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1.
Magn Reson Med ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576077

RESUMO

PURPOSE: To develop a method that achieves simultaneous brain and neck time-of-flight (ToF) magnetic resonance angiography (MRA) within feasible scan timeframes. METHODS: Localized quadratic (LQ) encoding is efficient for both signal-to-noise ratio (SNR) and in-flow enhancement. We proposed a spiral multiband LQ method to enable simultaneous intracranial and carotid ToF-MRA within a single scan. To address the venous signal contamination that becomes a challenge with multiband (MB) ToF, tilt-optimized non-saturated excitation (TONE) and partial-Fourier slice selection (PFSS) were further introduced in the LQ framework to mitigate the venous signal and improve artery contrast. A sequential spiral MB and LQ reconstruction pipeline was employed to obtain the brain-and-neck image volumes. RESULTS: The proposed MB method was able to achieve simultaneous brain and neck ToF-MRA within a 2:50-min scan. The complementarily boosted SNR-efficiency by MB and LQ acquisitions allows for the increased spatial coverage without increase in scan time or noticeable compromise in SNR. The incorporation of both TONE and PFSS effectively alleviated the venous contamination with improved small vessel sensitivity. Selection of scan parameters such as the LQ factor and flip angle reflected the trade-off among SNR, blood contrast, and venous suppression. CONCLUSIONS: A novel MB spiral LQ approach was proposed to enable fast intracranial and carotid ToF-MRA with minimized venous corruption. The method has shown promise in MRA applications where large spatial coverage is necessary.

2.
Br J Dermatol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576350

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. OBJECTIVE: To explore the effects of spesolimab treatment in patients with HS. METHODS: This randomized, double-blind, placebo-controlled, proof-of-clinical-concept study was conducted at 25 centers across 12 countries from May 3, 2021, to April 21, 2022. Patients had moderate-to-severe HS for ≥1 year before enrollment. Patients were randomized (2:1) to receive a loading dose of 3600 mg intravenous spesolimab (1200 mg at Weeks 0, 1, and 2) or matching placebo, followed by maintenance with either 1200 mg subcutaneous spesolimab every 2 weeks from Week 4-10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at Week 12. Secondary endpoints were the absolute change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of zero, absolute change from baseline in revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥1 flare (all at Week 12), and patient-reported outcomes (PROs). RESULTS: In this completed trial, randomized patients (N=52) received spesolimab (n=35) or placebo (n=17). The difference (95% confidence interval) versus placebo in least squares mean are reported. At Week 12, the percentage change in total AN count was similar between treatment arms: -4.1% (-31.7, 23.4). There was greater numerical improvement in the spesolimab arm, as measured by IHS4: -13.9 (-25.6, -2.3); percentage change from baseline in dT count: -96.6% (-154.5, -38.8); and the proportion of patients achieving a dT count of zero: 18.3% (-7.9, 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 versus placebo. Spesolimab demonstrated a favorable safety profile, similar to that observed in trials in other diseases. CONCLUSIONS: This exploratory proof-of-clinical-concept study supports the development of spesolimab as a new therapeutic option in HS. ClinicalTrials.gov identifier: NCT04762277.

3.
Clin Infect Dis ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598658

RESUMO

BACKGROUND: Although the SARS-CoV-2 vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. METHODS: A post-hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, COVID-19 vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS (NTIS) individuals starting at 14 days after completion of the primary series through the blinded phase for each of the four trials. An analysis of participants living with well-controlled HIV was conducted using the same methods. RESULTS: 3,852/30,351 (12.7%) Moderna participants, 3,088/29,868 (10.3%) Novavax participants, 3,549/32,380 (11.0%) AstraZeneca participants, and 5,047/43,788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (versus placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants vs NTIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with HIV. CONCLUSIONS: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared to those with non-tempered immune systems in the four COVID-19 vaccine randomized controlled efficacy trials.

