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The genomics era has facilitated discovery of new genes predisposing to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ERG as a novel autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor critical for definitive hematopoiesis, stem cell function and platelet maintenance. ERG colocalizes with other transcription factors including RUNX1 and GATA2 on promoters/enhancers of genes orchestrating hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 thrombocytopenic individuals from one family and 14 additional ERG variants in unrelated individuals with BMF/HM including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germline ERG variants included cytopenias (thrombocytopenia, neutropenia, pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense, 1 truncating) including 3 missense population variants were functionally characterized. Thirteen potentially pathogenic ETS domain missense variants displayed loss-of-function characteristics disrupting transcriptional transactivation, DNA-binding and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture, and to promote acute erythroleukemia when transplanted into mice, concordant with these variants being loss-of-function. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germline ERG variants has clinical implications for patient/family diagnosis, counselling, surveillance, and treatment strategies including selection of bone marrow donors or cell/gene therapy.
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Distantly related mammals (e.g. jerboa, tarsiers, kangaroos) have convergently evolved elongated hindlimbs relative to body size. Limb elongation is hypothesized to make these species more effective jumpers by increasing their kinetic energy output (through greater forces or acceleration distances), thereby increasing take-off velocity and jump distance. This hypothesis, however, has rarely been tested at the population level, where natural selection operates. We examined the relationship between limb length, muscular traits and dynamics using Longshanks mice, which were selectively bred over 22 generations for longer tibiae. Longshanks mice have approximately 15% longer tibiae and 10% longer femora compared with random-bred Control mice from the same genetic background. We collected in vivo measures of locomotor kinematics and force production, in combination with behavioral data and muscle morphology, to examine how changes in bone and muscle structure observed in Longshanks mice affect their hindlimb dynamics during jumping and clambering. Longshanks mice achieved higher mean and maximum lunge-jump heights than Control mice. When jumping to a standardized height (14â cm), Longshanks mice had lower maximum ground reaction forces, prolonged contact times and greater impulses, without significant differences in average force, power or whole-body velocity. While Longshanks mice have longer plantarflexor muscle bodies and tendons than Control mice, there were no consistent differences in muscular cross-sectional area or overall muscle volume; improved lunge-jumping performance in Longshanks mice is not accomplished by simply possessing larger muscles. Independent of other morphological or behavioral changes, our results point to the benefit of longer hindlimbs for performing dynamic locomotion.
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Membro Posterior , Locomoção , Animais , Membro Posterior/fisiologia , Membro Posterior/anatomia & histologia , Fenômenos Biomecânicos , Camundongos/fisiologia , Músculo Esquelético/fisiologia , Músculo Esquelético/anatomia & histologia , Masculino , Feminino , Tíbia/fisiologia , Tíbia/anatomia & histologia , Fêmur/fisiologia , Fêmur/anatomia & histologiaRESUMO
BACKGROUND: Indoor residual spraying (IRS) is one of the most effective malaria control tools. However, its application has become limited to specific contexts due to the increased costs of IRS products and implementation programmes. Selective spraying-selective spray targeted to particular areas/surfaces of dwellings-has been proposed to maintain the malaria control and resistance-management benefits of IRS while decreasing the costs of the intervention. METHODS: A literature search was conducted to find (1) studies that assessed the resting behaviour of Anopheles mosquitoes and (2) studies that evaluated the impact of selective spraying on entomological and malaria outcomes. Additional articles were identified through hand searches of all references cited in articles identified through the initial search. A cost model was developed from PMI VectorLink IRS country programmes, and comparative cost analysis reports to describe the overall cost benefits of selective IRS. RESULTS: In some studies, there appeared to be a clear resting preference for certain Anopheles species in terms of the height at which they rested. However, for other species, and particularly the major African malaria vectors, a clear resting pattern was not detected. Furthermore, resting behaviour was not measured in a standardized way. For the selective spray studies that were assessed, there was a wide range of spray configurations, which complicates the comparison of methods. Many of these spray techniques were effective and resulted in reported 25-68% cost savings and reduced use of insecticide. The reported cost savings in the literature do not always consider all of the IRS implementation costs. Using the IRS cost model, these savings ranged from 17 to 29% for programs that targeted Anopheles spp. and 18-41% for programmes that targeted Aedes aegypti. CONCLUSIONS: Resting behaviour is generally measured in a simplistic way; noting the resting spot of mosquitoes in the morning. This is likely an oversimplification, and there is a need for better monitoring of resting mosquitoes. This may improve the target surface for selective spray techniques, which could reduce the cost of IRS while maintaining its effectiveness. Reporting of cost savings should be calculated considering the entire implementation costs, and a cost model was provided for future calculations.
