Real-world Implications of Botulinum Neurotoxin A Immunoresistance for Consumers and Aesthetic Practitioners: Insights from ASCEND Multidisciplinary Panel.

Background: As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals' (HCPs') perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient's viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey. Methods: A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants' BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey. Results: Aesthetic BoNT-A patients' depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed. Conclusion: These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A.

The impact of earth-abundant metals as a replacement for Pd in cross coupling reactions.

Substitution of one metal catalyst for another is not as straightforward as simply justifying this change based on the availability and/or cost of the metals. Methodologies to properly assess options for reaction design, including multiple factors like a metal's availability, cost, or environmental indicators have not advanced at the pace needed, leaving decisions to be made along these lines more challenging. Isolated indicators can lead to conclusions being made in too hasty a fashion. Therefore, an extensive life cycle-like assessment was performed documenting that the commonly held view that methods using earth-abundant metals (and in this case study, Ni) are inherently green replacements for methods using palladium in cross-coupling reactions, and Suzuki-Miyaura couplings, in particular, is an incomplete analysis of the entire picture. This notion can be misleading, and unfortunately derives mainly from the standpoint of price, and to some degree, relative natural abundance associated with the impact of mining of each metal. A more accurate picture emerges when several additional reaction parameters involved in the compared couplings are considered. The analysis points to the major impact that use of organic solvents has in these couplings, while the metals themselves actually play subordinate roles in terms of CO2-release into the environment and hence, the overall carbon footprint (i.e., climate change). The conclusion is that a far more detailed analysis is required than that typically being utilized.

FXR Deletion Attenuates Intestinal Barrier Dysfunction in Murine Acute Intestinal Inflammation.

Accumulating literature suggests that the Farnesoid-X Receptor (FXR), a nuclear bile acid receptor best known for its role in bile acid homeostasis, is also a potent context-dependent regulator of inflammation. FXR may thus be relevant to several intestinal disease states including inflammatory bowel disease, necrotizing enterocolitis, and sepsis. In this study, we tested the effects of FXR deletion on acute murine intestinal inflammation. We found that FXR knockout (KO) mice were protected from intestinal injury and barrier dysfunction induced by LPS injection, dithizone/Klebsiella, and cecal ligation/puncture models. In the LPS model, RNA sequencing and qPCR analysis showed that this protection correlated with substantial reduction in LPS-induced pro-inflammatory gene expression, including lower tissue levels of Il1a, Il1b, and Tnf. Examining functional effects on the epithelium, we found that LPS-induced tight junctional disruption as assessed by internalization of ZO-1 and occludin was ameliorated in FXR KO animals. Taken together, these data suggest a role for FXR in the intestinal barrier during inflammatory injury.

A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI.

BACKGROUND: Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI. METHODS: 24 older adults with amnestic MCI (aMCI) due to possible Alzheimer's disease enrolled in a phase I trial of open-label accelerated iTBS to the left dorsolateral prefrontal cortex (8 stimulation sessions of 600 pulses of iTBS/day for 3 days). Participants rated common side effects during and after each session and retrospectively (at post-treatment and 4-week follow-up). They completed brain MRI (for safety assessments and electric field modeling), neuropsychiatric evaluations, and neuropsychological testing before and after treatment; a subset of measures was administered at follow-up. RESULTS: Retention was high (95%) and there were no adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participants reported high acceptability, minimal side effects, and low desire to quit despite some rating the treatment as tiring. Electric field modeling data suggest that all participants received safe and therapeutic cortical stimulation intensities. We observed a significant, large effect size (d=0.98) improvement in fluid cognition using the NIH Toolbox Cognition Battery from pre-treatment to post-treatment. CONCLUSIONS: Our findings support the safety, feasibility, and acceptability of accelerated iTBS in aMCI. In addition, we provide evidence of target engagement in the form of improved cognition following treatment. These promising results directly inform future trials aimed at optimizing treatment parameters. TRIAL REGISTRATION NUMBER: NCT04503096.

Spectroscopic characterization of europium binding to a calmodulin-EF4 hand peptide-polymer conjugate.

