bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyglutamine disease in peripheral tissues
Authors: Barwell Taylor , Seroude Laurent
Published: August 2023

This year is a milestone anniversary of the discovery that Huntington’s disease is caused by the presence of expanded polyglutamine repeats in the huntingtin gene leading to the formation of huntingtin aggregates. 30 years have elapsed and there is still no cure and the only FDA-approved treatment to alleviate the debilitating locomotor impairments presents several adverse effects. It has long been neglected that the huntingtin gene is almost ubiquitously expressed in many tissues outside of the nervous system. Growing evidence indicates that these peripheral tissues can contribute to the symptoms of the disease. New findings in Drosophila have shown that the selective expression of mutant huntingtin in muscle or fat is sufficient to cause detrimental effects in the absence of any neurodegeneration. In addition, it was discovered that a completely different tissue distribution of Htt aggregates in Drosophila muscles is responsible for a drastic aggravation of the detrimental effects. This review examines the peripheral tissues that express huntingtin with an added focus on the nature and distribution of the aggregates, if any.
Uncovering oligodendrocyte enhancers that control Cnp expression
Authors: Fan Chuandong , An Hongjoo , Kim Dongkyeong , Park Yungki
Published: August 2023

Oligodendrocytes (OLs) produce myelin sheaths around axons in the central nervous system (CNS). Myelin accelerates the propagation of action potentials along axons and supports the integrity of axons. Impaired myelination has been linked to neurological and neuropsychiatric disorders. As a major component of CNS myelin, 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) plays an indispensable role in the axon-supportive function of myelin. Notably, this function requires a high-level expression of CNP in OLs, as evidenced by downregulated expression of CNP in mental disorders and animal models. Little is known about how CNP expression is regulated in OLs. Especially, OL enhancers that govern CNP remain elusive. We have recently developed a powerful method that links OL enhancers to target genes in a principled manner. Here, we applied it to Cnp, uncovering two OL enhancers for it (termed Cnp-E1 and Cnp-E2). Epigenome editing analysis revealed that Cnp-E1 and Cnp-E2 are dedicated to Cnp. ATAC-seq and ChIP-seq data show that Cnp-E1 and Cnp-E2 are conserved OL-specific enhancers. Single cell multi-omics data that jointly profile gene expression and chromatin accessibility suggest that Cnp-E2 plays an important role in Cnp expression in the early stage of OL differentiation while Cnp-E1 sustains it in mature OLs.
Optimal placement of locally controlled voltage regulators in traditional distribution systems using the IMDE algorithm
Authors: Ahmadi Kamarposhti Mehrdad , Shokouhandeh Hassan , Kang Sun-Kyoung , Colak Ilhami , Barhoumi El Manaa , Eguchi Kei
Published: August 2023

One of the main goals of the designers of the power systems is the reduction of extra systems costs. The main part of these costs is related to energy loss, and the methods for loss reduction significantly lead to a cost reduction. The voltage regulators (VRs) can be used along the distribution feeders and the improvement of the network voltage profile results in the loss reduction of the system. However, the important problem is the installation location of this equipment to have the most profitability with the lowest cost. In this paper, the optimal placement of the VRs along the distribution systems is performed using intersect mutation differential evolution algorithm. The method aims to reduce loss and the primary investment and maintenance of the VRs. To this aim, the studies are performed on two scenarios for two standard distribution systems with 33 and 69 buses. A genetic algorithm (GA) is also utilized for the VRs placement to validate the results. The results show that the VRs reduce the loss to about 15% of the maximum system load. Moreover, the improved differential evolution algorithm performs better than the GA and makes the objective function in the minimum value.
Neurofilament Light Chain as a Biomarker of Neuronal Damage in Children With Malaria
Authors: Balanza Núria , Francis Caroline K , Crowley Valerie M , Weckman Andrea M , Zhong Kathleen , Baro Bàrbara , Varo Rosauro , Bassat Quique , Kain Kevin C ,   Rosiglitazone Adjunctive Therapy for Severe Malaria in Children (ROSI) Study Group, Mayor Alfredo , Manhiça Ana Rosa , Cossa Anelsio , Sitoe Antonio , Mucasse Campos , Erice Clara , Fonseca Crisóstomo , Mucasse Humberto , Bramugy Justina , Quimice Lazaro , Serghides Lena , Valente Marta , Gladstone Melissa , Vitorino Pio , Bila Rubao , Ajanovic Sara , Derpsch Yiovanna
Published: August 2023

