Evaluation of the intraepithelial papillary capillary loops in benign and malignant oral lesions by in vivo Virtual Chromoendoscopic Magnification: a preliminary study.

This preliminary study aims to establish the Virtual Chromoendoscopic Magnification (VCM) feasibility to visualize and distinguish the Intraepithelial Papillary Capillary Loops (IPCL) patterns of benign oral pathologies from malignant ones. Thirty-one consecutive subjects affected by oral lesions/pathologies underwent white light examination and VCM imaging by the Narrow Band Imaging System (Olympus Medical Systems Corp., Tokyo, Japan). A class system of four IPCL types corresponding to progressive vessel disarray was adopted. IPCL type IV were considered criterion of “malignancy”. A histopathological exam completed the diagnosis: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. IPCL patterns of benign oral entities ranged from types I to III. IPCL type IV was associated with malignancy in 4 out of 6 cases. Sensitivity, specificity, PPV, and NPV were 100%, 93%, 67% and 100%, respectively. This study preliminarily describes IPCL patterns of different oral mucosal diseases and confirms the association between IPCL IV and oral cancer.

Relativistic jet activity from the tidal disruption of a star by a massive black hole.

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

Erythema nodosum in kidney transplant recipient: a rare complication of pneumonia treatment.

Erythema nodosum (EN) is a cutaneous inflammatory reaction, usually reported in young women, but it is rarely observed among transplant patients. Localization in the lower extremities is typical, mostly involving the anterior surfaces of the legs. Several viral, bacterial, mycotic, and non-infectious etiologies, such as autommune disorders, drugs, inflammatory bowel diseases, sarcoidosis, pregnancy, and malignancies, have been found. We describe the case of a young woman kidney transplant recipient developing bilateral, erythematous, warm nodules localized on the anterior surface of her legs after antibiotic treatment for pneumonia with levofloxacin. Her immunosuppression was sirolimus and mycophenolate mofetil. EN was diagnosed by skin biopsy; microscopic examination showed septal panniculitis with granulomas. As a complete remission of the lesions was obtained in our patient after interruption of levofloxacin therapy, we suspect that levofloxacin was involved in the pathogenesis of EN. In fact, the management of EN is based on the treatment of underlying or associated conditions.

On the use of field programmable gate arrays in light detection and ranging systems.

This work aims to provide details on the latest technological developments regarding LiDAR (Light Imaging Detection And Ranging) systems, with particular reference to the techniques, architectures, and methodologies partially or entirely implemented by means of the FPGA (Field Programmable Gate Array) environment. Currently, LiDAR technology is considered of great interest as it is widely employed in a variety of application fields, such as automotive, seismology, archaeology, metrology, and military. For this reason, the required performances are gradually increasing, which leads to complex and stringent solutions. The growth in LiDAR systems' complexity suggests the use of high-end general-purpose computing units such as central processing units to perform very complex tasks and FPGAs to perform multiple tasks in real-time through the implementation of dedicated computational blocks. The latter, in recent architectures, are therefore used for the execution of specific tasks that require high computational speed and system flexibility. This paper reports some case studies recently applied in the LiDAR field, with the aim of illustrating the role of FPGA technology and its benefits.

[Non-alcoholic hepatic steatosis: the role of policosanols in associated hyperlipidemia]. / La steatosi epatica non alcolica: il ruolo dei policosanoli nelle iperlipemie associate.

AIM: The purpose of this study was to evaluate the efficacy of policosanols in the treatment of associated hyperlipidemia in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: We conducted a retrospective study on 52 patients with NAFLD. Pretreatment patients' data (total cholesterol, LDL cholesterol, triglycerides, ALT, and AST) were collected and analyzed. Furthermore, based on weight and height, we calculated the Body Mass Index (BMI) and, based on blood glucose and insulin levels, we estimated the Human Omeostatic Assesment Index (HOMA). After that, all patients were treated with a policosanols' supplement (Frilipid®) and a hypocaloric balanced diet, and then followed over time with quarterly inspections. We collected and analyzed data on three subsequent quarterly monitoring during treatment. RESULTS: The collected and analyzed data showed a significant reduction in total cholesterol, LDL cholesterol and HOMA index (P<0.002). It was also found a trend not statistically significant for a marked reduction in ALT, AST, triglycerides, and BMI. CONCLUSION: The use of policosanols is shown effective in the treatment of associated hyperlipidemia and insulin resistance in patients with fatty liver disease.

