bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal age and gonadotrophin elevation cooperatively decrease viable ovulated oocytes and increase ootoxicity, chromosome-, and spindle-misalignments: ‘2-Hit’ and ‘FSH-OoToxicity’ mechanisms as new reproductive aging hypotheses
Authors: Bernstein Lori R , Mackenzie Amelia C L , Durkin Keith , Kraemer Duane C , Chaffin Charles L , Merchenthaler Istvan 
Published: August 2023

AbstractWhile there is consensus that advanced maternal age (AMA) reduces oocyte yield and quality, the notion that high FSH reduces oocyte quality and causes aneuploidy remains controversial, perhaps due to difficulties controlling the confounding variables of age and FSH levels. Here, contributions of age and gonadotrophin elevation were separately controlled using a mouse model of human female reproductive aging. Ovulated oocytes were collected from young and midlife mice after 0-, 2.6-, or 17-day treatment with the FSH analog equine chorionic gonadotrophin (eCG), to model both exogenous FSH elevation within a single treatment cycle (as in controlled ovarian stimulation (COS)), and chronic endogenous FSH elevation during multiple cycles (as in diminished ovarian reserve). After 17-day eCG, fewer total oocytes/mouse are ovulated in midlife than young mice, and a precipitous decline in viable oocytes/mouse is observed in midlife but not young mice throughout eCG treatment. eCG is potently ootoxic to ovulatory oocytes and strongly induces chromosome- and spindle-misalignments within 2.6 days of eCG in midlife, but only after 17 days in young mice. These data indicate that AMA increases susceptibility to multiple adverse effects of elevated FSH activity in ovulated oocytes, including declines in total and viable oocytes/mouse, and induction of ootoxicity and aneuploidy. Two hypotheses are proposed for underlying causes of infertility in women. The FSH OOToxicity Hypothesis (‘FOOT Hypothesis’) posits that high FSH is ootoxic to ovulatory oocytes and that FSH ootoxicity is a root cause of low pregnancy success rates in naturally cycling women with high FSH and IUI patients undergoing COS. The ‘2-Hit Hypothesis’ posits that AMA increases susceptibility to FSH-induced ootoxicity and aneuploidy.
Low back pain-related healthcare utilization following intraosseous basivertebral nerve radiofrequency ablation: a pooled analysis from three prospective clinical trials
Authors: McCormick Zachary L , Curtis Timothy , Cooper Amanda , Wheatley Margo , Smuck Matthew 
Published: August 2023

Abstract

Background
The effectiveness and safety of intraosseous basivertebral nerve ablation (BVNA) for treating vertebrogenic pain is established, but low back pain-related healthcare utilization (LBPr-HU) following BVNA continues to be defined.

Methods
LBPr-HU data were pooled from 3 prospective studies. LBPr-HU categories of interest included non-invasive conservative care, opioid utilization, lumbosacral spinal injection (LSI), lumbosacral radiofrequency ablation (LRFA), and lumbosacral spinal surgery. Pre- and post-BVNA LBPr-HU were compared at both 1- and 5-years using McNemar’s test for proportions and paired t-tests for means.

Results
Two hundred forty-seven patients received BVNA and had 1-year follow-up; 205 had long-term follow-up (mean of 5.3 ± 1.33 years). Twenty-seven percent fewer participants initiated conservative care in the year post-BVNA compared to the year preceding BVNA (P &lt; .001; 95% CI 19.8–34.5). Of 77/247 participants taking opioids at baseline, 40.3% and 61.7% fewer were taking them at one-year and 5.3 ± 1.33 years post-BVNA, respectively (P &lt; .001). Of participants receiving LSIs in the year preceding BVNA, 81.2% fewer received LSI(s) in the year post-BVNA (P &lt; .001; 95% CI 70.7–90.7); a 76.4% reduction in LSIs was maintained through a mean of 5.3 ± 1.33 years post-BVNA. LRFA rates were 1.6% at 1-year post-BVNA and 8.3% at 5.3 ± 1.33 years post-BVNA. Lumbar fusion surgery was 0.8% at 1-year post-BVNA and 6.5% at 5.3 ± 1.33 years post-BVNA.