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Anopheles , Inseticidas , Malária , Controle de Mosquitos , Controle de Mosquitos/métodos , Controle de Mosquitos/economia , Animais , Malária/prevenção & controle , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Inseticidas/administração & dosagem , Inseticidas/economia , Humanos , Mosquitos Vetores/efeitos dos fármacosRESUMO
BACKGROUND: Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. METHODS: Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. RESULTS: The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. CONCLUSION: These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts.
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Malária Falciparum , Plasmodium falciparum , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Plasmodium falciparum/isolamento & purificação , Parasitemia/diagnóstico , Parasitemia/parasitologia , Anemia/diagnóstico , Anemia/sangue , Anemia/parasitologia , Espectrofotometria Infravermelho/métodos , Aprendizado de Máquina , Carga Parasitária , Adulto , Inteligência Artificial , Sensibilidade e Especificidade , Feminino , Adulto Jovem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Adolescente , Masculino , Pessoa de Meia-Idade , Programas de Rastreamento/métodosRESUMO
INTRODUCTION: Transportation databases have limited data regarding injury severity of pedestrian versus automobile patients. To identify opportunities to reduce injury severity, transportation and trauma databases were integrated to examine the differences in pedestrian injury severity at street crossings that were signalized crossings (SCs) versus nonsignalized crossings (NSCs). It was hypothesized that trauma database integration would enhance safety analysis and pedestrians struck at NSC would have greater injury severity. METHODS: Single-center retrospective review of all pedestrian versus automobile patients treated at a level 1 trauma center from 2014 to 2018 was performed. Patients were matched to the transportation database by name, gender, and crash date. Google Earth Pro satellite imagery was used to identify SC versus NSC. Injury severity of pedestrians struck at SC was compared to NSC. RESULTS: A total of 512 patients were matched (median age = 41 y [Q1 = 26, Q3 = 55], 74% male). Pedestrians struck at SC (n = 206) had a lower injury severity score (ISS) (median = 9 [4, 14] versus 17 [9, 26], P < 0.001), hospital length of stay (median = 3 [0, 7] versus 6 [1, 15] days, P < 0.001), and mortality (21 [10%] versus 52 [17%], P = 0.04), as compared to those struck at NSC (n = 306). The transportation database had a sensitivity of 63.4% (55.8%-70.4%) and specificity of 63.4% (57.7%-68.9%) for classifying severe injuries (ISS >15). CONCLUSIONS: Pedestrians struck at SC were correlated with a lower ISS and mortality compared to those at NSC. Linkage with the trauma database could increase the transportation database's accuracy of injury severity assessment for nonfatal injuries. Database integration can be used for evidence-based action plans to reduce pedestrian morbidity, such as increasing the number of SC.
