Virulence of Burkholderia pseudomallei ATS2021 Unintentionally Imported to United States in Aromatherapy Spray.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimABm allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

Dual client binding sites in the ATP-independent chaperone SurA.

The ATP-independent chaperone SurA protects unfolded outer membrane proteins (OMPs) from aggregation in the periplasm of Gram-negative bacteria, and delivers them to the ß-barrel assembly machinery (BAM) for folding into the outer membrane (OM). Precisely how SurA recognises and binds its different OMP clients remains unclear. Escherichia coli SurA comprises three domains: a core and two PPIase domains (P1 and P2). Here, by combining methyl-TROSY NMR, single-molecule Förster resonance energy transfer (smFRET), and bioinformatics analyses we show that SurA client binding is mediated by two binding hotspots in the core and P1 domains. These interactions are driven by aromatic-rich motifs in the client proteins, leading to SurA core/P1 domain rearrangements and expansion of clients from collapsed, non-native states. We demonstrate that the core domain is key to OMP expansion by SurA, and uncover a role for SurA PPIase domains in limiting the extent of expansion. The results reveal insights into SurA-OMP recognition and the mechanism of activation for an ATP-independent chaperone, and suggest a route to targeting the functions of a chaperone key to bacterial virulence and OM integrity.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Purpose: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. Methods: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Results: Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AMLs contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four ALs contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Conclusion: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

Stochasticity in Dietary Restriction-Mediated Lifespan Outcomes in Drosophila.

Dietary restriction (DR) is widely considered to be one of the most potent approaches to extend healthy lifespan across various species, yet it has become increasingly apparent that DR-mediated longevity is influenced by biological and non-biological factors. We propose that current priorities in the field should include understanding the relative contributions of these factors to elucidate the mechanisms underlying the beneficial effects of DR. Our work conducted in two laboratories, represents an attempt to unify DR protocols in Drosophila and to investigate the stochastic effects of DR. Across 64 pairs of survival data (DR/ad libitum, or AL), we find that DR does not universally extend lifespan. Specifically, we observed that DR conferred a significant lifespan extension in only 26.7% (17/64) of pairs. Our pooled data show that the overall lifespan difference between DR and AL groups is statistically significant, but the median lifespan increase under DR (7.1%) is small. The effects of DR were overshadowed by stochastic factors and genotype. Future research efforts directed toward gaining a comprehensive understanding of DR-dependent mechanisms should focus on unraveling the interactions between genetic and environmental factors. This is essential for developing personalized healthspan-extending interventions and optimizing dietary recommendations for individual genetic profiles.

Quantitative Assessment of Full-Time Equivalent Effort for kV-CBCT Guided Online Adaptive RT for Medical Physicists.

INTRODUCTION: With recent clinical adoption of online adaptive radiotherapy and the increased workload associated with adaptive radiotherapy, proper staffing for medical physicists is paramount to safe clinical operation. However, there is currently no consensus on the full-time equivalent (FTE) requirements for safe administration of CBCT-guided online adaptive radiotherapy. This study aims to quantitatively assess medical physics workload and staffing needs of a CBCT-guided online adaptive radiotherapy program. METHODS: We conducted a detailed analysis of the CBCT-guided adaptive planning and treatment workflows, encompassing tasks such as patient consultation, treatment planning, plan review, training, quality assurance, and treatment delivery. Utilizing data from machine logs, clinical database queries, and staff surveys, we present a framework for estimating FTE values for different staffing scenarios, considering medical physicists' roles as planners, adaptors, or both. RESULTS: FTE calculations, based on an example workload of 100 adaptive and 200 nonadaptive patients per year, for three staffing scenarios were provided: medical physicists as planners and adaptors (2.9 FTE), medical physicists as planners but not adaptors (2.6 FTE), and medical physicists as adaptors but not planners (1.4 FTE). These findings offer calculation guidance and benchmarks for staffing requirements in CBCT-guided online adaptive radiotherapy programs, emphasizing the need for specific staffing models to accommodate the complexities of adaptive radiotherapy. CONCLUSION: This study outlines a framework for calculating FTE requirements for medical physicists in a CBCT-guided online adaptive radiotherapy program. By analyzing the processes for three common adaptive radiotherapy workflows, this work can provide effective workforce planning and resource allocation estimates. This analysis can be used either prior to the implementation of an online adaptive radiotherapy program, for program development, or as a review of current practices to ensure operational efficiency and proper staffing levels are maintained.

