KIR2DL2/S2 and KIR2DS5 in alcoholic cirrhotic patients undergoing liver transplantation

IntroductionThe molecular mechanisms underlying alcoholic liver fibrosis and cirrhosis are not completely understood. Hepatic fibrosis involves the interplay of diverse cells and factors, including hepatic stellate cells (HSCs), Kupffer, NK cells, and T-lymphocyte subsets. Killer-cell immunoglobulin-like receptors (KIR) are membrane receptors involved in mediation between NK and activated HSCs, regulating NK cell function through their interaction with HLA-I molecules. The aim of this study was to analyse the genetic association between KIR genes and the susceptibility to or protection from alcoholic cirrhosis (AC) in a cohort of male AC patients undergoing liver transplantation (LT) with and without concomitant viral infections.Material and methodsKIR genotyping was performed in nuclear DNA extracted from 281 AC patients and compared with 319 male controls.ResultsSignificant differences between total AC patients and healthy controls were only found in the case of KIR2DL2 and KIR2DS5. KIR2DL2 was significantly underrepresented in non-viral AC patients (52.6% vs. 63.3%; p = 0.015), while patients heterozygous for KIR2DL2 were also underrepresented in the non-viral AC group compared with controls (p = 0.034). KIR2DS5 was overrepresented in this group compared with healthy controls (p = 0.002). All these observations were only evident in AC patients older than 54 years old.ConclusionsOur data suggest a contrary effect of KIR2DL2 and KIR2DS5 in AC patients older than 54 years, in whom the presence of KIR2DL2 appears to be protective against AC, whereas the presence of KIR2DS5 seems to promote the fibrotic process, particularly in patients with no associated viral infection.     

Studying host genetic background effects on multimorbidity of intestinal cancer development,type 2 diabetes and obesity in response to oral bacterial infection and high‐fat diet using the collaborative cross (CC) lines

BackgroundMultimorbidity of intestinal cancer (IC), type 2 diabetes (T2D) and obesity is a complex set of diseases, affected by environmental and genetic risk factors. High‐fat diet (HFD) and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.MethodsTo study the complexity of this multimorbidity, we used the collaborative cross (CC) mouse genetics reference population. We aimed to study the multimorbidity of IC, T2D, and obesity using CC lines, measuring their responses to HFD and oral bacterial infection. The study used 63 mice of both sexes generated from two CC lines (IL557 and IL711). For 12 weeks, experimental mice were maintained on specific dietary regimes combined with co‐infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, while control groups were not infected. Body weight (BW) and results of a intraperitoneal glucose tolerance test (IPGTT) were recorded at the end of 12 weeks, after which length and size of the intestines were assessed for polyp counts.ResultsPolyp counts ranged between 2 and 10 per CC line. The combination of HFD and infection significantly reduced (P < .01) the colon polyp size of IL557 females to 2.5 cm², compared to the other groups. Comparing BW gain, IL557 males on HFD gained 18 g, while the females gained 10 g under the same conditions and showed the highest area under curve (AUC) values of 40 000‐45 000 (min mg/dL) in the IPGTT.ConclusionThe results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance, and this effect is gender related.     

Test of the auricular surface sex estimation method in fetuses and non-adults under 5 years old from the Lisbon and Granada Reference Collections

International Journal of Legal Medicine - Non-adult sex estimation is an active field of forensic inquiry as morphological variations between males and females are subtle, but observable, even from...     

Grafting of Chitosan with Styrene and Maleic Anhydride via Nitroxide‐Mediated Radical Polymerization in Supercritical Carbon Dioxide

A novel synthesis route is used to produce chitosan‐graft‐poly(styrene‐maleic anhydride)‐OH‐TEMPO (CTS‐g‐PSMA‐T). A three‐step reaction scheme is proposed: 1) bromine 4‐OH‐TEMPO oxoammonium salt is synthesized. 2) Hydroxyl‐targeted groups in the CTS molecule are reacted with the synthesized salt in aqueous acid solution. A functionalization of 18.9% is achieved. 3) Graft copolymerization of styrene and maleic anhydride is done via NMRP by a unimolecular initiation system. The reaction is run in a dispersion in supercritical carbon dioxide (scCO₂) in the presence of camphorsulfonic acid (CSA) to avoid autopolymerization. A modified CTS with a graft content of 68% in weight is obtained.

