Does Comorbid Food Allergy Affect Response to Omalizumab in Patients with Asthma?

Background: The intrinsic link between food allergy and asthma is well-established, and comorbidity can exacerbate both conditions. Omalizumab, an anti-immunoglobulin E (IgE) antibody, has the biological plausibility to manage both conditions, but only a few small studies have assessed omalizumab in patients with comorbid asthma and food allergy. Patients and Methods: We conducted a post hoc analysis of placebo-controlled, randomized clinical trials (IA05 in children and 008/009 in adolescents/adults) and real-world observational studies (EXCELS and PROSPERO). For each study, patients with asthma were stratified by whether they had physician-reported food allergy, as per baseline characteristics data. Results: For patients with comorbid food allergy, there was evidence for increased atopy at baseline (numerically higher total IgE levels and atopic comorbidities). The collective body of evidence found that omalizumab consistently improved general and asthma-specific patient-centered outcomes (food allergy-specific outcomes were not available). For patients with asthma, omalizumab improved healthcare resource use (emergency room visits, hospitalizations, unscheduled doctor visits), quality of life (asthma-specific Asthma Quality of Life Questionnaire), productivity (missed work/school days and the Work Productivity and Activity Impairment: Asthma), and asthma outcomes (asthma exacerbations and Asthma Control Test score) regardless of comorbid food allergy. Conclusion: There was no loss of omalizumab efficacy even though patients with both asthma and food allergy appeared to be generally more atopic. Omalizumab may be a viable management option for patients with these comorbidities. Clinical trial registration: NCT00079937; NCT01922037; NCT00252135.

Food allergy and asthma are linked and if you have both conditions then you can feel worse. There is a treatment available, called omalizumab, that helps people with asthma and helps people with food allergy, but it's not clear if it can help people with both conditions. Here, we look at whether omalizumab can help people with bad to very bad asthma (also called moderate to severe asthma) who also have food allergy. We found that omalizumab improved many aspects of a person's life, including whether they visited the emergency room, were admitted to hospital, their quality of life, whether they missed school or work, and whether their asthma improved. These improvements occurred in all people with moderate to severe asthma, whether they had food allergy or did not have food allergy. This suggests that omalizumab can help people with both conditions.

Development and acceptability of a decision-aid for food allergy Oral immunotherapy in children.

BACKGROUND: Limited decision-support tools are available to help shared decision-making (SDM) regarding food oral immunotherapy (OIT) initiation. No current tool covers all foods, forms, and pediatric ages for which OIT is offered. METHODS: In compliance with International Patient Decision Aid Standards criteria, this pediatric decision-aid comparing OIT versus avoidance was developed in three stages. Nested qualitative data assessing OIT decisional needs were supplemented with evidence-synthesis from the OIT literature to create the prototype decision-aid content. This underwent iterative development with food allergy experts and patient advocacy stakeholders until unanimous consensus was reached regarding content, bias, readability, and utility in making a choice. Lastly, the tool underwent validated assessment of decisional acceptability, decisional conflict, and decisional self-efficacy. RESULTS: The decision-aid underwent 5 iterations, resulting in a 4-page written aid (Flesch-Kincaid reading level 6.1) explaining therapy choices, risks and benefits, providing self-rating for attribute importance for the options and self-assessment regarding how adequate the information was in decision-making. A total of n = 135 caregivers of food-allergic children assessed the decision-aid, noting good acceptability, high decisional self-efficacy (mean score 85.9/100) and low decisional conflict (mean score 20.9/100). Information content was rated adequate and sufficient, the therapy choices wording balanced, and presented without bias for a "best choice." Lower decisional conflict was associated with caregiver-reported anaphylaxis. CONCLUSIONS: This first pediatric OIT decision-aid, agnostic to product, allergen, and age has good acceptability, limited bias, and is associated with low decisional conflict and high decisional self-efficacy. It supports SDM in navigating the decision to start OIT or continue allergen avoidance.

Promoter Hypermethylation of the BRCA1 Gene as a Novel Biomarker for Prostate Cancer.

