GC × GC-HRMS with complementary ionization methods in the suspect screening analysis of fragrance allergens: overwhelming or justified?

Modern gas chromatography-mass spectrometry (GC-MS) allows for the analysis of complex samples, such as fragrances. However, identifying all the constituents in natural fragrance mixtures, especially allergens that need to be listed on product labels, is a significant challenge. This is primarily due to the high complexity of the sample and the fact that electron ionization, the most commonly used ionization method in GC-MS, produces numerous nonspecific fragment ions, often resulting in the absence or very low abundance of the molecular ion. These factors affect confidence in assigning the analyte. In this study, we demonstrate that the combination of GC × GC separation, with high mass resolution and accurate mass measurements, as well as chemical ionization in addition to traditional electron ionization, becomes an efficient tool for reliable qualitative analysis of a mixture containing 100 fragrance allergens, even when many of them are closely related species or isomers. The proposed approach expands the applicability of the comprehensive GC × GC-HRMS method, which includes complementary ionization techniques, from studies on anthropogenic priority pollutants and emerging contaminants to the analysis of natural products. Although targeted qualitative and quantitative analysis of allergens in the modern laboratories is well organized, GC × GC-HRMS, being a useful complement to routine quality control of volatile allergens in fragrances, definitely gives an additional contribution to the analytical cases when conventional 1D-GC-MS faces some problems or uncertainties.

Racial Disparities in Outcomes After Foot and Ankle Surgery: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis delved into the impact of race and ethnicity on outcomes following foot and ankle surgery, an area garnering increasing attention within the medical community. Despite significant literature on post-surgical clinical and functional outcomes, limited research has explored the influence of racial and ethnic factors on post-operative outcomes. In this study, data from 33 relevant studies, involving a total of 557,734 patients, were analyzed to assess outcomes across different racial and ethnic groups. Notably, only six studies met the criteria for inclusion in the final meta-analysis due to variations in outcome reporting. Findings revealed disparities in functional scores, pain levels, and resource utilization among different racial and ethnic cohorts. Specifically, non-White and minority patients exhibited higher rates of foot and ankle fractures and lower extremity surgeries, worse functional outcomes, increased pain, longer hospital stays, and a greater incidence of complications compared to their White counterparts. However, some studies presented contradictory results, emphasizing the necessity for further investigation to elucidate these discrepancies fully. This research underscores the importance of considering racial and ethnic factors in foot and ankle surgery outcomes and highlights the need for targeted interventions to address existing disparities.

EThcD as a Unique Tool for the Top-Down De Novo Sequencing of Intact Natural Ranid Amphibian Peptides.

De novo sequencing of any novel peptide/protein is a difficult task. Full sequence coverage, isomeric amino acid residues, inter- and intramolecular S-S bonds, and numerous other post-translational modifications make the investigators employ various chemical modifications, providing a variety of specific fragmentation MSn patterns. The chemical processes are time-consuming, and their yields never reach 100%, while the subsequent purification often leads to the loss of minor components of the initial peptide mixture. Here, we present the advantages of the EThcD method that enables establishing the full sequence of natural intact peptides of ranid frogs in de novo top-down mode without any chemical modifications. The method provides complete sequence coverage, including the cyclic disulfide section, and reliable identification of isomeric leucine/isoleucine residues. The proposed approach demonstrated its efficiency in the analysis of peptidomes of ranid frogs from several populations of Rana arvalis, Rana temporaria, and Pelophylax esculentus complexes.

Direct anterior compared to posterior approach for hip hemiarthroplasty following femoral neck fractures.

The differences in complication rates between the direct anterior and posterior approaches for hemiarthroplasty in elderly patients with femoral neck fractures are not yet fully understood. Dislocation, a severe complication associated with increased mortality and often requiring additional surgery, may occur less frequently with the direct anterior approach compared to the posterior approach. Careful consideration of patient demographics is essential when planning the surgical approach. Future research in this area should focus on robust randomized controlled trials involving elderly patients recovering from femoral neck fractures.

