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Chewing kinematics are well-documented in several mammal species with fused mandibular symphyses, but relatively understudied in mammals with an unfused symphysis, despite the fact that more than half of extant Mammalia have an unfused mandibular symphysis. The Wistar brown rat (Rattus norvegicus) is widely used in human health research, including studies of mastication or neurological studies where mastication is the output behavior. These animals are known to have unfused mandibular symphyses and proal jaw (rostrocaudal) motion during occlusion, but the lack of high resolution, 3-dimensional analysis of rat chewing leaves the functional significance of symphyseal mobility unknown. We used biplanar fluoroscopy and the X-ray reconstruction of moving morphology workflow to quantify chewing kinematics in 3 brown rats, quantifying overall jaw kinematics, including motions about the temporomandibular joint and unfused mandibular symphysis. During occlusion, the teeth and the mandibular condyle translate almost exclusively anteriorly (proal) during occlusion, with little motion in any other degrees of freedom. At the symphysis, we observed minimal flexion throughout the chew cycle. Overall, there are fundamental differences in jaw kinematics between rats and other mammals and therefore rats are not an appropriate proxy for ancestral mammal jaw mechanics. Additionally, differences between humans and rat chewing kinematics must be considered when using rats as a clinical model for pathological feeding research.
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OBJECTIVE: Maintaining a skilled public health workforce is essential but challenging given high turnover and that few staff hold a public health degree. Situating workforce development within existing structures leverages the strengths of different organizations and can build relationships to address public health challenges and health equity. We implemented and evaluated an innovative, sustainable model to deliver an established evidence-based public health (EBPH) training collaboratively among Prevention Research Centers (PRC), local and state health departments, and Public Health Training Centers (PHTC). DESIGN: Quantitative data: quasi-experimental, 1-group pre-post. Qualitative data: cross-sectional. Data were collected between December 2021 and August 2022. SETTING: Four US sites, each a partnership between a PRC, local or state health department, and a PHTC. PARTICIPANTS: Governmental public health staff and representatives from other organizations that implement public health programs in practice settings. MAIN OUTCOME MEASURES: Course participants completed a pre- and postcourse survey self-rating 14 skills on a 5-point Likert scale. Differences were analyzed using mixed effects linear models. In-depth interviews (n = 15) were conducted with course faculty and partners to understand: (1) resources contributed, (2) barriers and facilitators, (3) benefits and challenges, and (4) resources needed to sustain this model. Interviews were transcribed verbatim, and a thematic analysis identified themes. RESULTS: Statistically significant increases in all skills were observed from pre- to postcourse (n = 241 at post, 90% response). The skills with the largest increases were understanding economic evaluation enough to inform decision-making (mean change = 1.22, standard error [SE] = 0.05) and developing an action plan (mean change = 1.07, SE = 0.07). Facilitators to delivering the course included having a shared goal of workforce development, existing course curricula, and dedicated funding for delivering the course. CONCLUSIONS: Collaborative delivery of the EBPH training can ameliorate the effects of high staff turnover, strengthen academic-practice relationships, and promote population-wide health and health equity.
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Online apparel retail imagery is a prominent threat to women's body image, particularly segments such as activewear which emphasize the value of women's bodies. In a within-subjects experiment, we exposed women (N = 128) to imagery randomly selected from activewear, casualwear and homewares websites and measured their gaze behavior, physiological arousal, as well as subjective emotional states and body image ratings. Exposure to activewear retail imagery elicited significantly lower body image ratings, a higher negative emotional state, and a lower positive emotional state compared to the other website imagery conditions. Physiological arousal was significantly higher for both apparel imagery conditions compared to the homewares imagery condition. Body biased gaze behavior was significantly higher for the activewear imagery condition compared to the casualwear imagery condition. Notably, body shame moderated the self-reported but not the physiological experimental effects, such that women with higher body shame experienced stronger adverse changes in their body image and emotional state ratings following activewear exposure. Correlations revealed that self-reported experimental responses to activewear imagery were strongly associated with self-objectification, appearance comparison, disordered eating and body image coping attitudes. Thus, exposure to popular apparel may play a role in maintaining maladaptive body image attitudes and behaviors in women.
