Delivering Holistic Transgender and Nonbinary Care in the Age of Telemedicine and COVID-19: Reflections and Implications for Best Practices.

This review describes the authors' experiences in offering gender-affirming primary care and hormonal care using an evidence-based, interprofessional, and multidisciplinary approach. The authors offer references for best practices set forth by organizations and thought leaders in transgender health and describe the key processes they developed to respectfully deliver affirming care to transgender and nonbinary patients.

Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.

Schizophrenia (SCZ) is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were over-represented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis for dysfunction in cerebellar cortex in SCZ.

A morphine-paired environment alters c-Fos expression in the forebrain of rats displaying conditioned place preference or aversion.

The question of whether a common mechanism mediates both aversive and rewarding drug-paired cues is still unclear. In this study, we used a place preference conditioning paradigm to train rats to associate 1 chamber with morphine and the other chamber with saline. On the test day, rats were divided into those displaying conditioned place preferences (CPP) versus conditioned place aversion (CPA). After the test, all rats were killed and c-Fos immunocytochemistry was performed. For the control group, rats were treated with the same procedure except that the injections of morphine or saline had no association with the chambers. Compared with the control group, the CPP and CPA groups showed a significant increase of c-Fos expression in the dorsomedial striatum, central medial nucleus of the thalamus, and the basolateral amygdala. However, we saw no difference between CPP and CPA rats in any brain region examined. These results suggest that a morphine-paired environment can elicit neural activity in brain regions that are involved in emotional learning. Morphine-conditioned place preference and aversion may share a common neural circuitry elicited by a morphine-paired environment.

Morphine actions in the rat forebrain: role of protein kinase C.

Acute administration of morphine induces expression of the immediate-early gene (IEG) c-Fos in dorsomedial striatum, portions of cerebral cortex, and in several midline-intralaminar thalamic nuclei, partly via a trans-synaptic mechanism that involves activation of glutamate receptors. Because activation of protein kinase C (PKC) may occur following the activation of glutamate receptors, we determined whether pharmacological inhibition of PKC would attenuate morphine-induced c-Fos expression, and whether acute administration of morphine would induce translocation of PKC. The selective PKC antagonist NPC 15437 given 30 min prior to morphine significantly decreased morphine-induced c-Fos expression in striatum and cingulate cortex, but not in centrolateral thalamus. In another experiment, rats were given an acute dose of morphine, and immunocytochemical analysis was performed for the betaI and betaII isoforms of PKC. Morphine induced a rapid and transient translocation of PKC betaII, but not betaI, from perinuclear spots to plasma membrane in numerous cortical and striatal neurons. Prior administration of naloxone blocked this response. Ultrastructural studies confirmed translocation from Golgi apparatus to plasma membrane 15 min after morphine injection. Double immunocytochemistry at the light microscopic level demonstrated co-localization of translocated PKC betaII and c-Fos in some cortical neurons 90 min after morphine injection. These results support a role for PKC, especially PKC betaII, in the rapid effects of morphine on the brain.

Successful surgical management of a case of spontaneous epidural hematoma of the spine during pregnancy.

