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1.
Nature ; 600(7889): 468-471, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34853470

RESUMO

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.


Assuntos
Pé/anatomia & histologia , Pé/fisiologia , Fósseis , Marcha/fisiologia , Hominidae/classificação , Hominidae/fisiologia , Animais , Arquivos , Feminino , Hominidae/anatomia & histologia , Humanos , Imageamento Tridimensional , Lasers , Masculino , Modelos Biológicos , Pan troglodytes/anatomia & histologia , Pan troglodytes/fisiologia , Fotogrametria , Filogenia , Tanzânia , Ursidae/anatomia & histologia , Ursidae/fisiologia
2.
Am J Emerg Med ; 76: 155-163, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086181

RESUMO

INTRODUCTION: While the relationships between cardiovascular disease (CVD), stress, and financial strain are well studied, the association between recessionary periods and macroeconomic conditions on incidence of disease-specific CVD emergency department (ED) visits is not well established. OBJECTIVES: This retrospective observational study aimed to assess the relationship between macroeconomic trends and CVD ED visits. METHODS: This study uses data from the National Hospital Ambulatory Care Survey (NHAMCS), Federal Reserve Economic Database (FRED), National Bureau of Economic Research (NBER), and CVD groupings from National Vital Statistics (NVS) and Center for Medicare and Medicaid Services (CMS) from 1999 to 2020 to analyze ED visits in relation to macroeconomic indicators and NBER defined recessions and expansions. RESULTS: CVD ED visits grew by 79.7% from 1999 to 2020, significantly more than total ED visits (27.8%, p < 0.001). A national estimate of 213.2 million CVD ED visits, with 22.9 million visits in economic recessions were analyzed. A secondary group including a 6-month period before and after each recession (defined as a "broadened recession") was also analyzed to account for potential leading and lagging effects of the recession, with a total of 50.0 million visits. A significantly higher proportion of CVD ED visits related to heart failure (HF) and other acute ischemic heart diseases (IHD) was observed during recessionary time periods both directly and with a 6-month lead and lag (p < 0.05). The proportion of aortic aneurysm and dissection (AAA) and atherosclerosis (ASVD) ED visits was significantly higher (p = 0.024) in the recession period with a 6-month lead and lag. When controlled for common demographic factors, economic approximations of recession such as the CPI, federal funds rate, and real disposable income were significantly associated with increased CVD ED visits. CONCLUSION: Macroeconomic trends have a significant relationship with the overall mix of CVD ED visits and represent an understudied social determinant of health.


Assuntos
Doenças Cardiovasculares , Recessão Econômica , Idoso , Humanos , Estados Unidos/epidemiologia , Emergências , Determinantes Sociais da Saúde , Medicare , Doenças Cardiovasculares/epidemiologia , Serviço Hospitalar de Emergência
3.
Nutr Neurosci ; 26(9): 842-849, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35900205

RESUMO

Background: The current work involved monitoring two biomarkers in the plasma of children with ASD: the cofactor thiamine that is involved in neurotransmitters modulation for acetylcholine, and the compound histamine, which acts as a neuromodulator by regulating the release of other neurotransmitters. This is the first report to highlight the potential utilization of plasma levels of the selected two brain-related biomarkers in children with ASD.Methods: A total of 43 children with ASD of both genders (age 4-12 years) were involved in this study and compared to age and gender-matched control children (n = 42). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5), followed by an additional assessment using the Childhood Autism Rating Scale (CARS). All participants were Jordanian children on Mediterranean diet, and had no history of chronic illness or medications. Measurement of thiamine and histamine in plasma was performed using enzyme-linked immunosorbent assay (ELISA).Results: The outcomes revealed that average histamine levels (31.7 ± 18.5 ng/ml) of ASD group were 5.3× higher (p < .001) compared to their control (0.013 ± 0.011 ng/ml; 6.03 ± 4.25 ng/ml), while thiamine (10.78 ± 7.49 ng/ml) levels of ASD group were significantly lower (p < .001) than the control (37.92 ± 26.87 ng/ml; 0.209 ± 0.054 ng/ml).Conclusions: The study is proposing that monitoring of the plasma levels of thiamine and histamine as biomarkers for future evaluation and development of ASD therapies and nutritious diets.