Enhancing Precision in Radiation Therapy for Locally Advanced Lung Cancer: A Case Study of Cone-Beam Computed Tomography (CBCT)-Based Online Adaptive Techniques and the Promise of HyperSight™ Iterative CBCT.

This study explores the dosimetric benefits of cone-beam computed tomography (CBCT)-based online adaptive radiation therapy (oART) for a non-small-cell lung cancer (NSCLC) patient exhibiting significant tumor shrinkage during ChemoRT. The patient was prescribed 60 Gray (Gy) in 30 fractions and was initially treated with conventional RT. After the delivery of the first four treatment fractions, the patient's treatment course was converted to oART due to tumor shrinkage seen on CBCT. Current oART dose calculations use a synthetic CT (sCT) image derived from deformable image registration (DIR) of the planning CT to the daily CBCT, and, as the tumor regressed, the discrepancy between the CBCT and the sCT increased, leading to a re-simulation after the delivery of the ninth fraction. In this case report, we first investigated dosimetric differences leveraged by converting this patient from conventional RT to oART. With oART using sCT, the patient's target coverage remained consistent with the reference plan while simultaneously changing lung V20 by 7.8 ± 1.4% and heart mean by 3.4 ± 1.5 Gy. Then, using this new simulation CT and comparing it with iterative CBCT (iCBCT) images acquired with the new HyperSight™ (HS) (Varian Medical Systems, Inc., Palo Alto, CA, USA) imaging system on the Ethos, we investigated the impact of direct dose calculation on HS-iCBCT as compared to sCT. The HS-iCBCT generated a dose distribution similar to the CT reference, achieving a 96.01% gamma passing rate using Task Group-218 (TG-218) criteria. Results indicate that HS-iCBCT has the potential to better reflect daily anatomical changes, resulting in improved dosimetric accuracy. This study highlights the advantages of oART in the presence of tumor response to therapy and underscores HS-iCBCT's potential to provide CT-level dose calculation accuracy in oART for NSCLC patients.

Outer membrane protein assembly mediated by BAM-SurA complexes.

The outer membrane is a formidable barrier that protects Gram-negative bacteria against environmental threats. Its integrity requires the correct folding and insertion of outer membrane proteins (OMPs) by the membrane-embedded ß-barrel assembly machinery (BAM). Unfolded OMPs are delivered to BAM by the periplasmic chaperone SurA, but how SurA and BAM work together to ensure successful OMP delivery and folding remains unclear. Here, guided by AlphaFold2 models, we use disulphide bond engineering in an attempt to trap SurA in the act of OMP delivery to BAM, and solve cryoEM structures of a series of complexes. The results suggest that SurA binds BAM at its soluble POTRA-1 domain, which may trigger conformational changes in both BAM and SurA that enable transfer of the unfolded OMP to the BAM lateral gate for insertion into the outer membrane. Mutations that disrupt the interaction between BAM and SurA result in outer membrane assembly defects, supporting the key role of SurA in outer membrane biogenesis.

Molecular glues that inhibit specific Zn2+-dependent DUB activity and inflammation.

Deubiquitylases (DUBs) play a pivotal role in cell signalling and are often regulated by homo- or hetero-interactions within protein complexes. The BRCC36 isopeptidase complex (BRISC) regulates inflammatory signalling by selectively cleaving K63-linked polyubiquitin chains on Type I interferon receptors (IFNAR1). BRCC36 is a Zn2+-dependent JAMM/MPN DUB, a challenging ubiquitin protease class for the design of selective inhibitors. We identified first-in-class DUB inhibitors that act as BRISC molecular glues (BLUEs). BLUEs inhibit DUB activity by stabilising a BRISC dimer consisting of 16 subunits. The BLUE-stabilised BRISC dimer is an autoinhibited conformation, whereby the active sites and interactions with the recruiting subunit SHMT2 are blocked. This unique mode of action leads to highly selective inhibitors for BRISC over related complexes with the same catalytic subunit, splice variants and other JAMM/MPN DUBs. Structure-guided inhibitor resistant mutants confirm BLUEs on-target activity in cells, and BLUE treatment results in reduced interferon-stimulated gene (ISG) expression in human peripheral blood mononuclear cells from Scleroderma patients, a disease linked with aberrant IFNAR1 activation. BLUEs represent a new class of molecules with potential utility in Type I interferon-mediated diseases and a template for designing selective inhibitors of large protein complexes by promoting protein-protein interactions instead of blocking them.

