to perform typical weekly training loads (swim: 30–40 km, bike: 120–300 km, run 45–70 km) and was competitive as indicated by her continued improvement in ITU World Ranking during and beyond the assessment period. There is a delicate balance between health and performance that can become blurred especially for endurance athletes. Education (athletes, coaches, parents) and continued monitoring of specific indicators will enable evidence-based recommendations to be provided and help reduced the risk of health related issues while maximizing performance gains. Future research needs to longitudinally examine how performance on standardized tests in each discipline (e.g., 800-m swim, 20-km time trial, 5-km run) is impacted when aspects of the female athlete triad are present.

Dentoalveolar surgery including tooth extractions and dental implants placement is considered the major risk factor for developing medication-related osteonecrosis of the jaw (MRONJ).In this study, a patient series of MRONJ around dental implants were carefully analyzed to describe the findings and to assess the possible risk factors.Fifteen patients with peri-implant bone osteonecrosis were selected out of a group of 250 patients (6%). Patients were divided into 2 groups according to the temporal relationship. Group 1 (G1)-necrosis immediately after implant placement (from 2 to 10 months) and defined as "implant surgery-triggered" MRONJ. Group 2-necrosis distant (from 1 to 15 years) from implant placement and defined as "implant presence-triggered" MRONJ. Epidemiological and pharmacological variables were recorded as well as specific data about osteonecrosis and dental implants.G1 included 6 patients: 5 (83.4%) treated with oral bisphosphonates (BPs) for osteoporosis and 1 (16.6%) with intravenous BPs for breast cancer. Mean duration of BP therapy (BPT) was 83.7 months. G2 included 9 patients: 8 patients (88.89%) treated with intravenous BPs for malignant disease and 1 (11.11%) with oral BPs for osteoporosis.Data confirms that not only surgical insertion of dental implants is a potential risk factor for the development of osteonecrosis but also the presence itself of the implant into the bone can be associated with this disease. Therefore, it is necessary to inform of the increased risk for MRONJ also the patients who have already osteointegrated implants and are going to start the BPT.The risk is lower for patients receiving oral BPs but it exists and seems to be higher if the implant is located in the posterior areas, if the duration of BPT is more than 3 years and if the patient is under corticosteroid therapy.

Background The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer. Case presentation Here we report a controversial case of a self-healing lesion of the tongue in a 57 year-old woman. A clonal T-cell proliferation and CD30 negative immunohistochemical (IHC) profile could be documented. Discussion and conclusion In view of the very peculiar clinical and histological features, a retrospective diagnosis of a TUGSE with scarce eosinophilic infiltrate (possibly in regression), displaying CD30- T-clonal proliferation was eventually rendered. The patient did not report signs of recurrence after a 3-year follow-up period.

Diet is the primary source of cadmium-a proven Group 1 human carcinogen-for non-smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR) and HER2 status, in 8924 women recruited to a prospective study between 1987 and 1992. Dietary cadmium intake was estimated using a semi-quantitative food frequency questionnaire at baseline. During a median of 22 years of follow-up, 451 incident cases of breast cancer were identified through the Varese Cancer Registry. Multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer and receptor-defined breast cancer subtypes were estimated for quintiles of dietary cadmium intake, adjusting for confounding factors. Mean dietary cadmium intake was 7.8 (standard deviation 1.4) μg/day. Women with highest quintile of cadmium intake had a greater risk of breast cancer (HR 1.54; 95% CI, 1.06-2.22; p trend = 0.028) than those with lowest quintile of intake. Women premenopausal at recruitment had HR = 1.73 (95% CI, 1.10-2.71, highest vs. lowest quintile); postmenopausal women had HR = 1.32 (95% CI, 1.05-1.66 for each standard deviation increase in cadmium). Cadmium-related risk of breast cancer did not vary with ER, PR or HER2 status (p-heterogeneity not significant). These findings support the hypothesis that dietary cadmium is a risk factor for breast cancer.

Regular consumption of fish is generally recommended by authorities because fish is an important source of essential nutrients. However, the presence of potentially toxic contaminants in fish has raised many concerns about the food's safety for human health. In the present study, we used a validated semi-quantitative food frequency questionnaire to assess the dietary habits of a representative sample of 719 individuals (319 males and 400 females) aged 18-87 years residing in Northern Italy. We estimated weekly dietary intakes of Arsenic (As) and Mercury (Hg), and we compared them with safety standards set by the European Food Safety Authority. In this population, fish was the main contributor to As and Hg intake. The highest levels of As were in sardine, sole/flounder and cephalopods, and of Hg in the biggest, predatory fish. About the other foods, cereals were the second contributor to the intake of these elements, especially rice for As and bread for Hg, and high levels of As and Hg were also found in mushrooms, coffee and wine. Average weekly intake of both contaminants was below recommended safety limits.

