Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment

Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus‐sensitive. Rodents, previously subjected to 2‐week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose‐dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co‐administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions.     

Comparison of Serum Total IgA Levels in Severe and Mild COVID-19 Patients and Control Group

Journal of Clinical Immunology - The present study aimed to compare serum total IgA levels between severe and mild COVID-19 patients’ groups and the control group. In this cross-sectional...     

Multivariate scan statistics for disease surveillance

In disease surveillance, there are often many different data sets or data groupings for which we wish to do surveillance. If each data set is analysed separately rather than combined, the statistical power to detect an outbreak that is present in all data sets may suffer due to low numbers in each. On the other hand, if the data sets are added by taking the sum of the counts, then a signal that is primarily present in one data set may be hidden due to random noise in the other data sets.In this paper, we present an extension of the spatial and space-time scan statistic that simultaneously incorporates multiple data sets into a single likelihood function, so that a signal is generated whether it occurs in only one or in multiple data sets. This is done by defining the combined log likelihood as the sum of the individual log likelihoods for those data sets for which the observed case count is more than the expected. We also present another extension, where the concept of combining likelihoods from different data sets is used to adjust for covariates.Using data from the National Bioterrorism Syndromic Surveillance Demonstration Project, we illustrate the new method using physician telephone calls, regular physician visits and urgent care visits by Harvard Pilgrim Health Care members cared for by Harvard Vanguard Medical Associates, a large multi-specialty group practice in Massachusetts. For upper and lower gastrointestinal (GI) illness, there were on average 20 telephone calls, nine urgent care visits and 22 regular physician visits per day. The strongest signal was generated by a single data set and due to a familial outbreak of pinworm disease. The second and third strongest signals were generated by the combined strength of two of the three data sets.     

Repair of aortic coarctation in adults: the fate of hypertension

The benefit of coarctation repair on the resolution of systolic hypertension in adults has been questioned. In this retrospective study, hypertension was assessed in 38 adults (22 men, 16 women; mean age, 25.6 +/- 6.9 years; range, 16-39 years) who underwent coarctation repair between 1996 and 2006. Thirty patients had preoperative hypertension (mean systolic pressure, 158.3+/-18.6; range 140-200 mm Hg). At preoperative catheterization, the peak mean systolic gradient across the coarctation was 70.6 +/- 21.2 mm Hg (range, 38-120 mm Hg). Operative procedures were resection and end-to-end anastomosis (11 patients), patch aortoplasty (24) and resection with interposition of a Dacron tube graft (3). The patients were followed up for 2-90 months (mean, 37 +/- 23 months). Of the 30 patients with preoperative hypertension, 25 (83%) were normotensive at the last follow-up. The mean postoperative systolic blood pressure was significantly lower than the preoperative level. More than half of the patients (58%) were still taking antihypertensive medication. Surgical repair of coarctation of the aorta in adults can lead to regression of systolic hypertension and a decreased requirement for antihypertensive medication.     

An economic evaluation of voriconazole versus amphotericin B for the treatment of invasive aspergillosis in Canada.

BACKGROUND: Invasive aspergillosis (IA) is a serious fungal infection that affects immunocompromised patients. The Global Comparative Aspergillosis study demonstrated that voriconazole, a new broad-spectrum triazole, had better responses and improved survival compared with conventional amphotericin B deoxycholate (CAB) and other licensed antifungal therapy (OLAT) for the treatment of definite or probable aspergillosis. OBJECTIVES: To compare costs and outcomes of voriconazole and CAB for the treatment of definite or probable aspergillosis in Canada. METHODS: A cost-consequence decision tree model was designed to reflect the treatment pathways used in clinical practice when using voriconazole or CAB as primary therapy for IA. Therapy included initial treatment with either voriconazole or CAB and then switched to an OLAT in the event of an inadequate response, severe toxicity or intolerance. The principal data source used was the Global Comparative Aspergillosis study. RESULTS: The total cost of voriconazole when compared with CAB as initial therapy for IA was $38,319 versus $42,495 per patient, respectively, representing a 9.8% cost reduction for each patient treated with voriconazole. The higher mean cost in the CAB arm was primarily due to the high proportion of patients (73.7%) who were switched to an OLAT due to severe side effects or an inadequate response. Treating with voriconazole was a dominant strategy. The number of patients that had to be treated with voriconazole instead of CAB to save one additional life was eight. CONCLUSIONS: Voriconazole as primary treatment for IA increased the chances of successful treatment, improved survival and may represent a potential cost saving strategy in Canada.     

Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current

The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (I(K1)). In addition to differences in current density, atrial and ventricular I(K1) have differences in outward current profiles and in extracellular potassium ([K+]o) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular I(K1) in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than -30 mV (I approximately 0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, I(K1) rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, I(K1) did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1+/-0.1 pS in 15 cells, which corresponded with I(K1) in sheep atria (9.9+/-0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K+]o, whereas Kir2.3 currents did not increase. Correspondingly, guinea pig (but not sheep) atrial I(K1) showed an increase in outward currents in 10 mmol/L [K+]o. Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward I(K1) currents rectified completely and increased in high [K+]o-displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+]o were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of I(K1) in the heart.