Local interneurons in the murine visual thalamus have diverse receptive fields and can provide feature selective inhibition to relay cells.

By influencing the type and quality of information that relay cells transmit, local interneurons in thalamus have a powerful impact on cortex. To define the sensory features that these inhibitory neurons encode, we mapped receptive fields of optogenetically identified cells in the murine dorsolateral geniculate nucleus. Although few in number, local interneurons had diverse types of receptive fields, like their counterpart relay cells. This result differs markedly from visual cortex, where inhibitory cells are typically less selective than excitatory cells. To explore how thalamic interneurons might converge on relay cells, we took a computational approach. Using an evolutionary algorithm to search through a library of interneuron models generated from our results, we show that aggregated output from different groups of local interneurons can simulate the inhibitory component of the relay cell's receptive field. Thus, our work provides proof-of-concept that groups of diverse interneurons can supply feature-specific inhibition to relay cells.

Trace element, antioxidant and oxidant levels in spinal cord injury: different perspective on the effects of valproic acid.

OBJECTIVE: One of the most pronounced phenomena of spinal cord injury (SCI) pathology is various changes caused by oxidative stress due to secondary damage. In recent years, it has been understood that valproic acid (VPA) has neuroprotective properties other than its clinical effect. The aim of this study is to investigate whether there is a change in antioxidant activity and trace the element level due to SCI-induced secondary damage, and to examine whether VPA has an effect on this change. MATERIALS AND METHODS: Experimentally, spinal damage was induced in a total of sixteen rats by compressing the infrarenal and iliac bifurcation parts of the aorta for 45 minutes and these rats were equally divided into SCI (control) and SCI + VPA groups. The treatment group was injected with VPA (300 mg/kg) intraperitoneally once following SCI. In addition, the motor neurological functions of both groups after SCI were evaluated with the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and Rivlin's angle of incline test. The spinal cord tissues of both groups were homogenized and the supernatants were separated for biochemical analysis. RESULTS: The results showed that SCI significantly reduced catalase (CAT), glutathione peroxidase (GPx), total antioxidant status (TAS), magnesium (Mg), zinc (Zn) and selenium (Se) levels and increased total oxidative status (TOS), oxidative stress indices (OSI), chromium (Cr), iron (Fe), and copper (Cu) in damaged spinal cord tissue. In particular, the administration of VPA prior to the significant increase in the effect of SCI-secondary damage turned these negative findings into positive. CONCLUSIONS: Our findings show that the spinal cord tissue damaged during SCI is protected against oxidative damage thanks to the neuroprotective property of VPA. Furthermore, it is an important finding that this neuroprotective mechanism contributes to the maintenance of the level of essential elements and antioxidant activity against SCI-induced secondary damage.

Physiological aspect of apoptosis-regulating microRNAs expressions during fasting.

OBJECTIVE: Fasting is an activity that requires a certain calorie restriction without consuming food or drinks for a certain period of daytime. However, fasting triggers many complex events, including activating cellular stress response pathways, autophagy promotion, apoptosis pathways, and a change in hormonal balance. Among the many events affecting the regulation of apoptosis, the expression of microRNAs (miRNAs) plays an important role. Therefore, we aimed to investigate the levels and importance of miRNA expression in fasting. PATIENTS AND METHODS: The expressions of 19 miRNAs regulating different pathways from saliva samples, isolated by matching healthy university students (n = 34) as group 1 (fasting for 17 consecutive hours) and group 2 (testing 70 minutes after meal consumption), were examined using the real-time PCR method. RESULTS: In fasting, modulation of apoptotic pathways by miRNAs triggers anti-pathogenic effects, and the adaptation of abnormal cells in the body decreases. For this reason, vital diseases, such as cancer, can be treated by preventing the proliferation and growth of cancerous cells by increasing programmed cell death due to the downregulation expression mechanism of miRNAs. CONCLUSIONS: Our study aims to improve the knowledge about the mechanisms and functions of miRNAs in various apoptosis pathways during fasting and may be a model for further future physiological and pathological studies.

