bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA-B*57:01-dependent intracellular stress in keratinocytes triggers dermal hypersensitivity reactions to abacavir
Authors: Kazaoka Akira , Fujimori Sota , Yamada Yushiro , Shirayanagi Tomohiro , Gao Yuying , Kuwahara Saki , Sakamoto Naoki , Susukida Takeshi , Aoki Shigeki , Ito Kousei
Published: April 2024

Specific human leukocyte antigen (HLA) polymorphisms combined with certain drug administration strongly correlate with skin eruption. Abacavir hypersensitivity (AHS), which is strongly associated with HLA-B*57:01, is one of the most representative examples. Conventionally, HLA transmits immunological signals via interactions with T cell receptors on the cell surface. This study focused on HLA-mediated intracellular reactions in keratinocytes that might determine the onset of skin immunotoxicity by drug treatments. Abacavir exposure resulted in keratinocytes expressing HLA-B*57:01 exhibiting endoplasmic reticulum (ER) stress responses, such as immediate calcium release into the cytosol and enhanced HSP70 expression. In contrast, keratinocytes expressing HLA-B*57:03 (closely related to HLA-B*57:01) did not show these changes. This indicated that HLA-B*57:01 has a specific intracellular response to abacavir in keratinocytes in the absence of lymphocytes. Furthermore, abacavir exposure in HLA-B*57:01-expressing keratinocytes elevated the expression of cytokines/chemokines such as interferon-γ, interleukin-1β, and CCL27, and induced T lymphoblast migration. These effects were suppressed by ER stress relief using 4-phenylbutyrate (4-PB). HLA-B*57:01-transgenic mice also exhibited ER stress in epidermal areas following abacavir administration, and abacavir-induced skin toxicity was attenuated by the administration of 4-PB. Moreover, abacavir bound to HLA-B*57:01 within cells and its exposure led to HLA-B*57:01 protein aggregation and interaction with molecular chaperones in the ER of keratinocytes. Our results underscore the importance of HLA-mediated intracellular stress responses in understanding the onset of HLA-B*57:01-mediated AHS. We provide the possibility that the intracellular behavior of HLA is crucial for determining the onset of drug eruptions.
Efficacy of Rehabilitative Techniques on Pain Relief in Patients With Vulvodynia: A Systematic Review and Meta-Analysis
Authors: Calafiore Dario , Marotta Nicola , Curci Claudio , Agostini Francesco , De Socio Rita Ilaria , Inzitari Maria Teresa , Ferraro Francesco , Bernetti Andrea , Ammendolia Antonio , de Sire Alessandro
Published: April 2024

Objective

Vulvodynia is a chronic clinical condition characterized by provoked or non-provoked vulvar pain for at least 3 months of unknown etiology. The onset of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, such as pelvic floor muscle and autonomic dysfunction, and interpersonal factors. A stepwise approach of pelvic floor physical therapy as medical management is suggested. In this scenario, by this meta-analysis of randomized controlled trials, we aimed to evaluate the efficacy of rehabilitation interventions in patients with vulvodynia.

Methods

On October 13, 2022, PubMed, Scopus, and Web of Science were systematically searched for randomized controlled trials that assessed the efficacy of the rehabilitative approach to pain during intercourse in patients with vulvodynia. The quality assessment was performed with the Cochrane risk-of-bias tool for randomized trials. The trial registration number is CRD42021257449. At the end of the search, 9 studies were included for a total of 332 patients. A pairwise meta-analysis was performed to highlight the efficacy of rehabilitative approaches for reducing pain during intercourse, as measured with a visual analog scale or a numerical rating scale.

Results

Meta-analysis showed that all these rehabilitative approaches had an overall effect size of −1.43 (95% CI = −2.69 to −0.17) in decreasing vulvodynia pain in terms of the visual analog scale. In the subgroup analysis, a significant effect size in acupuncture (effect size = −2.36; 95% CI = −3.83 to −0.89) and extracorporeal shockwave therapy (effect size = −2.94; 95% CI = −4.31 to −1.57; I2 = 58%) was observed. According to the Cochrane risk-of-bias tool, a low risk of bias for outcome selection in 89% of studies.

Conclusion

Findings from this meta-analysis suggested that the physical agent modalities and complementary medicine techniques in people with vulvodynia appear to be more effective than placebo, sham, or waiting list. Further evidence on physical agent modalities and complementary therapies are warranted in the future.