Assuntos
Transtorno do Espectro Autista , Humanos , Criança , Masculino , Feminino , Pré-Escolar , Histamina/uso terapêutico , Tiamina , Jordânia , Biomarcadores , Dieta
4.
BMC Pediatr ; 22(1): 590, 2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229781

RESUMO

BACKGROUND: Vitamin and mineral supplements are widely used by children and adults diagnosed with autism spectrum disorder (ASD). Several studies have reported benefits of such supplements in resolving nutritional deficiencies, treating various metabolic problems and improving symptoms and overall quality of life. METHODS: This research survey collected evaluations from 161 people about the effectiveness of ANRC-Essentials Plus (ANRC-EP), a vitamin/mineral/micronutrient supplement designed for children and adults with autism. Although this was an open-label survey, results were compared with a three-month randomized double-blind placebo-controlled study of an earlier version of the supplement. Evaluations included the Parent Global Impressions of Autism (PGIA) and the Overall Benefit/Adverse Effect scale of the National Survey on Treatment Effectiveness for Autism (NSTEA). RESULTS: The participants reported substantially higher Average PGIA Scores than the placebo group in a similar previous study, with an estimated effect size of 0.66. Based on the NSTEA questionnaire, 73% of participants rated the Overall Benefit as Moderate, Good, or Great, with scores that were substantially higher than the NSTEA study found for multi-vitamins, the average of 58 nutraceuticals, and the average of 28 psychiatric and seizure medications. The Overall Adverse Effect score was low (0.25/3.0), similar or slightly higher than other nutraceuticals, and much lower than the average of 28 psychiatric and seizure medications (0.9/3.0). Sub-analysis found that the Overall Benefit of ANRC-EP was not significantly affected by gender, age, autism severity, diet quality, self-limited diet, use of psychiatric or seizure medications, dosage, developmental history, intellectual disability, or seizures. This indicates that ANRC-EP may be beneficial for a wide range of children and adults with ASD. A limitation of this study is the retrospective nature of the survey, and that participants who had good benefits were more likely to respond. CONCLUSIONS: This study found that ANRC-EP had significant benefits for a wide range of symptoms, and low adverse effects.


Assuntos
Transtorno do Espectro Autista , Micronutrientes , Adulto , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Suplementos Nutricionais , Humanos , Minerais/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Convulsões , Vitaminas/uso terapêutico
5.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36362265

RESUMO

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Microbiota , Criança , Humanos , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/terapia , Transtorno do Espectro Autista/metabolismo , Metagenômica , Estresse Oxidativo , Enxofre
6.
Planta ; 255(1): 4, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34841446

RESUMO

MAIN CONCLUSION: Metabolites in Rafflesia-infected and non-infected Tetrastigma were compared which may have applications in Rafflesia propagation. Benzylisoquinoline alkaloids, here reported for the first time in Vitaceae, were abundant in non-infected shoots and may be a form of defense. In Rafflesia-infected shoots, oxylipins, which mediate immune response, were elevated. Endemic to the forests of Southeast Asia, Rafflesia (Rafflesiaceae) is a genus of holoparasitic plants producing the largest flowers in the world, yet completely dependent on its host, the tropical grape vine, Tetrastigma. Rafflesia species are threatened with extinction, making them an iconic symbol of plant conservation. Thus far, propagation has proved challenging, greatly decreasing efficacy of conservation efforts. This study compared the metabolites in the shoots of Rafflesia-infected and non-infected Tetrastigma loheri to examine how Rafflesia infection affects host metabolomics and elucidate the Rafflesia infection process. Results from LC-MS-based untargeted metabolomics analysis showed benzylisoquinoline alkaloids were naturally more abundant in non-infected shoots and are here reported for the first time in the genus Tetrastigma, and in the grape family, Vitaceae. These metabolites have been implicated in plant defense mechanisms and may prevent a Rafflesia infection. In Rafflesia-infected shoots, oxygenated fatty acids, or oxylipins, and a flavonoid, previously shown involved in plant immune response, were significantly elevated. This study provides a preliminary assessment of metabolites that differ between Rafflesia-infected and non-infected Tetrastigma hosts and may have applications in Rafflesia propagation to meet conservation goals.


