•Mediterranean inlandsface marginalization due to factors stemming from natural constraints.•Abandonment was led by field agricultural use, slope and fragmentation.•Both abandonment and recovery ...activities are ongoing in Gennargentu-Mandrolisai.•Grasslands were the most recovered areas.•Encouraging coordination among farmerscould help mitigate the marginalization impacts.
Farmland abandonment is a growing issue in many mountainous regions worldwide, particularly in the Mediterranean basin. The central region of Gennargentu-Mandrolisai in Sardinia (Italy) is particularly susceptible to this trend due to its distinctive topography, its remote localisation and the distance from the primary urban centres of the region. In fact, this region was traditionally suited for agro-silvopastoral systems, but it was included in the national strategy for inland areas mainly because of the demographic decline and land abandonment. This paper aims to identify the main drivers of rural marginalisation, abandonment and de-anthropisation by combining qualitative and quantitative spatial data. Qualitative data were collected from 30 farmers’ interviews targeting young, dynamic, innovative farmers in order to identify possible triggers for maintaining agricultural activities. A diachronic analysis of land use from Corine Land Cover maps at five different dates over thirty years (1990, 2000, 2006, 2012 and 2018) was used to understand the main land use changes. The analysis of the surveyed farmland (1602 ha) showed that 21 % of the area was abandoned in the last three decades, and 15 % of abandoned land was recovered as farmland. The drivers of marginalisation identified by the farmers were analysed by a logistic regression model, which revealed that field management was influenced by ‘crop type’, ‘slope’ and ‘road distance from the farm buildings’. The interactions that arose between the natural characteristics and the traditional organisational system contributed to non-competitiveness and abandonment of farms in Gennargentu-Mandrolisai. The present data allow us to propose hypotheses on how agricultural activities could be shaped and how some drivers of marginality could be overcome thanks to the presence and the active work of many young farmers who are willing to further improve agriculture.
Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and ...deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APC
mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy.
•Educational initiatives should be introduced on the management of healthy women with germline BRCA1/2 mutations.•Risk-reducing bilateral salpingo-oophorectomy (RRBSO) should be performed by ...minimally invasive surgery.•It is mandatory for the physician to suggest hormone therapy to healthy BRCA1/2 mutation carriers.•Several hormonal compounds are available for this purpose, and the key is to tailor the treatment to the patient.•Genitourinary syndrome of the menopause is a chronic condition and local hormonal treatment is safe.•Caution is warranted when offering hormone therapy to healthy women older than 45 years with BRCA1/2 mutations.
Healthy women carrying pathogenic germline mutations in BRCA1 or BRCA2 genes have an increased risk of breast and ovarian cancer. Prophylactic gynecological surgery includes risk-reducing bilateral salpingo-oophorectomy, which, in selected cases, can be combined with hysterectomy. Prophylactic gynecological surgery is recommended after completion of childbearing and can be performed for women aged 35 or more for BRCA1 or 40 or more for BRCA2 mutation carriers. Risk-reducing bilateral salpingo-oophorectomy has several adverse effects related to estrogen deprivation, and so hormonal therapy could be the main strategy for healthy women. However, health professionals have many doubts about whether they are able to offer clear counseling on the management of early menopausal symptoms (i.e. vasomotor and genitourinary symptoms) in healthy women with a hereditary predisposition to female cancer. This ‘Ten-Point Guide’ summarizes the evidence regarding prophylactic gynecological surgery and supports healthcare providers in the management of healthy women carrying germline BRCA1 and BRCA2 mutations.
To overview the array of differential diagnoses among lipomatous tumours of the head and neck with special focus on their evaluation, three-dimensional assessment, and their available treatments.
The ...head and neck is an infrequent localization for lipomatous tumours, even though they represent the most common mesenchymal lesions. Lipoma, spindle cell/pleomorphic lipoma (SC/PL), atypical lipomatous tumour/well differentiated liposarcoma (ALT/WDLPS), de-differentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), and pleomorphic liposarcoma (PLPS) are the most distinctive histotypes. Lipoma and SC/PL present alterations of chromosomes 12 and 13, ALT/WDLPS and DDLPS both show the Mouse Double Minute 2 amplification, whereas MLPS presents a CHOP gene fusion. Diagnosis of PLPS is purely morphological as there is no pathognomonic genetic alteration identified to date. Radiological assessment can be challenging for the presence of nonadipose components within the lesion. Surgery is the mainstay of treatment, even though achieving true radicality in terms of a large cuff of healthy tissue surrounding the tumour is not always realistic in the head and neck. Adjuvant radiation, eventually in combination with systemic chemotherapy, has been shown to improve overall survival in patients with positive margins, high-grade, deep, and more than 5 cm lesions. Further studies should be aimed at the evaluation of the role of hadron therapy, as well as targeted drugs against overexpressed proteins.
