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The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post‐translational modification of cysteine residues to produce reactive persulfides. A persulfide‐specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by ZnII, O2, and H2S, with intermediates involving oxygen‐ and sulfur‐based radicals detected by mass spectrometry and optical spectroscopies. A small molecule ZnII complex exhibits analogous reactivity with H2S and O2, giving a persulfidated product. These data show that ZnII is not just a biological structural element, but also plays a critical role in mediating H2S‐dependent persulfidation. ZF persulfidation appears to be a general post‐translational modification and a possible conduit for H2S signaling. This work has implications for our understanding of H2S‐mediated signaling and the regulation of ZFs in cellular physiology and development. [ABSTRACT FROM AUTHOR]

The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post‐translational modification of cysteine residues to produce reactive persulfides. A persulfide‐specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by ZnII, O2, and H2S, with intermediates involving oxygen‐ and sulfur‐based radicals detected by mass spectrometry and optical spectroscopies. A small molecule ZnII complex exhibits analogous reactivity with H2S and O2, giving a persulfidated product. These data show that ZnII is not just a biological structural element, but also plays a critical role in mediating H2S‐dependent persulfidation. ZF persulfidation appears to be a general post‐translational modification and a possible conduit for H2S signaling. This work has implications for our understanding of H2S‐mediated signaling and the regulation of ZFs in cellular physiology and development. [ABSTRACT FROM AUTHOR]

The US Supreme Court and lower court provided further guidance on fair use defense. The US Copyright Office provided guidance on AI as an author. The Court of Appeals provided guidance on substantial similiarty, server test, abstraction-filtration-comparison, and discovery rule. [ABSTRACT FROM AUTHOR]

Background: Pelvic organ prolapse is a debilitating condition impacting lives of millions of women worldwide. Sacrocolpopexy (SCP) is considered an effective and durable surgical technique for treatment of apical prolapse. The aim of this study was to compare short-term outcomes including postoperative complications and unanticipated healthcare encounters between patients who underwent SCP with a mini-laparotomy approach compared to patients treated with laparoscopic and robotic-assisted laparoscopic SCP. Methods: This was a retrospective cohort study including patients treated for apical prolapse at a university affiliated urogynecology practice. Patients over the age of 18 who underwent abdominal SCP between 2019 and 2023 were included. The cohort was formed into two groups: (1) Patients who underwent SCP through a mini-laparotomy incision (Mini-lap group); (2) Patients who underwent laparoscopic or robotic-assisted laparoscopic SCP (Lap/Robot group). Results: A total of 116 patients were included in the final analysis. Ninety patients underwent either laparoscopic or robotic-assisted SCP, whereas 26 patients underwent SCP with a mini-laparotomy approach. Study participants exhibited a mean age of 63.1 ± 10.3 years, mean body mass index (BMI) of 25.8 ± 4.9 Kg/m2, and 77.6% of them identified as Caucasian. Upon comparison of demographic and past medical history between groups there were no statistically significant differences in age, BMI, menopausal status, race, parity or comorbid conditions. Patients in the Mini-lap group were less likely to have undergone previous abdominal surgery (11.5% vs. 50.6%, p < 0.001) and had more severe apical prolapse (stage 4 prolapse, 40% vs. 21.2%, p < 0.001) than their counterparts in the Lap/robot group. Regarding intraoperative parameters, length of surgery was significantly shorter in the Mini-lap group compared to the Lap/robot group (97.3 ± 35.0 min vs. 242.0 ± 52.6 min, p < 0.001). When focusing on the primary outcome, postoperative complications within the first 30 days after surgery, there were no differences noted between groups. Additionally, the number of unanticipated healthcare encounters, such as phone calls, clinic visits, emergency department visits, urgent care visits, readmissions and reoperations were similar between groups. Conclusions: Mini-laparotomy approach for SCP is safe with comparable intra- and postoperative complications, and unanticipated healthcare encounters compared to conventional minimally invasive methods. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Same-day discharge (SDD) is increasing in popularity following surgical repair of pelvic organ prolapse. The aim of this study was to evaluate factors associated with unplanned admission (UA) in women undergoing apical prolapse repair. Methods: This retrospective, observational cohort study included patients who underwent apical prolapse repair and planned same-day discharge (SDD) between March 2019 and December 2021. The cohort was divided into two groups: patients who were discharged on the same day as surgery (SDD group) and patients who had an unplanned admission (UA group). Demographic, pre-, intra-, and post-operative data were collected. Risk factors associated with unplanned admission were evaluated using univariate and multivariate analyses. Results: One-hundred and eighty-four cases of apical prolapse repair met the criteria for inclusion in the final analysis; this included 142 in the SDD group and 42 in the UA group. Patients in the UA group had significantly increased estimated blood loss, longer total operative time, later time arriving to the Post-Anesthesia Care unit (PACU) and longer overall stay in the PACU. No differences were observed in the 30-day complication rate, or 30-day unanticipated healthcare encounters, between groups. Multivariate analysis revealed that receiving ketorolac post-operatively was associated with a higher likelihood of SDD (OR=2.6, 95% CI 1.032–6.580, p=0.043). Conclusions: Among women undergoing apical prolapse repair, same-day discharge was associated with comparable immediate and 30-day complication rates. Within our cohort, post-operative treatment with ketorolac was associated with greater likelihood of SDD. [ABSTRACT FROM AUTHOR]

