Postnatal development and behavior effects of in-utero exposure of rats to radiofrequency waves emitted from conventional WiFi devices.

The present work investigated the effects of prenatal exposure to radiofrequency waves of conventional WiFi devices on postnatal development and behavior of rat offspring. Ten Wistar albino pregnant rats were randomly assigned to two groups (n=5). The experimental group was exposed to a 2.45GHz WiFi signal for 2h a day throughout gestation period. Control females were subjected to the same conditions as treated group without applying WiFi radiations. After delivery, the offspring was tested for physical and neurodevelopment during its 17 postnatal days (PND), then for anxiety (PND 28) and motricity (PND 40-43), as well as for cerebral oxidative stress response and cholinesterase activity in brain and serum (PND 28 and 43). Our main results showed that the in-utero WiFi exposure impaired offspring neurodevelopment during the first seventeen postnatal days without altering emotional and motor behavior at adult age. Besides, prenatal WiFi exposure induced cerebral oxidative stress imbalance (increase in malondialdehyde level (MDA) and hydrogen peroxide (H2O2) levels and decrease in catalase (CAT) and superoxide dismutase (SOD) activities) at 28 but not 43days old, also the exposure affected acethylcolinesterase activity at both cerebral and seric levels. Thus, the current study revealed that maternal exposure to WiFi radiofrequencies led to various adverse neurological effects in the offspring by affecting neurodevelopment, cerebral stress equilibrium and cholinesterase activity.

The use of low-level laser therapy for controlling the gag reflex in children during intraoral radiography.

The current literature suggests that low-level laser stimulation of the PC 6 acupuncture points may prevent gagging. This study aimed to determine if low-level laser therapy (LLLT) can reduce the gag reflex in children undergoing intraoral maxillary radiography. This randomized, controlled, double-blind clinical trial was conducted with 25 children with moderate-to-very severe gag reflexes who required bilateral periapical radiographic examination of the maxillary molar region. Children's anxiety levels were initially evaluated using Corah's Dental Anxiety Scale (DAS) to identify any possible relationship between gagging and anxiety. A control radiograph was taken of one randomly selected side in each patient after simulated laser application so that the patient was blinded to the experimental conditions (control group). Laser stimulation was then performed for the experimental side. A laser probe was placed on the Pericardium 6 (PC 6) acupuncture point on each wrist, and laser energy was delivered for 14 s (300 mW, energy density 4 J/cm(2)) at a distance of 1 cm from the target tissue. Following laser stimulation, the experimental radiograph was taken (experimental group). Gagging responses were measured using the Gagging Severity Criteria for each group. Data were analyzed using Spearman's rho correlations and Mann-Whitney U tests. Both mean and median gagging scores were higher in the control group than in the experimental group. Patients who were unable to tolerate the intraoral control radiography were able to tolerate the procedure after LLLT. Differences between gagging scores of the control and experimental groups were statistically significant (P = .000). There was no significant correlation between gagging severity and anxiety score (P > .05). A negative correlation was found between age and gagging score in the control group (P ˂ .05). Within the limitations of this study, LLLT of the PC 6 acupuncture points appears to be a useful technique for controlling the gag reflex in children during maxillary radiography.

Hydrogen-rich saline promotes survival of retinal ganglion cells in a rat model of optic nerve crush.

OBJECTIVE: To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC). METHODS: We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by H2. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated. RESULTS: H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H2 group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR. CONCLUSION: These results demonstrated that H2 protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.

Pathophysiology and natural history of anorectal sequelae following radiation therapy for carcinoma of the prostate.

PURPOSE: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. METHODS AND MATERIALS: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. RESULTS: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. CONCLUSIONS: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

Coaxially sighted intraocular lens light reflex for centration of the multifocal single piece intraocular lens.

Centration of multifocal Intraocular lenses (IOL) may be critical to ensure optimal function and prevent untoward side effects. Pharmacologic pupillary dilation and constriction may shift the physiologic location of the pupillary center rendering intraoperative positioning of multifocal IOL challenging. Similarly, the anterior capsular center is difficult to pinpoint and may not correspond to either the visual axis or the pupillary center. The visual axis is the only landmark that can be consistently identified prior, during and after cataract surgery. Centering diffractive multifocal IOL on the visual axis may allow more consistent placement and better outcome measures. In the following, we describe a simple technique to center multifocal single piece acrylic IOLs on the visual axis.

