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1.
Proc Natl Acad Sci U S A ; 120(4): e2209482119, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36649422

RESUMO

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis."


Assuntos
Agricultura , Tamanho Corporal , Indústria de Laticínios , Humanos , Aceleração , Europa (Continente) , Lactase
2.
Artigo em Inglês | MEDLINE | ID: mdl-39324855

RESUMO

OBJECTIVES: Continuous, noninvasive tools to monitor peripheral perfusion, such as perfusion index (PI), can detect hemodynamic abnormalities and assist in the management of critically ill children hospitalized with severe malaria. In this study of hospitalized children with severe malaria, we aimed to assess whether PI correlates with clinical markers of perfusion and to determine whether combining PI with these clinical measures improves identification of children with greater odds of mortality. DESIGN: Post hoc analysis of a prospective, multicenter, cohort study conducted between 2014 and 2017. SETTING: Two referral hospitals in Central and Eastern Uganda. PATIENTS: Six hundred children younger than 5 years old with severe malaria and 120 asymptomatic community children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PI was measured at 6-hour intervals for the first 24 hours of hospitalization. We compared PI to standard clinical perfusion measures such as capillary refill time, presence of cold peripheral limbs, or temperature gradient. Admission PI was highly correlated with clinical measures of perfusion. Admission PI was lower in children with severe malaria compared with asymptomatic community children; and, among the children with severe malaria, PI was lower in those with clinical features of poor perfusion or complications of severe malaria, such as shock and hyperlactatemia (all p < 0.02). Among children with severe malaria, lower admission PI was associated with greater odds of mortality after adjustment for age, sex, and severe malaria criteria (adjusted odds ratio, 2.4 for each log decrease in PI [95% CI, 1.0-5.9]; p = 0.045). Diagnostically, the presence of two consecutive low PI measures (< 1%) predicted mortality, with a sensitivity of 50% and a specificity of 76%. CONCLUSIONS: In severe malaria, PI correlates with clinical complications (including shock and elevated serum lactate) and may be useful as an objective, continuous explanatory variable associated with greater odds of later in-hospital mortality.

3.
Ecotoxicology ; 33(9): 1047-1061, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39264549

RESUMO

Despite the benefits derived from the use of pharmaceuticals, these compounds are currently considered contaminants of emerging concern because of their presence and persistence in the environment. This study aimed to determine the toxicity of 27 pharmaceuticals and the interaction effects of binary mixtures of selected compounds towards two model organisms: the microcrustacean Daphnia magna and the bacterium Aliivibrio fischeri (Microtox test). Six compounds, namely polymyxin B, polymyxin E, fluoxetine, diphenhydramine, clenbuterol and ketoprofen exhibited moderate toxicity towards D. magna. Additionally, three compounds (cefotaxime, polymyxin B, polymyxin E) also showed a moderate toxic effect on A. fischeri. The comparison of such results with model estimations showed inaccuracy in the predicted data, highlighting the relevance of experimental ecotoxicological assays. The assayed mixtures contained four selected drugs of high-hazard according to their reported concentrations in wastewater and surface water (diphenhydramine, trimethoprim, ketoprofen, and fluoxetine); data revealed interactions only in the fluoxetine-containing mixtures for D. magna, while all mixtures showed interactions (mostly synergistic) for Microtox. Chronic effects on the reproduction of D. magna were observed after exposure to fluoxetine and diphenhydramine, although higher sensitivity was determined for the latter, while the mixture of these compounds (which showed acute synergy in both models) also affected the reproduction patterns. Nonetheless, all the effects described at the acute or chronic level (for individual compounds or mixtures) were determined at concentrations higher than commonly reported at environmental levels. This work provides valuable ecotoxicological information for the risk assessment of pharmaceuticals and their mixtures in the environment.