Malaria can cause brain injury. Neurofilament light chain (NfL) is a biomarker of neuronal damage. Here we examined longitudinal plasma NfL levels in children aged 1–12 years with uncomplicated and severe malaria from Mozambique. NfL levels were similar in all malaria cases at hospital admission. However, levels increased over time and the increment was significantly higher in severe malaria cases with neurological manifestations (ie, coma, impaired consciousness, or repeated seizures). NfL may be useful to identify and quantify brain injury in malaria.
782 The Effect of Medical Comorbidites on Mortality in Burn Patients
Authors: Satahoo Shevonne S , Okeke Barbara , Kaufman Joyce I , Nabeta Geraldine , Pizano Louis R , Schulman Carl I
Published: August 2023

Introduction

Age, percent total burn surface area (TBSA) burn, and presence of inhalation injury have been well accepted as prognostic factors associated with burn injury. However, there may be additional comorbidities that affect mortality to consider. Recently published data include comorbidities specifically in the elderly population or focus on a specific comorbidity. As such, this analysis sought to identify comorbidities with a more comprehensive approach while focusing on the adult population.

Methods

The National Inpatient Sample was queried for all patients with age 18-65 years with ICD-9 codes for total body surface area (TBSA) burn ≥ 20% and non-elective admissions. Years included were 2013- third quarter of 2015. Age, race, comorbidities and mortality were recorded. Cases with missing data for mortality were excluded. Statistical analysis was done with Chi-Square testing. Mortality was then used to perform a binary logistic regression using these variables.

Results

There were 5545 weighted cases. The median age was 41.0 years (IQR 29-52 years). Mortality was 14.7%. The presence of AIDS, chronic blood loss anemia, chronic pulmonary disease, congestive heart failure, peptic ulcer disease (excluding bleeding), peripheral vascular disease, renal failure, rheumatoid arthritis/collagen vascular disease, and solid tumor without metastasis were not found to be statistically significant. The significant variables were then entered into a binary regression model on mortality. For the regression analysis, age, gender and race were also included. Age and race were statistically significant (p < 0.001 for both), while gender was not (p=0.072). While significant on univariate analysis, alcohol abuse (p=0.059), diabetes with chronic complications (p=0.244), metastatic cancer (p=0.999), psychoses (p=0.053) and valvular disease (p=0.998) were no longer significant on multivariate analysis. The results of the significant comorbidities are listed in the table. In those who died, there were increased odds of having coagulopathy, uncomplicated diabetes, liver disease, paralysis, pulmonary circulation disorders and obesity.

Conclusions

Identification of these significant comorbidities potentially highlights the need for updated models to assist clinicians in determining risk of mortality in burn patients. Theses comorbidities also point to the importance of resources for primary care physicians to optimize these patient populations and potentially minimize the risk of complications should patients become injured.

Applicability of Research to Practice
293 Risk of Clostridium Difficile Enterocolitis in SJS/TENS Patients Treated with Antibiotics
Authors: Skidmore Savannah , Hink Ashley , Kahn Steven A , Ozhathil Deepak
Published: August 2023

Introduction

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are both rare conditions derived from adverse drug reactions. SJS/TENS patients are often treated with antibiotics, both prophylactically and therapeutically, for secondary infections. However, the subsequent development of Clostridium Difficile (C. Difficile) enterocolitis is unknown. Due to the rarity of SJS/TENS, institution trials are limited in their data quantify the additional risk of sequelae such as enterocolitis development after antibiotic administration. Therefore, we used a large commercially available database derived from inpatient hospital coding data to assess the incidence of C. Difficile enterocolitis within 2 weeks of antibiotic administration after development of SJS/TENS.