Prostate cancer (PCa) is recognized as one of the most common malignancies that greatly affects the male population globally. Breast cancer gene 1 (BRCA1) is an important tumor suppressor gene that plays a central role in the maintenance of genomic integrity by promoting the repair of double-strand breaks of DNA. Here, we present a pilot study to examine the promoter methylation and gene expression of the BRCA1 gene in patients with PCa in Erbil governorate, Iraq. The collection of samples took place in Erbil City, Iraq, specifically at Rizgary Hospital, PAR Hospital, and Al-Mufti's private laboratory. A total of 40 tissue samples were collected from age-matched individuals, comprising 30 pathologically confirmed PCa cases and 10 normal prostatic tissue taken from individuals who, during diagnosis, were found to be negative for PCa. Data on demographic and clinical information, such as pathological stage, age, and prostate-specific antigen (PSA) level, were gathered from the medical records. The impact of the promoter methylation was forecasted using the DNA bisulfite conversion technique and methyl-specific PCR (MSP) with specific primers for the BRCA1 promoter region. The assessment of BRCA1 expression was conducted using quantitative real-time PCR (qPCR). Among the 30 patients examined, 76.6% (23 cases) were found to have BRCA1 promoter methylation, and none of the normal tissues appeared to have DNA methylation. BRCA1 promoter methylation was positively associated with the advanced stage of disease (p=0.01) and Gleason score (p=0.007). The analysis revealed a significant downregulation of the BRCA1 gene expression in methylated tumor samples as compared to non-methylated tumors and normal tissues, suggesting the role of epigenetic silencing. To the best of our knowledge, this is the first study investigating methylation status and level of BRCA1 mRNA transcripts among PCa patients in Iraq. Our findings suggest that promoter hypermethylation of the BRCA1 gene could serve as a viable biomarker for PCa, marking a significant discovery.

Prevalence and Factors Associated with Adherence to Iron-Folic Acid Supplementation Among Pregnant Women in Eastern Sudan: A Cross-Sectional Study.

Purpose: The present study was conducted to determine the prevalence and factors associated with adherence to iron-folic acid supplementation (IFAS) among pregnant women in eastern Sudan. Methods: A cross-sectional survey was conducted among pregnant women who obtained antenatal care (ANC) at Gadarif Maternal Hospital in eastern Sudan between May 1 and August 31, 2023. Face-to-face interview questionnaires were used to gather sociodemographic, obstetric, and clinical data (age, parity, education, residence, and previous medical diseases). Knowledge of anemia and IFAS was assessed. Multivariate analysis was performed to adjust for confounders. Results: A total of 568 pregnant women were enrolled in the present study. Among them, 449 (79.0%) adhered to the IFAS. The multivariate analysis showed that the adjusted odds ratio (AOR) of IFAS adherence increased with ANC visits > 4 (AOR = 1.68, 95.0% CI = 1.01-2.77) and knowledge of anemia (AOR = 2.06, 95.0% CI = 1.437-3.276). In the univariate analysis, maternal occupation and knowledge of IFAS adherence were the only factors associated with IFAS adherence. Maternal age, parity, gestational age, education, residence, occupation, medical insurance, medical disease, and husband's occupation were not associated with IFAS. Forgetfulness (71.0%), frustration from taking many drugs (54.6%), and unpleasant tests of the supplement (50.7%) were the main reasons for not taking the IFAS. Conclusion: About four out of five pregnant women adhered to the IFAS, indicating a good level of adherence, especially among women who attended more than four ANC visits and those with good knowledge of anemia. More attention is needed to encourage ANC to increase adherence to IFAS.

Who let the dogs out? A 10-year review of maxillofacial dog bite injuries.

Dog bites are common within the United Kingdom, with their incidence increasing over recent years. Bites to the head and neck region can have substantial and multifactorial implications for victims, and can provide a challenge to maxillofacial departments. This study is a 10-year retrospective review of head and neck dog bites that required input from the maxillofacial team within the Cwm Taf Morgannwg University Health Board. Data collected included demographics of the patients involved, relationship with and breed of dog, nature of the injury, treatment received, and nature of any complications. In total, 168 records matched our inclusion criteria. The median age of our cohort was 12 years, with 57.1% of patients being younger than 15. Of the patients, 52.4% were female. Eighty-three per cent of cases involved a known dog, with Jack Russells being the breed most commonly involved. The upper lip was the most commonly affected area (30.3%), followed by the cheek (24.5%). Twenty-eight per cent of patients were admitted for management in theatre, with 8% of the total patients experiencing a complication. In conclusion, head and neck dog bites most commonly affect children and the upper lip.