The emergence of biological ligand as an alternative to chemical ligands enables a sustainable lanthanide extraction route. In this study, a peptide originating from the loop of domain 4 calmodulin (EF4) was synthesized and the interaction with europium ions was monitored using time resolved laser fluorescence spectroscopy (TRLFS). Despite being retracted from its full protein structure, the twelve amino acids of calmodulin-EF4 showed binding to europium. Europium-peptide complex formation was evident by an increase in decay time from 110 to 187 µs. The spectra of europium bound to peptide can be easily distinguished from the free europium ion as the 5D0 → 7F2 peak intensifies. When europium bound to the peptide-polymer conjugate, the decay time was further increased to 259 µs. This suggests that lanthanide binding can be enhanced by immobilizing the short peptide into a polymer matrix. The europium-peptide/conjugate bond was reversible, triggered by pH, promoting peptide reusability. Due to the fact that the study was conducted exclusively in water, it suggests minimal use of chemicals is possible while maintaining peptide affinity. This makes the calmodulin-EF4 peptide an ideal candidate as biological ligand. This study lays the groundwork for developing a peptide-based filter material for lanthanide separation.

Bioorthogonal Metabolic Labeling of the Virulence Factor Phenolic Glycolipid in Mycobacteria.

Surface lipids on pathogenic mycobacteria modulate infection outcomes by regulating host immune responses. Phenolic glycolipid (PGL) is a host-modulating surface lipid that varies among clinical Mycobacterium tuberculosis strains. PGL is also found in Mycobacterium marinum, where it promotes infection of zebrafish through effects on the innate immune system. Given the important role this lipid plays in the host-pathogen relationship, tools for profiling its abundance, spatial distribution, and dynamics are needed. Here, we report a strategy for imaging PGL in live mycobacteria using bioorthogonal metabolic labeling. We functionalized the PGL precursor p-hydroxybenzoic acid (pHB) with an azide group (3-azido pHB). When fed to mycobacteria, 3-azido pHB was incorporated into the cell surface, which could then be visualized via the bioorthogonal conjugation of a fluorescent probe. We confirmed that 3-azido pHB incorporates into PGL using mass spectrometry methods and demonstrated selectivity for PGL-producing M. marinum and M. tuberculosis strains. Finally, we applied this metabolic labeling strategy to study the dynamics of PGL within the mycobacterial membrane. This new tool enables visualization of PGL that may facilitate studies of mycobacterial pathogenesis.

Establishing conditions for the generation and maintenance of estrogen receptor-positive organoid models of breast cancer.

Patient-derived organoid models of estrogen receptor-positive (ER+) breast cancer would provide a much-needed tool to understand drug resistance and disease progression better. However, the establishment and long-term maintenance of ER expression, function, and response in vitro remains a significant challenge. Here, we report the development of an ER+ breast tumor organoid medium (BTOM-ER) that conserves ER expression, estrogen responsiveness, and dependence, as well as sensitivity to endocrine therapy of ER+ patient-derived xenograft organoids (PDXO). Our findings demonstrate the utility of subtype-specific culture conditions that better mimic the characteristics of the breast epithelial biology and microenvironment, providing a powerful platform for investigating therapy response and disease progression of ER+ breast cancer.

Designing optimal behavioral experiments using machine learning.

Computational models are powerful tools for understanding human cognition and behavior. They let us express our theories clearly and precisely and offer predictions that can be subtle and often counter-intuitive. However, this same richness and ability to surprise means our scientific intuitions and traditional tools are ill-suited to designing experiments to test and compare these models. To avoid these pitfalls and realize the full potential of computational modeling, we require tools to design experiments that provide clear answers about what models explain human behavior and the auxiliary assumptions those models must make. Bayesian optimal experimental design (BOED) formalizes the search for optimal experimental designs by identifying experiments that are expected to yield informative data. In this work, we provide a tutorial on leveraging recent advances in BOED and machine learning to find optimal experiments for any kind of model that we can simulate data from, and show how by-products of this procedure allow for quick and straightforward evaluation of models and their parameters against real experimental data. As a case study, we consider theories of how people balance exploration and exploitation in multi-armed bandit decision-making tasks. We validate the presented approach using simulations and a real-world experiment. As compared to experimental designs commonly used in the literature, we show that our optimal designs more efficiently determine which of a set of models best account for individual human behavior, and more efficiently characterize behavior given a preferred model. At the same time, formalizing a scientific question such that it can be adequately addressed with BOED can be challenging and we discuss several potential caveats and pitfalls that practitioners should be aware of. We provide code to replicate all analyses as well as tutorial notebooks and pointers to adapt the methodology to different experimental settings.

