Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring.

Epidemiological studies have reported discrepant findings on the relationship between folic acid intake during pregnancy and risk for gestational diabetes mellitus (GDM). To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5× recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of diet-induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation are not due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (western and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the fetal offspring from supplemented dams but this differed between western and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype and has sex-specific effects on offspring pancreas and liver.

Ozone sauna therapy and pulsed electromagnetic field therapy could potentially improve outcome in women with diminished ovarian reserve undergoing assisted reproductive technology.

There are limited treatment options for women with severely diminished ovarian reserve (DOR) who experience repeatedly failed in vitro fertilization (IVF) cycles and with persistently thin endometrial lining thickness (EMT) during frozen embryo transfer cycles. Therefore, a large majority of patients resort to using donor oocytes and gestational carriers. Data from existing animal and human studies suggest that ozone sauna therapy (OST) and pulsed electromagnetic field therapy (PEMF) are emerging as potential therapeutic adjuncts for female reproduction. This study was conducted to assess the fertility outcome of OST + PEMF in vivo in patients undergoing IVF/frozen embryo transfe and the effects of OST in vitro on human granulosa cell (GC) function. Forty-four women with DOR underwent their 1st IVF cycle (Cycle 1), and then were administered transdermal and intravaginal OST + PEMF, twice a week for 3 weeks, followed by a 2nd IVF cycle (Cycle 2) using the same protocol as in Cycle 1. GCs collected from another six women who underwent egg retrieval were equally split and cultured with OST (test) or placed in room temperature (control) outside the OST chamber in the same room. The results demonstrated that Cycles 1 and 2 had no significant difference in the number of days of stimulation, baseline hormones measured, number of oocytes retrieved or peak estradiol levels. However, the number of embryos formed after OST + PEMF in Cycle 2 was significantly higher than the Cycle 1. Furthermore, EMT measured in Cycle 2 demonstrated a significant increase compared to Cycle 1 and all patients reached a satisfactory EMT of approximately 7 mm. In vitro studies demonstrated that OST led to a 5-fold significant increase in the aromatase enzyme while a significant 50% reduction was noted in the side-chain cleavage enzyme in GCs. Both OST + PEMF are known for their vasodilatory, anti-inflammatory, and antioxidant actions, which could enhance endometrial receptivity and increase the number of formed embryos without increasing the number of oocytes retrieved, suggesting an improvement in oocyte quality. Finally, ozone can alter genes involved in steroidogenesis suggesting that it could improve ovarian function.

Ozone Sauna Therapy (OST) and Pulsed Electromagnetic Field Therapy (PEMF) delivered via the HOCATT machine could improve endometriosis pain along with lowering serum inflammatory markers.

PROBLEM: Endometriosis, a common and challenging condition, is a pelvic inflammatory condition that causes chronic pelvic pain (CPP) and infertility. Even though standard medical therapies and surgeries can help CPP, a large percentage of women remain symptomatic following the conventional treatments. Thus, there is a need to study new non-traditional therapeutic adjuncts in this patient population to improve their quality of life. One non-traditional therapeutic agent is Ozone Sauna Therapy (OST) which has been shown to have an anti-inflammatory action, but no studies have been performed to assess the efficacy of OST in women with endometriosis suffering with CPP. Another non-traditional therapeutic agent is Pulsed Electromagnetic Field Therapy (PEMF) where one small pilot study has shown that PEMF exposure to women with endometriosis and pelvic pain showed dramatic relief in symptoms. METHOD OF STUDY: The HOCATT machine, by delivering a combination of both OST and PEMF in one machine, has been shown to improve fertility treatment outcome via in vitro fertilization (IVF) in older women by potentially improving oocyte quality. This study was conducted to assess the effect of the HOCATT machine use on the pain scale in patients struggling with CPP due to endometriosis. In the first study, eight women with endometriosis were administered transdermal and intravaginal OST + PEMF, twice a week for 3 weeks (total of 6 sessions). Once a week, the participants were asked to fill a pain scale. In the second study, 10 women were recruited in order to evaluate the changes in serum inflammatory markers following OST + PEMF exposure after 3-week period using the HOCATT machine twice a week (total of 6 sessions). RESULTS: The participants had a mean age of 39.7 ± 1.1 years. The results showed a significant improvement in pain scale following the fourth session (p < .05) and a significant drop in serum levels of the inflammatory markers CRP (p = .0438) and IL-1ß (p = .0031) and a significant increase in serum levels of IL-8 (p = .033). CONCLUSIONS: This pilot study suggests that a combination of OST and PEMF using the HOCATT machine could potentially represent potential therapeutic adjuncts for women with inflammatory disorders such as endometriosis. There is a definite need for larger cohort studies and even randomized trials in order to better assess the efficacy of OST and PEMF in women with other inflammatory disorders.

