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1.
Blood ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968152

ABSTRACT

Currently, the role of DNA methylation in the IgM-monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multi-omics prospective analysis was conducted integrating DNA methylation, RNA-seq and WES data in 34 subjects [23 WM, 6 IgM-MGUS, 5 normal controls]. Analysis was focused on defining differences between IgM-gammopathies (WM/IgM-MGUS) compared to controls, and specifically between WM and IgM-MGUS. Between groups, genome-wide DNA methylation analysis demonstrated a significant number of differentially methylated regions which were annotated according to genomic region. Next, integration of RNA-seq data was performed to identify potentially epigenetically deregulated pathways. We found that pathways involved in cell cycle, metabolism, cytokine/immune signaling, cytoskeleton, tumor microenvironment, and intracellular signaling were differentially activated and potentially epigenetically regulated. Importantly, there was a positive enrichment of CXCR4 signaling pathway along with several interleukin (IL-6, IL-8, IL15) signaling pathways in WM compared to IgM-MGUS. Further assessment of known tumor suppressor genes and oncogenes uncovered differential promoter methylation of several targets with concordant change in gene expression, including CCND1 and CD79B. Overall, this report defines how aberrant DNA methylation in IgM-gammopathies may play a critical role in the epigenetic control of oncogenesis and key cellular functions.

2.
Hosp Pediatr ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973365

ABSTRACT

BACKGROUND AND OBJECTIVES: Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis. METHODS: We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression. RESULTS: We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07). CONCLUSIONS: cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI.

3.
Pain ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981098

ABSTRACT

ABSTRACT: Using the Australiasian electronic Persistent Pain Outcomes Collaboration, a binational pain registry collecting standardized clinical data from paediatric ePPOC (PaedsePPOC) and adult pain services (AdultePPOC), we explored and characterized nationally representative chronic pain phenotypes and associations with clinical and sociodemographic factors, health care utilization, and medicine use of young people. Young people ≥15.0 and <25.0 years captured in PaedePPOC and AdultePPOC Australian data registry were included. Data from 68 adult and 12 paediatric pain services for a 5-year period January 2018 to December 2022 (first episode, including treatment information) were analysed. Unsupervised latent class analysis was applied to explore the existence of distinct pain phenotypes, with separate models for both services. A 3-phenotype model was selected from both paediatric and adult ePPOC data, with 693 and 3518 young people included, respectively (at least one valid indicator variable). Indicator variables for paediatric models were as follows: pain severity, functional disability (quasisurrogate "pain interference"), pain count, pain duration, pain-related worry (quasisurrogate "catastrophizing"), and emotional functioning; and, for adult models: pain severity, pain interference, pain catastrophizing, emotional functioning, and pain self-efficacy. From both services, 3 similar phenotypes emerged ("low," "moderate," "high"), characterized by an increasing symptom-severity gradient in multidimensional pain-related variables, showing meaningful differences across clinical and sociodemographic factors, health service utilization, and medicines use. Derived phenotypes point to the need for novel care models that differentially respond to the needs of distinct groups of young people, providing timely, targeted, age-appropriate care. To effectively scale such care, digital technologies can be leveraged to augment phenotype-informed clinical care.

