Psychological outcome measures guide research and clinical decision-making, yet many widely used tools were developed with limited psychometric rigour. Although advanced methods (e.g., item response theory, structural equation modelling) are now widely available, their added value in applied research remains uncertain and applied researcher perspective regarding such are unexplored. We aimed to address this gap in knowledge by examining key stakeholder perspective. To explore how these methods are perceived, we conducted semi-structured interviews with 21 stakeholders spanning psychometrics, clinical practice, applied research, statistics and academia. Data were analysed using reflexive thematic analysis. Analysis identified three overarching themes: (1) growing recognition that heterogeneity in latent traits challenges assumptions underlying many measures, (2) the enduring use of entrenched but psychometrically weak tools and (3) nuanced views on when advanced methods meaningfully influence research findings. Participants acknowledged gaps in psychometric literacy and emphasised the need for more training and collaboration with psychometricians. These findings highlighted persistent limitations in measurement practice, clarify contexts where psychometric methods add genuine value, and point to opportunities for strengthening outcome measurement in psychology and psychiatry research.
During recombinant adeno-associated virus (rAAV) production, certain components of the manufacturing system can be encapsidated as unwanted nucleic acid contaminants. Prior work has established that the p5 promoter is critical for efficient vector production and is responsible for a significant portion of this aberrant cross-packaging. The Rep binding element (RBE) and terminal resolution site (TRS)-mimic loop on p5 putatively facilitate off-target packaging of DNA directly adjacent to p5 into rAAV particles. To prevent this, we replaced AAV2 p5 with homologues from several closely related AAV serotypes. All homologues tested that maintained vector production efficiency continued to package p5-adjacent sequences. However, specific mutations of the TRS-mimic site prevented contaminant incorporation but reduced expression of p5-derived Rep proteins and overall production efficiency. When Rep78/68 isoform expression was restored, these new TRS-modified p5 plasmids enabled rAAV production at comparable titers, with significantly reduced p5-associated contaminants, irrespective of scale and serotype. P5-associated contaminants were also observed in the context of rAAV production using covalently closed linear DNA, for which the TRS-mimic modification also significantly reduced DNA contamination while maintaining vector titers. Our findings have implications for efficiently producing rAAVs with increased purity for gene therapy.
Thirty-six Polypay crossbred wether lambs (33.49 ± 2.81 kg) were used to determine the relative bioavailability of supplemental potentiated zinc oxide (PZO) in comparison to zinc sulfate (ZnSO4) and resulting effects on zinc (Zn) retention, nutrient digestibility, and nitrogen (N) balance. Wethers were sorted by body weight (BW) into 3 blocks and stagger-started on trial. On day -25 (relative to collection period start), wethers were housed in group pens and began a low-Zn diet (25 mg Zn/kg DM) that was fed for the entirety of the study. Wethers were moved to individual crates on day -10, where they acclimated for 5 days before dietary treatments began on day -5. Zinc treatments were top-dressed using ground corn as a carrier: 1) Control (CON) - no additional Zn supplementation, 2) HiZox® (PZO) - 40 mg of supplemented Zn from a potentiated Zn oxide, and 3) Zinc sulfate (ZS) - 40 mg of supplemented Zn from ZnSO4. Day 1 began a 5-day total collection period of feces and urine that was utilized for determination of Zn and N retention, as well as dry matter (DM), organic matter (OM), and neutral detergent fiber (NDF) digestibility. Blood was collected on day -5, before starting treatment, and on day 1 and day 5 of the collection period to assess circulating plasma Zn concentrations. Mineral solubility was evaluated and filtrate Zn content was analyzed. Data were analyzed using the mixed procedure of SAS 9.4 (SAS Institute, Cary, NC). Contrasts compared CON vs. ZINC (PZO and ZS together) and the two Zn sources (PZO vs. ZS). Significance was declared at P ≤ 0.05 and tendencies at 0.05 < P ≤ 0.10. Dietary treatment did not affect DM, OM, or NDF intake, fecal output, or N intake, fecal and urinary output, and retention (mg/d and percent of intake; P ≥ 0.24). Nitrogen retention was greater in wethers supplemented with Zn (P = 0.02). Zinc intake, fecal output, retention (mg/d and percent of intake), and apparent absorption were greater for ZINC compared with CON (P ≤ 0.01) but did not differ between Zn sources (P ≥ 0.44). The inclusion of supplemental Zn improved N apparent absorption (P = 0.02), however, no differences were observed between Zn sources (P = 0.25). The PZO was less soluble in both solutions compared to the ZS (P ≤ 0.01). These data indicate the potentiated Zn oxide has a similar relative bioavailability compared to Zn sulfate and elicited similar effects on diet digestibility and N utilization. Zinc is an essential mineral added to livestock diets to support growth and efficient nutrient use. This study compared a novel zinc oxide product with zinc sulfate, a commonly used zinc supplement, to evaluate how effectively each source would be utilized by wethers. Researchers measured how much zinc the wethers absorbed and retained, as well as the effects of zinc supplementation on diet digestibility and nitrogen utilization. Results showed the wethers supplemented with either zinc source performed similarly to each other and better than the lambs that received no zinc, indicating both sources effectively provided zinc to the wethers. In addition, zinc supplementation improved nitrogen absorption. These findings suggest that the novel zinc oxide is an effective alternative to zinc sulfate and that the addition of dietary zinc can improve nitrogen utilization in lambs.