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Deliberate and effortful attempts to gaze at the bodies of women is emerging as a valuable marker of sexual objectification in men. Some preliminary evidence suggests that pervasive body gaze behavior may also accompany insidious attitudes which can facilitate sexual assault. The present study aimed to further explore this potential by examining pervasive body gaze associations with explicit, implicit, and physiological sexual assault propensity measures. We presented 110 heterosexual male participants with images of fully and partially dressed women with and without injuries while measuring their skin conductance responses. We also captured implicit and explicit sexual assault measures in addition to self-reported pervasive body gaze behavior. Pervasive body gaze behavior was significantly correlated with rape myth acceptance attitudes, prior perpetration of sexual assault, a stronger implicit association between erotica and aggression, and lower physiological reactivity during exposure to partially dressed injured women. These findings suggest that body gaze towards women could be a behavioral marker for inclinations to victim blame, preferences for rough sexual conduct, and a physiological desensitization towards female victims. This study further validates a five item self-reported body gaze measure as a valuable tool for detecting deviant sexual objectification attitudes and affective states. As such, measurement and observation of body gaze behavior could be useful for developing risk assessments, estimating intervention efficacy, and enhancing public awareness.
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Peptide-enabled ribonucleoprotein delivery for CRISPR engineering (PERC) is a new approach for ex vivo genome editing of primary human cells. PERC uses a single amphiphilic peptide reagent to mediate intracellular delivery of the same pre-formed CRISPR ribonucleoprotein enzymes that are broadly used in research and therapeutics, resulting in high-efficiency editing of stimulated immune cells and cultured hematopoietic stem and progenitor cells (HSPCs). PERC facilitates nuclease-mediated gene knockout, precise transgene knock-in, and base editing. PERC involves mixing the CRISPR ribonucleoprotein enzyme with peptide and then incubating the formulation with cultured cells. For efficient transgene knock-in, adeno-associated virus (AAV) bearing homology-directed repair template DNA may be included. In contrast to electroporation, PERC is appealing as it requires no dedicated hardware and has less impact on cell phenotype and viability. Due to the gentle nature of PERC, delivery can be performed multiple times without substantial impact to cell health or phenotype. Here we report methods for improved PERC-mediated editing of T cells as well as novel methods for PERC-mediated editing of HSPCs, including knockout and precise knock-in. Editing efficiencies can surpass 90% using either Cas9 or Cas12a in primary T cells or HSPCs. Because PERC calls for only three readily available reagents - protein, RNA, and peptide - and does not require dedicated hardware for any step, PERC demands no special expertise and is exceptionally straightforward to adopt. The inherent compatibility of PERC with established cell engineering pipelines makes this approach appealing for rapid deployment in research and clinical settings.
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In their article on "Navigating the Field of Implementation Science Towards Maturity: Challenges and Opportunities," Chambers and Emmons describe the rapid growth of implementation science along with remaining challenges. A significant gap remains in training and capacity building. Formats for capacity building include university degree programs, summer training institutes, workshops, and conferences. In this letter, we describe and amplify on five key areas, including the need to (1) identify advanced competencies, (2) increase the volume and reach of trainings, (3) sustain trainings, (4) build equity focused trainings, and (5) develop global capacity. We hope that the areas we highlight will aid in addressing several key challenges to prioritize in future efforts to build greater capacity in implementation science.
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Fortalecimento Institucional , Ciência da Implementação , Fortalecimento Institucional/organização & administração , HumanosRESUMO
Knowledge of locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our Validated Systematic Integration (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state regulatory potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbor distinctive transcription factor binding motifs that are similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we show that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment.
