Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration

INTRODUCTION: Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn(−/0)) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn(−/0) mouse model. METHODS: To evaluate ADSC implant efficacy, Bgn(−/0) mice were intradiscally (L1-L2) injected with 8x10(4) ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn(−/0) mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area. RESULTS: After in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels. CONCLUSION: Overall, this work demonstrates that ADSC implant into degenerated disc of Bgn(−/0) mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Service discovery and composition in body area networks

In pervasive environments, Body Area Networks (BANs) are characterized by the mobility of their users. BANs can continuously interact with each other, thus enabling the provision of new applications and services at runtime. New complex services can be provided by composing simpler services available on neighbouring network nodes. However, since the topology of BANs is continuously changing due to users' movements, it is unfeasible to specify a-priori all possible configurations under which a given complex service can be composed. In order to address this issue, we introduce a two-layered service discovery and composition architecture, that proactively notifies a distributed service directory with changes in service availability. In order to cope with the network mobility and intermittent connectivity, our approach is to cluster nodes in the sensor network based on their connectivity patterns. We use a multi-agent state machine to recognize the availability of complex services and to provide them. Our solution is validated by a prototype implementation of our architecture, by the study of the statistical model of complex services, and by experimental evaluations

Strengths and Weaknesses of National Variety Trial Data for Multi-Environment Analysis: A Case Study on Grain Yield and Protein Content

Multi-environment trial studies provide an opportunity for the detailed analysis of complex traits. However, conducting trials across a large number of regions can be costly and labor intensive. The Australian National Variety Trials (NVT) provide grain yield and protein content (GPC) data of over 200 wheat varieties in many and varied environments across the Australian wheat-belt and is representative of similar trials conducted in other countries. Through our analysis of the NVT dataset, we highlight the advantages and limitations in using these data to explore the relationship between grain yield and GPC in the low yielding environments of Australia. Eight environment types (ETs), categorized in a previous study based on the time and intensity of drought stress, were used to analyze the impact of drought on the relationship between grain yield and protein content. The study illustrates the value of comprehensive multi-environment analysis to explore the complex relationship between yield and GPC, and to identify the most appropriate environments to select for a favorable relationship. However, the NVT trial design does not follow the rigor associated with a normal genotype × environment study and this limits the accuracy of the interpretation

Characterization of Small Micro-and Nanoparticles in Antarctic Snow by Electron Microscopy and Raman Micro-Spectroscopy

The impact of the anthropic activities in Antarctica is a concerning issue. According to the Scientific Committee on Antarctic Research, attention has to be paid to the next-generation contaminants deriving from both long-range atmospheric transport and local sources. In this study, the capabilities of transmission electron microscopy with energy-dispersive X-ray spectroscopy and Raman micro-spectroscopy were exploited to evaluate the size, morphology, and chemical composition of small micro- and nanoparticles, as well as their aggregates, in surface snow samples collected during the 2020–2021 austral summer in the coastal area of Victoria Land near the Mario Zucchelli research station. The presence of biological particles, mineral dust, sea salts, and small carbonaceous and plastic micro- and nanoparticles was assessed. Sulfate, carbonate, and nitrate minerals were detected in all the samples, whereas polyethylene, poly(ethylene-co-vinyl-acetate), and different kinds of carbonaceous materials were predominantly identified in the samples closest to the research base. The presence of small micro- and nanoparticles containing heavy metals and plastic polymers in samples collected in the areas surrounding the Italian research base highlights the impact of anthropogenic activities on the polar environment, suggesting the need for continuous monitoring to evaluate possible threats to the delicate Antarctic ecosystem

Frontiers in Anti-Cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-Angiogenic Add-On Therapy in Glioblastoma

Glioblastoma is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. Glioblastoma shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), has demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including glioblastoma. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss metformin’s potential antitumoral effects on glioblastoma, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of glioblastoma patients

Modulation of Neuroinflammation in the Central Nervous System: Role of Chemokines and Sphingolipids

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