The circadian response of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or intrinsic (retinal) network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years) with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux). Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO) was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells mediate this circadian variation.

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

Central 5-HT(2A) receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats.

Activation of 5-hydroxytryptamine (5-HT) 5-HT(1A), 5-HT(2C), 5-HT(3), and 5-HT(7) receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT(2A/2B) receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT(2A/2B) antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT(2A) antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT(2B) antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT(2A) receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT(2B) receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT(2A) receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

The influence of psychological state on the masseteric exteroceptive suppression reflex and somatosensory function.

OBJECTIVE: This study examined the somatosensory function in the trigeminal region and quantitative measures of the exteroceptive suppression (ES) period in the masseteric EMG, in relation to a psychological evaluation. METHODS: The ES in the surface EMG was recorded from the left masseter muscle in 12 men and 12 women. The stimulation intensity at which the ES appeared first and the lowest intensity at which the subjects reported it to be painful were defined as the electrical reflex threshold and electrical pain threshold, respectively. Three experimental sessions were scheduled. The state and trait anxiety inventory was used to evaluate the psychological status. RESULTS: The electrical reflex threshold significantly decreased (p<0.01), and the electrical pain threshold significantly increased (p<0.01) over the sessions in line with the effect on the state anxiety inventory (p<0.05). CONCLUSIONS: The present results illustrate that reflex parameters and electrical pain thresholds are associated with state anxiety. Possibly, habituation or decreased fear from the experimental set-up may play a role. SIGNIFICANCE: This is important when electrophysiology or quantitative sensory testing is used to assess trigeminal nociception, e.g., in orofacial pain conditions.

Spinal nerve ligation-induced activation of nuclear factor kappaB is facilitated by prostaglandins in the affected spinal cord and is a critical step in the development of mechanical allodynia.

This study investigated the effect of 5th and 6th lumbar nerve (L5/L6) spinal nerve ligation (SNL) on activated nuclear factor kappaB (NFkBa) in nuclear extracts from the lumbar dorsal horn of the rat, and its relationship to prostaglandin (PG)-dependent spinal hyperexcitability and allodynia 3 days later. Male Sprague-Dawley rats, fitted with intrathecal (i.t.) catheters, underwent SNL- or sham-surgery. Paw withdrawal threshold (PWT), electromyographic analysis of the biceps femoris flexor reflex, and immunoblotting of the spinal cord were used. Both allodynia (PWT

Kinesthetic motor imagery and spinal excitability: the effect of contraction intensity and spatial localization.

OBJECTIVE: Data on whether motor imagery (MI) modulates spinal excitability are equivocal. The purpose of this study was to determine if imagined muscle contractions of the left plantar flexor (PF) alter spinal excitability, and if so, to determine whether this alteration is intensity dependent and/or localized to the target muscles. Our research questions required two experiments. METHODS: In experiment 1, 16 healthy volunteers performed imagined muscle contractions using a kinesthetic approach with their left PF at 25% and 100% of imagined effort (IE). The soleus H-reflex was evoked during three conditions, which were separated by about 15s: rest (preceding MI), during MI, and recovery (following the cessation of MI). In experiment 2, a subset of subjects from experiment 1 performed MI with their left PF at 100% of IE, while either the soleus or flexor carpi radialis (FCR) H-reflex was measured. RESULTS: In experiment 1, we observed a facilitation of soleus H-wave amplitude during MI compared to the rest and recovery conditions (p<0.05). Furthermore, the soleus H-wave amplitude was greater during 100% than 25% of IE (p<0.05). In experiment 2, soleus and FCR H-wave amplitude increased during imagined muscle contractions of the left PF (p<0.05). These changes were independent of voluntary muscle activity. CONCLUSIONS: These findings suggest MI can increase spinal excitability by the intensity of imagined effort, but this effect is not fully localized to the task specific muscle. SIGNIFICANCE: These data provide evidence that MI can increase spinal excitability in healthy subjects, which suggests future studies are warranted to examine the clinical relevance of this effect. These studies are needed to help establish a therapeutic theory by which to advance motor function rehabilitation using MI.