Impact

This was the first systematic review and meta-analysis of randomized controlled trials to provide evidence on the efficacy of rehabilitation interventions in patients with vulvodynia.
The Heterogeneous Effects of Government Spending: It’s All About Taxes
Authors: Ferriere Axelle , Navarro Gaston
Published: April 2024

Historically, large changes in U.S. government spending induced fiscal efforts that were not all alike, with some using more progressive taxes than others. We develop a heterogeneous-agent New Keynesian model to analyse how the distribution of taxes across households shapes spending multipliers. The model yields empirically realistic distributions in marginal propensities to consume and labour elasticities, which result in lower responsiveness to tax changes for higher-income earners. In turn, multipliers are larger when spending is financed with higher tax progressivity—that is, when the tax burden falls more heavily on higher-income earners. This result is historically material. We estimate that, on average, tax rates increased more for top-income than for bottom-income earners after a spending shock. Thus, the typical U.S. spending shock was financed with higher tax progressivity. We further exploit the historical variation in the financing of spending to estimate progressivity-dependent multipliers, which we find consistent with the model.
Occurrence of Stemphylium Leaf Spot Caused by Stemphylium vesicarium in Commercial Celery Production Following an Onion Rotation
Authors: Abdelrhim Abdelrazek S. , Higgins Douglas S. , Hausbeck Mary K.
Published: April 2024

In 2022, lesions were observed on the lower leaves of ‘Fandango’ celery ( Apium graveolens L.) growing in a commercial field in Hamilton, Michigan. Brown spots were observed on the leaves’ adaxial surface and border extending to the petiole. Conidia were observed on the symptomatic tissue, and 25 fungal isolates, morphologically similar to Stemphylium vesicarium, were obtained. DNA was extracted from three isolates, and three primer sets were used to amplify and sequence the internal transcribed spacer (ITS) region and partial calmodulin ( cmdA) and glyceraldehyde-3-phosphate dehydrogenase ( gapdh) genes. The obtained sequences of the three isolates had 100% pairwise identity with S. vesicarium sequences MW798751 (ITS), MK675706 ( cmdA), and OQ925923 ( gapdh). A multilocus phylogenetic analysis (neighbor-joining tree) strongly supported clustering Michigan isolates into a single clade with S. vesicarium reference sequences. Isolates recovered from celery were pathogenic to ‘CR1’, ‘Tall Utah’, and ‘Challenger’ celery and ‘Bradley’ onion. S. vesicarium isolates isolated from symptomatic onion volunteers were pathogenic to the three celery cultivars. To our knowledge, this is the first report of S. vesicarium as a pathogen on celery causing leaf spot, and volunteer onion may be a source of Stemphylium in celery fields.
Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels
Authors: Cuenca John A. , Nates Joseph L. , Laserna Andres , Heatter Alba J. , Manjappachar Nirmala , Martin Peyton , Reyes Maria P. , Hernandez Mike , Hall Jacob , Ramirez Claudia M. , de Villalobos Diego H.
Published: April 2024

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center’s ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94–2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.
Nutrition knowledge, attitudes, and perceptions of Greek menopausal women
Authors: Papadima Evgenia-Ioanna , Vassilakou Tonia , Grigoriadis Themos , Boutsiadis Anastasios , Ivanidou Sofia , Kalampalikis Andreas , Michala Lina
Published: April 2024

Objective

Nutritional guidelines for postmenopausal women differ. This study aimed to assess postmenopausal women's knowledge, beliefs, and practices regarding nutrition during menopause and their dietary habits.

Methods

This cross-sectional study was conducted in a menopause clinic, and data from 105 women were analyzed. A nutrition knowledge, attitudes, and perceptions (KAP) questionnaire was designed, structured, and piloted before implementation, based on the Hellenic dietary guidelines. International Physical Activity Questionnaire—Greek version, MedDietScore, and Menopause-specific Quality of Life questionnaires were administered.

Results

The mean ± SD age of the women was 56.9 ± 4.6 years. The mean ± SD KAP score was 12.2 ± 3.5. Those who lived in rural areas had lower KAP scores than those who lived in urban areas (P = 0.004). Of all the women, 74.5% knew the Mediterranean diet pyramid, whereas 9.8% knew the Hellenic dietary guidelines. Women who had read the guidelines showed better knowledge of Mediterranean diet food groups (Pearson, 0.309; P = 0.039). Knowledge of dairy services was correlated with consumption of dairy products (P = 0.002). Furthermore, 76.4% were willing to participate in nutrition education programs. The International Physical Activity Questionnaire score was positively correlated with years of smoking (P = 0.002). Physical activity correlated with adherence to the Mediterranean diet (P = 0.044).

Conclusions

The majority of postmenopausal Greek women in this study were unaware of the Hellenic dietary guidelines. In general, women's knowledge of nutrition during menopause was moderate. Greek postmenopausal women are willing to participate in nutrition education programs, which should raise awareness of healthy lifestyles through nutrition, exercise, and smoking cessation.
Totally laparoscopic management of a giant sigmoid colon diverticulum: Case report and review of literature
Authors: Taranto Maria Laura , Taranto Domenico , Sessa Gabriella , Pizzuti Laura Micol , Mainenti Pier Paolo , Mazzarella Nicola , Pagano Gianluca , Porcelli Alberto , Corcione Francesco
Published: April 2024

The giant diverticulum of the sigmoid colon is a rare clinical condition characterized by a high risk of complications. Its etiology is multifactorial, with longstanding diverticular disease and motor dysfunction of the colon as risk factors. Even though its diagnosis could be challenging, clinicians can rely on barium enemas revealing the characteristic findings of a large, air-filled sac adjacent to the colon on a computed tomography scan and colonoscopy. The use of these tools aids in ruling out alternative diagnoses and confirming the presence of a diverticulum. Timely surgical management is essential, also in asymptomatic fit-for-surgery patients, to prevent potential complications.
Emerging Clinical Features of Acute Mastoiditis in Israel: A Registry Based Cohort
Authors: Samuel Orit , Saliba Walid , Stein Nili , Shiner Yotam , Cohen-Kerem Raanan
Published: April 2024

Background and Objectives:

Acute mastoiditis (AM) is a severe infection in the young population, with possible life-threatening complications. This study aimed to characterize AM presentation, symptoms and signs, complications, and management, over a period of 10 years.

