Adipose Tissue Dysfunction in Polycystic Ovary Syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity. METHODS: We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS. RESULTS: Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS. CONCLUSION: AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.

The association of patient age, race, and demographic features on reported pain and sedation dosing during procedural abortion: A retrospective cohort study.

OBJECTIVES: To explore impact of age, racial, demographic, and psychosocial factors on patients' dosage of analgesia and maximum pain score during procedural abortion. STUDY DESIGN: We performed retrospective chart review of pregnant individuals undergoing procedural abortion at our hospital-based abortion clinic from October 2019 through May 2020. Patients were stratified into age groups,<19 years, 19 to 35 years, and>35 years. We conducted the Kruskal-Wallis H test to evaluate for medication dosing or maximum pain score differences among groups. RESULTS: We included 225 patients in our study. We found no difference in fentanyl or midazolam dosing by age. The median fentanyl dose was 75 mcg and median midazolam dose was 2 mg in all three groups (p = 0.61, p = 0.99). White patients received higher median midazolam dosing than Black patients (2 and 3 mg, respectively, p < 0.01) despite similar pain scores. Despite no difference in pain scores, patients terminating for genetic anomaly received more fentanyl than those terminating for socioeconomic reasons (75 and 100 mcg, respectively, p < 0.01). CONCLUSIONS: In our limited study, we found that White race and induced abortion for genetic anomaly were associated with increased medication dosing, though age was not. Multiple demographic and psychosocial factors, as well as perhaps provider bias, play into both a patient's perception of pain and the dosage of fentanyl and midazolam they receive during abortion procedures. IMPLICATIONS: By acknowledging both patient factors and provider biases in medication dosing, we can provide more equitable abortion care.

Assessment of Stress Urinary Incontinence-Related Podcasts on Stitcher.

OBJECTIVE: To assess the quality, understandability, actionability, accuracy and commercial bias of podcasts regarding stress urinary incontinence (SUI). METHODS: The first 100 Stitcher podcasts from the search, "Stress urinary incontinence" were evaluated using the validated DISCERN criteria, PEMAT tool, and a Misinformation Likert Scale. The accuracy of information was assessed by comparison to the American Urological Association (AUA) SUI Guidelines. RESULTS: Common publisher types included health/wellness channels (66%). Low-moderate quality, poor understandability and misinformation was seen in 67% (DISCERN ≤3), 69% (PEMAT understandability ≤75%) and 17% of podcasts, respectively. Treatments discussed included pelvic floor muscle training (PFMT) (89%) and surgery (47%). Health and wellness channels had the most evidence of commercial bias (44%). Podcasts that discussed surgery more often emphasized shared decision-making (DISCERN15). CONCLUSION: SUI-related podcasts on Stitcher are mostly published by health/wellness channels and skewed toward discussing PFMT. Podcasts are often low-moderate quality, poorly understandable and often have commercial bias.

Characteristics of pelvic organ prolapse content available on social media.

AIMS: To analyze the quality, understandability, and actionability of pelvic organ prolapse (POP) content and to characterize creators of content and treatment options discussed on social media platforms YouTube, Instagram, and Pinterest. METHODS: A cross-sectional, qualitative study was conducted for each platform. A search for "pelvic organ prolapse" was conducted and the first 100 relevant results analyzed. Data collected include source characteristics, treatments discussed, and scores for each criterion of validated Patient Education Materials and Assessment Tool and DISCERN metrics to evaluate quality, actionability, and understandability. The χ 2 analysis, univariate and multivariate logistic regressions were done to assess correlations and the impact of variables on outcomes of interest across platforms. RESULTS: Low to moderate quality was present in 74.1% of posts. Poor understandability was seen in 37.1% of posts, and 56.1% had poor actionability. The most common publisher of content overall was health and wellness or physical therapy groups (44.6%). The most common YouTube publisher was doctors, hospitals, or clinics (49%). Pelvic floor muscle training was the most discussed treatment overall (57.4%). On YouTube surgery was discussed more frequently than Instagram or Pinterest (58% vs. 11% vs. 43%, p < 0.001. Pinterest posts had better understandability ratings than YouTube videos (odds ratio = 0.19; 95% confidence interval: [0.10-0.36]; p < 0.001). CONCLUSION: Information on popular platforms regarding POP demonstrates inconsistent quality and poor understandability and actionability. There is an opportunity for health care providers to direct patients to curated lists of high-quality educational content on these platforms. Awareness of information available on social media is an increasingly important aspect of patient care.