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BACKGROUND AND OBJECTIVES: Tolebrutinib is a covalent BTK inhibitor designed and selected for potency and CNS exposure to optimize impact on BTK-dependent signaling in CNS-resident cells. We applied a translational approach to evaluate three BTK inhibitors in Phase 3 clinical development in MS with respect to their relative potency to block BTK-dependent signaling and exposure in the CNS METHODS: We used in vitro kinase and cellular activation assays, alongside pharmacokinetic sampling of cerebrospinal fluid (CSF) in the non-human primate cynomolgus to estimate the ability of these candidates (evobrutinib, fenebrutinib, and tolebrutinib) to block BTK-dependent signaling inside the CNS. RESULTS: In vitro kinase assays demonstrated that tolebrutinib reacted with BTK 65-times faster than evobrutinib, while fenebrutinib, a classical reversible antagonist with a Ki value of 4.7 nM and slow off-rate (1.54 x 10-5 s-1), also had an association rate 1760-fold slower (0.00245 µM-1 * s-1). Estimates of cellular potency were largely consistent with the in vitro kinase assays, with an estimated IC50 of 0.7 nM for tolebrutinib against 33.5 nM for evobrutinib and 2.9 nM for fenebrutinib. We then observed that evobrutinib, fenebrutinib, and tolebrutinib achieved similar levels of exposure in non-human primate CSF after oral doses of 10 mg/kg. However, tolebrutinib CSF exposure (4.8 ng/mL) (kp,uu CSF=0.40) exceeded the IC90 (the estimated concentration inhibiting 90% of kinase activity) value, while evobrutinib (3.2 ng/mL) (kp,uu CSF=0.13) and fenebrutinib (12.9 ng/mL) (kp,uu CSF=0.15) failed to reach the estimated IC90 values. CONCLUSIONS: Tolebrutinib was the only candidate of the three that attained relevant CSF exposure in non-human primates.
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Tirosina Quinase da Agamaglobulinemia , Macaca fascicularis , Esclerose Múltipla , Inibidores de Proteínas Quinases , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia/metabolismo , Animais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/farmacocinética , Esclerose Múltipla/tratamento farmacológico , Humanos , Sistema Nervoso Central/efeitos dos fármacos , Pirazinas/farmacologia , Pirazinas/farmacocinética , Piperazinas , Piperidinas , Piridonas , PirimidinasRESUMO
BACKGROUND: The prevalence of super obesity (body mass index [BMI] > 50) continues to rise. However, the adoption of bariatric surgery in this population remains very low. There are limited studies evaluating the utility of endoscopic sleeve gastroplasty (ESG) in super obesity. OBJECTIVES: The purpose of this study is to evaluate the short-term safety profile of ESG in patients with super obesity using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. SETTING: United States. METHODS: We retrospectively analyzed patients who underwent ESG and sleeve gastrectomy (SG) from 2016 to 2021. Patients with BMI >50 who underwent ESG were compared to ESG patients with BMI <50 and also SG patients with BMI >50. Primary outcomes included the incidence of severe adverse events (AEs), hospital readmission, reintervention, and reoperation within 30 days of the primary procedure. Secondary outcomes included procedure time, hospital length of stay, and total body weight loss at 30 days. RESULTS: There were no significant differences in AE, reoperations, hospital readmissions, or reinterventions for patients with super obesity undergoing ESG, compared to patients with BMI below 50. Mean total body weight loss was greater in patients with super obesity. There were no significant differences in AEs for patients with super obesity who underwent ESG versus SG, although ESG patients had more hospital readmissions, reinterventions, and reoperations. CONCLUSIONS: ESG may be performed safely, with comparable safety to SG, in patients with BMI as high as 70. However, further studies are needed to validate the feasibility and long-term efficacy prior to clinical implementation.
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BACKGROUND: In Australia, sports broadcasting is afforded special alcohol advertising rights during daytime hours, which raises public health concerns, including short-term increases in alcohol consumption among the broad viewership of national sporting codes. METHODS: We conducted a content analysis across a sample of nationally televised finals matches (N = 16) from the Australian Football League (AFL) and the National Rugby League (NRL) to determine the prevalence of alcohol advertising video clips during these broadcasts. We also conducted an online experiment exposing participants (N = 345) to a randomly selected alcohol advertisement and measured the immediate effects on self-reported alcohol craving and drinking intentions. RESULTS: The prevalence of alcohol advertising video clips during AFL broadcasts was 3.9% and 1.8% for NRL. While, overall, alcohol advertisement video clip exposure did not impact craving or drinking intentions, a modest increase in craving was found for a subsample of risky drinking participants (N = 107) who also reported a preference for the specific alcoholic beverage being advertised. CONCLUSIONS: Video alcohol advertisements occurred less than 1 in 20 advertisements on average and exposure to alcohol advertising elicited a low, yet measurable, short-term increase in alcohol inclinations, among vulnerable adult drinkers when a desirable alcoholic beverage advertisement is viewed. SO WHAT?: Given that alcohol advertisements are most likely to increase consumption among risky drinkers, health messaging during sports broadcasts needs to specifically target these individuals.