Conclusions
In this aggregate analysis of patients with vertebrogenic pain, utilization of conservative care, opioids, LSIs, and LRFA were substantially reduced through 5 years post-BVNA compared to baseline. Lumbar fusion rates were less than half the published value at 5 years in similar populations.
Oxidative stress mediates associations between preoperative psychosocial phenotype and pain-related outcomes at 6 months following total knee arthroplasty: a longitudinal cohort study
Authors: Bruehl Stephen , Milne Ginger , Polkowski Gregory , Shinar Andrew , Anderson Sara , Mishra Puneet , Larach Daniel B , Martin Ryan , Billings Frederic T 
Published: August 2023

Abstract

Objective
Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS).

Design
A mixed between/within-subjects longitudinal cohort design.

Setting
A single academic medical center.

Subjects
Osteoarthritis patients (n = 91; 62.6% female) undergoing unilateral TKA.

Methods
We assessed depression, anxiety, and catastrophizing, as well as markers of central sensitization (widespread pain, temporal summation of pain) preoperatively. Blood samples were then obtained immediately prior to intraoperative tourniquet placement for quantification of in vivo biomarkers of systemic OS, F2-isoprostanes and isofurans. Post-TKA pain intensity (numeric rating scale worst pain [NRS], McGill Pain Questionnaire-2 [MPQ-2]) and function (PROMIS Pain Interference) were assessed at 6 months following TKA.

Results
Greater preoperative depression, catastrophizing, and widespread pain were associated with higher intraoperative combined OS (F2-isoprostanes+isofurans/2), which was in turn associated with higher post-TKA pain intensity and worse function (P &lt; .05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (P &lt; .05). Bootstrapped mediation analyses revealed significant (P &lt; .05) indirect (mediated) effects of depression (NRS Worst Pain, MPQ-2, PROMIS Pain Interference), anxiety (MPQ-2, PROMIS Pain Interference), and catastrophizing (PROMIS Pain Interference) on adverse long-term post-TKA outcomes via elevated OS. Central sensitization-related predictors demonstrated only direct effects (P &lt; .05) on post-TKA outcomes that were independent of OS mechanisms.

Conclusions
Results suggest that the adverse impact of depression, anxiety, and pain catastrophizing on post-TKA pain and functional outcomes are mediated in part by elevated OS.
Raising the Age of Marriage Entry and Child's Nutrition Intake? Evidence from the Reform of Ethiopia's Family Law
Authors: Efobi Uchenna 
Published: August 2023

Abstract
This study investigates the impact of a family law reform in Ethiopia that raises the age of marriage entry for females (among other aspects of the law) on the nutritional intake of the children of affected women. Using the difference-in-differences and event-study strategies, the result suggests that exposure to the reform led to a significant increase in dietary diversity (14 percent increase relative to the mean) and a significant increase in the likelihood of consuming fruits and vegetables, fruits and vegetables rich in vitamin A, green leafy vegetables, and animal-source foods. The effect does not appear to be due to changes in women's economic engagement, such as their agency and outside options. Instead, it seems to imply that the implementation of the reform affects women's social status in terms of their decision-making power over sexual and marital relations.
Intimate partner violence
Authors: Alhusen Jeanne , McDonald Maria , Emery Bethany 
Published: August 2023

Abstract:
Intimate partner violence (IPV) is a significant public health issue associated with substantial morbidity and mortality. NPs are ideally positioned to screen for and intervene in IPV, thereby mitigating the health risks IPV carries for women, infants, and young children. Safety planning and appropriate referrals to community-based resources are critical components of addressing IPV.
Beyond fluconazole
Authors: Hellier Susan D. , Wrynn Alexander F. 
Published: August 2023