Ten-Year Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant: A Prospective Cohort Study.

Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate [eGFR] 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia. In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation.

Venus: mass, gravity field, atmosphere, and ionosphere as measured by the mariner 10 dual-frequency radio system.

Analysis of the Doppler tracking data near encounter yields a value for the ratio of the mass of the sun to that of Venus of 408,523.9 +/- 1.2, which is in good agreement with prior determinations based on data from Mariner 2 and Mariner 5. Preliminary analysis indicates that the magnitudes of the fractional differences in the principal moments of inertia of Venus are no larger than 10(-4), given that the effects of gravity-field harmonics higher than the second are negligible. Additional analysis is needed to determine the influence of the higher order harmonics on this bound. Four distinct temperature inversions exist at altitudes of 56, 58, 61, and 63 kilometers. The X-band signal was much more rapidly attenuated than the S-band signal and disappeared completely at 52-kilometer altitude. The nightside ionosphere consists of two layers having a peak density of 10(4) electrons per cubic centimeter at altitudes of 140 and 120 kilometers. The dayside ionosphere has a peak density of 3 X 10(5) electrons per cubic centimeter at an altitude of 145 kilometers. The electron number density observed at higher altitudes was ten times less than that observed by Mariner 5, and no strong evidence for a well-defined plasmapause was found.

Mercury: results on mass, radius, ionosphere, and atmosphere from mariner 10 dual-frequency radio signals.

Analysis of the radio-tracking data from Mariner 10 yields 6,023,600 +/- 600 for the ratio of the mass of the sun to that of Mercury, in very good agreement with values determined earlier from radar data alone. Occultation measurements yielded values for the radius of Mercury of 2440 +/- 2 and 2438 +/- 2 kilometers at laditudes of 2 degrees N and 68 degrees N, respectively, again in close agreement with the average equatorial radius of 2439 +/- 1 kilometers determined from radar data. The mean density of 5.44 grams per cubic centimeter deduced for Mercury from Mariner 10 data thus virtually coincides with the prior determination. No evidence of either an ionosphere or an atmosphere was found, with the data yielding upper bounds on the electron density of about 1500 and 4000 electrons per cubic centimeter on the dayside and nightside, respectively, and an inferred upper bound on the surface pressure of 10(-8) millibar.

Living Kidney Donation Is Recipient Age Sensitive and Has a High Rate of Donor Organ Disqualifications.

BACKGROUND: Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks and ensure success. However, the proportion of donors disqualified has been poorly investigated. The aim of this work is to describe our experience and present the main reasons for missed donation. METHODS: This was a single-center, retrospective study of all potential donors and recipients evaluated for LDKT between January 2008 and December 2017. RESULTS: During the period of study, 81 donor-recipient pairs were evaluated. Of these, 45.7% were disqualified and 37 LDKTs were carried out. LDKT was the first choice in 68% of cases and preemptive in 20%; 60% of transplants were among family members. Sex distribution revealed a prevalence of females in the donor group (69%) and males in the recipient group (70%). The mean living donor age was 53 ± 9.5 years; the mean recipient age was lower in recipients listed in the living transplant program than those listed for cadaver transplantation (45.8 ± 13.4 vs 54.2 ± 11.08; P < .0001). Reasons for denial included hypertension (18.9%), deceased donor transplant performed during the study period (16.2%), urologic pathology (13.5%), incompatibility (13.5%), withdrawal of consent by donor or recipient (13.5%), psychological unsuitability (8.1%), donor cancer (5.4%), and reduced renal clearance (2.7%). CONCLUSION: LDKT is considered an option especially for younger recipients. Of the potential kidney living donors, 45.7% were disqualified during the evaluation, with medical reasons being the primary cause.

Global Performance Status Score: A New Tool to Assess Physical Performance in Kidney Transplant Patients.

