Downregulation of Carnitine Acyl-Carnitine Translocase by miRNAs 132 and 212 Amplifies Glucose-Stimulated Insulin Secretion

We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including nonfuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT; Slc25a20) is a direct target of these miRNAs. CACT is responsible for transporting long-chain acyl-carnitines into the mitochondria for β-oxidation. Small interfering RNA–mediated knockdown of CACT in β-cells led to the accumulation of fatty acyl-carnitines and enhanced IS. The addition of long-chain fatty acyl-carnitines promoted IS from rat insulinoma β-cells (INS-1) as well as primary mouse islets. The effect on INS-1 cells was augmented in response to suppression of CACT. A nonhydrolyzable ether analog of palmitoyl-carnitine stimulated IS, showing that β-oxidation of palmitoyl-carnitine is not required for its stimulation of IS. These studies establish a link between miRNA-dependent regulation of CACT and fatty acyl-carnitine–mediated regulation of IS.     

Surgical cancellation rates due to peri-operative hypertension: implementation of multidisciplinary guidelines across primary and secondary care

Patients with uncontrolled hypertension are at increased risk of complications during general anaesthesia but the number of patients whose surgery is delayed or cancelled due to hypertension remains unknown. Prospective, regional multicentre service evaluations were performed on consecutive patients undergoing elective surgery before and after the publication of new guidelines from the Association of Anaesthetists and the British Hypertensive Society. The aim was to quantify the number of operations cancelled due to hypertension alone and to assess impact of the guidelines on cancellation rates. In October 2013 (before the publication of the guidelines), 1.37% (95%CI 0.69–2.11%) of patients listed for elective surgery were cancelled solely due to raised blood pressure. This reduced significantly to 0.54% (95%CI 0.20–0.92%, p < 0.001) in 2018. There was a significant reduction in inappropriate cancellations for stage 1 or 2 hypertension from 2013 to 2018 (72 vs. 14, respectively, p < 0.001) in keeping with the recommendations in the guidelines. Furthermore, the number of patients being referred back to primary care for the management of hypertension reduced from 2013 to 2018 (85 vs. 30, respectively, p < 0.001). Our data suggest achievement of three major outcomes: reduced surgical cancellations due to hypertension alone; improved detection of significant hypertension before elective surgery; and reduced referral back to primary care from hospital for hypertension management. To the best of our knowledge, this is the first time the successful implementation of guidelines from the Association of Anaesthetists has been assessed on such a broad scale. Our data indicate that these guidelines have been effectively implemented in both primary and secondary care, which is likely to have made a positive psychosocial, physical and economic impact on patients and the NHS.     

Thanatophoric dwarfism in Libyan neonates — a report of 3 cases

Three cases of thanatophoric dwarfism are reported from Libya during a period of 16 months showing an incidence of 1:5600 total births. Polyhydramnios was associated with all the three cases and maternal diabetes in one. No known pattern of inheritance was found. One was stillborn and other two died within 30 minutes of birth. The detailed diagnostic features and differential diagnosis is described along with a brief review of literature.     

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.     

A survey of physicians' attitudes to transfusion practice in critically ill patients in the UK

This study aimed to examine the attitudes of intensivists and haematologists to the use of blood and blood products using a scenario-based postal questionnaire. One hundred and sixty-two intensivists and 77 haematologists responded to the survey. In four scenarios, the baseline haemoglobin thresholds for red cell transfusion ranged from 6 to 12 g.dl(-1). There was significant variation between scenarios (p <0.005). Increasing age, high Acute Physiology and Chronic Health Status II score, surgery, acute respiratory distress syndrome, septic shock and lactic acidosis significantly (p <0.005) modified the transfusion threshold. There were greater variations in the baseline threshold for platelet transfusion. The majority of respondents (72.3%) selected a baseline haemoglobin threshold between 9 and 10 g.dl(-1). The thresholds for platelet transfusion were far less consistent.     

Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics

Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics (n = 20), and (ii) stable on risperidone (n = 10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects (n = 20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.