Exploring the impact of community-based choral participation on cognitive function and well-being for persons with dementia: evidence from the Voices in Motion project.

OBJECTIVES: Music-based interventions are postulated to mitigate cognitive decline in individuals with dementia. However, the mechanisms underlying why music-based interventions facilitate cognitive benefits remain unknown. The present study examines whether a choral intervention can modulate patterns of cognitive change in persons with dementia and whether within-person variation in affect is associated with this change. METHODS: Thirty-three older adults with dementia engaged weekly in the Voices in Motion (ViM) study consisting of 3 choral seasons spanning 18-months. Performance on the Mini-Mental State Examination (MMSE) and the Positive and Negative Affect Schedule was assessed monthly within each choral season using a longitudinal intensive repeated-measures design. Three-level multilevel models were employed to disaggregate between- and within-person effects across short- (month-to-month) and long-term (season-to-season) intervals. RESULTS: ViM participants exhibited an annual MMSE decline of 1.8 units, notably less than the clinically meaningful 3.3 units indicated by non-intervention literature. Further, variability in negative affect shared a within-person time-varying association with MMSE performance; decreases in negative affect, relative to one's personal average, were linked to corresponding improvements in cognitive function. CONCLUSION: Engagement in the ViM choral intervention may attenuate cognitive decline for persons with dementia via a reduction of psychological comorbidities such as elevated negative affect.

Increasing the Representation of Black Men in Medicine by Addressing Systems Factors.

In 2015, data released by the Association of American Medical Colleges (AAMC) showed that there were more Black men applying and matriculating to medical school in 1978 than 2014. The representation of Black men in medicine is a troubling workforce issue that was identified by the National Academies of Sciences, Engineering, and Medicine as a national crisis. While premedical pathway programs have contributed to increased workforce diversity, alone they are insufficient to accelerate change. In response, the AAMC and the National Medical Association launched a new initiative in August 2020, the Action Collaborative for Black Men in Medicine, to address the systems factors that influence the trajectory to medicine for Black men. The authors provide a brief overview of the educational experiences of Black boys and men in the United States and, as members of the Action Collaborative, describe their early work. Using research, data, and collective lived experiences, the Action Collaborative members identified premedical and academic medicine systems factors that represented opportunities for change. The premedical factors include financing and funding, information access, pre-health advisors, the Medical College Admission Test, support systems, foundational academics, and alternative career paths. The academic medicine factors include early identification, medical school recruitment and admissions, and leadership accountability. The authors offer several points of intervention along the medical education continuum, starting as early as elementary school through medical school matriculation, for institutional leaders to address these factors as part of their diversity strategy. The authors also present the Action Collaborative's process for leveraging collective impact to build an equity-minded action agenda focused on Black men. They describe their initial focus on pre-health advising and leadership accountability and next steps to develop an action agenda. Collective impact and coalition building will facilitate active, broad engagement of partners across sectors to advance long-term systems change.

Choral singing and dementia: Exploring musicality as embodied and relational accomplishment.

This study explored the impact of participation in Voices in Motion (ViM), an intergenerational community choir program that involved persons with dementia, care partners, and high school students in Victoria, British Columbia, Canada. Data came from interviews with 23 duets, each consisting of a person with dementia and their care partner; additionally, five focus groups with 29 students across two ViM choirs were conducted. Choir rehearsals and concerts were also observed. The analysis revealed that those with dementia have an embodied ability to fully participate in the choir and perform songs despite cognitive decline and memory loss. Involvement in the choirs also facilitated the emergence of strong social relationships among participants while students reported gaining a deeper understanding of the everyday experiences of living with dementia. Through well-attended concerts and performances at public events, ViM also helped re-humanize persons living with dementia by challenging the narrative of decline and its associated stigma.

Flexible inhibitory control of visually evoked defensive behavior by the ventral lateral geniculate nucleus.

