Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation

There is convincing evidence that soluble HLA-A,-B,-C (sHLA-A,-B,-C) and soluble HLA-G (sHLA-G) antigens can induce apoptosis in CD8(+) activated T cells although there is scanty and conflicting information about the mechanism(s) by which sHLA-A,-B,-C antigens and sHLA-G antigens induce apoptosis. In this study we have compared the apoptosis-inducing ability of sHLA-A,-B,-C antigens with that of sHLA-G1 antigens in CD8(+) T lymphocytes and CD8(+) NK cells. Furthermore we have compared the inhibitory effect of sHLA-A,-B,-C antigens and of sHLA-G1 antigens on the activity of EBV-specific CD8(+) cytotoxic T lymphocytes (CTL). sHLA molecules were purified from serum and from the supernatant of HLA class I-negative cells transfected with one gene encoding either classical or non-classical HLA class I antigens. Both classical and non-classical sHLA class I molecules trigger apoptosis in CD8(+) T lymphocytes and in CD8(+) NK cells, which lack the T cell receptor, and their apoptotic potency is comparable. The binding of sHLA-A,-B,-C and sHLA-G1 molecules to CD8 leads to Fas ligand (FasL) up-regulation, soluble FasL (sFasL) secretion and CD8(+) cell apoptosis by Fas/sFasL interaction. Moreover, classical and non-classical sHLA class I molecules inhibit the cytotoxic activity of EBV-specific CD8(+) CTL. As the amount ofsHLA-G molecules detectable in normal serum is significantly lower than that of sHLA-A,-B,-C molecules, the immunomodulatory effects of sHLA class I molecules purified from serum are likely to be mainly attributable to classical HLA class I antigens. As far as the potential in vivo relevance of these findings is concerned, we suggest that classical sHLA class I molecules may play a major immunoregulatory role in clinical situations characterized by activation of the immune system and elevated sHLA-A,-B,-C serum levels. In contrast, non-classical HLA class I molecules may exert immunomodulatory effects in particular conditions characterized by elevated sHLA-G levels such as pregnancy and some neoplastic diseases.     

Factors influencing nurses' decision-making process on leaving in the peripheral intravascular catheter after 96 hours: a longitudinal study

The clinical and research debate on the peripheral intravascular (PIV) catheter length of stay in situ is ongoing. The principal aim of this study was to explore the factors behind a nurse's decision to leave a PIV in place for more than 96 hours. The study focused on 7 northern Italian hospitals in 2009. A consequent sample of 269 PIV catheters was included. Direct observation and interviews were adopted. The time of the expected PIV replacement was fixed at 96 hours after its positioning, in accordance with the international guideline. Several factors were taken into account in regard to replacement of the PIV catheters by nurses, ranging from analysis based on their own clinical experience with PIV complications and analysis of the patient's clinical situation to the critical analysis of their own work situation. This clinical decision-making process is valuable: leaving the PIV in place for more than 96 hours is a complex decision and not simply a guideline violation.     

High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.     

Tetracyclines in COVID‐19 patients quarantined at home: Literature evidence supporting real‐world data from a multicenter observational study targeting inflammatory and infectious dermatoses

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID‐19 outbreak, several dermatological patients contracted SARS‐CoV‐2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID‐19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21‐67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID‐19 outpatients with mild symptoms.     

Promoting awareness of neonatal menstruation

Neonatal uterine bleeding (NUB) has been carefully studied in the past through case reports, small series, clinical cohort studies, pathology investigations of fetal and neonatal. Following a historical recount, this review summarizes biological mechanisms conditioning NUB, starting from the persistence till birth of an 'ontogenetic progesterone resistance' (OPR), causing decreased responsiveness of target tissues to bioavailable progesterone. Several pregnancy-related conditions, such as preeclampsia, fetal growth restriction, prematurity, post-maturity and even Rhesus or ABO incompatibility, influence the occurrence of NUB. It seems therefore that the phenomenon is precipitated by chronic fetal distress. When present, OPR may persists until telarche; as a consequence, if pregnancy occurs in early teenage, the disorder known as “defective deep placentation” may ensue, increasing the risk of obstetrical syndromes. In the presence of NUB, retrograde shedding into the peritoneal cavity of endometrial stem/progenitor and niche cells may occur. There, given the right environment, these cells can survive and become activated at the time of telarche, causing the specific phenotype of early-onset endometriosis. In conclusion, neonatal menstruation is a fetal distress indicator and can alter the incidence of a variety of pathological conditions later in life. For this reason, it should be carefully recorded and the parents informed.     

