Engineering both intrinsic characteristic and local microenvironment of platinum sites toward highly efficient oxygen reduction reaction.

The optimization of the adsorption of oxygen-containing intermediates on platinum (Pt) sites of Pt-based electrocatalysts is crucial for the oxygen reduction reaction process. Currently, a large amount of researches mainly focus on modifying the bulk structure of the electrocatalysts, however, the vital role of solvent effect on the phase interfaces is often overlooked. Here, we successfully developed an electrocatalyst in which the ordered PtCo alloy anchors on the cobalt (Co) single-atoms/clusters decorated support (Co1,nNC) and its surface is further optimized using hydrophobic ionic liquid (IL). Experimental studies and theoretical calculations indicate that compressive stress on Pt lattice contributed by intrinsic structure and the local hydrophobicity caused by IL on the surface can suppress the stabilization of *OH on Pt. This synergistic effect affords outstanding catalytic performance, exhibiting a half-wave potential (E1/2) of 0.916 V vs. RHE and a mass activity (MA) of 1350.3 mA mgPt-1 in 0.1 mol/L perchloric acid (0.1 M HClO4) electrolyte, much better than the commercial Pt/C (0.849 V vs. RHE and 145.5 mA mgPt-1 for E1/2 and MA, respectively). Moreover, the E1/2 of IL-PtCo/Co1,nNC only lost 5 mV after 10,000 cyclic voltammetry (CV) cycles due to a strong and synergistic contact of the intermetallic PtCo alloy with the Co1,nNC support and IL. This research provides an effective method for designing efficient electrocatalysts by combining intrinsic structure and surface modification.

Postpartum Changes in Levator Plate Shape and Genital Hiatus Size After Vaginal Delivery.

INTRODUCTION AND HYPOTHESIS: Vaginal delivery is a risk factor for pelvic organ prolapse. We sought to quantify changes in level III pelvic support measurements at 7 weeks and 8 months following vaginal delivery. METHODS: This secondary analysis included primiparous women who underwent pelvic MRI and clinical examinations at 7 weeks and 8 months after vaginal delivery. Demographics and obstetrical data were abstracted. Mid-sagittal resting MRIs were used to perform level III measurements including urogenital hiatus (UGH), levator hiatus (LH), and mid-sagittal levator area (LA), and to trace the levator plate (LP). Using principal component analysis, 7-week and 8-month principal component scores (PC1s) and MRI measurements were compared using paired t test. If the PC1 score change from 7 weeks to 8 months was > 0, women were considered to have a more dorsally oriented LP shape. RESULTS: Of 76 participants, POP-Q values did not significantly differ between 7 weeks and 8 months, but MRI measurements improved (UGH: 3.9 ± 0.8 vs 3.5 ± 0.8, p < 0.001; LH: 5.4 ± 0.8 vs 5.2 ± 0.8, p = 0.01; LA: 18.0 ± 6.0 vs 15.2 ± 6.5, p < 0.001). Approximately 30% (22 out of 76) had a more dorsally oriented LP shape and larger level III measurements at 8 months than women with a more ventrally oriented LP shape (LA: 86.4% vs 1.9%, p < 0.001; LH: 16% vs 12%, p < 0.001; UGH: 59.1% vs 3.7%, p < 0.001). CONCLUSIONS: After vaginal delivery, most women had "recovery" of level III support-defined by smaller UGH, LH, and LA measurements-and a more ventrally oriented LP shape. However, nearly 30% had larger level III measurements and a more dorsally oriented LP shape, indicating "impaired recovery" of support.

Genetic Researchers' Use of and Interest in Research With Diverse Ancestral Groups.

