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1.
J Sex Res ; 61(6): 868-881, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973057

RESUMO

Since the initial development of the Sexual Experiences Survey (SES) four decades ago, the SES has been designed to measure a range of forms of sexual exploitation, including acts that are coercive but not legally sanctioned as well as acts that legally qualify as crimes. That feature was retained in the revised Sexual Experiences Survey-Victimization (SES-V) measure. This article reviews the theoretical and empirical literature that guided the development of the Illegal Sexual Exploitation module of the SES-V, which measures experiences of nonconsensual exploitation resulting in sexual contact and which is designed to correspond to legal definitions across multiple jurisdictions. This article addresses research and applied contexts in which the distinction between legal and illegal sexual exploitation is important and the challenges and limitations involved in writing survey items that correspond to legal definitions. It also discusses revisions made to the items that make up the Illegal Sexual Exploitation module of the SES-V as compared to the illegal items in prior versions of the SES, including a new operationalization of non-consent and an expansion of the sexual acts and exploitative tactics that are included. Finally, the article discusses directions for future research on the Illegal Sexual Exploitation module of the SES-V.


Assuntos
Vítimas de Crime , Humanos , Vítimas de Crime/legislação & jurisprudência , Delitos Sexuais/legislação & jurisprudência , Adulto , Comportamento Sexual , Inquéritos e Questionários/normas , Feminino , Masculino
2.
J Sex Res ; 61(6): 904-921, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973059

RESUMO

The new Sexual Experiences Survey-Victimization (SES-V) was designed to capture a larger range of sexual exploitation and to be applicable to more diverse populations than prior measures. This study represents the first administration of the SES-V in a national sample of adults (N = 347). Participants were recruited from a crowdsourcing platform and selected to reflect the national distribution in terms of age, sex, and race/ethnicity. Rates of sexual exploitation since age 14 were very high in this sample (90%), providing evidence that the SES-V was successful in capturing experiences on the low end of the severity continuum. Using the items corresponding to the FBI definition of rape, 60% of women and 29% of men endorsed rape on the SES-V. Compared to men, women reported higher rates of sexual exploitation overall, and higher rates of every type of sexual exploitation except technology-facilitated. The new SES-V also asks participants to estimate the number of separate instances of four types of sexual exploitation that they have experienced; results provided support for the value of these incident estimates in understanding the scope of sexual exploitation. Finally, this study evaluated new sexual acts and exploitative tactics that were added to the SES-V and found that they demonstrated utility and validity. These findings offer preliminary support for the validity and functionality of the SES-V, although the high prevalence of sexual exploitation on the SES-V is discussed as both a strength and limitation. Future research should evaluate prevalence and demographic differences in a larger national sample.


Assuntos
Vítimas de Crime , Humanos , Masculino , Feminino , Adulto , Vítimas de Crime/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto Jovem , Prevalência , Pessoa de Meia-Idade , Adolescente , Estupro/estatística & dados numéricos , Estupro/psicologia , Inquéritos e Questionários
3.
J Sex Res ; 61(6): 922-935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973058

RESUMO

The Sexual Experiences Survey-Victimization (SES-V; see Koss et al., 2024) revises the prior 2007 Sexual Experiences Survey-Short Form Victimization (SES-SFV) in many ways, including expanded measurement of verbally pressured and illegal sexual exploitation, as well as the addition of items that assess being made to perform a sexual act or to penetrate another person sexually. The current article describes two initial validity studies of the SES-V. Study 1 compared rates of self-reported verbal pressure and illegal sexual exploitation (e.g. rape) on a preliminary version of the SES-V and the SES-SFV in a sample of higher education students who completed both questionnaires online in a randomized order (N = 460). As expected, the preliminary SES-V produced higher rates than the SES-SFV, and continuous scores were strongly correlated. Responses to the made-to-penetrate (MTP) items suggested that some cisgender men and women may have misunderstood those items. Study 2 explored responses to the MTP items further by randomly assigning participants to complete items with either the Study 1 MTP language (n = 269) or revised language (n = 245). The revised language produced fewer implausible responses and was adopted in the final version of the SES-V. These findings provide initial support for the validity of the SES-V and the value of expanding the conceptualization of victimization to include a wider range of sexual exploitation. A research agenda for future validity research is suggested.