4.
Open Forum Infect Dis ; 11(7): ofae341, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39006315

ABSTRACT

Background: Antibiotic use is a major risk factor for recurrent Clostridioides difficile infection (CDI) due to the associated disruption in gut microbiota. Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660), is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent CDI in adults following standard-of-care antibiotic treatment. To investigate the impact of non-CDI antibiotics on the durability of RBL, a subgroup analysis was conducted on PUNCH™ Open-Label study participants who received non-CDI antibiotics during the period between RBL administration and up to 2 years after. Methods: Participants in PUNCH™ Open-Label who received non-CDI antibiotics after RBL administration were included in this subgroup analysis. Treatment response was defined as the absence of CDI diarrhea needing retreatment at the last evaluable time point (8 weeks, 6 months, 1 year, or 2 years) after RBL administration. Results: Among participants from PUNCH™ Open-Label, 43 received non-CDI antibiotics after RBL administration but before CDI recurrence as evaluated over a 2-year period. Across all evaluable time points, 86% (37/43) of participants had a treatment response regardless of when non-CDI antibiotic exposure occurred. Treatment response was sustained for a median 470 days (IQR, 212-648) from the first day of non-CDI antibiotic use. Most participants (5/6) with CDI recurrences received a high-risk antibiotic. Conclusions: RBL remained efficacious in participants with a history of recurrent CDI after subsequent non-CDI antibiotic exposure. Clinical Trials Registration: NCT02589847 (https://clinicaltrials.gov/study/NCT02589847).

5.
Trials ; 25(1): 478, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010232

ABSTRACT

BACKGROUND: Postpartum depression (PPD) affects 30-50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD. METHODS: The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum. DISCUSSION: The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children. TRIAL REGISTRATION: ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024.


Subject(s)
Depression, Postpartum , Randomized Controlled Trials as Topic , Humans , Female , Depression, Postpartum/prevention & control , Depression, Postpartum/psychology , Depression, Postpartum/diagnosis , Pregnancy , Affect , Adult , Risk Factors , Cognitive Behavioral Therapy/methods , Prenatal Care/methods , Cognition , Treatment Outcome , Cognitive Training
6.
Am J Trop Med Hyg ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981489

ABSTRACT

A comprehensive understanding of the spatial distribution and correlates of infection are key for the planning of disease control programs and assessing the feasibility of elimination and/or eradication. In this work, we used species distribution modeling to predict the environmental suitability of the Guinea worm (Dracunculus medinensis) and identify important climatic and sociodemographic risk factors. Using Guinea worm surveillance data collected by the Chad Guinea Worm Eradication Program (CGWEP) from 2010 to 2022 in combination with remotely sensed climate and sociodemographic correlates of infection within an ensemble machine learning framework, we mapped the environmental suitability of Guinea worm infection in Chad. The same analytical framework was also used to ascertain the contribution and influence of the identified climatic risk factors. Spatial distribution maps showed predominant clustering around the southern regions and along the Chari River. We also identified areas predicted to be environmentally suitable for infection. Of note are districts near the western border with Cameroon and southeastern border with Central African Republic. Key environmental correlates of infection as identified by the model were proximity to permanent rivers and inland lakes, farmlands, land surface temperature, and precipitation. This work provides a comprehensive model of the spatial distribution of Guinea worm infections in Chad 2010-2022 and sheds light on potential environmental correlates of infection. As the CGWEP moves toward elimination, the methods and results in this study will inform surveillance activities and help optimize the allocation of intervention resources.

7.
Euro Surveill ; 29(25)2024 Jun.
Article in English | MEDLINE | ID: mdl-38904110

ABSTRACT

BackgroundNon-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.AimTo describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.MethodsParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021-November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.ResultsWe received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23-1.54).ConclusionsOur study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccination , Humans , Prospective Studies , Female , Male , COVID-19/prevention & control , COVID-19/epidemiology , SARS-CoV-2/immunology , Middle Aged , Netherlands/epidemiology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Adult , Antibodies, Viral/blood , Vaccination/adverse effects , Vaccination/statistics & numerical data , Aged , Spike Glycoprotein, Coronavirus/immunology , Young Adult , Surveys and Questionnaires
9.
Blood Cancer J ; 14(1): 100, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902256