Visual Information Processing in the Ventral Division of the Mouse Lateral Geniculate Nucleus of the Thalamus.

Even though the lateral geniculate nucleus of the thalamus (LGN) is associated with form vision, that is not its sole role. Only the dorsal portion of LGN (dLGN) projects to V1. The ventral division (vLGN) connects subcortically, sending inhibitory projections to sensorimotor structures, including the superior colliculus (SC) and regions associated with certain behavioral states, such as fear (Monavarfeshani et al., 2017; Salay et al., 2018). We combined computational, physiological, and anatomical approaches to explore visual processing in vLGN of mice of both sexes, making comparisons to dLGN and SC for perspective. Compatible with past, qualitative descriptions, the receptive fields we quantified in vLGN were larger than those in dLGN, and most cells preferred bright versus dark stimuli (Harrington, 1997). Dendritic arbors spanned the length and/or width of vLGN and were often asymmetric, positioned to collect input from large but discrete territories. By contrast, arbors in dLGN are compact (Krahe et al., 2011). Consistent with spatially coarse receptive fields in vLGN, visually evoked changes in spike timing were less precise than for dLGN and SC. Notably, however, the membrane currents and spikes of some cells in vLGN displayed gamma oscillations whose phase and strength varied with stimulus pattern, as for SC (Stitt et al., 2013). Thus, vLGN can engage its targets using oscillation-based and conventional rate codes. Finally, dark shadows activate SC and drive escape responses, whereas vLGN prefers bright stimuli. Thus, one function of long-range inhibitory projections from vLGN might be to enable movement by releasing motor targets, such as SC, from suppression.SIGNIFICANCE STATEMENT Only the dorsal lateral geniculate nucleus (dLGN) connects to cortex to serve form vision; the ventral division (vLGN) projects subcortically to sensorimotor nuclei, including the superior colliculus (SC), via long-range inhibitory connections. Here, we asked how vLGN processes visual information, making comparisons with dLGN and SC for perspective. Cells in vLGN versus dLGN had wider dendritic arbors, larger receptive fields, and fired with lower temporal precision, consistent with a modulatory role. Like SC, but not dLGN, visual stimuli entrained oscillations in vLGN, perhaps reflecting shared strategies for visuomotor processing. Finally, most neurons in vLGN preferred bright shapes, whereas dark stimuli activate SC and drive escape behaviors, suggesting that vLGN enables rapid movement by releasing target motor structures from inhibition.

Empathy as a Concept from Bench to Bedside: A Translational Challenge.

Empathy is a multidimensional paradigm, and there currently is a lack of scientific consensus in its definition. In this paper, we review the possibility of compromising data during behavioral neuroscience experiments, including but not limited to those who study empathy. The experimental protocols can affect, and be affected by, empathy and related processes at multiple levels. We discuss several points to help researchers develop a successful translational pathway for behavioral research on empathy. Despite varying in their focus with no widely accepted model, current rodent models on empathy have provided sound translational explanations for many neuropsychiatric proof-of-concepts to date. Research has shown that empathy can be influenced by many parameters, some of which are to be reviewed in this paper. We emphasize the future importance of consistency in modeling proof of concept; efforts to create a multidisciplinary group which would include both bench scientists and clinicians with expertise in neuropsychiatry, and the consideration of empathy as an independent variable in animal behavioral experimental designs which is not the mainstream practice at present.

Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?

Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.

Correction of myopic astigmatism by small incision lenticule extraction: does laterality matter?

To evaluate the outcome after astigmatic correction of small incision lenticule extraction (SMILE) and to compare the refractive results of right eyes with left eyes. Patients who underwent SMILE surgery in our clinic between 2014 and 2016 (Visumax, Carl Zeiss Meditec, Germany) were retrospectively reviewed. Preoperative and postoperative manifest refractions and corrected and uncorrected visual acuities were evaluated and changes in refractive astigmatism were evaluated by vector analysis. One hundred twenty-one eyes from 82 patients with myopic astigmatism were included. The mean preoperative spherical equivalent was - 6 ± 1.7 (range from - 9.50 to - 1.25) D and the mean cylinderical power was - 1.5 ± 0.6 (range from - 3.75 to - 1.00) D. Postoperatively 71.8% of eyes had < 0.50 D cylinder magnitude. Vector analysis results based on laterality revealed that correction index was 0.87 ± 0.3 for left eyes and 0.72 ± 0.3 for right eyes (p 0.02). This study revealed that SMILE has favorable astigmatic correction affect but left eyes have better outcomes than right eyes.