Methods

: Our study utilized a large commercially available database. Inclusion criteria identified adult patients ( >18 years old) diagnosed with SJS/TENS between 2002 and 2022, who were treated with antibiotics within 2 weeks of diagnosis, and who subsequently went on to develop Clostridium Difficile enterocolitis within 6 months. We compared our cohort to a control group which did not receive antibiotics and propensity score matched them for age, sex, race, HIV status, cancer, transplant status, and severe sepsis and SIRS and analyzed the risk of developing C. Difficile enterocolitis.

Results

There were 4,792 SJS/TENS patients who did not receive antibiotics and 5,652 who did. Our matched cohorts contained 4,595 patients. The relative risk of mortality between our cohorts was 4.962 (RR: 2.562, CI 95% 2.125-3.088; p< 0.0001). SJS/TENS who received antibiotics developed C. Difficile 68/4595 vs 30/495 and had a relative risk of 0.827% (RR: 2.267, 1.478-3.476, CI 95%; p< 0.0001). Therefore, an SJS/TENS patient incurred a 2.267 times higher risk of developing C. difficile enterocolitis after receiving antibiotics.

Conclusions

While causality cannot be affirmed with retrospective data, our findings do suggest that patients with SJS/TENS due to the statistically significant risk of C. Difficile enterocolitis development. However, the overall absolute risk of C. difficile enterocolitis remains disproportionately low in this population that warrants further exploration.

Applicability of Research to Practice

SJS/TENS patients are difficult to develop evidence-based treatment plans for because of their rarity and the multitude of conflicting small cohort studies available in the literature. Our study utilizes a large database to more robustly suggest that clinicians should be cautious about administering antibiotics to patients diagnosed with SJS/TENS.
295 Topical Tranexamic Acid in Burn Surgery – A Randomized Controlled Trial
Authors: Colclough Robert Norheim , Almeland Stian Kreken , Ausen Kjersti , Brekke Ragnvald Ljones L , Nordgaard Håvard , Pleym Hilde , Spigset Olav
Published: August 2023

Introduction

Early excision and grafting of large burn wounds can result in considerable bleeding. Systemic use of tranexamic acid (TXA) generally reduces surgical bleeding by 30-40%, but its safety in burn surgery has not been studied. Topical use may provide a sufficient wound concentration with negligible risk of systemic adverse events. However, it is unclear whether topical use may delay wound re-epithelialization. This pilot double-blinded randomized controlled trial aimed to evaluate the therapeutic potential of topical TXA for reducing blood loss and the effect on wound re-epithelialization in burn surgery.

Methods

Between Jan 2021 – April 2022, burn patients at a single national burn center who needed at least two separate donor sites for split-thickness skin grafting were included. In total, 36 wound pairs in similar anatomical areas were made in 23 patients. Donor sites were infiltrated with tumescence containing epinephrine before harvesting. Paired wounds were randomized to topical application of standard epinephrine solution, with or without added TXA 25 mg/ml, before coverage with vaseline and dry gauze. Endpoints were time to re-epithelialization and surrogate bleeding estimates defined as net weight gain of dressings per cm2 wound area, bloodstain area per wound area, and visual rating of the amount of blood in dressings on the first postoperative day.

Results

There was no difference in healing time between wounds. The results trended towards less increase in dressing weight gain per cm2 of wound area in the TXA group, though not significant (p=0.12). However, when dividing the results in two at the median bleeding volume, there was a significant reduction in bleeding in the high-bleed group (p=0.012). Similar observations were made for the other two bleeding endpoints, but the differences did not reach statistical significance.