4.
Lancet ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38588689

RESUMO

BACKGROUND: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam. METHODS: As part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10-17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs. FINDINGS: Final samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9-13·5) in Kenya, 5·5% (4·3-6·9) in Indonesia, and 3·3% (2·7-4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3-10·6) in Kenya, 4·4% (3·4-5·6) in Indonesia, and 2·7% (2·2-3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0-2·0) and Viet Nam (1·0-1·9) to 4·6% (3·9-5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3-0·8) and Viet Nam (0·2-0·6) to 2·4% (1·9-2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1-0·4) and Viet Nam (0·1-0·3) to 1·0% (0·7-1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6-1·3) in Indonesia to 1·2% (0·9-1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1-15·9] in Indonesia to 14·7 [7·5-28·6] in Viet Nam). INTERPRETATION: NAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries. FUNDING: The University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company.

5.
J Interpers Violence ; : 8862605241245368, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591149

RESUMO

Sexual harassment inflicted by adolescents on their peers is a major public health issue, but its prevalence across childhood is not known. We provide the first nationally representative data on the prevalence of peer sexual harassment across childhood, using cross-sectional data from the Australian Child Maltreatment Study (ACMS). The ACMS surveyed 8,503 people aged 16 and over about their experiences of child maltreatment and associated health outcomes. The prevalence of peer sexual harassment was assessed using the Juvenile Victimization Questionnaire (JVQ)-R2 Adapted Version (ACMS), with survey data weighted to reflect characteristics of the Australian population. Overall, 1 in 10 (10.4% (95% Confidence Intervals (CI) [9.7, 11.3])) Australians experienced peer sexual harassment during childhood. Peer sexual harassment is an issue disproportionately affecting gender-diverse individuals (24.0%, 95% CI [15.5, 35.2]) and women (15.3%, 95% CI [14.0, 16.7%]), compared to men (5.0%, 95% CI [4.3, 5.9]). Rates of peer sexual harassment were also very high among sexuality diverse participants (prevalence estimates ranging between 14.2% and 29.8%). Peer sexual harassment was predominately inflicted by male peers (9.6%, 95% CI [8.9, 10.4]), compared to 1.8% (95% CI [1.5, 2.2]) reporting harassment from female peers. These findings have implications for understanding and reducing attitudes supporting peer sexual harassment in childhood, particularly against girls and gender and sexuality diverse youth, and associations with other gendered violence both in childhood and later life.

6.
Biochimie ; 223: 31-40, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579894

RESUMO

Leishmaniasis is a spectrum of conditions caused by infection with the protozoan Leishmania spp. parasites. Leishmaniasis is endemic in 98 countries around the world, and resistance to current anti-leishmanial drugs is rising. Our work has identified and characterised a previously unstudied galactokinase-like protein (GalK) in Leishmania donovani, which catalyses the MgATP-dependent phosphorylation of the C-1 hydroxyl group of d-galactose to galactose-1-phosphate. Here, we report the production of the catalytically active recombinant protein in E. coli, determination of its substrate specificity and kinetic constants, as well as analysis of its molecular envelope using in solution X-ray scattering. Our results reveal kinetic parameters in range with other galactokinases with an average apparent Km value of 76 µM for galactose, Vmax and apparent Kcat values with 4.46376 × 10-9 M/s and 0.021 s-1, respectively. Substantial substrate promiscuity was observed, with galactose being the preferred substrate, followed by mannose, fructose and GalNAc. LdGalK has a highly flexible protein structure suggestive of multiple conformational states in solution, which may be the key to its substrate promiscuity. Our data presents novel insights into the galactose salvaging pathway in Leishmania and positions this protein as a potential target for the development of pharmaceuticals seeking to interfere with parasite substrate metabolism.