5 Davies DJ, Hadis M, Di Pietro V, Lazzarino G, Forcione M, Harris G, Stevens A, Cheong Soon W, Goldenberg Oppenheimer P, Milward M, Belli A, Palin W. Photobiomodulation reduces hippocampal apoptotic cell death and produces a Raman spectroscopic "Signature." This meeting was hosted by Leeds Teaching Hospitals NHS Trust and the University of Leeds, 24-25 November 2022 at Hilton Leeds City, Leeds. Photobiomodulation for spinal cord injury: a systematic review and meta-analysis. [Extracted from the article]

Introduction and Hypothesis: The primary aim of this study was to compare the effect of bladder instillations using dimethyl sulfoxide (DMSO) with triamcinolone versus bupivacaine, triamcinolone, and heparin (BTH) in women with newly diagnosed interstitial cystitis/painful bladder syndrome. The primary outcome was improvement in symptoms measured using the O'Leary‐Sant Interstitial Cystitis Symptoms Index (ICSI) score. Secondary comparisons included changes in urinary frequency, nocturia, and bladder capacity. Materials and Methods: This was a prospective, randomized study. Patients with a recent diagnosis of interstitial cystitis/painful bladder syndrome (IC/PBS) were randomized 1:1 to treatment with either 6 weekly bladder instillations of DMSO with triamcinolone or BTH. During follow‐up visits, patients completed the ICSI questionnaire, and bladder capacity was determined through the retrograde filling of the bladder. The χ2 test or Student's t test were used for data analysis. Results: A total of 83 patients were randomized, and final analysis included 70 participants who completed the 6 weekly instillations (42 DMSO, 28 BTH). The groups were similar in baseline demographics and clinical characteristics, except for cystometric maximum capacity (DMSO 338.62± 139.44 mL, BTH 447.43 ± 180.38 mL, p = 0.01). In the DMSO group, 63% of patients had a greater than 29.5% reduction in total ICSI score versus 43% in the BTH group (p = 0.15). Nocturia and pain were significantly reduced in the DMSO group. There was a significant increase from baseline in bladder capacity for both groups. Conclusion: In women with newly diagnosed IC/PBS, bladder instillations with DMSO and triamcinolone provide greater improvement in pain and nocturia compared to BTH. [ABSTRACT FROM AUTHOR]

Injury to the adult mammalian central nervous system induces compensatory plasticity of spared axons "referred to as collateral axon sprouting "that can facilitate neural recovery. The contribution of reactive astrocytes to axon sprouting remains elusive. Here, we sought to investigate the role of axon degeneration-reactive astrocytes in the regulation of collateral axon sprouting that occurs in the mouse spinal cord after unilateral photothrombotic stroke of the primary motor cortex. We identified astrocytic leucine zipper-bearing kinase (LZK) as a positive regulator of astrocyte reactivity to corticospinal axon degeneration. Remarkably, genetic stimulation of astrocyte reactivity, via LZK overexpression in adult astrocytes, enhanced corticospinal axon sprouting. LZK promoted the production of astrocyte-derived ciliary neurotrophic factor (CNTF) that likely enhanced axon growth in mice with astrocytic LZK overexpression after injury. Our finding that LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting highlights the potential of engineering astrocytes to support injury-induced axon plasticity for neural repair. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Fecal incontinence (FI) has two primary subtypes: urgency fecal incontinence (UFI) and passive fecal leakage (PFL). The pathophysiology underlying the subtypes is incompletely understood. Objectives: To compare the bowel habits, physical examinations and pelvic floor anatomical defects in patients with UFI-dominant FI versus patients with PFL-dominant FI. Study design: This is a retrospective cross-sectional study of female patients who presented with fecal incontinence symptoms to our tertiary urogynecology center. All subjects underwent a comprehensive history, physical examination, 3D-static pelvic floor ultrasound, and 2D-dynamic ultrasound of the posterior compartment. Patients with UFI-dominant FI were compared to patients with PFL-dominant FI. Results: One hundred forty-five patients were included in the analysis; 57 categorized as UFI-dominant FI, 69 PFL-dominant FI and 19 categorized as having "both" leakage patterns. In comparing bowel habits, patient with UFI-dominant FI had more frequent bowel movements (15.5 ± SD 13.0/week vs. 10.9 ± SD 7.6 /week, p = 0.022) and were more likely to have loose stools (48.2% vs. 26.1%, p = 0.01). No statistically significant differences were observed in the prevalence of external anal sphincter defect (11.3% vs. 17.2%, p = 0.38) or internal anal sphincter defect (11.3% vs. 19%, p = 0.26) between groups. Finally, patients with UFI-dominant FI had a higher incidence of rectal hypermobility (loss of rectal support on Valsalva) (58% vs. 36.9%, p = 0.025). Conclusion: Patients with urge-predominant FI have increased frequency of bowel movements, looser stools, and increased rectal folding diagnosed via dynamic ultrasound as compared to patients with passive-dominant FI. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Urethral closure mechanism dysfunction in female stress urinary incontinence (SUI) is poorly understood. We aimed to quantify these mechanisms through changes in urethral shape and position during squeeze (voluntary closure) and Valsalva (passive closure) via endovaginal ultrasound in women with varying SUI severity. Methods: In this prospective cohort study, 76 women who presented to our tertiary center for urodynamic testing as preoperative assessment were recruited. Urodynamics were performed according to International Continence Society criteria. Urethral pressures were obtained during serial Valsalva maneuvers. Urethral lengths, thicknesses, and angles were measured in the midsagittal plane via dynamic anterior compartment ultrasound. Statistical shape modeling was carried out by a principal component analysis on aligned urethra shapes. Results: Age, parity, and BMI did not vary by SUI group. Ultrasound detected a larger retropubic angle, urethral knee-pubic bone angle (a novel measure developed for this study), and infrapubic urethral length measurements at Valsalva in women with severe SUI (p = 0.016, 0.015, and 0.010). Shape analysis defined increased "c" shape concavity and distal wall pinching during squeeze and increased "s" shape concavity and distal wall thickening during Valsalva (p < 0.001). It also described significant urethral shape differences across SUI severity groups (p < 0.001). Conclusions: Dynamic endovaginal ultrasound can visualize and allow for quantification of voluntary and passive urethral closure and variations with SUI severity. In women with severe SUI, excessive bladder neck and distal urethra swinging during Valsalva longitudinally compressed the urethra, resulting in a proportionally thicker wall at the mid-urethra and urethral knee. [ABSTRACT FROM AUTHOR]

A new structurally characterized ferrous corrole [FeII(ttppc)]− (1) binds one equivalent of dioxygen to form [FeIII(O2−.)(ttppc)]− (2). This complex exhibits a 16/18O2‐isotope sensitive ν(O‐O) stretch at 1128 cm−1 concomitantly with a single ν(Fe‐O2) at 555 cm−1, indicating it is an η1‐superoxo ("end‐on") iron(III) complex. Complex 2 is the first well characterized Fe‐O2 corrole, and mediates the following biologically relevant oxidation reactions: dioxygenation of an indole derivative, and H‐atom abstraction from an activated O−H bond. [ABSTRACT FROM AUTHOR]

A new structurally characterized ferrous corrole [FeII(ttppc)]− (1) binds one equivalent of dioxygen to form [FeIII(O2−.)(ttppc)]− (2). This complex exhibits a 16/18O2‐isotope sensitive ν(O‐O) stretch at 1128 cm−1 concomitantly with a single ν(Fe‐O2) at 555 cm−1, indicating it is an η1‐superoxo ("end‐on") iron(III) complex. Complex 2 is the first well characterized Fe‐O2 corrole, and mediates the following biologically relevant oxidation reactions: dioxygenation of an indole derivative, and H‐atom abstraction from an activated O−H bond. [ABSTRACT FROM AUTHOR]

This study evaluated the nutritional, economic, and environmental impacts of a Meatless Monday (MM) National School Lunch Program (NSLP) in a large urban US school district. After averaging the nutrient content of entrees across the week and comparing changes relative to recommendations, there were no pre-post differences >15%. Monday entrees offered post-MM required considerably less water to produce (−51%) and were associated with fewer greenhouse gas emissions (−74%). The MM program had little impact on entrée cost (−2.5%). Further research is needed to determine how MM program goals can be achieved within the NSLP context. [ABSTRACT FROM AUTHOR]

Minerva Surgical, Inc. v Hologic, Inc. No. 20–440, 594 US ___, United States Supreme Court, 29 June 2021 (Minerva) Hologic, Inc. v Minerva Surgical, Inc. , 957 F3d 1256 (Federal Circuit 2020) (' Hologic'), rehearing and rehearing en banc denied, petition for certiorari filed On 29 June 2021, the US Supreme Court issued a decision in Minerva Surgical, Inc. v Hologic, Inc. upholding the doctrine of assignor estoppel, which prevents inventors from challenging the validity of patents they have assigned to third parties. The court limited the scope of assignor estoppel to cases where the inventor made 'explicit or implicit representations' regarding the patentability of the claimed invention. [ABSTRACT FROM AUTHOR]

United States v Arthrex, Inc. Nos. 19-1434, 19-1452, 19-1458, 594 US ____, slip opinion, United States Supreme Court, 21 June 2021 (Arthrex III) Arthrex, Inc. v Smith & Nephew, Inc. , 941 F3d 1320 (Federal Circuit 2019) (' Arthrex I '), rehearing and rehearing en banc denied , 953 F3d 760 (Federal Circuit 2020) (' Arthrex II '), petition for certiorari filed On 21 June 2021, the United States Supreme Court issued a decision in United States v. Arthrex, Inc. finding that the authority of administrative patent judges (APJs) of the Patent Trial and Appeal Board to issue Final Written Decisions without review by a superior is inconsistent with their appointment as inferior officers under the Appointments Clause of the US Constitution. The Supreme Court sought to cure this constitutional violation by giving the Director of the United States Patent and Trademark Office more control over the rulings of APJs. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The current study was aimed at investigating the safety, efficiency, and durability of transvaginal sacrospinous ligament suture rectopexy in women with obstructed defecation symptoms (ODS) and significant rectal hypermobility/folding. Methods: This was a prospective case series study performed during December 2018 to July 2020. Women presenting to our center with pelvic organ prolapse electing for surgical treatment were screened for ODS utilizing the PFDI-20 questionnaire. Patients were eligible for inclusion if they reported OD symptoms accompanying >50% of bowel movements (BMs), BM frequency ≥3 per week, stool type 3 or 4 based on the Bristol stool chart, absence of dyssynergic Valsalva, and dynamic ultrasound indicating a rectal compression ratio >25%. Patients underwent transvaginal sacrospinous ligament rectopexy and were followed up at 2 and 12 months postoperatively. Results: A total of 20 patients underwent the procedure and completed the follow-up. Statistically significant improvements were observed in all OD symptoms and subjective improvement (94.7% ± 13.4 and 90.6% ± 18) at 2 and 12 months after the surgery respectively. Mean rectal compression ratio, detected via ultrasound, improved from 45.5% ± 18.4 preoperatively to 9.2% ± 13.7 at 2 months (p < 0.0001) and 19.6% ± 14.4 at 12 months (p < 0.0012). Surgical failure, defined as combined subjective (ODS >50% of bowel movements) and anatomical failure (rectal compression ratio >25%), occurred in 2 patients. Conclusion: Transvaginal sacrospinous ligament suture rectopexy was safe, feasible, and effectively treated ODS within this cohort of women undergoing POP surgery with rectal hypermobility confirmed by dynamic ultrasound. [ABSTRACT FROM AUTHOR]

A new nonheme iron(II) complex, FeII(Me3TACN)((OSiPh2)2O) (1), is reported. Reaction of 1 with NO(g) gives a stable mononitrosyl complex Fe(NO)(Me3TACN)((OSiPh2)2O) (2), which was characterized by Mössbauer (δ=0.52 mm s−1, |ΔEQ|=0.80 mm s−1), EPR (S=3/2), resonance Raman (RR) and Fe K‐edge X‐ray absorption spectroscopies. The data show that 2 is an {FeNO}7 complex with an S=3/2 spin ground state. The RR spectrum (λexc=458 nm) of 2 combined with isotopic labeling (15N, 18O) reveals ν(N‐O)=1680 cm−1, which is highly activated, and is a nearly identical match to that seen for the reactive mononitrosyl intermediate in the nonheme iron enzyme FDPnor (ν(NO)=1681 cm−1). Complex 2 reacts rapidly with H2O in THF to produce the N‐N coupled product N2O, providing the first example of a mononuclear nonheme iron complex that is capable of converting NO to N2O in the absence of an exogenous reductant. [ABSTRACT FROM AUTHOR]

A new nonheme iron(II) complex, FeII(Me3TACN)((OSiPh2)2O) (1), is reported. Reaction of 1 with NO(g) gives a stable mononitrosyl complex Fe(NO)(Me3TACN)((OSiPh2)2O) (2), which was characterized by Mössbauer (δ=0.52 mm s−1, |ΔEQ|=0.80 mm s−1), EPR (S=3/2), resonance Raman (RR) and Fe K‐edge X‐ray absorption spectroscopies. The data show that 2 is an {FeNO}7 complex with an S=3/2 spin ground state. The RR spectrum (λexc=458 nm) of 2 combined with isotopic labeling (15N, 18O) reveals ν(N‐O)=1680 cm−1, which is highly activated, and is a nearly identical match to that seen for the reactive mononitrosyl intermediate in the nonheme iron enzyme FDPnor (ν(NO)=1681 cm−1). Complex 2 reacts rapidly with H2O in THF to produce the N‐N coupled product N2O, providing the first example of a mononuclear nonheme iron complex that is capable of converting NO to N2O in the absence of an exogenous reductant. [ABSTRACT FROM AUTHOR]

On 24 February 2002, the US Supreme Court issued its decision in Unicolors, Inc. v H&M Hennes & Mauritz, LP , holding that an unintentional mistake of law is entitled to the benefit of the US Copyright Act's safe harbour provision, § 411(b)(1)(A). In so doing, the Court clarified that not only unintentional mistakes of fact made during the application process, but also unintentional mistakes of law may be evaluated under the US Copyright Act's safe harbour provision. [ABSTRACT FROM AUTHOR]

Obstructed defecation (OD) is common and may be related to compromised pelvic floor integrity. Magnetic resonance (MR) defecography and statistical shape modeling were used to define pelvic floor shape variations, hypothesizing that State (rest vs peak evacuation) and Group (control vs case) would significantly influence shape. 16 women underwent MR defecography (9 cases vs 7 controls). Midsagittal, 2D pelvic floors were segmented and aligned by corresponding points. Principal component scores were compared using a Two-Way Mixed MANOVA. Three modes described differences between State (p < 0.001) and Group (p = 0.023). The pelvic floor shape differed significantly between women with and without OD and during evacuation. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: To assess cognitive changes in women 12 months after starting anticholinergic medications for overactive bladder syndrome (OAB). Methods: We present a prospective cohort study assessing changes in cognition in women seen in a referral urogynecology practice. We compared women who started anticholinergic OAB medications with women not on anticholinergic OAB medications. The primary outcome was change over time on the Montreal Cognitive Assessment (MOCA) screening score. At enrollment, women completed a baseline MOCA screening, a Geriatric Depression Screen (GDS), and an assessment of medications to create an anticholinergic burden score (ACB). At 3, 6, 9, and 12 months after enrollment women were administered the MOCA, GDS, and a review of their medications and medical problems. Statistical analysis was performed using a linear mixed effects model taking into account correlated error terms given multiple MOCA assessments at various time points per patient. Results: A total of 106 women were enrolled, 60 in the OAB medication group and 46 in the control (non-OAB medication) group. The mean age was 77 years, 93% of women were Caucasian, and 98% completed high school, with no difference between groups. Over time there was no difference in change of MOCA score between the OAB and control groups when controlling for age, GDS score, and ACB score (p = 0.78). This association did not change when women with a neurological diagnosis were excluded (n = 6). On average MOCA scores for the OAB group increased by 0.76 over 12 months and the control group increased 0.39, with no difference between the groups (p = 0.53). Conclusions: We found no changes in MOCA scores between OAB medication and control groups after controlling for age, depression, and polypharmacy after 12 months of follow-up. [ABSTRACT FROM AUTHOR]

Domestic minor sex trafficking (DMST) is an increasingly recognized traumatic crime premised upon the control, abuse, and exploitation of youth. By definition, DMST is the "recruitment, harboring, transportation, provision, or obtaining of a person for the purpose of a commercial sex act" within domestic borders, in which the person is a U.S. citizen or lawful permanent resident under the age of 18 years. The present study described the demographics, psychosocial features, and trafficking experiences (e.g., environments of recruitment, relationship to trafficker, solicitation) of DMST victims. A total of 25 medical records of patients under the age of 18 who disclosed their involvement in DMST to medical providers between August 1, 2013, and November 30, 2015, were retrospectively reviewed. The majority of patients were female, and the mean age was 15.4 years old. Most patients lived at home and/or were accompanied at the evaluation by a parent/guardian. High rates of alcohol or substance use/abuse (92%), being placed in a group home or child protective services (CPS) custody (28%), a history of runaway behavior (60%), and/or exposure to other child maltreatment (88%) were identified. Our data indicated variation in reported trafficking experiences; however, patients commonly reported an established relationship with their trafficker (60%) and recruitment occurred primarily as a result of financial motivation (52%). Patients were prevalently recruited in settings where there were face-to-face interactions (56%), whereas the solicitation of sex-buyers occurred primarily online (92%). Victims who disclosed involvement in DMST had complicated psychosocial histories that may have rendered them susceptible to their exploitation, and reported a variety of DMST experiences perpetuated by traffickers. Although preliminary in nature, this study provided empirical evidence of the predisposing factors, motivations, and experiences of victimized youth uniquely from the perspective of patients who sought medical care. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The current study was aimed at addressing two questions: first, is any conventional vaginal prolapse repair effective in curing obstructed defecation symptoms, and second, is there evidence to suggest that a sacrocolpopexy will increase the risk of worsening or new-onset obstructed defecation symptoms? Methods: This is a sub-analysis of two major clinical trials performed by the Pelvic Floor Disorders Network: the Colpopexy and Urinary Reduction Efforts (CARE) trial and the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial. Two-year follow-up data were included. Demographics, pelvic organ prolapse quantification examination, and symptoms were compared between first, two surgical arms in the OPTIMAL study and second, CARE and OPTIMAL datasets using Chi-squared test for categorical variables and Student's t test or Mann–Whitney U test for continuous variables. Results: A total of 353 subjects form the OPTIMAL study and 279 subjects from the CARE study met the inclusion criteria. Regardless of trial, obstructed defecation symptoms were present in more than half of the patients at the initial visit before the surgical intervention, and interestingly, about one third of the patients were symptomatic at the 24-month follow-up in all surgical groups. Conclusion: The conventional vaginal prolapse surgeries, with or without posterior vaginal wall repair, improved obstructed defecation symptoms by 50%, but about 35% of patients were suffering from at least one of the aspects of obstructed defecation at the 24-month follow-up. It is also important to note that about a quarter of the patients experienced persisting or worsening of their obstructed defecation symptoms in the absence of anatomical failure. [ABSTRACT FROM AUTHOR]

Reaction of FeIII(O2˙−)(TPP) with 2,3-dimethylindole at −40 °C gives the ring-opened, dioxygenated N-(2-acetyl-phenyl)-acetamide product. The reaction was monitored in situ by low-temperature UV-vis and 1H NMR spectroscopies. This work demonstrates that a discrete iron(III)(superoxo) porphyrin is competent to carry out indole oxidation, as proposed for the tryptophan and indoleamine 2,3-dioxygenases. [ABSTRACT FROM AUTHOR]

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+ (hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain. [ABSTRACT FROM AUTHOR]

Limited research has examined the rapid growth of farm to school (FTS) programs in the US. Qualitative interviews (n = 24) framed by Diffusion of Innovations theory were used to explore FTS program adoption and expansion in Massachusetts. Program compatibility and relative advantages related to academics, school meal participation, and child health motivated initial engagement. Active classroom integration, implementation simplification, and strong support networks aided program expansion. Leadership and sustainability plans, garden maintenance partnerships, and Community Eligibility Provision participation hold promise to help further program diffusion. Future research should focus on providing additional evidence for FTS aspects salient to adoption and expansion. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Although the main function of the suspensory ligaments of the vaginal apex is to prevent its descent toward the vaginal introitus, there remains limited information regarding its normal physiological motion. This study was aimed at quantifying the motion of the non-prolapsed vaginal apex during strain and defecation maneuvers. Methods: This study represents a sub-analysis of a parent study that was aimed at evaluating rectal mobility with regard to obstructed defecation symptoms. Patients with normal apical vaginal support who had undergone MR defecography were entered into the study. For each patient, midsagittal images at rest, maximum strain, and maximum evacuation were utilized. The location of the cervicovaginal junction, S4–S5 intervertebral disc, sacral promontory, and hymen were identified. Vectors were calculated from each of these landmarks to the vaginal apex to compare vector angles and magnitudes across subjects. Results: Twelve patients were included in this study. At rest, the vagina extends from the hymen, which is inferior and posterior to the inferior symphysis pubis, to the vaginal apex at an angle of 45.2° ± 14.5° relative to the pubococcygeal line. This angle became more acute with strain and even more so during maximum evacuation (14.1° ± 9.0°, p < 0.001). Differences in the vector magnitude, although not statistically significant, showed a trend indicating shorter lengths with maximum evacuation. Conclusions: The vaginal apex is a highly mobile structure demonstrating significantly more mobility during defecation compared with strain. The data obtained contradict the general perception that the vaginal apex is relatively fixed within the pelvis of normally supported women. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Obstructed defecation symptoms (ODS) are common in women; however, the key underlying anatomic factors remain poorly understood. We investigated rectal mobility and support defects in women with and without ODS using pelvic floor ultrasound and MR defecography. Methods: This prospective case-control study categorized subjects based on questions 7, 8 and 14 on the PFDI-20, which asks about obstructed defecation symptoms. All subjects underwent an interview, examination and pelvic floor ultrasound, and a subset of 16 subjects underwent MR defecography. The cul de sac-to-anorectal junction distance at rest and during maximum strain was measured on ultrasound and MRI images. The 'compression ratio' was calculated by dividing the change in rectovaginal septum length by its rest length to quantify rectal folding and hypermobility during dynamic imaging and to correlate with ODS. Results: Sixty-two women were recruited, 32 cases and 30 controls. There were no statistically significant differences in age, parity, BMI or stage of rectocele between groups. A threshold analysis indicated the risk of ODS was 32 times greater (OR 32.5, 95% CI 4.8–217.1, p = 0.0003) among women with a high compression ratio (≥ 14) compared with those with a low compression ratio (< 14) after controlling for age, BMI, parity, stool type and BM frequency. Conclusions: Female ODS are associated with distinct alterations in rectal mobility and support that can be clearly observed on dynamic ultrasound. The defects in rectal support were quantifiable using a compression ratio metric, and these defects strongly predicted the likelihood of symptoms; interestingly, the presence or degree of rectocele defects played no role. These findings may provide new insight into the anatomic factors underlying female ODS. [ABSTRACT FROM AUTHOR]

Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut- brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut- brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed that SCFAs induced altered contralesional cortex connectivity. This was associated with SCFA-dependent changes in spine and synapse densities. RNA sequencing of the forebrain cortex indicated a potential involvement of microglial cells in contributing to the structural and functional remodeling. Further analyses confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFAs modulate poststroke recovery via effects on systemic and brain resident immune cells. [ABSTRACT FROM AUTHOR]

In the analysis of vertical integration by contract versus ownership, one event has dominated the discussion--General Motors' (GM) merger with Fisher Body in 1926. The debates have all been premised on the assumption that the 10-year contract between the parties signed in 1919 was a legally enforceable agreement. However, it was not. Because Fisher's promise was illusory the contract lacked consideration. This note suggests that GM's counsel must have known this. It raises a significant question in transactional engineering: what is the function of an agreement that is not legally enforceable? [ABSTRACT FROM AUTHOR]

The metabolic changes associated with the addition of 4 months of resistive exercise to an existing aerobic exercise program (AEX+RT, n = 7) were compared to a maintenance aerobic exercise program (AEX, n = 8) in overweight, older men. The subjects in this study had recently completed a 6-month aerobic exercise program (treadmill walking, 45 min/d, 2 d/wk). The AEX+RT group added 6 exercises on upper- and lower-body pneumatic-resistance machines (2 sets, 15 repetitions each, 2 d/wk) to an aerobic exercise program at ≥ 70% heart rate reserve for 30-40 min, 2 d/wk on treadmill, while the AEX group continued the same maintenance treadmill AEX program. There were no baseline differences in body weight, VO[sub2max], or glucose metabolism between groups. The AEX+RT group increased upper- and lower-extremity strength by 28 ± 4% and 46 ± 6%, respectively (p < .05), despite a 9% decrease in VO[sub2max] (p < .05). VO[sub2max] did not change in the AEX group. There was no change in the fasting glucose or insulin levels, or the 3-h glucose responses to an oral glucose load in either group. The insulin responses decreased by 25 ± 4% in the AEX+RT group (p < .01) but did not change in the AEX group. In conclusion, the addition of resistive exercise training to an existing aerobic exercise program may improve insulin sensitivity in overweight, older men, and thus prevent the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Whole-brain volumetric microscopy techniques such as serial two-photon tomography (STPT) can provide detailed information on the roles of neuroinflammation and neuroplasticity throughout the whole brain post-stroke. STPT automatically generates high-resolution images of coronal sections of the entire mouse brain that can be readily visualized in three dimensions. We developed a pipeline for whole brain image analysis that includes supervised machine learning (pixel-wise random forest models via the "ilastik" software package) followed by registration to a standardized 3-D atlas of the adult mouse brain (Common Coordinate Framework v3.0; Allen Institute for Brain Science). These procedures allow the detection of cellular fluorescent signals throughout the brain in an unbiased manner. To illustrate our imaging techniques and automated image quantification, we examined long-term post-stroke motor circuit connectivity in mice that received a motor cortex photothrombotic stroke. Two weeks post-stroke, mice received intramuscular injections of pseudorabies virus (PRV-152), a trans-synaptic retrograde herpes virus driving expression of green fluorescent protein (GFP), into the affected contralesional forelimb to label neurons in descending tracts to the forelimb musculature. Mice were sacrificed 3 weeks post-stroke. We also quantified sub-acute neuroinflammation in the post-stroke brain in a separate cohort of mice following a 60 min transient middle cerebral artery occlusion (tMCAo). Naive e450+-labeled splenic CD8+ cytotoxic T cells were intravenously injected at 7, 24, 48, and 72 h post-tMCAo. Mice were sacrificed 4 days after stroke. Detailed quantification of post-stroke neural connectivity and neuroinflammation indicates a role for remote brain regions in stroke pathology and recovery. The workflow described herein, incorporating STPT and automated quantification of fluorescently labeled features of interest, provides a framework by which one can objectively evaluate labeled neuronal or lymphocyte populations in healthy and injured brains. The results provide region-specific quantification of neural connectivity and neuroinflammation, which could be a critical tool for investigating mechanisms of not only stroke recovery, but also a wide variety of brain injuries or diseases. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Multiple publications have demonstrated the efficacy of percutaneous tibial nerve stimulation (PTNS) for overactive bladder syndrome (OAB). However, patient characteristics associated with successful treatment have not been well established. The aim of this study was to identify prognostic factors for successful PTNS treatment. Methods: This was a retrospective chart review of women who underwent PTNS therapy for OAB between January 2011–Decemeber 2017. Treatment success was defined by subjective improvement according to patient self-report and objective bladder diary parameters including the intervoiding interval, nocturia episodes and urgency urinary incontinence (UUI) episodes per day, before and after PTNS treatment. Baseline symptoms were dichotomized for each symptom based on severity. Results: One hundred sixty-two women with a mean age of 72.7 ± 11.3 years and BMI of 28.5 ± 7.1 were included in the study. There was a statistically significant improvement in all three OAB symptoms after treatment. Multivariable analysis revealed that a history of depression and anxiety was associated with subjective improvement, whereas decreased subjective improvement was associated with a history of hypertension, prior intravesical onabotulinnumtoxinA injection and sacral neuromodulation. While dichotomizing subjects into two groups defined by < 50% versus ≥ 50% improvement, depression/anxiety, urodynamic volume at first sensation to void and more severe baseline urgency urinary incontinence severity were all significant predictors of subjective improvement. Conclusions: Among women treated with PTNS for refractory OAB, a history of depression/anxiety and severe baseline urgency urinary incontinence were positive predictors of a successful PTNS outcome. [ABSTRACT FROM AUTHOR]