Methods:

This large-scale population-based cohort studied “Clalit Health Care” records, to include patients <18 years diagnosed with AM, hospitalized between the years 2008–2018. After validation, we investigated clinical symptoms and signs, pneumococcal vaccination status, complications, laboratory and microbiological parameters, imaging, antibiotic treatment and surgical interventions.

Results:

AM was diagnosed in 1189 patients, mean age of 2.71 years and 591 (49.71%) were female. Most presented with protrusion of pinna (83.1%), retro auricular redness (73.5%) and fever (71.8%). Patients <2 years of age had more symptoms (3.8 ± 1.4, opposed to 3.6 ± 1.5, P = 0.006) and showed higher white blood cell count and C-reactive protein values. Local and intracranial complications occurred in 233 (20.8%) and 75 (6.5%) patients, respectively. Complications were associated with increased white blood cell count and C-reactive protein and related to bacterial type, specifically Fusobacterium necrophorum (P < 0.0001), for which 50% had an intracranial complication. Between the years 2008–2018, Streptococcus pneumoniae-positive cultures decreased (30.9% to 10.3%, P > 0.0001) as opposed to group-A Streptococcus (10.9% to 30.9%, P = 0.002).

Conclusions:

This study shows a difference in AM appearance in the <2 years population and the association between white blood cell count, C-reactive protein and microbiology results with the occurrence of a complication. This may play a role in the management process, such as imaging and intervention needs. Although performed during the pneumococcal vaccine era, the disease microbiology was shown to change significantly throughout the study.
Is beauty worth the risk? Self-confidence is the key motivating factor driving tanning bed use among undergraduate students at South Dakota universities
Authors: Newton Jazmin , Ochoa Lauren , Reinschmidt Aly , Vassar John , Wellman Allen , Vargas Minga , Kenyon DenYelle , Frohm Marcus
Published: April 2024

Background:

Exposure to ultraviolet radiation is a leading risk factor for developing all types of skin cancer. In the United States, an estimated 7.8 million young adults engage in indoor tanning.

Objective:

Here, it is hypothesized that certain populations of students at undergraduate universities, namely sorority members, have a greater frequency of tanning bed usage than other groups of students and that regardless of sorority status, the most important motivating factor will be the intent to enhance one’s appearance.

Methods:

Undergraduate students at 2 state-funded universities were recruited for participation in this institutional review board-exempt survey via distribution to e-mail addresses and social media accounts affiliated with student organizations/clubs.

Results:

Among all respondents, the most common motivating factors for tanning bed use were the perception of improved self-appearance and boosted self-confidence. Female sorority members were more likely to use tanning beds and also more likely to report being motivated by enhanced appearance and self-confidence, than their female counterparts who were not sorority members.

Limitations:

The sample size (n = 321) and population of this study allows data to only be generalizable to surrounding states with similar demographics. The findings of this study are subject to recall bias as the data is self-reported.

Conclusion:

Tanning bed use remains a popular practice among young people. Understanding motivations for tanning bed use among populations at increased risk of partaking in this behavior allows for educating these groups on the risks associated with ultraviolet radiation exposure. It is crucial that providers continue to promote skin health and take steps to dissuade detrimental practices and possible habit-forming behaviors at the individual and state levels.
Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss
Authors: Harrison Megan S. , Driscoll Brittany G. , Farnsworth Jason , Hinton Ashley , Peppi Marcello , McLean Will , Parham Kourosh
Published: April 2024

Hypothesis

Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss.

Background

Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model.

Methods

Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure. Serum prestin levels were quantified using automated Western, and hair cell counts were obtained.

Results

All three doses induced an N-glycosylated ~134-kDa prestin burst; however, only the 3,000 and 4,000 mg/kg resulted in robust OHC loss. Prestin levels returned to baseline where they remained up to 15 weeks in the absence of OHCs.