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By providing spaces for recreation, physical activity, social gatherings, and time in nature, urban parks offer physical, mental, and social benefits to users. However, many urban residents face barriers to park use. The COVID-19 pandemic introduced new potential barriers to urban park access and use, including changes to daily life and employment, closure of park amenities and restrictions to public movement, and risk from the coronavirus itself. The mixed-methods PARCS study measured use and perceptions of a large urban park in St. Louis, Missouri before, during, and after local COVID-19 contingency measures and restrictions. We examine data from 1,157 direct observation assessments of park usership, an online survey of park users (n=561), interviews with key stakeholders (n=27), four focus groups (n=30), and a community-based participatory research sub-study (n=66) to comprehensively characterize the effects of the COVID-19 pandemic on park use. Park users who felt unsafe from the coronavirus experienced 2.65 higher odds of reducing park use. However, estimated park visits during COVID-19 contingency measures (n=5,023,759) were twice as high as post-contingency (n=2,277,496). Participants reported using the park for physical activity, recreation, time in nature, and socializing during the contingency period. Black, Hispanic/Latino, and young people were less likely to visit the park than others, suggesting an additional, disproportionate impact of the pandemic on minoritized and socioeconomically disadvantaged communities. This study highlights the role of public spaces like parks as resources for health and sites where urban health inequities can be alleviated in times of public crisis.
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The COVID-19 pandemic and other ongoing public health challenges have highlighted deficiencies in the US public health system. The United States is in a unique moment that calls for a transformation that builds on Public Health 3.0 and its focus on social determinants of health and partnerships with diverse sectors while also acknowledging how the pandemic altered the landscape for public health. Based on relevant literature, our experience, and interviews with public health leaders, we describe seven areas of focus within three broad categories to support transformational change. Contextual areas of focus include increasing accountability and addressing politicization and polarization. Topical areas of focus highlight prioritizing climate change and sharpening the focus on equity. Technical areas of focus include advancing data sciences, building the workforce, and enhancing communication capacity. A transformed public health system will depend highly on leadership, funding incentives, and both bottom-up and top-down approaches. A broad effort is needed by public health agencies, governments, and academia to accelerate the transition to a next phase for public health.
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COVID-19 , Saúde Pública , Humanos , COVID-19/epidemiologia , Estados Unidos , Determinantes Sociais da Saúde , Pandemias , Liderança , SARS-CoV-2 , PolíticaRESUMO
Backgrounds/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013-2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered "justified" if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined ("high-risk stigmata" and "worrisome features") 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions: Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.
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Increased proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs) is recognised as a universal hallmark of pulmonary arterial hypertension (PAH), in part related to the association with reduced pyruvate dehydrogenase (PDH) activity, resulting in decreased oxidative phosphorylation of glucose and increased aerobic glycolysis (Warburg effect). Perhexiline is a well-recognised carnitine palmitoyltransferase-1 (CPT1) inhibitor used in cardiac diseases, which reciprocally increases PDH activity, but is associated with variable pharmacokinetics related to polymorphic variation of the cytochrome P450-2D6 (CYP2D6) enzyme, resulting in the risk of neuro and hepatotoxicity in 'slow metabolisers' unless blood levels are monitored and dose adjusted. We have previously reported that a novel perhexiline fluorinated derivative (FPER-1) has the same therapeutic profile as perhexiline but is not metabolised by CYP2D6, resulting in more predictable pharmacokinetics than the parent drug. We sought to investigate the effects of perhexiline and FPER-1 on PDH flux in PASMCs from patients with PAH. We first confirmed that PAH PASMCs exhibited increased cell proliferation, enhanced phosphorylation of AKTSer473, ERK 1/2Thr202/Tyr204 and PDH-E1αSer293, indicating a Warburg effect when compared to healthy PASMCs. Pre-treatment with perhexiline or FPER-1 significantly attenuated PAH PASMC proliferation in a concentration-dependent manner and suppressed the activation of the AKTSer473 but had no effect on the ERK pathway. Perhexiline and FPER-1 markedly activated PDH (seen as dephosphorylation of PDH-E1αSer293), reduced glycolysis, and upregulated mitochondrial respiration in these PAH PASMCs as detected by Seahorse analysis. However, both perhexiline and FPER-1 did not induce apoptosis as measured by caspase 3/7 activity. We show for the first time that both perhexiline and FPER-1 may represent therapeutic agents for reducing cell proliferation in human PAH PASMCs, by reversing Warburg physiology.