Evaluation of the Efficacy of a Novel Dermatotomy Device for Central Venous Cannulation.

OBJECTIVE: To test the effectiveness of a novel wire-guided scalpel (Guideblade) to create a precise dermatotomy incision for central venous catheter (CVC) insertion. DESIGN: Prospective, nonrandomized interventional study. SETTING: Stanford University, single-center teaching hospital. PARTICIPANTS: Cardiac and vascular surgical patients (n = 100) with planned CVC insertion for operation. INTERVENTIONS: A wire-guided scalpel was used during CVC insertion. RESULTS: A total of 188 CVCs were performed successfully with a wire-guided scalpel without the need for additional equipment in 100 patients, and 94% of CVCs were accomplished with only a single dermatotomy attempt. "No bleeding" or "minimal bleeding" at the insertion site was observed in 90% of patients 30 minutes after insertion and 80.7% at the conclusion of surgery. CONCLUSION: The wire-guided scalpel was effective in performing dermatotomy for CVC with a 100% success rate and a very high first-attempt rate. The wire-guided scalpel may decrease bleeding at the CVC insertion site.

Twelve-Year Progression of Osteochondral Lesions of the Talus Observed Using Magnetic Resonance Imaging.

Osteochondral lesions of the talus are common injuries that are most often the result of trauma. The natural progression of osteochondral lesions is not well understood. It is still unclear which lesions eventually lead to joint degeneration and osteoarthritic changes and if the treatment method affects the progression. The existing literature surrounding this topic is sparse, with inconsistent findings. The presented images are taken from a 72-year-old man with bilateral osteochondral lesions of the talus. To our knowledge, this is the first published series of images illustrating the natural progression of a patient with bilateral osteochondral lesions of the talus over a 12-year time period.

An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery.

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier. BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40 to 50 times greater reporter expression in the CNS of human TFRC knockin mice. The enhanced tropism was CNS-specific and absent in wild-type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson's disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared with AAV9. These findings establish BI-hTFR1 as a potential vector for human CNS gene therapy.

Ankle Osteoarthritis.

Ankle osteoarthritis (OA) is less common than knee and hip OA, and 75% to 80% of all presentations are posttraumatic in nature, resulting from either ligamentous or bony injury to the ankle. While the ankle joint cartilage demonstrates capacity for self-restoration, the ankle joint is sensitive to aberrancies in biomechanics and the inflammatory milieu after an injury is thought to contribute to the onset of posttraumatic ankle OA. Conservative care for ankle OA is currently centered on pain reduction, and derivatives that may delay the progression of ankle OA are the subject of ongoing investigation. Surgical management for end-stage ankle OA currently focuses on ankle arthrodesis and total ankle arthroplasty. Specific indication for one procedure over the other is the topic of much debate. While total ankle arthroplasty has become more frequently used with the advent of newer generation systems, ankle arthrodesis may still be favored in younger patients with high-demand occupations.

Arthroscopic management of pediatric ankle fractures: a systematic review.

Background: Arthroscopic-assisted treatment of ankle fractures has proven useful in the adult population, but little evidence exists for the utilization of arthroscopic-assisted ankle fracture fixation in the pediatric population. The purpose of this systematic review is to examine the management of pediatric ankle fractures using arthroscopy. Methods: A systematic review was performed using PubMed, Web of Science, CINAHL, and MEDLINE from database inception to February 22nd, 2023. Inclusion criteria for this systematic review was pediatric population less than age 18, arthroscopic surgery management, and ankle fracture. Results: A total of 19 articles (n=30 patients) out of 176 articles met final inclusion criteria with all articles consisting of case reports or case series. The average patient age was 13.8±1.6 years. Sixteen of the patients (53%) had arthroscopic surgery along with an adjunct surgery as indicated, whereas 14 patients (47%) had arthroscopic surgery with or without percutaneous fixation. A high majority of patients demonstrated full range-of-motion and large improvements in function. Conclusions: Arthroscopy is used with percutaneous fixation or in adjunct to open approaches for pediatric ankle fracture management with good results. More research is needed to determine the utility of arthroscopy in the management of pediatric ankle fractures.