Abstract:
Vaginitis symptoms are among the most common reasons for patients to seek acute gynecological care. NPs who care for women and other patients with vaginas need to be up-to-date on diagnosis and treatment of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Two new antifungal medications for VVC are available. This article reviews vaginal physiology and provides an overview of VVC and RVVC pathophysiology, diagnosis, and treatment options.
Computed Tomography Analysis of Distal Tibia Physeal Fracture Patterns: A Classification and Technique for Optimizing Screw Trajectory
Authors: Sheth Mihir , Kitziger Raymond , Bindner Corey , Rosenfeld Scott B. 
Published: August 2023

Background:
Fractures involving the anterolateral distal tibia, often referred to as Tillaux or Triplane fractures, are often treated operatively to achieve an anatomic reduction of the ankle joint articular surface. Although axial images from computed tomography scans are commonly obtained to measure displacement, no studies have examined these fracture patterns in the axial plane. This information may be useful to guide screw trajectory with only fluoroscopic imaging intraoperatively.

Methods:
We queried an institutional radiology report database for all “Tillaux” or “triplane” fractures and manually reviewed to identify fractures with an anterolateral tibia fragment. The axial image immediately caudal to the physis or physeal scar was used for measurements. The angle between the incisura and the fracture line exiting the incisura was measured. The width of the fracture fragment and the anterior distal tibia was then measured perpendicular to the incisura, representing the width that would be seen on an intraoperative mortise. A cluster analysis was performed to identify fracture patterns.

Results:
The average age of patients included in the study was 16 ± 2 years. Sixty-nine patients met inclusion criteria 32 patients with Tillaux fractures (46.4%) and 37 patients with triplane fractures (53.6%) met study inclusion criteria for a total of 69 patients. The cluster analysis demonstrated 3 fracture patterns. For type 1 (n=16), the mean was 24.5 ± 6.5 degrees from the incisura and the mean distance from the tibiofibular joint was 21.1 ± 6.3%. For type 2 (n=20), the mean was 58.6 ± 7.2 degrees and the mean distance was 48.7 ± 8.9%. For type 3 (n=33), the mean was 88.6 ± 6.3 degrees and the mean distance was 49.1 ± 9.7%.

Conclusions:
This is the first study to identify that pediatric distal tibia physeal fractures occur in 3 common patterns with consistent fragment sizes and fracture planes. This information can optimize screw start point and trajectory in the axial plane when referencing a mortise x-ray and C-arm beam.

Level of Evidence:
Diagnostic, Level III.
Associations between childhood adversity and age at natural menopause
Authors: Kling Juliana M. , Saadedine Mariam , Faubion Stephanie S. , Shufelt Chrisandra L. , Mara Kristin C. , Enders Felicity T. , David Paru S. , Kapoor Ekta 
Published: August 2023

Abstract

Objective
Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause.

Methods
This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders.

Results
A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, −3.2 to 0.6; P = 0.18).

Conclusions
Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause.
Unmasked Neuropathic Pain After Neurectomy: A Case Series and Review of the Literature
Authors: Gomez-Rexrode Amalia E. , Kennedy Sarah H. , Brown David L. 
Published: August 2023

Summary:
Localization of neuropathic pain to a specific peripheral nerve origin relies on patient history, physical examination, and nerve blocks. Neurectomy of the involved nerve(s) can successfully alleviate patients’ pain. However, a subset of patients postoperatively describe persistent pain, but say that the pain “moved” to a new location (eg, from the dorsum of the foot to the lateral foot). This may be viewed as a treatment failure by the patient and surgeon alike. Further investigation, however, may localize the new pain to an additional, separate peripheral nerve injury, which was previously unrecognized by both parties. The mechanism involved is that of pain masking and unmasking. Successful treatment of the more prominent pain stimulus allows for recognition of a second, less-offending peripheral nerve injury. As the field of surgical treatment of chronic peripheral neuropathic pain advances, it is important to identify and define specific nuances of diagnosis and treatment via neurectomy. The term “diffuse noxious inhibitory control,” used to describe the pain-inhibits-pain pathway, may help explain the phenomenon of masking, whereby one pain generator is more prominent and shields another site from recognition and subsequent diagnosis. In this context, unmasked pain should be considered as a potential source of surgical treatment failure. We present a series of patients who, following improvement in the initial location of their pain, reported pain in a distinctly new peripheral nerve distribution, leading to reoperation.
Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults
Authors: Chin Jia Ying , Liu Chang , Lee Isabelle Xin Yu , Lin Molly Tzu Yu , Cheng Ching-Yu , Wong Jipson Hon Fai , Teo Cong Ling , Mehta Jodhbir S. , Liu Yu-Chi 
Published: August 2023