Assuntos
Vítimas de Crime , Humanos , Feminino , Masculino , Adulto , Adulto Jovem , Reprodutibilidade dos Testes , Inquéritos e Questionários/normas , Delitos Sexuais , Adolescente
4.
J Sex Res ; 61(6): 839-867, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973060

RESUMO

The Sexual Experiences Survey [SES] is considered the gold standard measure of non-consensual sexual experiences. This article introduces a new victimization version [SES-V] developed by a multidisciplinary collaboration, the first revision since 2007. The 2024 SES-V is designed to measure the construct of sexual exploitation since the 14th birthday. Notable revisions are adoption of a freely given permission standard for non-consent, introduction of new tactics and acts, including made to perform or to penetrate another person's body, tactics-first wording order, and emphasis on gender and sexual orientation inclusivity. The SES-V is modularized to allow whole or partial administration. Modules include Non-contact, Technology-facilitated, Illegal (largely penetrative), and Verbally pressured sexual exploitation. Tables provide item text, multiple scoring approaches, module follow-up, specific incident description and demographics. Future plans include developing a scoring algorithm based on weighting our hypothesized dimensions of sexual exploitation severity: invasiveness, pressure, and norm violation combined with frequency. This article is the first in a special issue on the SES-V. Subsequent articles focus on the taxonomies and literature that informed each module. The issue concludes with two empirical papers demonstrating the feasibility and validity of the SES-V: (1) psychometric comparison with the 2007 SES-SFV; and (2) prevalence data from a census-matched adult community sample.


Assuntos
Vítimas de Crime , Humanos , Vítimas de Crime/psicologia , Masculino , Adulto , Feminino , Adulto Jovem , Adolescente , Psicometria/instrumentação , Psicometria/normas , Pessoa de Meia-Idade , Inquéritos e Questionários/normas , Comportamento Sexual/psicologia
5.
Genetics ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039029

RESUMO

Mutating replication-dependent (RD) histone genes is an important tool for understanding chromatin-based epigenetic regulation. Deploying this tool in metazoans is particularly challenging because RD histones in these organisms are typically encoded by many genes, often located at multiple loci. Such gene arrangements make the ability to generate homogenous histone mutant genotypes by site-specific gene editing quite difficult. Drosophila melanogaster provides a solution to this problem because the RD histone genes are organized into a single large tandem array that can be deleted and replaced with transgenes containing mutant histone genes. In the last ∼15 years several different RD histone gene replacement platforms were developed using this simple strategy. However, each platform contains weaknesses that preclude full use of the powerful developmental genetic capabilities available to Drosophila researchers. Here we describe the development of a newly engineered platform that rectifies many of these weaknesses. We used CRISPR to precisely delete the RD histone gene array (HisC), replacing it with a multifunctional cassette that permits site-specific insertion of either one or two synthetic gene arrays using selectable markers. We designed this cassette with the ability to selectively delete each of the integrated gene arrays in specific tissues using site-specific recombinases. We also present a method for rapidly synthesizing histone gene arrays of any genotype using Golden Gate cloning technologies. These improvements facilitate generation of histone mutant cells in various tissues at different stages of Drosophila development and provide an opportunity to apply forward genetic strategies to interrogate chromatin structure and gene regulation.

6.
J Sex Res ; 61(6): 882-896, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38973062

RESUMO

This article describes the development of the Verbally Pressured Sexual Exploitation module of the Sexual Experiences Survey (SES)-Victimization (introduced by Koss et al., 2024). This module assesses the use of verbal or nonphysical, paraverbal pressure to obtain sexual acts without freely given permission. An interdisciplinary team of seven sexual exploitation researchers collaborated to create this module, with consultation from the full 15 member SES-V revision collaboration team. In this paper, we describe our process for developing this module. We briefly review empirical literature and theoretical frameworks (e.g., rape scripts, normative sexual scripts, intersectionality, and sex-positivity) that informed this work. Summary tables compare the SES-V items to verbal pressure items in prior versions of the SES and to other existing measures of violence. The comprehensive taxonomy developed herein includes six domains of Verbally Pressured sexual exploitation across 11 item stems. The components of the taxonomy include: positive verbal pressure, neutral verbal pressure, negative verbal pressure, substance-related pressure, postural violence, and threats to critical resources. The paper concludes with suggestions for future research, with priority on intersectional research that can illuminate the phenomenology and contexts of sexual exploitation against marginalized groups.


Assuntos
Vítimas de Crime , Humanos , Vítimas de Crime/psicologia , Vítimas de Crime/classificação , Feminino , Adulto , Masculino , Comportamento Sexual/psicologia , Comportamento Sexual/classificação , Delitos Sexuais/classificação , Delitos Sexuais/psicologia , Adulto Jovem
7.
Cureus ; 16(6): e62253, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39011213

RESUMO

Introduction Social media platforms have changed the way society communicates and collaborates. Prior research in healthcare discusses how social media can empower patients, dispel health-related misinformation, and help maintain a patient-centered practice. The goal of this study was to evaluate the use of #endoscopicspinesurgery on Instagram and create a blueprint for creating engaging posts on the social media platform. Methodology Public Instagram posts (n = 171) that utilized #endoscopicspinesurgery were collected over three months in 2022. Each post was assessed for photo and caption content, likes, comments, number of followers, and hashtag information. Engagement rates were calculated for each post to assess the active interaction of post characteristics and content. Results The majority of posts were published by medical professionals (72/171, 42.1%) and industry-related user accounts (55/171, 32.2%). Content related to training, conferences, and the operating room garnered the highest average engagement. Post characteristics (number of hashtags and number of post photos) were significantly associated with engagement. Conclusions Results highlighted general trends in creating engaging social media posts, such as using hashtags intentionally to increase searchability and visibility, having higher numbers of photos in a post and using high-quality photos, and understanding the dynamic social media algorithms that may affect post viewership. When structuring social media posts, users should be aware of the audience they want to attract and construct their content accordingly.

8.
bioRxiv ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38979215

RESUMO

Tight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the ON/OFF state of targets like the Hox genes. Trithorax encodes a methyltransferase specific to histone H3 lysine-4 (H3K4). However, there is no direct evidence that H3K4 regulates Polycomb group target genes in vivo . Here, we demonstrate two key roles for replication-dependent histone H3.2K4 in target control. We find that H3.2K4 antagonizes Polycomb group catalytic activity and that it is required for proper target gene activation. We conclude that H3.2K4 directly regulates expression of Polycomb targets.

9.
JACC Adv ; 3(4): 100896, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38939656
10.
Science ; 384(6700): eadn0886, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38843332

RESUMO

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express µ-opioid receptors (µORs). Disrupting µOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.


Assuntos
Analgésicos Opioides , Aprendizagem da Esquiva , Transtornos Relacionados ao Uso de Opioides , Oxicodona , Núcleos Parabraquiais , Córtex Pré-Frontal , Receptores Opioides mu , Recompensa , Animais , Masculino , Camundongos , Analgésicos Opioides/farmacologia , Conectoma , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/fisiologia , Transtornos Relacionados ao Uso de Opioides/metabolismo , Oxicodona/farmacologia , Núcleos Parabraquiais/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Células Piramidais/metabolismo , Receptores Opioides mu/metabolismo , Receptores Opioides mu/genética , Síndrome de Abstinência a Substâncias/metabolismo , Transcriptoma
11.
Artigo em Inglês | MEDLINE | ID: mdl-38863598

