Analysis of IDH and EGFR as biomarkers in glioblastoma multiforme: A case-control study.

Background: Glioblastoma multiforme (GBM) is a very aggressive primary central nervous system (CNS) tumor with limited therapeutic options and poor prognosis. This study aimed to analyze the association between single nucleotide polymorphisms (SNPs), including IDH1 rs121913500C > T, IDH2 rs11540478G > A, and EGFR rs1468727C > T, and their association on the risk and overall survival of GBM patients in Jordan. Methods: Using a case-control study design involving 63 GBM patients and 226 healthy controls was conducted at King Abdullah University Hospital in Jordan. DNA extraction was performed using formalin-fixed and paraffin-embedded tissue for GBM samples and blood samples for controls. SNPs analysis was performed using the Sequenom iPLEX assay sequencing technique. Survival outcomes were assessed using Cox models and hazard ratios (HR), and single-cell RNA (scRNA) analysis was performed from GSE70630. Results: The study showed a significant association between genotype frequency in GBM cases and controls for specific SNPs, including IDH1 rs121913500C > T, and EGFR rs1468727C > T. The G/G genotype of rs11540478 (IDH2) was associated with better prognostic outcomes in GBM patients. The scRNA analysis demonstrated the differential expression of IDH1, IDH2, and EGFR in GBM, with enrichment in central carbon metabolism in cancer. Conclusion: Our findings suggest that SNPs, particularly in IDH1 and IDH2 genes and EGFR, may serve as diagnostic and prognostic biomarkers for GBM. While the study underscores the clinical relevance of these genetic variants, further investigations with larger and more diverse populations are essential to validate and extend these associations.

Qualitative analysis of the Supraspinatus muscle fatty infiltration on MRI - Correlation of the Tangent sign with Goutallier grade at the Y view and Medial Scapular border in large retracted rotator cuff tears.

BACKGROUND: Surgically repairing rotator cuff tears with a higher extent of fatty infiltration is controversial. Current evidence supports performing rotator cuff repair in patients exhibiting Goutallier stage 3-4 fatty infiltration. However, the presence of retraction complicates accurate assessment using the Goutallier Classification, particularly on the lateral Y-view. A shift towards classifying fatty infiltration in more medial regions may enhance the precision of tissue quality quantification. The objective of this study was to analyze the uniformity of fatty infiltration within the entire supraspinatus muscle using the Goutallier Classification across three scapular Y-view sections and to examine the association between Goutallier grade, tangent sign, and modified Patte stage. METHODS: A retrospective evaluation was conducted on preoperative magnetic resonance imaging (MRI) scans from a consecutive series of 97 patients who had previously undergone arthroscopic rotator cuff repairs. Three supraspinatus sections on the MRI sagittal plane were identified: the lateral Y-view (section one), a medial section at the suprascapular notch anatomical landmark (section two), and a section 3 cm medial from the suprascapular notch Medial Scapular Body (section three). Goutallier grade, tangent sign, and modified Patte stage were used to evaluate fatty infiltration, muscle atrophy, and tendon retraction, respectively. RESULTS: Section one had the highest Goutallier grade, while section three had the lowest. Intra-observer rest retest reliability analysis showed excellent consistency in all sections with section one (ICC=0.920, 95% CI), section two (ICC=0.917, 95% CI), and section three (ICC=0.923, 95% CI) for Goutallier grade. Inter-observer reliability analysis also revealed excellent consistency in sections one (ICC=0.951, 95% CI), section two (ICC=0.949, 95% CI), and section three (ICC=0.922, 95% CI) for Goutallier grade. A strong correlation was observed between Goutallier grade and modified Patte stage (τb=0.43-0.56, p=0.001), and between Goutallier grade and tangent sign (τb=0.43-0.54, p=0.001) across all sections. CONCLUSION: The severity of fatty infiltration within the supraspinatus muscle belly is inconsistent, with the lateral portion being the most severe and the medial portion the least severe. Goutallier grade demonstrates a strong correlation with tangent sign and modified Patte stage. This suggests that tendon retraction results in a potential overestimation in the amount of fatty infiltration defining some tears unjustly irreparable when measuring at the traditionally described lateral Y-view position compared with 3cm medial.