ABSTRACT

Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis was used to identify a signature associated with high risk of early clinical failure independent of IPI and COO. Further analysis revealed the signature was associated with metabolic reprogramming and identified cases with a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. This novel and integrative approach is the first to identify a signature at diagnosis, in a real-world cohort of DLBCL, that identifies patients at high risk for early clinical failure and may have significant implications for design of therapeutic options.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/diagnosis , Male , Female , Gene Expression Profiling , Middle Aged , Transcriptome , Mutation , Gene Expression Regulation, Neoplastic , Transcription Factors/genetics , Biomarkers, Tumor/genetics , Aged , Prognosis , Tumor Microenvironment , Exome Sequencing , Adult , DNA-Binding Proteins/genetics , Treatment Failure
10.
bioRxiv ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38798577

ABSTRACT

The spectinamides are novel, narrow-spectrum semisynthetic analogs of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead MBX-4888A (Lee-1810), exhibit promising therapeutic profiles in mice, as single drugs and as partner agents with other anti-tuberculosis antibiotics including rifampin and/or pyrazinamide. To demonstrate that this translates to more effective cure, we first confirmed the role of rifampin, with or without pyrazinamide, as essential to achieve effective bactericidal responses and sterilizing cure in the current standard of care regimen in chronically infected C3HeB/FeJ mice compared to BALB/c mice. Thus, demonstrating added value in testing clinically relevant regimens in murine models of increasing pathologic complexity. Next we show that MBX-4888A, given by injection with the front-line standard of care regimen, is treatment shortening in multiple murine tuberculosis infection models. The positive treatment responses to MBX-4888A combination therapy in multiple mouse models including mice exhibiting advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in caseum, along with favorable effects with rifampin and pyrazinamide under conditions achieved in necrotic lesions. This study also provides an additional data point regarding the safety and tolerability of spectinamide MBX-4888A in long-term murine efficacy studies.

11.
Vet Rec ; 194(11): e4153, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38783549

ABSTRACT

BACKGROUND: Dogs are exposed to increasing environmental risk for developing heat-related illness (HRI), with 2022 recorded as the hottest year to date in the UK and most of Europe. METHODS: This study used VetCompass data to report the incidence risk, event fatality rate and canine risk factors for HRI in dogs presenting to Vets Now emergency care practices in the UK during 2022. RESULTS: From the clinical records of 167,751 dogs under care at Vets Now emergency clinics in 2022, 384 HRI events were identified. The 2022 incidence risk of HRI within the Vets Now caseload was 0.23% (95% confidence interval [CI]: 0.21%‒0.25%), with an event fatality rate of 26.56% (95% CI: 21.66%-32.25%). Multivariable analysis identified breed, age and sex/neuter status as risk factors for HRI. Brachycephalic dogs had 4.21 times the odds of HRI compared to mesocephalic dogs (95% CI: 3.22‒5.49, p < 0.001). LIMITATIONS: The clinical data used in this study were not primarily recorded for research and had some substantial levels of missing data (especially patient bodyweight). CONCLUSION: In order to protect canine welfare, improved long-term mitigation strategies are urgently needed to minimise HRI risk and associated fatality in UK dogs.


Subject(s)
Dog Diseases , Heat Stress Disorders , Animals , Dogs , Dog Diseases/epidemiology , United Kingdom/epidemiology , Male , Female , Risk Factors , Heat Stress Disorders/veterinary , Heat Stress Disorders/epidemiology , Incidence , Emergency Medical Services/statistics & numerical data
12.
Br J Dev Psychol ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700317

ABSTRACT

Gender is one of the most salient social identities, particularly during early adolescence. However, factors related to adolescents' gender attitudes remain underexamined. We examined links between adolescents' gender discrimination, felt-gender similarity, and intergroup gender attitudes. Participants were 270 adolescents in the United States (Mage = 12.95 years, SD = 1.33; 47.4% adolescent girls; 63.7% White, 12.2% Latinx, 10.7% Black, 4.1% Asian, 5.6% multiracial, and 3% indigenous). Path analyses showed that gender discrimination negatively predicted adolescents' attitudes towards own- and other-gender peers. Felt own-gender similarity positively predicted own-gender attitudes as expected, but other-gender similarity did not predict other-gender attitudes. Further, own- and other-gender similarity did not interact to predict adolescents' gender attitudes. However, adolescents' attitudes towards other-gender peers were more negatively impacted by gender discrimination for those who felt highly similar to own-gender peers than for those with average or low own-gender similarity. Findings inform potential strategies to improve adolescents' gender attitudes.

13.
J Youth Adolesc ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789876

ABSTRACT

Online appearance preoccupation may put adolescents at risk of developing mental health challenges, perhaps especially during early-to-middle adolescence. A random intercept cross-lagged panel model assessed within-person associations between appearance-related social media consciousness and depressive symptoms over three time-points with three months between waves. The sample (n = 1594) included U.S. adolescents aged 11-15 (Mage = 13; 47% girls, 46% boys, 7% another gender; 37% Latine, 33% White, 18% Black, 7% Asian). Within-person increases in appearance-related social media consciousness were associated with subsequent increases in depressive symptoms, but not vice versa. There was no evidence of gender differences and results were robust to controlling for both time on social media and offline self-objectification. Thus, online appearance concerns precede mental health challenges during early and middle adolescence.

14.
MMWR Morb Mortal Wkly Rep ; 73(20): 460-466, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38781111

ABSTRACT

Two doses of JYNNEOS vaccine are effective in preventing many mpox cases and can reduce the severity of symptoms in infected persons. However, infections among fully vaccinated persons can occur. During May 2022-May 2024, a total of 271 mpox cases among fully vaccinated persons were reported to CDC from 27 U.S. jurisdictions. These reported infections are estimated to have occurred in <1% of fully vaccinated persons. Compared with cases among unvaccinated persons, infections among fully vaccinated persons were more likely to occur among non-Hispanic White men aged 30-39 years, were associated with increased numbers of sexual partners, and resulted in less severe disease (p<0.001). Among infections in fully vaccinated persons with complete data, infections after vaccination were reported more commonly after receipt of heterologous (subcutaneous and intradermal) (46%) or homologous subcutaneous (32%) JYNNEOS vaccination than after homologous intradermal (22%) vaccination. Disparate time intervals from vaccination to infection among fully vaccinated persons suggest that immunity is not waning. The median interval between the second vaccine dose and illness onset was longer for cases among persons who had received 2 intradermal doses (median = 363 days; IQR = 221-444 days) compared with cases in persons who had received 2 subcutaneous doses (median = 263 days; IQR = 47-334 days) (p<0.001). The implications of this finding are not known; however, these data should increase confidence in the effectiveness of vaccine doses that were administered intradermally, the preferred method of administration during the peak of the outbreak when vaccine supply was limited. Persons recommended to receive the JYNNEOS vaccine should receive 2 doses, irrespective of the route of administration, and at this time, additional doses are not recommended for the affected population.


Subject(s)
Mpox (monkeypox) , Humans , Male , United States/epidemiology , Adult , Young Adult , Female , Middle Aged , Mpox (monkeypox)/epidemiology , Mpox (monkeypox)/prevention & control , Adolescent , 2019-nCoV Vaccine mRNA-1273/administration & dosage , Immunization, Secondary
15.
Vet J ; 305: 106123, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642699

ABSTRACT

Mobility is an essential aspect of a dog's daily life. It is defined as the ability to move freely and easily and deviations from an animals' normal mobility capabilities are often an indicator of disease, injury or pain. When a dog's mobility is compromised, often functionality (ability to perform activities of daily living [ADL]), is also impeded, which can diminish an animal's quality of life. Given this, it is necessary to understand the extent to which conditions impact a dog's physiological ability to move around their environment to carry out ADL, a concept termed functional mobility. In contrast to human medicine, validated measures of canine functional mobility are currently limited. The aim of this review is to summarise the extent to which canine mobility and functionality are associated with various diseases and how mobility and functional mobility are currently assessed within veterinary medicine. Future work should focus on developing a standardised method of assessing functional mobility in dogs, which can contextualise how a wide range of conditions impact a dog's daily life. However, for a true functional mobility assessment to be developed, a greater understanding of what activities dogs do on a daily basis and movements underpinning these activities must first be established.


