Descriptive Analysis of Footplate Position After Myopic Implantable Collamer Lens Implantation Using a Very High-Frequency Ultrasound Robotic Scanner.

Purpose: To assess the position of the haptics of the implantable collamer lens (ICL) in myopic eyes using a high-frequency ultrasound robotic scanner. Methods: This was a prospective, single-arm, observational study carried out at the Instituto Zaldivar SA (Mendoza, Argentina) in a sample of 52 eyes who have been submitted to successful ICL implantation prior to enrollment. Images of the eyes were obtained using a very-high frequency digital ultrasound robotic scanner (VHFDU) to establish the position of the ICL in the posterior chamber and its relation to the ciliary sulcus. New parameters for lens position analysis were also described. Results: In 81% of cases (42 eyes), the ICL rests on the ciliary body (CB) in both temporal and nasal sides, being slightly lower than 6% (3 eyes) those that rest on the sulcus in both sides, with significant correlations between ICL position and vault values (p<0.05). Cases in which the ICL position was CB-CB yielded central vault values across the whole range determined within the sample, but most of the eyes where the ICL rests on both the sulcus in one side and the CB in the other yield greater central vault values. Correlation was significant between ICL position and retroposition distance on the temporal side (Spearman's rho -0.487, p<0.001). A significant but weaker correlation was also found between ICL position and retroiridian space (p<0.05). Conclusion: ICL for myopia footplates tend to locate outside of the sulcus in a significant percentage of patients after successful implantation. VHFDU assessment in eyes implanted with an ICL to properly study the lens footplate position and posterior anatomical relations provides important additional information besides post-surgery vault.

Response of Practicing Chiropractors during the Early Phase of the COVID-19 Pandemic: A Descriptive Report.

OBJECTIVE: The coronavirus disease-2019 (COVID-19) pandemic has strained all levels of healthcare and it is not known how chiropractic practitioners have responded to this crisis. The purpose of this report is to describe responses by a sample of chiropractors during the early stages of the COVID-19 pandemic. METHODS: We used a qualitative-constructivist design to understand chiropractic practice during the COVID-19 pandemic, as described by the participants. A sample of chiropractic practitioners (doctors of chiropractic, chiropractors) from various international locations were invited to participate. Each described the public health response to COVID-19 in their location and the actions that they took in their chiropractic practices from April 20 through May 4, 2020. A summary report was created from their responses and common themes were identified. RESULTS: Eighteen chiropractic practitioners representing 17 locations and 11 countries participated. A variety of practice environments were represented in this sample, including, solo practice, mobile practice, private hospital, US Veterans Administration health care, worksite health center, and group practice. They reported that they recognized and abided by changing governmental regulations. They observed their patients experience increased stress and mental health concerns resulting from the pandemic. They adopted innovative strategies, such as telehealth, to do outreach, communicate with, and provide care for patients. They abided by national and World Health Organization recommendations and they adopted creative strategies to maintain connectivity with patients through a people-centered, integrated, and collaborative approach. CONCLUSION: Although the chiropractors in this sample practiced in different cities and countries, their compliance with local regulations, concern for staff and patient safety, and people-centered responses were consistent. This sample covers all 7 World Federation of Chiropractic regions (ie, African, Asian, Eastern Mediterranean, European, Latin American, North American, and Pacific) and provides insights into measures taken by chiropractors during the early stages of the COVID-19 pandemic. This information may assist the chiropractic profession as it prepares for different scenarios as new evidence about this disease evolves.

Review about gabapentin misuse, interactions, contraindications and side effects.

The current work is targeted to review the risks of gabapentin misuse, its potential interactions with other drugs, side effects and use contraindications. This review consists of a total of 99 biographical references (from the year 1983 to 2016). A publication search of PubMed was performed from January 1983 to December 2016. It included animal studies, clinical studies, case studies and reviews related to gabapentin misuse, potential interactions, side effects and use contraindications. The search terms were gabapentin, anticonvulsant and antiepileptic. In general, it seems that gabapentin has risks of being misused based on the increased level of prescriptions, related fatalities, recreational misuse and higher doses of self-administration. The main reasons for gabapentin misuse are as follows: getting high, alleviating opioid withdrawal symptoms and potentiating methadone effects. Some of the main substances that interact with gabapentin are morphine, caffeine, losartan, ethacrynic acid, phenytoin, mefloquine and magnesium oxide. Some of the side effects caused by gabapentin are teratogenicity, hypoventilation, respiratory failure and myopathy. Finally, reports in general contraindicate the use of gabapentin in conditions such as myasthenia gravis and myoclonus.

A biopsychological review of gambling disorder.

