Emerging Hepatotropic Viruses in Cats: A Brief Review

The possible role of viruses in feline liver disease has long remained neglected. However, in 2018, an analogue of human hepatitis B virus was identified in cats. Moreover, antibodies for human hepatitis E have been detected consistently at various prevalence rates in cats. Although the correlation between these viruses and the liver injury in cats must be clarified, hepatotropic viruses might represent an increasing risk for feline and public health.     

International clinimetric evaluation of the MG‐QOL15, resulting in slight revision and subsequent validation of the MG‐QOL15r

Introduction: The MG‐QOL15 is a validated, health‐related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze its clinimetric properties. Methods: We first performed Rasch analysis on >1,300 15‐item Myasthenia Gravis Quality of Life scale (MG‐QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG‐QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on >1,300 MG‐QOL15r scales. Results: The MGQOL15r performed slightly better than the MG‐QOL15. The 3‐response option MG‐QOL15r demonstrated better clinimetric properties than the 4‐ or 5‐option scales. Relative distributions of item and person location estimates showed good coverage of disease severity. Conclusions: The MG‐QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG‐QOL15. Muscle Nerve 54 : 1015–1022, 2016     

Vagus nerve stimulation in drug-resistant epilepsy: the efficacy and adverse effects in a 5-year follow-up study in Iran

Drug-resistant epilepsy seems like a different disease compared with easy to control epilepsy, and new strategies are needed to help these patients. Vagus nerve stimulation (VNS) therapy is the most frequently used neurostimulation modality for patients with drug-resistant epilepsy who are not eligible for seizure surgery. In this study, we aimed to evaluate the efficacy and adverse effects of VNS in patients with drug-resistant epilepsy in an open-label, prospective, long-term study in Iran. We selected 48 patients with partial-onset drug-resistant epilepsy. Implantations were performed in the neurosurgery department of Loghman Hospital, Tehran, Iran. Follow-up visits were done on monthly bases for 5 years. Forty-four patients completed the study. Mean age of patients was 24.4 years. Mean years of epilepsy history was 14 years. The mean number of anti-epileptic drugs did not significantly change over five years (p = 0.15). There was no exacerbation of epilepsy; however, one patient discontinued his therapy due to unsatisfactory results. Five patient had more than 50 %, and 26 patients (59 %) had 25–49 % reduction in the frequency of monthly seizures persistently. Overall mean frequency of monthly seizures decreased by 57.8, 59.6, 65, 65.9, and 67 %, in 1st, 2nd, 3rd, 4th, and 5th years of follow-up, respectively. Most common side effects were as follows: hoarseness (25 %) and throat discomfort (10 %). We found VNS as a safe and effective therapy for drug-resistant epilepsy, with an approximate long-term decrease in mean seizure frequency of 57.8–67 %. Thus, VNS is recommended for suitable patients in developing countries.     

Wavebreak formation during ventricular fibrillation in the isolated,regionally ischemic pig heart

Both fixed and dynamic heterogeneities were implicated in the mechanism of wavebreak (WB) generation during ventricular fibrillation (VF). However, their relative roles remain unclear. We hypothesized that during ischemic VF, the WBs are produced primarily because of a fixed heterogeneity; namely, the gradient of refractoriness across the ischemic border zone (BZ). Ischemia was induced in 15 isolated blood-perfused hearts by occluding the left anterior descending coronary artery. Simultaneous video imaging (approximately 32x32 mm2) of Di-4-ANEPPS fluorescence in the ischemic zone (IZ), the BZ, and the nonischemic zone (NIZ) was performed. Dominant-frequency maps were constructed to assess gradients of refractoriness during VF. We used singularity points analysis to quantify the incidence of WBs per square centimeter per second. During preischemic VF, the distribution of WBs was relatively uniform. Ischemia caused an increase of WBs in the BZ (from 6.2+/-2.8 to 10.8+/-4.0) and a decrease of WBs in the IZ (from 5.8+/-2.8 to 2.8+/-1.4), without a significant change in NIZ (from 6.4+/-2.3 to 4.1+/-1.7). This finding is fully consistent with the dominant-frequency distribution during ischemic VF: the average dominant frequency was significantly slower in IZ than in NIZ (7.8+/-0.7 versus 10.1+/-1.0 Hz), suggesting a large gradient in refractory periods across the BZ. We concluded that acute regional ischemia plays a dual role in the maintenance of VF, decreasing the incidence of WB in the IZ while increasing it in the BZ. This suggests a predominant role of fixed heterogeneities in the formation of WB during VF in acute regional ischemia.     

ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice

Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. Several studies also suggest a pivotal role for K_ATP channels in the seizure modulation. The aim of the present study was to evaluate the seizure threshold induced by pentylenetetrazole in diabetic mice at different times (3 days, 1–8 weeks) after induction of diabetes with streptozocin and to examine the possible role of ATP-sensitive potassium (K_ATP) channels in this manner.Our data showed a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after streptozocin injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The K_ATP channel opener cromakalim (0.1–30 μg/kg, i.p.) significantly increased the seizure threshold in control mice. Although the K_ATP channel blocker glibenclamide (0.5, 1 mg/kg) had no effect, it prevented the effects of the potent dose of cromakalim (30 μg/kg) on seizure threshold in control mice. Glibenclamide (1 mg/kg, i.p.) also decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with cromakalim (10 μg/kg, i.p.). Cromakalim (10 μg/kg, i.p.) significantly increased the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide (1 mg/kg, i.p.).We demonstrated a time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. This phenomenon might be due to the probable alteration in the K_ATP channel functioning during the diabetic condition.     

Transportability of the updated diabetes prediction model from Atherosclerosis Risk in Communities Study to a Middle Eastern adult population: community-based cohort study

We validated the transportability of the updated diabetes prediction model from Atherosclerosis Risk in Communities (ARIC) Study, to a Middle Eastern population. We investigated 3,721 participants of the Tehran Lipid and Glucose Study (TLGS) aged ≥20 years, free of diabetes at baseline. They underwent a standard 75gr 2-h post-challenge plasma glucose test that was repeated every 3 years using the same protocol. All the models were tested with respect to discrimination and calibration. We confirm the findings of Kahn et al. (Ann Intern Med 150(11):741–751, 2009) in a middle-aged, Middle Eastern population. We obtained the same predictive discrimination for the ARIC model (C statistic: men 0.790 and women 0.829) as for the TLGS’ own model (men 0.824 and women 0.847) and validated a good calibration for the updated ARIC diabetes prediction model in the TLGS sample. Among men, optimal cut-point was set to the score of 31 where the maximum value of sensitivity (71.6%) plus specificity (75.3%) was achieved. Among women, the optimal point was set to the score of 38 with sensitivity of 67.1% and specificity of 85.0%. The updated ARIC model predicted the individual diabetes risk with a high level of sensitivity and specificity in the TLGS population, which was comparable with that of original sample. More parsimonious model incorporating age, family history of diabetes, waist circumference, pulse rate, and fasting plasma glucose, which were significantly associated with the risk of incident diabetes in the TLGS population, could be equally effective in predicting diabetes.     

Sex differences and role of gonadal hormones on glutamate level in the nucleus accumbens in morphine tolerant rats: a microdialysis study

Sex differences are observed in the development of tolerance to the antinociceptive effect of opioid drugs such as morphine, but the precise underlying mechanism remains unclear. There are evidences about the interaction between gonadal hormones and neuromodulatory systems including opioidergic and glutamatergic systems. We examined the sex differences and the role of gonadal hormones on the glutamate level in the nucleus accumbens in morphine tolerant rats using in vivo microdialysis. A microdialysis probe was implanted into the left nucleus accumbens core of rats and CSF (cerebrospinal fluid) dialysates were collected. The concentration of glutamate was measured by high-performance liquid chromatography with a fluorescence detector. The results showed that after chronic morphine administration, tolerance to antinociceptive effects of morphine was significantly greater in male rats (P<0.001). Sex differences in tolerance to morphine disappeared with gonadectomy of animals. There was also a significant sex difference in the glutamate level in the nucleus accumbens of morphine tolerant rats (P<0.001), ovariectomy of female rats decreased the glutamate level significantly (P<0.001), while gonadectomy did not change the glutamate level in males significantly. In conclusion, these experiments demonstrate that the excitatory amino acid release in the nucleus accumbens may be modulated by an estrogen-sensitive mechanism and play a role in the morphine analgesia and tolerance.     

A meta-analysis of animal studies on disruption of spatial navigation by prenatal cocaine exposure

Water-maze testing has been used to assess prenatal cocaine (PCOC)-induced deficits in behavioral studies of spatial navigation and memory abilities. Effects of PCOC in acquisition or in probe trials over water-maze testing days were rarely detected. Despite an absence of effects of PCOC when data were collapsed over multiple days, there was a potential difference when examined during the first day of acquisition training, characterized by a PCOC-associated decrease in learning efficiency but not capacity. Here, we review studies of PCOC-related changes in day-1 water-maze acquisition training and examine the relationship between experimental methodologies and PCOC-treatment procedures and the variability in effect size estimates across studies. The results revealed a significant increase in latencies to goal platform on acquisition training day-1 in PCOC-exposed offspring vs. controls (effect size: r=0.44). Significant effects attributable to variations in the PCOC-treatment procedures across studies were also identified. The moderating variable of PCOC "dose" was significant as lower doses of PCOC exposure yielded larger treatment effects. "Duration" of PCOC exposure was not significant, although a trend for greater effects was observed in studies that employed longer daily treatment schedules or schedules administered in later gestational periods. This analysis identified a consistent difference in acquisition training day-1 of water-maze testing in PCOC-exposed offspring indicating a PCOC-induced deficiency in spatial learning. These findings of impaired spatial learning efficiency are of particular interest given clinical scenarios involving acutely impaired spatial memory and related learning in PCOC-exposed children that highlight the potential consequences in classroom learning.