Conclusion

The ~134-kDa prestin burst induced after CDX administration is N-glycosylated, representing a posttranslational modification of prestin. Serum prestin seems to be a promising biomarker when using therapeutics with ototoxic properties because it is not dependent on OHC loss as a necessary event, thus affording the opportunity for early detection and intervention.
Building a Practice Ready and Resilient Nursing Workforce
Authors: Nichols Lynn Stover , Pollio E. W. , Fifolt Matthew , Shirey Maria R.
Published: April 2024

Nurse leaders depend upon resiliency skills to support their practice. It is important to provide opportunities for nursing students to learn, practice, and observe these skills, which are needed to navigate challenging work environments. This article describes the impact of a resiliency curricular component in a grant-funded BSN elective course, Concepts of Primary Care. Program evaluation was performed using a pre/posttest format and 2 surveys, the Brief Resilience Scale (BRS) and the Brief Resilience Coping Scale (BRCS). Three open-ended questions were administered upon completion of the elective course. A concurrent nested design was utilized with a thematic analysis undertaken to analyze qualitative data. Analysis of quantitative data was performed using descriptive statistics. Undergraduate BSN students showed an overall increase in resiliency (BRS: P = .112; BCRS: P = .064), and responses to open-ended questions supported the ability to apply and analyze most of the resiliency skills presented during the didactic portion of the elective course. This course promoted the development and refinement of undergraduate BSN student resilience skills. Integration of resilience content in the primary care course also supported student professional development. The addition of resiliency concepts and skills into undergraduate nursing curricula is recommended to enhance the ability of novice nurses to address work-related challenges and promote career satisfaction for the future.
Effectively and Efficiently Reengineering the Nursing Work Environment by Applying a Conceptual Framework for Nurse Retention
Authors: Lackey Sarah , Antrum Vi-Anne
Published: April 2024

The nursing shortage that is upon us is the result of a confluence of factors, some simple and some complex. Legacy solutions are not working. Recovery from the current situation involves examining and reshaping the nursing work environment. Creative and innovative solutions are being developed and tested. The call for addressing the work environment is surfacing in the literature, yet methods for doing so in an orderly, progressive manner have been elusive. To solve complex problems, structure helps lead to clear thinking. This work presents a conceptual framework for nurse retention derived from concept analysis of initiatives with empirical outcomes for intent to stay, intent to leave, turnover, and retention. It layers in 2 simple theorists and presents an intuitive, understandable model to guide strategic planning and decision making. The Framework has been used for several applications, one of which is a unit-based action planning method that is systematic, cyclic, and uses data relevant to specific unit culture. Improvements occurred in retention and engagement metrics, work effectiveness scores, and cost. Nurse managers extol the process’s simplicity and ease of use, and the role the Framework plays in shaping the way they think about nurse retention.
Rebuilding Nursing Culture Through Application of Social Identity Theory and Inclusivity in Health Care Systems
Authors: Bernard Noreen , Geiger Robin A.
Published: April 2024

This article explores leader practices for rebuilding health system nursing culture by leveraging feedback from clinical nurses and applying Social Identity Theory (SIT) and inclusivity frameworks. An enriched nursing culture is the foundation of quality patient care, and as healthcare systems evolve, it becomes increasingly essential to foster a cohesive and inclusive environment in every aspect of employment practices. Social Identity Theory, which emphasizes how individuals define their self-concept through group affiliations, offers a lens to understand the interplay of identity, values, and behavior within nursing teams. Inclusivity practices are pivotal in creating a welcoming and diverse health care workplace. By employing these approaches, health care systems can rebuild and strengthen their nursing culture, improving retention, onboarding, job satisfaction, teamwork, and enhancing the quality of care provided to patients. This article delves into practical strategies and application of SIT and inclusivity practices to restructure and revitalize nursing culture, emphasizing the positive impact on health care outcomes. An exemplar demonstrating the impact of the voice of the clinician in program development highlights the application of SIT and inclusivity to create culture. It concludes with leader practices for rebuilding nursing culture to include contingent labor as part of the care team.
A Different Mindset for a Different Culture: Sustaining the Next-Generation Workforce
Authors: Shaw Carmen
Published: April 2024

The author is a nurse executive who shares insights into why company leaders must change their mindset in how they build the next-generation nursing workforce culture. Despite the national nursing shortage crisis, nurses continue to be the most trusted profession for the 22nd consecutive year in a row. Technology advancements, generational paradigm shifts, global and domestic business transformations, diversity, equity, inclusion, and employee well-being are trends that have directly impacted the need for these changes. We know that it is not just about recruiting but also about creating a culture where the ambitions, aspirations, and perspectives of the nursing workforce are honored. There are key company strategies that matter to creating a next-generation workforce culture and are transferable to health care. Leaders must think differently about the culture they have to build in order to attract and retain the next-generational nursing and clinical workforce.
Leadership Coaching for Team Support
Authors: Martin Christina , Delehanty Maura
Published: April 2024

Self-care quickly became a buzzword for health care workers during the recent pandemic. Strategies to improve self-care and build resiliency for our first-line workers were often seen in the literature or as topics at conferences and webinars. One strategy that was missing was the importance of leaders to be self-care role models for our employees. Just as leaders need to role model the organization’s values, they also need to role model self-care so employees can follow their example and be assured that their leader views self-care as important. Leadership coaching must now include self-care as a strategy to improve not only the leader’s mental, physical, and emotional health but also the health and wellness of their team as well as the entire organization.
Thrombocytopenia and Adverse Bleeding Events in Neonatal Lumbar Punctures in the Emergency Department
Authors: Le Duyen My , Vezzetti Robert , Earp Ada , Jung Alexandra , Aufricht Graham
Published: April 2024

Objective

Lumbar punctures are performed as part of a routine evaluation of neonates with fever in the emergency department. Current recommendations regarding performing a lumbar puncture in the presence of thrombocytopenia exist for children with leukemia and other cancers; however, there are no such recommendations for the general neonatal population. This study assesses the frequency of thrombocytopenia and adverse bleeding events in neonates who undergo a lumbar puncture to determine whether a complete blood count, and specifically the platelet count, should be reviewed before performing the lumbar puncture.