Assuntos
Aliivibrio fischeri , Daphnia , Poluentes Químicos da Água , Aliivibrio fischeri/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Animais , Poluentes Químicos da Água/toxicidade , Preparações Farmacêuticas , Testes de Toxicidade , Daphnia magna
4.
Clin Endocrinol (Oxf) ; 99(1): 52-57, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37143372

RESUMO

OBJECTIVE: Adrenal schwannomas and juxta-adrenal schwannomas are rare tumours. We aimed to summarise their clinical, biochemical and imaging characteristics. DESIGN: Single-centre retrospective study of eligible patients between 1995 and 2022. PATIENTS AND MEASUREMENTS: Patients with a histopathologic diagnosis of adrenal or juxta-adrenal schwannoma. RESULTS: Twenty-four patients were diagnosed with either primary adrenal schwannoma (8, 33%) or juxta-adrenal schwannoma (16, 67%). Most tumours (21, 88%) were discovered incidentally on imaging. All tumours were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumour size was 4 cm (range, 2-13 cm). Adrenal schwannomas were smaller when compared to juxta-adrenal schwannomas (median of 3.1 cm [range, 2-9 cm] vs. 4.6 cm [range, 2.3-13.3 cm], p = .037). On imaging, the tumours were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid-cystic in 7 (32%), heterogeneous in 14 (61%) and homogeneous in 9 (39%). The median unenhanced computed tomography attenuation was 30 Hounsfield units (HU) (range, 12-38 HU). Of the 20 patients who underwent complete hormonal testing, all had nonfunctioning tumours. There was no recurrence or new tumour development in our cohort. CONCLUSIONS: Adrenal and juxta-adrenal schwannomas are nonfunctioning benign tumours that present with indeterminate radiographic features, including large tumour size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumour is based on biopsy or resection.


Assuntos
Neoplasias das Glândulas Suprarrenais , Neurilemoma , Humanos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Fenótipo
5.
Histopathology ; 83(3): 426-434, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37195579

RESUMO

INTRODUCTION: Adamantinoma-like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) EWSR1::FLI1 translocation. There is debate on whether ALES resembles more sarcoma or carcinoma. METHODS: We performed RNA sequencing from two ALES cases and compared findings with skeletal Ewing's sarcomas and nonneoplastic thyroid tissue. ALES was investigated by in situ hybridization (ISH) for high-risk human papillomavirus (HPV) DNA and immunohistochemistry for the following antigens: keratin 7, keratin 20, keratin 5, keratins (AE1/AE3 and CAM5.2), CD45, CD20, CD5, CD99, chromogranin, synaptophysin, calcitonin, thyroglobulin, PAX8, TTF1, S100, p40, p63, p16, NUT, desmin, ER, FLI1, INI1, and myogenin. RESULTS: An uncommon EWSR1::FLI transcript with retained EWSR1 exon 8 was detected in both ALES cases. Regulators of EWSR1::FLI1 splicing (HNRNPH1, SUPT6H, SF3B1) necessary for production of a functional fusion oncoprotein, as well as 53 genes (including TNNT1, NKX2.2) activated downstream to the EWSR1::FLI1 cascade, were overexpressed. Eighty-six genes were uniquely overexpressed in ALES, most of which were related to squamous differentiation. Immunohistochemically, ALES strongly expressed keratins 5, AE1/AE3 and CAM5.2, p63, p40, p16, and focally CD99. INI1 was retained. The remaining immunostains and HPV DNA ISH were negative. CONCLUSION: Comparative transcriptomic profiling reveals overlapping features of ALES with skeletal Ewing's sarcoma and an epithelial carcinoma, as evidenced by immunohistochemical expression of keratin 5, p63, p40, CD99, the transcriptome profile, and detection of EWSR1::FLI1 fusion transcript by RNA sequencing.


