Cortisol fetal fluids concentrations and newborn outcome in term pregnancy small-sized purebred dogs.

In order to provide further information about canine perinatology, and because of the scarceknowledge about fetal fluids composition in dogs, the present study was aimed to assess the cortisolconcentrations in fetal fluids collected from small-sized purebred newborn puppies born by electivecesarean section, at term of pregnancy (Meloni et al, 2014). Furthermore weassessed possible correlations of amniotic and allantoic cortisol concentrations and newborn outcomeat 24 hours of age and with the newborn gender. Fetal fluids cortisol concentrations were alsoevaluated for correlation with maternal parity, litter-size, neonatal gender, birth weight and Apgar score(Veronesi et al, 2009). The study, performed on 50 born alive, normal weighed puppies, without grossphysical malformation, showed that cortisol concentration was higher in allantoic than in amniotic fluid(p<0.01), even if a strong positive correlation between the two fluids cortisol concentration was found(p<0.0001; R=0.83). Interestingly, higher amniotic (p<0.05) cortisol concentrations were associated topuppies not surviving at 24 hours after birth. Therefore it could be suggested that this parameter maybe useful for the recognition, at birth, of puppies needing special surveillance in the first day of age. Inrelation to the other evaluated parameters, no correlations with amniotic or allantoic cortisolconcentrations were found. In conclusion, the present results showed that in small-sized purebredpuppies, born at term by elective caesarean section, the evaluation of amniotic cortisol concentrationseems useful for the detection of puppies that need special surveillance during the first 24 hours of age,and should be coupled to the newborn evaluation by Apgar score

Biochemical composition of amniotic fluid in normal puppies at term of pregnancy: preliminary data

The full knowledge of the normal fetal fluids composition could be useful in the dog for the better management of newborns. The aim of the present study was to define the biochemical composition of amniotic fluid of puppies born by elective Caesarean section (CS) at term of pregnancy. The study enrolled 24 purebred bitches, classified into small size (<10 kg) and large size breeds (>20kg). All the bitches were healthy and clinically monitored from mating until parturition. For all the bitches an elective CS at term of pregnancy was performed [1]. For each puppy, the amniotic fluid was collected, immediately centrifuged and frozen at – 20° C until analysis for ALB, AMY, TB, CHOL, CK, ALP, GGT, AST, ALT, LDH, Mg, Ca, K, Na, Trig, BUN, Glc, TP, CREA, LIP, Cl, and GLOB. Data were analyzed by ANCOVA to verify the possible effects of parity, breed body size and newborn gender on amniotic biochemical composition. A total of 69 amniotic fluid samples were collected. The amniotic mean±SD and min-max values for each parameter were defined. LDH (p<0.01) and CK activity (p<0.05), as well as Glc concentrations (p<0.0001) were negatively influenced by the parity. AMY activity was significantly (p<0.05) higher in large sized (44.2±20.87 U/L) respect to small sized dogs (30.3±19.89 U/L), while lower (p<0.05) CHOL amniotic concentrations were found in small sized (3.0±2.71 mg/dl) as compared to large sized (3.9±2.93 mg/dl) dogs. Gender of the newborn did not influence the amniotic biochemical composition. The preliminary results of this study showed some similarities as well as some differences concerning the biochemical composition of the amniotic fluid in dogs at term of pregnancy if compared to data reported for the cat [2]. Furthermore, the results suggested that, in dogs, some amniotic parameters could be influenced by breed body size and by parity

Hair dehydroepiandrosterone (DHEA) concentrations in newborn dogs

During the last intrauterine fetal stage of development and the neonatal period the hypothalamic-pituitary-adrenal axis (HPA) is a key system. Apart of cortisol, the adrenals produce dehydroepiandrosterone (DHEA), the major steroid produced by the fetus itself, so that it could be considered as a marker of offspring HPA activity. Non invasive, long time-frame retrospective hormonal levels analysis were performed in the hair of humans and animals, but not in newborn puppies, and DHEA never investigated in puppies. This study was aimed to assess DHEA concentrations in the hair of newborn puppies, and to evaluate the influence of newborn age, gender, and breed size on DHEA concentrations. The study enrolled 116 spontaneously dead puppies, grouped on the base of mother bodyweight to small or medium-large breeds, and on the base of age at death. Hair samples were collected by shaving, and stored at room temperature until RIA analysis. The overall hair DHEA concentrations were 46.8±14.8 pg/mg. DHEA levels were 48.6±15.66 pg/mg in females vs 45.1±13.73 pg/mg in males, without significant differences. DHEA levels were 45.5±13.61 pg/mg in small size puppies and 47.8±15.61 pg/mg in medium-large size puppies, with no significant differences. DHEA concentrations in premature puppies (52.5±15.12 pg/mg) were significant higher (p<0.05) than in puppies dead between 1 and 30 days after birth (44.5±17.78 pg/mg), but similar to fresh term born-dead puppies (46.2±16.5 pg/mg).  This study demonstrated that DHEA is quantifiable in the hair of newborn dogs, and that DHEA levels are significantly influenced by the puppies age

