Experimental Design and Surgical Approach to Create a Spinal Fusion Model in a New Zealand White Rabbit (Oryctolagus cuniculus)

There are several animal models routinely used for study of the spinal fusion process and animal selection largely depends on the scientific question to be answered. This review outlines the advantages and disadvantages of various animal models used to study spinal fusion and describes the New Zealand White (NSW) rabbit which is the most popular preclinical model to study spinal fusion. We outline critical steps required in planning and performing spinal fusion surgery in this model. This includes determination of the required animal number to obtain statistical significance, an outline of appropriate technique for posterolateral fusion and other components of completing a study. As advances in drug delivery move forward and our understanding of the cascade of gene expression occurring during the fusion process grows, performing and interpreting preclinical animal models will be vital to validating new therapies to enhance spinal fusion.     

Evaluation of Biliary Enteric Anastomosis in Benign Biliary Disorders

Evaluation of various methods of biliary enteric anastomosis in benign biliary diseases (BBD). A surgeon operating for BBD needs to improve the internal drainage of bile to prevent stasis and its back-pressure effects. This is best obtained by biliary enteric anastomosis. A total of 121 cases of biliary enteric anastomosis in BBD were included in this study. The postoperative course and long-term outcome were studied prospectively. In the choledochoduodenostomy group, there were no leaks, no restrictures, and no mortality. Five (10.41 %) patients had cholangitis attacks and 2 (4.17 %) patients had sump syndrome. The choledochojejunostomy group had no leaks, no restrictures. Two (7.14 %) patients had repeated cholangitis and 2 (7.14 %) patients had sump syndrome, no mortality. The hepaticojejunostomy group had 3 cases of anastomotic leak of which 2 healed spontaneously and 1 needed resurgery. There was restricture in 2 cases, in which resurgery was successful—one death, no cholangiocarcinoma. Biliary enteric anastomosis is a safe and effective method for the management of BBD. The method should be selected according to the disease pathology and patient characteristics.     

Pregnancy in congenital cardiac disease: an increasing challenge for cardiologists and obstetricians -- a prospective multicenter study

OBJECTIVES: Aim of this study was to assess the occurrence of pregnancy-related complications of mother and child during pregnancy, delivery and puerperium in women with CCD prospectively. STUDY DESIGN, POPULATION: This prospective multicenter study included 122 pregnancies in 106 women with CCD (72 with, 34 without previous cardiac surgery). Patient age was 17-44, median 26 years. Cardiac and non-cardiac complications, mode of delivery, abortion, and CCD of the newborn were assessed. RESULTS: Initially all women were in Functional Class I or II. Worsening during pregnancy occurred in 25.5% (n=27), mainly during the second and third trimester. Significant problems due to bleeding, hypertension, rhythm disturbances, endocarditis, liver congestion, increasing cyanosis or death, occurred in 11.3%. Twelve per cent of deliveries were premature. Five women had therapeutic abortion, nine spontaneous abortions, nine preterm births, and one intrauterine death. Seventy-nine per cent (n=85) delivered spontaneously; 21.3% (n=23) had caesarean section. Of the 111 live born children, 5.4% (n=6) had a CCD. CONCLUSIONS: Most women with CCD and a good functional class before pregnancy tolerate pregnancy without major problems. However, pregnancy may induce serious cardiac and obstetric complications. The specific risks require an individualized multidisciplinary patient-management by experienced physicians.     

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.     

Mobile Phone Sensor Correlates of Depressive Symptom Severity in Daily-Life Behavior: An Exploratory Study

BackgroundDepression is a common, burdensome, often recurring mental health disorder that frequently goes undetected and untreated. Mobile phones are ubiquitous and have an increasingly large complement of sensors that can potentially be useful in monitoring behavioral patterns that might be indicative of depressive symptoms.ObjectiveThe objective of this study was to explore the detection of daily-life behavioral markers using mobile phone global positioning systems (GPS) and usage sensors, and their use in identifying depressive symptom severity.MethodsA total of 40 adult participants were recruited from the general community to carry a mobile phone with a sensor data acquisition app (Purple Robot) for 2 weeks. Of these participants, 28 had sufficient sensor data received to conduct analysis. At the beginning of the 2-week period, participants completed a self-reported depression survey (PHQ-9). Behavioral features were developed and extracted from GPS location and phone usage data.ResultsA number of features from GPS data were related to depressive symptom severity, including circadian movement (regularity in 24-hour rhythm; r=-.63, P=.005), normalized entropy (mobility between favorite locations; r=-.58, P=.012), and location variance (GPS mobility independent of location; r=-.58, P=.012). Phone usage features, usage duration, and usage frequency were also correlated (r=.54, P=.011, and r=.52, P=.015, respectively). Using the normalized entropy feature and a classifier that distinguished participants with depressive symptoms (PHQ-9 score ≥5) from those without (PHQ-9 score <5), we achieved an accuracy of 86.5%. Furthermore, a regression model that used the same feature to estimate the participants’ PHQ-9 scores obtained an average error of 23.5%.ConclusionsFeatures extracted from mobile phone sensor data, including GPS and phone usage, provided behavioral markers that were strongly related to depressive symptom severity. While these findings must be replicated in a larger study among participants with confirmed clinical symptoms, they suggest that phone sensors offer numerous clinical opportunities, including continuous monitoring of at-risk populations with little patient burden and interventions that can provide just-in-time outreach.     