Methods

This is a retrospective chart review of neonates 30 days or younger presenting to a single freestanding pediatric emergency department who received a lumbar puncture over the course of 11 years. The complete blood count was reviewed for thrombocytopenia, determined to be platelet count of less than 150,000/μL. The chart was reviewed for any documented adverse bleeding events associated with the lumbar puncture.

Results

A total population of 2145 was studied with 56 patients determined to be thrombocytopenic. Seven total bleeding events were identified: 1 in the thrombocytopenic group and 6 in the nonthrombocytopenic group. All bleeding events were deemed to be clinically significant, either resulting in prolonged hospital stay or required further workup and medical intervention. The percentage of clinically adverse bleeding events that were related to the lumbar puncture was 0 (0.0%; 95% confidence interval, 0.0%–6.4%) and 2 (0.1%; 95% confidence interval, 0.0%–0.3%) (P = 1.0) in the thrombocytopenic and nonthrombocytopenic groups, respectively.

Conclusions

Our results demonstrated a very low risk of bleeding events associated with lumbar punctures in neonates, with no increased risk in the thrombocytopenic group. As such, we conclude that waiting for the results of a complete blood count before performing the lumbar puncture in neonates without a known bleeding disorder is unnecessary.
Utility of Synovial Fluid Biomarkers for Culture-Positive Septic Arthritis in a Lyme Disease-Endemic Region
Authors: Dechnik Andzelika , Kahane Caroline G. , Nigrovic Lise E. , Lyons Todd W.
Published: April 2024

Objective

To evaluate the performance of synovial fluid biomarkers to identify children with culture-positive septic arthritis.

Methods

We identified children 6 months to 18 years old presenting to a single emergency department between 2007 and 2022 undergoing evaluation for septic arthritis defined by having a synovial fluid culture obtained. Our primary outcome was septic arthritis defined by a positive synovial fluid culture. We evaluated the ability of synovial fluid biomarkers to identify children with septic arthritis using area under the receiver operating characteristic curve (AUC) analyses. We measured the sensitivity and specificity of commonly used synovial fluid biomarkers.

Results

We included 796 children, of whom 79 (10%) had septic arthritis. Compared with synovial white blood cell count (AUC, 0.72; 95% confidence interval [CI], 0.65–0.78), absolute neutrophil count (AUC, 0.72; 95% CI, 0.66–0.79; P = 0.09), percent neutrophils (AUC, 0.66; 95% CI, 0.60–0.71; P = 0.12), and glucose (AUC, 0.78; 95% CI, 0.67–0.90; P = 0.33) performed similarly, whereas protein (AUC, 0.52; 95% CI, 0.40–0.63, P = 0.04) had lower diagnostic accuracy. Synovial fluid white blood cell count ≥50,000 cells/μL had a sensitivity of 62.0% (95% CI, 50.4%–72.7%) and a specificity of 67.0% (95% CI, 63.4%–70.4%), whereas a positive synovial fluid Gram stain had a sensitivity of 48.1% (95% CI, 36.5%–59.7%) and specificity of 99.1% (95% CI, 98.1%–99.7%) for septic arthritis.

Conclusions

None of the routinely available synovial fluid biomarkers had sufficient accuracy to be used in isolation in the identification of children with septic arthritis. New approaches including multivariate clinical prediction rules and novel biomarkers are needed.
Pediatric Epistaxis—Effectiveness of Conservative Management
Authors: Hadar Ayalon , Peleg Uri , Ghantous Jameel , Tarnovsky Yehuda , Cohen Adiel , Sichel Jean-Yves , Attal Pierre
Published: April 2024

Objectives

Epistaxis is an emergency medical condition that sometimes requires admission to the emergency department. Pediatric epistaxis differs from epistaxis in the older population in terms of etiology, severity, and management. Our objective was to identify the distinctive features of pediatric epistaxis and determine the appropriate management.

Methods

This was a retrospective study of 231 medical records of children (<18 years old) with epistaxis of a total of 1171 cases in the general population who presented to our medical center's emergency department between 2013 and 2018.

Results

Among 231 admissions, 10 children (4.3%) presented more than once. Male patients accounted for the majority of cases (64.5%), and the average age was 9.4 years. Two children were treated with aspirin because of cardiac valve disease. Anterior bleeding was detected in 101 cases (43.7%), whereas posterior origin was observed in 8 cases (3.5%). In 122 cases (52.8%), there was no active bleeding observed. Nose injury was the cause of epistaxis in 24 cases (10.4%), and 16 admissions (6.9%) followed nasal surgical interventions. Nineteen children (8%) had abnormal coagulation tests, and 7 patients (3%) received blood transfusions. Chemical cauterization was performed in 89 cases (39.3%), and anterior packing was needed in only 9 cases (3.9%). Nine children required hospitalization (3.9%), and 2 needed surgical intervention to control bleeding. Compared with the adult population, there were significantly fewer cases of active bleeding, recurrent epistaxis, anterior packing, or need for hospitalization in the pediatric population.

