Is There Uniformity in the Diagnosis of Learning Disability Globally?

Learning disabilities (LDs) are a group of neurodevelopmental deficits that negatively affect the acquisition, organization, retention, comprehension, or application of age appropriate knowledge. Persons with LD lead a subsidized quality of life, especially in academic/vocational and psychosocial domains. A certificate issued by the medical boards at a state or district level is required to avail benefits such as scribes or relaxations. This may be done through a series of assessments by psychologists, special educators, or other health-care professionals. The authors aim to understand if uniformity exists in the assessment methods used for the diagnosis of LD globally and to prepare a gap analysis for the same. A systematic review was performed on English literature articles published from January 2005 to August 2023. Full-text studies reporting assessment and diagnostic methods of LD were included. A total of 1246 records were identified through a manual search of an electronic database. Seven duplicates were removed and 1174 studies were excluded based on the relevance by screening titles, abstracts, and full texts. Sixty-five studies were included and analyzed. The authors found a lack of uniformity in this diagnostic protocol, leading to uncertainty in disability certification, doctor shopping, and additional stress for the patients, as well as added burden on the government. Identification of LD requires a multistep assessment process with culturally relevant tools and norms and the participation of a multidisciplinary team of experts.

Combining EEG and eye-tracking in virtual reality: Obtaining fixation-onset event-related potentials and event-related spectral perturbations.

Extensive research conducted in controlled laboratory settings has prompted an inquiry into how results can be generalized to real-world situations influenced by the subjects' actions. Virtual reality lends itself ideally to investigating complex situations but requires accurate classification of eye movements, especially when combining it with time-sensitive data such as EEG. We recorded eye-tracking data in virtual reality and classified it into gazes and saccades using a velocity-based classification algorithm, and we cut the continuous data into smaller segments to deal with varying noise levels, as introduced in the REMoDNav algorithm. Furthermore, we corrected for participants' translational movement in virtual reality. Various measures, including visual inspection, event durations, and the velocity and dispersion distributions before and after gaze onset, indicate that we can accurately classify the continuous, free-exploration data. Combining the classified eye-tracking with the EEG data, we generated fixation-onset event-related potentials (ERPs) and event-related spectral perturbations (ERSPs), providing further evidence for the quality of the eye-movement classification and timing of the onset of events. Finally, investigating the correlation between single trials and the average ERP and ERSP identified that fixation-onset ERSPs are less time sensitive, require fewer repetitions of the same behavior, and are potentially better suited to study EEG signatures in naturalistic settings. We modified, designed, and tested an algorithm that allows the combination of EEG and eye-tracking data recorded in virtual reality.

Convergence of inflammatory response: Salivary cytokine dynamics in coronavirus disease 2019 and periodontal disease.

Background: Periodontal disease is associated with immune dysregulation, and cytokines released can add on to the coronavirus disease 2019 (COVID-19)-associated cytokine storm, further worsening the related adverse outcomes. Specific studies investigating cytokine levels in COVID-19 patients with periodontal disease are lacking. Examining the correlation between these conditions could aid in categorizing risk categories, determining referrals, and strengthening oral hygiene protocols. The current study sought to evaluate cytokine levels in the saliva of COVID-19-positive patients with and without periodontal disease. Materials and Methods: Twenty-six COVID-19-positive patients were subjected to periodontal examination, saliva collection, and assessment of cytokine levels through cytokine bead-based multiplex assay, using fluorescence-encoded beads with flow cytometry (BD FACS LSRFortessa). Eleven cytokines were assessed (interleukin [IL] 2, 4, 6, 10, 17A, and interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2/monocyte chemoattractant protein-1), C-X-C motif chemokine ligand (CXCL) 8/IL 8, CXCL 9/monokine-induced gamma interferon [MIG]), and CXCL 10 (chemokine IFN-gamma inducible protein 10 kDa). The cytokine levels of the recruited subjects were also compared graphically with the salivary cytokine levels reported in the literature for health, COVID-19, and periodontal disease alone. Results: Out of 26 COVID-19-positive patients, 17 had periodontal disease. Levels of all cytokines were raised in patients with both diseases when compared to values reported in literature for health, periodontal disease alone, or COVID-19 alone. However, there was no statistical difference among the recruited subjects for IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-α, CCL2, CXCL 8, and CXCL 10. MIG levels were found to be higher in periodontally healthy, COVID-19-positive subjects (P = 0.01). Conclusions: Periodontal disease might contribute to the COVID-19-induced cytokine storm, potentially amplifying its impact.