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Active-duty service members (ADSM) and military Veterans represent a population with increased occupational risk for nerve injuries sustained both during training operations and wartime. Mechanisms of war-related nerve injuries have evolved over time, from the musket ball-related traumas described by S.W. Mitchell to complex blast injuries and toxic exposures sustained during Middle East conflicts in the 21st century. Commonly encountered nerve injury etiologies in this population currently include compression, direct trauma, nutritional deficits, traumatic limb amputation, toxic chemical exposures, or blast-related injuries. Expeditious identification and comprehensive, interdisciplinary treatment of combat-associated neuropathies, as well as prevention of these injuries whenever possible is critical to reduce chronic morbidity and disability for service members and to maintain a well-prepared military. However, diagnosis of a combat-associated nerve injury may be particularly challenging due to comorbid battlefield injuries or delayed presentation of neuropathy from military toxic exposures. Advances in imaging for nerve injury, including MRI and ultrasound, provide useful tools to compliment EMG in establishing a diagnosis of combat-associated nerve injury, particularly in the setting of anatomic disruption or edema. Surgical techniques can improve pain control or restoration of function. In all cases, comprehensive interdisciplinary rehabilitation provides the best framework for optimization of recovery. Further work is needed to prevent combat-associated nerve injuries and promote nerve recovery following injury.
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Background: The use of Designing for Dissemination and Sustainability (D4DS) principles and methods can support the development of research products (interventions, tools, findings) to match well with the needs and context of the intended audience and setting. D4DS principles and methods are not well-known or used during clinical and public health research; research teams would benefit from applying D4DS. This paper presents the development of a new digital platform for teams to learn and apply a D4DS process to their work. Methods: A user-centered design (UCD) approach engaged users (n=14) and an expert panel (n=6) in an iterative design process from discovery to prototyping and testing. We led five design sessions using Zoom and Figma software over a 5-month period. Users (71% academics; 29% practitioners) participated in at least 2 sessions. Following design sessions, feedback from users were summarized and discussed to generate design decisions. A prototype was then built and heuristically tested with 11 users who were asked to complete multiple tasks within the platform while verbalizing their decision-making using the 'think aloud' procedure. The System Usability Scale (SUS) was administered at the end of each testing session. After refinements to the platform were made, usability was reassessed with 7 of 11 same users to examine changes. Results: The interactive digital platform (the D4DS Planner) has two main components: 1) the Education Hub (e.g., searchable platform with literature, videos, websites) and 2) the Action Planner. The Action Planner includes 7 interactive steps that walk users through a set of activities to generate a downloadable D4DS action plan for their project. Participants reported that the prototype tool was moderately usable (SUS=66) but improved following refinements (SUS=71). Conclusions: This is a first of its kind tool that supports research teams in learning about and explicitly applying D4DS to their work. The use of this publicly available tool may increase the adoption, impact, and sustainment of a wide range of research products. The use of UCD yielded a tool that is easy to use. The future use and impact of this tool will be evaluated, and the tool will continue to be refined and improved.