The present review is an overview of previous experimental work on biopsychological aspects of gambling disorder. It includes the topics 1) gambling disorder from the neuroimaging and electroencephalography (EEG) perspective, 2) cognitive, executive functioning, and neuropsychological aspects of gambling disorder, and 3) rodent models of gambling disorder. Penalties and losses in gambling can differ in terms of brain activity. Also, specific patterns of brain activity, brain anatomical traits, EEG responses, and cognitive and executive performance can discriminate pathological gamblers from nonpathological gamblers. Also, pathological gamblers can display dysfunction in such brain areas as the insula, frontal lobe, and orbitofrontal cortex. Pathological gambling is a heterogeneous disorder that can vary depending on the severity of cognition, the style of gambling (strategic or not), the prospect of recovery, proneness to relapse, and proneness to treatment withdrawal. Finally, based on rodent models of gambling, the appropriateness of gambling decision is influenced by the presence of cues, the activity of dopamine receptors, and the activity of some brain areas (infralimbic, prelimbic, or rostral agranular insular cortex). Pathological gamblers differed in terms of frontoparietal brain activation compared to nonpathological gamblers (if winning or losing a game). Pathological gamblers had dysfunctional EEG activity. The severity of gambling was linked to the magnification and content of cognitive distortions. The insula was fundamental in the distortion of cognitions linked to result analysis during gambling activity.

α2δ-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse.

Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. α2δ-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates α2δ-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that α2δ-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the α2δ-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific α2δ-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin's effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that α2δ-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy.

Role of nucleus accumbens glutamatergic plasticity in drug addiction.

Substance dependence is characterized by a group of symptoms, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for alleviating withdrawal, exaggerated consumption beyond original intention, failure to reduce drug consumption, expending a considerable amount of time obtaining or recovering from the substance's effects, disregard of basic aspects of life (for example, family), and maintenance of drug consumption, despite facing adverse consequences. The nucleus accumbens (NAc) is a brain structure located in the basal forebrain of vertebrates, and it has been the target of addictive drugs. Different neurotransmitter systems at the level of the NAc circuitry have been linked to the different problems of drug addiction, like compulsive use and relapse. The glutamate system has been linked mainly to relapse after drug-seeking extinction. The dopamine system has been linked mainly to compulsive drug use. The glutamate homeostasis hypothesis centers around the dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on circuitry from the prefrontal cortex (PFC) to the NAc. After repetitive drug use, deregulation of this homeostasis increases the release of glutamate from the PFC to the NAc during drug relapse. Glial cells also play a fundamental role in this hypothesis; glial cells shape the interactions between the PFC and the NAc by means of altering glutamate levels in synaptic and extrasynaptic spaces. On the other hand, cocaine self-administration and withdrawal increases the surface expression of subunit glutamate receptor 1 (GluA1) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors at the level of the NAc. Also, cocaine self-administration and withdrawal induce the formation of subunit glutamate receptor 2 (GluA2), lacking the Ca(2+)-permeable AMPA receptors (CP-AMPARs) at the level of the NAc. Antagonism of the CP-AMPARs reduces cravings. It is necessary to pursue further exploration of the AMPA receptor subunit composition and variations at the level of the NAc for a better understanding of glutamatergic plastic changes. It is known that cocaine and morphine are able to induce changes in dendritic spine morphology by modifying actin cycling. These changes include an initial increase in spine head diameter and increases in AMPA receptor expression, followed by a second stage of spine head diameter retraction and reduction of the AMPA receptors' expression in spines. Besides glutamate and dopamine, other factors, like brain-derived neurotrophic factor (BDNF), can influence NAc activity and induce changes in dendritic spine density. BDNF also induces drug-related behaviors like self-administration and relapse. Neither apoptosis nor neurogenesis plays a relevant role in the neurobiological processes subjacent to cocaine addiction in adults (rodent or human). Different therapeutic drugs like N-acetylcysteine (NAC), modafinil, acamprosate, and topiramate have been tested in preclinical and/or clinical models for alleviating drug relapse. Moreover, these therapeutic drugs target the glutamatergic circuitry between the PFC and the NAc. NAC and acamprosate have shown inconsistent results in clinical trials. Modafinil and topiramate have shown some success, but more clinical trials are necessary. Based on the current review findings, it could be recommendable to explore therapeutic approaches that include synergism between different drugs and neurotransmitter systems. The discrepancy in the results of some therapeutic drugs between preclinical versus clinical trials for alleviating relapse or drug dependence could be linked to the scarce exploration of preclinical models that mimic polydrug abuse patterns, for example, cocaine plus alcohol. At the clinical level, the pattern of polydrug consumption is a phenomenon of considerable frequency. Finally, as a complement at the end, an updated summary is included about the role of glutamate in other neuropsychiatric disorders (for example, mood disorders, schizophrenia, and others).