BACKGROUND: Information on physical performance in renal transplantation is limited because of the shortage of specifically designed evaluation instruments. Therefore, we elaborated and validated the Global Performance Status (GloPerSta) score to provide a new and comprehensive tool, exploring the different components of physical performance in kidney transplant patients. METHODS: We elaborated the GloPerSta score on the basis of the data obtained from a cross-sectional study, in which we evaluated the physical performance of a cohort of kidney transplant patients. The results of these analyses were weighted to describe the different contribution of any single test, via the generation of a structural equation model, resulting in the definition of the GloPerSta. Then, to internally validate this score, we studied its correlation with clinical parameters and quality of life (evaluated as KDQOL-SF, Kidney Disease Quality of Life-Short Form) in the same patient population. RESULTS: We enrolled 132 patients in whom the functional tests revealed a great heterogeneity. GloPerSta allowed the stratification of the patients in 3 different physical performance categories (low: score 0-11; medium: 12-22; high: 23-33). Internal validation showed that GloPerSta was directly and significantly correlated with the quality of life and allograft function, independent of the time from transplantation. CONCLUSIONS: The GloPerSta is a reliable tool to assess physical performance in a kidney transplant population. Its application might be of help in identifying patients needing intensive and personalized rehabilitation programs.

Understanding Bone Damage After Kidney Transplantation: A Retrospective Monocentric Cross Sectional Analysis.

BACKGROUND: Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review. PATIENTS AND METHODS: We designed an observational retrospective cohort study to evaluate bone damage after KT. The prevalence of osteopenia, osteoporosis, bone fractures, and the associated risk factors were investigated. The following parameters were recorded before transplantation and at the last follow-up: demographic indexes, cumulative steroid dose (CSD), dialytic and transplantologic age, previous nephropathy, femoral and lumbar BMD, fractures, immunosuppressors, calcemia, phosphoremia, rejection episodes, estimated glomerular filtration rate, and parathyroid hormone and vitamin D levels. Stata software (Stata Corporation, College Station, Texas, United States) was used for the statistical analysis, to perform the Fisher's exact test, Kruskal-Wallis test, Student t test, as well as univariate and multivariate analyses. RESULTS: The analyzed cohort was composed of 297 patients (65.3% males and 34.7% females). Sixty percent of KT patients had normal BMD, 24% had osteopenia, and 15% had osteoporosis. Twelve percent were victims of bone fractures (8.4% minor, 2% femoral, and 1.7% vertebral). A significant correlation (P <.05) was observed for both osteopenia and osteoporosis with menopause, transplantologic age, CSD, previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors treatment (imTOR). CONCLUSION: This study confirms the correlation between CSD (both before and after transplantation) and post-transplantation bone damage. It also shows that a large fraction of these patients had normal BMD related with a low steroid dose in our protocols. This correlation between imTOR assumption and osteoporosis deserves attention and warrants further in vitro analyses to be performed.

[Subthalamic stimulation in a patient with multiple system atrophy: a clinicopathological report]. / Stimulation des noyaux sous-thalamiques dans l'atrophie multi-systématisée: à propos d'un cas anatomo-clinique.

INTRODUCTION: Efficacy of high frequency subthalamic nucleus (STN) stimulation has been demonstrated in idiopathic Parkinson's disease (IPD). However, since it may be difficult to differentiate IPD from multiple system atrophy with parkinsonian presentation (MSA-P), a few cases of MSA-P has been treated by deep brain stimulation (DBS) and showed no sustained improvement of clinical signs. We report a patient with a clinical misdiagnosed MSA-P, later confirmed by neuropathological study, who was improved by DBS for one year. CASE REPORT: A 63-year-old parkinsonian patient had been treated by levodopa for 6 years with a persistent good response. Over one year he progressively developed disabling fluctuations with severe axial syndrome and vegetative non motor symptoms in off periods. After checking usual contraindications, he was included in surgical procedure protocol (bilateral STN stimulation). During the first year after surgery, the clinical status improved with disappearance of non motor fluctuations, a 45 percent decrease of the OFF UPDRS III score, and a 39 percent reduction of the treatment. However after one year, axial symptoms reappeared with recurrent falls, as well as increasing dysarthry and swallowing difficulties which were only slightly improved by levodopa. He developed severe urinary disorders increased by a prostatic adenoma which led to surgical treatment. During the post operative period, 2 years after DBS, he died suddenly from an unexplained cause. A cerebral autopsy was performed and showed a good position of the two electrodes in the STN. Microscopic studies revealed severe neuronal depletion in the substantia nigra but no Lewy bodies. Immunohistochemical methods demonstrated numerous argyrophilic glial cytoplasmic inclusions positive for alpha-synuclein and ubiquitin in the STN, putamen, globus pallidus, pontine nuclei and cerebellar white matter, significant of MSA. CONCLUSION: This case shows that DBS can improve parkinsonian signs in MSA-P with persistent dopa sensitivity. However, probably because of striatal degeneration progression, this improvement is time limited and STN DBS cannot be recommended in MSA.