Concordance and discordance between maternal and newborn drug test results.

BACKGROUND: Screening for substance use is recommended during pregnancy, and many clinicians rely on urine drug screening to identify newborns at potential risk for withdrawal. OBJECTIVE: This study aimed to determine the concordance and discordance rates between maternal and neonatal drug testing at or near the time of delivery. STUDY DESIGN: This retrospective chart review was performed at a single institution that employs universal testing for those who consent. Results of maternal and neonatal urine drug testing via immunoassay at delivery were compared. RESULTS: Of 1573 singleton pregnancies, 233 mothers (14.8%) had a positive test result for any substance and 102 of their newborns (43.8%) had concordant positive test results. Of the 285 positive maternal test results for individual substances, 133 (46.7%) were concordant with newborn test results. After removing iatrogenic positives, there were 84 truly discordant pairs representing 5.9% of the total cohort of test pairs, but 29.5% of the pairs with maternal positive test results. When considering the outcome of a newborn positive test result, the overall sensitivity and specificity for the maternal test were 21.1% and 85.8%, respectively. The positive and negative predictive values were 46.7% and 96.4%, respectively. After excluding iatrogenic positive test results, the sensitivity and specificity for maternal testing were 97.8% and 99.4%, respectively, and the negative predictive value of maternal testing for all substances approached 100%. A total of 11 pairs of twins had at least 1 twin with a positive drug test result, and of these, 6 twin pairs (54.5%) had drug test results that were discordant from each other. CONCLUSION: There is a high rate of iatrogenic discrepancy in maternal and neonatal drug testing. After adjusting for iatrogenic positive test results, the negative predictive value of maternal testing is high. Many discrepancies, such as those in twins, remained unexplained by medication administration, and potential reasons for these discrepancies warrant further investigation.

Analysis of Pelvic Organ Prolapse-related Content on Pinterest.

OBJECTIVES: Our study is a cross-sectional, qualitative study analyzing pelvic organ prolapse-related content on Pinterest, a social media platform that also functions as a visual search engine. Primary outcomes assessed include quality, understandability, and actionability of content. Secondary outcomes include levels of misinformation and commercial bias. Our study further characterizes sources of prolapse content and treatment modalities discussed. METHODS: A Pinterest search was conducted using the term "pelvic organ prolapse," analyzing the first 100 relevant results. We examined the publisher of each pin and the writer of linked content. Using validated tools including the Patient Education Materials Assessment Tool and DISCERN criteria, we assessed understandability and actionability of content. We further compared content to professional guidelines for discussing and treating prolapse, evaluating for misinformation. We also evaluated for commercial bias and subjectively rated pin quality. RESULTS: Of pins evaluated, low understandability was found in 16, low actionability in 30, and low-to-moderate quality in 69. The most common publisher of pins was health and wellness groups, and the most common writer of content was physical therapists. Pelvic floor muscle training (PFMT) is the treatment modality discussed most frequently on Pinterest. CONCLUSIONS: Pinterest content discussing pelvic organ prolapse shows good levels of understandability for patients at all levels of health literacy. However, the number of pins showing poor actionability raises concern that content may not encourage readers to take direct steps toward prolapse assessment and management. In all, a majority of prolapse-related content on Pinterest was of low-to-moderate quality.

Review of Insurance Coverage for Abdominal Contouring Procedures in the Postbariatric Population.