Advances in cortical modulation of pain.

Pain is an intricate phenomenon composed of not only sensory-discriminative aspects but also of emotional, cognitive, motivational, and affective components. There has been ample evidence for the existence of an extensive cortical network associated with pain processing over the last few decades. This network includes the anterior cingulate cortex, forebrain, insular cortex, ventrolateral orbital cortex, somatosensory cortex, occipital cortex, retrosplenial cortex, motor cortex, and prefrontal cortex. Diverse neurotransmitters participate in the cortical circuits associated with pain processing, including glutamate, gamma-aminobutyric acid, dopamine, and opioids. This work examines recent rodent studies about cortical modulation of pain, mainly at a molecular level.

Reduction of inflammatory pain in female rats after NR2B NMDA cortical antagonism / Reducción del dolor inflamatorio en ratas hembras tras el antagonismo cortical de NR2B NMDA

Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. In this study, we used female adult Wistar rats to examine the effects of antagonizing the NR2B subunit of the NMDA receptor in phasic and tonic pain processes. All the rats underwent stereotaxic surgery for cortical cannula implantation and after at least one week of recovery, rats performed behavioral tests. For evaluating the effects of drugs on motor coordination rats were tested in the rotarod apparatus. Moreover, rats were evaluated in the paw withdrawal latency (PWL) to a noxious thermal stimulus. Furthermore, rats were tested in the formalinpain test. Rats that received the NR2B antagonist Ro 25-6981 before and after formalin injection showed significantly reduced pain responses in the formalin test, as compared with female control rats (p<0.05). In contrast, no differences among groups were found in the phasic pain test (Hargreaves) and the rotarod test. Taken together, these results suggest that cortical antagonism of the NR2B subunit of NMDA receptors is able to reduce inflammatory pain levels not only before, but after the formalin injection in females at different phases of the estrous cycle (AU)

Estudios han demostrado que los receptores de N-methyl-D-aspartato (NMDA) participan en el procesamiento del dolor en diferentes niveles del SNC. Este estudio empleó ratas hembras adultas Wistar para evaluar el antagonismo de la subunidad NR2B de NMDA en los procesos de dolor fásico y tónico. Se implantaron cánulas corticalmente con la cirugía estereotáxica y tras una semana de recuperación se realizaron pruebas conductuales. Se evaluaron los efectos del fármaco en la coordinación motora en el aparato de barra giratoria. Además, las ratas realizaron la prueba de latencia de retirada de la pata a un estímulo termal nocivo. Posteriormente, las ratas realizaron la prueba de formalina. Las ratas hembras que recibieron el antagonista de NR2B, Ro 25-6981, antes y después de la inyección de formalina denotaron respuestas de dolor significativamente menores en comparación con los controles (p<0.05). En contraste, no se encontraron diferencias significativas en la prueba de dolor fásico (Hargreaves) y la prueba de barra giratoria. En conjunto, estos resultados sugieren que el antagonismo cortical de la subunidad NR2B de los receptores NMDA es capaz de reducir los niveles de dolor inflamatorio, antes y después de la inyección de formalina en las distintas fases del ciclo estral (AU)

Reduction of inflammatory pain in female rats after NR2B NMDA cortical antagonism.

Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. In this study, we used female adult Wistar rats to examine the effects of antagonizing the NR2B subunit of the NMDA receptor in phasic and tonic pain processes. All the rats underwent stereotaxic surgery for cortical cannula implantation and after at least one week of recovery, rats performed behavioral tests. For evaluating the effects of drugs on motor coordination rats were tested in the rotarod apparatus. Moreover, rats were evaluated in the paw withdrawal latency (PWL) to a noxious thermal stimulus. Furthermore, rats were tested in the formalin-pain test. Rats that received the NR2B antagonist Ro 25-6981 before and after formalin injection showed significantly reduced pain responses in the formalin test, as compared with female control rats (p<0.05). In contrast, no differences among groups were found in the phasic pain test (Hargreaves) and the rotarod test. Taken together, these results suggest that cortical antagonism of the NR2B subunit of NMDA receptors is able to reduce inflammatory pain levels not only before, but after the formalin injection in females at different phases of the estrous cycle.

Exploration of sex differences in Rhes effects in dopamine mediated behaviors.