Case Series: Microbacterium aurum Bacteremia in Immunosuppressed Patients-An Emerging Threat.

Blood stream infection with Microbacterium species in humans is rare and frequently linked to the presence of immunosuppressed conditions such as patients on chemotherapy or corticosteroids. Presence of indwelling catheters is also a potential risk factor for M. aurum infection. No case report has been documented in the literature regarding the pathogenic potential of M. aurum in causing bacteremia. This is the first case series reporting bacteremia by M. aurum describing the risk factors and sensitivity pattern of this pathogen. In this case series, we have described bacteremia caused by M. aurum. The risk factors and sensitivity pattern of this pathogen have also been evaluated. Here, we describe the clinical course and presentation of three patients whose blood culture showed growth of M. aurum. Indwelling venous catheter for hemodialysis or for chemotherapy for the treatment of acute lymphoblastic leukemia was found to be a risk factor in two patients. Rheumatoid arthritis was the underlying condition in the second patient and was started on immunosuppressants. Blood samples were collected during the febrile period. The blood culture samples of all these patients had pure isolates of M. aurum, identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. All three patients were managed according to the sensitivity reports and were discharged in stable condition.

Imaging and MR Spectroscopy in Papillary Craniopharyngioma.

Sellar-suprasellar masses exhibit a diverse range of differential diagnoses and it is feasible to establish a preliminary diagnosis before surgery by evaluating conventional CT scans and contrast-enhanced MRI results. Nevertheless, certain cases may present with inconclusive findings, making it challenging to anticipate the underlying tissue composition accurately through imaging alone. Researchers have explored the application of Proton MR spectroscopy in analyzing suprasellar tumors, and their investigations have revealed that it can complement traditional MRI by enhancing the accuracy of preoperative diagnoses. In this context, we report three biopsy-proven cases of suprasellar papillary craniopharyngioma where the MRS spectra derived from the solid component exhibited noticeable lipid peaks alongside reduced levels of choline and NAA. These findings played a pivotal role in facilitating the correct preoperative identification of papillary craniopharyngioma.

Self-reported weekend temporal eating patterns of American adults differ from weekday: National Health and Nutrition Examination Surveys: 2015-20-prepandemic.

BACKGROUND: Weekend-weekday differences in time of ingestive events may be implicated in adverse metabolic and health outcomes. However, little is known about the nature of weekend-weekday differences in temporal eating behaviors of the US adult population. OBJECTIVE: The study aimed to examine weekend-weekday differences in temporal and energy characteristics of ingestive events self-reported by American adults. DESIGN: Observational; within-person comparative. PARTICIPANTS/SETTING: The data were from the National Health and Nutrition Examination Surveys (NHANES) 2015-March 2020 (pre-pandemic) for > 20 y old adults who provided one weekday (M-Th) and one weekend (F, S, Su) 24-h dietary recall (n=3564 men and 3823 women). MAIN OUTCOME MEASURES: Pre-specified primary temporal outcomes were recalled time of ingestive events, and the duration of ingestive and fasting windows. Secondary outcomes included frequency and energy characteristics of ingestive events. STATISTICAL ANALYSIS PERFORMED: Gender-specific, survey-weighted, multiple linear regression models that accounted for complex survey design with dummy covariates for weekend/weekday, mode of recall administration (in-person on day 1 and telephone on day 2), and a respondent-specific fixed intercept. RESULTS: In both men and women, the weekend recalled time of first ingestive event, breakfast, and lunch were later than weekday (p<0.0008); however, no statistically significant differences were observed in time of dinner and the last eating episode. The mean weekend ingestive window (interval between the time of first and last eating events of the day) was shorter by 24 minutes (95% CI -32, -11) in men and 18 minutes (95% CI -20, -15) in women, and the mean overnight fasting window was correspondingly longer (p <0.0001). No statistically significant differences were observed between weekend and weekday frequency of ingestive events. Energy density of weekend food selections reported by women, and of beverages by men was found to be higher than weekday (p<0.002). CONCLUSIONS: Weekend ingestive patterns were characterized by later time of first ingestive event, breakfast, and lunch, and selection of higher energy density foods and beverages.