Predictive factors for readmission after bariatric surgery: Experience of an obesity center.

Avoidable readmissions after bariatric surgery are a major burden on the healthcare systems. Rates of readmission after bariatric surgery have ranged from 1% up to 20%, but the factors that predict readmission have not been well studied. The objective of this study was to determine readmission rates following bariatric surgery and identify factors that contribute to early (within 90 days of surgery) and late readmission. A retrospective cohort study of 736 patients undergoing either Laparoscopic Sleeve Gastrectomy or Laparoscopic Roux-en-Y Gastric Bypass in Jordan University Hospital from 2016 to 2019. Demographic characteristics, co-morbidities, and readmissions were extracted from their medical records and analyzed. Multivariable logistic regression analysis was performed to determine which factors predict readmission. A total of 736 patients had bariatric surgery (Laparoscopic Sleeve Gastrectomy 89% vs Laparoscopic Roux-en-Y Gastric Bypass 11%) during the study period. Thirty-day readmission rate was 6.62% and an overall readmission rate of 23.23%. Common reasons for early readmission (within 90 days of surgery) were nausea, vomiting, and dehydration. Late readmissions were mainly caused by gallbladder stones. Three risk factors were identified that independently predicted readmission: the type of procedure being performed (P-value = .003, odds ratio [OR] 2.14, 95% confidence interval [CI] 1.32-3.49), depression (P-value = .028, OR 6.49, 95% CI 1.18-52.9) and preoperative body mass index (P-value = .011, OR 1.03, 95% CI 1.01-1.05). Several factors were identified that cause patients to represent and subsequently admitted into hospitals. Early readmission was usually due to nausea, vomiting, and dehydration, whereas late admissions were mostly due to biliary complications. Preoperative body mass index and depression were independent risk factors for readmission.

Emerging Trends and Innovations in the Treatment and Diagnosis of Atherosclerosis and Cardiovascular Disease: A Comprehensive Review towards Healthier Aging.

Cardiovascular diseases (CVDs) are classed as diseases of aging, which are associated with an increased prevalence of atherosclerotic lesion formation caused by such diseases and is considered as one of the leading causes of death globally, representing a severe health crisis affecting the heart and blood vessels. Atherosclerosis is described as a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease and to date, most pharmacological therapies mainly aim to control risk factors in patients with cardiovascular disease. Advances in transformative therapies and imaging diagnostics agents could shape the clinical applications of such approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, and gene therapy, which are emerging and likely to significantly impact CVD management in the coming decade. This review summarizes the current anti-atherosclerotic therapies' major milestones, strengths, and limitations. It provides an overview of the recent discoveries and emerging technologies in nanomedicine, cell therapy, and gene and immune therapeutics that can revolutionize CVD clinical practice by steering it toward precision medicine. CVD-related clinical trials and promising pre-clinical strategies that would significantly impact patients with CVD are discussed. Here, we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD medicine.

Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain-Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Combating Parkinson's disease with plant-derived polyphenols: Targeting oxidative stress and neuroinflammation.

Parkinson's disease (PD) is a devastating neurodegenerative disorder predominantly affecting the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra. Reactive oxygen species (ROS) generation plays a central role in the pathogenesis of PD and other neurodegenerative diseases. An imbalance between cellular antioxidant activity and ROS production leads to oxidative stress, contributing to disease progression. Dopamine metabolism, mitochondrial dysfunction, and neuroinflammation in dopaminergic neurons have been implicated in the pathogenesis of Parkinson's disease. Consequently, there is a pressing need for therapeutic interventions capable of scavenging ROS. Current pharmacological approaches, such as L-dihydroxyphenylalanine (levodopa or L-DOPA) and other drugs, provide symptomatic relief but are limited by severe side effects. Researchers worldwide have been exploring alternative compounds with less toxicity to address the multifaceted challenges associated with Parkinson's disease. In recent years, plant-derived polyphenolic compounds have gained significant attention as potential therapeutic agents. These compounds exhibit neuroprotective effects by targeting pathophysiological responses, including oxidative stress and neuroinflammation, in Parkinson's disease. The objective of this review is to summarize the current understanding of the neuroprotective effects of various polyphenols in Parkinson's disease, focusing on their antioxidant and anti-inflammatory properties, and to discuss their potential as therapeutic candidates. This review highlights the progress made in elucidating the molecular mechanisms of action of these polyphenols, identifying potential therapeutic targets, and optimizing their delivery and bioavailability. Well-designed clinical trials are necessary to establish the efficacy and safety of polyphenol-based interventions in the management of Parkinson's disease.