Assuntos
Magnoliopsida , Parasitos , Vitaceae , Animais , Flores , Reprodução
7.
Brain ; 143(1): 55-68, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834374

RESUMO

MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing MN1 have been reported in individuals with variable neurodevelopmental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres, in 8/10 individuals. Rhombencephalosynapsis has no previously known definitive genetic or environmental causes. Other frequent features included perisylvian polymicrogyria, abnormal posterior clinoid processes and persistent trigeminal artery. MN1 is encoded by only two exons. All mutations, including the recurrent variant p.Arg1295* observed in 8/21 probands, fall in the terminal exon or the extreme 3' region of exon 1, and are therefore predicted to result in escape from nonsense-mediated mRNA decay. This was confirmed in fibroblasts from three individuals. We propose that the condition described here, MN1 C-terminal truncation (MCTT) syndrome, is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Our data show that MN1 plays a critical role in human craniofacial and brain development, and opens the door to understanding the biological mechanisms underlying rhombencephalosynapsis.


Assuntos
Anormalidades Múltiplas/genética , Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Transtornos do Desenvolvimento da Linguagem/genética , Malformações do Sistema Nervoso/genética , Transativadores/genética , Proteínas Supressoras de Tumor/genética , Anormalidades Múltiplas/diagnóstico por imagem , Adolescente , Artéria Basilar/anormalidades , Artéria Basilar/diagnóstico por imagem , Artérias Carótidas/anormalidades , Artérias Carótidas/diagnóstico por imagem , Vermis Cerebelar/anormalidades , Vermis Cerebelar/diagnóstico por imagem , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Criança , Pré-Escolar , Estudos de Coortes , Hibridização Genômica Comparativa , Anormalidades Craniofaciais/diagnóstico por imagem , Feminino , Fibroblastos/metabolismo , Humanos , Imageamento Tridimensional , Lactente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Malformações do Sistema Nervoso/diagnóstico por imagem , Degradação do RNAm Mediada por Códon sem Sentido , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Síndrome , Tomografia Computadorizada por Raios X , Sequenciamento do Exoma , Sequenciamento Completo do Genoma
8.
Int J Mol Sci ; 22(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34830087

RESUMO

The kinase interaction motif protein tyrosine phosphatases (KIM-PTPs), HePTP, PTPSL and STEP, are involved in the negative regulation of mitogen-activated protein kinase (MAPK) signalling pathways and are important therapeutic targets for a number of diseases. We have used VSpipe, a virtual screening pipeline, to identify a ligand cluster distribution that is unique to this subfamily of PTPs. Several clusters map onto KIM-PTP specific sequence motifs in contrast to the cluster distribution obtained for PTP1B, a classic PTP that mapped to general PTP motifs. Importantly, the ligand clusters coincide with previously reported functional and substrate binding sites in KIM-PTPs. Assessment of the KIM-PTP specific clusters, using ligand efficiency index (LEI) plots generated by the VSpipe, ascertained that the binders in these clusters reside in a more drug-like chemical-biological space than those at the active site. LEI analysis showed differences between clusters across all KIM-PTPs, highlighting a distinct and specific profile for each phosphatase. The most druggable cluster sites are unexplored allosteric functional sites unique to each target. Exploiting these sites may facilitate the delivery of inhibitors with improved drug-like properties, with selectivity amongst the KIM-PTPs and over other classical PTPs.


Assuntos
Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Inibidores Enzimáticos/química , Sistema de Sinalização das MAP Quinases , Proteínas Tirosina Fosfatases , Sítio Alostérico , Humanos , Ligantes , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Proteínas Tirosina Fosfatases/química
9.
Hum Mutat ; 41(3): 641-654, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31769566

RESUMO

Visceral myopathy with abnormal intestinal and bladder peristalsis includes a clinical spectrum with megacystis-microcolon intestinal hypoperistalsis syndrome and chronic intestinal pseudo-obstruction. The vast majority of cases are caused by dominant variants in ACTG2; however, the overall genetic architecture of visceral myopathy has not been well-characterized. We ascertained 53 families, with visceral myopathy based on megacystis, functional bladder/gastrointestinal obstruction, or microcolon. A combination of targeted ACTG2 sequencing and exome sequencing was used. We report a molecular diagnostic rate of 64% (34/53), of which 97% (33/34) is attributed to ACTG2. Strikingly, missense mutations in five conserved arginine residues involving CpG dinucleotides accounted for 49% (26/53) of disease in the cohort. As a group, the ACTG2-negative cases had a more favorable clinical outcome and more restricted disease. Within the ACTG2-positive group, poor outcomes (characterized by total parenteral nutrition dependence, death, or transplantation) were invariably due to one of the arginine missense alleles. Analysis of specific residues suggests a severity spectrum of p.Arg178>p.Arg257>p.Arg40 along with other less-frequently reported sites p.Arg63 and p.Arg211. These results provide genotype-phenotype correlation for ACTG2-related disease and demonstrate the importance of arginine missense changes in visceral myopathy.