Conclusions

Epistaxis is significantly less severe in the pediatric population, with only a few cases requiring major intervention. Endoscopic examination of the entire nasal cavity and routine coagulation tests are not mandatory unless there is a history of recurrent epistaxis, known coagulopathy, antiplatelet/anticoagulation therapy, or a suspicion of juvenile idiopathic angiofibroma. We suggest using absorbable packs, which offer advantages over cauterization or nonabsorbable packs.
Management of Mandibular Condylar Sagittal Fracture Accompanied by Lateral Condylar Crest Defect
Authors: Wu Benxing , Lin Yuxin , Lv Kun
Published: April 2024

Background:

The sagittal fracture of the mandibular condyle can be fixed with absorbable long screws. Absorbable long screws are generally inserted from the lateral crest of the condyle and are as close as possible to the medial pole of the condyle to obtain sufficient retention force. However, in clinical practice, patients with locally comminuted condylar fractures and partial defects in the lateral crest are often encountered. We validated the use of absorbable plates and long screws to fix mandibular condylar fractures with lateral crest defects, and postoperative follow-up showed good results.

Methods:

The preoperative design indicated that if conventional long screws were used, more soft tissue need to be pulled downward to achieve the appropriate drilling angle. If an absorbable plate was used, the degree of downward pulling of soft tissue was smaller, which can better protect the parotid gland tissue and facial nerve. The surgery was performed according to the preoperative design, using an absorbable plate scheme.

Results and Discussion:

Postoperative CT confirmed a stable anatomical reduction of condyle. Four-month follow-up showed that the patient's facial shape, occlusion, and mouth opening were all good. Follow-up CT showed good fracture healing. It is feasible to use absorbable plates and long absorbable screws to fix mandibular condylar sagittal fracture accompanied by lateral condylar crest defect.
Analysis of the Correlation Between Dynamic Characteristics and Symptoms of Gastroesophageal Reflux Disease
Authors: Tian Yan , Zhang Weihao , Zhang Tingting , Liu Lan , Guo Jianqiang
Published: April 2024

Objective:

To investigate the esophageal motility characteristics of gastroesophageal reflux disease (GERD) and their relationship with symptoms.

Patients and Methods:

We examined 101 patients diagnosed with GERD by endoscopy and divided them into 3 groups as follows: nonerosive reflux disease (NERD), reflux esophagitis, and Barrett esophagus. Esophageal high-resolution manometry and the GERD Questionnaire were used to investigate the characteristics of esophageal dynamics and symptoms. In addition, the reflux symptom index was completed and the patients were divided into 7 groups according to symptoms. We then determined the correlation between dynamic esophageal characteristics and clinical symptoms.

Results:

Upper (UES) and lower (LES) esophageal sphincter pressures and the 4-second integrated relaxation pressure in the RE group were lower than those in the NERD group. The 4-second integrated relaxation pressure in the Barrett esophagus group was also lower than that in the NERD group. In the analysis of extraesophageal symptoms, high-resolution manometry showed significant differences in UES pressures among all groups. Further subgroup analysis showed that compared with the group without extraesophageal symptoms, the UES pressure of the groups with pharyngeal foreign body sensation, throat clearing, and multiple extraesophageal symptoms was lower.

Conclusions:

As GERD severity increases, motor dysfunction of the LES and esophageal body gradually worsens, and the LES plays an important role in GERD development. Decreased UES pressure plays an important role in the occurrence of extraesophageal symptoms, which is more noticeable in patients with pharyngeal foreign body sensation and throat clearing.
Prophylactic slowly resorbable mesh in midline laparotomy to limit incisional hernia incidence: the prospective ‘Mesh Augmented Reinforcement of Abdominal Wall Suture Line (MARS)’ cohort study protocol
Authors: Van Den Dop Louis Matthijs , Molina-Villar Jose M. , Mäkäräinen Elisa , Torkington Jared , Weyhe Dirk , Koncar Igor , Lange Johan F.
Published: April 2024

Background:

Incisional hernia (IH) after abdominal surgery is a frequent surgical complication. Risk factors associated with IH are midline incisions, patients with an abdominal aneurysm of the aorta, and high BMI. Preventive measures include the use of the small-bites suture technique and/or placing a prophylactic mesh for reinforcement of the midline closure. Although recommended for high-risk patients, many surgeons are still reluctant to place a prophylactic mesh due to related complications. To counter these concerns, new synthetic resorbable meshes are being developed, such as the Deternia Self-Gripping Resorbable Mesh (“investigational device”). However, the effectiveness of this mesh in IH prevention has not been proved.