BACKGROUND CONTEXT: A spontaneous epidural hematoma of the spine occurring during pregnancy is extremely rare. The development of a significant neurologic deficit may be rapid. Therefore, the neurosurgeon should be aware of the presentation, diagnosis and treatment options available. PURPOSE: The authors report a case of a spontaneous epidural hematoma of the spine during the third trimester of pregnancy, which was successfully managed with surgical evacuation. The case is unique in that the patient demonstrated a subacute presentation. STUDY DESIGN: The authors report a case of a 27-year-old primagravada presented with the subacute onset of progressive paraparesis. She became nonambulatory before admission. A magnetic resonance imaging study (MRI) demonstrated ventral epidural compression in the upper thoracic region. METHODS: A retrospective review of a case of spontaneous epidural hematoma of the spine during pregnancy was performed. The inpatient and outpatient charts were used to gather clinical information of the case, and the pertinent radiographs and images were reviewed. RESULTS: An urgent cesarean section was performed followed by evacuation of the epidural hematoma. The decompression was performed by means of a thoracic laminectomy with partial facetectomy. The patient had a prompt return of neurologic function. CONCLUSION: Spontaneous epidural hematoma of the spine should be suspected in the setting of acute back or neck pain with or without an associated progressive neurologic deficit. Spine surgeons and obstetricians should also recognize that a spinal epidural hematoma during pregnancy may also present subacutely, as illustrated in our case. Prompt diagnosis may be made with MRI, and evacuation of the hematoma should be performed, ideally before the onset of neurologic signs or symptoms. The prognosis for return of neurologic function is good after urgent evacuation.

Modulation of glutamate receptor expression by gonadal steroid hormones in the rat striatum.

The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) attenuates morphine-induced immediate-early gene expression in the rat striatum in a sexually dimorphic manner that depends in part on gonadal steroids. To determine if this effect was dependent on modulation of glutamate receptor gene expression, we studied the effect of gonadal hormones on levels of the NR1 subunit of NMDA receptor and the GluR2 subunit of the AMPA-subtype of glutamate receptor in the rat striatum, using autoradiographic immunocytochemistry. We found that ovariectomy decreased GluR2 immunoreactivity in the striatum, but no changes were seen in levels of NR1 following gonadectomy in either sex. Thus, the effects of gonadal steroids on NMDA receptor-mediated responses are not due to regulation of NR1 expression.

Immunolocalization of PICK1 in the ascending auditory pathways of the adult rat.

Protein that interacts with C-kinase alpha (PICK1) is a PDZ domain protein that interacts with many binding partners in the central nervous system (CNS), including activated protein kinase Calpha and subunits of the AMPA subtype of glutamate receptor. Almost nothing is known about the anatomic distribution of PICK1 in the intact adult CNS. By using PICK1 antisera and peroxidase immunocytochemistry, we report on the distribution of PICK1 in the ascending pathways of the central auditory system of the adult rat. PICK1-immunoreactivity (ir) was observed in many component nuclei of the central auditory system, including the dorsal cochlear nucleus, anteroventral cochlear nucleus, posteroventral cochlear nucleus, some divisions of the superior olivary complex, inferior colliculus, medial geniculate body, and primary auditory cortex. The general staining pattern for PICK1-immunoreactivity was somatodendritic with scattered puncta in neuropil and somatodendritic regions. The distribution of PICK1 partially overlaps with PKCalpha and glutamate receptor subunits such as GluR2. These data suggest that PICK1 may function in the regulation of PKCalpha and GluR2 localization in components of the rat auditory system, which may be a fundamental mechanism of synaptic transmission and/or plasticity. J. Comp. Neurol.

Sexually dimorphic effects of morphine and MK-801: sex steroid-dependent and -independent mechanisms.

Rats show gender differences in responses to morphine and the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801); the role of sex steroids in mediating these differences is unclear. We tested the overall hypothesis that circulating gonadal steroids determine the gender differences in morphine- and MK-801-induced behavior and c-Fos expression. Morphine caused a greater expression of c-Fos in the striatum of intact males than of that females, which was independent of sex steroids. MK-801 completely inhibited morphine-induced c-Fos in intact females but only caused partial inhibition in intact males; castrated males showed complete inhibition, which was reversed by testosterone, but gonadal steroids had no effect on this response in females. In thalamus, there was a large sex difference in the response to MK-801 that was independent of gonadal steroids. Behavioral responses to morphine were greater in males, but responses to MK-801 were greater in females; both were sex steroid independent. These findings show significant sex differences in response to morphine and MK-801 that are mediated by sex steroid-dependent and -independent mechanisms, which may be important in treatment outcomes of drug addiction.