RESUMO

Traditional interventions for academic procrastination often fail to capture the nuanced, individual-specific factors that underlie them. Large language models (LLMs) hold immense potential for addressing this gap by permitting open-ended inputs, including the ability to customize interventions to individuals' unique needs. However, user expectations and potential limitations of LLMs in this context remain underexplored. To address this, we conducted interviews and focus group discussions with 15 university students and 6 experts, during which a technology probe for generating personalized advice for managing procrastination was presented. Our results highlight the necessity for LLMs to provide structured, deadline-oriented steps and enhanced user support mechanisms. Additionally, our results surface the need for an adaptive approach to questioning based on factors like busyness. These findings offer crucial design implications for the development of LLM-based tools for managing procrastination while cautioning the use of LLMs for therapeutic guidance.

12.
Diabetologia ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910151

RESUMO

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

13.
Environ Health Perspect ; 132(6): 67002, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38829734

RESUMO

BACKGROUND: While limited studies have evaluated the health impacts of thunderstorms and power outages (POs) separately, few have assessed their joint effects. We aimed to investigate the individual and joint effects of both thunderstorms and POs on respiratory diseases, to identify disparities by demographics, and to examine the modifications and mediations by meteorological factors and air pollution. METHODS: Distributed lag nonlinear models were used to examine exposures during three periods (i.e., days with both thunderstorms and POs, thunderstorms only, and POs only) in relation to emergency department visits for respiratory diseases (2005-2018) compared to controls (no thunderstorm/no PO) in New York State (NYS) while controlling for confounders. Interactions between thunderstorms and weather factors or air pollutants on health were assessed. The disparities by demographics and seasons and the mediative effects by particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) and relative humidity (RH) were also evaluated. RESULTS: Thunderstorms and POs were independently associated with total and six subtypes of respiratory diseases in NYS [highest risk ratio (RR) = 1.12; 95% confidence interval (CI): 1.08, 1.17], but the impact was stronger when they co-occurred (highest RR = 1.44; 95% CI: 1.22, 1.70), especially during grass weed, ragweed, and tree pollen seasons. The stronger thunderstorm/PO joint effects were observed on chronic obstructive pulmonary diseases, bronchitis, and asthma (lasted 0-10 d) and were higher among residents who lived in rural areas, were uninsured, were of Hispanic ethnicity, were 6-17 or over 65 years old, and during spring and summer. The number of comorbidities was significantly higher by 0.299-0.782/case. Extreme cold/heat, high RH, PM2.5, and ozone concentrations significantly modified the thunderstorm-health effect on both multiplicative and additive scales. Over 35% of the thunderstorm effects were mediated by PM2.5 and RH. CONCLUSION: Thunderstorms accompanied by POs showed the strongest respiratory effects. There were large disparities in thunderstorm-health associations by demographics. Meteorological factors and air pollution levels modified and mediated the thunderstorm-health effects. https://doi.org/10.1289/EHP13237.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Serviço Hospitalar de Emergência , Exposição Ambiental , Material Particulado , Doenças Respiratórias , Tempo (Meteorologia) , Humanos , New York/epidemiologia , Poluentes Atmosféricos/análise , Serviço Hospitalar de Emergência/estatística & dados numéricos , Material Particulado/análise , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/efeitos adversos , Doenças Respiratórias/epidemiologia , Masculino , Feminino , Exposição Ambiental/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Criança , Adulto Jovem , Estações do Ano
14.
Prehosp Emerg Care ; : 1-7, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38935488

