LIGHT/TNFSF14 regulates estrogen deficiency-induced bone loss

Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T-cell co-stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor-κB ligand (RANKL). Predictably, LIGHT-deficient (Tnfsf14−/−) mice are protected from ovariectomy-dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag−/−Tnfsf14−/−) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Epidemiology, pathological aspects and genome heterogeneity of feline morbillivirus in Italy

Feline morbillivirus (FeMV) is an emerging morbillivirus first described in cats less than a decade ago. FeMV has been associated with chronic kidney disease of cats characterized by tubulointerstitial nephritis (TIN), although this aspect is still controversial and not demonstrated with certainty. To investigate FeMV prevalence and genomic characteristics, an epidemiological survey was conducted in a total number of 127 household cats originating from two Italian regions, Abruzzi and Emilia-Romagna. A total number of 69 cats originating from three feline colonies were also enrolled for the study. Correlation with TIN was investigated by employing a total number of 35 carcasses. Prevalence of FeMV RNA was higher in urine samples collected from cats of colonies (P = 31.8%, CI 95% 22.1–43.6) compared to household cats (P = 8.66%, CI 95% 4.9–14.9) and in young and middle-aged cats while prevalence of FeMV Abs was higher in old cats. Sequences obtained straight from infected biological samples, either partial or complete, cluster into two clades within FeMV genotype 1, distantly related to FeMV genotype 2. Immunohistochemistry analysis of kidney sections of FeMV RNA positive cats revealed immunoreactivity within epithelial cells of renal tubuli and inflammatory cells. However, statistically significant association between FeMV and renal damages, including TIN, was not demonstrated (p= 0.0695, Fisher exact test). By virus histochemistry performed with FeMV-negative feline tissues and a FeMV isolate, tropism for different cellular types such as inflammatory cells residing in blood vessels of kidney and brain, airway epithelial cells, alveolar macrophages and to a lesser extent, the central nervous system, was demonstrated. Additional studies are warranted in order to establish viral tropism and immune response during the early phases of infection and to disentangle the role of FeMV in co-infection processes

Water Dynamics at Protein Interfaces: Ultrafast Optical Kerr Effect Study

The behavior of water molecules surrounding a protein can have an important bearing on its structure and function. Consequently, a great deal of attention has been focused on changes in the relaxation dynamics of water when it is located at the protein surface. Here we use the ultrafast optical Kerr effect to study the H-bond structure and dynamics of aqueous solutions of proteins. Measurements are made for three proteins as a function of concentration. We find that the water dynamics in the first solvation layer of the proteins are slowed by up to a factor of 8 in comparison to those in bulk water. The most marked slowdown was observed for the most hydrophilic protein studied, bovine serum albumin, whereas the most hydrophobic protein, trypsin, had a slightly smaller effect. The terahertz Raman spectra of these protein solutions resemble those of pure water up to 5 wt % of protein, above which a new feature appears at 80 cm–1, which is assigned to a bending of the protein amide chain

Moral Distress Amongst American Physician Trainees Regarding Futile Treatments at the End of Life: A Qualitative Study.

BACKGROUND: Ethical challenges are common in end of life care; the uncertainty of prognosis and the ethically permissible boundaries of treatment create confusion and conflict about the balance between benefits and burdens experienced by patients. OBJECTIVE: We asked physician trainees in internal medicine how they reacted and responded to ethical challenges arising in the context of perceived futile treatments at the end of life and how these challenges contribute to moral distress. DESIGN: Semi-structured in-depth qualitative interviews. PARTICIPANTS: Twenty-two internal medicine residents and fellows across three American academic medical centers. APPROACH: This study uses systematic qualitative methods of data gathering, analysis and interpretation. KEY RESULTS: Physician trainees experienced significant moral distress when they felt obligated to provide treatments at or near the end of life that they believed to be futile. Some trainees developed detached and dehumanizing attitudes towards patients as a coping mechanism, which may contribute to a loss of empathy. Successful coping strategies included formal and informal conversations with colleagues and superiors about the emotional and ethical challenges of providing care at the end of life. CONCLUSIONS: Moral distress amongst physician trainees may occur when they feel obligated to provide treatments at the end of life that they believe to be futile or harmful.This study was funded by the Health Resources and Service Administration T32 HP10025-20 Training Grant, the Gates Cambridge Scholarship, Society of General Internal Medicine Founders Grant, and the Ho-Chiang Palliative Care Research Fellowship at the Johns Hopkins School of Medicine.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11606-015-3505-

Signatures of antagonistic pleiotropy in a bacterial flagellin epitope

Immune systems respond to “non-self” molecules termed microbe-associated molecular patterns (MAMPs). Microbial genes encoding MAMPs have adaptive functions and are thus evolutionarily conserved. In the presence of a host, these genes are maladaptive and drive antagonistic pleiotropy (AP) because they promote microbe elimination by activating immune responses. The role AP plays in balancing the functionality of MAMP-coding genes against their immunogenicity is unknown. To address this, we focused on an epitope of flagellin that triggers antibacterial immunity in plants. Flagellin is conserved because it enables motility. Here, we decode the immunogenic and motility profiles of this flagellin epitope and determine the spectrum of amino acid mutations that drives AP. We discover two synthetic mutational tracks that undermine the detection activities of a plant flagellin receptor. These tracks generate epitopes with either antagonist or weaker agonist activities. Finally, we find signatures of these tracks layered atop each other in natural Pseudomonads

Sindrome del tunnel carpale: malattia professionale o patologia correlata al lavoro?

La sindrome del tunnel carpale costituisce la pi\uf9 frequente neuropatia da compressione dell\u2019arto superiore, originando dall\u2019intrappolamento del nervo mediano nel canale carpale. Nel determinismo della sua comparsa risultano coinvolti numerosi fattori (precedenti fratture, traumatismi cronici, sport, hobbies, attivit\ue0 casalinghe). Vieppi\uf9, \ue8 noto che tale malattia riconosce come primo momento etiopatogenetico non solo ripetuti movimenti di flesso-estensione del polso, ma anche malattie sistemiche o condizioni parafisiologiche (menopausa, gravidanza). La sindrome del tunnel carpale, se \u201csecondaria\u201d si manifesta generalmente con carattere di bilateralit\ue0 soprattutto in donne tra i 30 ed i 60 anni. Di conseguenza risulta fondamentale, nel riconoscimento di una STC come malattia professionale, stabilire se la genesi sia prettamente professionale, ovvero connessa unicamente all\u2019attivit\ue0 lavorativa svolta, o se diversamente possa essere considerata una patologia associata al lavoro, provocata o aggravata dall\u2019azione concomitante di fattori professionali e non. Nel nostro studio abbiamo preso in considerazione un campione di videoterminalisti allo scopo di verificare la presenza di STC, attraverso la ricerca di sintomi soggettivi e segni obbiettivi, associati o meno alla presenza di un\u2019anamnesi positiva per disendocrinopatie, amiloidosi, mesenchimopatie, insufficienza renale cronica in terapia sostitutiva o conservativa, diabete mellito, menopausa, gravidanza al fine di stabilire se l\u2019attivit\ue0 lavorativa sia in grado di determinare una pi\uf9 elevata incidenza e prevalenza in particolari gruppi di lavoratori (esposti al medesimo rischio) rispetto alla popolazione generale