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BACKGROUND: Angiosarcoma (AS) of the breast is very rare, accounting for 1% of all soft tissue breast tumors. AS may present as primary tumors of the breast or as secondary lesions usually associated with previous radiotherapy. Commonly, secondary AS affects older women (median age 67-71 years) with a clinical history of breast cancer. The preferred site of onset of RIAS is the edge of radiation fields, where radiation doses and tumor necrosis may be heterogeneous, resulting in a DNA damage and instability. Radical surgery is the treatment of choice, but no clear consensus exists on surgical management of breast AS. CASE REPORT: We describe an atypical case of relapsed RIAS after radical mastectomy, treated with new surgery and, considering the higher risk of recurrence, subsequent adjuvant chemotherapy with weekly paclitaxel. CONCLUSIONS: The frequency of radiation-induced angiosarcomas (RIAS) after breast-conserving surgery and radiotherapy has been increased to 0.14-0.5% among long survivors. Nevertheless, even if RIAS continues to be prognostically an extremely unfavorable cancer due to a high rate of recurrence, distant spread, and median overall survival (OS) of about 60 months, the benefits of loco-regional breast radiotherapy are clearly higher than the risk in developing angiosarcoma. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glioblastoma (GBM) is a highly lethal disease despite integrated treatment comprising radiotherapy plus concomitant and adjuvant temozolomide, with a median overall survival of less than 15 months. For recurrent glioblastoma, there is yet no standard therapy, considering that Bevacizumab have failed to improve overall survival (OS) while regorafenib had a little benefit over standard chemotherapy. In addition, the disease control rate is almost exclusively stability, with a poor objective response rate. CASE REPORT: Here we present a case of rapid response to regorafenib in early glioblastoma progression at the end of adjuvant radiotherapy: after a single cycle of regorafenib the patient observed an impressive improvement in clinical condition, disappearance of headaches and a clear reduction of neoplastic tissue in MRI. A brief review about new radiological patterns in Magnetic Resonance Imaging (MRI) related to the introduction in clinical practice of antiangiogenic drugs and tyrosine kinase inhibitors has also been carried out. CONCLUSIONS: Regorafenib was certainly a first turning point in the second-line treatment of GBM, showing longer response rates and mostly disease stability than bevacizumab. A switch-maintenance strategy with tyrosine kinase inhibitors may represent a valid second-line therapeutic option. [ABSTRACT FROM AUTHOR]

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An analysis of a cotE cotH double mutant gene from Bacillus subtilis reveals that CotH may be localized in the inner coat. CotH is involved in the assembly of many proteins on the outer layer of the coat. Spores of the cotH null mutant, though impaired in germination, are resistant to heat, lysozyme and chloroform. The mutant spores are pleiotropically deficient in many coat proteins such as products of cotB, cotC and cotG. The cotH gene is located at 300 degrees on the B. subtilis genetic map between the two divergent genes, cotB and cotG.

Bacillus subtilis cells in the stationary growth phase secrete the vegetative catalase KatA when grown in a rich culture medium. The bacteria requires KatA activity to protect itself completely from oxidative stress and H2O2. Cytoplasmic catalase activity alone does not provide protection from oxidative stress. This suggests that the vegetative catalase is an extracellular enzyme rather than an endocellular enzyme. The bacterial cells present in a sporulation-inducing medium do not produce any catalase.

The variance of soil moisture, vegetation and evapotranspiration over land has been recognized to be strongly connected to the variance of precipitation. However, the feedbacks and couplings between these variables are still not well understood and quantified. Furthermore, soil moisture and vegetation processes are associated to a memory and therefore they may have important implications for predictability. In this study we apply a generalized linear method, specifically designed to assess the reciprocal forcing between connected fields, to the latest available observational datasets of global precipitation, evapotranspiration, vegetation and soil moisture content. For the first time a long global observational dataset is used to investigate the spatial and temporal land variability and to characterize the relationships and feedbacks between land and precipitation. The variables considered show a significant coupling among each other. The analysis of the response of precipitation to soil moisture evidences a robust coupling between these two variables. In particular, the first two modes of variability of the precipitation forced by soil moisture appear to have a strong link with volcanic eruptions and ENSO cycles, respectively, and these links are modulated by the effects of evapotranspiration and vegetation. It is suggested that vegetation state and soil moisture provide a biophysical memory of ENSO and major volcanic eruptions, revealed through delayed feedbacks on rainfall patterns. The third mode of variability reveals a trend very similar to the trend of the inter-hemispheric contrast in SST and appears to be connected to greening/browning trends of vegetation over the last three decades. [ABSTRACT FROM AUTHOR]

The cryptic ilvlH locus of Salmonella typhimurium has genetic information for two distinct subunits of acetohydroxy acid synthase III. We show that the ilvH-encoded subunit is normally translated and the lack of activity is due to early termination of translation within the promoter-proximal ilvl gene. Analysis of the 5′ region of the operon led to identification of the promoter and the amino-terminal part of ilvl. Expression of this gene in a mutant producing acetohydroxy acid synthase is due to a transversion which creates a UUA (leucine) codon in the place of a UGA (stop) codon present in position 12 of the wild-type coding region. [ABSTRACT FROM AUTHOR]

The use of the extra virgin olive oil as covering in food preserves presents some problems and still today object of study. With this research it was investigate the changes of some analytical parameters that occur during the storage in the olive oils used as covering in eggplant preserves. It was ascertained that in the oils in presence of the eggplants a drastic decrease of the total phenols was verified immediately after the thermal treatment affecting the oxidative processes. Besides it was observed that in all the oils stored under light the values of the K270. ∆K, the total chlorophylls and the 1,2-DG36/1,3-DG36 ratio were significantly changed. [ABSTRACT FROM AUTHOR]

Aging is one of the main risk factors for neurodegenerative disorders, which represent a global burden on healthcare systems. Therefore, identifying new strategies to slow the progression of brain aging is a compelling challenge. In this article, we first assessed the potential anti-aging effects of the Citrus flavanone naringenin (NAR), an activator of the enzyme sirtuin-1 (SIRT1), in a 3R-compliant and short-lived aging model (i.e., the nematode C. elegans). Then, we investigated the preventive effects of a 6-month treatment with NAR (100 mg/kg, orally) against brain aging and studied its mechanism of action in middle-aged mice. We demonstrated that NAR (100 μM) extends lifespan and improves healthspan in C. elegans. In the brain of middle-aged mice, NAR promotes the activity of metabolic enzymes (citrate synthase, cytochrome C oxidase) and increases the expression of the SIRT1 enzyme. Consistently, NAR up-regulates the expression of downstream antioxidant (Foxo3, Nrf2, Ho-1), anti-senescence (p16), and anti-inflammatory (Il-6, Il-18) markers. Our findings support NAR supplementation to slow the signs of brain aging., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The term hypomineralisation of molars and incisors (MIH), introduced in 2001 by Weerheijm et al., describes a clinical state of hypomineralisation of permanent molars with frequent involvement of the incisors. MIH is considered a global dental problem with a prevalence ranging from 2.4% to 40.2% in the entire world paediatric population. The continuous increase in the prevalence of enamel anomalies, including MIH, indicates the need to define new intervention protocols based on the technological advances that are revolutionising paediatric dentistry. The use of ozone associated with the selective and minimally invasive excavation of the dental tissue combines the antibacterial properties of the gas with an ultra-conservative approach aimed at the maximum conservation of the dental tissue. The operative protocol described can be an important tool in the prevention and treatment of MIH. The aim of this work is to illustrate an operative clinical protocol based on the combined use of selective excavation and ozone for the treatment of carious lesions in paediatric patients with MIH.

In recent years, the loop-mediated isothermal amplification (LAMP) technique, designed for microbial pathogen detection, has acquired fundamental importance in the biomedical field, providing rapid and precise responses. However, it still has some drawbacks, mainly due to the need for a thermostatic block, necessary to reach 63 °C, which is the BstI DNA polymerase working temperature. Here, we report the identification and characterization of the DNA polymerase I Large Fragment from Deinococcus radiodurans (DraLF-PolI) that functions at room temperature and is resistant to various environmental stress conditions. We demonstrated that DraLF-PolI displays efficient catalytic activity over a wide range of temperatures and pH, maintains its activity even after storage under various stress conditions, including desiccation, and retains its strand-displacement activity required for isothermal amplification technology. All of these characteristics make DraLF-PolI an excellent candidate for a cutting-edge room-temperature LAMP that promises to be very useful for the rapid and simple detection of pathogens at the point of care.