Animals can choose to act upon, or to ignore, sensory stimuli, depending on circumstance and prior knowledge. This flexibility is thought to depend on neural inhibition, through suppression of inappropriate and disinhibition of appropriate actions. Here, we identified the ventral lateral geniculate nucleus (vLGN), an inhibitory prethalamic area, as a critical node for control of visually evoked defensive responses in mice. The activity of vLGN projections to the medial superior colliculus (mSC) is modulated by previous experience of threatening stimuli, tracks the perceived threat level in the environment, and is low prior to escape from a visual threat. Optogenetic stimulation of the vLGN abolishes escape responses, and suppressing its activity lowers the threshold for escape and increases risk-avoidance behavior. The vLGN most strongly affects visual threat responses, potentially via modality-specific inhibition of mSC circuits. Thus, inhibitory vLGN circuits control defensive behavior, depending on an animal's prior experience and its anticipation of danger in the environment.

Sex-specific effects of neonatal oral sucrose treatment on growth and liver choline and glucocorticoid metabolism in adulthood.

Hospitalized preterm infants experience painful medical procedures. Oral sucrose is the nonpharmacological standard of care for minor procedural pain relief. Infants are treated with numerous doses of sucrose, raising concerns about potential long-term effects. The objective of this study was to determine the long-term effects of neonatal oral sucrose treatment on growth and liver metabolism in a mouse model. Neonatal female and male mice were randomly assigned to one of two oral treatments (n = 7-10 mice/group/sex): sterile water or sucrose. Pups were treated 10 times/day for the first 6 days of life with 0.2 mg/g body wt of respective treatments (24% solution; 1-4 µL/dose) to mimic what is given to preterm infants. Mice were weaned at age 3 wk onto a control diet and fed until age 16 wk. Sucrose-treated female and male mice gained less weight during the treatment period and were smaller at weaning than water-treated mice (P ≤ 0.05); no effect of sucrose treatment on body weight was observed at adulthood. However, adult sucrose-treated female mice had smaller tibias and lower serum insulin-like growth factor-1 than adult water-treated female mice (P ≤ 0.05); these effects were not observed in males. Lower liver S-adenosylmethionine, phosphocholine, and glycerophosphocholine were observed in adult sucrose-treated compared with water-treated female and male mice (P ≤ 0.05). Sucrose-treated female, but not male, mice had lower liver free choline and higher liver betaine compared with water-treated female mice (P < 0.01). Our findings suggest that repeated neonatal sucrose treatment has long-term sex-specific effects on growth and liver methionine and choline metabolism.

Non-canonical role for Lpar1-EGFP subplate neurons in early postnatal mouse somatosensory cortex.

Subplate neurons (SPNs) are thought to play a role in nascent sensory processing in neocortex. To better understand how heterogeneity within this population relates to emergent function, we investigated the synaptic connectivity of Lpar1-EGFP SPNs through the first postnatal week in whisker somatosensory cortex (S1BF). These SPNs comprise of two morphological subtypes: fusiform SPNs with local axons and pyramidal SPNs with axons that extend through the marginal zone. The former receive translaminar synaptic input up until the emergence of the whisker barrels, a timepoint coincident with significant cell death. In contrast, pyramidal SPNs receive local input from the subplate at early ages but then - during the later time window - acquire input from overlying cortex. Combined electrical and optogenetic activation of thalamic afferents identified that Lpar1-EGFP SPNs receive sparse thalamic innervation. These data reveal components of the postnatal network that interpret sparse thalamic input to direct the emergent columnar structure of S1BF.

Barriers to Care among Patients with Sarcoidosis: A Qualitative Study.

