Cortical activation in generalized seizures.

OBJECTIVE: Patients with generalized epilepsy exhibit different epileptiform events including asymptomatic interictal spikes (IS), absence seizures with spike-wave discharges (SWDs), and myoclonic seizures (MS). Our objective was to determine the spatiotemporal patterns of cortical activation in SWDs, IS, and MS in the Gabra1+/A322D juvenile myoclonic epilepsy mouse. METHODS: We fabricated affordable, flexible high-density electroencephalography (HdEEG) arrays and recorded spontaneous SWD, IS, and MS with video/HdEEG. We determined differences among the events in amplitude spectral density (ASD) in the δ/θ/α/ß/γ frequency bands at baseline (3.5-4.0 seconds before the first spike time, t0 ) and the prespike period (0.1-0.5 seconds before t0 ), and we elucidated the spatiotemporal activation during the t0 spike. RESULTS: All three events had an increase in ASD between baseline and prespike in at least one frequency band. During prespike, MS had the largest δ-band ASD, but SWD had the greatest α/ß/γ band ASD. For all three events, the ASD was largest in the anterior regions. The t0 spike voltage was also greatest in the anterior regions for all three events and IS and MS had larger voltages than SWD. From 7.5 to 17.5 msec after t0 , MS had greater voltage than IS and SWD, and maximal voltage was in the posterior parietal region. SIGNIFICANCE: Changes in spectral density from baseline to prespike indicate that none of these generalized events are instantaneous or entirely unpredictable. Prominent engagement of anterior cortical regions during prespike and at t0 suggest that common anterior neural circuits participate in each event. Differences in prespike ASD signify that although the events may engage similar brain regions, they may arise from distinct proictal states with different neuronal activity or connectivity. Prolonged activation of the posterior parietal area in MS suggests that posterior circuits contribute to the myoclonic jerk. Together, these findings identify brain regions and processes that could be specifically targeted for further recording and modulation.

Pelvic Floor Disorders Among Minority Women: Differences in Prevalence, Severity and Health-Related Social Needs.

OBJECTIVE: To characterize prevalence and severity of pelvic floor disorders (PFDs) in various health care settings and to examine unmet health-related social needs (HRSN) among minority women. MATERIALS AND METHODS: Minority women with PFDs were recruited from our academic urogynecology clinic, a general urology clinic at our institution's safety net hospital, and a community outreach mobile clinic. Questions from the Urinary Distress Index-6, Pelvic Organ Prolapse Distress Inventory-6, and Female Genitourinary Pain Index were used to identify patients with stress urinary incontinence, overactive bladder (OAB), and chronic pelvic pain syndrome (CPPS). RESULTS: Sixty-one (46.6%) women identified as Hispanic, 53 (40.4%) as Black, and 17 (12.9%) as Other. Overall, self-reported PFDs included stress urinary incontinence in 45%, OAB in 74.8%, and CPPS in 24.4% of women. Hispanic women were more likely to report OAB symptoms, compared to Black women (odds ratio (OR) 3.4 [1.2-10.2], P = .03) or Other women (OR = 5.1 [1.3-20.4], P = .02). Participants held a median of 5 unmet HRSN. Minority women facing issues with family and community support, transportation, and utilities were more likely to report CPPS symptoms, compared to those without psychosocial issues (support OR: 4.8 [1.7-13.7], P = .002; transportation OR: 2.0 [1.0-8.2], P = .05; utility OR: 7.0 [1.9-28.1], P = .005). CONCLUSION: Minority women with PFDs may have several unmet HRSNs which impact their ability to receive appropriate medical care. Our findings may assist in the development of effective strategies to improve health care outcomes for women dealing with PFDs.

Provision of HIV preexposure prophylaxis to female patients seeking family planning services in the United States.

OBJECTIVE: We conducted a scoping review to assess barriers to and facilitators of integrating HIV preexposure prophylaxis (PrEP) and family planning (FP) at the patient, provider, and implementation levels, and to identify gaps in knowledge. METHODS: We conducted a search of five bibliographic databases from database inception to March 2022: PubMed, CINAHL, Embase, Web of Science and Scopus. Two reviewers screened abstracts and full texts to determine eligibility based on a priori inclusion and exclusion criteria. We categorized studies by their relevance to patient, provider, and implementation barriers, and extracted data based on prespecified elements. RESULTS: Our initial search strategy yielded 1151 results, and 34 publications were included. Barriers to PrEP implementation in family planning settings included low PrEP knowledge among patients, hesitance to take PrEP due to perceived stigma, decreased willingness of providers unfamiliar with PrEP to prescribe PrEP, and limited financial and staffing resources that make prescribing and monitoring PrEP difficult. Facilitators included robust training for providers, stigma reduction efforts, leadership engagement, and increased resources specifically in settings with processes in place that ease the process of prescribing and monitoring PrEP. CONCLUSIONS: Advances in implementation strategy development, stigma reduction, and drug development will be essential to reinforcing PrEP care in family planning settings and thereby reducing the incidence of HIV in women through highly effective pharmacologic HIV prevention methods.