The use of variable renewable energy sources to generate electricity introduces a dependency on meteorological factors into power systems. With the renewables share growing globally, often driven by political pressures, the reliability and efficiency of power systems are increasingly affected by this dependency. In this paper, we investigate the impact of the natural variability of meteorological parameters on the European power system in 2030. We specifically focus on (1) analysing the main European weather patterns affecting renewable energy production and (2) understanding the co-variability of this production among European countries. The identification of a set of patterns in the behaviour of key power system operation indicators allows us to analyse the relationship between large-scale weather regimes and daily power system operations in a 2030 European energy context. Regarding renewable generation, analysis of the co-variability shows that European power systems tend to form two clusters, in each of which all the regions tend to show a positive correlation among themselves and a negative correlation with the other cluster. Our analysis of the most important large-scale weather regimes shows that during cyclonic patterns, the carbon intensity of all the European power systems is lower than normal, while the opposite happens during blocking regimes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 De Felice et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non-Small Cell Lung Cancer (NSCLC) with bone metastasis and poor performance status has the worst prognosis even in strong PD-L1 expression patients. Treatment approach includes immuno- or chemo-immunotherapy, Radiotherapy (RT) and Bone-Targeted Therapy (BTT) but there is insufficient data to suggest the best time to use each of them, alone or in combination. Using an integrated and synergistic treatment strategy with immunotherapy, radiotherapy, and Denosumab as BTT is probably the best treatment planning for metastatic NSCLC for both good and poor performance status patients, although more data are needed to confirm this approach. Here we describe an interesting case report on patient with extensive bone involvement from NSCLC and PS >2 treated simultaneously with radiotherapy, immunotherapy and BTT, achieving an excellent clinical benefit, radiological and metabolic complete response, as a sort of Lazarus effect. We analyzed our result comparing with currently published data about radio-immunotherapy or immunotherapy and BTT combination even though there is no published experience about integration of all 3 treatments. Approval studies often do not represent real-world experience (RWE), so we analyzed data from both RWE and clinical trials., (Copyright © 2023 Elsevier Inc. All rights reserved.)