Conclusions

Moistening a superficial wound surface with TXA 25 mg/ml does not impair wound re-epithelialization. Topical TXA may reduce bleeding from graft donor sites with low risk of systemic complications.

Applicability of Research to Practice

This pilot study suggests that topical TXA is of value in reducing bleeding in burn surgery without delaying donor site healing. The effect may be larger in wounds not prepared with epinephrine infiltration. More research is warranted regarding the optimal mode of topical drug delivery and systemic concentrations after topical application in burns. Furthermore, it remains to investigate whether topical TXA affects graft take.
297 Pressure in the Operating Room (OR): another Possible Contributor to Hospital Acquired Pressure Injuries (HAPIs)
Authors: Milazzo Thomas , Cartotto Robert , Loo Hannah , Rogers Alan D
Published: August 2023

Introduction

Burn patients are at risk for HAPIs. An unexamined factor that may contribute to HAPI development is the effect of pressure from the OR table. Burn patients often require multiple prolonged surgical procedures. The purpose of this study was to measure pressure on the buttocks and sacral area during burn OR procedures under general anesthesia (GA). This has not been previously assessed in the burn literature.

Methods

Prospective study of consecutive adult burn patients admitted to an ABA-verified burn center who required surgery under GA between 06/01/22 and 08/12/22. We studied only cases that were supine, including those with both legs down (BLD), one leg suspended (one leg up: 1LU) or both legs suspended (two legs up: 2LU). Pressures on the buttocks and sacral area were measured using a commercial sensor mat which sent continuous real-time pressure measurements wirelessly to a laptop computer. Thousands of individual pressure measurements were integrated and organized to show average and peak pressures over repetitive 10-minute intervals during the entire operative procedure. Also, a continuous visual color-coded map of the sacral and buttock areas showing high ( >75 mmHg-red), medium (10-75 mmHg -yellow) and low ( < 10 mmHg -blue/green) pressures was created for each procedure. Results are shown as mean ± SD.

Results

Recordings were completed in 41 procedures (35 acute excision & grafting, 5 reconstructive, 1 tracheostomy) among 28 patients ( 48 ± 17 yrs, % TBSA burn 19 ± 17, weight 80 ± 20 kg, BMI 27 ± 6). During BLD, over 125 ± 81 min, the average pressure (Pave) was 47 ± 7 mmHg and peak pressure (Ppeak) reached 82 ± 23 mmHg. During isolated 1LU periods, Pave was 53 ± 9 mmHg over 74 ± 58 minutes with a Ppeak of 93 ± 23 mmHg and during isolated 2LU, Pave and Ppeak were respectively 55 ± 10 mmHg over 78 ± 40 min and 98 ± 23 mmHg. Both Pave and Ppeak increased significantly from procedures with BLD to 1LU to 2LU (p< 0.001). Pave crept steadily upwards during both BLD and 1LU or 2LU procedures (Figure). We observed that Pave had a positive relationship with weight, regardless of operative position.

Conclusions

Prolonged moderate to high pressures are exerted on the sacral and buttock areas, especially with one or both legs suspended, during burn surgery. These novel observations suggest that pressure from the OR table could contribute to HAPI development.

Applicability of Research to Practice

With this risk identified, interventions to lower or interrupt pressure exposure during burn surgery should be identified next.
301 Youtube as a Source of Information for Skin Graft Procedures
Authors: Torres Grant B , Branski Ludwik K , Brondeel Kimberley C , Kamma Sai , Nus Bradley , Sledge Trey , Wu Kylie
Published: August 2023

Introduction

YouTube, one of the most popular sites on the internet, has become a primary source of healthcare information for patients. Although YouTube videos about skin graft procedures have accrued millions of views, there lacks a publication defining their educational quality. With recent articles revealing the misleading nature of healthcare information on YouTube, this study aims to evaluate the quality of videos pertaining to skin graft procedures.