High accuracy of noninvasive tests to diagnose Helicobacter pylori infection in very young children

OBJECTIVE: To validate the (13)C-urea-breath-test (UBT) and stool antigen test (HpSA) in children aged 5 years or younger, against invasive histologic study and rapid-urease-testing or culture. STUDY DESIGN: On all consecutive children aged 5 years or younger undergoing endoscopy in 1 single center during the last 7.5 years, UBT and HpSA were performed. RESULTS: Of a total of 184 children (median age 2.2 years, range 0.2-5.5), 30 were Helicobacter pylori-positive (16.3%). Sensitivity and specificity of UBT were 93.3% (95%CI 77.9%-99.2%) and 95.5% (90.9-98.2), with a cutoff of 5 per thousand, but specificity increased to 98.1% (94.4%-99.6%) with a cutoff of 8 per thousand. Sensitivity and specificity of HpSA were 93.3% (77.9%-99.2%) and 98.7% (95.4%-99.8%). CONCLUSION: Accuracy of noninvasive tests in our single-center study were satisfactory: specificity of UBT improved with a cutoff at 8%, and sensitivity of HpSA was high when determined locally without transportation after long or inadequate storage that could impair results.     

Excitability changes in human corticospinal projections to muscles moving hand and fingers while viewing a reaching and grasping action

Excitability of the H-reflex in the relaxed flexor digitorum superficialis (FDS) muscle was tested in five subjects observing a reaching and grasping action. The amplitude of the FDS H-reflex was modulated with a peak occurring during the hand-opening phase of the observed movement. When the H-reflex was facilitated by subliminal transcranial magnetic stimulation (TMS), the modulation was larger than for an unconditioned reflex of similar size. This suggests that the primary motor cortex excitability is modulated by action viewing and reasonably causes the motoneuronal excitability changes. Moreover, motor evoked potentials (MEPs) were elicited by supraliminal TMS in FDS, flexor carpi radialis (FCR) and first dorsal interosseus (FDI) when observing the same movement. MEP amplitude was modulated in FDS with the same time-course as the H-reflex, the peak excitability occurring during hand opening. In FDI, however, the maximal excitability occurred during finger closing while in FCR no correlation was found with the movement phases. Finally the EMG activity of FCR, FDS and FDI was recorded while the subjects were actually performing a grasping movement similar to the one observed. In all subjects and for each muscle there was a clear-cut correspondence between the time-course of the excitability modulation of MEPs and the temporal pattern of EMG recruitment. In conclusion, the present study suggests that 'motor resonance' subliminally activates the same motor pathways that would be overtly recruited in each observer when actually performing the observed movement, reproducing the personal strategy adopted in the same task.     

Normal-appearing white and grey matter damage in MS

Abstract The aims of this study were to improve, using a 3.0 Tesla (T) scanner and diffusion tensor (DT) magnetic resonance imaging (MRI) with sensitivity encoding, our understanding of: 1) the possible pathological substrates of normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis (MS) and 2) the factors associated to WM and GM atrophy in this condition. Conventional and DT MRI of the brain were acquired from 32 relapsing-remitting (RR) MS patients and 16 controls. Lesion load, WM (WMV), overall GM (GMV), and neocortical GM (NCV) volumes were measured. NAWM mean diffusivity (MD) and fractional anisotropy (FA), and GM MD were calculated. GMV and NCV were lower (p ≤ 0.001) in MS patients than controls, whereas WMV did not differ significantly. MS patients had higher NAWM and GM average MD and lower NAWM average FA (p ≤ 0.001) than controls. Moderate correlations were found between intrinsic lesion and tissue damage with both GM volumetric and diffusivity changes ()0.41 ≤ r ≤ 0.42, p ≤ 0.04). DT MRI and volumetry measurements at 3.0 T confirm the presence of NAWM and GM abnormalities in RRMS patients. Although histopathology was not available, axonal and neuronal damage and consequent reactive glial proliferation are the most likely substrates of the changes observed.