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The first binuclear Gd-complex of the 12-membered pyridine-based polyaminocarboxylate macrocyclic ligand PCTA was synthesized by C-C connection of the pyridine units through two different synthetic procedures. A dimeric AAZTA-ligand was also synthesized with the aim to compare the relaxometric results or the two ditopic Gd-complexes. Thus, the 1 H relaxometric study on [Gd2 PCTA2 (H2 O)4 ] and on [Gd2 AAZTA2 (H2 O)4 ]2- highlighted the remarkable rigidity and compactness of the two binuclear complexes, which results in molar relaxivities (per Gd), at 1.5 T and 298 K of ca. 12-12.6 mM-1  s-1 with an increase of ca. Saracatinib research buy 80 % at 1.5 T and 298 K (+70 % at 310 K) with respect to the corresponding mononuclear complexes.Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo aetiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY overexpression induces progressive hair greying (depigmentation) due to premature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.Nurse home visitors in Nurse-Family Partnership® (NFP) work with mothers experiencing social and economic adversities to improve their and their children's health. Collaboration between nurse home visitors and primary care providers (PCPs healthcare providers and social workers embedded within obstetrics, paediatrics and family medicine practices) can improve service delivery for families experiencing the greatest adversities. However, little is known about how and to what extent PCPs collaborate with home visiting nurses. We conducted a single exploratory case study between April 2019 and February 2020 to better understand how PCPs collaborate with home visiting nurses to meet family needs in one NFP site, purposefully selected for strong collaboration. We conducted in-depth qualitative interviews with 22 PCPs, including 5 nurses, 7 physicians, 7 social workers and 3 non-direct care professionals, including patient navigator and hospital executives. Interviews were recorded, transcribed, validated and coded inductively. Codes were grouped into broader categories and thematic memos across provider role were written to triangulate perspectives. Healthcare providers interacted with home visiting nurses mainly during the referral process, while social workers provided more specific examples of service co-ordination. In this case study, we saw mutual awareness, co-operation and collaboration to serve families with high needs. Even in this case, purposefully selected to represent strong collaboration, there were opportunities to enhance co-ordination to improve the health and social needs of young families experiencing adversity.The Hippo pathway is an evolutionarily conserved kinase cascade involved in the control of tissue homeostasis, cellular differentiation, proliferation, and organ size, and is regulated by cell-cell contact, apical cell polarity, and mechanical signals. Miss-regulation of this pathway can lead to cancer. The Hippo pathway acts through the inhibition of the transcriptional coactivators YAP and TAZ through phosphorylation. Among the various signaling mechanisms controlling the hippo pathway, activation of G12/13 by G protein-coupled receptors (GPCR) recently emerged. Here we show that a GPCR, the ghrelin receptor, that activates several types of G proteins, including G12/13, Gi/o, and Gq, can activate YAP through Gq/11 exclusively, independently of G12/13. We revealed that a strong basal YAP activation results from the high constitutive activity of this receptor, which can be further increased upon agonist activation. Thus, acting on ghrelin receptor allowed to modulate up-and-down YAP activity, as activating the receptor increased YAP activity and blocking constitutive activity reduced YAP activity. Our results demonstrate that GPCRs can be used as molecular switches to finely up- or down-regulate YAP activity through a pure Gq pathway.

Chronic liver disease increases the risk for periodontal disease and osteoporotic fractures, but its impacts on bone regeneration remain unknown. Herein, we studied the impact of liver cirrhosis on peri-implant bone formation.

A total of 20 male Wistar rats were randomly divided into two groups one with the common bile duct ligated (BDL) and the respective sham-treated control group (SHAM). After four weeks of disease induction, titanium mini-screws were inserted into the tibia. Successful induction of liver cirrhosis was confirmed by the presence of clinical symptoms. Another four weeks later, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contact (BIC) were determined by histomorphometric analysis.

Peri-implant bone formation was not significantly different between the SHAM and BDL groups. In the cortical compartment, the median percentage of peri-implant new bone was 10.1% (95% CI of mean 4.0-35.7) and 22.5% (13.8-30.6) in the SHAM and BDL groups, respectively (p=.26). Consistently, the new bone in direct contact with the implant was 18.1% (0.4-37.8) and 23.3% (9.2-32.8) in SHAM and BDL groups, respectively (p=.38). When measuring the medullary compartment, the new bone area was 7.1% (4.8-10.4) and 10.4% (7.2-13.5) in the SHAM and BDL groups, respectively (p=.17). Medullary new bone in direct contact with the implant was 10.0% (1.2-50.4) and 20.6% (16.8-35.3) in SHAM and BDL groups, respectively, and thus comparable between the two groups (p=.46).

Bile duct ligation has no significant impact on the early stages of peri-implant bone formation.

Bile duct ligation has no significant impact on the early stages of peri-implant bone formation.