The Phytoestrogen Quercetin Impairs Steroidogenesis and Angiogenesis in Swine Granulosa Cells In Vitro

Experimental evidence documents that nutritional phytoestrogens may interact with reproductive functions but the exact mechanism of action is still controversial. Since quercetin is one of the main flavonoids in livestock nutrition, we evaluated its possible effects on cultured swine granulosa cell proliferation, steroidogenesis, and redox status. Moreover, since angiogenesis is essential for follicle development, the effect of the flavonoid on Vascular Endothelial Growth Factor output by granulosa cells was also taken into account. Our data evidence that quercetin does not affect granulosa cell growth while it inhibits progesterone production and modifies estradiol 17β production in a dose-related manner. Additionally, the flavonoid interferes with the angiogenic process by inhibiting VEGF production as well as by altering redox status. Since steroidogenesis and angiogenesis are strictly involved in follicular development, these findings appear particularly relevant, pointing out a possible negative influence of quercetin on ovarian physiology. Therefore, the possible reproductive impact of the flavonoid should be carefully considered in animal nutrition

A Reaction Attack against Cryptosystems based on LRPC Codes

Rank metric is a very promising research direction for code-based cryptography. In fact, thanks to the high complexity of generic decoding attacks against codes in this metric, it is possible to easily select parameters that yield very small data sizes. In this paper we analyze cryptosystems based on Low-Rank Parity-Check (LRPC) codes, one of the classes of codes that are efficiently decodable in the rank metric. We show how to exploit the decoding failure rate, which is an inherent feature of these codes, to devise a reaction attack aimed at recovering the private key. As a case study, we cryptanalyze the recent McNie submission to NIST’s Post-Quantum Standardization process. Additionally, we provide details of a simple implementation to validate our approach

Interaction of an anticancer peptide fragment of azurin with p53 and its isolated domains studied by atomic force spectroscopy

p28 is a 28-amino acid peptide fragment of the cupredoxin azurin derived from Pseudomonas aeruginosa that preferentially penetrates cancerous cells and arrests their proliferation in vitro and in vivo. Its antitumor activity reportedly arises from post-translational stabilization of the tumor suppressor p53 normally downregulated by the binding of several ubiquitin ligases. This would require p28 to specifically bind to p53 to inhibit specific ligases from initiating proteosome-mediated degradation. In this study, atomic force spectroscopy, a nanotechnological approach, was used to investigate the interaction of p28 with full-length p53 and its isolated domains at the single molecule level. Analysis of the unbinding forces and the dissociation rate constant suggest that p28 forms a stable complex with the DNA-binding domain of p53, inhibiting the binding of ubiquitin ligases other than Mdm2 to reduce proteasomal degradation of p53

Climate change may cause the extinction of the butterfly Lasiommata petropolitana in the Apennines

Climate change represents a threat to narrow-ranged mountain species living in low-altitude massifs. We studied the disjunct Apennine population of Lasiommata petropolitana (Lepidoptera, Nymphalidae) in the Gran Sasso and Monti della Laga National Park. We quantified the altitudinal shifts undergone in the last decades (1964–2021) in the Alps and Apennines and estimated the local extinction risk due to climate change. We also sequenced the COI mitochondrial marker of seven Apennine specimens, comparing them with those available across the Palearctic. We projected the probability of presence for the species under a future climatic scenario using an ensemble forecasting approach. We found that, despite geographical isolation, the Apennine population of L. petropolitana displays a single widespread COI haplotype also occurring in most European populations. In the Alps and Apennines, this species has shifted uphill an average of 6.3 m per year since 1964. Accordingly, our model predicted a likely extinction in the Apennines by about 2060, due to a reduction of the climatic suitability in this region. Implications for insect conservation Implications for insect conservation Despite its potential loss in the Apennines would not erode mitochondrial diversity, L. petropolitana characterises the butterfly community of the Gran Sasso massif as an alpine enclave. The loss of the Apennine population, together with those of other orophilous butterflies, could trigger a homogenization of alpha and beta diversity and induce a loss of functional diversity in the impoverished high-altitude biotas. As habitat heterogeneity is a key aspect for populations to endure climate change, the maintenance of varied microhabitats, mainly through grazing management, could address the decline of this population.Open access funding provided by Università degli Studi di Firenze within the CRUI-CARE Agreement. This study was funded by the Ministero Italiano della Transizione Ecologica within the project “Ricerca e conservazione sui lepidotteri diurni di sei Parchi Nazionali dell’Appennino Centro-Settentrionale”. Support was also provided by the Academy of Finland (Academy Research Fellow, decision no. 328895) to VD. RV is supported by Grant PID2019-107078 GB-I00 funded by Ministerio de Ciencia e Innovación and Agencia Estatal de Investigació

Breast cancer in the elderly: Treatment of 1500 patients

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years). The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors

Transient global amnesia: Isolated event or healthy predictor? Clinical experience of an Italian Emergency Department