Acetaminophen (paracetamol) affects empathy-like behavior in rats: Dose-response relationship.

Empathy is the ability to recognize, process and respond to another's emotional state and empathic functions have been linked with a multitude of cognitive and affective processes. Impaired empathy has been linked to aggression and criminal behavior in society. Acetaminophen (paracetamol) is among the most common nonprescription (over the counter) analgesics in the world and has been already linked to reducing empathic behavior in humans. The aim of this study is to investigate the effects of acetaminophen on empathy-like behavior in Sprague Dawley rats, and we further explored the underlying mechanisms by analyzing empathy related neurohormones, e.g. oxytocin and vasopressin, in association with acetaminophen exposure in rats. Empathic behavior was assessed 30 min following acetaminophen administration (100, 200, and 400 mg/kg). The impact of single and repeated acetaminophen administrations on empathy-like behavior and anxiety level were evaluated separately. Empathy-like behavior was reduced with a single high dose of acetaminophen. Subsequent low dose administration of acetaminophen also reduced empathy-like behavior. In this study we also showed that acetaminophen decreased oxytocin and vasopressin levels in the prefrontal cortex and amygdalae. We found a negative correlation between delay in door opening time and measured prefrontal cortex oxytocin levels; we adjudged the latency in door opening time as enhanced empathic behavior which seemingly suggested the existence of a mechanism between empathy-like behavior and the prefrontal oxytocin. We observed that both a single high dose or repeated low dose administrations of acetaminophen reduced empathy-like behavior in correlation with a decrease in oxytocin and vasopressin levels in the prefrontal cortex and amygdala. Further research is needed to investigate the role of acetaminophen on the other empathic brain pathways.

The effects of acute foot shock stress on empathy levels in rats.

Empathy defined as the ability to understand and the share the feelings, thoughts, and attitudes of another, is an important skill in survival and reproduction. Among many factors that affect empathy include psychological stress, anxiety states. The aim of this study was to investigate the impact of acute psychological stress on empathic behavior and its association with oxytocin and vasopressin levels in amygdala and prefrontal cortex. Rats were subjected to 0.2 mA (low) and 1.6 mA (high) intensity of foot shock stress for duration of 20 min. Empathic behavior was found to be improved as a response to low intensity stress, but not to high intensity stress. As a response to lower intensity stress, vasopressin was increased in prefrontal cortex and amygdala; oxytocin was increased in only prefrontal cortex, and corticosterone levels increased in general. Anxiety indicators did not change in low intensity stress group yet; high intensity stress group demonstrated a lesser degree of anxiety response. High intensity stress group stayed unexpectedly more active in middle area of elevated plus maze test equipment, which may support impaired executive decision making abilities in the setting of high anxiety states. Further research is needed to investigate gender effects, the role of dopaminergic system and other stress related pathways in acute stress.

Statins reduce testicular and ocular VEGF: A potential compromise to microcirculation.

Microcirculation has great importance in eye and testicular tissue and is necessary to have adequate and appropriate amount of angiogenesis. It is known that high levels of Vascular Endothelial Growth Factor (VEGF) trigger uncontrolled angiogenesis, whereas inadequate VEGF can lead to decreased tissue perfusion and oxygenation. The aim of this study was to investigate effects of VEGF in testicular and ocular tissues in both non-diabetic and diabetic rats treated by statin. Atorvastatin (10 mg/kg daily given by orally gavage) was administered for two weeks. Diabetes was induced by streptozotocin, (STZ, 45 mg/kg/ip) in diabetic group's rats. Two weeks later from STZ injection, atorvastatin treatment was initiated in diabetic group. VEGF levels were measured by using ELISA. The VEGF levels were decreased in vitrous, ocular and testicular tissues of all statin-administered rats. In diabetic group VEGF levels were found to be decreased in testicular tissue and increased in ocular tissues. CONCLUSION: Statin use decreased in VEGF levels of testicular and ocular tissues in diabetic and non-diabetic rats. Statin treatment (anti-VEGF effect) had a protective effect in the development of diabetic retinopathy, yet statins may have a negative impact on tissues that depend on microcirculation by reducing VEGF levels. Further research is needed for statins' microcellular effects.