Subject(s)
Activities of Daily Living , Dog Diseases , Dogs/physiology , Animals , Dog Diseases/physiopathology , Movement , Quality of Life
16.
Clin Chem Lab Med ; 62(9): 1835-1844, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-38593236

ABSTRACT

OBJECTIVES: Integration of add-on testing in high-scale automated clinical laboratories constitute a valuable instrument not only for the clinicians and the general patient care, but also for the laboratory itself. Knowledge on sample quality and analytical stability upon storage is necessary to be able to offer add-on testing. The objectives of this study were to examine the analytical stability of 63 biochemical analytes in plasma and urine samples stored at 16 °C. METHODS: Samples were collected by professional laboratory technicians, analyzed at automated analyzers and stored in their primary, capped tube without separator for 10, 12, 16, 20 or 24 h at 16 °C. Stability was assessed by inspecting mean concentration of samples at baseline and examining if (A) mean concentration over time violated limits of bias, or if (B) individual sample concentrations violated limits of total error. RESULTS: The majority of the 63 analytes were stable for up to 24 h of storage. Few of the analytes were only suitable for add-on testing for 4, 6, 10, 12, 16 or 20 h of storage. One analyte, P-lactate dehydrogenase, was not found suitable for add-on testing when stored at 16 °C. CONCLUSIONS: Due to the increasing number of intelligent solutions for high-scale clinical laboratories, add-on testing has come to stay. Loss of stability could not be demonstrated for the majority of analytes after 10, 12, 16, 20 or 24 h of storage. This feature of analytical stability suggests that add-on testing is an acceptable tool for these analytes.


Subject(s)
Specimen Handling , Humans , Specimen Handling/standards , Temperature , Time Factors
17.
ACS Infect Dis ; 10(5): 1679-1695, 2024 05 10.
Article in English | MEDLINE | ID: mdl-38581700

ABSTRACT

Linezolid is a drug with proven human antitubercular activity whose use is limited to highly drug-resistant patients because of its toxicity. This toxicity is related to its mechanism of action─linezolid inhibits protein synthesis in both bacteria and eukaryotic mitochondria. A highly selective and potent series of oxazolidinones, bearing a 5-aminomethyl moiety (in place of the typical 5-acetamidomethyl moiety of linezolid), was identified. Linezolid-resistant mutants were cross-resistant to these molecules but not vice versa. Resistance to the 5-aminomethyl molecules mapped to an N-acetyl transferase (Rv0133) and these mutants remained fully linezolid susceptible. Purified Rv0133 was shown to catalyze the transformation of the 5-aminomethyl oxazolidinones to their corresponding N-acetylated metabolites, and this transformation was also observed in live cells of Mycobacterium tuberculosis. Mammalian mitochondria, which lack an appropriate N-acetyltransferase to activate these prodrugs, were not susceptible to inhibition with the 5-aminomethyl analogues. Several compounds that were more potent than linezolid were taken into C3HeB/FeJ mice and were shown to be highly efficacious, and one of these (9) was additionally taken into marmosets and found to be highly active. Penetration of these 5-aminomethyl oxazolidinone prodrugs into caseum was excellent. Unfortunately, these compounds were rapidly converted into the corresponding 5-alcohols by mammalian metabolism which retained antimycobacterial activity but resulted in substantial mitotoxicity.