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Pedestres , Ferimentos e Lesões , Humanos , Masculino , Adulto , Feminino , Acidentes de Trânsito/prevenção & controle , Meios de Transporte , Centros de Traumatologia , Bases de Dados Factuais , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/epidemiologiaRESUMO
BACKGROUND: This study aimed to assess whether moderate-to-vigorous physical activity (MVPA), sport and exercise as a proxy measure of muscle and bone strengthening activity, sedentary behaviour, and sleep were associated with total-body-less-head (TBLH) bone mineral content (BMC) and TBLH lean mass cross-sectionally and longitudinally from age 6 to 9 years and age 9 to 11 years to age 15 to 17 years. METHODS: We used longitudinal data from a population sample of Finnish children from the Physical Activity and Nutrition in Children study (age 6 to 9 years: n = 478, 229 females; age 9 to 11 years: n = 384, 197 females; age 15 to 17 years: n = 222, 103 females). Linear regression analysed the cross-sectional and longitudinal associations between accelerometer-assessed MVPA, sedentary time and sleep, and questionnaire-assessed sport and exercise participation and screen time with dual-energy X-ray absorptiometry-assessed TBLH BMC and lean mass. RESULTS: In females, MVPA at age 6 to 9 years was positively associated with TBLH BMC at age 15 to 17 years (ß = 0.008, p = 0.010). Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (ß = 0.020, p = 0.002) and lean mass (ß = 0.343, p = 0.040) at age 15 to 17 years. MVPA at age 9 to 11 years was positively associated with TBLH lean mass (ß = 0.272, p = 0.004) at age 15 to 17 years. In males, sleep at age 6 to 9 years was positively associated with TBLH lean mass (ß = 0.382, p = 0.003) at age 15 to 17 years. Sport and exercise at age 9 to 11 years was positively associated with TBLH BMC (ß = 0.027, p = 0.012) and lean mass (ß = 0.721, p < 0.001) at age 15 to 17 years. CONCLUSIONS: Promoting engagement in the 24-hour movement behaviours in childhood, particularly sport and exercise to strengthen muscle and bone, is important in supporting bone and lean mass development in adolescence. TRIAL REGISTRATION: NCT01803776; first trial registration date: 04/03/2013.
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Densidade Óssea , Osso e Ossos , Adolescente , Criança , Feminino , Humanos , Masculino , Absorciometria de Fóton , Densidade Óssea/fisiologia , Estudos Transversais , Exercício Físico/fisiologia , MúsculosRESUMO
OBJECTIVES: It is unclear if use of cesarean delivery in people with inflammatory bowel disease (IBD) is guideline-concordant. We compared the odds of cesarean delivery among primiparous individuals with IBD versus without, overall, and by disease characteristics, as well as time to subsequent delivery. METHODS: Retrospective matched population-based cohort study between 1 April 1994 and 31 March 2020. Primiparous individuals aged 15-55 years with IBD were matched to those without IBD on age, year, hospital, and number of newborns delivered. Primary outcome was cesarean delivery versus vaginal delivery. Multivariable conditional logistic regression analyses were performed to estimate the odds of cesarean delivery among individuals with and without IBD as a binary exposure, and a categorical exposure based on IBD-related indications for cesarean delivery. Time to subsequent delivery was evaluated using a Cox proportional hazard model. RESULTS: We matched 7472 individuals with IBD to 37 360 individuals without (99.02% match rate). Individuals with IBD were categorised as having perianal (PA) disease (IBD-PA, n = 764, 10.2%), prior ileal pouch-anal anastomosis (n = 212, 2.8%), or IBD-Other (n = 6496, 86.9%). Cesarean delivery rates were 35.4% in the IBD group versus 30.4% in their controls (adjusted odds ratio 1.27; 95% CI 1.20-1.34). IBD-ileal pouch-anal anastomosis had a cesarean delivery rate of 66.5%, compared to 49.9% in IBD-PA and 32.7% in IBD-Other. There was no significant difference in the rate of subsequent delivery in those with and without IBD (adjusted hazard ratio 1.03; 95% CI 1-1.07). CONCLUSIONS: The higher risk of cesarean delivery in people with IBD reflects guideline-concordant use. Individuals with and without IBD were equally likely to have a subsequent delivery with similar timing.
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Cesárea , Doenças Inflamatórias Intestinais , Humanos , Feminino , Cesárea/estatística & dados numéricos , Adulto , Gravidez , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Complicações na Gravidez/epidemiologia , Estudos de Coortes , Fatores de RiscoRESUMO
BACKGROUND: Ultraviolet (UV)-exposure behaviors can directly impact an individual's skin cancer risk, with many habits formed during childhood and adolescence. We explored the utility of a photoaging smartphone application to motivate youth to improve sun safety practices. METHODS: Participants completed a preintervention survey to gather baseline sun safety perceptions and behaviors. Participants then used a photoaging mobile application to view the projected effects of chronic UV exposure on participants' self-face image over time, followed by a postintervention survey to assess motivation to engage in future sun safety practices. RESULTS: The study sample included 87 participants (median [interquartile (IQR)] age, 14 [11-16] years). Most participants were White (50.6%) and reported skin type that burns a little and tans easily (42.5%). Preintervention sun exposure behaviors among participants revealed that 33 (37.9%) mostly or always used sunscreen on a sunny day, 48 (55.2%) experienced at least one sunburn over the past year, 26 (30.6%) engaged in outdoor sunbathing at least once during the past year, and zero (0%) used indoor tanning beds. Non-skin of color (18 [41.9%], p = .02) and older (24 [41.4%], p = .007) participants more often agreed they felt better with a tan. Most participants agreed the intervention increased their motivation to practice sun-protective behaviors (wear sunscreen, 74 [85.1%]; wear hats, 64 [74.4%]; avoid indoor tanning, 73 [83.9%]; avoid outdoor tanning, 68 [79%]). CONCLUSION: The findings of this cross-sectional study suggest that a photoaging smartphone application may serve as a useful tool to promote sun safety behaviors from a young age.