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G protein-coupled receptors (GPCRs) are central to the functioning of the hypothalamic-pituitary-gonadal axis (HPG axis) and include the rhodopsin-like GPCR family members, neurokinin 3 receptor, kappa-opioid receptor, kisspeptin 1 receptor, gonadotropin-releasing hormone receptor, and the gonadotropin receptors, luteinizing hormone/choriogonadotropin receptor and follicle-stimulating hormone receptor. Unsurprisingly, inactivating variants of these receptors have been implicated in a spectrum of reproductive phenotypes, including failure to undergo puberty, and infertility. Clinical induction of puberty in patients harbouring such variants is possible, but restoration of fertility is not always a realisable outcome, particularly for those patients suffering from primary hypogonadism. Thus, novel pharmaceuticals and/or a fundamental change in approach to treating these patients are required. The increasing wealth of data describing the effects of coding-region genetic variants on GPCR function has highlighted that the majority appear to be dysfunctional as a result of misfolding of the encoded receptor protein, which, in turn, results in impaired receptor trafficking through the secretory pathway to the cell surface. As such, these intracellularly retained receptors may be amenable to 'rescue' using a pharmacological chaperone (PC)-based approach. PCs are small, cell permeant molecules hypothesised to interact with misfolded intracellularly retained proteins, stabilising their folding and promoting their trafficking through the secretory pathway. In support of the use of this approach as a viable therapeutic option, it has been observed that many rescued variant GPCRs retain at least a degree of functionality when 'rescued' to the cell surface. In this review, we examine the GPCR PC research landscape, focussing on the rescue of inactivating variant GPCRs with important roles in the HPG axis, and describe what is known regarding the mechanisms by which PCs restore trafficking and function. We also discuss some of the merits and obstacles associated with taking this approach forward into a clinical setting.
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The current global outbreak of artificial stone silicosis is a recrudescence of a major occupational disease in the context of a novel exposure source. Respirable crystalline silica exposure, even without frank pneumoconiosis, is associated with an increased risk of respiratory infection. Empyema is a well-recognized complication of bacterial pneumonia; pneumonia among working-age adults, in turn, has been epidemiologically linked to occupational exposure to fumes and dust, including silica. A connection between empyema and silica dust inhalation has not been reported, however, whether through antecedent pneumonia or another mechanism. We describe a case of silicosis initially presenting with empyema in a 31-year-old Computerized Numerical Control stone-cutting machine operator who had heavy exposure to artificial stone and other rock dust.
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OBJECTIVE: To compare the biomechanical properties of lateral femoro-fabella ligament suture (FFLS) and lateral suture with a bone anchor suture (BAS) for management of feline cranial cruciate ligament disease. ANIMALS: 12 femurs from 6 mature cat cadavers. METHODS: The samples were collected from April to June 2023. The specimens had an FFLS and, subsequently, BAS placed and were positioned into a biomechanical testing machine, preloaded from 5 N to 15 N for 100 cycles, and subsequently, a load to suture failure was applied. The displacement at 5 N and 15 N, the total precycle displacement (millimeters), the force at 3 mm displacement and at failure (newtons), the displacement at failure (millimeters), and the stiffness to failure (Newton:millimiter) were recorded. Nonparametric Wilcoxon signed-rank tests were used to compare data between the 2 groups. RESULTS: The displacement at 5 N and 15 N and the total precycle displacement were significantly higher in the FFLS group compared to the BAS group. Additionally, the FFLS group results showed less consistent displacement and marked variability. The force (newtons) at 3 mm displacement was higher in the BAS group. There was no significant difference in force and no significant difference in displacement at failure between the 2 groups. However, the stiffness to failure (N/mm) was significantly higher in the BAS group. CONCLUSION: BAS represented a more stable and reliable femur attachment for extracapsular suture in cats. CLINICAL RELEVANCE: To demonstrate the stability and reliability between BAS and FFLS and influence implant selection in the treatment of cranial cruciate ligament rupture in cats with evaluation of biomechanical properties.
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Cadáver , Técnicas de Sutura , Animais , Gatos , Fenômenos Biomecânicos , Técnicas de Sutura/veterinária , Ligamento Cruzado Anterior/cirurgia , Âncoras de Sutura , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/veterinária , Feminino , Masculino , Fêmur/cirurgiaRESUMO
During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1ß and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.