Subject(s)
Antitubercular Agents , Mycobacterium tuberculosis , Oxazolidinones , Prodrugs , Prodrugs/pharmacology , Prodrugs/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Mycobacterium tuberculosis/drug effects , Oxazolidinones/pharmacology , Oxazolidinones/chemistry , Animals , Microbial Sensitivity Tests , Mice , Humans , Linezolid/pharmacology , Linezolid/chemistry , Drug Resistance, Bacterial , Mitochondria/drug effects , Mitochondria/metabolism
18.
Chem Sci ; 15(16): 5802-5813, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38665509

ABSTRACT

Poly(vinyl chloride) (PVC) is one of the highest production volume polymers due to its many applications, and it is one of the least recycled due to its chemical structure and frequent formulation with additives. Developing efficient PVC recycling techniques would enable PVC waste to be reused or repurposed in other processes. Within this context, the literature on PVC modification offers considerable insight into versatile reaction pathways, potentially inspiring new approaches for repurposing PVC waste into value-added products. This perspective provides an overview of PVC functionalization through a lens of chemical recycling, discussing various PVC reactivity trends and their applications with a critical assessment and future outlook of their recycling implications.

19.
J Pediatr Orthop B ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38595083

ABSTRACT

In the surgical treatment of tarsal coalitions, it is unclear whether interposition material should be used to prevent recurrence. The aim of this review was to systematically examine the results of different interposition tissues after surgical resection of tarsal coalitions in children. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent investigators systematically searched electronic databases (PubMed, Embase, Cochrane) and included original articles reporting outcomes of tarsal coalition resection. The quality of included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Out of 294 articles, 21 studies examining 436 patients (581 feet), were included. The mean age was 12.2 years (range 7-18). There were 153 talocalcaneal, 425 calcaneonavicular, 2 naviculocuboidal, and 1 naviculocuneiform coalitions. The mean follow-up time was 58 months (range 12-276). In 96 feet, solely resection was performed. Resection and interposition were performed with muscle/tendon (n = 178), fat graft (n = 176), other material (n = 36), or a combination of interposition techniques (n = 95). Eighteen studies reported on recurrence, which was found in 45 of 485 feet (9%). The highest recurrence (17%) was described after muscle/tendon interposition for calcaneonavicular coalitions. However, a statistical comparison could not be performed. The included studies were diverse and the scientific quality was generally low (MINORS mean 7, range 3-20). Coalition resection with various interposition techniques results in low recurrence rates. It is unclear which interposition material shows the best results.

20.
Arch Sex Behav ; 53(5): 1621-1632, 2024 May.
Article in English | MEDLINE | ID: mdl-38561481

ABSTRACT

Hookup culture has transformed the sexual behavior of emerging adults. Feminism, a movement that has advocated for liberating women from sexual repression, may be associated with hookup endorsement attitudes. This study explores the associations among multiple dimensions of feminism, gender, and hookup culture endorsement. Participants included 318 emerging adults (46% women; Mage = 22.2 years; 51% White, 27% Asian, 5% Hispanic/Latinx, 9% Black, 1% Middle Eastern, 1% American Indian, 6% Multiracial) from five Anglophone countries (62% U.S., 23% United Kingdom, 9% Canada, 5% Australia, 1% New Zealand), who completed the Feminist Beliefs and Behavior Scale and Endorsement of Hookup Culture Index via an anonymous, online survey. Participants were categorized according to their feminist identity label (feminist, non-feminist) and feminist belief system (hold feminist beliefs, hold non-feminist beliefs). A series of ANCOVAs was conducted, revealing that women who identified as feminist and/or held feminist beliefs reported significantly higher endorsement of hookup culture compared to non-feminist women with non-feminist beliefs. Neither dimension of feminism predicted hookup culture endorsement in men. When comparing feminist-identifying women and men, the gender disparity in hookup culture endorsement was eliminated. Together, these findings highlight how social movements, such as feminism, may be associated with young women's attitudes towards hookups, and may ultimately shape their sexual experiences.


Subject(s)
Feminism , Sexual Behavior , Humans , Female , Male , Young Adult , Sexual Behavior/psychology , Adult , Surveys and Questionnaires , Canada , Adolescent , Australia , United States , New Zealand
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