Comparative analysis of geriatric hip fracture management outcomes in teaching and nonteaching hospitals in Jordan.

Hip fractures are common orthopedic injuries that have significant impacts on patients and healthcare systems. Previous studies have shown varying outcomes for hip fracture management in different settings, with diverse postoperative outcomes and complications. While teaching hospital settings have been investigated, no studies have specifically examined hip fracture outcomes in teaching hospitals in Jordan or the broader Middle East region. Therefore, the aim of this study was to investigate this important outcome. A cohort comprising 1268 patients who underwent hip fracture fixation from 2017 to 2020 was analyzed for nine distinct outcomes. These outcomes encompassed time to surgery, ICU admissions, perioperative hemoglobin levels, length of hospital stay, readmission rates, revision procedures, and mortality rates at three time points: in-hospital, at 6-months, and at 1-year post-surgery. The analysis of 1268 patients (616 in teaching hospitals, 652 in non-teaching hospitals) showed shorter mean time to surgery in teaching hospitals (2.2 days vs. 3.6 days, p < 0.01), higher ICU admissions (17% vs. 2.6%, p < 0.01), and more postoperative blood transfusions (40.3% vs. 12.1%, p < 0.01). In-hospital mortality rates were similar between groups (2.4% vs. 2.1%, p = 0.72), as were rates at 6-months (3.1% vs. 3.5%, p = 0.65) and 1-year post-surgery (3.7% vs. 3.7%, p = 0.96). Geriatric hip fracture patients in teaching hospitals have shorter surgery times, more ICU admissions, and higher postoperative blood transfusion rates. However, there are no significant differences in readmission rates, hospital stays, or mortality rates at various intervals.

Association between carpal height ratio and ulnar variance in normal wrist radiography.

INTRODUCTION: The wrist joint is a complex anatomical structure, and various radiographic parameters are utilized to assess its normal alignment and orientation. Among these parameters are carpal height ratio (CHR) and ulnar variance (UV). Previous literature has indicated that factors such as age and gender may influence these parameters; However, there is a lack of studies investigating these differences specifically in the Middle East or Jordan. Additionally, no prior research has explored the relationship between UV and CHR. Therefore, the objective of this study is to investigate these critical radiological parameters and their associations. METHODOLOGY: A cross-sectional study design was employed, wherein a total of 385 normal wrist X-rays were reviewed, and CHR and UV were measured. Intra-observer and inter-observer reliability assessments were conducted to ensure the consistency and accuracy of measurements. Additionally, the association between UV and CHR was measured and plotted for further analysis. RESULTS: In our study, the mean CHR was 0.5 (range: 0.4 to 1.5), and the mean UV was - 0.3 mm (range: -5.8 mm to 4.1 mm). We found a significant negative correlation between CHR and age (p < 0.05). No significant gender differences were observed in UV and CHR. Additionally, a weak positive correlation was found between UV and CHR (Pearson correlation coefficient = 0.13, p = 0.01; adjusted R2 = 0.014, p = 0.02). CONCLUSION: Age correlated significantly with a decline in carpal height ratio. Additionally, ulnar variance had a week positive yet significant correlation with carpal height ratio. LEVEL OF EVIDENCE: Cross-sectional study, Level III.

A Rare Case of Membranous Nephropathy Complicated by Chylothorax.