The Hawaiian phoneme inventory includes a consonant ('okina) typically described as glottal stop. Recent studies have found that 'okina is rarely produced with full glottal closure utterance-medially, and is instead produced as a period of creaky phonation. This study investigated the acoustic correlates of utterance-initial 'okina following a pause. Although visible creaky phonation did not occur for utterance-initial 'okina, several reliable acoustic correlates were found during the first vowels of utterances that started with 'okina. Vowels preceded by 'okina had higher fundamental frequency, more abrupt onsets of acoustic energy, greater acoustic energy both in the fundamental frequency and across all frequency ranges, lower harmonics-to-noise ratios, and higher jitter than vowels that started without a preceding 'okina. Linear discriminant analyses of the data showed that these acoustic correlates were able to correctly categorize ∼75% of productions. Although no concurrent articulatory data were collected, arguments are provided to suggest that 'okina is regularly produced as full glottal closure utterance-initially in Hawaiian, possibly because of effects of prosodic strengthening. We believe the present study is the first to establish a relationship between utterance-initial glottal stop and these acoustic effects on the following vowel.
Inhibition of terminal complement activation is an effective therapeutic strategy for acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD), but it increases the risk of invasive meningococcal infections. Consequently, vaccination against meningococcal serogroups A, C, W, Y, and B is mandatory for all patients receiving complement inhibitors. This article provides expert consensus recommendations for managing meningococcal vaccination in patients with NMOSD and gMG receiving complement-inhibiting therapies in Germany, Austria, and Switzerland. The timing and procedures of vaccination should be adapted to the underlying diagnosis and the individual risk of disease exacerbation in this population. In NMOSD, treatment often must begin promptly, particularly after an acute attack; in such cases, vaccination should be administered at treatment initiation together with antibiotic prophylaxis. By contrast, treatment urgency in gMG is typically lower, allowing vaccination to be completed in advance and thereby avoiding antibiotic exposure, which may worsen gMG symptoms. For both diseases, ceftriaxone is recommended as first-line therapy for suspected infection, rifampicin for prophylaxis, and either rifampicin or intramuscular ceftriaxone for post-exposure chemoprophylaxis. Patients should also carry a standby dose of ciprofloxacin for emergency self-administration at the first signs of meningitis, followed by immediate clinical evaluation. These recommendations should be reviewed regularly and updated as necessary to reflect emerging evidence and new vaccine options. How to prevent serious infections during treatment for NMOSD and myasthenia gravis Blocking terminal complement activation is an effective treatment for people with acetylcholine receptor antibody–positive generalized myasthenia gravis (gMG) and aquaporin-4 antibody–positive neuromyelitis optica spectrum disorder (NMOSD). However, this treatment increases the risk of serious meningococcal infections. For this reason, all patients receiving complement inhibitors must be vaccinated against meningococcal serogroups A, C, W, Y, and B. This article presents expert consensus recommendations on how to manage meningococcal vaccination in patients with NMOSD and gMG receiving complement-inhibiting therapies in Germany, Austria, and Switzerland. The timing and approach to vaccination should be adapted to the specific disease and to each patient’s risk of worsening symptoms. In NMOSD, treatment often needs to start quickly, especially after an acute attack. In these cases, vaccination should be given at the start of complement inhibitor therapy together with preventive antibiotic treatment. In contrast, treatment for gMG is usually less urgent. This often allows vaccination to be completed before therapy begins and helps avoid antibiotic use, which may worsen gMG symptoms. For both diseases, ceftriaxone is recommended as the first treatment if infection is suspected. Rifampicin is recommended for preventive antibiotic treatment, and either rifampicin or intramuscular ceftriaxone can be used after possible exposure to infection. Patients should also carry a standby dose of ciprofloxacin to take immediately if early signs of meningitis appear, followed by urgent medical evaluation. These recommendations should be reviewed regularly and updated as new evidence and vaccines become available.
