Hida theory over some unitary Shimura varieties without ordinary locus

We develop Hida theory for Shimura varieties of type A without ordinary locus. In particular we show that the dimension of the space of ordinary forms is bounded independently of the weight and that there is a module of $\Lambda$-adic cuspidal ordinary forms which is of finite type over $\Lambda$, where $\Lambda$ is a twisted Iwasawa algebra

Eigenvarieties for non-cuspidal modular forms over certain PEL Shimura varieties

Generalizing the recent method of Andreatta, Iovita, and Pil-loni for cuspidal forms, we construct eigenvarieties for symplectic and unitary groups that parametrize systems of eigenvalues of overconvergent and locally analytic p-adic modular forms of a fixed 'degree of cuspidality'. The dimension of our eigenvarieties depends on this degree of cuspidality, it is maximal for cuspidal forms and it is 1 for forms that are 'not cuspidal at all'. Studying the relations between the eigenvarieties we have constructed, we are able to prove a conjecture of Urban about the dimension of the irreducible components of Hansen's eigenvariety in the case of the group GSp 4 over Q

Amelioration of injury-induced tissue acidosis by a nonsteroidal analgesic attenuates antinociceptive effects of the pH-dependent opioid agonist NFEPP

Opioid agonists are powerful drugs for managing pain. However, their central side effects are limiting their use and drugs with similar potency, but a lower risk profile are needed. (+/-)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenylpropionamide (NFEPP) is a novel opioid agonist that preferentially activates opioid receptors at acidic extracellular pH. NFEPP was designed to activate peripheral opioid receptors in injured tissue, therefore precluding side effects elicited at normal pH in brain or intestinal wall. Considering the common combination of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) in multimodal analgesia, we investigated the interaction between NFEPP and a widely prescribed prototypical NSAID, diclofenac (DCF), in a rat model of unilateral hindpaw inflammation induced by complete Freund's adjuvant. We evaluated the effects of systemically applied DCF on the paw tissue pH, on the expression of inflammatory mediators in immune cells from inflamed paws and on the expression of opioid receptors in dorsal root ganglia. Additionally, we investigated the antinociceptive efficacy of NFEPP injected into the inflamed paws after DCF treatment. We found that DCF reduced inflammation-induced nociceptive responses and tissue acidosis, but did not change the mRNA expression of IL-1 beta, TNF-alpha, IL-6, IL-4, NGF, or of mu-, delta-, or kappa-opioid receptors. The treatment with DCF moderately reduced the antinociceptive efficacy of NFEPP, suggesting a correlation between an increase in local tissue pH and the decreased antinociceptive effect of this pH-sensitive opioid agonist

Transepicondylar distance measured on MRI can predict the length of the graft required for different anterior cruciate ligament reconstruction (ACLR) techniques useful for revision surgery

BACKGROUND: The aim of this study is to find a correlation between linear measurements and the graft length required for different anterior cruciate ligament (ACL) revision techniques, to extract formulas to predict required graft length during the preoperative planning. METHODS: At time 0 and 30 days later, two observers measured eight linear distances on standard 2D knee magnetic resonance imaging (MRI), and nine curved distances on 3D MRI sequences, corresponding to different techniques for ACL revision, anatomic anterolateral ligament (ALL) reconstruction, and lateral extrarticular tenodesis (LET). Intra- and interobserver reliability was tested for 2D and 3D measurements. The correlation between 2D and 3D measurements was tested. The 2D measurements with highest repeatability and reproducibility, and with strongest correlation with 3D measurements were used to extract formulas to calculate the graft length from 2D values. RESULTS: Fifty MRIs acquired with both 2D and 3D sequences were used. The intra- and interobserver reliability of linear 2D measurement was high, with the transepicondylar distance (TD) showing the highest reproducibility and repeatability. The intra- and interobserver reliability of 3D measurements was lower than 2D, but acceptable for all measurements except for ALL reconstruction. The TD showed the strongest correlation with 3D measurements. The formulas extracted to calculate the graft length from the TD proved to be accurate. CONCLUSION: Accurate formulas were created to calculate the graft length needed for different ACL revision techniques and ALL reconstruction/LET techniques from TD. These formulas can be used during preoperative planning of ACL revision cases

Characterization of some Italian V. vinifera L. grape varieties on the basis of their flavonol profile

"Suspect screening metabolomics" is a mid-way approach between "targeted" and "untargeted" analysis. For this aim, a new database of putative grape and wine metabolites (GrapeMetabolomics ) was expressly constructed. Currently, this database contains around 1,100 compounds. By performing UHPLC/QTOF mass spectrometry analysis in both positive and negative ionization mode, in a grape extract averaging 320–450 putative compounds are identified. Most of these compounds are important grape metabolites, including flavonols, anthocyanins, and stilbene derivatives. In the present study, this approach was focalized on the characterization of flavonols of 18 important Italian red and white grape varieties and the method provided the identification of 15 flavonols. By performing statistical analysis (Principal Component Analysis and Cluster Analysis), the effect of the variety on the flavonol composition of the grapes was studied. Both the red and white samples fell into three different groups, respectively, on the basis of their flavonol profiles. Because the samples were cultivated in the same vineyard, their profile potentially was not affected by cultural or environmental factors. Anyway, these preliminary results will have to be confirmed by the study of grape samples collected in different years and from different vineyards

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins’ putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins’ effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins’ antidepressant effects while also improving our understanding of the physiopathological basis of depression

Polyphenol metabolomics of twenty Italian red grape varieties

“Suspect screening analysis”method to study grape metabolomics, was performed. This method is a middle-way “targeted” and “untargeted”approach aiming at identifying the largest number of metabolites in grape samples. A new database of putative grape and wine metabolites (GrapeMetabolomics), which currently contains around 1,100 compounds, was constructed by CREA at Conegliano. By performing high-resolution mass spectrometry analysis of the grape extract in both positive and negative ionization mode, averaging 320- 450 putative compounds are identified. Most of them are grape polyphenols, such as anthocyanins, flavonols and stilbene derivatives. By performing PCA and Cluster Analysis the composition in anthocyanins and flavonols of 20 Italian red grape varieties, was studie

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound-guided fine-needle aspiration cytology (US-FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US-FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US-FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low-Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1-2 primary tumor and breast-conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines