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1.
ACS Omega ; 9(27): 29739-29750, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39005812

ABSTRACT

Polyelectrolyte microparticles (MPs) synthesized on calcium carbonate cores are considered a promising basis for new drug delivery systems. It is known that microparticles entering a physiological environment absorb proteins on their surface, which can change the properties of the microparticles and alter their functional activity. This study aimed to compare the compositions of the adsorbed protein layer formed on microparticles with the core/shell and shell structures obtained by layer-by-layer deposition. The difference in the microparticle structure was associated with changes in their surface topography and ζ-potential. These microparticles were incubated with human serum or plasma at 37°C for 24 h. The adsorbed proteins were eluted and analyzed by means of SDS-PAGE. The protein composition of the eluates was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS); a total of 357 proteins were identified, and 183 of them were detected in all samples. Our results demonstrate that the relative abundance of proteins of different functional groups (immunoglobulins, complement proteins, and apolipoproteins) varied depending on the structure and surface characteristics of the polyelectrolyte microparticles and the incubation medium. Our findings expand the understanding of the influence of the physicochemical properties of the microparticles on their interaction with proteins, which can help to improve the design of microparticles for drug delivery.

2.
AEM Educ Train ; 8(4): e11009, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38993542

ABSTRACT

Background: The Accreditation Council for Graduate Medical Education has tasked residency programs to prioritize resident wellness, reduce trainee stress, and prevent burnout. Grief and bereavement can significantly impact residents' wellness during difficult clinical training schedules. There are no best practices on how to support residents during this time. Methods: In a split academic county emergency medicine (EM) residency, this pilot study documents a resident-driven change to scheduling practices for bereavement leave. An advisory group of residents, chief residents, and program directors informally polled peer institutions to develop bereavement leave guidelines. Considerations were made to balance resident wellness, education, and patient care in developing a bereavement scheduling policy. Results: The bereavement policy was adopted in January 2023, aiming to "support the resident during a difficult time and reduce concerns around shift coverage" following the death of a family member without impacting sick call. The number of covered days depended on the relationship of the resident to the deceased. Residents covering bereavement days for their peers were financially compensated. During the first 7 months following implementation, five residents utilized the policy. These residents noted this to be the most positive impact on the residency during the past year. Based on resident feedback, the scope was expanded to include grave medical illness of a family member as an implementation criterion. Conclusions: This article outlines the creation, implementation, and benefits of a bereavement scheduling policy within an EM residency. Describing this approach will provide guidance for other residencies to adopt similar wellness-focused strategies.

3.
Transplantation ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946037

ABSTRACT

BACKGROUND: Descriptions of eosinophils in transbronchial biopsy (TBBx) pathology reports after lung transplantation (LTx) are associated with poor long-term outcomes. The absence of routine reporting and standardization precludes accurate assessment of this histologic predictor. A systematic reporting scheme for the presence of TBBx eosinophils after LTx was implemented. This report aims to assess this scheme by describing the presence, pattern, and gradation of TBBx eosinophils and clinical associations. METHODS: A prospective cross-sectional study of all TBBx reports was performed including all patients presenting for a surveillance or diagnostic TBBx between January 2020 and June 2023. Each TBBx was systematically reported in a blinded manner. Mixed-effects logistic regression was performed to measure the association between concurrent clinical and histologic features, and the presence of TBBx eosinophils. RESULTS: A total of 410 TBBx reports from 201 patients were systematically reported. In 43.8% recipients, any TBBx eosinophils were detected and in 17.1% recipients, higher-grade eosinophils (≥3 per high power field) were present. Adjusted analysis showed that retransplantation, A- and B-grade cellular rejection, positive bronchoalveolar lavage (BAL) bacterial microbiology, and elevated blood eosinophil count were independently associated with the presence of any TBBx eosinophils. Diagnostic "for-cause" procedures were independently associated with higher quantities of TBBx eosinophils. CONCLUSIONS: Systematic reporting demonstrates that TBBx eosinophils are a distinct inflammatory response associated with rejection, infection, and peripheral eosinophilia. Although these findings require multicenter external validation, standardized reporting for TBBx eosinophils may assist in identifying recipients at risk of poor outcomes and provides a platform for mechanistic research into their role after lung transplantation.

4.
Article in English | MEDLINE | ID: mdl-38961756

ABSTRACT

PURPOSE: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. METHODS: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient-reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. RESULTS: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. CONCLUSIONS: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. LEVEL OF EVIDENCE: Level IV.

5.
Alzheimers Dement ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38982845

ABSTRACT

INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. HIGHLIGHTS: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

6.
Parasit Vectors ; 17(1): 298, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982497

ABSTRACT

BACKGROUND: Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. METHODS: In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. RESULTS: We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. CONCLUSIONS: This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis.


Subject(s)
Angiostrongylus cantonensis , Larva , Snails , Strongylida Infections , Animals , Snails/parasitology , Strongylida Infections/diagnosis , Strongylida Infections/parasitology , Strongylida Infections/veterinary , Angiostrongylus cantonensis/isolation & purification , Angiostrongylus cantonensis/physiology , Mouth/parasitology , Angiostrongylus/isolation & purification , Angiostrongylus/physiology , Rats , Humans
7.
Materials (Basel) ; 17(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38998270

ABSTRACT

Composite phosphor ceramics for warm white LED lighting were fabricated with K2SiF6:Mn4+ (KSF) as both a narrowband red phosphor and a translucent matrix in which yellow-emitting Y3Al5O12:Ce3+ (YAG) particles were dispersed. The emission spectra of these composites under blue LED excitation were studied as a function of YAG loading and thickness. Warm white light with a color temperature of 2716 K, a high CRI of 92.6, and an R9 of 77.6 was achieved. A modest improvement in the thermal conductivity of the KSF ceramic of up to 9% was observed with the addition of YAG particles. In addition, a simple model was developed for predicting the emission spectra based on several parameters of the composite ceramics and validated with the experimental results. The emission spectrum can be tuned by varying the dopant concentrations, thickness, YAG loading, and YAG particle size. This work demonstrates the utility of KSF/YAG composite phosphor ceramics as a means of producing warm white light, which are potentially suitable for higher-drive applications due to their increased thermal conductivity and reduced droop compared with silicone-dispersed phosphor powders.

8.
Plants (Basel) ; 13(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38999661

ABSTRACT

Plant density is increasing in modern olive orchards to improve yields and facilitate mechanical harvesting. However, greater density can reduce light quantity and modify its quality. The objective was to evaluate plant morphology, biomass, and photosynthetic pigments under different red/far-red ratios and photosynthetically active radiation (PAR) combinations in an olive cultivar common to super-high-density orchards. In a greenhouse, young olive trees (cv. Arbequina) were exposed to low (L) or high (H) PAR with or without lateral FR supplementation (L+FR, L-FR, H+FR, H-FR) using neutral-density shade cloth and FR light-emitting diode (LED) modules. Total plant and individual organ biomass were much lower in plants under low PAR than under high PAR, with no response to +FR supplementation. In contrast, several plant morphological traits, such as main stem elongation, individual leaf area, and leaf angle, did respond to both low PAR and +FR. Total chlorophyll content decreased with +FR when PAR was low, but not when PAR was high (i.e., a significant FR*PAR interaction). When evaluating numerous plant traits together, a greater response to +FR under low PAR than under high PAR appeared to occur. These findings suggest that consideration of light quality in addition to quantity facilitates a fuller understanding of olive tree responses to a light environment. The +FR responses found here could lead to changes in hedgerow architecture and light distribution within the hedgerow.

9.
Int J Mol Sci ; 25(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39000326

ABSTRACT

Decades of research have identified genetic and environmental factors involved in age-related neurodegenerative diseases and, to a lesser extent, neuropsychiatric disorders. Genomic instability, i.e., the loss of genome integrity, is a common feature among both neurodegenerative (mayo-trophic lateral sclerosis, Parkinson's disease, Alzheimer's disease) and psychiatric (schizophrenia, autism, bipolar depression) disorders. Genomic instability is associated with the accumulation of persistent DNA damage and the activation of DNA damage response (DDR) pathways, as well as pathologic neuronal cell loss or senescence. Typically, DDR signaling ensures that genomic and proteomic homeostasis are maintained in both dividing cells, including neural progenitors, and post-mitotic neurons. However, dysregulation of these protective responses, in part due to aging or environmental insults, contributes to the progressive development of neurodegenerative and/or psychiatric disorders. In this Special Issue, we introduce and highlight the overlap between neurodegenerative diseases and neuropsychiatric disorders, as well as the emerging clinical, genomic, and molecular evidence for the contributions of DNA damage and aberrant DNA repair. Our goal is to illuminate the importance of this subject to uncover possible treatment and prevention strategies for relevant devastating brain diseases.


Subject(s)
DNA Damage , Genomic Instability , Mental Disorders , Neurodegenerative Diseases , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/genetics , Mental Disorders/metabolism , Mental Disorders/etiology , Mental Disorders/genetics , DNA Repair , Animals
10.
Science ; 385(6704): 46-53, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38963838

ABSTRACT

Large language models trained on sequence information alone can learn high-level principles of protein design. However, beyond sequence, the three-dimensional structures of proteins determine their specific function, activity, and evolvability. Here, we show that a general protein language model augmented with protein structure backbone coordinates can guide evolution for diverse proteins without the need to model individual functional tasks. We also demonstrate that ESM-IF1, which was only trained on single-chain structures, can be extended to engineer protein complexes. Using this approach, we screened about 30 variants of two therapeutic clinical antibodies used to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We achieved up to 25-fold improvement in neutralization and 37-fold improvement in affinity against antibody-escaped viral variants of concern BQ.1.1 and XBB.1.5, respectively. These findings highlight the advantage of integrating structural information to identify efficient protein evolution trajectories without requiring any task-specific training data.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Directed Molecular Evolution , Humans , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/genetics , Antibodies, Viral/immunology , Antibody Affinity , Antigen-Antibody Complex/chemistry , COVID-19/virology , COVID-19/immunology , Models, Molecular , Protein Conformation , Protein Engineering , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Directed Molecular Evolution/methods
11.
Proc Natl Acad Sci U S A ; 121(28): e2322203121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968122

ABSTRACT

Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)-a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types.


Subject(s)
Single-Cell Analysis , Male , Humans , Single-Cell Analysis/methods , Animals , Mice , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/drug therapy , Antigens, Surface/metabolism , Antigens, Surface/genetics , Antigens, Neoplasm/metabolism , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/drug therapy , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/metabolism , Carcinoma, Neuroendocrine/drug therapy , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/drug therapy
12.
BMJ Open ; 14(7): e084581, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960457

ABSTRACT

OBJECTIVES: Develop and validate short and rapid forms of the 36-item Menstrual Practice Needs Scale (MPNS-36). DESIGN: Item reduction prioritised content validity and was informed by cognitive interviews with schoolgirls in Bangladesh, performance of scale items in past research and stakeholder feedback. The original MPNS-36 was revalidated, and short and rapid forms tested in a cross-sectional survey. This was followed by further tests of dimensionality, internal consistency and validity in multiple cross-sectional surveys. SETTING AND PARTICIPANTS: Short form (MPNS-SF) and rapid form (MPNS-R) measures were developed in a survey of 313 menstruating girls (mean age=13.51) in Khulna, Bangladesh. They were further tested in the baseline survey of the Adolescent Menstrual Experiences and Health Cohort, in Khulna, Bangladesh (891 menstruating girls, mean age=12.40); and the dataset from the MPNS-36 development in Soroti, Uganda (538 menstruating girls, mean age=14.49). RESULTS: The 18-item short form reflects the six original subscales, with the four core subscales demonstrating good fit in all three samples (Khulna pilot: root mean square error of approximation (RMSEA)=0.064, 90% CI 0.043 to 0.084, Comparative Fit Index (CFI)=0.94, Tucker-Lewis Index (TLI)=0.92. Cohort baseline: RMSEA=0.050, 90% CI 0.039 to 0.062, CFI=0.96, TLI=0.95. Uganda: RMSEA=0.039, 90% CI 0.028 to 0.050, CFI=0.95, TLI=0.94). The 9-item rapid form captures diverse needs. A two-factor structure was the most appropriate but fell short of adequate fit (Khulna pilot: RMSEA=0.092, 90% CI 0.000 to 0.158, CFI=0.93, TLI=0.89). Hypothesised associations between the MPNS scores and other constructs were comparable between the MPNS-36 and MPNS-SF in all populations, and replicated, with attenuation, in the MPNS-R. Internal consistency remained acceptable. CONCLUSIONS: The MPNS-SF offers a reliable and valid measure of adolescent girls' menstrual hygiene experience while reducing participant burden, to support implementation and improve measurement in menstrual health research. The MPNS-R provides a brief measure with poorer structural validity, suited to short surveys and including menstrual health within broader research topics.


Subject(s)
Menstruation , Psychometrics , Humans , Female , Bangladesh , Cross-Sectional Studies , Uganda , Adolescent , Reproducibility of Results , Surveys and Questionnaires , Child , Needs Assessment
14.
Article in English | MEDLINE | ID: mdl-38976113