Methods:

The Mesh Augmented Reinforcement of Abdominal Wall Suture Line (MARS) study is a European, multicentre, prospective, single-arm study. A total of 120 patients scheduled for elective midline laparotomy, and for that reason at risk of developing IH, will be recruited in ~12 sites after informed consent. The sample size was estimated based on greater than 80% power, two-sided alpha of 0.05, an expected 12 month IH rate of 8% and a predefined performance goal of 18% (10% clinical margin). Midline incisions will be closed by the small bites closure technique with a minimum 4:1 suture-to-wound length ratio and reinforced by mesh placement in the retrorectus position. The primary outcome will be IH occurrence at 12-month postoperatively, evaluated both clinically and by ultrasound. Secondary outcomes will include mesh-related and postoperative complications, surgical characteristics, IH incidence at 2 and 3 years after surgery, and quality of life.

Discussion:

Currently, no conclusive evidence is available for synthetic resorbable meshes in a prophylactic setting to prevent IH. The MARS study will be the first prospective cohort study to investigate resorbable synthetic meshes and small bites closure to reduce IH incidence.
Use of In-Training Examination Scores as a Fellowship Candidate Evaluation Metric: Time for a Change
Authors: Hong Christopher X. , Russell Colin B. , Southworth Elizabeth A. , Fairchild Pamela S.
Published: April 2024

In the field of obstetrics and gynecology (OB/GYN), the Council on Resident Education in Obstetrics and Gynecology (CREOG) administers an annual in-training examination to all OB/GYN residents as a formative educational tool for assessing medical knowledge and promoting self-improvement. Although the CREOG examination is not designed or intended for knowledge certification, many OB/GYN subspecialty fellowship programs request and use CREOG examination scores as a metric to evaluate fellowship candidates. Among the 57 gynecology-based urogynecology fellowship programs, 30 programs (53%) request CREOG examination scores to be submitted by candidates, as of March 2023. Although the use of CREOG examination scores as an evaluation metric may constitute a minor component within the fellowship match process, this practice fundamentally contradicts the intended purpose of the examination as an educational self-assessment. In addition, it introduces the potential for bias in fellowship recruitment, lacks psychometric validity in predicting specialty board examination failure, and shifts the CREOG examination from its original intention as low-stakes self-assessment into a high-stakes examination akin to a certification examination. For these reasons, we call upon the urogynecology community to prioritize the educational mission of the CREOG examination and reconsider the practice of requesting or using CREOG examination scores in the fellowship match progress.
Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment
Authors: Jung Na-Yeon , Je Yuri , Ham Hong-Gi , Park Yu Hyun , Kim Tae-Yun , Go Min-su , Lee Hye-In , Kim Da Eun , Lee Myung Jun , Seo Sang Won , Kim Eun-Joo
Published: April 2024

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.
New knowledge on anti-IgLON5 disease
Authors: Gaig Carles , Sabater Lidia
Published: April 2024

Purpose of review

Anti-IgLON5 disease is characterized by a distinctive sleep disorder, associated with a heterogeneous spectrum of neurological symptoms. Initial autopsies showed a novel neuronal tauopathy predominantly located in the tegmentum of the brainstem. Recently, new diagnostic red flags, biomarkers predictors of response to immunotherapy, and novel insights into the autoimmune pathogenesis of the disease have been reported.

Recent findings

Patients with diagnosis of neurodegenerative dementia, progressive supranuclear palsy (PSP) or with motor-neuron disease (MND)-like syndrome have been reported to have IgLON5 antibodies, which are the hallmark of anti-IgLON5 disease. Second, low levels of neurofilament light chain in serum and cerebrospinal fluid of patients at disease onset could be a predictor of immunotherapy response. Recent neuropathological studies indicate that the neuronal tau deposits occur late in the course of the disease. Moreover, IgLON5 antibodies induce cytoskeletal changes in cultured hippocampal neurons suggesting that the tauopathy could be secondary of the IgLON5 antibody effects.

Anti-IgLON5 disease can mimic and should be considered in atypical presentations of MND, neurodegenerative dementia and PSP. Neurofilament light chain levels seem promising biomarker for disease prognosis. Finally, the neuropathological and in vitro experimental studies strengthen the autoimmune hypothesis of the disease.
Gaps in the wall of a perivascular space act as valves to produce a directed flow of cerebrospinal fluid: a hoop-stress model
Authors: Gan Yiming , Thomas John H. , Kelley Douglas H.
Published: April 2024

The flow of cerebrospinal fluid (CSF) along perivascular spaces (PVSs) is an important part of the brain’s system for clearing metabolic waste. Astrocyte endfeet bound the PVSs of penetrating arteries, separating them from brain extracellular space. Gaps between astrocyte endfeet might provide a low-resistance pathway for fluid transport across the wall. Recent studies suggest that the astrocyte endfeet function as valves that rectify the CSF flow, producing the net flow observed in pial PVSs by changing the size of the gaps in response to pressure changes. In this study, we quantify this rectification based on three features of the PVSs: the quasi-circular geometry, the deformable endfoot wall, and the pressure oscillation inside. We provide an analytical model, based on the thin-shell hoop-stress approximation, and predict a pumping efficiency of about 0.4, which would contribute significantly to the observed flow. When we add the flow resistance of the extracellular space (ECS) to the model, we find an increased net flow during sleep, due to the known increase in ECS porosity (decreased flow resistance) compared to that in the awake state. We corroborate our analytical model with three-dimensional fluid–solid interaction simulations.
Elastic response of a cylinder loaded by a Hertzian contact pressure and maintained in equilibrium by its inertia
Authors: Mora Pierric , Treyssède Fabien , Laguerre Laurent
Published: April 2024