Studies have shown that Ras homolog enriched in striatum (Rhes) proteins are highly expressed in areas of the central nervous system that have high dopaminergic innervation. In this study, we used Rhes mutant mice (Wild type, Rhes KO, Rhes Heterozygous) of both sexes to explore differences in the effects of Rhes protein levels in basal levels of activity, anxiety, and stereotypy, in relation to sex. Adult male and female mice were evaluated in an open field test for measuring basal levels of activity and anxiety for 5 consecutive days, and they were tested in the apomorphine-induced stereotypy paradigm. Rhes protein levels affected basal levels of activity but it was not found to be related to sex differences. Moreover, a decrease in Rhes protein levels was linked to a nonsignificant anxiolytic effect, mainly in female mice. Finally, a decrease in Rhes protein levels does not affect dopamine D(1) and D(2) receptor (D(1)/D(2)) synergism in female or male mice. Together, these results suggest that Rhes protein levels affect locomotion activity, and have an influence in anxiety depending on sex; Rhes protein levels do not affect D(1)/D(2) synergism in both sexes.

Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats.

BACKGROUND: Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. METHODS: In this study, we used adult Wistar rats to examine gender differences in the effects of NR2B NMDA antagonism at the level of the anterior cingulate cortex in phasic pain, and in the first and second phases of a formalin test. Rats underwent stereotactic surgery for cannula implantation in the anterior cingulate cortex. After recovery, paw withdrawal latency to a noxious thermal stimulus was assessed. Rats were also subjected to a formalin pain test whereby 60 µL of 5% formalin was injected into the right hind paw. RESULTS: Female and male rats that received Ro 25-6981, an NR2B antagonist, before formalin injection showed significantly reduced pain responses to the formalin test compared with saline-injected control rats (P < 0.05). No gender differences in phasic pain responses were found in rats treated with Ro 25-6981. CONCLUSION: These results suggest that cortical antagonism of the NR2B subunit reduces inflammatory pain levels in both genders of rat.

The Ras homolog Rhes affects dopamine D1 and D2 receptor-mediated behavior in mice.

Dopamine activates five different receptor subtypes and a complex array of intracellular signaling pathways. Rhes is a striatally expressed guanidine triphosphate-binding protein involved in dopamine signaling. Here we have used mutant mice to test whether Rhes (Ras homolog enriched in striatum) is involved in D1 and D2 dopamine receptor-mediated behaviors. Rhes was not necessary for the expression of normal D1/D2 receptor synergism, as measured by apomorphine-induced stereotypy. The stereotypic responses to D1/D2 costimulation and to D2 stimulation alone were significantly increased in mice lacking Rhes, but D1 receptor-mediated grooming was reduced in these mice. These results suggest that Rhes is normally inhibitory to behaviors induced by D1/D2 receptor costimulation and by D2 receptor stimulation alone. Rhes, however, seems to facilitate the D1-specific behavior of grooming.

Evaluation of morphine analgesia and motor coordination in mice following cortex-specific knockout of the N-methyl-D-aspartate NR1-subunit.

Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in morphine analgesia and motoric processes at different levels of the central nervous system. In this study, we used cortex-specific NR1 knockout (KO) mice (C57BL/6 strain) to elucidate the role of cortical NMDA receptors in morphine analgesia and motor coordination. On post-natal day 20, mice (CTL and KO) received vehicle (saline) or morphine (10 mg/kg) and paw withdrawal latency (PWL) to a noxious thermal stimulus was measured. On post-natal day 21, motor coordination was measured using the rotating pole test. No differences in KO mice were found with respect to PWL following administration of saline or morphine (p>0.05). However, sex-dependent differences were found in motor coordination, with male KO mice showing a greater motor impairment in the rotating pole test than female KO mice (p<0.05). The present results demonstrate that NMDA receptors are involved in both the analgesic effects of morphine and motor coordination, with the existence of sex-related differences in motor coordination.

Decreased pain response in mice following cortex-specific knockout of the N-methyl-D-aspartate NR1 subunit.

Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. In this study, we used cortex-specific NR1 knockout mice (C57BL/6 strain) to elucidate the role of cortical NMDA receptors in pain processes. On post-natal day 20, paw withdrawal latency (PWL) to a noxious thermal stimulus was measured in male and female knockout (KO), control (Ctrl), and C57BL/6 (C57) mice. Twenty-four hours later, the same mice were tested in the formalin-pain assay (20 microl of 5% formalin injected into one hind-paw). The results show that KO mice (both male and female) have significantly reduced pain responses during both early and late phases of formalin test, as compared with Ctrl and C57 mice (p<0.01). By contrast, no differences among groups were found in PWL to a noxious thermal stimulus. Taken together, these results demonstrate dissociation in the role of cortical NMDA receptors in mediating different types of pain.