ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Abstracts from other journals

The aim of the present study was to clinically evaluate fissure sealants on the occlusal fissures and buccal pits of permanent first and second molars after 20 and 15 years, respectively. The population consisted of 72 children, each of whom had had their four first molars sealed between 1977 and 1980. At the annual examinations, all caries-free, newly erupted second molars were sealed. When sealant was applied to the second molars, the first molars were checked and sealant was reapplied to those that had deficient sealants. At the follow-up, when the subjects were 26–27 years of age, 27 in the original group had moved from the community. Thus, the present result is based on 45 subjects. One hundred and fifty-three sealed first molars and 161 sealed second molars were available for inspection. At the follow-up examination of the first molars 20 years after sealant had been applied, 65% showed complete retention, 22% partial retention without caries, and 1306 caries or restoration in the occlusal fissures or buccal pits. At the 15-year follow-up of the second molars, the corresponding figures were 65%, 30% and 5%, respectively. Of the restored or carious molars, significantly more were found in the mandible than in the maxilla ( P  < 0.001). This longitudinal study showed that pit and fissure sealants, applied during childhood, have a long-lasting, caries-preventive effect.     

Muscular disorders in tension-type headache

In order to evaluate the diagnostic criteria for muscular disorders in tension-type headache, pericranial muscle tenderness and pressure pain thresholds were studied in a random sample population of 735 adults aged 25–64. In addition, quantitative EMGs were recorded in 547 of these subjects. The correlation between the three diagnostic tests was assessed and the discriminality and cut-off points were analysed using Receiver Operating Characteristics analysis. Local tenderness from the temporal muscles was closely related to the total tenderness scores from 14 pairs of muscles. In chronic tension-type headache, tenderness was positively related to EMG and inversely related to pain thresholds. In the episodic form the total tenderness score was inversely related to pain thresholds, whereas no significant relation to EMG was noted. The Receiver Operating Characteristics curves indicated that tenderness recorded by manual palpation was the most specific and sensitive test, whereas EMG and pain thresholds were of limited diagnostic value. Eighty-seven percent of subjects with the chronic, and 66% of subjects with the episodic form were found to have a "muscular disorder" defined as increased tenderness recorded by either manual palpation or pressure algometry and/or increased EMG levels. However, muscle tenderness increased significantly during pain, so the headache state should be considered in future studies. Suggestions for revision of the present diagnostic criteria for muscular disorders are given.     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

Turnaround time and barriers to treatment of newly diagnosed cancer in Uganda: a mixed-methods longitudinal study

IntroductionCancer represents a growing public health concern. Late-stage at diagnosis, limited access to effective treatment, and loss to follow-up are responsible for dismal outcomes.ObjectiveTo describe care pathways, turnaround times, and identify barriers to timely initiation of cancer treatmentMethodsUsing a sequential mixed-methods design involving focus group discussions, we followed up 50 participants between January, and June 2018. We computed the median observed turnaround time to treatment (TTT) at each care step and reported delay as deviations from the proposed ideal turnaround times.ResultsThe ideal TTT with either chemotherapy, or radiotherapy, or surgery was 8, 14, and 21 days respectively. At a median follow-up time of 35.5 days (IQR 17–66), only 29 of the 50 study participants had completed all steps between registration and initiation of treatment, and the observed median TTT was 16 days (9 – 22 days) for chemotherapy, and 30 days (17 – 49 days) for radiotherapy, reflecting a significant delay (p-value = 0.017). Reported barriers were; shortage of specialists, patients required visits to outside facilities for staging investigations, prohibitive costs, poor navigation system and time wastage.ConclusionsWhen compared to the recommended ideal turnaround time, there was significant institutional delay in access to chemotherapy and radiotherapy attributed to multiple external and internal healthcare system barriers.