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Purpose : Removal of impacted third molars, can be associated with complications such as pain, edema, trismus, that can increase the morbidity of this procedure. The purpose of this study is to determine whether the Er:YAG laser is effective in reducing pain, swelling and trismus compared to rotary instruments in removing impacted lower third molars (3 LM`s). Methods : For this systematic review the searches were carried out independently by 2 researchers and the articles were selected according to the inclusion and exclusion criteria previously established. The predictor variable was the study group (Er:YAG laser versus rotatory instruments). The main outcome was the analysis of post-operative pain, edema and trismus after third molars extractions. Data analysis included the risk of bias evaluation (RoB 2 Cochrane) and meta-analysis with random effects I2 based heterogeneity and 95% confidence. Results : In the initial results, 1371 articles were found and 6 RCT were selected to compose this study. A total of 299 3 LM`s were removed, 126 with the Er:YAG laser, 142 with a drill and 31 with a piezoelectric instrument. The results of this meta-analysis showed that in the laser group there was a significant reduction in edema (1.82 [CI95% = -3.06 to -0.57] cm (p=0.004)) and complications (p=0.0004), a slight reduction in pain after 2 days (p =0.030) and there was no variation in trismus (p=0.200) when compared to the drill group. The surgery/osteotomy time was shorter in the drill group. Only 1 study presented low risk of bias. Conclusion : The Er:YAG laser has been shown to be effective in reducing edema, pain and complications in impacted lower third molar surgeries. however due to the lack of standardization in Er:YAG laser therapy, new controlled and standardized studies should be performed with the aim of proving the efficacy of this therapeutic modality.

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 Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund This work was financially supported by grants from "Ministero della Salute Italiano"(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from "Associazione Italiana Cancro" (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

The aim of this study was to examine the relationship between resting morning heart rate variability (HRV) metrics and indirect markers of hydration status in elite male athletes. Twenty-two field hockey players (age 26.8 ± 3.4 yr; height 178.4 ± 6.3 cm; body mass 76.2 ± 7.4 kg) were monitored over 10-d during a pre-Olympic training camp. Measurement of heart rate variability (HRV) during an orthostatic challenge, urine specific gravity (Usg, first morning void) and body mass were captured on seven of the mornings. Individual generalized linear mixed models evaluated the relationships between supine and standing HRV metrics with Usg and day-to-day change in body mass. No meaningful relationships were identified between supine (estimates −0.002 to 0.001) or standing (−0.002 to 0.003) HRV metrics and Usg as well as between supine (−0.003 to 0.016) or standing (−0.004 to 0.006) HRV metrics and changes in body mass. These outcomes indicate that supine and standing HRV metrics are not influenced by indirect indices of hydration status in elite male field hockey players.

COVID-19 pandemic has become a significant international public health problem. In addition to dealing with the pandemic’s impact on mental health, parents need to cope with specific changes in their routines caused by social distance measures. This study aimed to investigate common mental disorders (CMD) symptoms in Brazilian parents during the COVID-19 pandemic and its associated factors. A total of 232 Brazilian parents ranging from 20 to 48 years old (M = 33.85; SD = 4.83) with children aged 1–36 months (M = 17.00; SD = 9,87) participated in an online survey. Parents answered a sociodemographic questionnaire, Self-Report Questionnaire (SRQ-20), Perceived Stress Scale (PSS-4), and Parenting Sense of Competence Scale. Chi-square tests, correlations, and multiple linear regression were performed. Results showed that parents’ symptoms of CMD were negatively associated to perceived parental competence (β =− 0.130; p = 0.011) and family income (β =− 0.190; p = 0.024). Furthermore, perceived stress was the most related variable to parents’ symptoms of CMD (β = 0.618; p

Background The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic. Methods The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March–May 2020), II (June–September 2020), and III (October–December 2020). Results Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (> 200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency ( Conclusion This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic.

Background The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. Methods Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. Results DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. Conclusion These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

Objectives: To analyze psychological profiles, pain and oral symptoms in patients with oral lichen planus (OLP). Materials and methods: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes) and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered. Results: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value

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.

This paper aims to validate the performance capabilities of a Pressure Reducing Turbine (PRT) with respect to initial predictions based on analytic calculations. The designed equipment was installed in a beverage facility, located in Brazil. The validation procedure consists of analyzing the data collected in several periods of PRT’s operation, accessed remotely via an online server. The analysis of empirical data identifies the behavior of two key variables: generated power and effective efficiency. However, the observed boundary conditions differed significantly from expected values, forcing the turbine to operate in off-design conditions. The turbine model was hence refined and used to predict the PRT’s performance in such conditions. Results showed satisfactory accuracy for both power and efficiency predictions.