Importance: Genetic researchers must have access to databases populated with data from diverse ancestral groups to ensure research is generalizable or targeted for historically excluded communities. Objective: To determine genetic researchers' interest in doing research with diverse ancestral populations, which database stewards offer adequate samples, and additional facilitators for use of diverse ancestral data. Design, Setting, and Participants: This survey study was conducted from June to December 2022 and was part of an exploratory sequential mixed-methods project in which previous qualitative results informed survey design. Eligible participants included genetic researchers who held US academic affiliations and conducted research using human genetic databases. Exposure: Internet-administered survey to genetic research professionals. Main Outcomes and Measures: The survey assessed respondents' experience and interest in research with diverse ancestral data, perceptions of adequacy of diverse data across database stewards (ie, private, government, or consortia), and identified facilitators for encouraging use of diverse ancestral data. Descriptive statistics, χ2 tests, and z tests were used to describe respondents' perspectives and experiences. Results: A total of 294 researchers (171 men [58.5%]; 121 women [41.2%]) were included in the study, resulting in a response rate of 20.4%. Across seniority level, 109 respondents (37.1%) were senior researchers, 85 (28.9%) were mid-level researchers, 71 (24.1%) were junior researchers, and 27 (9.2%) were trainees. Significantly more respondents worked with data from European ancestral populations (261 respondents [88.8%]) compared with any other ancestral population. Respondents who had not done research with Indigenous ancestral groups (210 respondents [71.4%]) were significantly more likely to report interest in doing so than not (121 respondents [41.2%] vs 89 respondents [30.3%]; P < .001). Respondents reported discrepancies in the adequacy of ancestral populations with significantly more reporting European samples as adequate across consortium (203 respondents [90.6%]), government (200 respondents [89.7%]), and private (42 respondents [80.8%]) databases, compared with any other ancestral population. There were no significant differences in reported adequacy of ancestral populations across database stewards. A majority of respondents without access to adequate diverse samples reported that increasing the ancestral diversity of existing databases (201 respondents [68.4%]) and increasing access to databases that are already diverse (166 respondents [56.5%]) would increase the likelihood of them using a more diverse sample. Conclusions and Relevance: In this survey study of US genetic researchers, respondents reported existing databases only provide adequate ancestral samples for European populations, despite their interest in other ancestral populations. These findings suggest there are specific gaps in access to and composition of genetic databases, highlighting the urgent need to boost diversity in research samples to improve inclusivity in genetic research practices.

Functional Anatomy of Urogenital Hiatus Closure: the Perineal Complex Triad Hypothesis.

INTRODUCTION: Urogenital hiatus enlargement is a critical factor associated with prolapse and operative failure. This study of the perineal complex was performed to understand how interactions among its three structures: the levator ani, perineal membrane, and perineal body-united by the vaginal fascia-work to maintain urogenital hiatus closure. METHODS: Magnetic resonance images from 30 healthy nulliparous women with 3D reconstruction of selected subjects were used to establish overall geometry. Connection points and lines of action were based on perineal dissection in 10 female cadavers (aged 22-86 years), cross sections of 4 female cadavers (aged 14-35 years), and histological sections (cadavers aged 16 and 21 years). RESULTS: The perineal membrane originates laterally from the ventral two thirds of the ischiopubic rami and attaches medially to the perineal body and vaginal wall. The levator ani attaches to the perineal membrane's cranial surface, vaginal fascia, and the perineal body. The levator line of action in 3D reconstruction is oriented so that the levator pulls the medial perineal membrane cranio-ventrally. In cadavers, simulated levator contraction and relaxation along this vector changes the length of the membrane and the antero-posterior diameter of the urogenital hiatus. Loss of the connection of the left and right perineal membranes through the perineal body results in diastasis of the levator and a widened hiatus, as well as a downward rotation of the perineal membrane. CONCLUSION: Interconnections involving the levator ani muscles, perineal membrane, perineal body, and vaginal fascia form the perineal complex surrounding the urogenital hiatus in an arrangement that maintains hiatal closure.

A unified pelvic floor conceptual model for studying morphological changes with prolapse, age, and parity.

