The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy

Abstract Diabetic retinopathy (DR) is a remarkable microvascular complication of diabetes and it has been considered the leading cause of legal blindness in working-age adults in the world. Several overlapping and interrelated molecular pathways are involved in the development of this disease. DR is staged into different levels of severity, from the nonproliferative to the advanced proliferative form. Over the years the progression of DR evolves through a series of changes involving distinct types of specialized cells: neural, vascular and glial. Prior to the clinically observable vascular complications, hyperglycemia and inflammation affect retinal glial cells which undergo a wide range of structural and functional alterations. In this review, we provide an overview of the status of macroglia and microglia in the course of DR, trying to briefly take into account the complex biochemical mechanisms that affect the intimate relationship among neuroretina, vessels and glial cells

The Effect of Optimally Timed Osteopathic Manipulative Treatment on Length of Hospital Stay in Moderate and Late Preterm Infants: Results from a RCT

Introduction. Little research has been conducted looking at the effects of osteopathic manipulative treatment (OMT) on preterm infants. Aim of the Study. This study hypothesized that osteopathic care is effective in reducing length of hospital stay and that early OMT produces the most pronounced benefit, compared to moderately early and late OMT. A secondary outcome was to estimate hospital cost savings by the use of OMT. Methods. 110 newborns ranging from 32- to 37-week gestation were randomized to receive either OMT or usual pediatric care. Early, moderately early, and late OMT were defined as <4, <9, and <14 days from birth, respectively. Result. Hospital stay was shorter in infants receiving late OMT (−2.03; 95% CI −3.15, −0.91; P<0.01) than controls. Subgroup analysis of infants receiving early and moderately early OMT resulted in shorter LOS (early OMT: −4.16; −6.05, −2.27; P<0.001; moderately early OMT: −3.12; −4.36, −1.89; P<0.001). Costs analysis showed that OMT significantly produced a net saving of €740 (−1309.54, −170.33; P=0.01) per newborn per LOS. Conclusions. This study shows evidence that the sooner OMT is provided, the shorter their hospital stay is. There is also a positive association of OMT with overall reduction in cost of care

In Vivo Distribution of Corneal Epithelial Dendritic Cells in Patients With Glaucoma

The purpose of this study was to evaluate dendritic cell (DC) distribution, morphology, and DC density in the entire cornea of medically controlled glaucoma patients (MCGP), using in vivo confocal microscopy (IVCM).Fifty MCGP were enrolled, 15 patients with dry eye, and 15 healthy subjects served as controls. Patients were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire and then underwent tear film break-up time (BUT), corneal staining, and Schirmer test (ST) I and then IVCM. In vivo confocal microscopy evaluated the limbal and central DC density, the DCs morphology and distribution. Relationships among DC density, OSDI score, and corneal staining were analyzed.Medically controlled glaucoma patients were divided into 2 groups; group 1 (29 eyes) was tested with one drug; group 2 (21 eyes) was tested with ≥2 drugs. Dendritic cells were significantly higher at limbus than at central cornea in both groups. Limbal DCs were found in the 86.7%, 89.7%, 90.4%, and 93.3% of eyes in controls, groups 1 and 2, and DED; central corneal DCs were found in the 26.6%, 75.9%, 80.9%, and 86.6% of eyes in controls, groups 1 and 2, and DED. Dendritic cell density was higher in glaucoma groups and DED than in controls (P < 0.001). Group 2 and DED presented DC density significantly higher compared with group 1 (P < 0.05). In group 1 DC density was higher in patients taking preserved drugs than in those taking preservative-free drugs (P < 0.05). Dendritic cell density was higher in DED than in group 2 (P < 0.05). Dendritic cell density significantly correlated with corneal staining and OSDI (P < 0.001).Dendritic cells increase in the entire cornea of MCGP, with a higher density at limbus. These modifications may take part in the induction of the glaucoma-related ocular surface disease

Determinants of SARS-CoV-2 Contagiousness in Household Contacts of Symptomatic Adult Index Cases