Small-Town America's Despair: Infected Substance Users Needing Outpatient Parenteral Therapy and Risk Stratification.

Background  An active intravenous substance use disorder is often the primary cause of infectious diseases in this population of users and creates a barrier to successful parenteral antimicrobial management. The dilemma is compounded by dramatically limited resources in small US towns. Methods This retrospective review from January 2014 through July 2016 aimed to develop a risk stratification approach to aid rural healthcare providers in determining who among patients with addictive disorders could safely be discharged for outpatient antimicrobial therapy with a peripherally inserted central catheter (PICC). Results The high-risk group had a greater likelihood of noncompliance with antimicrobial therapy completion, as well as subsequent illicit drug use during that time frame, compared with the moderate- and low-risk groups. The low-risk group and most of the moderate-risk group could be safely discharged into the community with PICC lines. Conclusions Key in the risk stratification proposal was identifying risk behaviors and determining their degree. Such information provides pivotal delineators in developing risk stratification criteria.

The cost of a recalcitrant intravenous drug user with serial cases of endocarditis: Need for guidelines to improve the continuum of care.

We report a case of an intravenous drug user (IVDU) patient who had 4 episodes of endocarditis within a 2-year time period in rural Georgia. The institutional cost was approximately $380,000. The lack of an established transitional care plan for IVDUs to outpatient care is a common phenomenon at institutions. Guidelines are essential to optimize the quality of care rendered to IVDUs with such infections, to assist providers in utilizing limited resources, and to limit the cost to the institutions.

Synaptic Contributions to Receptive Field Structure and Response Properties in the Rodent Lateral Geniculate Nucleus of the Thalamus.

Comparative physiological and anatomical studies have greatly advanced our understanding of sensory systems. Many lines of evidence show that the murine lateral geniculate nucleus (LGN) has unique attributes, compared with other species such as cat and monkey. For example, in rodent, thalamic receptive field structure is markedly diverse, and many cells are sensitive to stimulus orientation and direction. To explore shared and different strategies of synaptic integration across species, we made whole-cell recordings in vivo from the murine LGN during the presentation of visual stimuli, analyzed the results with different computational approaches, and compared our findings with those from cat. As for carnivores, murine cells with classical center-surround receptive fields had a "push-pull" structure of excitation and inhibition within a given On or Off subregion. These cells compose the largest single population in the murine LGN (∼40%), indicating that push-pull is key in the form vision pathway across species. For two cell types with overlapping On and Off responses, which recalled either W3 or suppressed-by-contrast ganglion cells in murine retina, inhibition took a different form and was most pronounced for spatially extensive stimuli. Other On-Off cells were selective for stimulus orientation and direction. In these cases, retinal inputs were tuned and, for oriented cells, the second-order subunit of the receptive field predicted the preferred angle. By contrast, suppression was not tuned and appeared to sharpen stimulus selectivity. Together, our results provide new perspectives on the role of excitation and inhibition in retinothalamic processing. SIGNIFICANCE STATEMENT: We explored the murine lateral geniculate nucleus from a comparative physiological perspective. In cat, most retinal cells have center-surround receptive fields and push-pull excitation and inhibition, including neurons with the smallest (highest acuity) receptive fields. The same is true for thalamic relay cells. In mouse retina, the most numerous cell type has the smallest receptive fields but lacks push-pull. The most common receptive field in rodent thalamus, however, is center-surround with push-pull. Thus, receptive field structure supersedes size per se for form vision. Further, for many orientation-selective cells, the second-order component of the receptive field aligned with stimulus preference, whereas suppression was untuned. Thus, inhibition may improve spatial resolution and sharpen other forms of selectivity in rodent lateral geniculate nucleus.