BACKGROUND: Following bariatric surgery, patients develop problems related to lax abdominal skin that may be addressed by contouring procedures. Third-party insurers have subjective requirements for coverage of these procedures that can limit patient access. The authors sought to determine how well third-party payers cover abdominal contouring procedures in this population. METHODS: The authors conducted a cross-sectional analysis of insurance policies for coverage of panniculectomy, lower back excision, and circumferential lipectomy. Abdominoplasty was evaluated as an alternative to panniculectomy. Insurance companies were selected based on their market share and state enrolment. A list of medical necessity criteria was abstracted from the policies that offered coverage. RESULTS: Of the 55 companies evaluated, 98 percent had a policy that covered panniculectomy versus 36 percent who would cover lower back excision (p < 0.0001), and one-third provided coverage for circumferential lipectomy. Of the insurers who covered panniculectomy, only 30 percent would also cover abdominoplasty. Documentation of secondary skin conditions was the most prevalent criterion in panniculectomy policies (100 percent), whereas impaired function and secondary skin conditions were most common for coverage of lower back excision (73 percent and 73 percent, respectively). Frequency of criteria for panniculectomy versus lower back excision differed most notably for (1) secondary skin conditions (100 percent versus 73 percent; p = 0.0030), (2) weight loss (45 percent versus 7 percent; p = 0.0106), and (3) duration of weight stability (82 percent versus 53 percent; p = 0.0415). CONCLUSIONS: For the postbariatric population, panniculectomy was covered more often and had more standardized criteria than lower back excision or circumferential lipectomy. However, all have vast intracompany and interpolicy variations in coverage criteria that may reduce access to procedures, even among patients with established indications.

A Review of National Insurance Coverage of Post-bariatric Upper Body Lift.

INTRODUCTION: Recent years have seen an increased utilisation of upper body lift following massive weight loss. Although it is typically considered cosmetic, the recurrent skin conditions and decline in quality of life may warrant medical necessity. We evaluated current insurance coverage and characterised policy criteria for upper body lift in the post-bariatric population. METHODS: We defined upper body lift as a combination of mastopexy and upper back excision (UBE) and conducted a cross-sectional analysis of US insurance policies. Insurance companies were selected based on their enrolment data and market share. A web-based search and telephone interviews were conducted to identify the policy. Criteria were abstracted from the publicly available policies that offered coverage. RESULTS: Of the 56 insurance companies assessed, 5% would consider coverage of both procedures. Although fewer companies held established policies for UBE than mastopexy in the post-bariatric population (79% vs 96%, p = 0.0081), there were significantly more policies that offered pre-approval for UBE than for mastopexy (30% vs 5%, p = 0.0017). Three medical necessity criteria were common to both procedures: evidence of functional impairment, secondary skin conditions, and medical photographs. CONCLUSION: Policy criteria for coverage of mastopexy or UBE differ greatly between companies. Further evaluation of medical necessity criteria for post-bariatric mastopexy and UBE with the establishment of a standardised guideline is needed. We propose a comprehensive list of reporting recommendations to help optimise authorisation of upper body lift in the post-bariatric population, and we urge plastic surgeons to challenge current definition of "cosmetic" by insurance companies. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Methods for fabrication and evaluation of a 3D microengineered model of myelinated peripheral nerve.

OBJECTIVE: The cost and low success rates of the neurological drug development pipeline have diverted the pharmaceutical industry to 'nerve-on-a-chip' systems as preclinical models to streamline drug development. We present a novel micro-engineered 3D hydrogel platform for the culture of myelinated embryonic peripheral neural tissue to serve as an effective in vitro model for electrophysiological and histological analysis that could be adopted for preclinical testing. APPROACH: Dorsal root ganglions (DRG) from 15 d old embryonic rats were cultured in 3D hydrogel platforms. The interaction between Schwann cells (SC) and neurons during axonal development and regeneration affects the direction of growth and the synthesis of myelin sheaths. Induction of myelination was performed with two approaches: the addition of exogenous SC and promoting migration of endogenous SC. MAIN RESULTS: Histological analysis of the preparation utilizing exogenous SC showed aligned, highly fasciculated axonal growth with noticeable myelin sheaths around axons. Separately, electrophysiological testing of the preparation utilizing endogenous SC showed increased amplitude of the compound action potential and nerve conduction velocity in the presence of ascorbic acid (AA). SIGNIFICANCE: This platform has immense potential to be a useful and translatable in vitro testing tool for drug discovery and myelination studies.