Assuntos
Adamantinoma , Carcinoma , Infecções por Papillomavirus , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Adamantinoma/diagnóstico , Adamantinoma/genética , Adamantinoma/química , Glândula Tireoide/patologia , Transcriptoma , Queratina-5/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Fatores de Transcrição/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo
6.
Ecotoxicology ; 32(3): 383-393, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36995476

RESUMO

Despite their environmental implications, ecotoxicological information regarding pesticide mixtures is relatively scarce. This study aimed to determine the ecotoxicity of individual pesticide formulations and their mixtures (insecticides and fungicides), which are applied during the production cycle of potato, according to agricultural practices from a Latin American region in Costa Rica. Two benchmark organisms were employed: Daphnia magna and Lactuca sativa. First, the evaluation of individual formulations (chlorothalonil, propineb, deltamethrin+imidacloprid, ziram, thiocyclam and chlorpyrifos) revealed differences between available EC50 for active ingredients (a.i.) and their respective formulations toward D. magna; on the contrary, no information could be retrieved from scientific literature for comparison in the case of L. sativa. In general, acute toxicity was higher toward D. magna than L. sativa. Moreover, interactions could not be determined on L. sativa, as the chlorothalonil formulation was not toxic at high levels and the concentration-response to propineb could not be fitted to obtain an IC50 value. The commercial formulation composed of deltamethrin+imidacloprid followed the concentration addition model (when compared with parameters retrieved from individual a.i.) and the other three mixtures evaluated (I: chlorothalonil-propineb-deltamethrin+imidacloprid; II: chlorothalonil-propineb-ziram-thiocyclam; III: chlorothalonil-propineb-chlorpyrifos) produced an antagonistic effect on D. magna, thus suggesting less acute toxicity than their individual components. Subsequent chronic studies showed that one of the most toxic mixtures (II) negatively affected D. magna reproduction at sublethal concentrations indicating that this mixture poses a risk to this species if these pesticides co-exist in freshwater systems. These findings provide useful data to better estimate the impact of real agricultural practices related to the use of agrochemicals.


Assuntos
Clorpirifos , Praguicidas , Solanum tuberosum , Ziram , Animais , Praguicidas/toxicidade , Praguicidas/análise , Clorpirifos/toxicidade , Costa Rica , Ziram/farmacologia , Daphnia
7.
Bull Environ Contam Toxicol ; 111(4): 51, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752279

RESUMO

Animal husbandry wastewaters represent an important source of pharmaceuticals into the environment. This work aimed to evaluate the occurrence of pharmaceuticals and their hazard in wastewater from a model dairy farm from Costa Rica. Among the seven pharmaceuticals detected (acetaminophen, caffeine, carbamazepine, ibuprofen, ketoprofen, risperidone, sulfamethazine), caffeine, ibuprofen and acetaminophen showed the highest concentrations, while caffeine, carbamazepine and risperidone were the most frequently detected compounds. High (HQ ≥ 1) or medium (0.1 ≤ HQ < 1) hazard were estimated for three (caffeine, ibuprofen, risperidone) and two (acetaminophen, ketoprofen) pharmaceuticals, respectively; similarly, high overall hazard (∑HQ) and significant ecotoxicity were determined in samples from all sampling points. According to our results, the release of these aqueous matrices is a matter of environmental concern, as the treated wastewater is used for farm irrigation or directly released into nearby water streams. This work contributes to the knowledge on the scarcely described occurrence and risk of pharmaceuticals in Latin American regions.


Assuntos
Cetoprofeno , Poluentes Químicos da Água , Animais , Águas Residuárias , Cafeína , Ibuprofeno , Acetaminofen , Fazendas , Risperidona , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Água , Carbamazepina/análise , Preparações Farmacêuticas
8.
Clin Endocrinol (Oxf) ; 95(1): 47-57, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33721367