With increasing maternal cannabis use, there is a need to investigate the lasting impact of prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main psychotropic compound in cannabis, on cognitive/memory function. The endocannabinoid system (ECS), which relies on polyunsaturated fatty acids (PUFAs) to function, plays a crucial role in regulating prefrontal cortical (PFC) and hippocampal network-dependent behaviors essential for cognition and memory. Using a rodent model of prenatal cannabis exposure (PCE), we report that male and female offspring display long-term deficits in various cognitive domains. However, these phenotypes were associated with highly divergent, sex-dependent mechanisms. Electrophysiological recordings revealed hyperactive PFC pyramidal neuron activity in both males and females, but hypoactivity in the ventral hippocampus (vHIPP) in males, and hyperactivity in females. Further, cortical oscillatory activity states of theta, alpha, delta, beta, and gamma bandwidths were strongly sex divergent. Moreover, protein expression analyses at postnatal day (PD)21 and PD120 revealed primarily PD120 disturbances in dopamine D1R/D2 receptors, NMDA receptor 2B, synaptophysin, gephyrin, GAD67, and PPARα selectively in the PFC and vHIPP, in both regions in males, but only the vHIPP in females. Lastly, using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), we identified region-, age-, and sex-specific deficiencies in specific neural PUFAs, namely docosahexaenoic acid (DHA) and arachidonic acid (ARA), and related metabolites, in the PFC and hippocampus (ventral/dorsal subiculum, and CA1 regions). This study highlights several novel, long-term and sex-specific consequences of PCE on PFC-hippocampal circuit dysfunction and the potential role of specific PUFA signaling abnormalities underlying these pathological outcomes., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Cannabis has shown therapeutic potential in mood and anxiety-related pathologies. However, the two primary constituents of cannabis, cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC) produce distinct effects on molecular pathways in neural circuits associated with affective disorders. Moreover, it has been proposed that the combination of THC: and CBD may have unique synergistic properties. In the present study, the effects of a 1:100 THC: CBD ratio edible formulation were tested in behavioural, neuronal and molecular assays for anxiety and depressive-like endophenotypes. Adult male and female Sprague-Dawley rats were stressed for 14 days. Then, for three weeks, open field, elevated plus maze, light/dark box, social interaction, sucrose preference, and the forced swim test were performed 90 minutes after acute consumption of CBD (30 mg/kg), THC (0.3 mg/kg), or 1:100 combination of THC:CBD. After behavioural tests, in vivo, neuronal electrophysiological analyses were performed in the ventral tegmental area and prefrontal cortex (PFC). Furthermore, western-blot experiments examined the expression of biomarkers associated with mood and anxiety disorders, including protein kinase B (Akt), glycogen synthase kinase-3 (GSK-3), BDNF, mTOR, D1, and D2 receptor in nucleus accumbens (NAc) and PFC.Edible THC:CBD produces significant anxiolytic and antidepressant effects only in stressed male rats. In most cases, the combination of THC and CBD had stronger effects than either phytochemical alone. These synergistic effects are associated with alterations in Akt/GSK3 and D2-R expression in NAc and BDNF expression in PFC. Furthermore, THC:CBD reverses chronic stress-induced alterations in PFC neuronal activity. These findings demonstrate a novel synergistic potential for THC:CBD edible formulations in stress-related pathologies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Immune checkpoint inhibitors (ICIs) are specific monoclonal antibodies directed against inhibitory targets of the immune system, mainly represented by programmed death-1 (PD1) ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), thus enabling an amplified T-cell-mediated immune response against cancer cells. These drugs have significantly improved prognosis in patients with advanced metastatic cancer (e.g., melanoma, non-small cell lung cancer, renal cell carcinoma). However, uncontrolled activation of anti-tumor T-cells could trigger an excessive immune response, possibly responsible for multi-organ damage, including, among others, lymphocytic myocarditis. The incidence of ICIs-induced myocarditis is underestimated and the patients affected are poorly characterized. The diagnosis and management of this condition are mainly based on expert opinion and case reports. EKG and ultrasound are tests that can help identify patients at risk of myocarditis during treatment by red flags, such as QRS complex enlargement and narrowing of global longitudinal strain (GLS). Therapy of ICI-related myocarditis is based on immunosuppressors, monoclonal antibodies and fusion proteins. A future strategy could involve the use of microRNAs. This review considers the current state of the art of immune-related adverse cardiovascular events, focusing on histological and clinical features, diagnosis and management, including current treatments and future pharmacological targets.

Early life exposure to Endocrine Disruptor Chemicals (EDCs), such as the organophosphate pesticide Chlorpyrifos (CPF), affects the thyroid activity and dependent process, including the glucose metabolism. The damage of thyroid hormones (THs) as a mechanism of action of CPF is underestimated because the studies rarely consider that TH levels and signaling are customized peripherally. Here, we investigated the impairment of metabolism/signaling of THs and lipid/glucose metabolism in the livers of 6-month-old mice, developmentally and lifelong exposed to 0.1, 1, and 10 mg/kg/die CPF (F1) and their offspring similarly exposed (F2), analyzing the levels of transcripts of the enzymes involved in the metabolism of T3 ( Dio1 ), lipids ( Fasn , Acc1 ), and glucose ( G6pase , Pck1 ). Both processes were altered only in F2 males, affected by hypothyroidism and by a systemic hyperglycemia linked to the activation of gluconeogenesis in mice exposed to 1 and 10 mg/kg/die CPF. Interestingly, we observed an increase in active FOXO1 protein due to a decrease in AKT phosphorylation, despite insulin signaling activation. Experiments in vitro revealed that chronic exposure to CPF affected glucose metabolism via the direct modulation of FOXO1 activity and T3 levels in hepatic cells. In conclusion, we described different sex and intergenerational effects of CPF exposure on the hepatic homeostasis of THs, their signaling, and, finally, glucose metabolism. The data points to FOXO1-T3-glucose signaling as a target of CPF in liver.