Clinical Presentation and Outcomes of Alpha-Gal Syndrome.

BACKGROUND AND AIMS: Alpha-Gal Syndrome (AGS) is an IgE-mediated allergic reaction to galactose-α-1,3-galactose, primarily linked with lone star tick bites in the US. It presents with symptoms ranging from urticaria and gastrointestinal (GI) manifestations to delayed anaphylaxis following red meat consumption. We aimed to study AGS patients' clinical manifestations, diagnosis, and outcomes. METHODS: A retrospective chart review of patients who underwent serological testing for suspected AGS between 2014-2023 at Mayo Clinic was performed. Patients with positive serology were age and sex-matched with those who tested negative. Clinical characteristics of seropositive cohort with and without GI symptoms were compared, and outcomes assessed. RESULTS: Of 1260 patients who underwent testing, 124 tested positive for AGS. They were matched with 380 seronegative controls. AGS patients reported a higher frequency of tick bites (OR 26.0 [95% CI 9.8-68.3]), prevalence of urticaria (56 % vs. 37%; P=.0008) and were less likely to have asthma (OR 0.4 [0.3 to 0.7]). They had a lower prevalence of heartburn (6% vs. 12%; P=.03) and bloating (6% vs. 13%; P=.03). 47% had GI symptoms and higher proportion were female than those without GI symptoms (69% vs. 35%; P=.002). During a mean follow up of 27 months, 22 of 40 patients reported symptom resolution after avoiding red meat, and 7 were able to transition to regular diet. CONCLUSION: A diagnosis of AGS should be strongly considered in patients with a history of tick bites and clinical presentation of allergic or GI manifestations. Dietary intervention is effective in most but not all patients.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

A rare case of Sporadic Creutzfeldt-Jakob disease at a remote mountain hospital in the Indian Himalayan Region.

Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative spongiform encephalopathy that causes neuronal derangement secondary to prion protein. Its initial diagnosis is often complex and challenging due to non-specific clinical presentation, lack of awareness, and low clinical suspicion. This disease is invariably fatal, and most patients die within 12 months of presentation. Definite diagnosis of prion disease requires neuropathological analysis, usually done at autopsy. Here, we present the autopsy findings of a 57-year-old male patient, illustrating the complexity of diagnosing this disease early in the clinical course and the need for a broad differential diagnosis at the onset.

Systematic content analysis of self-help smokeless tobacco cessation smartphone applications available in India.

Background: The content of smartphone applications (apps) that offer smoking cessation interventions has been appraised in the past. Considering the high prevalence of smokeless tobacco (SLT) use in Southeast Asia, identifying high-quality and credible apps for SLT cessation would be more helpful. Objective: This study evaluated the technical quality of apps for SLT cessation and their content adherence with the standard tobacco cessation guidelines. Materials and methods: A systematic search of SLT cessation smartphone apps freely available in the Google PlayStore was conducted using nine relevant search terms, and the first fifty apps under each search term were identified. The technical quality of the apps was rated using the Mobile App Rating Scale (MARS). Adherence of the app content to the standard tobacco cessation guidelines was also determined. Results: Three apps were found to be relevant for SLT cessation. However, none of the apps was high-quality or incorporated existing evidence on SLT cessation. Conclusion: Adherence of these apps to the tobacco cessation guidelines by the National Tobacco Control Program (NTCP), India and the National Institute for Health and Care Excellence (NICE), U.K., was limited only to a few checklist parameters.