Several 2-dimensional and 3-dimensional measurements have been used to assess changes in pelvic floor structures and shape. These include assessment of urogenital and levator hiatus dimensions, levator injury grade, levator bowl volume, and levator plate shape. We argue that each assessment reflects underlying changes in an individual aspect of the overall changes in muscle and fascial structures. Vaginal delivery, aging, and interindividual variations in anatomy combine to affect pelvic floor structures and their connections in different ways. To date, there is no unifying conceptual model that permits the evaluation of how these many measures relate to one another or that reflects overall pelvic floor structure and function. Therefore, this study aimed to describe a unified pelvic floor conceptual model to better understand how the aforementioned changes to the pelvic floor structures and their biomechanical interactions affect pelvic organ support with vaginal birth, prolapse, and age. In this model, the pelvic floor is composed of 5 key anatomic structures: the (1) pubovisceral, (2) puborectal, and (3) iliococcygeal muscles with their superficial and inferior fascia; (4) the perineal membrane or body; and (5) the anal sphincter complex. Schematically, these structures are considered to originate from pelvic sidewall structures and meet medially at important connection points that include the anal sphincter complex, perineal body, and anococcygeal raphe. The pubovisceral muscle contributes primarily to urogenital hiatus closure, whereas the puborectal muscle is mainly related to levator hiatus closure, although each muscle contributes to the other. Dorsally and laterally, the iliococcygeal muscle forms a shelflike structure in women with normal support that spans the remaining area between these medial muscles and attachments to the pelvic sidewall. Other features include the levator plate, bowl volume, and anorectal angle. The pelvic floor conceptual model integrates existing observations and points out evident knowledge gaps in how parturition, injury, disease, and aging can contribute to changes associated with pelvic floor function caused by the detachment of one or more important connection points or pubovisceral muscle failure.

Early Magnetic Resonance Imaging Features of New Paramagnetic Rim Lesions in Multiple Sclerosis.

OBJECTIVE: To determine early magnetic resonance imaging (MRI) features of new multiple sclerosis (MS) lesions that will develop into paramagnetic rim lesions (PRLs), which have been associated with progressive tissue injury in MS. METHODS: New contrast-enhancing lesions observed on routine clinical MRI were imaged at 7 T within 4 weeks of observation, and 3 and 6 months later. The 6-month MRI was used to classify PRL status (PRL or non-PRL). The relationship between early lesion characteristics and subsequent PRL status was assessed using generalized linear mixed effects models. Random forest classification was performed to classify early predictors of subsequent PRL status. RESULTS: From 93 contrast-enhancing lesions in 23 MS patients, 37 lesions developed into a PRL. In lesions that developed into PRLs compared with those that did not, the average lesion T1 on the initial 7 T MRI was 1994 ms compared with 1,670 ms (p-value <0.001), and the average volume was 168.7 mL compared with 44 mL (p-value <0.001) in lesions that did not. These volume differences were also found on 3 T scans (p-value <0.001), and for intensity-normalized T1 -w (p-value = 0.011) and fluid-attenuated inversion recovery (p-value = 0.005). The area under the receiver operating characteristic curve for the random forest classification with leave-one-out cross-validation was found to be 0.86 using initial 7 T features. INTERPRETATION: New MS lesions that evolve into PRLs can be identified early in lesion evolution. These findings suggest that biological mechanisms underlying PRL development begin early, which has important implications for clinical trials targeting PRLs development and subsequent therapeutics. ANN NEUROL 2023;94:736-744.

Effect of gastrodin against cognitive impairment and neurodegeneration in APP/PS1 mice via regulating gut microbiota-gut-brain axis.

Gastrodin (Gas) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of Gas against cognitive impairment via regulating gut microbiota. APPswe/PSEN1dE9 transgenic (APP/PS1) mice were treated intragastrically with Gas for 4 weeks, and then cognitive deficits, deposits of amyloid-ß (Aß) and phosphorylation of tau were analyzed. The expression levels of insulin-like growth factor-1 (IGF-1) pathway-related proteins, such as cAMP response element-binding protein (CREB), were detected. Meanwhile, gut microbiota composition was evaluated. Our results showed that Gas treatment significantly improved cognitive deficits and Aß deposition in APP/PS1 mice. Moreover, Gas treatment increased the level of Bcl-2 and decreased level of Bax and ultimately inhibited neuronal apoptosis. Gas treatment markedly increased the expression levels of IGF-1 and CREB in APP/PS1 mice. Moreover, Gas treatment improved abnormal composition and structure of gut microbiota in APP/PS1 mice. These findings revealed that Gas actively participated in regulating the IGF-1 pathway to inhibit neuronal apoptosis via the gut-brain axis and that it can be considered a new therapeutic strategy against Alzheimer's disease.

Assessment of daily variation in pelvic anatomy in women with and without pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Symptoms of pelvic organ prolapse (POP) can affect quality of life and are reported to progress during the day, although this was never objectified. The aim of this study is to determine whether the pelvic anatomy changes during the day using upright magnetic resonance imaging (MRI), in POP patients and asymptomatic women. METHODS: In this prospective study 15 POP patients and 45 asymptomatic women were included. Upright MRI scans were obtained three times per day. The distances from the lowest points of the bladder and cervix to a standardized reference (pelvic inclination correction system) line were determined. A principal component analysis was performed on the levator plate (LP) shape. Statistical differences between time points and the groups were determined for the bladder, cervix, and LP shape. RESULTS: For all women a significant decrease in bladder and cervix height of -0.2 cm (p<0.001) was seen between morning/midday and afternoon scans. A significant difference in bladder descent during the day between POP patients and asymptomatic women was found (p=0.004). Individual differences in bladder position in the POP group of up to 2.2 cm between the morning and afternoon scan were reported. There was a significant difference in LP shape (p<0.001) between the groups but there were no significant changes during the day. CONCLUSIONS: This study found no clinically relevant pelvic anatomy changes during the day. Still, on an individual level differences can be large, so repeating clinical examination at the end of the day can be recommended in patients when anamnesis and physical examination do not match.

A comparison of MRI-based pelvic floor support measures between young and old women with prolapse.

INTRODUCTION AND HYPOTHESIS: We sought to 1) test the hypothesis that young women (≤45 years) with pelvic organ prolapse have a higher prevalence of major levator ani muscle (LAM) defects than old women (≥70 years) with prolapse and 2) compare level II/III measurements between young and old women with prolapse and age-matched controls to evaluate age-related mechanistic differences in the disease process. METHODS: A secondary analysis examined four groups of parous women: young prolapse (YPOP, n = 17); old prolapse (OPOP, n = 17); young controls (YC, n = 15); old controls, (OC, n = 13). Prolapse was defined as any compartment at or beyond the hymen with vaginal bulge symptoms. Genital hiatus (GH) was measured on clinical exam. Major LAM defects and level II/III measurements (UGH: urogenital hiatus, LA: levator area, and apex location) were assessed on MRI at rest and strain, and the difference (Δ) between measurements calculated. Principal component analysis was used to evaluate levator plate (LP) shape. RESULTS: Major LAM defects occurred in 42% of YPOP and 47% of OPOP (p > .99). GHrest was 1.5 cm larger in OPOP versus YPOP (p < .001) and 2 cm larger in OPOP versus OC (p < .001). Regardless of prolapse status, LArest and UGHrest on MRI increased with age. YPOP had larger ΔLA (p = .04), ΔUGH (p = .03), and Δapex than OPOP (p = .01). Resting LP shape was more dorsally oriented in OPOP versus YPOP (p = .02) and OC versus YC (p = .004). CONCLUSIONS: Prolapse in young women cannot be solely explained by a higher LAM defect prevalence. GH size and other measures of level II/III pelvic support worsen with age regardless of prolapse status.

Variations in structural support site failure patterns by prolapse size on stress 3D MRI.

INTRODUCTION AND HYPOTHESIS: Our objective was to develop a standardized measurement system to evaluate structural support site failures among women with anterior vaginal wall-predominant prolapse according to increasing prolapse size using stress three-dimensional (3D) magnetic resonance imaging (MRI). METHODS: Ninety-one women with anterior vaginal wall-predominant prolapse and uterus in situ who had undergone research stress 3D MRI were included for analysis. The vaginal wall length and width, apex and paravaginal locations, urogenital hiatus diameter, and prolapse size were measured at maximal Valsalva on MRI. Subject measurements were compared to established measurements in 30 normal controls without prolapse using a standardized z-score measurement system. A z-score greater than 1.28, or the 90th percentile in controls, was considered abnormal. The frequency and severity of structural support site failure was analyzed based on tertiles of prolapse size. RESULTS: Substantial variability in support site failure pattern and severity was identified, even between women with the same stage and similar size prolapse. Overall, the most common failed support sites were straining hiatal diameter (91%) and paravaginal location (92%), followed by apical location (82%). Impairment severity z-score was highest for hiatal diameter (3.56) and lowest for vaginal width (1.40). An increase in impairment severity z-score was observed with increasing prolapse size among all support sites across all three prolapse size tertiles (p < 0.01 for all). CONCLUSIONS: We identified substantial variation in support site failure patterns among women with different degrees of anterior vaginal wall prolapse using a novel standardized framework that quantifies the number, severity, and location of structural support site failures.

Hiatal failure: effects of pregnancy, delivery, and pelvic floor disorders on level III factors.

INTRODUCTION AND HYPOTHESIS: The failure of the levator hiatus (LH) and urogenital hiatus (UGH) to remain closed is not only associated with pelvic floor disorders, but also contributes to recurrence after surgical repair. Pregnancy and vaginal birth are key events affecting this closure. An understanding of normal and failed hiatal closure is necessary to understand, manage, and prevent pelvic floor disorders. METHODS: This narrative review was conducted by applying the keywords "levator hiatus" OR "genital hiatus" OR "urogenital hiatus" in PubMed. Articles that reported hiatal size related to pelvic floor disorders and pregnancy were chosen. Weighted averages for hiatal size were calculated for each clinical situation. RESULTS: Women with prolapse have a 22% and 30% larger LH area measured by ultrasound at rest and during Valsalva than parous women with normal support. Women with persistently enlarged UGH have 2-3 times higher postoperative failure rates after surgery for prolapse. During pregnancy, the LH area at Valsalva increases by 29% from the first to the third trimester in preparation for childbirth. The enlarged postpartum hiatus recovers over time, but does not return to nulliparous size after vaginal birth. Levator muscle injury during vaginal birth, especially forceps-assisted, is associated with increases in hiatal size; however, it only explains a portion of hiatus variation-the rest can be explained by pelvic muscle function and possibly injury to other level III structures. CONCLUSIONS: Failed hiatal closure is strongly related to pelvic floor disorders. Vaginal birth and levator injury are primary factors affecting this important mechanism.

Age, parity, and prolapse: interaction and influence on levator bowl volume.

INTRODUCTION AND HYPOTHESIS: The objective was to test the hypotheses that a linear relationship exists between age and levator bowl volume (LBV); and that age, parity, and prolapse are independently associated with LBV. METHODS: We conducted a secondary analysis of data from nulliparous women, parous controls, and prolapse (Pelvic Organ Prolapse Quantification (POP-Q) Ba ≥ 1 cm) cases from each of three age groups: young (≤40), mid-age (50-60), and older (≥70). LBV was measured using MRI at rest and Valsalva as the 3D space contained above the levator ani muscles and below the sacrococcygeal junction-to-inferior pubic point reference plane. Linear regression models were used to examine the effects of age, parity, prolapse, and their interactions (age*parity and age*prolapse) on LBV. RESULTS: Each group consisted of 9-12 women. LBVRest increased with age in a nonlinear fashion. For nulliparous women, the median value increased 4.7% per decade from the young to mid-age group and 84% per decade from the mid-age to older group; for parous controls, the corresponding increases were 38% and -0.5%; and for women with prolapse, they were 46% and 11%. Age and prolapse status (both p<0.001) were found to be significant independent predictors of LBVRest. Interactions between age*prolapse (p=0.003) and age*parity (p=0.045) were also independently associated with LBVRest. CONCLUSIONS: Parity and prolapse influence how age affects LBVRest. In nulliparous women, age had little effect on LBVRest until after mid-age. For women with prolapse, LBVRest increased at a much earlier age, with the biggest difference occurring between young and mid-age women.