Adaptation of cutaneous stumble correction when tripping is part of the locomotor environment.

We recently showed that cutaneous reflexes evoked by stimulating the superficial peroneal (SP; innervates foot dorsum) nerve are modulated according to the level of postural threat. Context-related modulation was observed mainly in contralateral (c) responses but not in the ipsilateral responses. This lack of effect on ipsilateral (i) cutaneous reflexes might have been caused by the general nature of the whole body perturbation. We therefore hypothesized that context-relevant mechanical perturbations applied to the dorsum of the foot by an instrumented rod at early swing during walking would produce differences in ipsilateral cutaneous reflex amplitudes, consistent with the functional relevance of the SP nerve in stumble correction responses. Subjects walked on a motorized treadmill under four conditions: 1) normal, 2) normal with mechanical perturbations at the foot dorsum, 3) arms crossed, and 4) arms crossed with mechanical perturbations at the foot dorsum. Electrical stimulation of the SP nerve was delivered at five phases of the step cycle, and cutaneous reflexes were compared between all conditions for each phase of the step cycle. Reflex responses were generally found to be modulated in amplitude during walking conditions in which mechanical perturbations were delivered, particularly in ipsilateral tibialis anterior (iTA), which showed a marked reduction in inhibition. The results indicated cutaneous reflexes in iTA and contralateral medial gastrocnemius (cMG) were influenced by the threat of a trip, induced by applying mechanical perturbations to the foot dorsum during walking. This task-related gating of cutaneous reflexes was not generalized to all muscles, thus suggesting a functional role in the maintenance of stability during locomotion.

Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision.

Rod and cone photoreceptors detect light and relay this information through a multisynaptic pathway to the brain by means of retinal ganglion cells (RGCs). These retinal outputs support not only pattern vision but also non-image-forming (NIF) functions, which include circadian photoentrainment and pupillary light reflex (PLR). In mammals, NIF functions are mediated by rods, cones and the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). Rod-cone photoreceptors and ipRGCs are complementary in signalling light intensity for NIF functions. The ipRGCs, in addition to being directly photosensitive, also receive synaptic input from rod-cone networks. To determine how the ipRGCs relay rod-cone light information for both image-forming and non-image-forming functions, we genetically ablated ipRGCs in mice. Here we show that animals lacking ipRGCs retain pattern vision but have deficits in both PLR and circadian photoentrainment that are more extensive than those observed in melanopsin knockouts. The defects in PLR and photoentrainment resemble those observed in animals that lack phototransduction in all three photoreceptor classes. These results indicate that light signals for irradiance detection are dissociated from pattern vision at the retinal ganglion cell level, and animals that cannot detect light for NIF functions are still capable of image formation.

Immediate electrical stimulation enhances regeneration and reinnervation and modulates spinal plastic changes after sciatic nerve injury and repair.

We have studied whether electrical stimulation immediately after nerve injury may enhance axonal regeneration and modulate plastic changes at the spinal cord level underlying the appearance of hyperreflexia. Two groups of adult rats were subjected to sciatic nerve section followed by suture repair. One group (ES) received electrical stimulation (3 V, 0.1 ms at 20 Hz) for 1 h after injury. A second group served as control (C). Nerve conduction, H reflex, motor evoked potentials, and algesimetry tests were performed at 1, 3, 5, 7 and 9 weeks after surgery, to assess muscle reinnervation and changes in excitability of spinal cord circuitry. The electrophysiological results showed higher levels of reinnervation, and histological results a significantly higher number of regenerated myelinated fibers in the distal tibial nerve in group ES in comparison with group C. The monosynaptic H reflex was facilitated in the injured limb, to a higher degree in group C than in group ES. The amplitudes of motor evoked potentials were similar in both groups, although the MEP/M ratio was increased in group C compared to group ES, indicating mild central motor hyperexcitability. Immunohistochemical labeling of sensory afferents in the spinal cord dorsal horn showed prevention of the reduction in expression of substance P at one month postlesion in group ES. In conclusion, brief electrical stimulation applied after sciatic nerve injury promotes axonal regeneration over a long distance and reduces facilitation of spinal motor responses.

Neuromuscular consequences of reflexive covert orienting.