Background: Chylothorax can be classified into traumatic and nontraumatic based on the etiology. Nephrotic syndrome is a very rare cause of nontraumatic chylothorax in adults. Case presentation: A 66-year-old woman with membranous nephropathy who was non-compliant with her management, presented with dyspnea, and was found to have a large right sided chylothorax. Her chylothorax was secondary to membranous nephropathy after excluding other causes, which has been rarely reported in literature. Conclusion: This case highlights the possibility of nephrotic syndrome causing chylothorax, especially in patients with undiagnosed nephrotic syndrome or patients non-compliant with their management. When evaluating a patient with chylothorax, providers should consider nephrotic syndrome in the differential diagnosis. LEARNING POINTS: Chylothorax can be secondary to nephrotic syndrome which has been rarely reported in literature.Providers should be aware of nephrotic syndrome as a cause of chylothorax especially in patients with undiagnosed nephrotic syndrome or non-compliance with their management.Treatment of underlying cause is usually sufficient for spontaneous resolution of chylothorax with or without pleural fluid evacuation.

Adolescents With a High Burden of New-Onset Mood Symptoms After Sport-Related Concussion Benefit From Prescribed Aerobic Exercise, a Secondary Analysis of 2 Randomized Controlled Trials.

OBJECTIVE: Approximately 20% of students with sport-related concussion (SRC) report new symptoms of anxiety and depression which may be associated with delayed recovery and increased risk for developing a mood disorder. Early prescribed aerobic exercise facilitates recovery in athletes with concussion-related exercise intolerance. We studied the effect of aerobic exercise treatment on new mood symptoms early after SRC. DESIGN: Exploratory secondary analysis of 2 randomized controlled trials (RCT). SETTING: Sports medicine clinics associated with UB (Buffalo, NY), CHOP (Philadelphia, PA), and Boston Children's Hospital (Boston, MA). PARTICIPANTS: Male and female adolescents (aged 13-18 years) diagnosed with SRC (2-10 days since injury). INTERVENTIONS: Participants were randomized to individualized targeted heart rate aerobic exercise (n = 102) or to a placebo intervention designed to mimic relative rest (n = 96). MAIN OUTCOME MEASURES: Incidence of Persisting Post-Concussive Symptoms (PPCS, symptoms ≥28 days). RESULTS: First RCT recruited from 2016 to 2018 and the second from 2018 to 2020. Of 198 adolescents, 156 (79%) reported a low burden (mean 1.2 ± 1.65/24) while 42 (21%) reported a high burden (mean 9.74 ± 3.70/24) of emotional symptoms before randomization. Intervention hazard ratio for developing PPCS for low burden was 0.767 (95% CI, 0.546-1.079; P = 0.128; ß = 0.085) and for high burden was 0.290 (95% CI, 0.123-0.683; P = 0.005; ß = 0.732). CONCLUSIONS: High burden of mood symptoms early after injury increases risk for PPCS, but the sports medicine model of providing early targeted aerobic exercise treatment reduces it. Nonsports medicine clinicians who treat patients with a high burden of new mood symptoms after concussion should consider prescribing aerobic exercise treatment to reduce the risk of PPCS and a mood disorder.

Endobronchial Ultrasonography to Assess and Evaluate Tracheobronchial Tree Invasion in cT4b Esophageal Cancer Patients Treated with Definitive Chemoradiotherapy: Assessment of Resectability.

BACKGROUND: In cT4b esophageal cancer, accurate assessment of tracheobronchial tree invasion after definitive chemoradiotherapy (dCRT) aids in the selection of patients for whom an oncologic radical esophagectomy can be achieved. The current report aimed to determine the accuracy of endobronchial ultrasound in assessing tumor invasion in the tracheobronchial tree after dCRT in patients with cT4b esophageal cancer. METHODS: Esophageal cancer patients with suspicion of tracheobronchial tree invasion on the diagnostic contrast-enhanced computed tomography (CT) who underwent a staging endobronchial ultrasonography (EBUS) were eligible for inclusion in this study. To assess the accuracy of the EBUS in assessing tumor ingrowth in the tracheobronchial tree after dCRT, patients who had an EBUS during restaging and underwent surgery were included in the final analysis. RESULTS: The final analysis included 26 patients. For 18 (90%) of 20 patients in whom the anatomy of the tracheobronchial tree was restored on the restaging EBUS and tumor invasion was considered to be absent, a radical esophagectomy was achieved. In six patients, persistent ingrowth was observed during the restaging EBUS. For these patients, the EBUS was repeated after a median of 9 weeks. Tumor invasion was considered to be absent in four patients, and a radical resection was achieved in three of these patients. CONCLUSION: The EBUS provides valuable information on the assessment of tracheobronchial tree invasion in cT4b esophageal cancer patients after dCRT. This information could aid in the proper selection of patients who benefit from a curative but highly invasive esophagectomy.