7.
Child Maltreat ; : 10775595241246534, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627990

RESUMO

This study aimed to explore key characteristics of the out-of-home care subgroup of a nationally representative Australian sample. To ensure that mental health services are appropriately targeted, it is critical that we understand the differential impacts of childhood experiences for this cohort. Using the Australian Child Maltreatment Study (N = 8503), we explored patterns of childhood maltreatment and adversity of participants who reported ever being placed in out-of-home care, such as foster care or kinship care. In addition, the prevalence of current and lifetime diagnosis of four mental health disorders were explored. Results showed that the care experienced subgroup reported more types of maltreatment and adverse experiences than the control group. They were also more likely to meet diagnostic threshold for post-traumatic stress disorder, generalised anxiety disorder and major depressive disorder than the control group. These findings can be used to guide mental health practitioners to target interventions more effectively within the out-of-home care cohort.

8.
Skin Health Dis ; 4(2): e343, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577038

RESUMO

Background: Generalised pustular psoriasis (GPP) is a rare and chronic skin disease historically treated with therapies that were originally intended to treat plaque psoriasis (PsO). However, GPP and plaque PsO have distinct pathogeneses and clinical courses. Objectives: This study aimed to further characterise the unique genetic background of GPP by summarising evidence on the frequency and type of IL36RN gene mutation, a gene that normally suppresses proinflammatory responses, in patients with GPP compared to patients with GPP and plaque PsO, and patients with plaque PsO only. Methods and Results: A targeted literature review was conducted to identify studies reporting IL36RN mutations and/or HLA-Cw6 allele frequency in patients with GPP. Meta-analyses showed a significantly higher rate of IL36RN mutations in the GPP-only population compared to the GPP + plaque PsO population (OR 3.51; 95% CI 2.29, 5.38). Monoallelic mutations of IL36RN were found in up to 33.3%, and biallelic mutations in up to 73.2% of patients with GPP (GPP-only and GPP + plaque PsO), in contrast with mono- and biallelic frequencies of only 0%-11.9% and 0%, respectively, in patients with plaque PsO only. Mean age-of-onset ranged from 5.9 to 48.9 years old, with most studies reporting a GPP age-of-onset between 20 and 40 years old. Twenty-one mutations were identified in the biallelic state and three in monoallelic. The most reported mutations were c.115 + 6T > C (p. Arg10ArgfsX1) (18 studies); c.227 C > T (p.Pro76Leu) (10 studies); and c.338 C > T (p.Ser113Leu) (8 studies). Mutations varied depending on geography and ethnicity, with the most frequently reported mutation predominantly reported in East Asian studies and international studies that included Asian patients. Rates of HLA-Cw6, the risk allele most strongly associated with plaque PsO, were 0%-28.6% for patients with GPP, similar to rates in the general population (10.5%-20%). Conclusion: Considering the differences between GPP and plaque PsO in aetiology and disease symptoms, effective, GPP-specific treatment options are needed, and recent research suggests that blockade of IL-36 signalling may be an effective target for treatment of GPP.

9.
J Mol Biol ; : 168571, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604528

RESUMO

Extracellular vesicles and particles (EVPs) play a crucial role in mediating cell-to-cell communication by transporting various molecular cargos, with small non-coding RNAs (ncRNAs) holding particular significance. A thorough investigation into the abundance and sorting mechanisms of ncRNA within EVPs is imperative for advancing their clinical applications. We have developed EVPsort, which not only provides an extensive overview of ncRNA profiling in 3,162 samples across various biofluids, cell lines, and disease contexts but also seamlessly integrates 19 external databases and tools. This integration encompasses information on associations between ncRNAs and RNA-binding proteins (RBPs), motifs, targets, pathways, diseases, and drugs. With its rich resources and powerful analysis tools, EVPsort extends its profiling capabilities to investigate ncRNA sorting, identify relevant RBPs and motifs, and assess functional implications. EVPsort stands as a pioneering database dedicated to comprehensively addressing both the abundance and sorting of ncRNA within EVPs. It is freely accessible at https://bioinfo.vanderbilt.edu/evpsort/.

