Finite Element Model of Ocular Adduction by Active Extraocular Muscle Contraction

PurposeIn order to clarify the role of the optic nerve (ON) as a load on ocular rotation, we developed a finite element model (FEM) of incremental adduction induced by active contractility of extraocular muscles (EOMs), with and without tethering by the ON.MethodsThree-dimensional (3-D) horizontal rectus EOM geometries were obtained from magnetic resonance imaging of five healthy adults, and measured constitutive tissue properties were used. Active and passive strain energies of EOMs were defined using ABAQUS (Dassault Systemes) software. All deformations were assumed to be caused by EOM twitch activation that rotated the eye about a fixed center. The medial rectus (MR) muscle was commanded to additionally contract starting from 26 degrees adducted position, and the lateral rectus (LR) to relax, further adducting the eye either with or without loading by the ON. Tridimensional heat maps were generated to represent the stress and strain distributions.ResultsTensions in the EOMs were physiologically plausible during incremental adduction. Force in the MR increased from 10 gm at 26 degrees adduction to approximately 28 gm at 32 degrees adduction. Under identical MR contraction, adduction with ON loading reached 32 degrees but 36 degrees without it. Maximum and minimum principal strains within the MR were 16% and 22%, respectively, but when ON loading was included, resulting stress and strain were concentrated at the optic disc.ConclusionsThis physiologically plausible method of simulating EOM activation can provide realistic input to model biomechanical behavior of active and passive tissues in the orbit to clarify biomechanical consequences of ON traction during adduction.     

Potential effect of opium addiction on lipid profile and blood glucose concentration in type 2 diabetic patients in Iran

Background: Diabetes is one of the most common chronic diseases in the world. People believe that opium improves blood glucose and lipid profiles in these patients and controversial studies show the effect of consumption of opium in controlling these indices. Accordingly, this study aimed to compare the serum levels of blood indices such as fasting blood glucose (FBS), Hemoglobin A1c (HbA1c) and lipid profile in opium users and non-users in type ΙΙ diabetic patients.

Methods: In this cross-sectional study, among type II diabetic patients referred to the Diabetes Clinic of Birjand 45 opium users and 135 non-users were selected and entered the study by the convenience sampling method.

Results: The results of this study showed that the mean serum levels of FBS, HbA1c, and serum lipid profiles were not significantly different between the two groups of opium users and non-users, but the levels of triglyceride (TG) were significantly 0.18 unit higher in the opium users, compared to non-opium users.

Conclusion: According to the results, the use of opium does not affect the indices of blood glucose, HbA1c and serum lipid profiles except triglyceride in diabetic patients. The general belief that opioid use reduces biochemical indices does not seem to be correct.

Abbreviations: FBS: fasting blood sugar; HbA1c: Hemoglobin A1c; LDL: low-density lipoprotein; HDL: High-density lipoproteins; HDL-C: High-density lipoproteins-cholesterol; BMI: Body mass index; IQR: Inter quartile range; TG: triglyceride; TC: total cholesterol; NS: non-significant; S: significant; ATN: Acute tubular necrosis     

Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients

Background

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.

Methods

A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.

Results

TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.

Conclusions

TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.     

Facial and bilateral acral porokeratosis with nail dystrophy: A case report

Porokeratosis is a rare disorder of keratinization with unknown etiology. It exhibits both sporadic and autosomal dominant inheritance. The lesions are sharply demarcated, hyperkeratotic, and annular with distinct keratotic edges. The cornoid lamella is the histological hallmark of porokeratosis. Porokeratosis lesions on the face may have a superficial or a destructive nature. To our knowledge there are only a few cases of facial porokeratosis that have been reported. We report a sporadic form of facial and bilateral acral porokeratosis with nail dystrophy.     

Validation of the functional rating index for the assessment of athletes with neck pain

AIM: To validate the culturally-adapted Persian Functional Rating Index(PFRI) for assessing neck pain(NP) in athletes. METHODS: In this cross-sectional study, 100 athletes with NP and 50 healthy athletes participated and responded to the PFRI. Fifty athletes with NP completed the PFRI for at least 7 d later to establish test-retest reliability. RESULTS: The athletes with NP responded to all items, indicating excellent clinical utility. No floor and ceiling effects were found, indicating content validity and responsiveness. The PFRI revealed capability to discriminate between the athletes with NP and healthy athletes. The PFRI demonstrated strong correlation with the Numerical Rating Scale(Spearman's rho = 0.94), and the Persian Neck Disability Index(Pearson r = 0.995), supporting criterion and construct validity. Internal consistency reliability was high(Cronbach's α coefficient: 0.97). The test-retest reliability was excellent(ICCagreement = 0.96). The absolute reliability values of standard error of measurement and smallest detectable change were 3.2 and 8.84, respectively. An exploratory factor analysis yielded one factor explaining 78.03% of the total variance. CONCLUSION: The PFRI is a valid and reliable measure of functional status in athletes with NP.     