Objective: The aim of our retrospective study is to compare the long-term recurrence rate of the benign oral squamous papilloma (OSP) with different laser-assisted treatments and conventional proce...

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

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

Biological tissues (including oral mucosa) can absorb and re-emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as "autofluorescence" (AF). Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope® system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer.

Radiation hard thin-film solar cell technologies are necessary in order to achieve a step forward in the specific power of solar arrays for space applications. In this article, we analyze the degradation of nanowire (NW) solar cells under high energy particles. GaAs NW solar cells have been irradiated with protons of 100 and 350 keV at different fluences. The radiation hardness of the NW solar cells in all the cases is remarkable in comparison with GaAs planar solar cells and prior literature. Design guidelines to optimize the specific power of NW solar cells for space applications by jointly increasing their efficiency and radiation hardness are presented.

Background: Gingival melanin hyperpigmentation is due to excessive deposition of melanin granules. The duration of pigmentation reappearance after treatment using different laser wavelengths remain...

Huntington disease (HD) is a devastating and presently untreatable neurodegenerative disease characterized by progressively disabling motor and mental manifestations. The sigma-1 receptor (&sigma, 1R) is a protein expressed in the central nervous system, whose 3D structure has been recently determined by X-ray crystallography and whose agonists have been shown to have neuroprotective activity in neurodegenerative diseases. To identify therapeutic agents against HD, we have implemented a drug repositioning strategy consisting of: (i) Prediction of the ability of the FDA-approved drugs publicly available through the ZINC database to interact with &sigma, 1R by virtual screening, followed by computational docking and visual examination of the 20 highest scoring drugs, and (ii) Assessment of the ability of the six drugs selected by computational analyses to directly bind purified &sigma, 1R in vitro by Surface Plasmon Resonance and improve the growth of fibroblasts obtained from HD patients, which is significantly impaired with respect to control cells. All six of the selected drugs proved able to directly bind purified &sigma, 1R in vitro and improve the growth of HD cells from both or one HD patient. These results support the validity of the drug repositioning procedure implemented herein for the identification of new therapeutic tools against HD.

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.

Context. Wide-field spectrometers are needed to deal with current astrophysical challenges that require multiband observations at millimeter wavelengths. An example of these is the KIDs Interferometer Spectrum Survey (KISS), which uses two arrays of kinetic inductance detectors (KIDs) coupled to a Martin-Puplett interferometer (MPI). KISS has a wide instantaneous field of view (1 deg in diameter) and a spectral resolution up to 1.45 GHz in the 120-180 GHz electromagnetic band. The instrument is installed on the 2.25 m Q-U-I JOint TEnerife telescope in Teide Observatory (Tenerife, Canary Islands), at an altitude of 2395 m above sea level. Aims. This work presents an original readout modulation method developed to improve the sky signal reconstruction accuracy for types of instruments for which a fast sampling frequency is required both to remove atmospheric fluctuations and to perform full spectroscopic measurements on each sampled sky position. Methods. We first demonstrate the feasibility of this technique using simulations. Then, we apply such a scheme to on-sky calibration. Results. We show that the sky signal can be reconstructed to better than 0.5% for astrophysical sources, and to better than 2% for large background variations such as in "skydip", in an ideal noiseless scenario. The readout modulation method is validated by observations on-sky during the KISS commissioning campaign. Conclusions. We conclude that accurate photometry can be obtained for future KID-based MPI., 11 pages, 10 figures, accepted for publication in A&A