Lymphocytes influence intracranial aneurysm formation and rupture: role of extracellular matrix remodeling and phenotypic modulation of vascular smooth muscle cells.

BACKGROUND: Intracranial aneurysms (IA) are increasingly recognized as a disease driven by chronic inflammation. Recent research has identified key mediators and processes underlying IA pathogenesis, but mechanistic understanding remains incomplete. Lymphocytic infiltrates have been demonstrated in patient IA tissue specimens and have also been shown to play an important role in abdominal aortic aneurysms (AAA) and related diseases such as atherosclerosis. However, no study has systematically examined the contribution of lymphocytes in a model of IA. METHODS: Lymphocyte-deficient (Rag1) and wild-type (WT; C57BL/6 strain) mice were subjected to a robust IA induction protocol. Rates of IA formation and rupture were measured, and cerebral artery tissue was collected and utilized for histology and gene expression analysis. RESULTS: At 2 weeks, the Rag1 group had significantly fewer IA formations and ruptures than the WT group. Histological analysis of unruptured IA tissue showed robust B and T lymphocyte infiltration in the WT group, while there were no differences in macrophage infiltration, IA diameter, and wall thickness. Significant differences in interleukin-6 (IL-6), matrix metalloproteinases 2 (MMP2) and 9 (MMP9), and smooth muscle myosin heavy chain (MHC) were observed between the groups. CONCLUSIONS: Lymphocytes are key contributors to IA pathogenesis and provide a novel target for the prevention of IA progression and rupture in patients.

Catatonia secondary to synthetic cannabinoid use in two patients with no previous psychosis.

BACKGROUND AND OBJECTIVES: Synthetic cannabinoids (SC) have become widely abused as recreational drugs, and are now known to carry risk of severe mental and physical health effects. Catatonia, spanning the gamut from motor retardation to agitation, can constitute a psychiatric emergency for which benzodiazepines are the mainstay of treatment. The purpose of this paper is to report on an unusual occurrence of catatonia in the context of synthetic cannabinoid use, and a discussion of treatment options that have been helpful as adjuncts to benzodiazepines. METHODS: We present two cases of catatonia occurring in context of SC use. The first patient was using SC quasi-daily for 18 months. The second patient used a large quantity over a two-week period. Both patients were admitted to our emergency center with catatonia and no overt psychosis or mood symptoms. RESULTS: The absence of pre-existing mood or psychotic disorder and the severity of catatonic symptoms separates these cases from other cases reported in the literature. Additionally, pharmacological management targeting gamma-aminobutyric acid (GABA) and serotonin neurotransmitter systems were used, specifically aripiprazole and valproic acid, supplementing benzodiazepine administration; these were needed for optimal symptom control. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The above-reported cases are highly significant because of the severity of catatonic symptoms requiring inpatient hospitalization, the potential for rapid and severe decompensation with catatonia, and the atypical/unexpected development of catatonia with SC use.

Age-related changes affect rat rotator cuff muscle function.

BACKGROUND: The influence of age on rotator cuff function and muscle structure remains poorly understood. We hypothesize that normal aging influences rotator cuff function, muscle structure, and regulatory protein expression in an established rat model of aging. METHODS: Seventeen rats were obtained from the National Institute on Aging. The supraspinatus muscles in 11 middle-aged (12 months old) and 6 old (28 months old) rats were studied for age-related changes in rotator cuff neuromuscular function by in vivo muscle force testing and electromyography (EMG). Changes in muscle structure and molecular changes were assessed with quantitative immunohistochemistry for myogenic determination factor 1 (MyoD) and myogenic factor 5 (Myf5) expression. RESULTS: Old animals revealed significantly decreased peak tetanic muscle force at 0.5 N and 0.7 N preload tension (P < .05). The age of the animal accounted for 20.9% of variance and significantly influenced muscle force (P = .026). Preload tension significantly influenced muscle force production (P < .001) and accounted for 12.7% of total variance. There was regional heterogeneity in maximal compound motor action potential (CMAP) amplitude in the supraspinatus muscle; the proximal portion had a significantly higher CMAP than the middle and distal portions (P < .05). The expression of muscle regulatory factors MyoD and Myf5 was significantly decreased in old animals compared with middle-aged animals (P < .05). CONCLUSIONS: The normal aging process in this rat model significantly influenced contractile strength of the supraspinatus muscle and led to decreased expression of muscle regulatory factors. High preload tensions led to a significant decrease in force production in both middle-aged and old animals.