Polyvinyl Alcohol Hydrogel Hemiarthroplasty of First Metatarsophalangeal Joint Hallux Rigidus.

Background Hallux rigidus (HR) is the most common arthritic condition of the foot. Although first metatarsophalangeal joint (MTPJ) arthrodesis has been the historical gold-standard treatment, polyvinyl alcohol (PVA) hydrogel implants have gained popularity as a joint-sparing technique. However, recent studies have shown variable failure rates of PVA hydrogel implants. The purpose of this study was to report the five-year experience with PVA hydrogel implants performed by a single surgeon. Methodology Health records were queried from August 2016 to 2021 for patients who underwent primary PVA hydrogel implant hemiarthroplasty for symptomatic late-stage HR. Patient demographics and postoperative outcomes variables were evaluated. Kaplan-Meier analysis was used to evaluate implant survival. A total of 146 PVA hydrogel implant procedures were performed with a minimum six-month follow-up. Results The majority of patients were female (n = 103, 70.5%), with a mean age of 58.1 (±10.1) years, body mass index of 27.3 (±5.2) kg/m2, and American Society of Anesthesiologists score <3 (n = 131, 89.7%). The majority had stage II or III disease (n = 115, 78.8%). Patients experienced significant improvement in visual analog scale score (p < 0.0001) and hallux dorsiflexion (p = 0.0005). There were 22 (15.1%) complications, including implant subsidence (n = 15, 10.3%), deep infection (n = 6, 4.1%), and hypertrophic ossification (n = 1, 0.7%). Revision surgeries were required in 12.3% (n = 18) of patients at an average of 9.4 (±9.2) months postoperatively. This included nine (6.2%) revision PVA hydrogel implant procedures and nine (6.2%) first MTJP arthrodesis. The one- and two-year survival rates for MTPJ arthrodesis (n = 9) were 95.9% and 86.3%, respectively. Conclusions In the largest single-surgeon series reported, first MTPJ hemiarthroplasty with a PVA hydrogel implant significantly improved pain and hallux dorsiflexion at an average of 14.5 months postoperatively. There was a high two-year survivorship of 86.3% until failure which required first MTPJ arthrodesis. Future studies should be performed to refine the indications for PVA hydrogel implants and identify risk factors.

Association of Radiographic Soft Tissue Thickness With Revision Total Ankle Arthroplasty Following Primary Total Ankle Arthroplasty: A Minimum of 5-year Follow-up.

Background: The incidence of primary total ankle arthroplasty (TAA) is rising, with a corresponding increase in revision surgeries. Despite this, research on risk factors for revision TAA following primary TAA remains limited. Radiographic soft tissue thickness has been explored as a potential predictor for outcomes in hip, knee, and shoulder arthroplasty, but its role in TAA has not been assessed. This study aimed to assess the predictive value of radiographic soft tissue thickness for identifying patients at risk of requiring revision surgery following primary TAA. Methods: A retrospective study was conducted on 323 patients who underwent primary TAA between 2003 and 2019. Radiographic measurements of soft tissue thickness were obtained from preoperative radiographs. Two novel radiographic measures of soft tissue thickness were developed and assessed (tibial tissue thickness and talus tissue thickness). Clinical variables including age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, diabetes, smoking status, primary diagnosis, and implant type were recorded. Logistic regression analysis was used to assess the predictive value of soft tissue thickness and BMI for revision TAA. Results: The rate of revision surgery was 4.3% (14 of 323 patients). Patients requiring revision had significantly greater tibial tissue (3.54 vs 2.48 cm; P = .02) and talus tissue (2.79 vs 2.42 cm; P = .02) thickness compared with those not requiring revision. Both the tibial tissue thickness (odds ratio 1.16 [1.12-1.20]; P < .01) and the talus tissue thickness (odds ratio: 1.10 [1.05-1.15]; P < .01) measurements were significant predictors of revision TAA in multivariable logistic regression models. However, BMI was not a significant predictor of revision TAA. The two metrics demonstrated excellent interrater reliability. Conclusion: Greater soft tissue thickness was a better predictor of revision TAA compared with BMI. These findings suggest that radiographic soft tissue thickness may be a valuable tool for assessing the risk of the need for revision TAA following primary TAA. Further research is needed to validate and explore the potential impact on clinical practice. Level of Evidence: Level III, comparative study.