Corticosteroids for improving patient-relevant outcomes in HELLP syndrome: a systematic review and meta-analysis.

BACKGROUND: We conducted this updated systematic review to assess the effects of corticosteroids vs. placebo or no treatment for improving patient-relevant outcomes in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. METHODS: CENTRAL, MEDLINE/PubMed, Web of Science, and Scopus, from the date of inception of the databases to February 3, 2024 were searched. Reference lists of included studies and systematic reviews were thoroughly searched. We included RCTs that enrolled women with HELLP syndrome, whether antepartum or postpartum, to receive any corticosteroid versus placebo or no treatment. No language or publication date restrictions were made. We used a dual independent approach for screening titles and abstracts, full text screening, and data extraction. Risk of bias was assessed in the included studies using Cochrane's RoB 2 tool. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. GRADE approach was used to assess certainty of evidence for the pre-specified outcomes. RESULTS: Fifteen trials (821 women) compared corticosteroids with placebo or no treatment. The effect of corticosteroids is uncertain for the primary outcome i.e., maternal death (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.25 to 2.38, very low certainty evidence). Out of 6 studies reporting maternal death, 5 were judged overall to have "low risk" of bias. The effect of corticosteroids is also uncertain for other important outcomes including pulmonary edema (RR 0.70, 95% CI 0.23 to 2.09), dialysis (RR 3, 95% CI 0.13 to 70.78), liver morbidity (hematoma, rupture, and failure; RR 0.22, 95% CI 0.03 to 1.83), or perinatal death (0.64, 95% CI 0.21 to 1.97) because of very low certainty evidence. Low certainty evidence suggests that corticosteroids have little or no effect on the need for platelet transfusion (RR 0.98, 95% CI 0.60 to 1.60) and may result in a slight reduction in acute renal failure (RR 0.67, 95% CI 0.40 to 1.12). Subgroup and sensitivity analyses showed results that were similar to the primary synthesis. CONCLUSIONS: In women with HELLP syndrome, the effect of corticosteroids vs. placebo or no treatment is uncertain for patient-relevant outcomes including maternal death, maternal morbidity, and perinatal death. These uncertainties regarding this critical question should be addressed by adequately powered rigorous trials. SYSTEMATIC REVIEW REGISTRATION: Center for Open Science, osf.io/yzku5.

Intranasal Immunization for Zika in a Pre-Clinical Model.

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of -19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.

Improvement in Sexual Dysfunction in Patients With Hypertrophic Cardiomyopathy Undergoing Septal Myectomy: A Prospective Study.

Background: Septal myectomy improves symptoms in the majority of patients with obstructive hypertrophic cardiomyopathy (HCM), but there are limited prospective data on functional outcomes after operation. Objectives: The authors investigated quality of life measures and prevalence of sexual dysfunction before and after septal myectomy for obstructive HCM. Methods: Between January 2018 and October 2019, 436 patients underwent transaortic septal myectomy at our clinic. All patients were screened for eligibility, and 197 (45.2%) were enrolled in this prospective survey study. Patients received a questionnaire pertaining to quality of life and sexual health before and within 4 to 6 months postoperatively, and 113 (57.4%) completed the follow-up survey. Results: The mean age of the 54 (47.8%) women and 59 (52.2%) men was 54.7 ± 14.1 years. Quality of life, including both mental and physical components, improved significantly in both men (P < 0.001) and women (P < 0.001). Women reported mild sexual dysfunction at baseline, and following septal myectomy, they experienced significant (P < 0.05) improvement in most domains pertaining to sexual health. In men, the International Index of Erectile Function median score was 23 (IQR: 7.0-29.5), which is consistent with mild dysfunction at baseline, and there was significant improvement following surgery in young (age ≤55 years) men (P < 0.001). Conclusions: Quality of life is significantly improved following septal myectomy in patients with obstructive HCM. Both women and men reported mild sexual dysfunction at baseline, and women and younger men (age ≤55 years) experienced significant improvements in sexual health.