Continuous intra jejunal infusion of levodopa-carbidopa intestinal gel by jejunal extension tube placement through percutaneous endoscopic gastrostomy for patients with advanced Parkinson's disease: a preliminary study.

OBJECTIVE: Levodopa is the gold standard in the pharmacological treatment of Parkinson's disease (PD) and its oral administration is associated with the development of disabling motor and non-motor complications in advanced disease. Levodopa is rapidly metabolized and has a short plasma half-life thus requiring frequent, repeated dosing. Impaired gastric emptying is common in PD, and likely contributes to the unpredictable motor responses observed with orally-dosed levodopa. A new therapeutic protocol for patients with advanced PD include a carbidopa/levodopa combination using continuous, modulated enteral administration achieved inserting a Jejunal Extension Tube Placement through Percutaneous Endoscopic Gastrostomy (PEG-J). The aim of this work is to assess efficacy and safety of levodopa-carbidopa intestinal gel (LCIG) delivered continuously through an intrajejunal percutaneous tube (PEG-J). PATIENTS AND METHODS: We enrolled 11 adults with advanced PD and preserved sensitivity to L-dopa. For pre-procedural endoscopic evaluation each patient underwent a diagnostic esophagogastroduodenoscopy (EGD) 7 days before PEG-J placement to evaluate the presence of gastric anatomical or wall anomalies and the presence of oesophageal or gastric varices. Treatment with LCIG, consisting of a water-based suspension containing micronized levodopa (20 mg/mL) and carbidopa (5 mg/mL) in methylcellulose (Duodopa®), was administered by continuous jejunal infusion for 12h/day using a portable pump (CADD-Legacy) by PEG-J. Clinical evaluations were performed at baseline (T0) before LCIG initiation, and after 3 (T3) and 6 (T6) months of therapy. The efficacy and safety outcomes were assessed by using the Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III and IV. RESULTS: Mean age of patients was 71.18 ± 5.4 SD at LCIG initiation. Out of the 11 patients, 2 (18%) dropped-out LCIG at T3. Patients showed statistically significant (p < 0.05) higher performances in activities of daily living and a statistically significant (p < 0.001) lower incidence and severity of motor fluctuations, as rating by UPDRS part IV, compared to their best oral therapy. During observational period, 5 patients experienced adverse events. Success rate for PEG-J placement was 100%. CONCLUSIONS: Our work shows that continuous intrajejunal infusion of LCIG ensures a reduction in motor Fluctuations compared to oral administration of levodopa-carbidopa in advanced PD. Based on our results and on the evidence emerging in the literature, this therapeutic approach should be the gold standard for therapy in these patients.

[Systemic Candida albicans infection with neuromeningeal complication in a premature infant]. / Complication neuroméningée d'une infection systémique à Candida albicans chez un prématuré

INTRODUCTION: Systemic maternal-fetal Candida albicans infections are uncommon diseases with a poor outcome. An associated cerebromeningeal infection increases morbidity. We present a case of neuromeningeal candidiasis following systemic neonatal infection in a premature infant. Management and therapeutic difficulties are outlined. OBSERVATION: The patient was a male infant born preterm at 30 weeks gestation. During his first week of life, he developed a systemic infection with an associated symptomatic hydrocephalus. Systemic candidaisis with neuromeningeal complication was diagnosed five weeks later. Despite treatment including cerebrospinal fluid (CSF) shunting and antimycotic medications (flucytosin and amphotericin B), the candidal infection did not resolve. Infectious and mechanical complications of the CSF drainage were treated by several surgical interventions during the following months. At 10 months of life, there was clinical and laboratory evidence of active persistent neuromeningeal candidaisis. Finally, candidal infection was eradicated with intravenous administration of fluconazole. After five year follow-up, the intellectual and psychological status of the patient was quite satisfactory, and no neurological deficits were found on clinical examination. DISCUSSION: Management of neuromeningeal candidaisis in premature infants is a challenging task particularly because of delayed diagnosis. Candida infection should routinely be suspected in cases of systemic infection with neurological impairment in premature infants. Fluconazole may constitute an efficient therapeutic option.