Understanding which posts spark conversation, and how large those conversations grow, is vital for moderation, resource allocation, and anticipating information cascades on Reddit and other social platforms. We study discussion initiation and growth on Reddit by modelling whether a root post receives any comments and how large the resulting thread becomes. Using reconstructed threads from r/politics, r/CryptoCurrency, and r/Conspiracy, we extract compact textual, semantic, temporal, domain, and author features from each post. We train subreddit-specific classifiers with small, transparent feature sets and use SHAP for interpretation. Across communities, the external domain a post links to, and, in news ecosystems, the domain's centrality, consistently emerge as predictors of both the start and scale of discussion. Author activity is also predictive: posts from highly active users are more likely to receive comments. Simple textual cues help too: longer subjects and fewer question marks are associated with a higher likelihood of eliciting replies. Community context moderates these effects: in r/politics, linking familiar mid-tier but well-connected news sources is associated with larger threads, while the r/Conspiracy and r/CryptoCurrency communities prefer novel sources. Predicting whether a discussion will start is notably easier than forecasting its eventual size, as adjacent size classes are often confounded. Still, a concise, interpretable feature set captures a substantial proportion of the predictive signal. Our results suggest practical applications for triage: flagging posts likely to trigger substantial discussion could support targeted, pre-emptive moderation and fact-checking without relying on complex, opaque models.
There has been a growing trend of combining traditional Chinese medicine and Western medicine, but the safety of co-prescribing Salvia miltiorrhiza (Danshen) and anticoagulants remains uncertain. This study aimed to evaluate the bleeding risk following the concurrent prescribing of S. miltiorrhiza and anticoagulants in a real-world setting. A self-controlled case series study was conducted. This study used the Chang Gung Research Database to identify adult patients co-prescribed oral anticoagulants and S. miltiorrhiza, and having records of bleeding events. Bleeding events included any bleeding event (gastrointestinal, intracranial, or urogenital bleeding) and major bleeding events (hemorrhages requiring hospitalization or transfusion). Exposure periods were defined as days of concurrent prescribing of S. miltiorrhiza and anticoagulants, while control periods included days of anticoagulant use without S. miltiorrhiza. Conditional Poisson regression was applied to estimate bleeding risk during exposure periods relative to control periods, and results were presented as adjusted incidence rate ratio (aIRR) and 95% confidence interval (95%CI). Among 525 patients receiving both medications, 146 experienced bleeding events. The risk of any bleeding increased significantly during days 1-14 (aIRR: 3.98; 95% CI: 3.29-4.77) and days 15-28 (aIRR: 3.99; 95% CI: 3.23-4.79) after concurrent prescribing of S. miltiorrhiza and anticoagulants. Elevated risks of gastrointestinal bleeding (aIRR: 3.79; 95% CI: 2.95-4.53) and intracranial hemorrhage (aIRR: 3.59; 95% CI: 2.79-5.03) were observed within the first 14 days. Concurrent use of S. miltiorrhiza and anticoagulants significantly increased bleeding risk, particularly during the first 28 days of coadministration. These findings highlight the need for careful monitoring during the initial period of combined therapy. Concurrent use of Danshen (a Chinese herbal medicine) and anticoagulants may increase bleeding risk Danshen, also known as Salvia miltiorrhiza, is a traditional Chinese medicine that is commonly used for heart and circulation problems. In Taiwan, Danshen is frequently prescribed together with modern Western medications. One group of these medicines, called anticoagulants, are commonly used to prevent blood clots in people with conditions such as atrial fibrillation or heart disease. While anticoagulants are effective, they can increase the risk of bleeding. It has been uncertain whether using Danshen at the same time might make this risk even greater. In this study, we used a large medical records database to investigate the real-world safety of taking Danshen together with anticoagulants. We included 525 adults who were prescribed both treatments and 146 of them had records of bleeding events. To minimize differences between individuals, we applied a self-controlled case series (SCCS) study design, where each patient served as their own control. We found that the risk of bleeding was significantly higher during the first 28 days after patients started taking Danshen with an anticoagulant. The risk was especially high for gastrointestinal and intracranial bleeding. On average, the first bleeding event happened about 16 days after starting combined treatment. Importantly, most patients in our study already had a high baseline risk of bleeding, but even after adjusting for other factors, the increased risk remained clear. These findings suggest that patients who take Danshen alongside anticoagulants should be monitored carefully, particularly during the first few weeks of combined use. This study highlights the need for careful communication about herbal and conventional medicine use.