ABSTRACT

Eukaryotic cell rheology has important consequences for vital processes such as adhesion, migration, and differentiation. Experiments indicate that cell cytoplasm can exhibit both elastic and viscous characteristics in different regimes, while the transport of fluid (cytosol) through the cross-linked filamentous scaffold (cytoskeleton) is reminiscent of mass transfer by diffusion through a porous medium. To gain insights into this complex rheological behaviour, we construct a computational model for the cell cytoplasm as a poroviscoelastic material formulated on the principles of nonlinear continuum mechanics, where we model the cytoplasm as a porous viscoelastic scaffold with an embedded viscous fluid flowing between the pores to model the cytosol. Baseline simulations (neglecting the viscosity of the cytosol) indicate that the system exhibits seven different regimes across the parameter space spanned by the viscoelastic relaxation timescale of the cytoskeleton and the poroelastic diffusion timescale; these regimes agree qualitatively with experimental measurements. Furthermore, the theoretical model also allows us to elucidate the additional role of pore fluid viscosity, which enters the system as a distinct viscous timescale. We show that increasing this viscous timescale hinders the passage of the pore fluid (reducing the poroelastic diffusion) and makes the cytoplasm rheology increasingly incompressible, shifting the phase boundaries between the regimes.

15.
J Card Fail ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986838

ABSTRACT

BACKGROUND: The ATHENA-HF clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. METHODS: We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effect and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. RESULTS: Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly larger with spironolactone treatment compared to placebo at 72 hours (0.23±0.55 vs 0.03±0.60 mEq/L, P=0.042) and 96 hours (0.32±0.51 vs 0.13±0.72 mEq/L, P=0.046). While potassium supplementation was similar at treatment start and 24 hours, spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P=0.048), 72 hours (21% vs 37%; P=0.013), and 96 hours (11% vs 38%; P<0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide, net fluid loss, urine output, or dyspnea relief between any of the potassium groups, with no effect modification by treatment exposure. CONCLUSIONS: Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting.

16.
Front Public Health ; 12: 1244353, 2024.
Article in English | MEDLINE | ID: mdl-38947352

ABSTRACT

Introduction: The Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce. Methods: A retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010-2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/). Results: A total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021). Conclusion: Infections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.


Subject(s)
Tuberculosis, Multidrug-Resistant , United Arab Emirates/epidemiology , Humans , Retrospective Studies , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Male , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Female , Adult , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Middle Aged , Drug Resistance, Bacterial , Adolescent , Microbial Sensitivity Tests , Young Adult , Population Surveillance
17.
Nat Struct Mol Biol ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898101

ABSTRACT

Epilepsy is a common neurological disorder characterized by abnormal activity of neuronal networks, leading to seizures. The racetam class of anti-seizure medications bind specifically to a membrane protein found in the synaptic vesicles of neurons called synaptic vesicle protein 2 (SV2) A (SV2A). SV2A belongs to an orphan subfamily of the solute carrier 22 organic ion transporter family that also includes SV2B and SV2C. The molecular basis for how anti-seizure medications act on SV2s remains unknown. Here we report cryo-electron microscopy structures of SV2A and SV2B captured in a luminal-occluded conformation complexed with anticonvulsant ligands. The conformation bound by anticonvulsants resembles an inhibited transporter with closed luminal and intracellular gates. Anticonvulsants bind to a highly conserved central site in SV2s. These structures provide blueprints for future drug design and will facilitate future investigations into the biological function of SV2s.

18.
Sci Total Environ ; 942: 173567, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38848918

ABSTRACT

The increasing trend of using agricultural wastes follows the concept of "waste to wealth" and is closely related to the themes of sustainable development goals (SDGs). Carbon-neutral technologies for waste management have not been critically reviewed yet. This paper reviews the technological trend of agricultural waste utilization, including composting, thermal conversion, and anaerobic digestion. Specifically, the effects of exogenous additives on the contents, fractionation, and fate of phosphorus (P) and potentially toxic elements (PTEs) during the composting process have been comprehensively reviewed in this article. The composting process can transform biomass-P and additive-born P into plant available forms. PTEs can be passivated during the composting process. Biochar can accelerate the passivation of PTEs in the composting process through different physiochemical interactions such as surface adsorption, precipitation, and cation exchange reactions. The addition of exogenous calcium, magnesium and phosphate in the compost can reduce the mobility of PTEs such as copper, cadmium, and zinc. Based on critical analysis, this paper recommends an eco-innovative perspective for the improvement and practical application of composting technology for the utilization of agricultural biowastes to meet the circular economy approach and achieve the SDGs.


Subject(s)
Agriculture , Composting , Phosphorus , Phosphorus/analysis , Agriculture/methods , Composting/methods , Waste Management/methods
20.
Ann Intern Med ; 177(6): JC70, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38830211

ABSTRACT

SOURCE CITATION: Auer R, Schoeni A, Humair JP, et al. Electronic nicotine-delivery systems for smoking cessation. N Engl J Med. 2024;390:601-610. 38354139.


Subject(s)
Counseling , Electronic Nicotine Delivery Systems , Smoking Cessation , Humans , Smoking Cessation/methods , Adult , Male , Female , Middle Aged
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