RESUMO

OBJECTIVE: To describe the presentation and outcomes of patients with adrenal ganglioneuromas (AGNs). DESIGN: Single-centre retrospective cohort study (1 January 1995 to 31 December 2019) and systematic review of literature (1 January 1980 to 19 November 2019). PATIENTS: Diagnosed with histologically confirmed AGN. MEASUREMENTS: Baseline clinical, imaging and biochemical characteristics, recurrence rates and mortality. Subgroup analysis was performed on tumours with histologic elements of ganglioneuroma and pheochromocytoma (ie composite tumours). RESULTS: The cohort study included 45 patients with AGN, 20 (44%) of which had composite tumours. Compared to pure AGN, patients with composite tumour were older (median age, 62.5 vs. 35 years, p < .001), had smaller tumours (median size, 3.9 vs. 5.7 cm, p = .016) and were discovered incidentally less frequently (65% vs. 84%, p = .009). No recurrences or ganglioneuroma-specific mortality occurred during follow-up (range, 0-266 months). The systematic review included 14 additional studies and 421 patients. The mean age of diagnosis was 39 years, and 47% were women. AGNs were discovered incidentally in 72% of patients, were predominantly unilateral (99%) and had a mean diameter of 5.8 cm and an unenhanced computed tomography (CT) attenuation of -118 to 49 Hounsfield units (HU). On imaging, 69% of AGNs were homogenous, 41% demonstrated calcifications, and 40% were lobulated. CONCLUSIONS: AGNs are rare benign tumours that present with variable imaging features including large size, unenhanced CT attenuation >20 HU, calcifications and lobulated shape. Imaging characteristics can assist in establishing a diagnosis and avoiding an unnecessary adrenalectomy. The association of pheochromocytomas with AGNs is frequent. Diagnosis should include biochemical testing.


Assuntos
Neoplasias das Glândulas Suprarrenais , Ganglioneuroma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Estudos de Coortes , Feminino , Ganglioneuroma/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos
9.
J Environ Sci Health B ; 54(1): 54-60, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30460875

RESUMO

We report on the rates of decomposition of a group of N-methylcarbamate (NMC) pesticides (carbaryl, carbofuran and propoxur) under pre-determined tropical field conditions. Rates of decomposition for three NMCs were determined at pH 7.08 and T = 20 °C and pH 7.70 and T = 33 °C respectively, as follows: carbaryl (78 days and 69 days); carbofuran (143 days and 83 days) and propoxur (116 days and 79 days). Investigation on methods for removal of NMCs and their phenolic decomposition products shows that activated charcoal outperforms zeolite, alumina, diatomaceous earth, cellulose and montmorillonite clay in the removal of both NMCs and phenols from aqueous solution. Furthermore, metal complexation studies on the NMCs and phenols showed that Fe (III) forms a complex with isopropoxyphenol (IPP) within which the Fe:IPP ratio is 1:3, indicative of the formation of a metal chelate complex with the formula Fe(IPP)3.


Assuntos
Carbamatos/química , Metais/química , Praguicidas/química , Praguicidas/isolamento & purificação , Bentonita/química , Biodegradação Ambiental , Carbaril/química , Carbaril/isolamento & purificação , Carbofurano/química , Carbofurano/isolamento & purificação , Celulose/química , Argila/química , Hidrólise , Fenóis/química , Propoxur/química , Propoxur/isolamento & purificação , Soluções/química , Clima Tropical , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Zeolitas/química
10.
Annu Rev Entomol ; 63: 575-598, 2018 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-29068707

RESUMO

Body size is a key life-history trait influencing all aspects of an organism's biology. Ants provide an interesting model for examining body-size variation because of the high degree of worker polymorphism seen in many taxa. We review worker-size variation in ants from the perspective of factors internal and external to the colony that may influence body-size distributions. We also discuss proximate and ultimate causes of size variation and how variation in worker size can promote worker efficiency and colony fitness. Our review focuses on two questions: What is our current understanding of factors influencing worker-size variation? And how does variation in body size benefit the colony? We conclude with recommendations for future work aimed at addressing current limitations and ask, How can we better understand the contribution of worker body-size variation to colony success? And, what research is needed to address gaps in our knowledge?