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory noninfectious disease of the bone that predominantly affects children and adolescents. Bisphosphonates (BPs) are used to treat of CNO with most clinical experience involving pamidronate. Neridronate (NER) is an amino BP with a chemical structure and potency close to pamidronate. This study aims to evaluate the effectiveness and safety of NER in patients with CNO. Monocentric retrospective cohort study. This is a retrospective cohort study conducted on patients included in the monocentric CAMELOT (Chronic non-bActerial osteoMyELitis: A mOnocentric regisTry) registry. Response to treatment was evaluated semiquantitatively based on clinical, laboratory, and radiological domains. The cohort consisted of 27 subjects. Thirteen (48%) received NER alone. At baseline, patients receiving NER alone tended to have a higher rate of vertebral fractures than those treated with combination therapy (46% vs 29%; p = 0.4). The median number of peripheral lesions at magnetic resonance imaging was clearly lower in patients treated with NER alone (0 (interquartile range (IQR) 0-2) vs 2 (IQR 1-5); p = 0.01). An overall response (complete or partial) to NER was documented in all but one patient (96%). Six patients (22%) achieved a complete response in all the three domains, 83% of whom (n = 5) received NER without any other concomitant treatments. Interestingly, using a Receiver Operating Characteristic-derived cutoff of 2 years from CNO diagnosis, all patients who achieved a complete response (100%) had received NER within the first 2 years from diagnosis, compared with 57% (n = 12) of those who did not (p = 0.07). No long-term NER complications were observed. Neridronate appears to be a safe and effective option for CNO, particularly in patients with recent-onset disease, spinal involvement, and fewer peripheral lesions. Early initiation may be associated with higher rates of complete response, though further studies are needed to confirm these findings. Neridronate treatment for chronic nonbacterial osteomyelitis: Real-world evidence on effectiveness, safety, and the importance of early treatment Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease that can cause bone pain, swelling, and fractures, particularly affecting children and young adults. Because the disease is uncommon, there is limited information on the best treatment options and on their long-term safety. Neridronate is a medication that reduces bone inflammation and is increasingly used in CNO, but real-life data on its effectiveness are still scarce. In this study, we analyzed patients with CNO included in the CAMELOT registry, a single-center database that collects clinical information from routine care. We evaluated how well patients responded to neridronate by looking at symptoms, blood tests for inflammation, and imaging findings. We also assessed possible side effects. A total of 27 patients were included. Almost half received neridronate alone, while others received it together with additional treatments. Overall, neridronate was effective in nearly all patients, with improvement seen in symptoms, laboratory markers, or imaging findings. About one in five patients achieved a complete response, meaning improvement in all evaluated areas. Most of these patients were treated with neridronate alone. Importantly, all patients who achieved a complete response had started neridronate within two years of being diagnosed with CNO. This suggests that earlier treatment may lead to better outcomes. Neridronate was well tolerated, and no long-term safety concerns were observed during follow-up. In summary, neridronate appears to be a safe and effective treatment for chronic nonbacterial osteomyelitis, especially when started early in the disease course and in patients with spinal involvement or fewer affected bones. Further studies are needed to confirm these findings in larger groups of patients.