Purpose:
The aim of this study was to investigate age-related changes in corneal nerves and corneal epithelial cell parameters and to establish age-adjusted reference values.

Methods:
A total of 7025 corneal nerve images and 4215 corneal epithelial images obtained using in vivo confocal microscopy from 281 eyes of 143 healthy participants were included. Seven corneal nerve parameters and 3 corneal epithelial cell parameters were quantified using 2 automatic analytic software and analyzed across 6 age groups ranging from 21 to 80 years.

Results:
There was a declining trend in all 7 nerve parameters with advancing age. In particular, corneal nerve fiber length and corneal nerve fiber density demonstrated a significant decrease in subjects aged 65 years or older compared with subjects younger than 65 years (10.8 ± 2.6 mm/mm2 vs. 9.9 ± 2.0 mm/mm2, P = 0.011 in corneal nerve fiber length; 15.8 ± 5.2 fibers/mm2 vs. 14.4 ± 4.3 fibers/mm2, P = 0.046 in corneal nerve fiber density), whereas corneal nerve fractal dimension demonstrated a borderline significant decrease (P = 0.057). Similarly, there was a general declining trend in all epithelial cell parameters with advancing age. Corneal epithelial cell circularity was significantly lower in subjects aged 65 years and older as compared to subjects younger than 65 years (0.722 ± 0.021 μm2 vs. 0.714 ± 0.021 μm2; P = 0.011).

Conclusions:
Advancing age results in reduced corneal nerve metrics and alteration of corneal cell morphology. Aging effects should be considered when evaluating patients with corneal neuropathy.
Transient band keratopathy associated with epithelial ingrowth treated with antimetabolites
Authors: Frigoletto Evan , Amireskandari Annahita , Mauger Thomas 
Published: August 2023

Introduction:
To report a case of visually significant band keratopathy associated with ocular inflammation in the setting of epithelial ingrowth, both of which resolved after repeated antimetabolite treatments.

Patient and Clinical Findings:
A 74-year-old woman with a history of uveitis–glaucoma–hyphema syndrome after complicated cataract surgery presented with epithelial ingrowth in the right eye and diffuse central band keratopathy after posterior chamber intraocular lens (IOL) removal and pars plana vitrectomy and anterior chamber IOL placement.

Diagnosis, Intervention, and Outcomes:
After multiple intraocular injections of antimetabolites, the epithelial ingrowth and visually significant band keratopathy resolved.

Conclusions:
Treating the underlying source of inflammation, such as epithelial ingrowth with antimetabolites, was associated with clearance of the band keratopathy without further intervention.
Metformin Protects Against Noise-Induced Hearing Loss in Male Mice
Authors: Kennedy Catherine L. , Shuster Benjamin , Amanipour Reza , Milon Beatrice , Patel Priya , Elkon Ran , Hertzano Ronna 
Published: August 2023

Hypothesis
Metformin treatment will protect mice from noise-induced hearing loss (NIHL).

Background
We recently identified metformin as the top-ranking, Food and Drug Administration–approved drug to counter inner ear molecular changes induced by permanent threshold shift–inducing noise. This study is designed to functionally test metformin as a potential otoprotective drug against NIHL.