RESUMO

OBJECTIVES: Medical Priority Dispatch System (MPDS) is a system used to assign medical 9-1-1 calls to one of 35 chief complaints that are further categorized in order of increasing priority, Alpha through Echo. In this descriptive study we demonstrate the methodology of matching MPDS codes to a county mortality registry. We also evaluated the ability of select MPDS codes (fall, respiratory, sick person, and abdominal pain) to predict mortality up to 30 d for all ages transported by Alameda County Emergency Medical Services (EMS). METHODS: Using Alameda County EMS data, we conducted a retrospective review of all EMS encounters that occurred from November 1, 2011, to November 1, 2016. To describe mortality in this population, we identified unique patients and linked them to the Alameda County Public Health Death Registry. We identified mortality at 48 h, 7 d, and 30 d after an EMS encounter. RESULTS: Approximately 99% of the EMS encounters were matched with unique patient identifiers, yielding a study sample of 202,431 (4% less than age 18, 53% between ages 18-65, and 43% over age 65). Patients with a respiratory chief complaint had the highest mortality percentage in each age group (0.23%, 2.7%, and 14.55% respectively). There was no correlation between the MPDS code and mortality for patients less than age 18. An increase in Alpha through Echo designation for respiratory complaints in patients 18-65 and older than 65 years corresponded with an increase in 30-day mortality. CONCLUSIONS: This study demonstrates an upward trend in mortality with increasing acuity of Alpha through Echo designations for adult patients with respiratory complaints. Mortality increased with age in this cohort. Most of the deaths occurred after 7 days.

15.
Proteomics ; : e2400078, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824665

RESUMO

The human gut microbiome plays a vital role in preserving individual health and is intricately involved in essential functions. Imbalances or dysbiosis within the microbiome can significantly impact human health and are associated with many diseases. Several metaproteomics platforms are currently available to study microbial proteins within complex microbial communities. In this study, we attempted to develop an integrated pipeline to provide deeper insights into both the taxonomic and functional aspects of the cultivated human gut microbiomes derived from clinical colon biopsies. We combined a rapid peptide search by MSFragger against the Unified Human Gastrointestinal Protein database and the taxonomic and functional analyses with Unipept Desktop and MetaLab-MAG. Across seven samples, we identified and matched nearly 36,000 unique peptides to approximately 300 species and 11 phyla. Unipept Desktop provided gene ontology, InterPro entries, and enzyme commission number annotations, facilitating the identification of relevant metabolic pathways. MetaLab-MAG contributed functional annotations through Clusters of Orthologous Genes and Non-supervised Orthologous Groups categories. These results unveiled functional similarities and differences among the samples. This integrated pipeline holds the potential to provide deeper insights into the taxonomy and functions of the human gut microbiome for interrogating the intricate connections between microbiome balance and diseases.

16.
Diabetes Care ; 47(8): 1276-1298, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38912694

RESUMO

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.


Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/diagnóstico , Humanos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Consenso , Ilhotas Pancreáticas/imunologia
17.
J Hepatol ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914313

RESUMO

BACKGROUND & AIMS: Metabolic-dysfunction associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements. METHODS: Following medical diagnosis of MASH, subjects were randomized to treatment (n=16) or control (n=8). Liver fat (MRS), 18-hour plasma biochemical measurements, and isotopically-labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO2peak) were also measured mid-intervention. Treatment subjects were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Control subjects continued physician-directed care. RESULTS: Treatment induced significant (P<0.05) reductions in body weight, fat mass, and liver injury, while VO2peak (P<0.05) and fatty acid (NEFA) suppression (P=0.06) were improved. Both groups exhibited reductions in total energy intake, HbA1c, hepatic insulin resistance, and liver fat (P<0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO2peak and resolution of liver disease, despite no group differences in peripheral insulin sensitivity. CONCLUSIONS: Exercise and energy-restriction elicited significant and clinically-meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH. CLINICAL TRIAL NUMBER: NCT03151798.

20.
Dermatol Ther (Heidelb) ; 14(5): 1211-1227, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38724841

RESUMO

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

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