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Comportamentos Relacionados com a Saúde , Aplicativos Móveis , Smartphone , Queimadura Solar , Humanos , Adolescente , Masculino , Feminino , Criança , Queimadura Solar/prevenção & controle , Protetores Solares/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/etiologia , Banho de Sol/psicologia , Promoção da Saúde/métodos , Inquéritos e Questionários , Luz Solar/efeitos adversosRESUMO
How the COVID-19 pandemic, and the deaths that occurred during the acute phase of the pandemic (2020-2021), will be remembered is yet to be determined. Writing from a UK perspective, this short article reflects on the way in which memory, narratives and death are constructed, contested and (re)produced. Drawing on the authors' respective sociological sub-fields, it makes a case for an ongoing sociological appraisal of emergent COVID-19 narratives, that can encompass and intertwine understandings of temporality, accountability and loss.
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OBJECTIVE: Clinical research is a growing part of the academic clinician's job, and documenting areas of low self-efficacy can inform training initiatives. SAMPLE: 182 US academic veterinary clinicians. METHODS: A survey of academic veterinary clinicians was distributed to 31 US institutions. Self-efficacy was assessed with a modified Clinical Research Appraisal Instrument-12. The relationship between research self-efficacy and completion of formal research training and years of experience was evaluated. RESULTS: Respondents were predominantly junior to midcareer faculty. The lowest reported confidence was in performing advanced statistical analyses (3; 0 to 10). Other low-confidence tasks included designing a qualitative methods study (4; 0 to 10), terminating a collaboration that isn't working (5; 0 to 10), describing a funding agency's review/award process (5; 0 to 10), establishing a timeline for a grant application (5; 0 to 10), establishing collaborator and consultant agreements (5; 0 to 10), and asking staff to leave the project team (5; 0 to 10). Completion of a formal research training program was significantly associated with improved self-efficacy in many tasks. Years of experience was also associated, especially in project management and interpersonal interactions. CLINICAL RELEVANCE: These results highlight the need for targeted training opportunities for academic veterinary clinicians in biostatistical support, qualitative study design methods, and aspects of communication and interpersonal skills that are important for developing and leading effective research teams. Range of confidence suggests that development opportunities in all domains will improve self-efficacy for some clinicians. Future studies should focus on the impact of formal training sessions on various domains of self-efficacy and on targeted mentoring in supporting confidence in more experiential learning domains.
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Autoeficácia , Médicos Veterinários , Estados Unidos , Médicos Veterinários/psicologia , Humanos , Pesquisa Biomédica , Inquéritos e Questionários , Educação em Veterinária , Masculino , Feminino , Coleta de Dados , Medicina Veterinária , AnimaisRESUMO
Introduction: Veterinary biobanks store samples for future use and distribute samples to academic researchers and industry entities; however, informed consent provided by owners for pets contributing to biobanks can be complicated by limited understanding of goals, purpose, and logistics of biobanking. Methods: This survey-based study aimed to gather feedback from pet owners on how they viewed allowing their pet to contribute to a veterinary biobank, with the goal of identifying opportunities to improve education, awareness of veterinary biobanking initiatives, and the consent processes. An electronic survey was distributed to a listserv of 2,119 pet owners and responses were received from 118 respondents (5.6%). Results: Most respondents (67%) were not familiar with the concept of veterinary biobanking prior to having responded to the survey. Most (89%) were willing to allow their healthy pet to contribute samples to a veterinary biobanking program. Ninety-five percent would allow their sick pet to contribute. Most were neutral about financial incentives as a motivator to participate, although 40% indicated that if their pet's condition resulted in a decision to humanely euthanize, they would be more likely to contribute to the biobank if the veterinary biobanking program covered the cost of euthanasia. Common concerns included security/confidentiality (36%), that results would not be shared with them (33%) or that samples would be used for other purposes beyond those advertised (22%). Discussion: These results suggest veterinary biobanking initiatives are well received by owners and most are willing to allow their pets to participate. Respondent concerns represent opportunities for veterinary biobanks to improve messaging and dissemination of results from work they support.