Methods

YouTube was searched for various terms such as “Skin Graft Procedures” and “Skin Graft Surgery” with content stratified by total view count. After applying exclusion criteria, the top 84 most viewed videos were assessed, 24 of which implicating burn injuries. Four independent reviewers rated the material with the Global Quality Scale (GQS; 5 = highest quality, 1 = lowest quality) to judge educational value based upon factors such as publisher credibility, delivery of accurate information, and presence of biases. Viewership, source, educational modality, and date of upload were also collected from each video and compiled for further analysis.

Results

The mean GQS score of all videos was 2.60. Videos uploaded by physicians (80.1%) had a significantly higher average GQS score than those not uploaded by physicians (p < 0.01). When grouped by modality, patient-friendly delivery methods (animations, news reports, etc.) contained the lowest quality information, while physician-led presentations provided the highest educational value (p < 0.01). Assessment of videos split into cohorts based on viewership noted a significantly higher GQS in videos with lower view counts (p < 0.05). There was no correlation between upload date and quality.

Conclusions

Overall, skin graft videos found on YouTube provide low quality information. This is especially true for the “popular” videos, where an inverse correlation was found between view count and GQS score. Likewise, patient-friendly videos received the lowest GQS scores amongst the cohorts. Alternatively, videos performed by physicians, most notably physician-led presentations, significantly improved the educational quality of videos pertaining to skin graft procedures. As such, further analysis of skin graft videos found on YouTube could poise physician involvement in producing videos of high educational quality while potentially bridging the gap spanning quality content and video popularity.

Applicability of Research to Practice

With online platforms such as YouTube evolving into conventional sources of healthcare information, physicians must act to improve the quality of online content to better guide patients in navigating treatment options and making healthcare decisions.
Drug approval delays in hematologic malignancies between Europe and the US and between Japan and the US: a clinical perspective
Authors: Matsuda Kensuke , Nagai Sumimasa , Sugimoto Koichi
Published: August 2023

Objective

Since novel therapeutic agents for malignancies are developed rapidly mainly in the US, the interval of approval timing between the US and other countries is an important issue. Among them, drugs for hematologic malignancies tended to have a particularly long delays in Japan, but its characteristics have not been fully understood. This study assessed the approval delays in drugs for hematologic malignancies in Japan compared with that in Europe.

Methods

Using the public database of Europe, Japan and the US, we analyzed the differences in drug approval delays between Europe and the US and between Japan and US according to disease. New molecular entity drugs for hematologic malignancies that were already approved in the US and were approved from April 2010 to March 2022 in Europe or Japan were identified.

Results

The results showed the longer drug approval delays in Japan compared with that in Europe (29 vs. 9.4 months, median), presumably due to the lower proportion of participation in global clinical trials (37 vs. 94%). Notably, the participation rate in global clinical trials varied widely by disease in Japan, resulting in a greater difference in drug approval delays by disease. In contrast, when focusing on early phase trials, Japanese participation was uniformly very limited regardless of the disease.

Conclusions

The current study provided data that can be used as a basis for discussion on how to improve drug approval delays in drugs for hematologic malignancies.
Slicing Through the Layers of Pediatric Unintentional Injury With the Swiss Cheese Model: A Topical Review
Authors: Pugliese Brian J , Barton Benjamin K
Published: August 2023

Pediatric unintentional injury significantly burdens children, families, and society. Behavioral researchers have examined the problem for decades, identifying many risk factors and greatly enhancing knowledge of the injury antecedent process. Approaches using theories and models to guide inquiry into etiology and prevention are still needed. We offer an approach borrowed from the field of human factors to enhance understanding and prevention. We focus our exploration on an error modeling and accident investigation tool called the Swiss Cheese Model. We first introduce the basic elements of the model. Next, we apply error modeling concepts to example scenarios drawn from real unintentional incidents and discuss the implications for understanding etiology and prevention. Finally, potential future directions are discussed to illustrate paths for the advancement of injury etiology and prevention.
Long-term outcomes of whole-pelvis radiation therapy using volumetric modulated arc therapy for high-risk prostate cancer
Authors: Takemura Reiko , Ishii Kentaro , Hosokawa Yukinari , Morimoto Hideyuki , Matsuda Shogo , Ogino Ryo , Shibuya Keiko
Published: August 2023