Transient global amnesia (TGA) is a clinical syndrome characterized by reversible anterograde amnesia, in which the patient is alert, self-awareness appears intact and other neurological symptoms are absent. The diagnosis is based on the following criteria: i) witnessed event; ii) acute onset of anterograde amnesia; iii) no accompanying neurological symptoms; iv) no alteration of consciousness; v) no epileptic features; vi) resolution within 24 hours; vii) exclusion of other causes. We conducted a cohort study at the Department of Emergency Medicine on 119 patients with TGA diagnosis from 2010 to 2014, with follow-up evaluation by telephone interview. The objectives of our study were to evaluate the frequency of subsequent episodes, to identify predisposing factors, and to investigate whether TGA is a possible predictor of neurological disease. The frequency of comorbidity in our population was in line with literature. We observed a recurrence rate of 9.5%, with a prevalence for the male gender, while no other factor correlates with TGA recurrence. TGA was not a predictor of further neurological diseases. In conclusion, TGA is a benign pathology with a low probability of relapse. Accordingly, management in Emergency Department should be based on a correct initial clinical classification for rapid discharge

An unexpected turn of events: A rare case of Acquired Haemophilia A after a violin spider bite

We report an interesting clinical case of Acquired Haemophilia A (AHA) after a probable Loxosceles rufescens spider bite in a 73- year-old woman, admitted to an Emergency Department (ED) of Central Italy during April 2019. AHA is a rare disease, whose acute clinical manifestations are not widely known by most ED physicians; its prompt recognition and treatment are crucial to avoid fatal bleeding. In particular, the development of AHA after a violin spider bite (another rare and poorly characterized clinical condition) has never been described. Therefore, our case report could provide useful insight into the understanding and treatment of such unusual and possibly life-threatening conditions

Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p &lt; 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p &lt; 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p &lt; 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Loco regional failure pattern after lumpectomy and breast irradiation in 4185 patients with T1 and T2 breast cancer. Implications for nodal irradiation

The aim of this study is to determinate incidence and risk factors for loco regional failure (LRR) (breast, supraclavicular, axillary and internal mammary nodes) and indications for nodal irradiation. From January 1980 to December 2001, 4,185 patients with T1-T2 breast cancer were treated with conservative surgery and whole breast radiotherapy without nodal irradiation at the University of Florence. The median age was 55 years (range 19-86). All patients were followed for a median of eight years (range 3 months to 20 years). Multivariate analysis showed as independent prognostic factors for isolated nodal relapse (NR) the presence of more than three positive lymph nodes (PAN) (p = 0.001), angiolymphatic invasion (p = 0.002) and pT2 (p = 0.02). However, only 4.8% of patients with more than three PAN developed NR as the only site of recurrence. Having one to three PAN was not associated with an increased risk of NR. We believe that it is not necessary to prescribe nodal irradiation to patients with negative or one to three PAN. Regarding patients with more than three PAN, the number of isolated NR is also small to routinely justify a node irradiation

The isolated Erebia pandrose Apennine population is genetically unique and endangered by climate change

1. Climate change is causing shifts in the distribution of many species and populations inhabiting mountain tops are particularly vulnerable to these threats because they are constrained in altitudinal shifts. Apennines are a relatively narrow and low mountain chain located in Southern Europe, which hosts many isolated populations of mountain species. The butterfly Erebia pandrose was recorded for the last time in the Apennines in 1977, on the top of a single massif (Monti della Laga). 2. We confirmed the presence of a small, isolated population of E. pandrose in the Apennines, at a distance of more than 400¿km to any other known populations. Then, we examined the cytochrome c oxidase subunit 1 mitochondrial DNA marker of this species across the Palaearctic area and estimated the potential decline over the Alps and the Apennines due to future climatic changes. 3. The Apennine population represents an endemic lineage characterised by eight mutations over the 658¿bp analysed (1.2%). In the Alps and Apennines, this species has shifted uphill more than 3 m per year since the end of the 19th century and more than 22 m per year since 1995. Species distribution models suggested that these mountain populations will experience a generalised loss of climatic suitability, which, according to our projections, could lead to the extinction of the Apennine population in a few decades. 4. Erebia pandrose has the potential to become a flagship species for advertising the risk of losing unique fractions of genetic diversity for mountain species.funded by the project: ‘Ricerca e conservazione sui lepidotteri diurni di sei Parchi Nazionali dell'Appennino centro-settentrionale’. Support for this research was also provided by ‘La Caixa’ Foundation (ID 100010434) to M.M. (grant LCF/BQ/DR20/11790020), by the Academy of Finland to V.D. (Academy Research Fellow, decision no. 328895) and by project PID2019-107078GB-I00/AEI/10.13039/501100011033 to R.V.1 Introduction 2 Materials and methods 2.1 Data collection 2.2 COI analyses 2.3 Species distribution modelling 2.4 Elevational shifts of E. pandrose records through time 3 Results 3.1 COI structure 3.2 Climate change effects 4 Discussion 4.1 The population of Monte Gorzano 4.2 What is the future for E. pandrose on the Apennines? 4.3 Erebia pandrose in the context of preserving Apennine butterflies 5 Conclusions Acknowledgements Conflict of interes