12.
Acta Psychol (Amst) ; 246: 104273, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38636402

RESUMO

Attachment styles influence mental health and relationships through life. Few studies examine the adolescent factors associated with adult attachment styles. This paper examines the association between adolescent emotional and behavioral problems and maternal-adolescent communication with attachment style in early adulthood. Data from 3423 participants in a birth cohort study were examined. At 14-years, participants' mothers completed the Parent-Adolescent Communication Scale. Participants completed the Youth Self-Report at 14-years which measures internalizing and externalizing symptoms, and the Attachment Style Questionnaire (ASQ) at 21-years. The ASQ comprises five domains of internal working models of interpersonal relationships and attachment style: confidence (security), discomfort with closeness and relationships as secondary (avoidance), need for approval and preoccupation with relationships (anxiety). Associations were examined using general linear models. After adjustments, internalizing symptoms score was associated with all domains of attachment and externalizing symptoms score was associated with four domains of attachment insecurity, but not attachment security. Low openness in maternal-adolescent communication was most strongly associated with decreased confidence and high problem maternal-adolescent communication was associated with viewing relationships as secondary. Adolescents with emotional and behavioral problems and maternal-adolescent communication may benefit from attachment-based interventions to support the development of healthy relationships and attachments in young adulthood.

13.
Mol Cancer Ther ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641404

RESUMO

KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the RTK/MAPK pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway. MRTX0902 augmented the antitumor activity of the KRAS G12C inhibitor adagrasib when dosed in combination in eight out of twelve KRAS G12C-mutant human non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) xenograft models. Pharmacogenomic profiling in preclinical models identified cell cycle genes and the SOS2 homolog as genetic co-dependencies and implicated tumor suppressor genes (NF1, PTEN) in resistance following combination treatment. Lastly, combined vertical inhibition of RTK/MAPK pathway signaling by MRTX0902 with inhibitors of EGFR or RAF/MEK led to greater downregulation of pathway signaling and improved antitumor responses in KRAS-MAPK pathway-mutant models. These studies demonstrate the potential clinical application of dual inhibition of SOS1 and KRAS G12C and additional SOS1 combination strategies that will aide in the understanding of SOS1 and RTK/MAPK biology in targeted cancer therapy.

14.
Plants (Basel) ; 13(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38611542

RESUMO

This study aims to establish an Agrobacterium-mediated transformation system for use with the 'MiniMax'soybean cultivar. MiniMax is a mutant soybean whose growth cycle is around 90 days, half that of most other soybean varieties, making it an optimal model cultivar to test genes of interest before investing in modification of elite lines. We describe an efficient protocol for Agrobacterium-mediated transformation using MiniMax seeds. It uses a modified 'half seed' regeneration protocol for transgenic soybean production, utilizing the rapid generation MiniMax variety to obtain T1 seeds in approximately 145 days. Addition of phloroglucinol (PG) to the regeneration protocol was key to obtaining high-efficiency rooting of the regenerated shoots. Transfer to soil was accomplished using an organic soil amendment containing nutrients and mycorrhiza for plants to thrive in the greenhouse. This combination of genotype and stimulants provides a transformation protocol to genetically engineer MiniMax seeds with a transgenic lab-to-greenhouse production efficiency of 4.0%. This is the first report of MiniMax soybean whole plant transformation and heritable T1 transmission. This protocol provides an ideal resource for enhancing the genetic transformation of any soybean cultivar.

15.
Nat Mater ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622325

RESUMO

A magnon is a collective excitation of the spin structure in a magnetic insulator and can transmit spin angular momentum with negligible dissipation. This quantum of a spin wave has always been manipulated through magnetic dipoles (that is, by breaking time-reversal symmetry). Here we report the experimental observation of chiral spin transport in multiferroic BiFeO3 and its control by reversing the ferroelectric polarization (that is, by breaking spatial inversion symmetry). The ferroelectrically controlled magnons show up to 18% modulation at room temperature. The spin torque that the magnons in BiFeO3 carry can be used to efficiently switch the magnetization of adjacent magnets, with a spin-torque efficiency comparable to the spin Hall effect in heavy metals. Utilizing such controllable magnon generation and transmission in BiFeO3, an all-oxide, energy-scalable logic is demonstrated composed of spin-orbit injection, detection and magnetoelectric control. Our observations open a new chapter of multiferroic magnons and pave another path towards low-dissipation nanoelectronics.