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Vector-borne diseases, including dengue, leishmaniasis and malaria, may be more common among individuals whose occupations or behaviours bring them into frequent contact with these disease vectors outside of their homes. A systematic review was conducted to ascertain at-risk occupations and situations that put individuals at increased risk of exposure to these disease vectors in endemic regions and identify the most suitable interventions for each exposure. The review was conducted in accordance with PRISMA guidelines on articles published between 1945 and October 2021, searched in 16 online databases. The primary outcome was incidence or prevalence of dengue, leishmaniasis or malaria. The review excluded ecological and qualitative studies, abstracts only, letters, commentaries, reviews, and studies of laboratory-acquired infections. Studies were appraised, data extracted, and a descriptive analysis conducted. Bite interventions for each risk group were assessed. A total of 1170 articles were screened and 99 included. Malaria, leishmaniasis and dengue were presented in 47, 41 and 24 articles, respectively; some articles presented multiple conditions. The most represented populations were soldiers, 38% (43 of 112 studies); refugees and travellers, 15% (17) each; migrant workers, 12.5% (14); miners, 9% (10); farmers, 5% (6); rubber tappers and missionaries, 1.8% (2) each; and forest workers, 0.9% (1). Risk of exposure was categorised into round-the-clock or specific times of day/night dependent on occupation. Exposure to these vectors presents a critical and understudied concern for outdoor workers and mobile populations. When devising interventions to provide round-the-clock vector bite protection, two populations are considered. First, mobile populations, characterized by their high mobility, may find potential benefits in insecticide-treated clothing, though more research and optimization are essential. Treated clothing offers personal vector protection and holds promise for economically disadvantaged individuals, especially when enabling them to self-treat their clothing to repel vectors. Secondly, semi-permanent and permanent settlement populations can receive a combination of interventions that offer both personal and community protection, including spatial repellents, suitable for extended stays. Existing research is heavily biased towards tourism and the military, diverting attention and resources from vulnerable populations where these interventions are most required like refugee populations as well as those residing in sub-Saharan Africa.
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Sweet's syndrome (SS), or acute febrile neutrophilic dermatosis, characteristically presents with fever, dermal neutrophilic infiltrates, and neutrophilia. It typically manifests as tender erythematous plaques; however, various variants are documented, including bullous. Malignancy-associated Sweet's syndrome (MASS) can present as a paraneoplastic syndrome in those with established cancers or with undiagnosed malignancies. We present a 72-year-old male with a three-day history of a progressive bullous, erythematous papular rash starting on his right forearm and spreading to his extremities, trunk, palms, and soles. It was mildly pruritic but nontender. He had no recent febrile illnesses. On examination, the rash was violaceous with tense bullae overlying edematous targetoid papules coalescing into plaques. Histopathologic analysis of punch biopsies from his abdomen and thigh demonstrated dense inflammatory infiltrates of neutrophils, eosinophils, histiocytes, and lymphocytes, suggestive of neutrophilic dermatosis, or Sweet's syndrome. He was treated with prednisone 1 mg/kg with improvement in his cutaneous symptoms, and a malignancy workup was initiated. Blood work showed elevated free kappa, lambda light chains, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. A positron emission tomography (PET) scan revealed lesions in the esophagus and kidney. He was referred to Heme/Onc, GI, and Urology. He was diagnosed with esophageal adenocarcinoma stage IIb and a renal mass. He has since completed neoadjuvant chemotherapy and radiation, is s/p robotic Ivor-Lewis esophagectomy with no evidence of residual carcinoma on pathology, and is undergoing surveillance with imaging every three months for his renal mass. This case highlights the importance of rapid identification of MASS and the impact dermatologists can make in getting these patients the potentially lifesaving care they need.