We derive the compliance of an elastic cylinder submitted to a line Hertzian contact. The cylinder is maintained in static equilibrium by bulk forces that are proportional to rigid body motions. Displacements are measured by setting integral gauges that amount to prescribing zero net linear and angular momentum, if the problem were to depend upon time. Various cases are covered, representing either infinitesimal or finite contact displacements, including partial slip. The developments are illustrated by revisiting a classical example in what could be called
The heavy cylinder on a vibrating soil
. The four contact resonances and forced response of the system are given in closed form in the quasi-static approximation, and compared against a reference numerical solution. The formulae can also be used as building blocks to assemble the compliance matrix of a system comprising several cylinders.
The MET growth signaling complex drives Alzheimer’s Disease-associated brain pathology in aged Shugoshin 1 mouse cohesinopathy model
Authors: Rao Chinthalapally V. , Crane Julie , Fowler Ben , Zhang Yuting , Yamada Hiroshi Y.
Published: April 2024

The understanding on molecular processes toward Late-onset Alzheimer’s Disease (LOAD) has been insufficient to design LOAD intervention drugs. Previously, we discovered transgenic genomic instability model mice Sgo1-/+ accumulate cerebral amyloid-beta in old age. We proposed the “amyloid-beta accumulation cycle” hypothesis, in which cytotoxic, mitogenic and aneuploidgenic amyloid can create an autonomous mitotic cycle leading to accumulation of itself. However, the nature of the growth signaling that drives cells toward pathogenic mitotic cycle remained unidentified. In this study, we hypothesized that the aged Sgo1-/+ mice brains would show signs of mitogenic signaling activation, and searched for growth signaling activated in the vicinity of amyloid-beta, with spatial analysis on the cortex and hippocampus of Sgo1-/+ mice in middle-age and old-age. The analysis indicated activations of kinase signaling p42/44 MAPK ERK1/2, AMPK, JNK, Wnt signaling via GSK3 inactivation, as well as increases of p-TAU and other AD biomarkers, PLCG1, EGFR, MET, Neurofibromin and RAS. Immune activation markers CD45 and CD31 were also elevated in the microenvironment. A majority of activated growth signaling components are of the oncogenic MET signaling complex. The discovery supports repurposing of cancer drugs targeting the MET signaling complex and EGFR-RAS-MAPK axis for intervention and/or treatment of genomic instability-driven AD.
Microbial diversification is maintained in an experimentally evolved synthetic community
Authors: Al-Tameemi Zahraa , Rodriguez-Verdugo Alejandra
Published: April 2024

Microbial communities are incredibly diverse. Yet, the eco-evolutionary processes originating and maintaining this diversity remain understudied. Here, we investigate the patterns of diversification forPseudomonas putidaevolving in isolation and withAcinetobacter johnsoniileaking resources used byP. putida. We experimentally evolved four experimental replicates in monoculture and co-culture for 200 generations. We observed thatP. putidadiversified into two distinct morphotypes that differed from their ancestor by single-point mutations. One of the most prominent mutations hit thefleQgene encoding the master regulator of flagella and biofilm formation. We experimentally confirmed thatfleQmutants were unable to swim and formed less biofilm than their ancestor, but they also produced higher yields. Interestingly, thefleQgenotype and other mutations swept to fixation in monocultures but not in co-cultures. In co-cultures, the two lineages stably coexisted for approximately 150 generations. We hypothesized thatA. johnsoniimodulates the coexistence of the two lineages through frequency-dependent selection. However, invasion experiments with two genotypes in monoculture and co-culture did not support this hypothesis. Instead, we found that, at the population level, the two morphotypes coexisted at similar relative abundances in the presence ofA. johnsoniiwhereas, in its absence, one of the morphotypes was overrepresented in the population. Overall, our study suggests that interspecies interactions play an important role in shaping patterns of diversification in microbial communities.

Importance

In nature, bacteria live in microbial communities and interact with other species, for example, through the exchange of resources leaked into the external environment (i.e., cross-feeding interactions). The role that these cross-feeding interactions play in shaping patterns of diversification remains understudied. Using a simple bacterial system in which one species cross-feeds resources to a second species (commensal species), we showed that the commensal species diversified into two subpopulations that persisted only when the cross-feeder partner was present. We further observed loss-of-function mutations in flagellar genes that were fixed in monocultures but not in co-cultures. Our findings suggest that cross-feeding species influence patterns of diversification of other species. Given that nutrient leakage is pervasive in microbial communities, the findings from this study have the potential to extend beyond our specific bacterial system. Importantly, our study has contributed to answering the larger question of whether species evolved differently in isolation versus when interacting with other species.