Visual stimulus presentation activates the oculomotor network without requiring a gaze shift. Here, we demonstrate that primate neck muscles are recruited during such reflexive covert orienting in a manner that parallels activity recorded from the superior colliculus (SC). Our results indicate the presence of a brainstem circuit whereby reflexive covert orienting is prevented from shifting gaze, but recruits neck muscles, predicting that similarities between SC and neck muscle activity should extend to other cognitive processes that are known to influence SC activity.

A toolbox for light control of Drosophila behaviors through Channelrhodopsin 2-mediated photoactivation of targeted neurons.

In order to study the function of specific neural circuits, we generated UAS-Channelrhodopsin2 (ChR2) transgenic Drosophila and established a ChR2-based system that enables specific activation of targeted neurons in larval and adult fruit flies with blue light illumination, under the control of a newly designed light source that provides fully programmable stimulation patterns. We showed that stimulating selectively the nociceptor of larvae expressing ChR2 elicited light-induced 'pain' response, confined freely behaving larvae in defined area and directed larva migration along a preset route. In freely behaving adult flies, rapid photoactivation of targeted gustatory sensory neurons, dopaminergic modulatory neurons and motor neurons triggered the proboscis extension response, escaping reflex and changes in the locomotion pattern, respectively, with precise temporal control. This non-invasive method for remote control of animal behaviors also provides a potential tool for conducting 'gain of function' studies toward understanding how animal behaviors are controlled by neural activity.

Epidural spinal cord stimulation plus quipazine administration enable stepping in complete spinal adult rats.

We hypothesized that epidural spinal cord stimulation (ES) and quipazine (a serotonergic agonist) modulates the excitability of flexor and extensor related intraspinal neural networks in qualitatively unique, but complementary, ways to facilitate locomotion in spinal cord-injured rats. To test this hypothesis, we stimulated (40 Hz) the S(1) spinal segment before and after quipazine administration (0.3 mg/kg, ip) in bipedally step-trained and nontrained, adult, complete spinal (mid-thoracic) rats. The stepping pattern of these rats was compared with control rats. At the stimulation levels used, stepping was elicited only when the hindlimbs were placed on a moving treadmill. In nontrained rats, the stepping induced by ES and quipazine administration was non-weight bearing, and the cycle period was shorter than in controls. In contrast, the stepping induced by ES and quipazine in step-trained rats was highly coordinated with clear plantar foot placement and partial weight bearing. The effect of ES and quipazine on EMG burst amplitude and duration was greater in flexor than extensor motor pools. Using fast Fourier transformation analysis of EMG bursts during ES, we observed one dominant peak at 40 Hz in the medial gastrocnemius (ankle extensor), whereas there was less of dominant spectral peak in the tibialis anterior (ankle flexor). We suggest that these frequency distributions reflect amplitude modulation of predominantly monosynaptic potentials in the extensor and predominantly polysynaptic pathways in the flexor muscle. Quipazine potentiated the amplitude of these responses. The data suggest that there are fundamental differences in the circuitry that generates flexion and extension during locomotion.

Facilitation of spinal reflexes assists performing but not learning an obstacle-avoidance locomotor task.

The aim of this study was to investigate spinal reflex (SR) modulation during the performance and learning of a precision locomotor task. Healthy subjects had to minimize foot clearance when repeatedly stepping on a treadmill over a randomly approaching obstacle. The subjects walked with reduced vision and were informed about the approaching obstacle and task performance by acoustic warning and feedback signals, respectively. SRs were randomly evoked by tibial nerve stimulation (with non-nociceptive and nociceptive stimulus intensity) during the mid-stance phase in both normal and pre-obstacle stepping. Foot clearance and electromyographic activity of the tibialis anterior and biceps femoris muscles of the right leg were analysed. Only if a delay was introduced between warning signal and nerve stimulation, was the SR amplitude in both muscles enhanced prior to obstacle steps compared with normal steps for both stimulus intensities. Thus, the reflex enhancement depended on the subject's awareness of the approaching obstacle. Improved performance was reflected in a decreased foot clearance, but did not correlate with the course of SR amplitude. It is concluded that obstacle stepping is associated with a facilitation of SR pathways, probably by supraspinal drive. This facilitation might provide assistance in safe obstacle stepping, e.g. to compensate quickly if resistance is encountered.