Changes in cardinal ligament length and curvature with parity and prolapse and their relation to level III hiatus measures.

INTRODUCTION AND HYPOTHESIS: Test the hypotheses that (1) cardinal ligament (CL) straightening and lengthening occur with parity and prolapse, (2) CL straightening occurs before lengthening, and (3) CL length is correlated with level III measures. METHODS: We performed a secondary analysis of MRIs from women in three groups: (1) nulliparous with normal support, (2) parous with normal support, and (3) uterine prolapse (POP-Q point C > - 4 and Ba > 1 cm). The 3D stress MRI images at rest and maximal Valsalva were analyzed. CLs were traced from their origin to cervico-vaginal insertions. Curvature ratio was calculated as curved length/straight length. Level III measures included urogenital hiatus (UGH), levator hiatus (LH), and levator bowl volume (LBV), and their correlations with CL length were calculated. RESULTS: Ten women were included in each group. Compared to the nulliparous group, CL length was 18% longer in parous controls (p = .04) and 59% longer with prolapse (p < .01) at rest, while at Valsalva, CL length was 10% longer in parous controls (p = .21) and 49% longer with prolapse (p < .01). Curvature ratios showed 18% more straightening in women with prolapse compared to parous controls (p < .01). Curved CL length and level III measures were moderately to strongly correlated: UGH (rest: R = 0.68, p < .01; Valsalva: R =0.80, p < .01), LH (rest: R = 0.60, p < .01; Valsalva: R = 0.78, p < .01), and LBV (rest: R = 0.71, p < .01; Valsalva: R =0.89, p < .01). CONCLUSION: Our findings suggest that the CLs undergo three times as much lengthening with prolapse as with parity; however, straightening only occurs with prolapse. Strong correlations exist between level I and level III support.

Analysis of long-term structural failure after native tissue prolapse surgery: a 3D stress MRI-based study.

INTRODUCTION AND HYPOTHESIS: We sought to identify postoperative structural failure sites associated with long-term prolapse recurrence and their association with symptoms and satisfaction. METHODS: Women who had a research MRI prior to native-tissue prolapse surgery were recruited for examination, 3D stress MRI, and questionnaires. Recurrence was defined by Pelvic Organ Prolapse Quantification System (POP-Q)Ba/Bp > 0 or C > -4. Measurements were performed at rest and maximum Valsalva ("strain") including vaginal length, apex location, urogenital hiatus (UGH), and levator hiatus (LH). Measures were compared between subjects and to women with normal support. Failure frequency was the proportion of women with measurements outside the normal range. Symptoms and satisfaction were measured using validated questionnaires. RESULTS: Thirty-one women participated 12.7 years after surgery-58% with long-term success and 42% with recurrence. Failure site comparisons between success and failure were: impaired mid-vaginal paravaginal support (62% vs. 28%, p = 0.01), longer vaginal length (54% vs. 22%, p = 0.03), and enlarged urogenital hiatus (54% vs. 22%, p = 0.03). Apical paravaginal location had the lowest failure frequency (recurrence: 15% vs. success: 7%, p = 0.37). Patient satisfaction was high (recurrence: 5.0 vs. success: 5.0, p = 0.86). Women with bothersome bulge symptoms had a 33% larger UGH strain on POP-Q (p = 0.01), 8.7% larger resting UGH (p = 0.046), 11.5% larger straining LH (p = 0.01), and 9.3% larger resting LH (p = 0.01). CONCLUSIONS: Abnormal low mid-vaginal paravaginal location (Level II), long vaginal length (Level II), and large UGH (Level III) were associated with long-term prolapse recurrence. Patient satisfaction was high and unrelated to anatomical recurrence. Bothersome bulge symptoms were associated with hiatus enlargement.