4D SPECT/CT: A Hybrid Approach to Primary Hyperparathyroidism.

Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to visualize diseased parathyroid glands in patients with complex medical profiles or in whom other imaging modalities fail. We review the advantages and disadvantages of traditional imaging modalities used in preoperative assessment of patients with primary hyperparathyroidism: ultrasound, SPECT, and 4D CT. We describe a scheme for optimizing and individualizing preoperative imaging of patients with hyperfunctioning parathyroid glands using traditional modalities in tandem with 4D SPECT/CT. Using the input from radiologists, endocrinologists, and surgeons, we apply patient criteria such as large body habitus, concomitant multiglandular disease, multinodular thyroid disease, confusing previous imaging, and unsuccessful previous surgery to create an imaging paradigm that uses 4D SPECT/CT yet is cost-effective, accurate, and limits extraneous radiation exposure. 4D SPECT/CT capitalizes on the strengths of SPECT and 4D CT and addresses limitations that exist when these modalities are used in isolation. In select patients with complicated clinical parameters, preoperative imaging with 4D SPECT/CT can improve accuracy yet remain cost-effective.

Epidemiology and Clinical Features of Burkholderia Bacteremia at a Hospital in India.

Burkholderia spp. are opportunistic pathogens that cause infection in patients with disrupted immunity. The study intended to demonstrate the epidemiology and clinical features associated with Burkholderia spp. bacteremia. This retrospective study was performed to assess the clinical and laboratory characteristics of patients whose blood cultures were growing Burkholderia spp. and, based on their underlying comorbidities, were subjected to survival analysis from January 2022 to December 2022 at a university hospital in northern India. Three hundred patients with Burkholderia spp. bacteremia were included in this study conducted over 1 year. The mean age of the patients was 33.86 years with a male predominance of 56.67% (170/300, 56.67%). Underlying malignancies (207/300, 69.0%) were the most common clinical diagnosis, and catheter in situ (300/300, 100.0%) was the most common risk factor. Burkholderia cenocepacia (244/300, 81.33%) was the most common Burkholderia spp. isolated. All isolates were highly susceptible to minocycline. Kidney disease (P = 0.029), hypertension (P = 0.005), type 2 diabetes mellitus (P = 0.039), and respiratory disease (P <0.001) in patients were significantly associated with death owing to Burkholderia spp. bacteremia, whereas patients with malignancies (P <0.001) and undergoing treatment were significantly associated with a better outcome when the microorganism was susceptible to empirical antibiotics. The presence of indwelling devices, mechanical ventilation (P <0.001), and a hemodialysis catheter (P = 0.026) were statistically significant risk factors associated with poor outcomes.

Characterization of Leuconostoc lactis Bacteremia during a 2-year Study at a Tertiary Care Center in North India-An Observational Analysis.

Leuconostoc species are regarded as important causes for many infections in immunocompromised patients. In this study, we assessed the characteristics of Leuconostoc spp. causing bacteremia in patients at our center. This observational analysis was conducted in the microbiology laboratory of a tertiary care center in northern India from July 2021 to July 2023. Patients in whom blood culture bottles were positive for Leuconostoc lactis were included in the study. Culture isolates were identified by MALDI-ToF MS as L. lactis and tested for antibiotic sensitivity results by Kirby-Bauer disk diffusion method. Demographic and clinical details were collected and analyzed. During the study period, 6,742 blood culture bottles flagged positive. Among these, L. lactis was isolated from 14 (0.21%) patients. The median patient age was 34 years. The male-to-female ratio was 2.5:1. All the patients with L. lactis bacteremia had an underlying condition leading to immunosuppression (e.g., carcinoma and chronic kidney disease). All the patients with L. lactis bacteremia had an intravascular device present at the time of bacteremia. All isolates in the study were sensitive to doxycycline, high level gentamicin, minocycline, ampicillin-sulbactam, and linezolid. Mortality was attributed to bacteremia by L. lactis in five patients. Appropriate and timely identification of the Leuconostoc species is important for the clinician to tailor regimens for the patients.