CDKL5 regulates p62-mediated selective autophagy and confers protection against neurotropic viruses.

Virophagy, the selective autophagosomal engulfment and lysosomal degradation of viral components, is crucial for neuronal cell survival and antiviral immunity. However, the mechanisms leading to viral antigen recognition and capture by autophagic machinery remain poorly understood. Here, we identified cyclin-dependent kinase-like 5 (CDKL5), known to function in neurodevelopment, as an essential regulator of virophagy. Loss-of-function mutations in CDKL5 are associated with a severe neurodevelopmental encephalopathy. We found that deletion of CDKL5 or expression of a clinically relevant pathogenic mutant of CDKL5 reduced virophagy of Sindbis virus (SINV), a neurotropic RNA virus, and increased intracellular accumulation of SINV capsid protein aggregates and cellular cytotoxicity. Cdkl5-knockout mice displayed increased viral antigen accumulation and neuronal cell death after SINV infection and enhanced lethality after infection with several neurotropic viruses. Mechanistic studies demonstrated that CDKL5 directly binds the canonical selective autophagy receptor p62 and phosphorylates p62 at T269/S272 to promote its interaction with viral capsid aggregates. We found that CDKL5-mediated phosphorylation of p62 facilitated the formation of large p62 inclusion bodies that captured viral capsids to initiate capsid targeting to autophagic machinery. Overall, these findings identify a cell-autonomous innate immune mechanism for autophagy activation to clear intracellular toxic viral protein aggregates during infection.

Real-time correlation of crystallization and segmental order in conjugated polymers.

Modulating the segmental order in the morphology of conjugated polymers is widely recognized as a crucial factor for achieving optimal electronic properties and mechanical deformability. However, it is worth noting that the segmental order is typically associated with the crystallization process, which can result in rigid and brittle long-range ordered crystalline domains. To precisely control the morphology, a comprehensive understanding of how highly anisotropic conjugated polymers form segmentally ordered structures with ongoing crystallization is essential, yet currently elusive. To fill this knowledge gap, we developed a novel approach with a combination of stage-type fast scanning calorimetry and micro-Raman spectroscopy to capture the series of specimens with a continuum in the polymer percent crystallinity and detect the segmental order in real-time. Through the investigation of conjugated polymers with different backbones and side-chain structures, we observed a generally existing phenomenon that the degree of segmental order saturates before the maximum crystallinity is achieved. This disparity allows the conjugated polymers to achieve good charge carrier mobility while retaining good segmental dynamic mobility through the tailored treatment. Moreover, the crystallization temperature to obtain optimal segmental order can be predicted based on Tg and Tm of conjugated polymers. This in-depth characterization study provides fundamental insights into the evolution of segmental order during crystallization, which can aid in designing and controlling the optoelectronic and mechanical properties of conjugated polymers.

Ceria nanomaterials containing ytterbium: low and high concentration - luminescence analyzed in the near infrared region.

Lanthanide based ceria nanomaterials are important practical materials due to the redox properties that are useful in the avenues pertaining to technology and life sciences. Sub 10 nm spherical and highly monodisperse Ce1-xYbxO2-y (0.04 ≤ x ≤ 0.22) nanoparticles were synthesized by thermal decomposition, annealed separately at 773 K and 1273 K for 2 hours and characterized. Elemental mapping for Yb3+ doped ceria nanoparticles shows homogeneous distribution of Yb3+ atoms in the ceria with low Yb3+ content annealed at 773 K and 1273 K for 2 hours. However, clusters are observed for 773 K annealed ceria samples with high concentration of Yb3+. These clusters are not detected in 1273 K annealed nanomaterials. Introducing small amounts of Yb3+ ions into the ceria lattice as spectroscopic probes can provide detailed information about the atomic structure and local environments allowing the monitoring of small structural changes, such as clustering. The emission spectra observed at room temperature and at 4 K have a manifold of bands that corresponds to the 2F5/2 → 2F7/2 transition of Yb3+ ions. Some small shifts are observed in the Stark splitting pattern depending on the sample and the annealing conditions. The deconvolution by PARAFAC analysis yielded luminescence decay kinetics as well as the associated luminescence spectra of three species for each of the low Yb3+ doped ceria samples annealed at 773 K and one species for the 1273 K annealed samples. However, the ceria samples with high concentration of Yb3+ annealed at the two temperatures showed only one species with lower decay times as compared to the low Yb3+ doped ceria samples.