A variety of etiologies can lead a patient to present with symptoms that appear manic. A wide differential should be considered, including delirium, which may in turn be caused by multiple etiologies. Substance ingestion, specifically of dietary supplements, is one potential trigger that is not always considered. A 40-year-old male patient with a history of long-standing attention-deficit/hyperactivity disorder (ADHD), anxiety, and depression presented with anxiety, restlessness, memory gaps, nausea, low appetite, and insomnia. Prior to admission, the patient started taking an herbal supplement for 15 days and stopped taking lisdexamfetamine for 1.5 weeks. Upon initial presentation, the patient was hypertensive and tachycardic. The physical exam was significant for bilateral conjunctival injection and hand tremors. He was disoriented to time and had tangential, pressured speech. A comprehensive medical work-up was largely unremarkable. The urine drug screen was positive for amphetamines and marijuana. The Psychiatry Consultation and Liaison Service evaluated this patient and diagnosed him with delirium, possibly secondary to the supplement side effects. The supplement was discontinued, and the patient's symptoms resolved within 24 hours. While many diagnoses were considered for this patient, delirium, possibly triggered by starting a new herbal supplement, was determined to be the most likely etiology. Many supplements have not been well-studied and are inadequately regulated. This case highlights the potential for clinically significant adverse effects associated with supplement use and emphasizes the need for further research into their safety profiles, pharmacokinetics, and neuropsychiatric consequences to improve patient care and education.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated multisystemic small vessel inflammatory disease. Its diverse clinical presentation overlaps both within its own phases and with other disorders, complicating diagnosis. We present a case of a 60-year-old female who developed symptoms suggestive of giant cell arteritis (GCA) with polymyalgia rheumatica (PMR) shortly after starting treatment with dupilumab for severe rhinosinusitis. On further evaluation, the temporal artery biopsy was negative for arteritis, and the skin biopsy confirmed the diagnosis of EGPA. This case emphasizes the importance of recognizing shared symptoms and constantly reassessing vasculitis patients. Timely and accurate diagnosis is crucial for unique treatment strategies tailored for each vasculitis. This case also brings attention to the fact that some anti-asthma drugs, including dupilumab, can potentially unmask pre-existing subclinical EGPA. Although there are few documented cases of EGPA diagnosed after dupilumab treatment, this association requires further investigation, as current literature is uncertain whether it acts as a trigger versus lacking a direct impact on disease treatment.
Hypersensitivity reactions to second-generation antipsychotics and mood stabilizers are uncommon and can lead to serious complications. These medicines are generally well tolerated, but there have been reports of unusual allergic reactions, such as hives or itching, associated with these drugs. The patient is a 45-year-old woman who presented with a recurrence of a manic episode of bipolar I disorder and developed skin complications and itching after receiving valproate and levetiracetam. She subsequently experienced severe skin allergic reactions, including hives and itching, after taking various second-generation antipsychotics, including risperidone, aripiprazole, and quetiapine. These allergic reactions occurred shortly after starting the medication and resolved after discontinuing the drug. The purpose of this case report is to highlight the importance of being aware of the possibility of concomitant hypersensitivity with various antipsychotic and anticonvulsant medications, which can affect the diagnosis and treatment of the disease.
Preoperative anemia (PA) and red blood cell transfusion (RBT) are associated with decreased survival in several cancers. In muscle-invasive bladder cancer (MIBC), anemia is frequent and may be worsened by neoadjuvant chemotherapy (NAC). While PA's impact is known in patients undergoing cystectomy without NAC, its prognostic value in the current multimodal approach remains unclear. We retrospectively analyzed patients with cT2-T4 N0-N2 M0 MIBC treated with cisplatin-based NAC followed by radical cystectomy and lymphadenectomy between 2011 and 2022. We recorded the lowest hemoglobin value from NAC start to surgery (PA), use of RBT during NAC, and iron or vitamin B9/B12 supplementation. This monocentric cohort included 175 patients (77% men, median age 65); 79% received dose-dense-MVAC, 75% had ≥ 4 cycles, median follow-up was 59 months. PA was present in 95%, with 58.2% having grade > 1. Among these, 50% received ≥ 1 transfusion, and 34.7% received supplementation. PA grade > 1 was significantly associated with worse OS (HR = 2.67, p = 0.006), RFS (HR = 2.00, p = 0.019), and SS (HR = 3.35, p = 0.003) versus PA grade 0-1. Other independent prognostic factors for OS included neutrophil count > 7 G/L (HR = 2.71, p = 0.010) and ypN+ (HR = 10.35, p < 0.001). RBT had no significant impact. This retrospective analysis demonstrated that PA grade > 1 negatively impacts overall survival, independent of other prognostic factors, in patients with MIBC treated with NAC. However, it remains necessary to determine whether - and how - optimizing hemoglobin levels before cystectomy could improve outcomes.