Abdominal Wall Endometriosis: A Case Report and Literature Review of Pfannenstiel Incision Endometrioma.

We depict a unique case of a 39-year-old woman who presented to the emergency department with complaints of right upper quadrant pain. Work-up and a computed tomography (CT) scan revealed acute cholecystitis and the patient underwent laparoscopic cholecystectomy without complication. At this time, an incidental mass was discovered in the subcutaneous fat adjacent to the abdominal wall. The patient returned six months later with progressive, cyclic abdominal pain since her last hospital admission. Initial admission lab work was within normal limits and a urine pregnancy test was negative. Physical exam revealed tenderness around her previous cesarean section scar. Repeat CT revealed an enlarging, spiculated mass adherent to the abdominal wall. After imaging confirmation, the patient underwent complete open surgical excision for the removal of the mass. Post-surgical biopsy confirmed endometrial gland and stroma consistent with abdominal wall endometrioma. The patient was discharged with adjuvant therapy and recommended follow-up with the surgeon and her obstetrician-gynecologist. The radiological diagnosis, guidelines, and decision-making for initiating interventional treatment are discussed in this report. Our purpose in documenting this case is to present a rare diagnosis of an atypical location for an endometrioma on the abdominal wall, in a patient with prior cesarean delivery. Although this patient was treated with open excision, different interventional radiology treatments from radiofrequency ablation and focused ultrasound were discussed. In doing so, we hope to contribute to the systematic literature review on surgical excision as a treatment option for Pfannenstiel incision endometrioma.

Development of an algorithm for analysis of routes: Case studies using novice and older drivers.

INTRODUCTION: This study addresses the lack of methods to quantify driver familiarity with roadways, which poses a higher risk of crashes. METHOD: We present a new approach to assessing driving route diversity and familiarity using data from the DrivingApp, a smartphone-based research tool that collects trip-level information, including driving exposure and global positioning system (GPS) data, from young novice drivers (15-19 years old) to older drivers (67-78 years old). Using these data, we developed a GPS data-based algorithm to analyze the uniqueness of driving routes. The algorithm creates same route trip (SRT) arrays by comparing each trip of an identified user, employing statistically determined thresholds for GPS coordinate proximity and trip overlap. The optimal thresholds were established using a General Linear Model (GLM) to examine distance, and repeated observations. The Adjusted Breadth-First Search method is applied to the SRT arrays to prevent double counting or trip omission. The resulting list is classified as geographically distinct routes, or unique routes (URs). RESULTS: Manual comparison of algorithm output with geographical maps yielded an overall precision of 0.93 and accuracy of 0.91. The algorithm produces two main outputs: a measure of driving diversity (number of URs) and a measure of route-based familiarity derived from the Rescorla-Wagner model. To evaluate the utility of these measures, a Gaussian mixture model clustering algorithm was used on the young novice driver dataset, revealing two distinct groups: the low-frequency driving group with lower route familiarity when having higher route diversity, whereas the high-frequency driving group with the opposite pattern. In the older driver group, there was a significant correlation found between the number of URs and Geriatric Depression Score, or walking gait speed. PRACTICAL APPLICATIONS: These findings suggest that route diversity and familiarity could complement existing measures to understand driving safety and how driving behavior is related to physical and psychological outcomes.

The role of procedural factors on the outcomes of embolization followed by radiosurgery for the treatment of brain arteriovenous malformations: systematic review and proportional meta-analyses.