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Acute respiratory distress syndrome (ARDS) presents a formidable challenge in critical care, often resulting in high mortality rates, particularly in severe cases or those compounded by preexisting conditions. Despite substantial advancements in critical care, the heterogeneous nature of ARDS necessitates nuanced clinical approaches. ARDS is generally diagnosed through clinical evaluation, radiographic imaging, and laboratory tests, as well as acute onset, bilateral lung infiltrates on imaging, and a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspiratory oxygen concentration (FiO2) ratio of less than 300 mmHg. Management involves measurements to improve oxygenation and provide mechanical ventilation to assist breathing. The typical manifestation of ARDS is diffuse lung involvement, which affects multiple lobes symmetrically. Here, we report an unusual case of ARDS in a 53-year-old female who was brought into the hospital in an unresponsive state, exhibiting hypoxic and hypotension requiring intubation. Subsequent imaging revealed a distinctive pattern: the preservation of the right middle lobe, diverging from the conventional diffuse pulmonary affliction. This case underscores the need for clinical vigilance and adaptability, as such atypical presentations can confound diagnosis and management, posing unique clinical challenges. This case highlights the importance of recognizing ARDS' diverse presentations. Moreover, understanding the mechanisms behind the lobar sparing could provide greater insight into the disease heterogeneity and guide tailored therapeutic approaches. The imperative for further research into these uncommon presentations is clear, as it may be vital to improving outcomes for a broader spectrum of ARDS patients.
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Necrolytic acral erythema (NAE) is an uncommon cutaneous disorder characterized by a symmetric acral distribution of erythematous plaques with underlying epidermal necrosis. While typically presenting in the context of hepatitis C virus (HCV) infection, NAE can also present secondary to nutritional deficiency or systemic disease. We present a case of NAE in a 66-year-old patient with no history of HCV infection status post gastric bypass who had a three-month history of eating only mushroom soup. The patient underwent a punch biopsy and was tested for a variety of nutritional deficiencies. Biopsy demonstrated partial necrosis of the upper epidermis, with subjacent re-epithelialization, squamatization, and vacuolopathy of the basal epidermis. He was treated with zinc replacement therapy after initial trials of tacrolimus and clobetasol were unsuccessful. At follow-up, he had significant improvement of the lesions. This case provides an example of an atypical presentation of NAE in the absence of HCV infection that presented as a complication of gastric bypass-associated nutritional deficiency.
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Introduction: Modic changes (MC) are signs of vertebral pathology visible on magnetic resonance (MR) images that have been associated with low back pain (LBP) and disc degeneration in people. Multiple breeds of dogs also develop MCs and coincident back pain. However, the association between breed, MC, and spinal pathologies has yet to be fully elucidated. This study aimed to identify the prevalence of MC that occur spontaneously in the lumbar vertebral column of dogs diagnosed with intervertebral disc disease (IVDD) and examine their association with demographic criteria and the disc width index (DWI). Methods: Medical records and lumbar vertebral column MR images were examined from 104 dogs (831 intervertebral disc spaces and adjacent vertebrae), which were divided into three groups: chondrodystrophic dogs (CD; n =54) and non-chondrodystrophic dogs (NCD; n =30) with IVDD as the primary diagnosis, and control dogs (n =20) with other spinal diseases as their primary diagnosis. Results: Increasing age and a diagnosis of IVDD were significantly associated with MC in dogs (p < 0.001 and p = 0.0062, respectively). In CD dogs with IVDD, Type 2 MC were most prevalent, whereas, in NCD dogs, Type 3 MC were the most prevalent type. Type 2 MC were distributed nearly equally across the lumbar vertebral column, while Type 3 MC were primarily detected at the level of L7-S1. Discussion: This study demonstrated that MC developed spontaneously in dogs, are common in dogs diagnosed with IVDD, and the type observed varies by breed. Further research is needed to understand the pathogenesis of MC; however, the increased presence of Type 2 MC in CD dogs, similar to what is found in people with disc degeneration, suggests that CD dogs could serve as models for MC in people.
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Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.