Investigation of biological effects of some Mannich Bases containing Bis-1,2,4- Triazole.

In this study, the effects of Mannich bases containing bis-1,2,4-triazole on the levels of in vivo malondialdehyde (MDA) and antioxidant vitamins (A, E, C) were examined in serum, livers and kidneys of rats. DA and vitamin (A, E, C) levels were determined by high performance liquid chromatography (HPLC). Antioxidant effect was investigated by determining the MDA levels in Saccharomyces cerevisiae cells as in vitro. Furthermore, the antitumor effects of compounds were investigated against MCF-7 human breast cancer cells. Interrelations of results among control and compound groups were evaluated using SPSS statistical software package. As a result, some of the compounds showed effective biological activity when compared to control conditions. The test compounds used in this study may be effective for utilization in the selection and design of model compounds for further studies.

Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2.

Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a ß-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3-5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS.

Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model.

The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK). To test the validity of the model, we studied the effect of standard antimanic medications lithium (47.5 mg/kg) or valproic acid (200 mg/kg) twice/day for 15 days in attenuating manic-like behaviors in the LHK rat. Compared with pre-kindling behaviors, LHK rats displayed significantly increased sexual self-stimulation (P = 0.034), excessive rearing (P = 0.0005), feeding (P = 0.013), and grooming (P = 0.007) during the kindling interval. LHK rats also drank more alcohol during the mania-induction days compared with baseline ethanol consumption levels (P = 0.01). Moreover, LHK rat exhibited increased total locomotor activity (P = 0.02) with reduced rest interval (P < 0.001) during the mania induction and post-mania days compared with baseline activity levels and rest intervals. Chronic administration of lithium or valproic acid significantly attenuated manic-like behaviors in the LHK rat model. Given the behavioral phenotype and the response to standard antimanic medications, the LHK rats may provide a model for studying manic psychopathology in humans.

Effects of pleural opening on respiratory function tests in cardiac surgery: a prospective study.

PURPOSE: To show the effects on lung function of the opening pleura in patients undergoing cardiac surgery. SUBJECTS AND METHODS: 66 patients were included. Patients were allocated into two groups. In group 1 (n=21) pleura was intact, in group 2 (n=45) pleura was opened. Both groups were compared prospectively in terms of preoperative and on the post-operative 5th day pulmonary function tests (PFT), preoperative, postoperative first and fifth day arterial blood gas analysis, preoperative and postoperative first day mixt venous oxygen saturation, bleeding, operation periods, pulmonary complications, intensive care and hospital stay period and mortality. RESULTS: There was significant decrease in all PFT indicators on 5th post-operative day in group 2 (p < 0.01). Although there was a significant decrease in FEV1 on 5th post-operative day in group 1 (p < 0.001), other pulmonary functions parameters were not change significantly (p > 0.025). In group 2 much more decline in pulmonary function test parameters than group 1 were observed (p < 0.05). There was not statistically significant difference in blood gas analysis and mixed venous oxygen saturation values in group 1 (p > 0.05). But in group 2 except pH and PaCO2, other blood gas measurements were significantly decreased on the postoperative first and fifth day (p < 0.008). In group 2 except pH and PCO2, other parameters were less than the other Group (p < 0.01). The drained amount was still significantly higher in group 2 (p < 0.001). The frequency of the revision due to bleeding was observed much more in group 2. CONCLUSIONS: Protection of the integrity of pleura may have positive effects on pulmonary functions in cardiac surgery.

Single-stage repair of adult aortic coarctation and concomitant coronary artery disease: an unusual surgical approach through median sternotomy.

Surgical repair of postductal aortic coarctation associated with severe coronary artery disease is in most cases a difficult decision to make. As staged procedures are associated with a higher rate of morbidity and mortality, simultaneous operative management of both pathologies is desirable. We describe a case of a 51-year-old man who was referred to our department for surgical treatment of postductal aortic coarctation and concomitant coronary artery disease, which we managed with single-stage surgery through median sternotomy.