Antigenicity of Recombinant Maltose Binding Protein-Mycobacterium avium subsp. paratuberculosis Fusion Proteins with and without Factor Xa Cleaving

Mycobacterium avium subsp. paratuberculosis causes Johne''s disease (JD) in ruminants. Proteomic studies have shown that M. avium subsp. paratuberculosis expresses certain proteins when exposed to in vitro physiological stress conditions similar to the conditions experienced within a host during natural infection. Such proteins are hypothesized to be expressed in vivo, are recognized by the host immune system, and may be of potential use in the diagnosis of JD. In this study, 50 recombinant maltose binding protein (MBP)-M. avium subsp. paratuberculosis fusion proteins were evaluated using serum samples from sheep infected with M. avium subsp. paratuberculosis, and 29 (58%) were found to be antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and removal of the MBP tag was marginally enhanced.     

Hypoglycaemia in type 1 diabetes: technological treatments,their limitations and the place of psychology

Advances in technology allowing improved insulin delivery and glucose monitoring can significantly reduce the burden of hypoglycaemia when used appropriately. However, limitations of the current technology, and the skills, commitment and motivation required to use them, mean that it does not work for all people. Education and informed professional support are key to success. In the context of problematic hypoglycaemia, data suggest that newer technology has lower efficacy and uptake in those with most need. Identifying the causes of hypoglycaemia and understanding some of the underlying behavioural drivers may prove useful and psycho-educational strategies may be effective in selected individuals. Ultimately, as in many spheres of medicine, successful management of problematic hypoglycaemia depends upon matching the right treatment to the right individual.     

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.     

To transfer or not to transfer: Aged care nurses’ decision-making in transferring residents to the emergency department

BackgroundNurses are key decision makers in residential aged care facilities and play a significant role in the transfer of residents from residential aged care facilities to emergency departments. There is scant literature about the role of nurses in the transfer decision-making process.AimTo describe the experiences of residential aged care facility nurses who engage in decision-making to transfer residents to emergency department.MethodsThis research has adopted interpretive qualitative approach of phenomenography. In-depth interviews were undertaken with 20 residential aged care facility nurses across two sites. Uniquely, drawing was used as one way to collect rich, textured data in these in-depth interviews.FindingsSix categories emerged to represent residential aged care facility nurses’ conceptions of decision-making about transferring a resident to the emergency department: “Being a marionette”; “Too dumb to have an opinion”; “Making the family happy”; “Not about the resident”; “Having experience”; and “Being on your own”.DiscussionResidential aged care facility nurses experienced decision-making as not being able to do what is right for the resident most of the time due to a myriad of factors, with heavy influence of other key stakeholders.ConclusionDecision-making is described as a professional responsibility wherein residential aged care facility nurses face dilemmas related to the transfer of a resident to the emergency department and perceived as a constraint.     

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes

Aims/hypothesis

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention.

Methods

We conducted [¹⁵O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA).

Results

Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2?±?35.5 vs 422.7?±?237.1; neuroglycopenic scores, 34.8?±?88.8 vs 478.9?±?311.1; both p?<?0.002). There were subtle differences (p?<?0.005, k?≥?50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia.

Conclusions/interpretation

Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

     

Clinical profile and response to steroids in post-fever retinitis: a nine-year experience from a referral institute in the rural hinterland of Central India

Purpose

To describe the demographics, clinical features, and treatment outcomes with systemic steroids in eyes presenting with post-fever retinitis (PFR) from Central India.

Methods

Single-center, retrospective analysis of 147 eyes of 98 PFR cases between 2011 and 2019.

Results

Mean age of the study cohort was 33.46?±?12.76 years, with 72 males and 26 females. The mean interval between the onset of fever and the diminution of vision was 21.10?±?13.54 days (range 0–60 days). The number of PFR cases increased over the nine years with 89 cases (90.1%) presenting during winters. Unilateral involvement was seen in 49 cases, while 49 had bilateral involvement. Clinical characteristics included: multifocal retinitis (n?=?122; 61.2%), hemorrhages (n?=?132; 89.8%), disc edema (n?=?57; 38.8%), anterior chamber reaction (n?=?28; 19%), and vitritis (n?=?103; 70.1%). Treatment included intravenous followed by oral steroids in 70 patients and oral steroids exclusively in 23; five patients denied treatment. The visual acuity improved from 1.09?±?0.52 LogMAR to 0.29?±?0.42 LogMAR (p?<?0.05).

Conclusion

There has been an increase in the prevalence of PFR cases over the last decade with clustering during the winters. Multifocal retinitis, retinal hemorrhages, and vitritis were the most common clinical findings in our series. The retinitis resolved with improvement in vision following steroid therapy in all eyes.