Preoperative level II/III MRI measures predicting long-term prolapse recurrence after native tissue repair.

INTRODUCTION AND HYPOTHESIS: To identify preoperative level II/III MRI measures associated with long-term recurrence after native tissue prolapse repair. METHODS: Women who previously participated in pelvic floor research involving MRI prior to undergoing primary native tissue prolapse repair were recruited to return for repeat examination and MRI. Recurrence was defined by POP-Q (Ba/Bp > 0 or C > -4), repeat surgery, or pessary use. Preoperative MR images were used to perform five level II/III measurements including a new levator plate (LP) shape analysis at rest and maximal Valsalva. Principal component analysis (PCA) was used to evaluate LP shape variations. Principal component scores calculated for two independent shape variations were noted. RESULTS: Thirty-five women were included with a mean follow-up of 13.2 ± 3.3 years. Nineteen (54%) were in the success group. There were no statistical differences between success versus recurrence groups in demographic, clinical, or surgical characteristics. Women with recurrence had a larger preoperative resting levator hiatus [median 6.4 cm (IQR 5.7, 7.1) vs. 5.8 cm (IQR 5.3, 6.3), p = 0.03]. This measure was associated with increased odds of recurrence (OR 8.2, CI 1.4-48.9, p = 0.02). Using PCA, preoperative LP shape PC1 scores were different between success and recurrence groups (p = 0.02), with a more dorsally oriented LP shape associated with recurrence. CONCLUSIONS: Larger preoperative levator hiatus at rest and a more dorsally oriented levator plate shape were associated with prolapse recurrence at long-term follow-up. For every 1 cm increase in preoperative resting levator hiatus, the odds of long-term prolapse recurrence increases 8-fold.

A new 3D stress MRI measurement strategy to quantify surgical correction of prolapse in three support systems.

AIMS: The aim of this study was to develop and test the feasibility of a magnetic resonance imaging (MRI)-based measurement strategy to evaluate the effectiveness of surgical procedures in restoring normal anatomy in all three systems of pelvic floor support and quantify the structural changes induced by prolapse surgery. METHODS: Patients underwent clinical examination and stress MRI preoperatively and again 3 months postoperatively. Preoperative and postoperative measures of three MRI-based structural support systems were made: (1) vaginal wall, (2) apical and paravaginal support, and (3) hiatal closure system. Preoperative to postoperative structural changes were calculated and compared to normal values, and bivariate associations were determined. RESULTS: The three structural support systems were successfully quantified for both preoperative and postoperative MRIs regardless of operative approaches in all 15 women in the pilot group. Apical support was restored to normal in 11 of 12 patients who underwent an apical suspension procedure and 9 of 14 patients with a posterior repair had normalization of genital hiatus size. Mid-vaginal paravaginal location was elevated an average of 2.5 ± 2.0 cm despite no paravaginal repairs being performed. Paravaginal location improvements were also significantly correlated with apical elevation (r values 0.99-0.87, p < 0.001). CONCLUSIONS: A strategy that quantifies structural-specific preoperative impairments and improvements after prolapse surgery was successfully developed. Early findings reveal that prolapse surgery is more successful in restoring normal anatomy at Level I than Level III. Improvement in paravaginal location is significantly correlated with apical elevation.

Does preoperative resting genital hiatus size predict surgical outcomes?