Association of amniotic uric acid, glucose, lactate and creatinine concentrations and lactate/creatinine ratio with newborn survival in small-sized dogs – preliminary results

In order to define the normal composition of canine amniotic fluid and to detect differences between surviving and non-surviving newborn puppies, the present study determined the uric acid, glucose, lactate and creatinine concentrations and the lactate to creatinine ratio in amniotic fluids collected during elective Caesarean section from small-sized purebred bitches. The possible relationship between newborn survival and the studied parameters, as well as the effects of maternal parity, fetal gender and Apgar score were assessed. The study enrolled 27 small-sized purebred bitches submitted to elective Caesarean section at term. After opening the fetal membranes, amniotic fluid samples were collected aseptically from the amniotic sac of each fetus. The data obtained from 74 amniotic fluid samples collected from 27 bitches showed that amniotic glucose concentration was lower (P < 0.05) in non-surviving than in surviving puppies. Within the normal, surviving puppies, amniotic glucose concentration was higher (P < 0.05) in male than in female newborns, and the lactate/creatinine ratio was significantly higher in multiparous than in primiparous bitches (P < 0.05). These preliminary results demonstrate the relevance of amniotic glucose, but not of uric acid, lactate, creatinine and the lactate to creatinine ratio for detecting puppies at risk of death immediately after birth

Identification of a serum and urine extracellular vesicle signature predicting renal outcome after kidney transplant

Background A long-standing effort is dedicated towards the identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant. Methods We characterized 37 surface antigens by flow cytometry, in serum and urine EVs from 58 patients who were evaluated before, and at 10-14 days, 3 months and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year. Results Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated with patient outcome at univariate analysis and were able to predict patient outcome at receiver operating characteristics curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome. Conclusions An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant

Cell-Cycle Inhibition by Helicobacter pylori L-Asparaginase

Helicobacter pylori (H. pylori) is a major human pathogen causing chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. One of the mechanisms whereby it induces damage depends on its interference with proliferation of host tissues. We here describe the discovery of a novel bacterial factor able to inhibit the cell-cycle of exposed cells, both of gastric and non-gastric origin. An integrated approach was adopted to isolate and characterise the molecule from the bacterial culture filtrate produced in a protein-free medium: size-exclusion chromatography, non-reducing gel electrophoresis, mass spectrometry, mutant analysis, recombinant protein expression and enzymatic assays. L-asparaginase was identified as the factor responsible for cell-cycle inhibition of fibroblasts and gastric cell lines. Its effect on cell-cycle was confirmed by inhibitors, a knockout strain and the action of recombinant L-asparaginase on cell lines. Interference with cell-cycle in vitro depended on cell genotype and was related to the expression levels of the concurrent enzyme asparagine synthetase. Bacterial subcellular distribution of L-asparaginase was also analysed along with its immunogenicity. H. pylori L-asparaginase is a novel antigen that functions as a cell-cycle inhibitor of fibroblasts and gastric cell lines. We give evidence supporting a role in the pathogenesis of H. pylori-related diseases and discuss its potential diagnostic application

Urokinase Plasminogen Receptor and the Fibrinolytic Complex Play a Role in Nerve Repair after Nerve Crush in Mice, and in Human Neuropathies

Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients &gt;17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p &lt; 0.001) and be vaccinated (37% vs. 12.7%, p &lt; 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at &lt;20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p &lt; 0.001) and immune suppressed (66.4% vs. 35.2%, p &lt; 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Evolución del concepto etnia/raza y su impacto en la formulación de políticas para la equidad The evolution of the ethnicity/race concept and its impact on framing policies that promote equity

Acknowledging the differences between individuals based on their unique identity is a basic requirement for achieving equity. A review of international human rights efforts and the recommendations and declarations of global conferences and regional summits as they redirect policy to battle discrimination shows a positive evolution in the concept of ethnicity/race. This is evident in the transition from using "invisible" differences as an equalizing measure to respecting lifestyle diversity and acknowledging that individuals have a right to be valued for their differences. This evolution in the ethnicity/race concept has been pivotal to building multiethnic, multicultural, and multilingual nations in which minority groups are involved in framing equitable health policies and programs. This study covers the time period from 1948 to the present day, identifying four stages in the concept's evolution that coincide with milestones in the political and social relationship between government institutions and ethnic minority groups. The results of these five decades of positive progress is a heightened appreciation for differences, which underlies multiethnic societies and surpasses any one of the tangible benefits received by minority groups. The progress of democratic societies depends heavily on this concept, one that ensure a stronger foundation for future development