Medial scapular body (MSB) Goutallier classification: MRI-based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.

BACKGROUND: The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal magnetic resonance imaging (MRI) sections at the medial scapular body, the Medial Scapular Body-Goutallier Classification (MSB-GC) will improve reliability and repeatability, giving a more representative approximation to the degree of fatty infiltration, as compared with the original Y-view. METHODS: Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0-4) at 3 defined sections: section 1, original Y-view; section 2, level of suprascapular notch; and section 3, 3 cm medial to the suprascapular notch on MRI scans. Six subspecialist fellowship-trained shoulder surgeons and 3 musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients. RESULTS: Of 80 scans, 78% (n = 62) were massive cuff tears involving the supraspinatus, infraspinatus, and subscapularis tendons. Interobserver reliability (consistency between observers) for Goutallier grade was excellent for all 3 predefined sections (range: 0.87-0.95). Intraobserver reliability (repeatability) for Goutallier grade was excellent for all 3 sections and 4 rotator cuff muscles (range: 0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (P < .001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles: 42.5% of both supraspinatus and infraspinatus were downgraded by 1, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2, and 2.5% of supraspinatus were downgraded by 3. CONCLUSION: This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision making, which should be studied further in clinical studies.

Production and Release of Proinflammatory Mediators by the Cockroach Allergen Bla g 1 via a Shared Membrane-Destabilization Mechanism.

The cockroach allergen Bla g 1 encloses an exceptionally large hydrophobic cavity, which allows it to bind and deliver unsaturated fatty acid ligands. Bla g 1-mediated delivery of naturally occurring (nMix) ligands has been shown to destabilize lipid membranes, contributing to its digestive/antiviral functions within the source organism. However, the consequences of this activity on Bla g 1 allergenicity following human exposure remain unknown. In this work, we show that Bla g 1-mediated membrane disruption can induce a proinflammatory immune response in mammalian cells via two complementary pathways. At high concentrations, the cytotoxic activity of Bla g 1 induces the release of proinflammatory cytosolic contents including damage-associated molecular patterns (DAMPs) such as heat-shock Protein-70 (HSP70) and the cytokine interleukin-1 (IL-1ß). Sublytic concentrations of Bla g 1 enhanced the ability of phospholipase A2 (PLA2) to extract and hydrolyze phospholipid substrates from cellular membranes, stimulating the production of free polyunsaturated fatty acids (PUFAs) and various downstream inflammatory lipid mediators. Both of these effects are dependent on the presence of Bla g 1's natural fatty-acid (nMix) ligands with CC50 values corresponding to the concentrations required for membrane destabilization reported in previous studies. Taken together, these results suggest that mechanisms through which Bla g 1-mediated lipid delivery and membrane destabilization could directly contribute to cockroach allergic sensitization.

Bioinspired ferromagnetic NiFe2O4 nanoparticles: Eradication of fungal and drug-resistant bacterial pathogens and their established biofilm.