AIM: To determine whether preoperative genital hiatus at rest is predictive of medium-term prolapse recurrence. METHODS: We conducted a retrospective study of women who underwent native tissue prolapse surgery from 2002 to 2017 with pelvic organ prolapse quantification data including resting genital hiatus at one of three time points: preoperatively, 6 weeks, and ≥1 year postoperatively. Demographics and clinical data were abstracted from the chart. Prolapse recurrence was defined by anatomic outcomes (Ba > 0, Bp > 0, and/or C ≥ -4) or retreatment. Descriptive statistics, bivariate analyses, and logistic regression analyses were performed. RESULTS: Of the 165 women included, 36 (21.8%) had prolapse recurrence at an average of 1.5 years after surgery. Preoperative resting genital hiatus did not differ between women with surgical success versus recurrence (3.5 cm [interquartile range, IQR 2.25, 4.0) vs 3.5 cm (IQR 3.0, 4.0), p = 0.71). Point Bp was greater in the recurrence group at every time point. Preoperative Bp (odds ratio [OR] 1.24, confidence interval [CI] [1.06-1.45], p = 0.01) and days from surgery (OR 1.001, CI [1.000-1.001], p < 0.01) were independently associated with recurrence. Preoperative genital hiatus at rest and strain were significantly larger among women who underwent a colpoperineorrhaphy (rest: 4.0 [3.0, 4.5] cm vs 3.5 [3.0, 4.0] cm, p < 0.01; strain: 6.0 [4.0, 6.5] cm vs 5.0 [4.0, 6.0] cm, p = 0.01). CONCLUSIONS: Preoperative genital hiatus at rest was not associated with prolapse recurrence when the majority of women underwent colpoperineorrhaphy. Preoperative Bp was more predictive of short-term prolapse recurrence. For every 1 cm increase in point Bp, there is a 24% increased odds of recurrence.

Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.

Human brain organoids represent remarkable platforms for recapitulating features of human brain development and diseases. Existing organoid models do not resolve fine brain subregions, such as different nuclei in the hypothalamus. We report the generation of arcuate organoids (ARCOs) from human induced pluripotent stem cells (iPSCs) to model the development of the human hypothalamic arcuate nucleus. Single-cell RNA sequencing of ARCOs revealed significant molecular heterogeneity underlying different arcuate cell types, and machine learning-aided analysis based on the neonatal human hypothalamus single-nucleus transcriptome further showed a human arcuate nucleus molecular signature. We also explored ARCOs generated from Prader-Willi syndrome (PWS) patient iPSCs. These organoids exhibit aberrant differentiation and transcriptomic dysregulation similar to postnatal hypothalamus of PWS patients, indicative of cellular differentiation deficits and exacerbated inflammatory responses. Thus, patient iPSC-derived ARCOs represent a promising experimental model for investigating nucleus-specific features and disease-relevant mechanisms during early human arcuate development.

Novel 3D MRI technique to measure perineal membrane structural changes with pregnancy and childbirth: Technique development and measurement feasibility.

INTRODUCTION AND HYPOTHESIS: We aimed to develop and validate a new MRI-based perineal membrane reconstruction and morphological measurement technique, and test its feasibility on nulliparous and parous women to determine the effects of pregnancy and childbirth on the perineal membrane. METHODS: The perineal membrane was traced on high-resolution MRI using 3D Slicer® and analyses performed using Rhinoceros 6.0 SR23®. Validation was done by comparing MRI-based perineal membrane reconstruction to dissection measurements in a cadaver. Feasibility of reconstruction was assessed in the following three groups: nulliparous (NP), primiparous women who underwent cesarean delivery (CD), and primiparous women with vaginal delivery (VD). The following parameters were measured: (1) swinging door angle, (2) bony and (3) soft tissue attachment lengths, (4) separation at perineal body level, (5) surface area, and (6) hiatal area. ANOVA and post-hoc comparisons were performed, and the effect sizes (d) were reported. RESULTS: Model reconstruction was similar to cadaver dissection findings. Morphological measurements were feasible in all women (NP, n = 10; CS, n = 6; VD, n = 19). Swinging door angle was 13o greater in CD (p = 0.03; d = 1.15) and 16o greater in VD (p < 0.001; d = 1.41) compared to NP. VD showed 13% larger separation at the perineal body than NP (p = 0.097, d = 0.84) and 23% larger hiatal area than CD (p = 0.14, d = 0.94). CONCLUSION: This novel and anatomically validated MRI-based perineal membrane reconstruction technique is feasible. Preliminary findings show that pregnancy and childbirth both influence perineal membrane morphology with VD being associated with the largest swinging door angle and perineal body separation.