Adequate differential diagnosis of the histotypes collected under the umbrella term of head and neck lipomatous tumours plays a fundamental role in treatment and follow-up of these lesions and requires specific expertise with referral to high-volume centres.
Collagen represents one of the most widely used biomaterial for scaffolds fabrication in tissue engineering as it represents the mechanical support of natural tissues. It also provides physical ...scaffolding for cells and it influences their attachment, growth, and tissue regeneration. Among all fibrillary collagens, type I is considered one of the gold standard for scaffolds fabrication, thanks to its high biocompatibility, biodegradability, and hemostatic properties. It can be extracted by chemical and enzymatic protocols from several collagen‐rich tissues, such as tendon and skin, of different animal species. Both the extraction processes and the manufacturing protocols for scaffolds fabrication provide structural and mechanical changes that can be tuned in order to deeply impact the properties of the final biomaterial. The aim of this review is to discuss the role of X‐rays to study structural changes of type I collagen from fresh collagen‐rich tissues (bovine, equine, fish) to the final scaffolds, with the aim to screen across available collagen sources and scaffolds fabrication protocols to be used in tissue regeneration.
Bovine, equine, tilapia fish type I collagen are studied by wide and small angle X‐ray scattering to evaluate the multilevel structure of raw materials and final scaffolds, and to screen across collagen sources and scaffolds fabrication protocols available for tissue engineering.
Abstract
Context
Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic and ...renal vascular function and structure, and induces epigenetic modifications.
Subjects and Methods
Forty hypertensive patients with type 2 diabetes were randomly assigned to 4-week treatment with dapagliflozin 10 mg or hydrochlorothiazide (HCT) 12.5 mg. Routine analyses; plasma renin activity; aldosterone, catecholamine, and 24-hour urinary electrolyte levels; flow-mediated dilation (FMD) of the brachial artery; carotid-femoral pulse-wave velocity (PWV); augmentation index; and resistive index and dynamic renal resistive index (DRIN) were measured at baseline and after treatment. Circulating miRNAs (miRs) related to heart failure (miR30e-5p, miR199a-3p), endothelial dysfunction (miR27b and miR200b), and renal function (miR130b-3p, miR21-5p) were assessed and related to the effects of treatments.
Results
Dapagliflozin and HCT marginally lowered blood pressure. Fasting glucose was lowered, whereas 24-hour diuresis, glycosuria, and osmolar clearance were increased by dapagliflozin (P < 0.001 for all), without affecting sodium excretion and glomerular filtration rate. Magnesium levels significantly increased after dapagliflozin treatment (P = 0.02). Neither dapagliflozin nor HCT modified FMD or PWV. DRIN did not vary in the dapagliflozin group, whereas it increased in the HCT group (P = 0.047 for time by treatment interaction). Both treatments induced variations in the expression of some miRs; dapagliflozin, but not HCT, significantly up-regulated miR30e-5p and downregulated miR199a-3p.
Conclusion
A putative epigenetic regulation of the protecting cardiovascular effect exerted by SGLT2 inhibitors was found. Dapagliflozin might exert nephroprotection by preserving renal vasodilating capacity.
Hemodynamic and systemic vascular effects of dapagliflozin undergo epigenetic regulation that favorably affects two miRs involved in heart failure.
Purpose
Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In ...this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity).
Methods
Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ).
Results
14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (
p
= 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91,
p
< 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people.
Conclusions
Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.
Autophagosomes are double-membraned vesicles that traffic harmful or unwanted cellular macromolecules to the vacuole for recycling. Although autophagosome biogenesis has been extensively studied, ...autophagosome maturation, i.e., delivery and fusion with the vacuole, remains largely unknown in plants. Here, we have identified an autophagy adaptor, CFS1, that directly interacts with the autophagosome marker ATG8 and localizes on both membranes of the autophagosome. Autophagosomes form normally in Arabidopsis thaliana cfs1 mutants, but their delivery to the vacuole is disrupted. CFS1’s function is evolutionarily conserved in plants, as it also localizes to the autophagosomes and plays a role in autophagic flux in the liverwort Marchantia polymorpha. CFS1 regulates autophagic flux by bridging autophagosomes with the multivesicular body-localized ESCRT-I component VPS23A, leading to the formation of amphisomes. Similar to CFS1-ATG8 interaction, disrupting the CFS1-VPS23A interaction blocks autophagic flux and renders plants sensitive to nitrogen starvation. Altogether, our results reveal a conserved vacuolar sorting hub that regulates autophagic flux in plants.
Highlights • Recurrent urinary tract infections are common in postmenopausal women. • Vaginal estrogens reduce the incidence of urinary tract infections. • Probiotics, cranberry extracts and d ...-mannose are effective in reducing the risk of urinary tract infections. • Further wide-scale randomized studies are needed to identify several methods to reduce the use of antibiotics.
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