Macrolide overuse and resulting resistance crippled the applicability of one of the most important and successful classes of antibiotics. The rising incidence of invasive infections caused by β-hemolytic group A and group B streptococci have been paralleled with marked increases in erythromycin and clindamycin resistance. As a result, resistant invasive group A and group B Streptococcus infections have been classified by the CDC as a concerning level threat since 2019. Acquisition of erythromycin resistance methylase (erm) genes is a major contributor of the MLSB [macrolide (i.e., erythromycin), lincosamide (i.e., clindamycin), and streptogramin B] resistance phenotype in US isolates. The erm-encoded enzymes utilize the methyl-group from S-adenosyl-L-methionine (SAM) to methylate the adenosine A2058 residue of bacterial ribosomal RNA, which serves as the overlapping rRNA target site for the three MLSB classes of antibiotics. The major mechanism that regulates Erm methyltransferase production is translational attenuation in the 5' regulatory region upstream of the erm coding sequence. The 5' regulatory region of erm includes at least one short leader peptide ermL, with the leader peptide ribosome binding site (SD1), non-translational stem-loop structures, and the erm start codon with its ribosome binding site (SD2). Binding of a macrolide antibiotic to the ribosome causes stalling during translation of the ermL peptide, which disrupts and alters the formation of inhibitory mRNA hairpins in the erm 5' regulatory region, thereby releasing the erm SD2-site from the posterior stem-loop hairpin, thus allowing Erm protein translation. The streptococcal ErmA, ErmB, and ErmT proteins have conserved structures with primary sequence conservation of residues involved in SAM- and rRNA-binding activity, as well as a high-level of structural conservation. However, the observed variation in the erm 5' regulatory region sequences, transcript expression, and ribosome methylation levels associated with these genes and proteins underscore the regulatory complexity of Erm expression. This review aims to present insights into mechanisms of Erm-mediated resistance, trends in streptococcal epidemiology and treatment, and progress in the development of improved MLSB drugs that effectively block erm-mediated resistance.
Patent ductus arteriosus (PDA) is associated with increased morbidities and mortality in extremely preterm infants. The biological effect of acetaminophen on the closure of ductus has been shown; however, the effective and safe dosage for early treatment of the most preterm infants remains unknown. In a single-centre, randomised, controlled, double-blind, phase II pilot trial, extremely low gestational age (ELGA, <28 wk) and/or birth weight (<1000g) infants were randomized to intravenous paracetamol or 0.45% saline-placebo. The treatment started before 96 hours age, with loading dose of 20mg/kg and maintenance of 7.5mg/kg every six hours for nine days. Ductal patency was assessed prior to trial initiation and monitored daily, using cardiac ultrasound. Primary outcome was the duration of ductal closure. Secondary outcomes included ductal closure rates, treatment of symptomatic PDA, serum paracetamol levels, long-term morbidities, and mortality. After consent, 40 infants were randomly allocated soon after birth. The intention-to-treat analysis included 39 infants; 19 had paracetamol and 20 placebos. The median (IQR) ductal closure time was 3 (10) days in the paracetamol group, vs 14 (20) days in the placebo group (p=0.031). Ductus was closed in 15 (75%) vs 7 (35%) infants, respectively, p=0.016 (number needed to treat, NNT=3). Three infants in the placebo group received post-study treatment for PDA. The numbers of adverse events were similar in both study groups. Early, nine-day paracetamol administration, compared to placebo, significantly shortened the ductal closure time without increase in adverse events in ELGA infants. Trial registration EudraCT 2018-000566-11; ClinicalTrials.gov NCT03641209.
Respiratory allergic diseases are experiencing changes influenced by genetic factors, environmental shifts, and social and demographic elements. These evolving patterns, together with rapid advances in diagnosis and treatment, require a thorough review of emerging trends. To examine future directions in managing respiratory allergic diseases, focusing on changing disease patterns, environmental factors, diagnostic innovations, and therapeutic advances toward precision medicine. A literature search was conducted in PubMed and Scopus databases covering 2015-2025. Studies addressing human populations with allergic rhinitis or asthma were included, emphasizing emerging patterns, environmental factors, diagnostic technologies, and therapeutic innovations, while reviews, conference proceedings, case reports, and studies without clinical relevance were excluded. Initial screening identified 52 studies, and 21 additional studies were identified through complementary searches, resulting in 73 studies in the final analysis. Climate change is a key factor affecting disease patterns, with pollen seasons starting 10-40 days earlier and yearly emissions increasing by up to 200%. Regarding pathogenesis, early-life rhinovirus C infections with IgE sensitization significantly increase asthma risk (HR = 4.06), while severe asthma shows 40-84% eosinophilic patterns, depending on the assessment approach. On the diagnostic front, advances include multiplex platforms, proteomic biomarkers, and microRNAs. Therapeutically, innovations encompass biologics combined with allergen immunotherapy, nanobody-based therapeutics, and microbiota interventions. These developments point toward personalized management of respiratory allergic diseases. However, challenges remain in research with underrepresented populations and accessibility. Moving forward, the key priority is integrating this diverse knowledge into practical strategies that advance precision medicine in respiratory allergic diseases.