Obstructive sleep apnoea syndrome (OSAS) is a sleep-disordered breathing characterized by nocturnal collapses of the upper airway resulting in cycles of blood oxygen partial pressure oscillations, which lead to tissue and cell damage due to intermittent hypoxia (IH) episodes. Since OSAS-derived IH may lead to cognitive impairment through not fully cleared mechanisms, herein we developed a new in vitro model mimicking IH conditions to shed light on its molecular effects on microglial cells, with particular attention to the inflammatory response. The in vitro model was set-up and validated by measuring the hypoxic state, HIF-1α levels, oxidative stress by ROS production and mitochondrial activity by MTS assay. Then, the mRNA and protein levels of certain inflammatory markers (NF-κB and interleukin 6 (IL-6)) after different IH treatment protocols were investigated. The IH treatments followed by a normoxic period were not able to produce a high inflammatory state in human microglial cells. Nevertheless, microglia appeared to be in a state characterized by increased expression of NF-κB and markers related to a primed phenotype. The microglia exposed to IH cycles and stimulated with exogenous IL-1β resulted in an exaggerated inflammatory response with increased NF-κB and IL-6 expression, suggesting a role for primed microglia in OSAS-driven neuroinflammation., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Although the imbalance of circulating levels of Thyroid Hormones (THs) affects female fertility in vertebrates, its involvement in the promotion of Premature Ovarian Aging (POA) is debated. Therefore, altered synthesis of THs in both thyroid and ovary can be a trait of POA. We investigated the relationship between abnormal TH signaling, dysthyroidism, and POA in evolutionary distant vertebrates: from zebrafish to humans. Ovarian T3 signaling/metabolism was evaluated by measuring T3 levels, T3 responsive transcript, and protein levels along with transcripts governing T3 availability (deiodinases) and signaling (TH receptors) in distinct models of POA depending on genetic background and environmental exposures (e.g., diets, pesticides). Expression levels of well-known ( Amh , Gdf9 , and Inhibins) and novel ( miR143/145 and Gas5 ) biomarkers of POA were assessed. Ovarian dysthyroidism was slightly influenced by genetics since very few differences were found between C57BL/6J and FVB/NJ females. However, diets exacerbated it in a strain-dependent manner. Similar findings were observed in zebrafish and mouse models of POA induced by developmental and long-life exposure to low-dose chlorpyrifos (CPF). Lastly, the T3 decrease in follicular fluids from women affected by diminished ovarian reserve, as well as of the transcripts modulating T3 signaling/availability in the cumulus cells, confirmed ovarian dysthyroidism as a common and evolutionary conserved trait of POA.

Chronic exposure to Δ-9-tetrahydrocannabinol (THC) during adolescence is associated with long-lasting cognitive impairments and enhanced susceptibility to anxiety and mood disorders. Previous evidence has revealed functional and anatomical dissociations between the posterior vs. anterior portions of the hippocampal formation, which are classified as the dorsal and ventral regions in rodents, respectively. Notably, the dorsal hippocampus is critical for cognitive and contextual processing, whereas the ventral region is critical for affective and emotional processing. While adolescent THC exposure can induce significant morphological disturbances and glutamatergic signaling abnormalities in the hippocampus, it is not currently understood how the dorsal vs. ventral hippocampal regions are affected by THC during neurodevelopment. In the present study, we used an integrative combination of behavioral, molecular, and neural assays in a neurodevelopmental rodent model of adolescent THC exposure. We report that adolescent THC exposure induces long-lasting memory deficits and anxiety like-behaviors concomitant with a wide range of differential molecular and neuronal abnormalities in dorsal vs. ventral hippocampal regions. In addition, using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), we show for the first time that adolescent THC exposure induces significant and enduring dysregulation of GABA and glutamate levels in dorsal vs. ventral hippocampus. Finally, adolescent THC exposure induced dissociable dysregulations of hippocampal glutamatergic signaling, characterized by differential glutamatergic receptor expression markers, profound alterations in pyramidal neuronal activity and associated oscillatory patterns in dorsal vs. ventral hippocampal subregions., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)