Facile Blending Strategy for Boosting the Conjugated Polymer Semiconductor Transistor's Mobility.

The optimization of field-effect mobility in polymer field-effect transistors (FETs) is a critical parameter for advancing organic electronics. Today, many challenges still persist in understanding the roles of the design and processing of semiconducting polymers toward electronic performance. To address this, a facile approach to solution processing using blends of PDPP-TVT and PTPA-3CN is developed, resulting in a 3.5-fold increase in hole mobility and retained stability in electrical performance over 3 cm2 V-1 s-1 after 20 weeks. The amorphous D-A conjugated structure and strong intramolecular polarity of PTPA-3CN are identified as major contributors to the observed improvements in mobility. Additionally, the composite analysis by X-ray photoelectron spectroscopy (XPS) and the flash differential scanning calorimetry (DSC) technique showed a uniform distribution and was well mixed in binary polymer systems. This mobility enhancement technique has also been successfully applied to other polymer semiconductor systems, offering a new design strategy for blending-type organic transistor systems. This blending methodology holds great promise for the practical applications of OFETs.

Template MRI scans reliably approximate individual and group-level tES and TMS electric fields induced in motor and prefrontal circuits.

Background: Electric field (E-field) modeling is a valuable method of elucidating the cortical target engagement from transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), but it is typically dependent on individual MRI scans. In this study, we systematically tested whether E-field models in template MNI-152 and Ernie scans can reliably approximate group-level E-fields induced in N = 195 individuals across 5 diagnoses (healthy, alcohol use disorder, tobacco use disorder, anxiety, depression). Methods: We computed 788 E-field models using the CHARM-SimNIBS 4.0.0 pipeline with 4 E-field models per participant (motor and prefrontal targets for TMS and tES). We additionally calculated permutation analyses to determine the point of stability of E-fields to assess whether the 152 brains represented in the MNI-152 template is sufficient. Results: Group-level E-fields did not significantly differ between the individual vs. MNI-152 template and Ernie scans for any stimulation modality or location (p > 0.05). However, TMS-induced E-field magnitudes significantly varied by diagnosis; individuals with generalized anxiety had significantly higher prefrontal and motor E-field magnitudes than healthy controls and those with alcohol use disorder and depression (p < 0.001). The point of stability for group-level E-field magnitudes ranged from 42 (motor tES) to 52 participants (prefrontal TMS). Conclusion: MNI-152 and Ernie models reliably estimate group-average TMS and tES-induced E-fields transdiagnostically. The MNI-152 template includes sufficient scans to control for interindividual anatomical differences (i.e., above the point of stability). Taken together, using the MNI-152 and Ernie brains to approximate group-level E-fields is a valid and reliable approach.

Effects of PK-guided prophylaxis on clinical outcomes and FVIII consumption for patients with moderate to severe Haemophilia A.

INTRODUCTION: In recent years, there has been increased focus on individualizing treatment for persons with hemophilia including pharmacokinetic-guided (PK) dosing. AIMS: In this retrospective study clinical outcomes before and after PK-guided prophylaxis were examined. MATERIALS AND METHODS: Eight Haemophilia Treatment Centres from the United States participated in the study and included 132 patients classified into two cohorts: those undergoing a PK-assessment for product switch (switchers) or to optimize treatment (non-switchers). Subset analyses for the two most common products and patients with dosing per prescription label were included for annual bleeding rates (ABR), mean weekly consumption outcomes, and annualized cost of prophylaxis. RESULTS: The most common products before and after index date were octocog alfa, rurioctocog alfa pegol, and efmoroctocog alfa. Seventy-four (56%) patients were identified as switchers and 58 (44%) patients were classified as non-switchers. The majority of patients (78.0%) experienced either a decrease in ABR post-index or maintained 0 ABR during pre- and post-index time periods, with similar proportions identified in both switchers (77.0%) and non-switchers (79.3%) populations. Non-switchers were identified as having no significant change in cost of therapy, while switchers experienced increased cost of therapy driven by higher price of extended half-life products. Within subset analyses, patients receiving rurioctocog alfa pegol and efmoroctocog alfa had mean ABR under 1 after index date. CONCLUSION: PK-guided prophylaxis has the potential to improve clinical outcomes without increase in cost of therapy for patients maintaining product and can aid in maintaining effective protection against bleeds in those switching product.

EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression.

BACKGROUND: Medulloblastoma is the most common pediatric brain malignancy. Patients with the Group 3 subtype of medulloblastoma (MB) often exhibit MYC amplification and/or overexpression and have the poorest prognosis. While Group 3 MB is known to be highly dependent on MYC, direct targeting of MYC remains elusive. METHODS: Patient gene expression data were used to identify highly expressed EYA2 in Group 3 MB samples, assess the correlation between EYA2 and MYC, and examine patient survival. Genetic and pharmacological studies were performed on EYA2 in Group 3 derived MB cell models to assess MYC regulation and viability in vitro and in vivo. RESULTS: EYA2 is more highly expressed in Group 3 MB than other MB subgroups and is essential for Group 3 MB growth in vitro and in vivo. EYA2 regulates MYC expression and protein stability in Group 3 MB, resulting in global alterations of MYC transcription. Inhibition of EYA2 tyrosine phosphatase activity, using a novel small molecule inhibitor (NCGC00249987, or 9987), significantly decreases Group 3 MB MYC expression in both flank and intracranial growth in vivo. Human MB RNA-seq data show that EYA2 and MYC are significantly positively correlated, high EYA2 expression is significantly associated with a MYC transcriptional signature, and patients with high EYA2 and MYC expression have worse prognoses than those that do not express both genes at high levels. CONCLUSIONS: Our data demonstrate that EYA2 is a critical regulator of MYC in Group 3 MB and suggest a novel therapeutic avenue to target this highly lethal disease.

Selective and pH-Independent Detection of Ba2+ in Water by a Benzo-21-crown-7-Functionalized BODIPY.

Herein, we report on highly Ba2+ selective fluorescence sensing in water by a fluorescent probe consisting of a benzo-21-crown-7 as a Ba2+ binding unit (ionophore) and a tetramethylated BODIPY fluorophore as a fluorescence reporter. This fluorescent probe showed a Ba2+ induced fluorescence enhancement (FE) by a factor of 12±1 independently of the pH value and a high Ba2+ sensitivity with a limit of detection (LOD) of (17.2±0.3) µM. Moreover, a second fluorescent probe consisting of the same BODIPY fluorophore, but a benzo-18-crown-6 as a cation-responsive binding moiety, showed an even higher FE upon Ba2+ complexation by a factor of 85±3 and a lower LOD of (13±3) µM albeit a lower Ba2+ selectivity. The fluorescence sensing mechanism of Ba2+ was further investigated by time-resolved fluorescence as well as transient absorption spectroscopy (TAS) and it turned out that within these probes a blocking of a photoinduced electron transfer (PET) by Ba2+ is very likely responsible for the FE.

Addressing the Real-World Challenges of Immunoresistance to Botulinum Neurotoxin A in Aesthetic Practice: Insights and Recommendations from a Panel Discussion in Hong Kong.

With increasing off-label aesthetic indications using higher botulinum neurotoxin A (BoNT-A) doses and individuals starting treatment at a younger age, particularly in Asia, there is a greater risk of developing immunoresistance to BoNT-A. This warrants more in-depth discussions by aesthetic practitioners to inform patients and guide shared decision-making. A panel comprising international experts and experienced aesthetic practitioners in Hong Kong discussed the implications and impact of immunoresistance to BoNT-A in contemporary aesthetic practice, along with practical strategies for risk management. Following discussions on a clinical case example and the results of an Asia-Pacific consumer study, the panel concurred that it is a priority to raise awareness of the possibility and long-term implications of secondary non-response due to immunoresistance to BoNT-A. Where efficacy and safety are comparable, a formulation with the lowest immunogenicity is preferred. The panel also strongly favored a thorough initial consultation to establish the patient's treatment history, explain treatment side effects, including the causes and consequences of immunoresistance, and discuss treatment goals. Patients look to aesthetic practitioners for guidance, placing an important responsibility on practitioners to adopt risk-mitigating strategies and adequately communicate important risks to patients to support informed and prudent BoNT-A treatment decisions.

Prospective evaluation of lipid management following acute coronary syndrome in Saudi Arabia.