HIV, opioid use, and alterations to the gut microbiome: elucidating independent and synergistic effects.

Background: The microbiome is essential to immune development, defense against pathogens, and modulation of inflammation. Microbial dysbiosis has been reported in various diseases including human immunodeficiency virus (HIV) and opioid use disorder (OUD). Notably, people living with HIV (PLWH) have been reported to both have higher rates of OUD and use opioids at higher rates than the general public. Thus, studying gut microbial alterations in people living with HIV and with OUD could elucidate mechanisms pertaining to how these conditions both shape and are shaped by the microbiome. However, to date few studies have investigated how HIV and OUD in combination impact the microbiome. Aim of review: Here, we review previous studies outlining interactions between HIV, opioid use, and microbial dysbiosis and describe attempts to treat this dysbiosis with fecal microbial transplantation, probiotics, and dietary changes. Key scientific concepts of review: While the limited number of studies prevent overgeneralizations; accumulating data suggest that HIV and opioid use together induce distinct alterations in the gut microbiome. Among the three existing preclinical studies of HIV and opioid use, two studies reported a decrease in Lachnospiraceae and Ruminococcaceae, and one study reported a decrease in Muribaculaceae in the combined HIV and opioid group relative to HIV-alone, opioid-alone, or control groups. These bacteria are known to modulate immune function, decrease colonic inflammation, and maintain gut epithelial barrier integrity in healthy individuals. Accordingly, modulation of the gut microbiome to restore gut homeostasis may be attempted to improve both conditions. While mixed results exist regarding treating dysbiosis with microbial restoration in PLWH or in those with opioid dependency, larger well-defined studies that can improve microbial engraftment in hosts hold much promise and should still be explored.

Re-Evaluating the Association Between Hormonal Contraception and Breast Cancer Risk.

This review aims to summarize and assess key studies investigating the relationship between hormonal contraception and breast cancer risk. Approximately two-thirds of breast cancers express the estrogen receptor, and long-term exposure to estrogen is a debated risk factor for breast cancer development. This hypothesis is based on prior studies looking at reproductive risk factors (endogenous estrogen exposure) along with hormone replacement therapy (exogenous hormone exposure). Historically accepted reproductive risk factors include age at menarche, age at first delivery, and parity. Exogenous hormone exposure encompasses both receipt of hormonal contraception and menopausal hormone replacement therapy. This review highlights the reported risks associated with the most common hormonal contraception methods including oral, transdermal, and transvaginal routes. Large observational studies of the past and more recent works are summarized highlighting gaps in knowledge. Several themes emerge: difficulty accounting for well-established risk factors in analyses of epidemiologic studies, challenges determining whether associations between hormonal contraception and breast cancer are due to the exogenous hormones themselves or to increased engagement with the medical system, and discrepancies between statistically significant and clinically significant risk, odds, and hazard ratios. Understanding the strengths and limitations of these studies will help providers in and outside of oncology support women making decisions regarding both cancer risk-reduction and family planning.

Functional connectivity in the dorsal network of the cervical spinal cord is correlated with diffusion tensor imaging indices in relapsing-remitting multiple sclerosis.

Focal lesions may affect functional connectivity (FC) of the ventral and dorsal networks in the cervical spinal cord of people with relapsing-remitting multiple sclerosis (RRMS). Resting-state FC can be measured using functional MRI (fMRI) at 3T. This study sought to determine whether alterations in FC may be related to the degree of damage in the normal-appearing tissue. Tissue integrity and FC in the cervical spinal cord were assessed with diffusion tensor imaging (DTI) and resting-state fMRI, respectively, in a group of 26 RRMS participants with high cervical lesion load, low disability, and minimally impaired sensorimotor function, and healthy controls. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in the normal-appearing white matter in the RRMS group relative to controls. Average FC in ventral and dorsal networks was similar between groups. Significant associations were found between higher FC in the dorsal sensory network and several DTI markers of pathology in the normal-appearing tissue. In the normal-appearing grey matter, dorsal FC was positively correlated with axial diffusivity (AD) (r = 0.46, p = 0.020) and mean diffusivity (MD) (r = 0.43, p = 0.032). In the normal-appearing white matter, dorsal FC was negatively correlated with FA (r = -0.43, p = 0.028) and positively correlated with RD (r = 0.49, p = 0.012), AD (r = 0.42, p = 0.037) and MD (r = 0.53, p = 0.006). These results suggest that increased connectivity, while remaining within the normal range, may represent a compensatory mechanism in response to structural damage in support of preserved sensory function in RRMS.

Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.