Assuntos
Actinas/genética , Substituição de Aminoácidos , Arginina , Estudos de Associação Genética , Predisposição Genética para Doença , Pseudo-Obstrução Intestinal/diagnóstico , Pseudo-Obstrução Intestinal/genética , Mutação , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Adulto , Colo/anormalidades , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Fenótipo , Bexiga Urinária/anormalidades , Sequenciamento do Exoma , Adulto Jovem
10.
Ann Neurol ; 86(5): 695-703, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31461177

RESUMO

OBJECTIVE: To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed Diseases Program. METHODS: Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing, and the phage-display assay, VirScan, for viral immune responses. An etiological diagnosis was established postmortem. RESULTS: Using VirScan, enrichment of dengue viral antibodies was detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months antemortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency, and sequencing of the virus demonstrated wild-type dengue virus in the central nervous system. INTERPRETATION: Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self-limiting, and chronic dengue infections have not been previously reported. Our findings suggest that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019;86:695-703.


Assuntos
Dengue/complicações , Dengue/patologia , Encefalite Viral/etiologia , Encefalite Viral/patologia , Doença Crônica , Demência , Vírus da Dengue , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Exp Biol ; 223(Pt 22)2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33077640

RESUMO

Disorders of the volume, pressure or circulation of the cerebrospinal fluid (CSF) lead to disease states in both newborns and adults; despite this significance, there is uncertainty regarding the basic mechanics of the CSF. The suboccipital muscles connect to the dura surrounding the spinal cord, forming a complex termed the 'myodural bridge'. This study tests the hypothesis that the myodural bridge functions to alter the CSF circulation. The suboccipital muscles of American alligators were surgically exposed and electrically stimulated simultaneously with direct recordings of CSF pressure and flow. Contraction of the suboccipital muscles significantly changed both CSF flow and pressure. By demonstrating another influence on CSF circulation and pulsatility, the present study increases our understanding of the mechanics underlying the movement of the CSF.


Assuntos
Jacarés e Crocodilos , Adulto , Animais , Dura-Máter , Humanos , Recém-Nascido , Movimento , Músculos do Pescoço/anatomia & histologia
12.
Appl Opt ; 59(29): 9174-9184, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33104629

RESUMO

Using a Monte Carlo algorithm to simulate the scattering of sunlight in an atmosphere-ocean system, the degree of circular polarization of light in the ocean has been calculated at multiple depths and directions. In this system circularly polarized light is produced by the reflection of light from beneath the surface at an incident angle greater than the critical angle. We present the results of these simulations for different solar angles, wavelengths of light, and models that include the presence of aerosols in the atmosphere and hydrosols in the water.

13.
BMC Pediatr ; 20(1): 557, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317469

RESUMO

BACKGROUND: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism. METHODS: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods. RESULTS: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave-one-out cross-validation allowed classification of samples as belonging to one of the two groups of mothers with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules. CONCLUSIONS: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.


Assuntos
Transtorno do Espectro Autista , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Ácido Fólico , Humanos , Mães
14.
Can Vet J ; 61(5): 521-524, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32355352

RESUMO

A 5-year-old llama was presented for unilateral cryptorchidism. Clinical findings included an abdominally retained right testicle. Surgical treatment consisted of laparoscopic removal of the abdominally retained testicle and routine closed castration of the descended testicle, which is presented as a therapeutic option for cryptorchidectomy. Key clinical message: Laparoscopic exploration and castration should be considered as a suitable surgical treatment for a llama with abdominally retained testicles.


Cryptorchidectomie laparoscopique chez un lama mature. Un lama âgé de 5 ans fut présenté avec une cryptorchidie unilatérale. Les trouvailles cliniques incluaient une rétention abdominale du testicule droit. Le traitement chirurgical consistait en un retrait par laparoscopie du testicule retenu dans la cavité abdominale et une castration fermée de routine du testicule descendu, ce qui est présenté comme une option thérapeutique lors de cryptorchidectomie.Message clinique clé :L'exploration laparoscopique et la castration devraient être considérées comme un traitement chirurgical approprié pour un lama avec des testicules retenus dans l'abdomen.(Traduit par Dr Serge Messier).