This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78 Gy in 39 fractions to the prostate and 46.8 Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85–108) months. The median age was 72 (IQR = 67–75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6–56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.
Corporate disclosure, ESG and green fintech in the energy industry
Authors: Lee Joseph , Serafin Alberto Mattia , Courteau Clément
Published: August 2023

This article examines the crucial role of non-financial disclosure in achieving environmental sustainability across economies and legal systems, focusing on the Corporate Sustainability Reporting Directive (CSRD). It scrutinizes the efficacy of current reporting regimes and their capacity to capture the distinct nature of company activities. The study underscores the importance of flexibility tools in customizing disclosure obligations to individual companies, striking a balance between competing informational interests and adhering to principles of reasonableness and proportionality. It highlights the double materiality criteria and the ‘comply or explain’ mechanism as pivotal in tailoring reporting duties. Moreover, the article argues for better integration of fintech and greentech to modernize the disclosure obligation, making the disclosed information digitally tagged and machine-readable. It also investigates the potential for technology to ease the existing negative or preventive approach characterizing enforcement mechanisms, possibly setting the incentive for information disclosure. The conclusions encompass policy recommendations aiming to harness the opportunities offered by technology in the context of CSRD, aligning the reporting duties with contemporary needs.
Triose phosphate utilization in leaves is modulated by whole-plant sink–source ratios and nitrogen budgets in rice
Authors: Zhou Zhenxiang , Zhang Zichang , van der Putten Peter E L , Fabre Denis , Dingkuhn Michael , Struik Paul C , Yin Xinyou
Published: August 2023

Triose phosphate utilization (TPU) is a biochemical process indicating carbon sink–source (im)balance within leaves. When TPU limits leaf photosynthesis, photorespiration-associated amino acid exports probably provide an additional carbon outlet and increase leaf CO2 uptake. However, whether TPU is modulated by whole-plant sink–source relations and nitrogen (N) budgets remains unclear. We address this question by model analyses of gas-exchange data measured on leaves at three growth stages of rice plants grown at two N levels. Sink–source ratio was manipulated by panicle pruning, by using yellower-leaf variant genotypes, and by measuring photosynthesis on adaxial and abaxial leaf sides. Across all these treatments, higher leaf N content resulted in the occurrence of TPU limitation at lower intercellular CO2 concentrations. Photorespiration-associated amino acid export was greater in high-N leaves, but was smaller in yellower-leaf genotypes, panicle-pruned plants, and for abaxial measurement. The feedback inhibition of panicle pruning on rates of TPU was not always observed, presumably because panicle pruning blocked N remobilization from leaves to grains and the increased leaf N content masked feedback inhibition. The leaf-level TPU limitation was thus modulated by whole-plant sink–source relations and N budgets during rice grain filling, suggesting a close link between within-leaf and whole-plant sink limitations.
Effects of film-formingPichiaandCandidayeasts on cider and wine as post-fermentation contaminants
Authors: Lorenzini Marilinda , Cappello Maria Stella , Green Anthony , Zapparoli Giacomo
Published: August 2023

Film-forming yeasts are potential sources of defects in alcoholic beverages. The aim of this study is to assess the growth capacity of Pichia and Candida film-forming yeasts in cider and wine and the effects on their chemical composition. Cider, partially and fully fermented wine were inoculated with strains of C. californica, P. fermentans, P. kluyveri, P. kudriavzevii, P. manshurica, and P. membranifaciens to simulate a post-fermentative contamination. The former three species grew only in cider. Pichia manshurica and P. kudriavzevii displayed high viability in wine up to 13.18% (v v–1) ethanol. Significant changes in odour-active molecules from different chemical groups were observed in cider and wine in the inoculated samples, compared to the non-inoculated ones. Cider is more susceptible to contamination by all of the species tested, due to its low alcohol content, while P. membranifaciens, P. manshurica, and P. kudriavzevii are additionally potential spoilage agents of wine. This study highlights the risk of cider and wine contamination by film-forming yeasts. Their impact on aroma profiles depends on their ability to grow and their metabolism. This study contributes to an understanding of the possible physiological and metabolic mechanisms responsible for film formation and chemical changes in alcoholic beverages.
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

