Natural Tregs, CD4+CD25+ inhibitory hybridomas, and their cell contact dependent suppression

The natural CD4+CD25+ T regulatory (Treg) lymphocyte has emerged as a critical cell for controlling immune responses to self, foreign proteins, and pathogens. Identified initially by the constitutive expression of CD4 and CD25, natural Tregs suppress a variety of immune cells and responses, including CD4+CD25− proliferation and IL-2 production, and CD8 cell proliferation, IFNγ production and CTL activity. Although natural Tregs require activation with specific antigen to attain their suppressive phenotype, once activated they execute inhibition in an antigen specific as well as non-specific (bystander) fashion. Treg suppression depends on IL-2, CD25, and cell:cell contact. The use of live cell imaging in vivo and in vitro to visualize the dynamic cell:cell interactions involving natural Tregs as well as the CD4+CD25+ Treg inhibitory hybridoma RD6 has refined the mechanistic models of contact dependent Treg suppression.     

Valproatverordnungen bei Mädchen und Frauen im gebärfähigen Alter in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Aufgrund des teratogenen Potenzials von Valproat wurden die Empfehlungen zur Risikoaufklärung und Verordnung bei...     

Long-term performance of instrumental activities of daily living (IADL) in young and middle-aged stroke survivors: Results from SAHLSIS outcome

Background: Although stroke prevalence is increasing and large proportions of stroke survivors are expected to live many years after stroke onset, research on the long-term consequences of stroke for instrumental activities of daily living (IADL) is limited.

Aim: To explore performance of IADL seven years post-stroke onset and identify predictors of long-term IADL performance based on commonly employed acute measures and demographic characteristics in young and middle-aged stroke survivors.

Methods: Data on stroke survivors were collected from SAHLSIS. IADL performance was assessed at 7 years using the Frenchay Activities Index (FAI). Demographic data and baseline measures were assessed as predictors of FAI outcome, using logistic regression.

Results: 237 stroke survivors with a median age of 63 at follow-up were included. Participants had predominantly suffered a mild stroke and >90% lived at home with no community services. Mean FAI was 25.7(score range 0-45), indicating reduced levels of participation in IADL. Frequency of performance of IADL was lowest for work/leisure activities. Gender, cohabitation status, initial stroke severity and baseline score on mRS were independently associated with IADL outcome.

Conclusions: Reduced levels of participation in IADL persist many years after stroke onset and indicate a need to adapt a long-term perspective on stroke rehabilitation.     

Patients' health in contract and fee-for-service care. I. A descriptive comparison

Fee-for-service care, paying afterwards for services provided, is the traditional adult patient financial system in dentistry in Sweden. The public dental health service (PDHS) in the county of V?rmland has since 1999 also an alternative system, contract care. There, a fixed sum of money is paid annually for dental care, which then is received without additional costs. This study compares the demographics, general health and oral health-related quality of life (OHRQoL) in the patient financial systems fee-for-service and contract care in the PDHS in V?rmland. A questionnaire was answered by 1,324 patients, response rate 57%. A non-response analysis was undertaken. The non-response analysis showed that the likelihood for answering the questionnaire was higher for women, for respondents in contract care and for increasing age. Further analyses revealed that the non-respondents were healthier than the respondents and that experience of pain in the mouth was the only variable increasing the likelihood of response. General health was studied with the SF-36 and OHRQoL with the OHIP-14. The demographics studied were gender, age, birth country, marital status, education and social network. The results showed that there were differences in patients' health between the patient financial systems. Respondents in contract care had better OHRQoL than those in fee-for-service care. They also had better general health in four of the dimensions of SF-36, were younger, better educated, born in Sweden and were married/living with somebody to a larger extent than fee-for-service care respondents. Fee-for-service care respondents experienced higher social affinity with their housing area. In conclusion, patients in contract care had better general health and OHRQoL than patients in fee-for-service care. There were social differences in choice of financial system and biased non-response.     