BACKGROUND: Multimodal therapy for brain arteriovenous malformations (bAVM) with embolization followed by stereotactic radiosurgery (E + SRS) has shown varying outcomes. Its benefits over other treatment modalities have been questioned. The goal of this systematic review was to determine the factors associated with cure and complication rates of this treatment strategy. METHODS: A literature search in Medline and Global Index Medicus, from inception to October 2023, was performed. Studies reporting relevant outcome data from bAVM patients treated with E + SRS were included. Data on several patient, lesion and procedure-related factors were collected. Embolization intent was classified as Targeted (of high-risk features), Devascularizing (feeder embolization/flow reduction) and Occluding (intent-to-cure, nidus embolization). The primary outcome was obliteration rate. Secondary outcomes were post-SRS bleeding (PSB), post-embolization neurological complications (PENC) and post-SRS neurological complications (PSNC). Subgroup analyses included embolic agent, embolization intent and radiosurgery type. Proportional meta-analyses and meta-regressions were performed. RESULTS: Forty-one studies were included in the review. The pooled obliteration rate was 56.45% (95% CI 50.94 to 61.88). Meta-regression analyses showed higher obliteration rates with Copolymers and lower obliteration rates with Devascularizing embolization. The pooled PSB, PENC and PSNC rates were 5.50%, 13.75% and 5.02%, respectively. Meta-regression analyses showed higher rates of PSB, PENC and PSNC with Devascularizing embolization, Liquid & Solid embolic agents and Targeted & Devascularizing intent, respectively. CONCLUSION: Embolic agent and embolization intent were procedural factors associated with treatment outcomes of E + SRS in the management of bAVM patients. The efficacy and safety profiles favor copolymers as embolic agents and disfavor Devascularizing as embolization intent. STUDY REGISTRATION: The protocol of the systematic review was registered in PROSPERO as CRD42023474171.

Residues 2 to 7 of α-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways.

Amyloid formation by α-synuclein (αSyn) occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Deciphering the residues that regulate αSyn amyloid fibril formation will not only provide mechanistic insight but may also reveal targets to prevent and treat disease. Previous investigations have identified several regions of αSyn to be important in the regulation of amyloid formation, including the non-amyloid-ß component (NAC), P1 region (residues 36 to 42), and residues in the C-terminal domain. Recent studies have also indicated the importance of the N-terminal region of αSyn for both its physiological and pathological roles. Here, the role of residues 2 to 7 in the N-terminal region of αSyn is investigated in terms of their ability to regulate amyloid fibril formation in vitro and in vivo. Deletion of these residues (αSynΔN7) slows the rate of fibril formation in vitro and reduces the capacity of the protein to be recruited by wild-type (αSynWT) fibril seeds, despite cryo-EM showing a fibril structure consistent with those of full-length αSyn. Strikingly, fibril formation of αSynΔN7 is not induced by liposomes, despite the protein binding to liposomes with similar affinity to αSynWT. A Caenorhabditis elegans model also showed that αSynΔN7::YFP forms few puncta and lacks motility and lifespan defects typified by expression of αSynWT::YFP. Together, the results demonstrate the involvement of residues 2 to 7 of αSyn in amyloid formation, revealing a target for the design of amyloid inhibitors that may leave the functional role of the protein in membrane binding unperturbed.

A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes.

In-depth multiomic phenotyping provides molecular insights into complex physiological processes and their pathologies. Here, we report on integrating 18 diverse deep molecular phenotyping (omics-) technologies applied to urine, blood, and saliva samples from 391 participants of the multiethnic diabetes Qatar Metabolomics Study of Diabetes (QMDiab). Using 6,304 quantitative molecular traits with 1,221,345 genetic variants, methylation at 470,837 DNA CpG sites, and gene expression of 57,000 transcripts, we determine (1) within-platform partial correlations, (2) between-platform mutual best correlations, and (3) genome-, epigenome-, transcriptome-, and phenome-wide associations. Combined into a molecular network of > 34,000 statistically significant trait-trait links in biofluids, our study portrays "The Molecular Human". We describe the variances explained by each omics in the phenotypes (age, sex, BMI, and diabetes state), platform complementarity, and the inherent correlation structures of multiomics data. Further, we construct multi-molecular network of diabetes subtypes. Finally, we generated an open-access web interface to "The Molecular Human" ( http://comics.metabolomix.com ), providing interactive data exploration and hypotheses generation possibilities.

Innovative fixed bed bioreactor platform: Enabling linearly scalable adherent cell biomanufacturing with real-time biomass prediction from nutrient consumption.