Assuntos
Formigas , Variação Biológica da População , Tamanho Corporal , Animais , Evolução Biológica , Interação Gene-Ambiente , Características de História de Vida
11.
Histopathology ; 69(6): 930-936, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27454570

RESUMO

AIMS: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. METHODS AND RESULTS: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. CONCLUSION: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.


Assuntos
Neoplasias dos Seios Paranasais/genética , Sarcoma/genética , Adulto , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Coativador 1 de Receptor Nuclear/genética , Proteínas de Fusão Oncogênica/genética , Fatores de Transcrição Box Pareados/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores , Fatores de Transcrição/genética
12.
Chaos ; 26(1): 013103, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26826855

RESUMO

Measurements of Lagrangian single-point and multiple-point statistics in a quasi-two-dimensional stratified layer system are reported. The system consists of a layer of salt water over an immiscible layer of Fluorinert and is forced electromagnetically so that mean-squared vorticity is injected at a well-defined spatial scale ri. Simultaneous cascades develop in which enstrophy flows predominately to small scales whereas energy cascades, on average, to larger scales. Lagrangian correlations and one- and two-point displacements are measured for random initial conditions and for initial positions within topological centers and saddles. Some of the behavior of these quantities can be understood in terms of the trapping characteristics of long-lived centers, the slow motion near strong saddles, and the rapid fluctuations outside of either centers or saddles. We also present statistics of Lagrangian velocity fluctuations using energy spectra in frequency space and structure functions in real space. We compare with complementary Eulerian velocity statistics. We find that simultaneous inverse energy and enstrophy ranges present in spectra are not directly echoed in real-space moments of velocity difference. Nevertheless, the spectral ranges line up well with features of moment ratios, indicating that although the moments are not exhibiting unambiguous scaling, the behavior of the probability distribution functions is changing over short ranges of length scales. Implications for understanding weakly forced 2D turbulence with simultaneous inverse and direct cascades are discussed.

13.
Adv Anat Pathol ; 21(3): 151-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24713984

RESUMO

Adrenocortical carcinoma is a rare endocrine tumor with a poor prognosis. These tumors can be diagnostically challenging, and diagnostic algorithms and criteria continue to be suggested. Myxoid and oncocytic variants are important to recognize to not confuse with other tumors. In addition, the diagnostic criteria are different for oncocytic adrenal carcinomas than conventional carcinomas. Adrenocortical carcinomas usually occur in adults, but can also occur in children. In children these tumors are diagnostically challenging as the histologic features of malignancy seen in an adult tumor may not be associated with aggressive disease in a child. Adrenocortical carcinomas occur with increased frequency in Beckwith-Wiedemann and Li-Fraumeni syndromes, but most occur sporadically. Gene expression profiling by transcriptome analysis can discriminate adrenocortical carcinomas from adenomas and divide carcinomas into prognostic groups. The increasing understanding of the pathogenesis of these tumors may provide increasing treatment targets for this aggressive tumor.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/patologia , Humanos , Gradação de Tumores , Prognóstico
14.
JCEM Case Rep ; 2(1): luad143, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38192879

RESUMO

Estrogen-secreting adrenocortical carcinoma (ACC) is exceedingly rare, representing 1% to 2% of all ACCs. We present a case of a 65-year-old man diagnosed with an estrogen-secreting, 4.3-cm right adrenal mass discovered during work-up for bilateral gynecomastia. Gynecomastia and hyperestrogenism resolved after laparoscopic adrenalectomy, and pathology was reported as adrenocortical adenoma. However, 5 years later, he again developed bilateral gynecomastia because of recurrent hyperestrogenism. Imaging revealed multiple metastases in the abdomen. Urine steroid profiling demonstrated increased androgen precursors, androgen metabolites, and glucocorticoid precursors. Ultrasound-guided biopsy of one of the metastases confirmed ACC. Initial therapy included debulking surgery with removal of metastatic lesions. Mitotane therapy was initiated 4 weeks later along with hydrocortisone for anticipated mitotane-induced adrenal insufficiency. Histopathology from the adrenalectomy specimen 5 years earlier was rereviewed and confirmed ACC. Estrogen-secreting adrenal tumors are exceedingly rare, and the majority are malignant. This case underlines the importance of making an initial accurate diagnosis of adrenal malignancy that allows better surgical planning and appropriate monitoring. Indeterminate imaging characteristics of the adrenal mass, as well as the presentation with estrogen excess, suggested an elevated risk for ACC. Initial pathology-based misdiagnosis illustrates the need for an expert adrenal pathologist to review these rare tumors.