Computer-Controlled Optical Surfacing (CCOS) has been greatly developed and widely used for precision optical fabrication in the past three decades. It relies on robust dwell time solutions to determine how long the polishing tools must dwell at certain points over the surfaces to achieve the expected forms. However, as dwell time calculations are modeled as ill-posed deconvolution, it is always non-trivial to reach a reliable solution that 1) is non-negative, since CCOS systems are not capable of adding materials, 2) minimizes the residual in the clear aperture 3) minimizes the total dwell time to guarantee the stability and efficiency of CCOS processes, 4) can be flexibly adapted to different tool paths, 5) the parameter tuning of the algorithm is simple, and 6) the computational cost is reasonable. In this study, we propose a novel Universal Dwell time Optimization (UDO) model that universally satisfies these criteria. First, the matrix-based discretization of the convolutional polishing model is employed so that dwell time can be flexibly calculated for arbitrary dwell points. Second, UDO simplifies the inverse deconvolution as a forward scalar optimization for the first time, which drastically increases the solution stability and the computational efficiency. Finally, the dwell time solution is improved by a robust iterative refinement and a total dwell time reduction scheme. The superiority and general applicability of the proposed algorithm are verified on the simulations of different CCOS processes. A real application of UDO in improving a synchrotron X-ray mirror using Ion Beam Figuring (IBF) is then demonstrated. The simulation indicates that the estimated residual in the 92.3 mm × 15.7 mm CA can be reduced from 6.32 nm Root Mean Square (RMS) to 0.20 nm RMS in 3.37 min. After one IBF process, the measured residual in the CA converges to 0.19 nm RMS, which coincides with the simulation.

Introdução: A Trombocitopenia imune induzida por medicamentos é caracterizada, geralmente, por um quadro abrupto de plaquetopenia, resultante da ligação da droga a alguma proteína plaquetária com formação de um neoantígeno, que então desencadeia resposta imune com destruição plaquetária. Sulfonamidas, heparina e rifampicina são exemplos de drogas associadas a este mecanismo. Além disso, novos medicamentos, especialmente os “biológicos”, podem induzir plaquetopenia por outras vias e sua identificação também é de importância clínica. Objetivo: Relatamos dois casos de trombocitopenia medicamentosa onde destaca-se a importância do diagnóstico e acompanhamento clínico-laboratorial para o tratamento adequado do paciente. Caso1: Paciente 50 anos, feminino previamente hígida com contagem normal de plaquetas apresentou quadro de petéquias em membros inferiores. Hemograma: Leucócitos totais = 4.840/mm3, Hb= 13,2g/dL, RDW=13,4%, e Plaquetas=2.000/mm³. No esfregaço sanguíneo confirmou-se a plaquetopenia (ausência de grumos e de macrotrombócitos). Paciente encontrava-se em uso de sulfametoxazol/trimetoprina há cerca de 15 dias por infecção de partes moles. Sete dias após a suspensão da medicação a contagem plaquetária estava em 430.000/mm3, estável há cerca de 9 meses. Caso 2: Paciente de 2 anos, masculino, realizou hemograma que evidenciou Leucócitos = 9.780/mm3, Hb= 11,4 g/dl, RDW 14,1 %, Plaquetas = 79.000/mm³, VPM = 10,4 fL. No esfregaço observou-se a redução do número de plaquetas e raros macrotrombócitos. O paciente fizera, há 4 dias, uso do medicamento ZolgensmaR (Onasemnogene abeparvovec), medicamento do tipo biológico usado como terapia genética para o tratamento da atrofia muscular espinhal (AME), doença genética rara que acomete 1/10.000 nascidos vivos. Cerca de 7 dias após, as plaquetas estavam em 150.000/mm3, estável há 6 meses. Discussão: A trombocitopenia induzida por drogas pode ser de caráter não imune (supressão medular/toxicidade) ou de fundo imune. Esta ocorre geralmente pela formação de neoantígenos, tem início abrupto, pode acarretar plaquetas < 20.000/mm3 e ser sintomática. Apesar de raro, algumas medicações são classicamente relacionadas a este quadro, como as sulfonamidas, descrita no primeiro caso. Exceto pela relação com uso de medicamentos, esta condição pode ser de difícil diferenciação em relação à púrpura trombocitopenica imune. O caso 2 trata-se de uma criança com AME em uso de ZolgensmaR, terapia gênica que utiliza um vetor viral para introduzir material genético modificado no organismo (gene SMN1, sem o qual há perda de neurônios motores no tronco cerebral e medula espinhal). O capsídeo viral induz importante reação inflamatória e a plaquetopenia é comum (>90% dos casos), apesar de raramente 90%.

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

Oral granular cell tumor (GCT) is a relatively rare, benign lesion that can easily be misdiagnosed. Particularly, the presence of pseudoepitheliomatous hyperplasia might, in some cases, lead to the hypothesis of squamous cell carcinoma. Surgical excision is the treatment of choice. Recurrence has been reported in up to 15% of cases treated with conventional surgery. Here, we reported a case of GCT of the tongue in a young female patient, which was successfully treated through 445 nm diode laser excision. Laser surgery might reduce bleeding and postoperative pain and may be associated with more rapid healing. Particularly, the vaporization effect on remnant tissues could eliminate GCT cells on the surgical bed, thus hypothetically leading to a lower rate of recurrence. In the present case, complete healing occurred in 1 week, and no recurrence was observed after 6 months. Laser surgery also allows the possibility to obtain second intention healing. Possible laser-induced histopathological artifacts should be carefully considered.