16.
Eur Spine J ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607406

RESUMO

PURPOSE: Aerobic exercise produces beneficial outcomes in patients with low back pain and partially attenuates the fibrotic changes to the multifidus in a model of intervertebral disc (IVD) degeneration. More targeted exercise might be required to fully attenuate these fibrotic alterations. This study aimed to investigate whether activation of the multifidus induced by neurostimulation could reduce fibrosis of the multifidus in a model of IVD degeneration in sheep. METHODS: IVD degeneration was induced in 18 merino sheep via a partial thickness unilateral annulus fibrosus lesion to the L1/2 and L3/4 IVDs. All sheep received an implantable neurostimulation device that provides stimulation of the L2 medial branch of the dorsal ramus. Three months after surgery, the animals were assigned to Injury or Activated groups. Activated animals received neurostimulation and the Injury group received no stimulation. Six months after surgery, the multifidus was harvested at L2 and L4. Van Gieson's, Sirius Red and immunofluorescence staining for Collagen-I and -III and quantitative PCR was used to examine fibrosis. Muscle harvested from a previous study without IVD injury was used as a control. RESULTS: Neurostimulation of the multifidus attenuated IVD degeneration dependent increases in the connective tissue, including Collagen-I but not Collagen-III, compared to the Injury group at L4. No measures of the multifidus muscle at L2, which received no stimulation, differed between the Injury and Activated groups. CONCLUSIONS: These data reveal that targeted activation of the multifidus muscle attenuates IVD degeneration dependent fibrotic alterations to the multifidus.

17.
Am J Bot ; : e16318, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654555

RESUMO

PREMISE: Numerous studies have found a positive association between dioecy and polyploidy; however, this association presents a theoretical conflict: While polyploids are predicted to benefit from self-reproduction for successful establishment, dioecious species cannot self-reproduce. We propose a theoretical framework to resolve this apparent conflict. We hypothesize that the inability of dioecious species to self-reproduce hinders their establishment as polyploids. We therefore expect that genera with many dioecious species have fewer polyploids, leading to a negative association between polyploidy and dioecy across genera. METHODS: We used three publicly available databases to determine ploidy and sexual systems for 131 genera and 546 species. We quantified (1) the relationship between the frequency of polyploid species and the frequency of dioecious species across genera, and (2) the proportion of polyploids with hermaphroditism and dioecy across species, adjusting for phylogenetic history. RESULTS: Across genera, we found a negative relationship between the proportion of polyploids and the proportion of dioecious species, a consistent trend across clades. Across all species, we found that sexual system (dioecious or not) was not associated with polyploidy. CONCLUSIONS: Polyploids are rare in genera in which the majority of species are dioecious, consistent with the theory that self-reproduction favors polyploid establishment. The low frequency of polyploidy among dioecious species indicates the association is not as widespread as previously suggested. Our findings are consistent with previous studies identifying a positive relationship between the two traits, but only if polyploidy promotes a transition to dioecy, and not the reverse.