Playing Hide-and-Seek with Tyrosine Kinase Inhibitors: Can We Overcome Administration Challenges?

Tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy against various types of cancers through molecular targeting mechanisms. Over the past 22 years, more than 100 TKIs have been approved for the treatment of various types of cancer indicating the significant progress achieved in this research area. Despite having significant efficacy and ability to target multiple pathways, TKIs administration is associated with challenges. There are reported inconsistencies between observed food effect and labeling administration, challenges of concomitant administration with acid-reducing agents (ARA), pill burden and dosing frequency. In this context, the objective of present review is to visit administration challenges of TKIs and effective ways to tackle them. We have gathered data of 94 TKIs approved in between 2000 and 2022 with respect to food effect, ARA impact, administration schemes (food and PPI restrictions), number of pills per day and administration frequency. Further, trend analysis has been performed to identify inconsistencies in the labeling with respect to observed food effect, molecules exhibiting ARA impact, in order to identify solutions to remove these restrictions through novel formulation approaches. Additionally, opportunities to reduce number of pills per day and dosing frequency for better patient compliance were suggested using innovative formulation interventions. Finally, utility of physiologically based pharmacokinetic modeling (PBPK) for rationale formulation development was discussed with literature reported examples. Overall, this review can act as a ready-to-use-guide for the formulation, biopharmaceutics scientists and medical oncologists to identify opportunities for innovation for TKIs.

Point prevalence of metabolic syndrome in HIV positive patients.

Introduction: Human immunodeficiency virus (HIV)-related morbidity and mortality have declined over time, but this increased longevity may lead to the development of other diseases, which may further manifest as the metabolic syndrome (MS). Method: To find out the point prevalence of MS in HIV positive patients, a cross-sectional prospective observational study was conducted on 200 patients who approached ART plus Centre of Government Medical College and Hospital Jammu, including 50 symptomatic patients HIV negative as controls. Results: The mean age group in MS was 37.85 ± 6.61. Males consisted of 55% (110) and females consisted of 45% (90). The overall prevalence of MS was 13.5%, with prevalence in males being 16.3% and in females 10%. Patients receiving first line highly active antiretroviral therapy (HAART) showed a 24% prevalence, while that of second line HAART showed a 14% prevalence. Central obesity (47.3%) was the most common component of MS followed by hyperglycemia (43.3%), hypertriglyceridemia (38.6%), and low high density cholesterol (HDL-C) level (38.6%). Out of 84 males with MS, 94% (79) males were having hypertriglyceridemia, 88% (74) were hypertensive, and 72% (60) were having FBS >=100. Out of 66 females with MS, 100% (66) females had central obesity and 88% (58) had hypertriglyceridemia and low HDL-C levels. Conclusion: The metabolic complications as a result of treatment with HAART leave HIV patients at a risk of developing cardiovascular disease and diabetes in spite of improvements in morbidity and mortality. Risk factors like central obesity, hypertension, hyperglycemia, and hypertriglyceridemia should be taken into consideration well before to prevent the add-on effect of developing MS.

Understanding youth and young adult cannabis use in Canada post-legalization: a scoping review on a public health issue.