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

This work aims to investigate the application of RFID technology (Radio Frequency IDentification) to CFRPs (Carbon Fiber Reinforced Polymers) components to improve traceability and support logistics in the race car industry. Several RFID tags able to withstand the harsh processing environment, e.g., high temperature and pressures, have been considered. In order to hide the tag, it was decided to insert it into the component before polymerization, instead of bonding it outside. This technical approach improves the aesthetics and allows the tag to act as an anti-counterfeiting device. However, the readability of a passive RFID tag within CFRP must be evaluated. To better clarify the readability of the tag within CRFP an experimental campaign was conducted with samples based on real laminate mock-ups. The experiments were carried out on a square laminate sample with grooves to house the tag of different size and geometry and different types of composite plies that covers it. It has been observed how the composite cover could affect the reading distance in comparison to the control configuration, i.e., cover-free situation.

Talbot-Lau x-ray interferometry has been implemented to map electron density gradients in High Energy Density Physics (HEDP) experiments. X-ray backlighter targets have been evaluated for Talbot-Lau X-ray Deflectometry (TXD). Cu foils, wires, and sphere targets have been irradiated by 10–150 J, 8–30 ps laser pulses, while two pulsed-power generators (∼350 kA, 350 ns and ∼200 kA, 150 ns) have driven Cu wire, hybrid, and laser-cut x-pinches. A plasma ablation front generated by the Omega EP laser was imaged for the first time through TXD for densities >1023 cm−3. Backlighter optimization in combination with x-ray CCD, image plates, and x-ray film has been assessed in terms of spatial resolution and interferometer contrast for accurate plasma characterization through TXD in pulsed-power and high-intensity laser environments. The results obtained thus far demonstrate the potential of TXD as a powerful diagnostic for HEDP.

Dietary intake to trace elements may represent the most relevant source of exposure for the general, non-occupationally population, but some of them have been rarely evaluated. We measured content of fifteen trace elements (antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium) in 908 food and beverage samples through inductively coupled plasma mass spectrometry. We estimated their dietary intake using a validated semi-quantitative food frequency questionnaire collected from a population of the Emilia-Romagna Region in Northern Italy. We compared our estimates with tolerable upper intake levels reported by international agencies and we assessed the non-carcinogenic risk through calculation of total hazard quotient for each trace element according to the US-EPA approach. Overall, estimates of their dietary intake were substantially similar to those reported from other countries, and they fell below the tolerable upper intake levels provided by international agencies. The total hazard quotient for each trace element was below 1. Our findings provide updated estimates of food levels and dietary intake of trace elements far frequently evaluated in a sample of Italian adult consumers. They also suggest that any non-carcinogenic risk associated with intake of investigated trace elements may be ruled out in our population.

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.

Objectives The present review provides information about which molecules appear to be the main fluorophores in skin and oral mucosa, together with their clinical applications. Design The MEDLINE database was searched, using “oral mucosa AND fluorophores”, “skin AND fluorophores”, “epidermal AND fluorophores”, “dermal AND fluorophores” and “cutaneous AND fluorophores” as entry terms. We searched the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The level of evidence in the studies was assessed using the Classification of the Oxford Centre for Evidence-based Medicine (CEBM) Levels for Diagnosis. Results Five papers and 17 were primarily focused on description of fluorophores in oral mucosa and skin Evidence exists that fluorophores of oral mucosa and skin are mainly proteins such as collagen, elastin, keratin and tryptophan. Other possible fluorophores identified are: porphyrins, advanced glycation end products, flavins, lipopigment, nicotinamide adenine dinucleotide, flavin adenine dinucleotide, pheomelanin, eumelanin and components of lipofuscin. Clinical applications of oral mucosal autofluorescence (AF) are related to management of malignant and potentially malignant lesions. In the skin, AF has been used for acne assessment, diagnosis of sweat-gland pathologies, glycemic control and management of malignant lesions and as a marker for skin aging. Conclusion Fluorophores stimulated through AF devices are implied in different physiologic and pathologic processes. AF seems to be useful for several clinical applications, especially in skin department. Because most of the studies show a low level of evidence, further studies are necessary in such a promising and fascinating field.