Rocket Dynamics of Capped Nanotubes: A Molecular Dynamics Study.

The study of nanoparticle motion has fundamental relevance in a wide range of nanotechnology-based fields. Molecular dynamics simulations offer a powerful tool to elucidate the dynamics of complex systems and derive theoretical models that facilitate the invention and optimization of novel devices. This research contributes to this ongoing effort by investigating the motion of one-end capped carbon nanotubes within an aqueous environment through extensive molecular dynamics simulations. By exposing the carbon nanotubes to localized heating, propelled motion with velocities reaching up to ≈0.08 nm ps-1 was observed. Through systematic exploration of various parameters such as temperature, nanotube diameter, and size, we were able to elucidate the underlying mechanisms driving propulsion. Our findings demonstrate that the propulsive motion predominantly arises from a rocket-like mechanism facilitated by the progressive evaporation of water molecules entrapped within the carbon nanotube. Therefore, this study focuses on the complex interplay between nanoscale geometry, environmental conditions, and propulsion mechanisms in capped nanotubes, providing relevant insights into the design and optimization of nanoscale propulsion systems with various applications in nanotechnology and beyond.

CilioGenics: an integrated method and database for predicting novel ciliary genes.

Uncovering the full list of human ciliary genes holds enormous promise for the diagnosis of cilia-related human diseases, collectively known as ciliopathies. Currently, genetic diagnoses of many ciliopathies remain incomplete (1-3). While various independent approaches theoretically have the potential to reveal the entire list of ciliary genes, approximately 30% of the genes on the ciliary gene list still stand as ciliary candidates (4,5). These methods, however, have mainly relied on a single strategy to uncover ciliary candidate genes, making the categorization challenging due to variations in quality and distinct capabilities demonstrated by different methodologies. Here, we develop a method called CilioGenics that combines several methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF) network analysis, and text mining) to predict the ciliary capacity of each human gene. Our combined approach provides a CilioGenics score for every human gene that represents the probability that it will become a ciliary gene. Compared to methods that rely on a single method, CilioGenics performs better in its capacity to predict ciliary genes. Our top 500 gene list includes 258 new ciliary candidates, with 31 validated experimentally by us and others. Users may explore the whole list of human genes and CilioGenics scores on the CilioGenics database (https://ciliogenics.com/).

A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Breast Cancer High-Penetrance Genes BRCA1 and BRCA2 Mutations Using Next-Generation Sequencing Among Iraqi Kurdish Women.

Background BRCA1 and BRCA2 genes are the main high-penetrance genes that are responsible for most cases of inherited breast cancer. The present study aimed to detect the frequencies of inherited breast cancer caused by BRCA1 and BRCA2 genes among Kurdish breast cancer patients, including all the exome of these two genes, using next-generation sequencing (NGS). Methodology Seventy women who were diagnosed with breast cancer and registered at Nanakali Hospital in Erbil, Iraq, were included. Blood samples were collected for molecular testing (polymerase chain reaction (PCR)) targeting all exomes of BRCA1 and BRCA2 genes. All exome regions are sequenced by NGS using the Miseq system (Illumina Inc., San Diego, CA). Obtained data were visualized using Integrative Genomics Viewer (IGV 2.3 Software, Broad Institute, Cambridge, MA). Data were interpreted based on the National Center for Biotechnology Information (NCBI), Clinically Relevant Variation (ClinVar) archives, and other databases. Results Among 70 samples, more than forty-two variants have been detected, 20 on BRCA1 and 22 on BRCA2. Regarding clinical significance, six (14.28%) variants were pathogenic, four of them on the BRCA1 gene, which were: c.3607C>T, c.3544C>T, c.68_69del, and c.224_227delAAAG, and two pathogenic variants were on BRCA2 gene: c.100G>T, and c.1813delA. Also, two (4.76%) variants were conflict interpretations of pathogenicity, one (2.38%) was a variant of uncertain significant VUS, and the rest 29 (69%) variants were benign. In addition, four new variants (three in BRCA1 and one in BRCA2 gene), never previously reported, were identified. Conclusions In conclusion, analyzing the BRCA1/2 genes provide a better prediction for the risk of developing breast cancer in the future. Variant types and frequencies differ among different populations and ethnicities, the common mutations worldwide may not be prevalent in the Kurdish population. The current research findings will be useful for future screening studies of these two genes in the Kurdish population.