18.
Obes Sci Pract ; 10(2): e751, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38655127

RESUMO

Background: Non-alcoholic fatty liver disease (NAFLD) is recognized as a prevalent determinant of cardiometabolic diseases. The association between NAFLD and obesity warrants further research on how NAFLD modifies associations between body mass index (BMI) and Waist circumference (WC) with cardiometabolic risk (CMR). Objective: This study assessed whether NAFLD modifies associations between BMI and WC with 5-year changes in CMR in 2366 CARDIA study participants. Methods: Non-contrast CT was used to quantify liver attenuation, with ≤51 Hounsfield Units (HU) used to define NAFLD in the absence of secondary causes of excess liver fat. The dependent variable was the average Z score of fasting glucose, insulin, triglycerides [log], (-) high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure(SBP). Multivariable linear regression was used to estimate the associations between BMI and WC with CMR. Effect modification by NAFLD was assessed by an interaction term between NAFLD and BMI or WC. Results: The final sample had 539 (23%) NAFLD cases. NAFLD modified the association of BMI and WC with CMR (interaction p < 0.0001 for both). BMI and WC were associated with CMR in participants without NAFLD (p < 0.001), but not among those with NAFLD. Participants with NAFLD and normal BMI and WC had CMR estimates that were higher than those without NAFLD in the obese categories. Among those without NAFLD the 5 years CMR change estimate was 0.09 (95% CI: 0.062, 0.125) for BMI ≥30 kg/m2 compared to -0.06 (-0.092, -0.018) for BMI < 25 kg/m2, and among those with NAFLD, these estimates were 0.15 (0.108, 0.193) and 0.16 (-0.035, 0.363). Conclusions: NAFLD modifies associations of BMI and WC with CMR. Compared with BMI and WC, NAFLD was more strongly associated with CMR. In the presence of NAFLD, BMI and WC were not associated with CMR. These findings have implications for clinical screening guidelines.

19.
J Vis Exp ; (206)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38647320

RESUMO

Fuel treatments and other forest restoration thinning practices aim to reduce wildfire risk while building forest resilience to drought, insects, and diseases and increasing aboveground carbon (C) sequestration. However, fuel treatments generate large amounts of unmerchantable woody biomass residues that are often burned in open piles, releasing significant quantities of greenhouse gases and particulates, and potentially damaging the soil beneath the pile. Air curtain burners offer a solution to mitigate these issues, helping to reduce smoke and particulates from burning operations, more fully burn biomass residues compared to pile burning, and eliminate the direct and intense fire contact that can harm soil beneath the slash pile. In an air curtain burner, burning takes place in a controlled environment. Smoke is contained and recirculated by the air curtain, and therefore burning can be conducted under a variety of climatic conditions (e.g., wind, rain, snow), lengthening the burning season for disposal of slash material. The mobile pyrolysis unit that continuously creates biochar was specifically designed to dispose of residual woody biomass at log landings, green wood at landfills, or salvaged logged materials and create biochar in the process. This high-carbon biochar output can be used to enhance soil resilience by improving its chemical, physical, and biological properties and has potential applications in remediating contaminated soils, including those at abandoned mine sites. Here, we describe the general use of this equipment, appropriate siting, loading methods, quenching requirements, and lessons learned about operating this new technology.

20.
J Pers Soc Psychol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635183

RESUMO

People's motivational processes, well-being, and performance are likely to be facilitated through the support of others. Self-determination theory argues that interpersonal supports for autonomy, competence, and relatedness are crucial to achieve these outcomes. In the present study, we provide a comprehensive examination of this formulation based on a meta-analytic database consisting of 4,561 effect sizes from 881 independent samples (N = 443,556). Our results indicate that supports for autonomy, competence, and relatedness were strongly positively related with the satisfaction of these basic needs and strongly negatively related to their frustration. Interpersonal supports for basic needs were strongly positively related with subjective well-being and exhibited small to moderate positive associations with performance. Moderation analyses showed general stability of effects across cultures, although correlations of autonomy support to autonomous motivation weakened as a function of individualism. The opposite pattern was observed for the correlation between relatedness support and intrinsic motivation. Some effects also declined as a function of sample age and lag in measurements. We also find that competence- and relatedness-supportive behaviors explained incremental variance in basic need satisfaction even after controlling for the more established effects of autonomy support. In addition, lateral need supports explained incremental variance in basic need satisfaction after controlling for vertical sources of support. In sum, our results are consistent with the premise that to support optimal motivation, well-being, and performance, a broad set of behaviors that nurture all three basic needs, together with different sources of interpersonal support, should be considered to yield the most benefit. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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