Chordomas are rare neoplasms of the axial skeleton, with a predilection for the clival region. The lack of data about intracranial chordomas has led to inconsistent reporting of their clinical behavior and management principles. We performed a systematic review and meta-analysis with the aim of reporting on clinical behavior and management in the literature. We performed an electronic search of the MEDLINE, EMBASE, LILACS, Web of Science, Cochrane, and CINAHL databases. We included studies of patients with intracranial chordoma that had undergone surgical management with 5-year data available. The weighted mean estimate of 5-year OS was 77.4% (95% CI, 72.9-81.7%) whilst the 5-year PFS estimate was 49.4% (95% CI, 41.6-57.3%). A wide variety of surgical approaches were utilised, with transcranial approaches being the commonest. Surgeons achieved gross total resection in 29.4% of cases (95% CI, 17.6-43.0%), Sub-total resection in 60.9% of cases (95% CI, 40.2-79.8%) and partial resection in 19.7% (95% CI; 11.9 to 28.9%). The total complication rate was 28.5% (95% CI, 18.4-39.8%), with the commonest being new cranial nerve palsy (weighted mean 11.1%, 95% CI, 7.11-15.7%). Our review demonstrates that a wide range of management options exist in the literature. These should be tailored to each patient based on factors including tumoral location, local involvement and capabilities of the surgical team. The outcomes of chordoma management have largely been stable with no improvement despite improvements in modern surgical techniques.

Aicardi–Goutieres syndrome is a genetically determined infantile encephalopathy, manifesting as progressive microcephaly, psychomotor retardation, and in ∼25% of patients, death in early childhood. Aicardi–Goutieres syndrome is caused by mutations in any of the genes encoding TREX1 , RNASEH2-A , -B , -C and SAMHD1 , with protein dysfunction hypothesized to result in the accumulation of nucleic acids within the cell, thus triggering an autoinflammatory response with increased interferon-α production. Astrocytes have been identified as a major source of interferon-α production in the brains of patients with Aicardi–Goutieres syndrome. Here, we study the effect of interferon-α treatment on astrocytes derived from immortalized human neural stem cells. Chronic interferon-α treatment promoted astrocyte activation and a reduction in cell proliferation. Moreover, chronic exposure resulted in an alteration of genes and proteins involved in the stability of white matter (ATF4, eIF2Bα, cathepsin D, cystatin F), an increase of antigen-presenting genes (human leukocyte antigen class I) and downregulation of pro-angiogenic factors and other cytokines (vascular endothelial growth factor and IL-1). Interestingly, withdrawal of interferon-α for 7 days barely reversed these cellular alterations, demonstrating that the interferon-α mediated effects persist over time. We confirmed our in vitro findings using brain samples from patients with Aicardi–Goutieres syndrome. Our results support the idea of interferon-α as a key factor in the pathogenesis of Aicardi–Goutieres syndrome relating to the observed leukodystrophy and microangiopathy. Because of the sustained interferon-α effect, even after withdrawal, therapeutic targets for Aicardi–Goutieres syndrome, and other interferon-α-mediated encephalopathies, may include downstream interferon-α signalling cascade effectors rather than interferon-α alone. * Abbreviations : CST7 : cystatin F GFAP : glial fibrillary acidic protein IFN-α : interferon-alpha VEGF : vascular endothelial growth factor

The aim of this study is to evaluate the possible intraoperative advantages of Nd:YAG laser and quantic molecular resonance (QMR) scalpel in oral soft tissue surgery. One hundred sixty-three interventions were evaluated. Group 1 (G1) included 77 interventions performed with Nd:YAG laser, group 2 (G2) 45 with QMR scalpel, and group 3 (G3) 41 with cold blade. Parameters analyzed were as follows: speed of incision, time of intervention, intraoperative bleeding, number of stitches, patient compliance, and operator comfort. Data were analyzed using software STATA 12 (StataCorp LP, College Station, TX, USA). Mean speed of incision was 0.54 mm/s in G1, 2.83 mm/s in G2, and 1.58 mm/s in G3, Nd:YAG laser being the slowest. However, no significant differences among times of intervention were found. In particular, interventions in G1 (221.15 ± 220.89 s) have a mean duration lower than G2 (280.56 ± 248.31 s) and G3 (316.10 ± 248.69 s). Intraoperative bleeding occurred in 29.9 % (n = 23/77) of interventions in G1, 97.8 % (n = 44/45) in G2, and 97.6 % (n = 40/41) in G3 (p < 0.0001). Mean number of stitches in G1 was statistically lower (G1, 0.10; G2, 2.07; G3, 2.29; p < 0.0001). No differences with regard to patient compliance were detected. Operator comfort was higher in G1 (p < 0.0003). Nd:YAG laser and QMR scalpel give several advantages in oral mucosal surgery: Nd:YAG laser cuts tissue slowly, but it provides a good visibility and excellent hemostasis. QMR scalpel allows a very rapid cutting with no considerable temperature increase, but there is major risk of bleeding and need for sutures with lower operator comfort.

There is no methodological standardization of velocity thresholds for the quantification of distances covered in various locomotor activities for women’s soccer matches, especially for high-speed running and sprinting. Applying velocity thresholds used for motion analysis of men’s soccer has likely created skewed observations about high-intensity movement demands for the women’s game because these thresholds do not accurately reflect the capabilities of elite female players. Subsequently, a cohesive view of the locomotor characteristics of women’s soccer does not yet exist. The aim of this commentary is to provide suggestions for standardizing high-speed running and sprint velocity thresholds specific to women’s soccer. The authors also comment on using generic vs individualized thresholds, as well as age-related considerations, to establish velocity thresholds.

There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies.

Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/ stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with a-smooth muscle actin (α-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.