Mucolytic Drugs Ambroxol and Bromhexine: Transformation under Aqueous Chlorination Conditions.

Bromhexine and ambroxol are among the mucolytic drugs most widely used to treat acute and chronic respiratory diseases. Entering the municipal wastewater and undergoing transformations during disinfection with active chlorine, these compounds can produce nitrogen- and bromine-containing disinfection by-products (DBPs) that are dangerous for aquatic ecosystems. In the present study, primary and deep degradation products of ambroxol and bromhexine obtained in model aquatic chlorination experiments were studied via the combination of high-performance liquid and gas chromatography with high-resolution mass spectrometry. It was shown that at the initial stages, the reactions of cyclization, hydroxylation, chlorination, electrophilic ipso-substitution of bromine atoms with chlorine, and oxidative N-dealkylation occur. Along with known metabolites, a number of novel primary DBPs were tentatively identified based on their elemental compositions and tandem mass spectra. Deep degradation of bromhexine and ambroxol gives twenty-four identified volatile and semi-volatile compounds of six classes, among which trihalomethanes account for more than 50%. The specific class of bromhexine- and ambroxol-related DBPs are bromine-containing haloanilines. Seven of them, including methoxy derivatives, were first discovered in the present study. One more novel class of DBPs associated with bromhexine and ambroxol is represented by halogenated indazoles formed through dealkylation of the primary transformation products containing pyrazoline or tetrahydropyrimidine cycle in their structure.

Examining the Evidence Regarding Smoking and Patient Outcomes for Isolated Meniscus Pathology: A Comprehensive Systematic Review and Meta-Analysis.

Smoking is a well-known cause of impairment in wound healing and postoperative outcomes; however, its effects on treating meniscus issues remain unclear. This study assesses the relationship between smoking and meniscus treatment outcomes. PubMed, Scopus, Cochrane, and CINAHL were searched from inception to 24 December 2023. Inclusion criteria encompassed studies examining smoking's impact on patient outcomes regarding meniscus pathology. A secondary PubMed search targeted randomized controlled trials (RCTs) in the top ten orthopedic journals focusing on meniscus pathology and smoking as a demographic variable. Meta-analysis of six studies (n = 528) assessed meniscus failure rate based on smoking status. Eighteen observational studies (n = 8353 patients; 53.25% male; mean age: 51.35 ± 11.53 years; follow-up: 184.11 ± 117.34 months) were analyzed, covering meniscus repair, meniscectomy, allograft transplant, conservative care, and arthroscopy. Results showed four studies (36.36%) linked smoking with worse meniscus repair outcomes, while seven studies (63.64%) did not find significant associations. Meta-analysis from six studies showed no significant impact of smoking on repair failure (p = 0.118). Regarding meniscectomy, one study (33.33%) identified a significant association with smoking, but two did not. Only one (3.8%) of the RCTs in leading orthopedic journals included smoking as a factor. The evidence on smoking's effect on meniscus treatment is mixed, necessitating further investigation.

Mechanism of Injury for Traumatic Mid-Foot Lisfranc Injuries: Impact of the COVID-19 Pandemic.