Scalable single-use adherent cell-based biomanufacturing platforms are essential for unlocking the full potential of cell and gene therapies. The primary objective of this study is to design and develop a novel fixed bed bioreactor platform tailored specifically for scaling up adherent cell culture. The bioreactor comprises a packed bed of vertically stacked woven polyethylene terephthalate mesh discs, sandwiched between two-fluid guide plates. Leveraging computational fluid dynamics modeling, we optimized bioreactor design to achieve uniform flow with minimal shear stress. Residence time distribution measurements demonstrated excellent flow uniformity with plug flow characteristics. Periodic media sampling coupled with offline analysis revealed minimal gradients of crucial metabolites (glucose, glutamine, lactate, and ammonia) across the bioreactor during cell growth. Furthermore, the bioreactor platform demonstrated high performance in automated cell harvesting, with ≈96% efficiency and ≈98% viability. It also exhibited linear scalability in both operational parameters and performance for cell culture and adeno-associated virus vector production. We developed mathematical models based on oxygen uptake rates to accurately predict cell growth curves and estimate biomass in real-time. This study demonstrates the effectiveness of the developed fixed-bed bioreactor platform in enabling scalable adherent cell-based biomanufacturing with high productivity and process control.

Automated monitoring of electrocatalyst corrosion as a function of electrochemical history and electrolyte formulation.

Automated platforms assessing the stability of electrocatalysts are key to accelerate the deployment of clean energy technologies. Here, we present a robust system that allows the study of corrosion behavior in conjunction with the electrochemical protocol and electrolyte composition over many individual electrodes. Oxygen reduction reaction on Pt is used as a proof-of-concept platform, where the influence of the potential window and phosphoric acid (PA) addition on Pt dissolution is probed. A total of 72 hours of automated operation was realized with actions including liquid management, cell cleaning, aliquoting, PA injection, and bubble detection and removal, demonstrating further advancements in automated stability testing for electrocatalysts.

Age and dose dependent changes to the bone and bone marrow microenvironment after cytotoxic conditioning with busulfan.

Preparative regimens before Hematopoietic Cell Transplantation (HCT) damage the bone marrow (BM) microenvironment, potentially leading to secondary morbidity and even mortality. The precise effects of cytotoxic preconditioning on bone and BM remodeling, regeneration, and subsequent hematopoietic recovery over time remain unclear. Moreover, the influence of recipient age and cytotoxic dose have not been fully described. In this study, we longitudinally investigated bone and BM remodeling after busulfan treatment with low intensity (LI) and high intensity (HI) regimens as a function of animal age. As expected, higher donor chimerism was observed in young mice in both LI and HI regimens compared to adult mice. Noticeably in adult mice, significant engraftment was only observed in the HI group. The integrity of the blood-bone marrow barrier in calvarial BM blood vessels was lost after busulfan treatment in the young mice and remained altered even 6 weeks after HCT. In adult mice, the severity of vascular leakage appeared to be dose-dependent, being more pronounced in HI compared to LI recipients. Interestingly, no noticeable change in blood flow velocity was observed following busulfan treatment. Ex vivo imaging of the long bones revealed a reduction in the frequency and an increase in the diameter and density of the blood vessels shortly after treatment, a phenomenon that largely recovered in young mice but persisted in older mice after 6 weeks. Furthermore, analysis of bone remodeling indicated a significant alteration in bone turnover at 6 weeks compared to earlier timepoints in both young and adult mice. Overall, our results reveal new aspects of bone and BM remodeling, as well as hematopoietic recovery, which is dependent on the cytotoxic dose and recipient age.

An Epidemiological Study of Physical-Mental Multimorbidity in Youth: Une étude épidémiologique de la morbidité physique-mentale chez les jeunes.

OBJECTIVE: This epidemiological study estimated the lifetime prevalence of chronic physical illness (i.e., an illness that lasted or was expected to last ≥6 months) and 6-month prevalence of mental disorder and multimorbidity (i.e., ≥1 physical illness and ≥1 mental disorder) in youth. Associations between physical illness and mental disorder were quantified, including the number of illnesses. Secondary objectives examined factors associated with mental disorder, after controlling for physical illness. METHODS: Data come from 10,303 youth aged 4-17 years in the 2014 Ontario Child Health Study (OCHS). Physical illness was measured using a list of chronic conditions developed by Statistics Canada. Mental disorders were measured using the OCHS Emotional Behavioural Scales. The Health Utility Index Mark III assessed overall functional health. RESULTS: Weighted prevalence estimates showed 550,090 (27.8%) youth had physical illness, 291,986 (14.8%) had mental disorder, and 108,435 (5.4%) had multimorbidity. Physical illness was not associated with mental disorder. However, youth with 2 physical illnesses, as compared to no physical illnesses, had increased odds of having any mental (OR = 1.75 [1.08, 2.85]), mood (OR = 2.50 [1.39, 4.48]) and anxiety disorders (OR = 2.40 [1.33, 4.31]). Mean functional health scores demonstrated a dose-response association across health status categories, with the highest scores among healthy youth and the lowest scores among multimorbid youth (all p < .05). CONCLUSION: Chronic physical illness and mental disorders are prevalent in youth. Youths with 2 physical illnesses have a higher likelihood of mental disorders. Higher functional health scores protected against all mental disorders. Mental health interventions for youth should promote strong overall functional health.