Novel candidate genes in esophageal atresia/tracheoesophageal fistula identified by exome sequencing

The various malformations of the aerodigestive tract collectively known as esophageal atresia/tracheoesophageal fistula (EA/TEF) constitute a rare group of birth defects of largely unknown etiology. Previous studies have identified a small number of rare genetic variants causing syndromes associated with EA/TEF. We performed a pilot exome sequencing study of 45 unrelated simplex trios (probands and parents) with EA/TEF. Thirteen had isolated and 32 had nonisolated EA/TEF; none had a family history of EA/TEF. We identified de novo variants in protein-coding regions, including 19 missense variants predicted to be deleterious (D-mis) and 3 likely gene-disrupting (LGD) variants. Consistent with previous studies of structural birth defects, there is a trend of increased burden of de novo D-mis in cases (1.57-fold increase over the background mutation rate), and the burden is greater in constrained genes (2.55-fold, p = 0.003). There is a frameshift de novo variant in EFTUD2, a known EA/TEF risk gene involved in mRNA splicing. Strikingly, 15 out of 19 de novo D-mis variants are located in genes that are putative target genes of EFTUD2 or SOX2 (another known EA/TEF gene), much greater than expected by chance (3.34-fold, p value = 7.20e−5). We estimated that 33% of patients can be attributed to de novo deleterious variants in known and novel genes. We identified APC2, AMER3, PCDH1, GTF3C1, POLR2B, RAB3GAP2, and ITSN1 as plausible candidate genes in the etiology of EA/TEF. We conclude that further genomic analysis to identify de novo variants will likely identify previously undescribed genetic causes of EA/TEF.Subject terms: Diseases, Genetics     

Possible anti‐obesity effects of phytosterols and phytostanols supplementation in humans: A systematic review and dose–response meta‐analysis of randomized controlled trials

Present meta‐analysis investigates the effects of phytosterols and phytostanol (PS) supplementation on anthropometric indices, using data from randomized controlled trials. We performed a systematic search in the databases: PubMed, Scopus, Cochran, and Web of Science. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were presented. Overall, 79 randomized controlled trials investigated the effects of PS on anthropometric indices. Meta‐analysis results did not reveal any significant effect of PS supplementation on weight (66 trials‐WMD: ?0.083 kg; CI [?0.233, 0.066]; I² = 42.5%), percentage fat mass (6 trials‐WMD: ?0.090%; CI [?0.789, 0.610]; I² = 0.0%), and waist circumference (WC; 5 trials‐WMD: ?0.039 cm; CI [?0.452, 0.374]; I² = 0.0%). However, body mass index (BMI) significantly decreased after PS supplementation (39 trials‐WMD: ?0.063 kg/m2, p = 0.024, I² = 25.1%). Subgroup analyses showed that PS supplementation in subjects with baseline BMI ≥25 and hyperlipidemic significantly decreased body weight and BMI. The overall results showed that although PS supplementation did not affect anthropometric indices (except BMI), baseline status regarding BMI and hyperlipidemia and also dose and duration could be contributing factors for favorable effects.     

1,3,4-Thiadiazol derivative functionalized-Fe3O4@SiO2 nanocomposites as a fluorescent probe for detection of Hg2+ in water samples

5-Amino-1,3,4-thiadiazole-2-thiol was used to synthesize a novel fluorescent functionalizing group on a Fe₃O₄@SiO₂ magnetic nanocomposite surface for detection of heavy metal ions in water samples. The prepared probe was characterized by using X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and a vibrating sample magnetometer. Among various tested ions, the new nanocomposite responded to Hg²⁺ ions with an intense fluorescence “turn-off”. The limit of detection of the probe shows that it is sensitive to the minimum Hg²⁺ concentration of 48.7 nM. Theoretical calculations were done for estimating binding energies of the three possible bonding modes and the visualized molecular orbitals were presented.

VBYT-Fe₃O₄@SiO₂ fluorescent probe was designed for sensitive detection of mercury in water samples.     

Influence of nicotinic receptor modulators on CB2 cannabinoid receptor agonist (JWH133)-induced antinociception in mice

Delta9-tetrahydrocannabinol is the active component in cannabis and has long been associated with pain relief. This effect is believed to be mediated through central and peripheral CB1 and peripheral CB2 receptors. We have explored the possible antinociceptive effect of a CB2 receptor agonist, JWH133, using the formalin test in mice. The drug was administered by the intracerebroventricular and intraperitoneal routes. Although no antinociceptive effect was observed after intracerebroventricular administration of JWH133, when the drug was administered by the intraperitoneal route, it produced an analgesic effect. The influence of nicotinic cholinergic receptor modulators, nicotine and mecamylamine, on antinociceptive effect of JWH133 was also studied. Nicotine increased and mecamylamine decreased the antinociceptive effect of JWH133. It is concluded that JWH133-induced analgesia is influenced by nicotinic cholinergic receptor activity.     

Single whisker experience started on postnatal days 0, 5 or 8 changes temporal characteristics of response integration in layers IV and V of rat barrel cortex neurons

Neonatal single whisker experience changes the response properties of spared barrel neurons to deflections of principal and adjacent whiskers. However little is known about the temporal characteristics of the paired whisker inputs. To address this issue we used computer controlled mechanical displacement of paired whiskers in control and plucked animals (plucking of all whiskers but D2 started at 0, 5 and 8 postnatal days). The principal whisker (PW) and its caudal adjacent whisker (AW) were deflected simultaneously or serially at different inter-stimulus intervals (10, 20, 30, 50 and 100 ms). Neuronal responses were recorded in D2 spared barrel both in layers IV and V. In the control group, combined deflection of AW prior to PW led to suppression of ON and OFF responses to PW deflection both in layers IV and V. The magnitude of this suppression was strongly dependent on the inter-stimulus intervals (ISIs). At almost all tested ISIs, whisker plucking from P0, P5 and P8 weakened suppressive interactions in layers IV and V barrel neurons for both ON and OFF responses. The most decrease in inhibitory interactions was observed in P5 plucked animals. Principal whisker-evoked ON responses were increased only in P0 plucked animals both in layers IV and V. AW-evoked ON responses are decreased in P5 plucked animals in layer IV. The available data suggest that sensory experience can modulate temporal aspects of response integration and receptive field properties of layers IV and V neurons in barrel cortex. These changes have different critical periods.