15.
IEEE Trans Vis Comput Graph ; 30(1): 913-923, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37906495

RESUMO

Interaction is critical for data analysis and sensemaking. However, designing interactive physicalizations is challenging as it requires cross-disciplinary knowledge in visualization, fabrication, and electronics. Interactive physicalizations are typically produced in an unstructured manner, resulting in unique solutions for a specific dataset, problem, or interaction that cannot be easily extended or adapted to new scenarios or future physicalizations. To mitigate these challenges, we introduce a computational design pipeline to 3D print network physicalizations with integrated sensing capabilities. Networks are ubiquitous, yet their complex geometry also requires significant engineering considerations to provide intuitive, effective interactions for exploration. Using our pipeline, designers can readily produce network physicalizations supporting selection-the most critical atomic operation for interaction-by touch through capacitive sensing and computational inference. Our computational design pipeline introduces a new design paradigm by concurrently considering the form and interactivity of a physicalization into one cohesive fabrication workflow. We evaluate our approach using (i) computational evaluations, (ii) three usage scenarios focusing on general visualization tasks, and (iii) expert interviews. The design paradigm introduced by our pipeline can lower barriers to physicalization research, creation, and adoption.

16.
Commun Med (Lond) ; 4(1): 190, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363031

RESUMO

BACKGROUND: Deep learning techniques excel at identifying tumor-infiltrating lymphocytes (TILs) and immune phenotypes in hematoxylin and eosin (H&E)-stained slides. However, their ability to elucidate detailed functional characteristics of diverse cellular phenotypes within tumor immune microenvironment (TME) is limited. We aimed to enhance our understanding of cellular composition and functional characteristics across TME regions and improve patient stratification by integrating H&E with adjacent immunohistochemistry (IHC) images. METHODS: A retrospective study was conducted on patients with Human Papillomavirus-positive oropharyngeal squamous cell carcinoma (OPSCC). Using paired H&E and IHC slides for 11 proteins, a deep learning pipeline was used to quantify tumor, stroma, and TILs in the TME. Patients were classified into immune inflamed (IN), immune excluded (IE), or immune desert (ID) phenotypes. By registering the IHC and H&E slides, we integrated IHC data to capture protein expression in the corresponding tumor regions. We further stratified patients into specific immune subtypes, such as IN, with increased or reduced CD8+ cells, based on the abundance of these proteins. This characterization provided functional insight into the H&E-based subtypes. RESULTS: Analysis of 88 primary tumors and 70 involved lymph node tissue images reveals an improved prognosis in patients classified as IN in primary tumors with high CD8 and low CD163 expression (p = 0.007). Multivariate Cox regression analysis confirms a significantly better prognosis for these subtypes. CONCLUSIONS: Integrating H&E and IHC data enhances the functional characterization of immune phenotypes of the TME with biological interpretability, and improves patient stratification in HPV( + ) OPSCC.


In this study, we investigated whether differences in the immune cell population surrounding head and neck cancers impact disease progression. We used advanced computer programs to analyze tissue samples from tumors and nearby lymph nodes, a part of the immune system. These tumor and lymph node samples were stained to show the structure of the tissue and to identify the different types of immune cells present. We grouped patients into different categories based on differences in their immune cells. We found that patients with certain patterns of immune cells tended to have better outcomes. This method could help doctors predict how well patients will respond to treatments.