Rationale: Lower-income patients with sarcoidosis experience worse outcomes than those with higher incomes. The reasons for these disparities are not well understood. Objectives: To identify patient-reported barriers to and facilitators of self-empowered care among patients with sarcoidosis residing in high- and low-median-income zip-code areas. Methods: Patients with biopsy-proven sarcoidosis who had received pharmacologic treatment within the past year and who were cared for in a sarcoidosis clinic of a large, urban medical system were included. Focus groups were stratified by high- and low-median-income zip-code areas. Transcriptions were analyzed using grounded theory. Results: Five focus groups were created; two included patients living in zip-code areas with high median incomes ($84,263; interquartile range [IQR], $79,334-$89,795), and three included patients living in zip-code areas with low median incomes ($27,470; IQR, $22,412-27,597). Patients with sarcoidosis from low-income and high-income zip-code areas reported remarkably similar experiences. Patients reported that sarcoidosis was a burden owing to its disease manifestations and the adverse effects of treatment, which led to a compromised ability to perform their activities of daily living at home or at work. Reported barriers to care included perceived inadequate knowledge about sarcoidosis among providers, communication barriers with providers, and the high cost of treatment. Patients from low-income zip-code areas experienced discrimination related to race and income, which served to compound their mistrust. Patients sought to overcome these barriers through self-empowerment, including independent learning, self-advocacy, medication nonadherence, and use of alternative therapies. Conclusions: Patients with sarcoidosis who lived in high- and low-income zip-code areas expressed similar overall concerns regarding sarcoidosis care. However, patients from low-income zip-code areas more frequently expressed concerns about racial and income-based discrimination. Patients from both groups addressed these barriers through self-empowerment, which included not adhering to prescribed therapies. Future work should focus on the effects of culturally and socioeconomically congruent, community-engaged interventions for quality of life of patients with sarcoidosis.

A socially-engaged lifestyle moderates the association between gait velocity and cognitive impairment.

Objective: Cognitive status has been linked to impaired gait velocity, and diminished social and physical engagement. To date, the potential moderating influence of lifestyle engagement on gait-cognitive status associations has not been systematically explored. The present investigation examines whether a socially- or physically-engaged lifestyle moderates the association between diminished gait velocity and likelihood of amnestic mild cognitive impairment (a-MCI) classification.Methods: Participants (aged 65+, Mage=73 years) were classified as either healthy controls (n = 30) or a-MCI (n = 24), using neuropsychological test scores and clinical judgement. Gait velocity was indexed using a GAITRite computerized walkway, engaged lifestyle (social and physical subdomains) were measured using a well-validated self-report measure, the revised Activity Lifestyle Questionnaire.Results: Logistic regression, evaluating likelihood of a-MCI classification, yielded a significant interaction between a socially-engaged lifestyle and gait velocity (b=.01, SE=.003, p=.015). Follow-up simple effects were derived for two levels (+/-1SD) of social engagement; for individuals 1 SD below the mean, the association between gait velocity and increased likelihood of a-MCI classification was exacerbated (probability of a-MCI classification for those with slower gait velocity was 60% higher for individuals 1 SD below vs 1 SD above the mean of social engagement). Physically-engaged lifestyle did not significantly moderate the gait-cognitive status association.Conclusions: The significant moderating influence of social engagement has several implications, including the likelihood that distinct mechanisms underlie the relationships of social engagement and gait velocity to cognitive function, the value of social variables for well-being, and the potential utility of socially-based interventions that may prevent/delay a-MCI onset.

Anxiety among women experiencing medically complicated pregnancy: A systematic review and meta-analysis.

BACKGROUND: Symptoms of anxiety are common among pregnant and postpartum women, and 15%-20% of pregnancies are affected by medical complications. Despite this, little is known about the relationship of medical complications in pregnancy and women's experience of anxiety. The purpose of this research was to conduct a systematic review and meta-analysis of differences in anxiety symptom severity among women experiencing a medically complicated versus a medically uncomplicated pregnancy. METHODS: This work was guided by the PRISMA reporting process. Electronic databases MEDLINE and PsycINFO were searched to identify studies that met the inclusion criteria. An adaptation of the Newcastle-Ottawa Quality Assessment Scale for case-control studies was used to perform a quality assessment review. A random-effects meta-analysis was used to calculate the estimated average standardized mean differences. RESULTS: Based on the five studies which met our inclusion criteria, findings provide evidence of higher levels of anxiety symptoms among pregnant women experiencing a medically complicated versus a medically uncomplicated pregnancy. Despite considerable heterogeneity, all mean difference estimates are in the direction of greater anxiety in the high-risk groups. CONCLUSIONS: Women experiencing a medically complex pregnancy report higher levels of anxiety symptoms compared to women experiencing a medically uncomplicated pregnancy.

Ozone and pulsed electro-magnetic field therapies improve endometrial lining thickness in frozen embryo transfer cycles: Three case reports.

RATIONALE: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles. PATIENT CONCERNS: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness. DIAGNOSES: Infertility undergoing FET cycles. INTERVENTIONS: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy. OUTCOMES: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer. LESSONS: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.

Ozone therapy: a potential therapeutic adjunct for improving female reproductive health.