Aims: To investigate patient characteristics associated with overactive bladder (OAB) symptom improvement after 1 year of monthly percutaneous tibial nerve stimulation (PTNS) therapy. Methods: This was a retrospective chart review of women who underwent PTNS for refractory OAB symptoms between January 2011 and December 2017 in our tertiary center. Patients who received 12 monthly PTNS maintenance treatments after achieving success with 12 weekly PTNS treatments were included in the study. Reports on subjective changes in urinary frequency, nocturia, and urgency urinary incontinence were submitted at each visit. Patients were categorized to symptom improve and no improve groups. A multivariate analysis was performed to identify patient characteristics that predicted symptomatic improvement. Results: Sixty‐six patients were identified. Average subjective improvement after 12 monthly sessions compared with 12 weekly sessions was 5.2% on a scale of −100% to +100%. A history of urogynecologic surgery remained a significant negative predictor of symptom change from 12 weekly sessions to 12 monthly treatment sessions (odds ratio, 0.19; P = .01). Conclusions: OAB symptoms remain relatively stable after 12 monthly treatments of PTNS, as compared with the 12‐week time point. A history of urogynecologic surgery was a negative predictor of OAB symptom improvement in patients receiving monthly PTNS for at least 12 months. [ABSTRACT FROM AUTHOR]

Background: A study conducted as part of the development of the Eleventh International Classification of Mental Disorders for Primary Health Care (ICD-11 PHC) provided an opportunity to test the relationships among depressive, anxious and somatic symptoms in PHC. Method: Primary care physicians participating in the ICD-11 PHC field studies in five countries selected patients who presented with somatic symptoms not explained by known physical pathology by applying a 29-item screening on somatic complaints that were under study for bodily stress disorder. Patients were interviewed using the Clinical Interview Schedule-Revised and assessed using two five-item scales that measure depressive and anxious symptoms. Structural models of anxious-depressive symptoms and somatic complaints were tested using a bi-factor approach. Results: A total of 797 patients completed the study procedures. Two bi-factor models fit the data well: Model 1 had all symptoms loaded on a general factor, along with one of three specific depression, anxiety and somatic factors [ x 2 (627) = 741.016, p < 0.0011, RMSEA = 0.015, CFI = 0.911, TLI = 0.9]. Model 2 had a general factor and two specific anxious depression and somatic factors [ x 2 (627) = 663.065, p = 0.1543, RMSEA = 0.008, CFI = 0.954, TLI = 0.948]. Conclusions: These data along with those of previous studies suggest that depressive, anxious and somatic symptoms are largely different presentations of a common latent phenomenon. This study provides support for the ICD-11 PHC conceptualization of mood disturbance, especially anxious depression, as central among patients who present multiple somatic symptoms. [ABSTRACT FROM AUTHOR]

The H-atom transfer (HAT) reactivity of a corrolazine cobalt superoxide with weak O–H and N–H substrates has been demonstrated. Kinetic analysis shows relatively fast rates of HAT with diphenylhydrazine (DPH). A kinetic isotope effect (KIE) and Eyring activation parameters are consistent with an HAT mechanism. [ABSTRACT FROM AUTHOR]