Effective intravitreal gene delivery to retinal pigment epithelium with hyaluronic acid nanospheres.

Inherited retinal degeneration (IRD) can cause a wide range of different forms of vision loss and blindness, and in spite of extensive advancements in gene therapy research, therapeutic approaches for targeting IRDs are still lacking. We have recently developed an approach for the intravitreal co-delivery of hyaluronic-acid nanospheres (HA-NSs) with sulfotyrosine (ST), effectively reaching the outer retina from the vitreal cavity. Here, our goal was to understand whether DNA-filled HA-NSs could generate gene expression in the outer retina. TxRed-labeled HA-NSs were compacted with plasmid DNA carrying a GFP reporter gene and intravitreally injected into the mouse retina. Follow-up at 4 weeks showed widespread gene expression in the outer retina and reduced, albeit present, expression at 8 weeks post-injection. Further analysis revealed this expression to be largely localized to the retinal pigment epithelium (RPE). These data show that intravitreal delivery of HA-NSs is a promising non-viral platform for the delivery of therapeutic genes and can generate pan-tissue, persistent gene expression in the RPE.

Arthroscopic Repair of Posterosuperior Rotator Cuff Tears Using a Modified Mason-Allen Suture Technique With a Transosseous-Equivalent Construct: A Technical Note.

Iterative evolutions in arthroscopic rotator cuff repair aim to improve its biomechanical and biological properties. This technical note describes an arthroscopic rotator cuff repair technique that combines the advantages of a modified Mason-Allen suture technique with the advantages of an arthroscopic transosseous-equivalent construct. Two alternatives for creating this construct are described. The Mason-Allen stitch is easy to perform, is cost-effective, and increases tissue security without tendon strangulation. The arthroscopic transosseous-equivalent construct increases footprint contact pressure and coverage, aiding healing of the repaired rotator cuff.

Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders.

Given the absence of approved treatments for pathogenic variants in Peripherin-2 (PRPH2), it is imperative to identify a universally effective therapeutic target for PRPH2 pathogenic variants. To test the hypothesis that formation of the elongated discs in presence of PRPH2 pathogenic variants is due to the presence of the full complement of rhodopsin in absence of the required amounts of functional PRPH2. Here we demonstrate the therapeutic potential of reducing rhodopsin levels in ameliorating disease phenotype in knockin models for p.Lys154del (c.458-460del) and p.Tyr141Cys (c.422 A > G) in PRPH2. Reducing rhodopsin levels improves physiological function, mitigates the severity of disc abnormalities, and decreases retinal gliosis. Additionally, intravitreal injections of a rhodopsin-specific antisense oligonucleotide successfully enhance the physiological function of photoreceptors and improves the ultrastructure of discs in mutant mice. Presented findings shows that reducing rhodopsin levels is an effective therapeutic strategy for the treatment of inherited retinal degeneration associated with PRPH2 pathogenic variants.

Navigated augmented reality through a head-mounted display leads to low deviation between planned, intra- and postoperative parameters during glenoid component placement of reverse shoulder arthroplasty: a proof-of-concept case series.