Combined hormonal contraception (CHC) is habitually not prescribed to breastfeeding women due to concerns of decreased milk production. This habit is based on inconclusive studies that examined lactation suppression of CHC with high-dose Ethinylestradiol (EE ≥ 30 µg/day). Notably, the effect of oral CHC with current low-dose EE (20 µg/day EE), and of vaginal rings (15 µg/day EE), has not yet been studied. Here, we examine their effect on breastmilk production. This study included 172 breastfeeding women, and evaluated self-reported breastmilk production, with and without hormonal contraception. Breastfeeding women using CHC with low-dose EE, either orally (N = 20), or vaginally (N = 32), were asked to complete a questionnaire, at two time-points: (1) Before starting CHC, and (2) some 7-10 days after. The questionnaire recorded 12 variables linked with breastfeeding. As a control group, breastfeeding women using progestin-only pills (POP, N = 54) with Desogestrel 75 µg/day, were used. As another control group, breastfeeding women using no hormonal contraception (N = 66) were also asked to complete the same questionnaire. Vaginal rings, but not oral CHC pills, containing low-dose EE, are associated with a reduction of self-reported expressed breastmilk volume by 20%. Likewise, vaginal rings, but not oral pills, are correlated with impairment of 5 out of 12 breastfeeding variables, namely: (1) breastfeeding interval, (2) self-expressed milk volume, (3) use of milk substitutes, (4) number of night-feedings, and (5) full diapers. Vaginal rings with low-dose EE (15 µg/day) are associated with a modest, yet significant, decrease in self-expressed breastmilk volume. In contrast, oral CHC pills with low-dose EE (20 µg/day) are not associated with a significant impact on breastmilk production. These findings may have clinical implications for prescribers and patients.
Valproate, commonly used for epilepsy and bipolar disorder, carries known teratogenic risks when taken by women during pregnancy. In 2023, the Medicines and Healthcare products Regulatory Agency (MHRA) issued updated guidance suggesting a possible link between valproate use in males around conception and neurodevelopmental disorders in offspring. However, awareness among male patients and documentation of advice in general practice remains inconsistent. To ensure that 100% of male patients on valproate were informed of MHRA guidance regarding family planning risks and advised on effective contraception within a 2-month period. Using EMIS, 22 male patients on valproate were identified. An Accurx text message was sent outlining MHRA guidance, contraception advice, and encouraging contact if planning a family. The text auto-coded advice into the EMIS record. Follow-up phone calls were made over two attempts to confirm receipt and provide verbal guidance where needed. All 22 patients received the text; only one responded. Phone contact was successful with 18 patients: eight confirmed receiving the text, and 10 had not. Five were already aware of the MHRA alert, while 13 were informed during calls. Four patients could not be contacted. No patients requested further information or took additional action such as starting contraception or seeking pharmacist advice. This quality improvement project improved documentation and patient awareness of valproate-associated family planning risks. Text messaging alone was ineffective; personalised phone calls were more successful. Future strategies should include routine medication reviews, pharmacist-led discussions, and system alerts to ensure ongoing patient education.
Microalgae have emerged as a potential candidate for environmental remediation and as a source of value-added products. Exogenous phytohormone supplementation in microalgae regulates biological processes and induces various signal transduction pathways. This study uses the Scopus database to identify key contributors, advance research areas, and analyze global trends in microalgal cell stimulation for bioactive compound production over 14 years. Our study started with a search using the keywords "Microalgae," "Phytohormone," "Heavy metal," "Metal tolerance," "Biomass," "Growth," "Pigment," and "Lipid," retrieving studies from the Scopus database published between 2010 and 2024. Bibliometric tools such as VOSviewer and Bibliometrix were employed to analyze and evaluate the obtained documents. The initial search yielded 283 documents, including research and review articles, and after extensive screening, 217 publications remained for analysis. China stands out as a major contributing country, and the Kunming University of Science and Technology is leading the field. Bioresource Technology and the Journal of Applied Phycology are the top journals in the study domain. Microalgae demonstrate high efficiency in nutrient removal, heavy metal bioremediation, CO₂ sequestration, and the reduction of emerging contaminants. Advanced multiomics approaches will help mitigate microalgal stress responses and support the design of more effective microalgae-bacteria consortia for wastewater treatment. Researchers should focus on targeted studies of metabolic pathways and genetic regulation in response to environmental stressors. The present study will be a valuable contribution to the field of microalgal biotechnology and in understanding their relationship with phytohormones for enhancing the biosynthesis of bioactive compounds.