Background During the COVID-19 pandemic, Americans transitioned away from their normal routines, drove in motor vehicles less, and reduced their physical activity, ultimately influencing the incidence and nature of orthopedic injuries that were operatively managed. The purpose of this study was to evaluate the effect of the COVID-19 pandemic lockdown and subsequent deconditioning on the mechanism of injury and severity of Lisfranc injury. Methods This retrospective study included patients with a traumatic Lisfranc injury who were surgically treated by a foot and ankle fellowship-trained orthopedic surgeon between 2015 and 2021. Electronic health records were queried for patient demographics, mechanism of injury, physical exam findings, and pain scores. Preoperative radiographs were reviewed to grade Lisfranc injuries using the previously described Nunley-Vertullo classification system. Descriptive and univariate statistics were performed to compare 15 patients in the pre-COVID-19 cohort and 15 patients in the post-COVID-19 cohort. Results In the pre-COVID-19 cohort, 80% (n=12/15) of the patients were female, the mean age was 46±15 years, the mean BMI was 29.7±7 kg/m2, and the mean follow-up period was 18.1±12 months. In the post-COVID-19 cohort, 53% (n=8/15) of the patients were female, the mean age was 48.5±17 years, the mean BMI was 31.4±7 kg/m2, and the mean follow-up period was 9.5±4 months. Significantly higher proportions of plantar ecchymosis (n=8/15, 53%), neuropathic pain (n=7/15, 47%), and swelling (n=12/15, 80%) were present in the post-COVID-19 cohort. A low-energy mechanism of injury was sustained by 73% (n=11/15) of the pre-COVID-19 cohort and 80% (n=12/15) of the post-COVID-19 cohort. Lisfranc injuries for the pre-COVID-19 cohort and the post-COVID-19 cohort demonstrated the following classifications: Grade 1 (33%, n=5/15 vs. 40%, n=6/15), Grade 2 (60%, n=9/15 vs. 53%, n=8/15), and Grade 3 (7%, n=1/15 vs. 7%, n=1/15). Conclusion Although a higher proportion of plantar ecchymosis, neuropathic pain, and swelling was observed, there was no association between a low mechanism of injury and a higher grade of Lisfranc injury following the COVID-19 pandemic.

Reliable detection of stochastic epigenetic mutations and associations with cardiovascular aging.

Stochastic epigenetic mutations (SEMs) have been proposed as novel aging biomarkers to capture heterogeneity in age-related DNA methylation changes. SEMs are defined as outlier methylation patterns at cytosine-guanine dinucleotide sites, categorized as hypermethylated (hyperSEM) or hypomethylated (hypoSEM) relative to a reference. Because SEMs are defined by their outlier status, it is critical to differentiate extreme values due to technical noise or data artifacts from those due to real biology. Using technical replicate data, we found SEM detection is not reliable: across 3 datasets, 24 to 39% of hypoSEM and 46 to 67% of hyperSEM are not shared between replicates. We identified factors influencing SEM reliability-including blood cell type composition, probe beta-value statistics, genomic location, and presence of SNPs. We used these factors in a training dataset to build a machine learning-based filter that removes unreliable SEMs, and found this filter enhances reliability in two independent validation datasets. We assessed associations between SEM loads and aging phenotypes in the Framingham Heart Study and discovered that associations with aging outcomes were in large part driven by hypoSEMs at baseline methylated probes and hyperSEMs at baseline unmethylated probes, which are the same subsets that demonstrate highest technical reliability. These aging associations were preserved after filtering out unreliable SEMs and were enhanced after adjusting for blood cell composition. Finally, we utilized these insights to formulate best practices for SEM detection and introduce a novel R package, SEMdetectR, which uses parallel programming for efficient SEM detection with comprehensive options for detection, filtering, and analysis.

Understanding Breast Cancer Surgery Through Tiktok: an Analysis of Video Content and Viewer Engagement.