Ozone is emerging as a new adjunct therapeutic agent for female infertility. We here present a review of the literature, to date, pertaining to the effect of ozone therapy on tubal, ovarian, endometrial, and vaginal factors that could potentially affect female fertility. It also presents data pertaining to the relationship of ozone therapy on pelvic adhesion formation. Most data were performed on animals and very few human studies existed in the literature. Results suggested that ozone therapy could have beneficial effect on tubal occlusion, could protect from endometritis and vaginitis, might protect ovaries from ischemia and oocyte loss and finally might lead to less formation of pelvic adhesions. There is a critical need for human studies pertaining to ozone therapy, especially using safe methods of administration, such as transdermally or intravaginally, on female fertility.

The Meaning of a Visual Arts Program for Older Adults in Complex Residential Care.

ABSTRACTThis qualitative study explores the experiences of older adults participating in a creative visual arts program at a residential care facility in Victoria, British Columbia. A narrative inquiry approach was used to conduct face-to-face interviews with 10 residents and three program staff in addition to the systematic observations of program activities and an arts exhibit. The findings reveal the program fostered a sense of community among participants and enhanced their sense of self-worth as artists. A public art exhibition at a community centre underlined the value of residents' artwork and gave meaning and purpose to their involvement in the program. Findings show the importance of arts programs in fostering creativity in later life and illustrate how people living in institutions can experience multiple dimensions of the self through artistic forms of expression. This study highlights the need to increase access to arts programs for individuals living in residential care.

Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits.

How neuronal connections are established and organized into functional networks determines brain function. In the mammalian cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made toward parsing interneuron diversity, yet the molecular mechanisms by which interneuron-specific connectivity motifs emerge remain unclear. In this study, we investigated transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits in mouse. We found that whether interneurons form synapses on the dendrites, soma, or axon initial segment of pyramidal cells is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus, cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.

Post Your Journey: Instagram as a Support Community for People With Fibromyalgia.

Fibromyalgia is a chronic illness with primary symptoms of widespread pain and fatigue. Social media applications have become a recent resource allowing individuals with fibromyalgia to interact in a virtual community devoted to the illness. This study explores how such a community develops and maintains itself on Instagram and the ways it creates social capital for its users. Data are derived from Instagram posts and open-ended questionnaires completed by users living with fibromyalgia who use the application. Using content analysis and semiotic methodology, the study analyzes the diverse ways in which users shared their experiences with fibromyalgia, the management of its symptoms, and issues encountered in accessing health care systems. Instagram aids in the development of a community by facilitating intimate and supportive interactions about the illness and the creation of personalized day-to-day narratives accessible to all. Norms of trust, acceptance, and reciprocity characterize the diversity of interactions in this community.

Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.

Studies of cortical connectivity using optical circuit mapping methods.

An important consideration when probing the function of any neuron is to uncover the source of synaptic input onto the cell, its intrinsic physiology and efferent targets. Over the years, electrophysiological approaches have generated considerable insight into these properties in a variety of cortical neuronal subtypes and circuits. However, as researchers explore neuronal function in greater detail, they are increasingly turning to optical techniques to bridge the gap between local network interactions and behaviour. The application of optical methods has increased dramatically over the past decade, spurred on by the optogenetic revolution. In this review, we provide an account of recent innovations, providing researchers with a primer detailing circuit mapping strategies in the cerebral cortex. We will focus on technical aspects of performing neurotransmitter uncaging and channelrhodopsin-assisted circuit mapping, with the aim of identifying common pitfalls that can negatively influence the collection of reliable data.

Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican.

Activity-dependent neuronal plasticity is a fundamental mechanism through which the nervous system adapts to sensory experience. Several lines of evidence suggest that parvalbumin (PV+) interneurons are essential in this process, but the molecular mechanisms underlying the influence of experience on interneuron plasticity remain poorly understood. Perineuronal nets (PNNs) enwrapping PV+ cells are long-standing candidates for playing such a role, yet their precise contribution has remained elusive. We show that the PNN protein Brevican is a critical regulator of interneuron plasticity. We find that Brevican simultaneously controls cellular and synaptic forms of plasticity in PV+ cells by regulating the localization of potassium channels and AMPA receptors, respectively. By modulating Brevican levels, experience introduces precise molecular and cellular modifications in PV+ cells that are required for learning and memory. These findings uncover a molecular program through which a PNN protein facilitates appropriate behavioral responses to experience by dynamically gating PV+ interneuron function.