Allogeneic HSCT (allo-HSCT) is indicated in high risk pediatric AML patients in CR1 and in all patients in CR2. The myeloablative busulfan-based conditioning for HSCT has been accepted commonly as the standard in them, but its short- and long-term complications forced the development of alternative regimens. Treosulfan started to be used in pediatric HSCT patients in the year 2000 due to its better toxicity profile along with sufficient myeloablative, antileukemic and immunosuppressive effects. The objective of the study was to evaluate the long-term results of the first allo-HSCT after treosulfan-based regimens in children with AML in CR1 or CR2. This retrospective analysis evaluated 85 children (0.8-18.3 years; median 6.5) with AML in CR1 or CR2, who between 2000 and 2022 underwent the first allo-HSCT from a matched sibling (MSD) (n = 23) or matched unrelated (MUD) (n = 62) donor after a treosulfan-based conditioning regimen. No patients died due to early regimen-related toxicity (RRT), and the most frequent early RRT grade ≥ 3 (acc. CTCAE) was oral (15.3%) and gastrointestinal (2.4%) mucositis. Granulocyte and platelet engraftment was achieved by 78/85 (91,8%) patients. All patients who survived beyond day +30 achieved granulocyte engraftment. The rate of complete donor chimerism was 93.5%. Acute GvHD II-IV occurred in 31.8%, extensive chronic GvHD in 8.2% of patients. The rate of acute GvHD after MSD- and MUD-HSCT was comparable, while the incidence of chronic GvHD tended to be higher after MSD-HSCT. The overall rate of non-relapse mortality (NRM) was 5.9% and was related to infection or GvHD; in all children in this group, pre-HSCT risk factors of NRM were identified. The five-year probability of relapse-free survival (76.9%), event-free survival (71.3%), and overall survival (75.4%) did not correlate with remission status (CR1 or CR2) or donor type. One patient (1.2%) developed secondary malignancy. Overall, the treosulfan-based regimen seems to be safe and effective in pediatric AML patients and provides an alternative to the busulfan-based one, especially in patients with pretransplant risk factors of severe regimen-related toxicities.
AAPM Report No. 365 recommends that medical physics graduate programs offer courses covering both mathematical and statistical methods (Section 3.1.7) as well as computational methods and medical informatics (Section 3.1.8). While our program seeks to incorporate both of these essential areas into the curriculum, various financial and programmatic constraints have necessitated a more streamlined approach. Accordingly, this work presents a single 2-semester-hour course designed to address these topics in an integrated format. In this paper, we present our efforts in developing a new teaching approach that addresses both AAPM Report No. 365 recommendations in one course. The major challenge of designing this course was the insufficient number of semester hours allocated to teaching both topics. To overcome this obstacle, we implemented a novel approach to homework assignments. Unlike the traditional approach in which students complete homework manually, students in this class were asked to write computer programs to solve most homework questions. These carefully designed assessments not only enhanced students' understanding of the course materials but also required them to utilize appropriate computational methods. Recognizing that students had varying levels of coding experience from their undergraduate studies, the program instructed them, prior to starting the program, to acquire foundational Python skills through self-guided learning to prepare for this course. In addition, basic Python programming guidance was provided with each homework assignment to support students with less coding experience. The final course covered the following key mathematical concepts: signals and systems, Fourier series and transform, probability, statistical inference, image quality, optimization methods, and an introduction to artificial intelligence with an emphasis on machine learning. To complete the homework assignments, students developed coding skills in data visualization, numerical integration, convolution, continuous-time/discrete-time/fast Fourier transforms, random number generator, point estimation, confidence interval, hypothesis testing, linear models, DICOM, the Rose model, conjugate-gradient descent, iterative methods for solving systems of linear equations, and support vector machines. The course was offered in the Spring 2024 and Spring 2025 semesters and received generally positive evaluations, with some noted challenges per the Course and Teacher Rating reports. Overall, students reported that the course was educationally beneficial; however, some indicated that the coding-based assignments were demanding. We successfully developed and implemented a course that covers mathematical and statistical methods as well as computational methods and medical informatics as recommended in AAPM Report No. 365.