Refractory gastric antral vascular ectasia: a new endoscopic approach.

Gastric antral vascular ectasia (GAVE) is an uncommon disorder observed in patients with liver cirrhosis, causing upper gastro-intestinal haemorrhage. GAVE is diagnosed through esophagogastroduodenoscopy and is characterized by the presence of visible columns of red tortuous enlarged vessels along the longitudinal folds of the antrum (i.e., so-called watermelon stomach). Pharmacological, endoscopic and surgical approaches have been proposed for the treatment of GAVE. Endoscopy represents the gold standard for GAVE treatment. The most widely used endoscopic approach is represented by Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Argon plasma coagulation (APC) has been proven to be more efficient in terms of costs and complication rates than and equally effective as Nd:YAG. Other endoscopic procedures proposed for this treatment are banding ligature (EBL) and sclerotherapy with Polidocanol. Refractory GAVE represents a therapeutic challenge because it may cause persistent anemia, often leading to repeated blood transfusions due to the inefficacy of pharmacological and endoscopic therapeutic approaches. Endoscopic band ligation (EBL) has been shown to be superior to APC in the treatment of refractory GAVE. Surgical antrectomy by Billroth I anastomosis can be considered in selected cases. In this study, we report a successful endoscopic treatment of refractory GAVE by using a combination of submucosal injection of 1% Polidocanol at the four antral quadrants and subsequent application of APC on the visible antral lesions in two patients.

PEGylation of growth hormone-releasing hormone (GRF) analogues.

Synthetically produced GRF1-29 (Sermorelin) has an amino acid composition identical to the N-terminal 29 amino acids sequence of the natural hypothalamic GHRH1-44 (Figure 1). It maintains bioactivity in vitro and is almost equally effective in eliciting secretion of endogenous growth hormone in vivo. The main drawbacks associated with the pharmaceutical use of hGRF1-29 relate to its short half-life in plasma, about 10-20 min in humans, which is caused mostly by renal ultrafiltration and enzymatic degradation at the N terminus. PEGylation has been considered as one valid approach to obtain more stable forms of the peptide, with a longer in vivo half-life and ultimately with increased pharmacodynamic response along the somatotropic axis (endogenous GH, IGF-1 levels). Different PEGylated GRF conjugates were obtained and their bioactivity was tested in vitro and in vivo by monitoring endogenous growth hormone (GH) serum levels after intravenous (i.v.) injection in rats, and intravenous and subcutaneous (s.c.) injection in pigs. It was found that GRF-PEG conjugates are able to bind and activate the human GRF receptor, although with different potency. The effect of PEG molecular weight, number of PEG chains bound and position of PEGylation site on GRF activity were investigated. Mono-PEGylated isomers with a PEG5000 polymer chain linked to Lys 12 or Lys 21 residues, showed high biological activity in vitro, which is similar to that of hGRF1-29, and a higher pharmacodynamic response as compared to unmodified GRF molecule.

Investigation of surface properties of some polymers by a thermodynamic and mechanical approach: possibility of predicting mucoadhesion and biocompatibility.

Mucoadhesive properties of several polymers, such as sodium alginate, hydroxypropylmethyl cellulose, scleroglucan, xanthan gum, polyacrylic acid (Carbopol), and poly co-(methyl vinyl ether-maleic anhydride) (Gantrez), have been investigated by comparing a thermodynamical and a mechanical approach. Surface properties of polymers in the dry state have been studied by contact angle measurements and thermodynamical parameters derived by using different equations. This tensile adhesive strength of polymers in hydration conditions was measured by a modified DuNoy tensiometer. Comparison of the two different approaches has allowed us to conclude that thermodynamical consideration on surface energy can be used to evaluate mucoadhesive properties of materials. Data obtained with the two methods yielded a good linear correlation. Calculation of surface free energy of the considered materials also allowed a prediction of the water-polymer interface free energy: biocompatibility, defined according to the minimal interfacial free energy concept, could consequently be evaluated.