Physical-Mental Multimorbidity in Ontario YouthPlain Language SummaryThis study examined mental disorders in Ontario youth with and without chronic physical illnesses. Youth with at least one physical illness and one mental disorder have physical-mental multimorbidity. 27.8% of youth had chronic physical illness (that lasted at least six months), 14.8% had mental disorder, and 5.4% had multimorbidity. Risk factors for any mental, mood, and anxiety disorders included living with two chronic physical illnesses. Overall functional health of youth declined from youth that were healthy (no physical illness or mental disorder), chronic physical illness only, mental illness only, to multimorbid youth. Youth mental health interventions should promote strong overall functional health.

On the"Staple" Effect in the d-Glucose Acetylation by Choline-Chloride Ethylene Glycol and Choline-Chloride Urea Deep Eutectic Solvents.

This work employs hybrid quantum mechanics molecular mechanics simulations coupled with an umbrella sampling technique to investigate the acetylation of d-glucose with acetic anhydride in two deep eutectic solvents (DESs): choline-chloride ethylene glycol (ChCl/Etg) and choline-chloride urea (ChCl/U). The reaction proceeds spontaneously, with activation free energy barriers of 18.19 ± 0.15 and 19.83 ± 0.15 kcal/mol for ChCl/Etg and ChCl/U, respectively. These values align with literature data for similar reactions in ionic liquids, highlighting the potential of DESs as green reaction media for wood modifications, while minimizing lignocellulosic matrix degradation. Energy pair distribution analysis, radial distribution functions, and noncovalent interactions reveal a more solvated transition state compared to the initial reactant state within ChCl/Etg, facilitating the acetylation reaction. Interestingly, combined distribution function analysis unveils a "staple" effect in both solvents, potentially hindering efficient product separation. The work further explores hydrogen bond networks and Kamlet-Taft solvatochromic parameters to elucidate the role of solvents in the reaction mechanism. It was observed that a notable decrease in activation energy is accompanied by increasing net basicity, along with a reduction in the "staple" effect. This suggests that solvent parameters could serve as an effective screening tool for identifying novel and efficient DESs for wood modifications.

Fungicide resistance in Botrytis cinerea and identification of Botrytis species associated with blueberry in Michigan.

Botrytis blossom blight and fruit rot, caused by Botrytis cinerea, is a significant threat to blueberries, potentially resulting in substantial economic losses if not effectively managed. Despite the recommendation of various cultural and chemical practices to control this pathogen, there are widespread reports of fungicide resistance, leading to decreased efficacy. This study aimed to characterize the resistance profile of B. cinerea isolated from blighted blossoms and fruit in 2019, 2020 and 2022 (n = 131, 40, and 37 for the respective years). Eight fungicides (fludioxonil, thiabendazole, pyraclostrobin, boscalid, fluopyram, fenhexamid, iprodione, and cyprodinil) were tested using conidial germination at specific discriminatory doses. Additionally, 86 isolates were phylogenetically characterized using the internal transcribed spacer regions (ITS) and the protein coding genes: glyceraldehyde-3-phosphate dehydrogenase (G3PDH), heat-shock protein 60 (HSP60), and RNA polymerase II second largest subunit (RPB2). This revealed higher fungicide resistance frequencies in 2020 and 2022 compared to 2019. Over all 3 years, over 80% of the isolates were sensitive to fludioxonil, fluopyram, and fenhexamid. Pyraclostrobin and boscalid showed the lowest sensitivity frequencies (<50%). While multi-fungicide resistance was observed in all the years, none of the isolates demonstrated simultaneous resistance to all tested fungicides. Botrytis cinerea was the most prevalent species among the isolates (74) with intraspecific diversity detected by the genes. Two isolates were found to be closely related to B. fabiopsis, B. galanthina, and B. caroliniana and 10 isolates appeared to be an undescribed species. This study reports the discovery of a potentially new species sympatric with B. cinerea on blueberries in Michigan.