BACKGROUND: Breast cancer is the most common cancer in adolescents and young adults. Social media, particularly TikTok, has emerged as a crucial platform for sharing health information in this population. This study aims to characterize breast cancer surgery information on TikTok, focusing on content reliability, viewer reception, and areas for improvement. METHODS: We queried the search terms "breast cancer surgery," "mastectomy," and "lumpectomy" on TikTok, evaluating the top 50 videos for each. After watching each video, characteristics were recorded including: creator characteristics, video metrics, viewer reception, and video content. Statistical analysis was performed using Spearman's rank correlations and t-tests. RESULTS: A total of 138 videos were analyzed (excluding 12 duplicates from the initial 150). These videos received 4,895,373 likes and 109,705 comments. The most common content types were storytelling (57%) and education (20%), and the most common creator types were patients (77.3%) and physicians (10.3%). Videos with educational content by physicians were rare (6.5%). Engagement varied on the basis of video length, search terms, and creator characteristics. Overall, viewer comments predominantly expressed support and interest. CONCLUSIONS: Our study reveals that information on breast cancer surgery is widely shared on TikTok and has high viewer engagement. Factors influencing impact include video length, creator background, and search terms. While social media has democratized information sharing, there is a relative lack of physician creators providing objective and educational content. We highlight opportunities for health professionals to engage in social media as a tool for health education and ensure diverse and reliable healthcare content on these platforms.

In vitro activities and mechanisms of action of anti-cancer molecules from African medicinal plants: a systematic review.

Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this pathology. Management is often complicated by the high treatment costs, side effects and the increasing occurrence of resistance to treatments. The identification of new active ingredients extracted from endemic medicinal plants is definitively an interesting approach for the implementation of new therapeutic strategies: their extraction is often lower cost; their identification is based on an ethnobotanical history and a tradipratic approach; their use by low-income populations is simpler; this can help in the development of new synthetic molecules that are more active, more effective and with fewer side effects. The objective of this review is to document the molecules derived from African medicinal plants whose in vitro anti-cancer activities and the mechanisms of molecular actions have been identified. From the scientific databases Science Direct, PubMed and Google Scholar, we searched for publications on compounds isolated from African medicinal plants and having activity on cancer cells in culture. The data were analyzed in particular with regard to the cytotoxicity of the compounds and their mode of action. A total of 90 compounds of these African medicinal plants were selected. They come from nine chemical groups: alkaloids, flavonoids, polyphenols, quinones, saponins, steroids, terpenoids, xanthones and organic sulfides. These compounds have been associated with several cellular effects: i) Cytotoxicity, including caspase activation, alteration of mitochondrial membrane potential, and/or induction of reactive oxygen species (ROS); ii) Anti-angiogenesis; iii) Anti-metastatic properties. This review points out that the cited African plants are rich in active ingredients with anticancer properties. It also stresses that screening of these anti-tumor active ingredients should be continued at the continental scale. Altogether, this work provides a rational basis for the selection of phytochemical compounds for use in clinical trials.

Age-Invariant Genes: Multi-Tissue Identification and Characterization of Murine Reference Genes.

Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they serve as reference genes (often called housekeeping genes) in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan. Here, we build upon a common pipeline for identifying reference genes in RNA-seq datasets to identify age-invariant genes across seventeen C57BL/6 mouse tissues (brain, lung, bone marrow, muscle, white blood cells, heart, small intestine, kidney, liver, pancreas, skin, brown, gonadal, marrow, and subcutaneous adipose tissue) spanning 1 to 21+ months of age. We identify 9 pan-tissue age-invariant genes and many tissue-specific age-invariant genes. These genes are stable across the lifespan and are validated in independent bulk RNA-seq datasets and RT-qPCR. We find age-invariant genes have shorter transcripts on average and are enriched for CpG islands. Interestingly, pathway enrichment analysis for age-invariant genes identifies an overrepresentation of molecular functions associated with some, but not all, hallmarks of aging. Thus, though hallmarks of aging typically involve changes in cell maintenance mechanisms, select genes associated with these hallmarks resist fluctuations in expression with age. Finally, our analysis concludes no classical reference gene is appropriate for aging studies in all tissues. Instead, we provide tissue-specific and pan-tissue genes for assays utilizing reference gene normalization (i.e., RT-qPCR) that can be applied to animals across the lifespan.