Knee replacement surgery as a human clinical model of the effects of ischaemia/reperfusion upon skeletal muscle

The temporal pattern of metabolic alterations in muscle tissue during total ischaemia and reperfusion are not well-characterized in humans with respect to glutathione, amino acids and energy-rich compounds. In the present study, knee replacement surgery was used as a clinical model to elucidate this pattern of metabolic alterations. Patients (n=15) undergoing elective knee replacement surgery employing tourniquet ischaemia were studied. Muscle biopsies were taken from the quadriceps femoris muscle on the operated side preoperatively, at maximal ischaemia and after 24 h of reperfusion. The biopsies were analysed for glutathione, amino acids and energy-rich compounds. In addition the patients were randomized to receive either glucose or a mannitol infusion in the 24 h following tourniquet ischaemia. During ischaemia, muscle lactate increased by 400% (P<0.05) and phosphocreatine decreased by 70% (P<0.05). During the subsequent 24 h of reperfusion, muscle-reduced glutathione and total glutathione decreased by 27% and 22% (P<0.05) respectively. The muscle amino acid pattern changed during ischaemia with an increase in alanine by 65% (P<0.001) and a decrease in glutamate by 29% (P<0.001). During the reperfusion part of the study, no differences attributable to the infusion of mannitol or glucose were observed. During tourniquet ischaemia and subsequent reperfusion, changes in glutathione metabolism developed, indicating oxidative stress. Knee replacement surgery as a clinical model was useful during the ischaemia period, whereas the reperfusion period was dominated by the general changes seen postoperatively.     

Dyspepsia in Montenegrin chronic kidney disease patients undergoing hemodialysis: endoscopic and histopathological features

Purpose

The main purpose of this study was to analyze the characteristics of dyspepsia and contributing factors in Montenegrin maintenance hemodialysis patients.

Methods

The study included 43 patients undergoing hemodialysis with symptoms of dyspepsia and 40 control dyspeptic subjects with preserved kidney function. All subjects underwent an interview about dyspeptic symptoms, physical and biochemical examination, and upper gastrointestinal endoscopy with pathohistological analysis of biopsy specimens.

Results

Early satiety, bloating and heartburn were the most common symptoms in hemodialysis patients but without significant difference in frequency in relation to controls. Chronic kidney disease patients had statistically lower concentration of total proteins and albumin (p?<?0.001), as well lower BMI values (p?=?0.002). Despite this, no significant correlation of laboratory parameters with dyspeptic symptoms was found. Pathohistological examination indicated that the most common finding in hemodialysis patients was chronic active gastritis (58%), while chronic atrophic gastritis was significantly more common in dialytic patients (p?=?0.032). Patients on hemodialysis had more frequently atrophy of corpus mucosa, which was positively related to dialysis duration (p?=?0.001) and negatively related to pH values (p?=?0.004) and bicarbonate concentration (p?=?0.049). Helicobacter pylori was considerably more common in patients who underwent shorter time on hemodialysis (p?<?0.001) and had higher values of bicarbonate (p?=?0.037).

Conclusion

Maintenance hemodialysis patients are at risk for chronic gastric diseases that correlated with both dialysis vintage and duration.

     

Depressive disorder and antidepressants from an epigenetic point of view

Depressive disorder is a complex, heterogeneous disease that affects approximately 280 million people worldwide. Environmental, genetic, and neurobiological factors contribute to the depressive state. Since the nervous system is susceptible to shifts in activity of epigenetic modifiers, these allow for significant plasticity and response to rapid changes in the environment. Among the most studied epigenetic modifications in depressive disorder is DNA methylation, with findings centered on the brain-derived neurotrophic factor gene, the glucocorticoid receptor gene, and the serotonin transporter gene. In order to identify biomarkers that would be useful in clinical settings, for diagnosis and for treatment response, further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed. Studies on cornerstone antidepressants, such as selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, norepinephrine, and dopamine reuptake inhibitors and their effects on depressive disorder are available, but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies. In addition, two novel drugs, ketamine and esketamine, are being investigated particularly in association with treatment of resistant depression, which is one of the hot topics of contemporary research and the field of precision psychiatry.     

Congenital left ventricular diverticulum: A rare cause of cardiac arrhythmia

Congenital left ventricular diverticula are rare cardiac malformations that usually remain asymptomatic. However, life-threatening complications as ventricular arrhythmias, systemic embolism, spontaneous rupture and development of valvular regurgitation, are described. Diagnosis is based on excluding coronary artery disease, traumatic or inflammatory causes, and other underlying cardiomyopathies. Treatment is directed towards the potential complications, yielding mainly therapy of ventricular arrhythmia. Surgical resection is required for larger-sized congenital aneurysms with adverse hemodynamic effects. We present two cases of a left ventricular diverticulum causing cardiac arrhythmia which led to further surgical treatment.