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BACKGROUND: "Regeneration time" (RT) denotes the time required to obtain a stable mortality rate for mosquitoes exposed to insecticide-treated nets (ITNs) after three consecutive washes of a net in a day. The RT informs the wash interval used to artificially age ITNs to simulate their lifetime performance under user conditions (20 washes). RT was estimated following World Health Organization (WHO) longitudinal method (LM) procedures. Longitudinal evaluation may introduce heterogeneity due to mosquito batch variability, complicating RT determination. To overcome this, nets at each stage of regeneration (i.e., 1, 2, 3, 5 and 7 days post wash) were prepared in advance and refrigerated; then, a complete regeneration series was tested with a single mosquito batch on 1 testing day, completing four series over 4 days. This study compared the complete series method (CSM) against the LM. METHODS: The overall heterogeneity in the methods for estimating RT of one incorporated alpha-cypermethrin and piperonyl butoxide (PBO) and one incorporated permethrin with PBO ITNs was determined using laboratory-reared resistant Anopheles arabiensis under standard laboratory conditions. LM methods and CSM were compared in two experiments with refrigerated nets acclimated for (i) 2 h (test 1) and (ii) 3 h (test 2). Four regeneration replicates per day were tested per ITN product with 50 mosquitoes exposed per replicate (equivalent sample size to LM). The heterogeneity from these methods was compared descriptively. RESULTS: The intra-method variability for unwashed pieces was minimal, with variance of 1.26 for CSM and 1.18 for LM. For unwashed nets, LM had substantially greater variance and ratio of LM:CSM was 2.66 in test 1 and 2.49 in test 2. The magnitude of mortality measured in bioassays depended on sample acclimation after refrigeration. CONCLUSIONS: The CSM is a convenient method for determining the regeneration times. ITNs are prepared in advance, reducing pressure to prepare all samples to start on a single day. A complete regeneration series of samples is removed from the refrigerator, defrosted and evaluated on a single day with one mosquito batch reducing the influence of mosquito batch heterogeneity on results. Replicates can be conducted over several days but do not have to be conducted on consecutive days, allowing easy facility scheduling.
Assuntos
Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Controle de Mosquitos , Animais , Anopheles/fisiologia , Anopheles/efeitos dos fármacos , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Fatores de Tempo , Piretrinas/farmacologia , Permetrina/farmacologia , Malária/prevenção & controle , Malária/transmissão , Butóxido de Piperonila/farmacologiaRESUMO
Objective: This study aimed to describe the diagnostic discrimination and reliability of a novel technique for quantifying lumbosacral articular process displacement (LSAPD) on dorsal plane computed tomography (DPCT) imaging in dogs with and without degenerative lumbosacral stenosis (DLSS). Study design: DPCT surveys of the lumbosacral vertebral column were performed with dogs positioned in extension and flexion. LSAPD is defined as the distance between the cranial aspects of the L7 and S1 articular processes. The LSAPD ratio is identified by dividing the LSAPD by the length of the L7 articular process. Intraclass correlation coefficients (ICCs) for intra- and inter-observer reliability were calculated, and logistic regressions were used to test for the association of LSAPD and LSAPD ratio with odds of DLSS. Significance was set at 0.05. Receiver operator characteristic (ROC) curves were calculated to determine diagnostic discrimination and optimal cutoff for LSAPD and LSAPD ratio in the diagnosis of DLSS. Results: Intra- and inter-observer reliabilities were excellent for most measurements. In the current cohort, excluding covariates, the area under the curve (AUC) (95%CI) for LSAPD and LSAPD ratio measured in a flexed position were both 0.89 (0.82-0.96), suggesting potentially excellent discrimination for using this measurement as a marker for diagnosing DLSS, pending further studies. The cutoffs for flexed LSAPD and LSAPD ratio that maximizes Youden's index were ≥ 1.2 mm and ≥ 9%, respectively. When age and weight were subsequently included as covariates in a multivariable analysis, a significant relationship between LSAPD or LSAPD ratio and odds of diagnosis of DLSS was not demonstrated, suggesting the need for a larger sample size. Conclusion: The results of this study suggest that measurements of LSAPD and LSAPD ratio on DPCT are feasible and reliable, although their diagnostic discrimination in DLSS should be evaluated further in future prospective studies.