     

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV‐seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12‐month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non‐CMV infection, graft loss, and all‐cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve‐month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS‐adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01–0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29–0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late‐onset disease.     

The effect of three human recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony- stimulating factor, and interleukin-3) on phagocyte oxidative activity

Hematopoietic growth factors not only modulate blood progenitor cell activity but also alter the function of mature phagocytes. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 1 ng/mL for 60 min) did not stimulate luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMNs) in suspension but primed PMN for as much as a 15-fold increase in chemiluminescence in response to f-met- leu-phe (fMLP). Mixed mononuclear leukocytes (monocytes [approximately 20%] and lymphocytes [approximately 80%]; MNL) chemiluminescence was very low even after rhGM-CSF priming, but MNLs added to the PMNs (PMN- MNL) resulted in near doubling of rhGM-CSF-primed PMN fMLP-stimulated chemiluminescence. The enhancing factor(s) from MNLs were inherent rather than induced by the GM-CSF, and purified lymphocytes increased GM-CSF-primed PMN chemiluminescence equal to mixed MNLs. We could not detect cell-free "enhancing factor(s)," but cell-to-cell contact further enhanced rhGM-CSF-primed fMLP-stimulated PMN-MNL oxidative activity by 40%. Polyclonal rabbit anti-tumor necrosis factor (TNF) (but not preimmune serum) decreased both fMLP-stimulated rhGM-CSF- primed PMNs and PMN-MNL chemiluminescence, suggesting that TNF on the PMN surface is enhancing GM-CSF-primed chemiluminescence. GM-CSF priming markedly increased PMN superoxide release (sevenfold), but PMN superoxide release was not further enhanced by the presence of MNLs. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and interleukin-3 (rhIL-3) displayed much smaller effects on pure PMNs and mixed PMN-MNL chemiluminescence and superoxide release than rhGM-CSF. rhGM-CSF primes PMNs for increased oxidative activity more than rhG-CSF and rhIL-3. Maximal oxidative activity was observed when mixed PMN-MNL were primed with GM-CSF in a cell pellet-promoting cell-to-cell contact. This enhanced activity can be attributed, in part, to both inherent enhancing factor(s) on lymphocytes and PMN-associated TNF induced by GM-CSF.     

Studies on thyroid activity in deoxycorticosterone-salt and Goldblatt two-kidney, one-clip hypertensive rats

In this paper we studied the role of thyroid gland function in two experimental hypertension models with different pathophysiological mechanisms: deoxycorticosterone-salt (DOCA-salt, volume dependent) and Goldblatt 2-kidney, 1-clip (2K1C, renin dependent). DOCA-salt hypertensive rats showed lower T3 and T4 serum levels by the third week of induced hypertension. Goldblatt 2K1C hypertensive rats, however, exhibited normal values for both hormones. Treatment with thyroxine accelerated the evolution of hypertension and did not affect the PRA of DOCA-salt rats. Radiothyroidectomy inhibited DOCA-salt and Goldblatt 2K1C hypertension, and prevented the suppression of PRA in DOCA-salt rats, without altering PRA or serum aldosterone in Goldblatt 2K1C rats. These results suggest that: a) a thyroid depressing factor is not activated in Goldblatt 2K1C rats; b) thyroidectomy interferes with the suppressor effect of mineralocorticoid on renin secretion; and c) normal thyroid activity is required for the hypertensive effect of the renin-angiotensin-aldosterone system in Goldblatt 2K1C rats.     

A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI.