The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions.

Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion's trajectory to cancer

Managing multiple pressures for cetaceans’ conservation with an Ecosystem-Based Marine Spatial Planning approach

Despite the recognized important ecological role that cetaceans play in the marine environment, their protection is still scarcely enforced in the Mediterranean Sea even though this area is strongly threatened by local human pressures and climate change. The piecemeal of knowledge related to cetaceans' ecology and distribution in the basin undermines the capacity of addressing cetaceans' protection and identifying effective conservation strategies. In this study, an Ecosystem-Based Marine Spatial Planning (EB-MSP) approach is applied to assess human pressures on cetaceans and guide the designation of a conservation area in the Gulf of Taranto, Northern Ionian Sea (Central-eastern Mediterranean Sea). The Gulf of Taranto hosts different cetacean species that accomplish important phases of their life in the area. Despite this fact, the gulf does not fall within any area-based management tools (ABMTs) for cetacean conservation. We pin down the Gulf of Taranto being eligible for the designation of diverse ABMTs for conservation, both legally and non-legally binding. Through a risk-based approach, this study explores the cause-effect relationships that link any human activities and pressures exerted in the study area to potential effects on cetaceans, by identifying major drivers of potential impacts. These were found to be underwater noise, marine litter, ship collision, and competition and disturbance on preys. We draw some recommendations based on different sources of available knowledge produced so far in the area (i.e., empirical evidence, scientific and grey literature, and expert judgement) to boost cetaceans’ conservation. Finally, we stress the need of sectoral coordination for the management of human activities by applying an EB-MSP approach and valuing the establishment of an ABMT in the Gulf of Taranto

Traumatic brain injury: A forensic approach: A literature review

Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide. This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histological examinations with particular attention paid to immunohistochemistry and molecular biology. In the light of the results of this mini-review, an accurate forensic approach can be considered mandatory in the examination of suspected TBI with medico-legal importance, in order to gather all the possible evidence to corroborate the diagnosis of a lesion that may have caused, or contributed to, death. From this point of view, only the use of an evidence-based protocol can reach a suitable diagnosis, especially in those cases in which there are other neuropathological conditions (ischemia, neurodegeneration, neuro-inflammation, dementia) that may have played a role in death. This is even more relevant when corpses, in an advanced state of decomposition, are studied, where the radiological, macroscopic and histological analyses fail to give meaningful answers. In these cases, immune-histochemical and molecular biology diagnostics are of fundamental importance and a forensic neuropathologist has to know them. Particularly, MiRNAs are promising biomarkers for TBI both for brain damage identification and for medico-legal aspects, even if further investigations are required to validate the first experimental studies. In the same way, the genetic substrate should be examined during any forensic examination, considering its importance in the outcome of TBI

Top-down cascading effects driven by the odontocetes in the Gulf of Taranto (Northern Ionian Sea, Central Mediterranean Sea)

An investigation of the marine food web in the Gulf of Taranto (Northern Ionian Sea, Central Mediterranean Sea) was carried out to explore the top-down cascading effects driven by the Odontocetes. The food web was analysed by a mass-balance model using 51 functional groups and detailing the trophic impacts of the striped and common bottlenose dolphins, the Risso's dolphin and the sperm whale during the period 2010-2014. Odontocetes resulted top-predators with the highest TL estimated for the Risso's dolphin (TL=5.40) and the lowest for the common bottlenose dolphin (TL=4.47). The striped dolphin played the highest top-down control, showing cascading effects up to the 3rd TL. The Risso's dolphin and the sperm whale played similar cascading effects, but weaker than the striped dolphin. Understanding pattern and strengthen of trophic controls played by the Odontocetes within the food web could contribute to identify the basal mechanisms involved in the ecosystem functioning

Environmental variables and machine learning models to predict cetacean abundance in the Central-eastern Mediterranean Sea

: Although the Mediterranean Sea is a crucial hotspot in marine biodiversity, it has been threatened by numerous anthropogenic pressures. As flagship species, Cetaceans are exposed to those anthropogenic impacts and global changes. Assessing their conservation status becomes strategic to set effective management plans. The aim of this paper is to understand the habitat requirements of cetaceans, exploiting the advantages of a machine-learning framework. To this end, 28 physical and biogeochemical variables were identified as environmental predictors related to the abundance of three odontocete species in the Northern Ionian Sea (Central-eastern Mediterranean Sea). In fact, habitat models were built using sighting data collected for striped dolphins Stenella coeruleoalba, common bottlenose dolphins Tursiops truncatus, and Risso's dolphins Grampus griseus between July 2009 and October 2021. Random Forest was a suitable machine learning algorithm for the cetacean abundance estimation. Nitrate, phytoplankton carbon biomass, temperature, and salinity were the most common influential predictors, followed by latitude, 3D-chlorophyll and density. The habitat models proposed here were validated using sighting data acquired during 2022 in the study area, confirming the good performance of the strategy. This study provides valuable information to support management decisions and conservation measures in the EU marine spatial planning context

Review adverse effects of anabolic-androgenic steroids: A literature review

Anabolic-androgenic steroids (AASs) are a large group of molecules including endoge-nously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes’ performance, minimizing androgenic effects. AAS use is very popular and 1–3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue. The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs. Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field. In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation

A LEED structural analysis of the Co(100) surface

The structure of the clean Co(1010) surface has been analysed by LEED. Application of a recently developed computational scheme reveals the prevalence of the termination A in which the two topmost layers exhibit a narrow spacing of 0.62 Å, corresponding to a 12.8(±0.5)% contraction with respect to the bulk value, while the spacing between the second and third layer is slightly expanded by 0.8(±0.2)%

Mistrial or Misdiagnosis: The Importance of Autopsy and Histopathological Examination in Cases of Sudden Infant Bronchiolitis-Related Death

Pediatrics, among all the branches of medicine, is a sector not particularly affected by a high number of claims. Nevertheless, the economic value of the compensation is significantly high, for example, in cases of children who suffered multiple disabilities following perinatal lesions with a long life expectancy. In Italy, most of the claims for compensation concern surgical pathologies and infections. Among these latter, the dominant role is taken by respiratory tract infections. In this context, the purpose of this manuscript is to present a case series of infant deaths in different emergency-related facilities (ambulances, emergency rooms) denounced by relatives. Following these complaints, the autopsy was performed, and subsequent histological examinations revealed the presence of typical and pathognomonic histological findings of acute viral bronchiolitis, whose morphological appearance is poorly reported in the literature. The analysis of these cases made it possible to highlight the following conclusions: the main problems in diagnosing sudden death causes, especially in childhood, are the rapidity of death and the scarce correlation between the preexistent diseases and of the cause of death itself. For all these reasons, the autopsy, either clinical or medicolegal, is mandatory in cases of sudden unexpected infant death to manage claim requests because only the histological examinations performed on samples collected during the autopsy can reveal the real cause of death

Retrospective 8-year study on the antibiotic resistance of uropathogens in children hospitalised for urinary tract infection in the emilia-romagna region, italy

The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospital-ised for UTI between January 1st, 2012, and June 30th, 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to anti-microbial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and ration-alise antibiotic consumption must be implemented

Surgical Antimicrobial Prophylaxis in Abdominal Surgery for Neonates and Paediatrics: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs), i.e., surgery-related infections that occur within 30 days after surgery without an implant and within one year if an implant is placed, complicate surgical procedures in up to 10% of cases, but an underestimation of the data is possible since about 50% of SSIs occur after the hospital discharge. Gastrointestinal surgical procedures are among the surgical procedures with the highest risk of SSIs, especially when colon surgery is considered. Data that were collected from children seem to indicate that the risk of SSIs can be higher than in adults. This consensus document describes the use of preoperative antibiotic prophylaxis in neonates and children that are undergoing abdominal surgery and has the purpose of providing guidance to healthcare professionals who take care of children to avoid unnecessary and dangerous use of antibiotics in these patients. The following surgical procedures were analyzed: (1) gastrointestinal endoscopy; (2) abdominal surgery with a laparoscopic or laparotomy approach; (3) small bowel surgery; (4) appendectomy; (5) abdominal wall defect correction interventions; (6) ileo-colic perforation; (7) colorectal procedures; (8) biliary tract procedures; and (9) surgery on the liver or pancreas. Thanks to the multidisciplinary contribution of experts belonging to the most important Italian scientific societies that take care of neonates and children, this document presents an invaluable reference tool for perioperative antibiotic prophylaxis in the paediatric and neonatal populations