While 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

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 < .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 < .001). Of participants receiving LSIs in the year preceding BVNA, 81.2% fewer received LSI(s) in the year post-BVNA (P < .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

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 < .05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (P < .05). Bootstrapped mediation analyses revealed significant (P < .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 < .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

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.
Effect of Cucurbit Host, Production Region, and Season on the Population Structure of Pseudoperonospora cubensis in Florida
Authors: Shirley Andrew M. , Vallad Gary E. , Quesada-Ocampo Lina , Dufault Nicholas , Raid Richard
Published: August 2023

Pseudoperonospora cubensis, the causal agent of Cucurbit downy mildew (CDM), is one of the most important diseases affecting cucurbit production in the United States. This disease is especially damaging to Florida production areas, as the state is a top producer of many cucurbit species. In addition, winter production in central and south Florida likely serves as a likely source of P. cubensis inoculum for spring and summer cucurbit production throughout the eastern United States, where CDM is unable to overwinter in the absence of a living host. Over 2 years (2017 and 2018) and four seasons (spring 2017, spring 2018, fall 2017, and fall 2018), 274 P. cubensis isolates were collected from cucurbit hosts at production sites in south, central, and north Florida. The isolates were analyzed with 10 simple sequence repeat (SSR) markers to establish population structure and genetic diversity and further assigned to a clade based on a qPCR assay. Results of population structure and genetic diversity analyses differentiated isolates based on cucurbit host and clade (1 or 2). Of the isolates assigned to clade by qPCR, butternut squash, watermelon, and zucchini were dominated by clade 1 isolates, whereas cucumber isolates were split 34 and 59% between clades 1 and 2, respectively. Clade assignments agreed with isolate clustering observed within discriminant analysis of principal components (DAPC) based on SSR markers, although watermelon isolates formed a group distinct from the other clade 1 isolates. For seasonal collections from cucumber at each location, isolates were typically skewed to one clade or the other and varied across locations and seasons within each year of the study. This variable population structure of cucumber isolates could have consequences for regional disease management. This is the first study to characterize P. cubensis populations in Florida and evaluate the effect of cucurbit host and clade-type on isolate diversity and population structure, with implications for CDM management in Florida and other United States cucurbit production areas.
Intimate partner violence
Authors: Alhusen Jeanne , McDonald Maria , Emery Bethany
Published: August 2023

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

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.
Understanding the Interplay between Iron Deficiency and Congestive Heart Failure: A comprehensive review
Authors: Kotak Kopal , Aggarwal Kanishk , Garg Shreya , Gupta Vasu , Anamika FNU , Jain Rohit
Published: August 2023

Iron is an essential micronutrient for abounding physiological processes in the body, and its deficiency can be caused by various factors, such as low iron intake due to economic difficulties or loss of appetite, decreased iron absorption due to gastrointestinal issues, or increased iron loss due to hemorrhages or proteinuria. Iron deficiency is a prevalent issue among heart failure (HF) patients and is a significant contributor to anemia, affecting 30–50% of patients regardless of their gender, ethnicity, or left ventricular ejection fraction. Individuals with HF have high levels of pro-inflammatory cytokines, which can inhibit erythropoiesis by degrading the membrane iron exporter ferroportin, mediated by an increased release of hepcidin. In addition, elevated sympathetic and renin-angiotensin-aldosterone system activity retains salt and water, resulting in high cardiac output HF in people with normal left ventricular function. This review provides an overview of iron deficiency and HF.
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

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

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.