BACKGROUND: Identifying determinants of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission in settings of contagion is fundamental to inform containment strategies. We assessed SARS-CoV-2 cycle threshold value (Ct) from the first diagnostic nasal–pharyngeal swab of symptomatic index cases and which demographic or clinical characteristics among cases and contacts are associated with transmission risk within households. METHODS: This is a retrospective prevalence study on secondary SARS-CoV-2 cases (SC) among the household contacts of symptomatic adult index cases randomly sampled from all the SARS-CoV-2-positive diagnostic nasopharyngeal swabs analyzed at our regional referral hospital (Amedeo di Savoia Hospital, Turin, Italy) in March, 2020. Index cases underwent a telephone survey to collect their demographic and clinical data and all their household contacts. The Ct value of RdRp gene from the first diagnostic swab of index cases was recorded and index cases were grouped according to Ct tertiles (A < first tertile, first ≤ B ≤ second tertile, C ≥ second tertile). Post hoc analysis was performed in SC as well as contacts that did not undergo SARS-CoV-2 testing but developed compatible signs and symptoms. Non-parametric tests and generalized linear models were run. RESULTS: Index (n = 72) and contact (n = 164) median age was 54 (48–63) and 32 (20–56) years, respectively. A total of 60, 50, and 54 subjects were contacts of group A, B, and C index cases, respectively; 35.9% of contacts were SC. Twenty-four further subjects (14.6%) met the criteria for symptom-based likely positive SC. The secondary attack rate was 36.0% (28.6–43.4), assuming a mean incubation period of 5 days and a maximum infectious period of 20 days. SC prevalence differed between Ct groups (53.3% A, 32.0% B, 20.4% C; p < 0.001). No difference in SC was found according to sex, presence of signs/symptoms, and COVID-19 severity of index cases, or according to contacts’ sex and number per household. The age of both index cases [aOR 4.52 (1.2–17.0) for 60 vs. ≤45 years old] and contacts [aOR 3.66 (1.3–10.6) for 60 vs. ≤45years old] and the Ct of the index [aOR 0.17 (0.07–0.4) for Ct ≥ 31.8 vs. Ct < 24.4] independently associated with SC risk. Sensitivity analysis including symptoms-based likely positive SC supported all the previous results. CONCLUSION: In confined transmission settings such as households, PCR Ct values may inform on the contagiousness of infected subjects and age may modulate transmission/contagion risk

Correction to: Accuracy and inter-observer agreement of the nice and kudo classifications of superficial colonic lesions: a comparative study

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Consensus document on controversial issues for the treatment of infections of the central nervous system: bacterial brain abscesses

Summary Background Bacterial brain abscesses remain a serious central nervous system problem despite advances in neurosurgical, neuroimaging, and microbiological techniques and the availability of new antibiotics. The successful treatment of brain abscesses requires surgery, appropriate antibiotic therapy, and eradication of the primary source; nevertheless many controversial issues on the management of this serious infection remain unresolved. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues were: (1) Which patients with bacterial brain abscesses can be managed safely using medical treatment alone? (1a) What is the efficacy in terms of outcome, tolerability, cost/efficacy, and quality of life of the different antibiotic regimens used to treat bacterial cerebral abscesses? (1b) Which antibiotics have the best pharmacokinetics and/or tissue penetration of brain and/or brain abscess? 2) What is the best surgical approach in terms of outcome in managing bacterial brain abscesses? Results are presented and discussed in detail. Methods A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied

A Survey on Design Methodologies for Accelerating Deep Learning on Heterogeneous Architectures

In recent years, the field of Deep Learning has seen many disruptive and impactful advancements. Given the increasing complexity of deep neural networks, the need for efficient hardware accelerators has become more and more pressing to design heterogeneous HPC platforms. The design of Deep Learning accelerators requires a multidisciplinary approach, combining expertise from several areas, spanning from computer architecture to approximate computing, computational models, and machine learning algorithms. Several methodologies and tools have been proposed to design accelerators for Deep Learning, including hardware-software co-design approaches, high-level synthesis methods, specific customized compilers, and methodologies for design space exploration, modeling, and simulation. These methodologies aim to maximize the exploitable parallelism and minimize data movement to achieve high performance and energy efficiency. This survey provides a holistic review of the most influential design methodologies and EDA tools proposed in recent years to implement Deep Learning accelerators, offering the reader a wide perspective in this rapidly evolving field. In particular, this work complements the previous survey proposed by the same authors in [203], which focuses on Deep Learning hardware accelerators for heterogeneous HPC platforms

A djuvant treatment in patients at high risk of recurrence of thymoma: Efficacy and safety of a three-dimensional conformal radiation therapy regimen

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. METHODS: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. RESULTS: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. CONCLUSION: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma

Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab

Nivolumab is one of the most commonly used monoclonal antibodies for advanced non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor. Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimination. Immune system regulation and immunodeficiency is frequent in non-small cell lung cancer patients. To date, no data have been reported about the relationship between nivolumab and VD. The aim of this study was to quantify plasma 25-hydroxyVD (25-VD) and 1,25-VD, nivolumab, and its anti-antibody before starting treatment (baseline) and at 15, 45 and 60 days of therapy. VD-pathway-associated gene single nucleotide polymorphisms (SNPs) were also evaluated. Molecules were quantified through enzyme-linked immunosorbent assay, and SNPs through real-time PCR. Forty-five patients were enrolled. Median nivolumab concentrations were 12.5 ug/mL, 22.3 ug/mL and 27.1 ug/mL at 15, 45 and 60 days respectively. No anti-nivolumab antibodies were found. Correlations were observed between nivolumab concentrations and 25-VD levels. Nivolumab concentrations were affected by VD-pathway-related gene SNPs. VDBP AC/CC genotype and baseline 25-VD &lt; 10 ng/mL predicted a nivolumab concentration cut-off value of &lt;18.7ug/mL at 15 days, which was associated with tumor progression. This is the first study showing VD marker predictors of nivolumab concentrations in a real-life context of non-small cell lung cancer treatment