BACKGROUND: Navigated augmented reality (AR) through a head-mounted display (HMD) has led to accurate glenoid component placement in reverse shoulder arthroplasty (RSA) in an in-vitro setting. The purpose of this study is to evaluate the deviation between planned, intraoperative, and postoperative inclination, retroversion, entry point, and depth of the glenoid component placement during RSA, assisted by navigated AR through an HMD, in a surgical setting. METHODS: A prospective, multicenter study was conducted. All consecutive patients undergoing RSA in 2 institutions, between August 2021 and January 2023, were considered potentially eligible for inclusion in the study. Inclusion criteria were as follows: age >18 years, surgery assisted by AR through an HMD, and postoperative computed tomography (CT) scans at 6 weeks. All participants agreed to participate in the study and informed consent was provided in all cases. Preoperative CT scans were undertaken for all cases and used for 3-dimensional (3D) planning. Intraoperatively, glenoid preparation and component placement were assisted by a navigated AR system through an HMD in all patients. Intraoperative parameters were recorded by the system. A postoperative CT scan was undertaken at 6 weeks, and 3D reconstruction was performed to obtain postoperative parameters. The deviation between planned, intraoperative, and postoperative inclination, retroversion, entry point, and depth of the glenoid component placement was calculated. Outliers were defined as >5° for inclination and retroversion and >5 mm for entry point. RESULTS: Seventeen patients (9 females, 12 right shoulders) with a mean age of 72.8 ± 9.1 years (range, 47.0-82.0) met inclusion criteria. The mean deviation between intra- and postoperative measurements was 1.5° ± 1.0° (range, 0.0°-3.0°) for inclination, 2.8° ± 1.5° (range, 1.0°-4.5°) for retroversion, 1.8 ± 1.0 mm (range, 0.7-3.0 mm) for entry point, and 1.9 ± 1.9 mm (range, 0.0-4.5 mm) for depth. The mean deviation between planned and postoperative values was 2.5° ± 3.2° (range, 0.0°-11.0°) for inclination, 3.4° ± 4.6° (range, 0.0°-18.0°) for retroversion, 2.0 ± 2.5 mm (range, 0.0°-9.7°) for entry point, and 1.3 ± 1.6 mm (range, 1.3-4.5 mm) for depth. There were no outliers between intra- and postoperative values and there were 3 outliers between planned and postoperative values. The mean time (minutes : seconds) for the tracker unit placement and the scapula registration was 03:02 (range, 01:48 to 04:26) and 08:16 (range, 02:09 to 17:58), respectively. CONCLUSION: The use of a navigated AR system through an HMD in RSA led to low deviations between planned, intraoperative, and postoperative parameters for glenoid component placement.

Management of type 2 diabetes in New Zealand: a scoping review of interventions with measurable clinical outcomes.

OBJECTIVE: This review aimed to assess the effectiveness of interventions for type 2 diabetes (T2D) management in New Zealand on clinical outcomes, and explore the factors impacting their feasibility and acceptability. STUDY DESIGN: Scoping review. METHODS: Three databases (PubMed, Web of Science and Scopus) were searched between January 2000 and July 2023. Reference lists of included studies were hand searched to identify additional articles. RESULTS: The search yielded 550 publications, of which 11 were included in the final review. Most interventions (n = 10) focussed on education and seven were delivered by health professionals. Supporting factors for interventions included clinical/peer support (n = 8) and whanau (family) involvement (n = 6). Hindering factors included non-adherence (n = 4) and high drop-out (n = 4). Most studies reported modest improvement in HbA1c and weight at six months, but minimal change in HbA1c, weight, lipids, renal profile, and blood pressure by two years. CONCLUSION: Future interventions should involve culturally appropriate approaches to improve engagement and acceptability while addressing lifestyle and medication adherence for T2D management. T2D interventions not widely disseminated via academic channels need to be further identified.

Exploring the dynamics of human scent in forensic canine analysis: Factors shaping identification accuracy.

Using specially trained canines in forensic analysis to identify individual human scents is a well-established method, capitalizing on dogs' exceptional olfactory abilities. This study investigates the survival of human scent under extreme weather conditions in the Kingdom of Bahrain. Five experienced German Shepherd police dogs, trained for human scent tracking, participated in the experiments. The study was conducted during Bahrain's hot summer season, characterized by high temperatures, high humidity, and occasional strong winds. Three common surfaces-sand, grass, and asphalt-were selected to represent scenarios where human scent might be detected. The findings revealed that human scent persisted for approximately 8-11 hours on sand and grass but only 1-3 hours on asphalt, highlighting the impact of surface type on scent survival. The research also examined the effect of temperature on scent survival, testing at three different temperatures: 30°C, 40°C, and 50°C. The results demonstrated that scent durability varied across types of articles and temperature conditions. For instance, at 30°C, human scent remained detectable for up to 93 days on leather but only 27-28 days on silk cloth. At 40°C, leather allowed the scent to last 64-65 days, while wood surfaces had the shortest duration. The scent lasted 37-39 days on jeans cloth at a temperature of 50°C but only 3-4 days on wood. The data gathered can be beneficial for forensic investigations in semi-desert areas involving canine olfaction, offering guidance on the timing and likelihood of scent detection.

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis.

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011-30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.