Nickel ferrite nanoparticles (NiFe2O4 NPs) were synthesized using the medicinally important plant Aloe vera leaf extract, and their structural, morphological, and magnetic properties were characterized by x-ray diffraction (XRD), fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized NPs were soft ferromagnetic and spinel in nature, with an average particle size of 22.2 nm. To the best of our understanding, this is the first comprehensive investigation into the antibacterial, anticandidal, antibiofilm, and antihyphal properties of NiFe2O4 NPs against C. albicans as well as drug-resistant gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative multidrug resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) bacteria. NiFe2O4 NPs showed potent antimicrobial activity (MIC 1.6-2 mg/mL) against the test pathogens. NiFe2O4 NPs at 0.5 mg/mL suppressed biofilm formation by 49.5-53.1 % in test pathogens. The study found that the NPs not only prevent the formation of biofilm, but also eliminate existing mature biofilms by 50.5-75.79 % at 0.5 mg/mL, which was further validated by SEM. SEM examination revealed a reduction in the number of cells that form biofilms and adhere to the surface. Additionally, it considerably impeded the colonization and aggregation of the biofilm strains on the glass surface. Light microscopic examination demonstrated that NPs effectively prevent the expansion of hyphae, filaments, and yeast-to-hyphae transformation in C. albicans, resulting in a substantial decrease in their ability to cause infection. Moreover, SEM images of the treated cells exhibited the presence of wrinkles, deformities, and impaired cell walls, which suggests an alteration and instability of the membrane. This study demonstrated the efficacy of the greenly manufactured NPs in suppressing the proliferation of candida, drug-resistant bacteria, and their preexisting biofilms, as well as yeast-to-hyphae transformation. Therefore, these NPs with broad spectrum applications could be utilized in health settings to mitigate biofilm-related health conditions caused by pathogenic microbial strains.

Testing the Validity and Reliability of a Standardized Virtual Examination for Concussion.

Background and Objectives: We determined inter-modality (in-person vs telemedicine examination) and inter-rater agreement for telemedicine assessments (2 different examiners) using the Telemedicine Buffalo Concussion Physical Examination (Tele-BCPE), a standardized concussion examination designed for remote use. Methods: Patients referred for an initial evaluation for concussion were invited to participate. Participants had a brief initial assessment by the treating neurologist. After a patient granted informed consent to participate in the study, the treating neurologist obtained a concussion-related history before leaving the examination room. Using the Tele-BCPE, 2 virtual examinations in no specific sequence were then performed from nearby rooms by the treating neurologist and another neurologist. After the 2 telemedicine examinations, the treating physician returned to the examination room to perform the in-person examination. Intraclass correlation coefficients (ICC) determined inter-modality validity (in-person vs remote examination by the same examiner) and inter-rater reliability (between remote examinations done by 2 examiners) of overall scores of the Tele-BCPE within the comparison datasets. Cohen's kappa, κ, measured levels of agreement of dichotomous ratings (abnormality present vs absent) on individual components of the Tele-BCPE to determine inter-modality and inter-rater agreement. Results: For total scores of the Tele-BCPE, both inter-modality agreement (ICC = 0.95 [95% CI 0.86-0.98, p < 0.001]) and inter-rater agreement (ICC = 0.88 [95% CI 0.71-0.95, p < 0.001]) were reliable (ICC >0.70). There was at least substantial inter-modality agreement (κ ≥ 0.61) for 25 of 29 examination elements. For inter-rater agreement (2 telemedicine examinations), there was at least substantial agreement for 8 of 29 examination elements. Discussion: Our study demonstrates that the Tele-BCPE yielded consistent clinical results, whether conducted in-person or virtually by the same examiner, or when performed virtually by 2 different examiners. The Tele-BCPE is a valid indicator of neurologic examination findings as determined by an in-person concussion assessment. The Tele-BCPE may also be performed with excellent levels of reliability by neurologists with different training and backgrounds in the virtual setting. These findings suggest that a combination of in-person and telemedicine modalities, or involvement of 2 telemedicine examiners for the same patient, can provide consistent concussion assessments across the continuum of care.

Rectal Stricture Caused by a Rare Plasmacytoid Urothelial Carcinoma.

Malignant rectal strictures are uncommon, but they may pose a diagnostic challenge in clinical practice. We report the case of an 85-year-old male with an initially puzzling presentation of abdominal distention and discomfort. The patient was ultimately diagnosed with a rectal stricture caused by a plasmacytoid variant of urothelial cell carcinoma originating from the bladder. This case emphasizes the necessity of considering unique etiologies when evaluating rectal strictures and the aggressive character of this type of urothelial carcinoma.