A human hair keratin hydrogel scaffold enhances median nerve regeneration in nonhuman primates: an electrophysiological and histological study.

A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 Macaca fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a NeuraGen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. The keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (CMAP) latency and recovery of baseline nerve conduction velocity (NCV) compared with the saline-treated nerves. Histological evaluation was performed on retrieved median nerves and abductor pollicis brevis (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger nerve area in the keratin group compared with the saline group and the keratin APB muscles had a significantly higher myofiber density than the saline group. This is the first published study to show that an acellular biomaterial hydrogel conduit filler can be used to enhance peripheral nerve regeneration and motor recovery in an NHP model.

The effect of human hair keratin hydrogel on early cellular response to sciatic nerve injury in a rat model.

Peripheral nerve injuries requiring surgery can be repaired by autograft, the clinical "gold standard", allograft, or nerve conduits. Most published clinical studies show the effectiveness of nerve conduits in small size defects in sensory nerves. Many preclinical studies suggest that peripheral nerve regeneration through conduits can be enhanced and repair lengths increased with the use of a biomaterial filler in the conduit lumen. We have previously shown that a luminal hydrogel filler derived from human hair keratin (HHK) can improve electrophysiological and histological outcomes in mouse, rabbit, and non-human primate nerve injury models, but insight into potential mechanisms has been lacking. Based on the premise that a keratin biomaterial (KOS) hydrogel provides an instantaneous structural matrix within the lumen, the current study compares the cellular behavior elicited by KOS hydrogel to Matrigel (MAT) and saline (SAL) conduit fillers in a 1 cm rat sciatic nerve injury model at early stages of regeneration. While there was little difference in initial cellular influx, the KOS group showed earlier migration of dedifferentiated Schwann cells (SC) from the proximal nerve end compared to the other groups. The KOS group also showed faster SC dedifferentiation and myelin debris clearance, and decreased macrophage infiltration during Wallerian degeneration of the distal nerve tissue.

Resistance of composite and amalgam core foundations retained with and without pins and bonding agents.

To compare the resistance of different amalgam and composite core foundations retained by pins, bonding agents, or both, 100 molars were mounted in acrylic resin and their occlusal surfaces were reduced to expose dentin. Pins were inserted at the four line angles of the teeth and matrices were placed. Bonding agents were applied according to the manufacturers' instructions. Amalgam was handcondensed and composite was incrementally added and photocured. Restorations were adjusted to produce specimens (n = 10) 5 mm in height with a 1 mm bevel at the axial-occlusal surface. After immersion in deionized water for 24 hours, specimens were loaded at a 45 degree angle on their beveled surfaces in a Universal Testing Machine at a crosshead speed of 0.02 in./minute. ANOVA and Tukey's tests indicated that FluoroCore 2 (with or without pins) was statistically stronger than all other combinations (p < 0.05).

Toward a classification of isodynamic feed-forward motifs.

A preceding study analysed how the topology of network motifs affects the overall rate of the underlying biochemical processes. Surprisingly, it was shown that topologically non-isomorphic motifs can still be isodynamic in the sense that they exhibit the exact same performance rate. Because of the high prevalence of feed-forward functional modules in biological networks, one may hypothesize that evolution tends to favour motifs with faster dynamics. As a step towards ranking the efficiency of feed-forward network motifs, we use a linear flow model to prove theorems establishing that certain classes of motifs are isodynamic. In partitioning the class of all motifs on n nodes into equivalence classes based upon their dynamics, we establish a basis for comparing the efficiency/performance rates of different motifs. The potential biological importance of the theorems is briefly discussed and is the subject of an ongoing large-scale project.