BACKGROUND: Canada legalized recreational cannabis in 2018, and one of the primary objectives of the Cannabis Act was to protect youth by reducing their access to cannabis and providing public education. Canada has the highest prevalence of cannabis use worldwide, particularly among youth and young adults under the age of 25. Cannabis use is linked with many adverse effects for youth and young adults including psychosis, anxiety, depression, respiratory distress, cannabinoid hyperemesis syndrome, and impaired cognitive performance. Despite the high prevalence of cannabis use and the evolution of policies in Canada and globally, significant knowledge and research gaps remain regarding youth and young adult cannabis use. The aim of this scoping review is to map the extent, nature, and range of evidence available on youth and young adult cannabis use in Canada since its legalization, in order to strengthen policies, services, treatments, training, and public education strategies. METHODS: Using a scoping review framework developed by Arksey and O'Malley, along with the PRISMA-ScR guidelines, we conducted a rigorous search in five academic databases: MEDLINE, Embase, APA PsycINFO, CINAHL and Web of Science Core Collection. We included empirical studies that collected data in Canada after the legalization of recreational cannabis (October 2018) and focused on youth or young adults < 30. Two reviewers independently screened articles in two stages and extracted relevant information from articles meeting the inclusion criteria. RESULTS: Of the 47 articles meeting our inclusion criteria, 92% used quantitative methods, 6% were qualitative, and 2% used a mixed-methods approach. Over two-thirds (68%) used secondary data. These studies were categorized into six focus areas: (1) prevalence, patterns, and trends, (2) cannabis-related injuries and emergency department (ED) visits, (3) rates and patterns during the pandemic, (4) perceptions of cannabis use, (5) prevention tools, and (6) cannabis-related offenses. Key findings from the studies reviewed include an increase in cannabis use among 18-24-year-olds post-legalization, with mixed results for youth under 18. ED visits for intentional and unintentional cannabis-related injuries have increased in young children and teens. Perception studies show a mix of concern and normalization of cannabis use. Though limited, prevention studies are promising in raising awareness. A decline in cannabis-related offenses was noted by one study. The review highlights several research gaps, including the need for more qualitative data, disaggregation of demographic data, intervention research, and comprehensive studies on the physical and mental health impacts of cannabis use among youth and young adults. CONCLUSION: Maintaining a public health approach is critical, with a focus on reducing the high prevalence of cannabis use among youth and young adults. This involves implementing prevention strategies to minimize harms, enhancing public education, minimizing commercialization, reducing youth access to cannabis, promoting guidelines for lower-risk cannabis use and harm reduction strategies, and increasing training for healthcare providers.

Loss of the yeast transporter Agp2 upregulates the pleiotropic drug-resistant pump Pdr5 and confers resistance to the protein synthesis inhibitor cycloheximide.

The transmembrane protein Agp2, initially shown as a transporter of L-carnitine, mediates the high-affinity transport of polyamines and the anticancer drug bleomycin-A5. Cells lacking Agp2 are hyper-resistant to polyamine and bleomycin-A5. In these earlier studies, we showed that the protein synthesis inhibitor cycloheximide blocked the uptake of bleomycin-A5 into the cells suggesting that the drug uptake system may require de novo synthesis. However, our recent findings demonstrated that cycloheximide, instead, induced rapid degradation of Agp2, and in the absence of Agp2 cells are resistant to cycloheximide. These observations raised the possibility that the degradation of Agp2 may allow the cell to alter its drug resistance network to combat the toxic effects of cycloheximide. In this study, we show that membrane extracts from agp2Δ mutants accentuated several proteins that were differentially expressed in comparison to the parent. Mass spectrometry analysis of the membrane extracts uncovered the pleiotropic drug efflux pump, Pdr5, involved in the efflux of cycloheximide, as a key protein upregulated in the agp2Δ mutant. Moreover, a global gene expression analysis revealed that 322 genes were differentially affected in the agp2Δ mutant versus the parent, including the prominent PDR5 gene and genes required for mitochondrial function. We further show that Agp2 is associated with the upstream region of the PDR5 gene, leading to the hypothesis that cycloheximide resistance displayed by the agp2Δ mutant is due to the derepression of the PDR5 gene.