17.
Cancers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893183

RESUMO

The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20-30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC.

18.
Chemosphere ; 346: 140443, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303394

RESUMO

Pharmaceuticals comprise a complex group of emerging pollutants. Despite the significant number of pharmaceuticals used in veterinary medicine, the input of these compounds into the environment due to livestock activities has been scarcely described. This work assays for the first time in Central America the occurrence of pharmaceuticals in farm wastewater in an area devoted to dairy production, and in the surrounding surface waters. Among 69 monitored pharmaceuticals, a total of eight compounds were detected in wastewater samples collected from seven dairy farms after three sampling campaigns. Six pharmaceuticals were considered either of high (albendazole, lovastatin and caffeine) or intermediate estimated hazard (ciprofloxacin, acetaminophen and ketoprofen) based on the HQ approach, while 26% of the samples were considered of high estimated hazard according to the cumulative ∑HQ approach. Similarly, when ecotoxicological tests were applied, all the samples showed some level of toxicity towards Daphnia magna, and most samples towards Vibrio fischeri and Lactuca sativa. Fourteen pharmaceuticals were detected in surface water samples collected in the surroundings of the dairy production farms, including rural and urban areas. Seven out of these compounds showed high estimated risk (risperidone, diphenhydramine, trimethoprim, fluoxetine, ofloxacin, caffeine and ibuprofen), while three (gemfibrozil, ciprofloxacin and cephalexin) exhibited intermediate estimated risk. In a similar worrisome way, 27% of these samples were estimated to pose high environmental risk according to the pharmaceutical content. Despite being nontoxic for D. magna or V. fischeri, frequent inhibition (>20%) of GI in L. sativa was determined in 34% of surface water samples; such findings raise concern on the apparent inceptive environmental pollution and risk within the area. According to the pharmaceutical content patterns in both kinds of studied matrices, no clear evidence of significant contamination in surface water due to livestock activities could be retrieved, suggesting a main role of urban influence.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , América Latina , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Cafeína , Monitoramento Ambiental , Água , Ciprofloxacina , Preparações Farmacêuticas
19.
Front Microbiol ; 15: 1357839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384273

RESUMO

The biopurification systems (BPS) or biobeds are employed for the treatment of pesticide-containing wastewater of agricultural origin. The use of these devices for pesticide removal requires the proper optimization of the composition of biomixtures (BPS active matrix) according to the target pesticides applied on a specific crop and the available materials used in their elaboration. This work aims to design a biomixture for the simultaneous treatment of several pesticides applied in coffee crops, according to local practices in Costa Rica. Three biomixtures containing either coffee husk, coconut fiber or rice husk (as the lignocellulosic substrate) were applied for the removal of 12 pesticides. The profiles of pesticide elimination and the mineralization of radiolabeled chlorpyrifos (14C-chlorpyrifos) revealed that the best performance was achieved with the coconut fiber biomixture, even though similar detoxification patterns were determined in every biomixture (according to immobilization in Daphnia magna and germination tests in Lactuca sativa). The optimization of this biomixture's composition by means of a central composite design permitted the definition of two optimal compositions (compost:soil:coconut fiber, % v/v) that maximized pesticide removal: i. 29:7.3:63.7 and ii. 11:7.3:81.7. The validation of these optimized compositions also included the use of an alternative soil from another coffee farm and resulted in overall DT50 values of 7.8-9.0 d for the pesticide mixture. Considering the removal kinetics in the optimized biomixture, a 1 m3 BPS prototype was dimensioned to be eventually used in local coffee farms. This work provides relevant information for the design and implementation of BPS at on-farm conditions for the treatment of pesticide-containing wastewater of a major crop.

20.
Lancet Glob Health ; 12(2): e331-e340, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190831

RESUMO

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.


Assuntos
Cuidados Críticos , Estado Terminal , Humanos , Criança , Adolescente , Consenso , Estado Terminal/terapia , Técnica Delphi , Coleta de Dados
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