Prismatomerin, a new iridoid from Prismatomeris tetrandra. Structure elucidation, determination of absolute configuration, and cytotoxicity

A new complex iridoid, prismatomerin (1), has been isolated from the leaves of Prismatomeris tetrandra, together with the known glucoside gaertneroside (4). The structures of 1 and 4 were determined by spectroscopic analysis, notably 2D NMR techniques. The (1R,5S,8S,9S,10S)-(-) absolute configuration of prismatomerin (1) was determined by comparison of the vibrational circular dichroism (VCD) spectrum calculated using density functional theory and the experimental VCD spectrum of the O-acetyl derivative 3. Prismatomerin (1) showed remarkable antitumor activity and also interfered with mitotic spindle formation.     

Identification and characterization of solid-state nature of 2-chloromandelic acid

The racemate and enantiomers of 2-chloromandelic acid were characterized by SS-NMR, XRPD, and FTIR. The binary melting point phase diagram was constructed by DSC (differential scanning calorimetry). The solid-state nature of 2-chloromandelic acid was identified to be a racemic compound. The crystal structure of racemic compound was determined to be monoclinic P2(1)/c.     

A cybernetic view on wind-up

Wind-up is described traditionally as a frequency dependent increase in the excitability of spinal cord neurons, evoked by electrical stimulation of afferent C-fibers. Different kinds of wind-up have been reported, but wind-up of Abeta fibers in hyperalgesic states has gained little attention. In this paper, we present a cybernetic view on Abeta fiber wind-up and consider the involved molecular mechanisms as feedback and feedforward processes. Furthermore, our previous hypothesis, the sprouting phenomenon, is included in this view. Considering the proposed model, wind-up in hyperalgesic states might leave out in three different ways: (1) blocking the NMDA receptors by increasing extracellular Mg2+, 2) blocking the receptors and channels that contribute to Ca2+ inward current, and 3) blocking the Abeta fibers by local anesthetics. It seems that wind-up may be inhibited more effectively by using these three blocking mechanisms simultaneously, because in this case, the feedback process (main controller), the feedforward process (trigger), and Abeta stimulation (trigger) would be inhibited concurrently. Wind up may aggravate the pain in clinical hyperalgesic situations such as post-surgical states, some neuropathic pains, fibromyalgia syndrome, and post-herpetic neuralgia. Surely, clinical studies are needed to validate the effectiveness of our abovementioned suggestions in relieving such clinical pains.     

Normobaric hyperoxia induces ischemic tolerance and upregulation of glutamate transporters in the rat brain and serum TNF-alpha level

Recent studies suggest that intermittent and prolonged normobaric hyperoxia (HO) results in ischemic tolerance to reduce ischemic brain injury. In this research, we attempted to see changes in excitatory amino acid transporters (EAATs) and TNF-α levels following prolonged and intermittent hyperoxia preconditioning. Rats were divided into four experimental groups, each of 21 animals. The first two were exposed to 95% inspired HO for 4 h/day for 6 consecutive days (intermittent HO, InHO) or for 24 continuous hours (prolonged HO, PrHO). The second two groups acted as controls, and were exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated), sham-operated (without MCAO), and intact (without any surgery) subgroups. After 24 h from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit score (NDS) and infarct volume were measured in MCAO-operated subgroups. EAATs expression and serum TNF-α levels were assessed in sham-operated and intact subgroups. Preconditioning with prolonged and intermittent HO decreased NDS and upregulated EAAT1, EAAT2, and EAAT3 and increased serum TNF-α levels significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, the intermittent and prolonged HO seems to partly exert their effects via increase serum TNF-α levels and upregulation of EAATs.