Methods
Male and female B6CBAF1/J mice were obtained at 7 to 8 weeks of age. A cohort of the females underwent ovariectomy to simulate menopause and eliminate the effect of ovarian-derived estrogens. At 10 weeks of age, mice underwent a permanent threshold shift–inducing noise exposure (102.5 or 105 dB SPL, 8–16 kHz, 2 h). Auditory brainstem response (ABR) thresholds were obtained at baseline, 24 h after noise exposure, and 1 week after noise exposure. Mice were administered metformin (200 mg/kg/d) or a saline control in their drinking water after the baseline ABR and for the remainder of the study. After the 1-week ABR, mice were euthanized and cochlear tissue was analyzed.

Results
Metformin treatment reduced the 1-week ABR threshold shift at 16 kHz (p < 0.01; d = 1.20) and 24 kHz (p < 0.01; d = 1.15) as well as outer hair cell loss in the 32–45.5 kHz range (p < 0.0001; d = 2.37) in male mice. In contrast, metformin treatment did not prevent hearing loss or outer hair cell loss in the intact or ovariectomized female mice.

Conclusions
Metformin exhibits sex-dependent efficacy as a therapeutic for NIHL. These data compel continued investigation into metformin's protective effects and demonstrate the importance of evaluating the therapeutic efficacy of drugs in subjects of both sexes.
Effects of Early Vestibular Rehabilitation in Patients With Acute Vestibular Disorder: A Systematic Review and Meta-Analysis
Authors: Kamo Tomohiko , Ogihara Hirofumi , Azami Masato , Momosaki Ryo , Fushiki Hiroaki 
Published: August 2023

Objectives
To investigate the effect of early vestibular rehabilitation on physical function and dizziness in patients with acute vestibular disorders.

Databases Reviewed
The electronic databases examined included PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (via Dialog), and PEDro.

Methods
The inclusion criteria in terms of the study participants were patients 20 years and older with an acute unilateral peripheral vestibular disorder. We included individual randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and crossover trials. The outcomes were gait, balance (eyes open, eyes close), activities of daily living, dizziness, and vestibular function. Early vestibular rehabilitation was defined as rehabilitation within 14 days of vestibular disorder onset or surgery. Main outcome measures were gait, balance (eyes open, eyes close), activities of daily living, dizziness, and vestibular function.

Results
Twelve trials involving 542 participants were included. Early vestibular rehabilitation improved the Dizziness Handicap Inventory by −7.18 (95% confidence interval [CI], −10.48 to −3.88), balance during eyes close by −1.40 (95% CI, −2.42 to −0.39), and dizziness by −1.47 (95% CI, −2.74 to −0.21) compared with no intervention or placebo.

Conclusion
The present study demonstrated that early vestibular rehabilitation improved the Dizziness Handicap Inventory, balance (eyes close), and subjective dizziness in a patient with acute vestibular disorders. This result indicates that early vestibular rehabilitation can promote vestibular compensation.
Treatment of invasive candidiasis in the era of Candida resistance
Authors: Paiva José-Artur , Pereira José Manuel 
Published: August 2023

Purpose of review
The increasing incidence of drug-resistant Candida brings a new challenge to the treatment of invasive candidiasis. Although cross-resistance among azoles and echinocandins was generally uncommon, reports of multidrug-resistant (MDR) Candida markedly increased in the last decade. The purpose of this review is to understand mechanisms and risk factors for resistance and how to tackle antifungal resistance.

Recent findings
The paper describes the action of the three main classes of antifungals - azoles, echinocandins and polyenes – and Candida's mechanisms of resistance. The current evolution from cross-resistance to multiresistance among Candida explains the modern glossary − multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) – imported from bacteria. MDR Candida most commonly involves acquired resistance in species with intrinsic resistance, therefore it mostly involves C. glabrata, C. parapsilosis, C. krusei, C guilliermondii or C. auris, which is intrinsically multidrug resistant. Finally, strategies to tackle antifungal resistance became clearer, ideally implemented through antifungal stewardship.

Summary
Avoiding antifungal's overuse and selecting the best drug, dose and duration, when they are needed, is fundamental. Knowledge of risk factors for resistance, microbiological diagnosis to the species, use of susceptibility test supported by antifungal stewardship programs help attaining effective therapy and sustaining the effectiveness of the current antifungal armamentarium.