OBJECTIVES: To evaluate LDL-C control in patients within 6 months after hospitalization for ACS in Saudi Arabia. METHODS: This multicenter, prospective, observational registry evaluates LDL-C control in patients within 6 months after hospitalization for ACS in Saudi Arabia between December 2017 and October 2019. The study aimed at recruiting 170 patients and data were collected retrospectively at baseline and prospectively at 2 subsequent visits. RESULTS: 201 patients were included at baseline, 193 completed the 3-month visit and 186 completed the 6-month visit. Post-ACS, virtually all patients were prescribed high-intensity statins and LDL-C levels decreased consistently. However, at LDL-C target assessment, 57.1% of patients still had LDL-C levels >55 mg/dL, while 62.6% of patients had achieved LDL-C level decrease >50%. The composite milestone of LDL-C decrease >50% and LDL-C levels <55 mg/dL was met by 20.6% of study patients. Importantly, 37% of patients did not have LDL-C reading post-ACS and the primary outcome was only valuable for 126 out of 201 patients (63%). CONCLUSION: Levels and decrease of LDL-C from baseline achieved in this study are suboptimal, according to updated 2019 ESC/EAS guidelines. While statins were prescribed to all patients post-ACS, the recommended add-on treatments were largely overlooked. Gaps in dyslipidemia management linger, despite clear updated guidelines.

Problem Gambling Among Adolescents in Uganda: A Cross-sectional Survey Study.

In recent years, gambling has evolved and grown substantially with new gambling activities and facilities being introduced, making gambling products and opportunities more available than ever before in Uganda. While the growth of gambling industry is considered to have a beneficial impact on the economy, it is increasingly becoming a social and public health issue especially among a minority of young people who experience problem gambling, which can damage personal, family, vocational, and academic pursuits. The present study estimated the prevalence of problem gambling and identified the socio-demographic, school, environmental and health risks of problem gambling among secondary school students in Mbarara Municipality, Uganda. A cross-sectional study was conducted among secondary school students in Mbarara Municipality. A total of 921 students from 12 schools were recruited using cluster sampling. An ordinal logistic regression model was used to explore the relationship between problem gambling and the socio-demographic, academic, environmental and health variables. Of 905 participants, 362 reported having ever gambled (40%), and 160 were classified as problem gamblers (17.7%; 44.2% among those who had ever gambled). Problem gambling was significantly associated with being male, being non-religious, other religion (African traditional religion), having employment (outside of school), distance to nearest gambling venue, parental gambling, peer gambling, substance use, risky sexual behavior, and psychological distress. The present study found a very high prevalence of problem gambling among Ugandan secondary school students. Therefore, there is need to institute public health measures towards raising awareness, prevention and treatment of problem gambling among Ugandan adolescents.

Magnetic resonance imaging detects onset and association with lung disease severity of bronchial artery dilatation in cystic fibrosis.

Background: Bronchial artery dilatation (BAD) is associated with haemoptysis in advanced cystic fibrosis (CF) lung disease. Our aim was to evaluate BAD onset and its association with disease severity by magnetic resonance imaging (MRI). Methods: 188 CF patients (mean±sd age 13.8±10.6 years, range 1.1-55.2 years) underwent annual chest MRI (median three exams, range one to six exams), contributing a total of 485 MRI exams including perfusion MRI. Presence of BAD was evaluated by two radiologists in consensus. Disease severity was assessed using the validated MRI scoring system and spirometry (forced expiratory volume in 1 s (FEV1) % pred). Results: MRI demonstrated BAD in 71 (37.8%) CF patients consistently from the first available exam and a further 10 (5.3%) patients first developed BAD during surveillance. Mean MRI global score in patients with BAD was 24.5±8.3 compared with 11.8±7.0 in patients without BAD (p<0.001) and FEV1 % pred was lower in patients with BAD compared with patients without BAD (60.8% versus 82.0%; p<0.001). BAD was more prevalent in patients with chronic Pseudomonas aeruginosa infection versus in patients without infection (63.6% versus 28.0%; p<0.001). In the 10 patients who newly developed BAD, the MRI global score increased from 15.1±7.8 before to 22.0±5.4 at first detection of BAD (p<0.05). Youden indices for the presence of BAD were 0.57 for age (cut-off 11.2 years), 0.65 for FEV1 % pred (cut-off 74.2%) and 0.62 for MRI global score (cut-off 15.5) (p<0.001). Conclusions: MRI detects BAD in patients with CF without radiation exposure. Onset of BAD is associated with increased MRI scores, worse lung function and chronic P. aeruginosa infection, and may serve as a marker of disease severity.