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.

This field-based observational study was designed to examine the intraindividual variation of first morning body mass and urine specific gravity (Usg) in male hockey players (n = 22) during a 10-day training camp. It was also designed to evaluate the prevalence and interrelationship of morning hypohydration and postmatch dehydration using Usg and changes in body mass, respectively. Body mass and Usg were measured upon waking; body mass was also measured before and after matches. Individual means,SD, and coefficient of variation (CV) were calculated for morning body mass and Usg using 3, 6, and 8 days. Daily prevalence for euhydration and postmatch dehydration using morning Usg (−2%), respectively, were determined. Measurement of morning body mass and Usg for 3 days had low variability (CV 1% in 50–85% of players, with up to 40% experiencing changes >−2%. Postmatch changes in body mass were unrelated to Usg the subsequent morning. These outcomes can be helpful in establishing criteria for detecting meaningful changes in morning body mass and Usg in similar settings, helping to monitor hydration status in elite male athletes. Despite ample fluid availability and consumption, many players experienced hypohydration and dehydration during the camp, indicating that careful monitoring and an individual fluid replacement approach are warranted in these environments.

Umbilical cord blood (UCB) is an alternative source for hematopoietic stem cells allogeneic hematopoietic stem cell transplantation in the absence of compatible donor. UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD) but is associated with slower engraftment and slower immune reconstitution as compared to other sources. Dendritic cells (DC) and Natural Killer cells (NK) play a central role in the development of GVHD, the graft versus leukemia (GvL) effect, and in the control of infectious complications. We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DC, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. In the UCB samples, there were higher counts of CD56brightCD16-NK cells (median 0.024×109/L), as compared to the PB samples (0.012×109/L, PHighlightsCD56brightCD16- NK cells are more frequent in UCB than in PB.Plasmacytoid dendritic cells are more frequent in UCB than in PB.Non-classical monocytes are more frequent in PB than in UCB.

This study aimed to evaluate the prevalence of MRONJ in patients treated with prosthetic implant rehabilitation. We evaluated the risk of MRONJ genesis comparing implant surgery with the development of necrosis after correct implant osteointegration. The implants' presence in these patients is a possible risk factor of necrosis development. The presence of implant might cause a reactivation of osteoclasts.

One of the most frequent monoclonal antibodies linked to MRONJ is Denosumab. In our study, attention was focused on different therapeutic approaches considering patients treated only with Denosumab or in combination with other drugs associated with the genesis of ONJ. We considered two different clinical approaches: sites treated without surgery; sites treated with traditional surgery or Er:YAG laser (2940nm, 250mJ, 20Hz). In our study, the discontinuation of the drug was evaluated in relation to treatment outcomes.

The COVID-19 pandemic has rapidly affected every country and overwhelmed many healthcare systems. Intensive caretreatment may be needed for extended durations. Patients experience consequences of respiratory illness and post-intensive care illness (1,2). Endoscopic procedures, such as endoscopic ultrasound-guided gallbladder transmural drainage, can reduce surgicalinterventions, intensive-care admissions, and long-term complications (3). EUS-guided gallbladder drainage is efficient and safe, with a low rate of adverse events. A 54-year-old man, recently recovered from severe COVID-19+ pneumonia and still judged unfit for futhher intubation, wastreated by EUS-guided gallbladder drainage for severe acute cholecistytis by a 10x15-mm electrocautery-enhanced lumen-apposing stent.

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

In a recent study our research group described a non-invasive sampling procedure based on [...]

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

Background: Several noninvasive diagnostic tools have been developed to aid the early detection of oral cancer and for evaluation before definitive biopsy. Among these, devices evaluating a tissues...

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.

We present a fully modular and scalable software pipeline for processing electron microscope (EM) images of brain slices into 3D visualization of individual neurons and demonstrate an end-to-end segmentation of a large EM volume using a supercomputer. Our pipeline scales multiple packages used by the EM community with minimal changes to the original source codes. We tested each step of the pipeline individually, on a workstation, a cluster, and a supercomputer. Furthermore, we can compose workflows from these operations using a Balsam database that can be triggered during the data acquisition or with the use of different front ends and control the granularity of the pipeline execution. We describe the implementation of our pipeline and modifications required to integrate and scale up existing codes. The modular nature of our environment enables diverse research groups to contribute to the pipeline without disrupting the workflow, i.e. new individual codes can be easily integrated for each step on the pipeline.