Assuntos
Camelídeos Americanos , Criptorquidismo/cirurgia , Criptorquidismo/veterinária , Laparoscopia/veterinária , Animais , Masculino , Orquiectomia/veterinária
15.
Mo Med ; 117(5): 475-479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33311758

RESUMO

At A.T. Still University's Kirksville College of Osteopathic Medicine, Still Caring Health Connection is a student-run organization that hosts free clinic nights for the underserved. The clinics are beneficial for patients and medical students because patients receive needed medical attention and medical students get early clinical exposure. During the clinics, medical students use portable ultrasound machines to guide diagnoses. When surveyed about their use of ultrasound on clinic nights, most students responded positively.


Assuntos
Medicina Osteopática , Clínica Dirigida por Estudantes , Estudantes de Medicina , Instituições de Assistência Ambulatorial , Humanos , Ultrassonografia
16.
Artigo em Inglês | MEDLINE | ID: mdl-30259097

RESUMO

American alligators (Alligator mississippiensis) held inverted exhibit tonic immobility, combining unresponsiveness with flaccid paralysis. We hypothesize that inverting the alligator causes a gravitationally promoted increase in right aortic blood flowing through the foramen of Panizza, with a concurrent decrease in blood flow through the primary carotid, and thereby of cerebral perfusion. Inverting the alligator results in displacement of the liver, post-pulmonary septum, and the heart. EKG analysis revealed a significant decrease in heart rate following inversion; this decrease was maintained for approximately 45 s after inversion which is in general agreement with the total duration of tonic immobility in alligators (49 s). Doppler ultrasonography revealed that following inversion of the alligator, there was a reversal in direction of blood flow through the foramen of Panizza, and this blood flow had a significant increase in velocity (compared to the foraminal flow in the prone alligator). There was an associated significant decrease in the velocity of blood flow through the primary carotid artery once the alligator was held in the supine position. Tonic immobility in the alligator appears to be a form of vasovagal syncope which arises, in part, from the unique features of the crocodilian heart.


Assuntos
Jacarés e Crocodilos/fisiologia , Hemodinâmica/fisiologia , Postura/fisiologia , Jacarés e Crocodilos/anatomia & histologia , Animais , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiologia , Eletrocardiografia , Coração/anatomia & histologia , Coração/diagnóstico por imagem , Coração/fisiologia , Fígado/diagnóstico por imagem , Fígado/fisiologia , Movimento/fisiologia , Síncope/veterinária , Ultrassonografia Doppler
17.
Bioorg Med Chem Lett ; 28(6): 993-996, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29501395

RESUMO

Sesquiterpene compounds are widely known for their numerous pharmacological activities. Herein the focus of the authors was on α-Santonin, a sesquiterpene lactone from the Artemisia genus: the aim was to determine whether α-Santonin could be considered in the treatment of inflammation and pain. To this purpose, a small series of derivatives was designed and screened in silico against the enzyme COX-2 along with the parent compound. Drug-likeness parameters were also assessed. The compounds were eventually synthesized, and few were tested to determine their efficacy in the inhibition of COX-2 activity and expression. Overall, compound A2 was the only one with a detectable inhibitory potential of COX-2 activity whilst two of its ether derivatives demonstrated improved ability in the inhibition of COX-2 expression.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Desenho de Fármacos , Santonina/farmacologia , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Santonina/síntese química , Santonina/química , Relação Estrutura-Atividade
18.
Anaerobe ; 49: 121-131, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29274915

RESUMO

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.


Assuntos
Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/microbiologia , Bactérias/metabolismo , Fezes/química , Microbioma Gastrointestinal , 2-Propanol/análise , 2-Propanol/metabolismo , Adolescente , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Biomarcadores/análise , Biomarcadores/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Fezes/microbiologia , Feminino , Humanos , Masculino , Neurotransmissores/análise , Neurotransmissores/metabolismo
19.
Molecules ; 23(2)2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29414924

RESUMO

The use of computational tools for virtual screening provides a cost-efficient approach to select starting points for drug development. We have developed VSpipe, a user-friendly semi-automated pipeline for structure-based virtual screening. VSpipe uses the existing tools AutoDock and OpenBabel together with software developed in-house, to create an end-to-end virtual screening workflow ranging from the preparation of receptor and ligands to the visualisation of results. VSpipe is efficient and flexible, allowing the users to make choices at different steps, and it is amenable to use in both local and cluster mode. We have validated VSpipe using the human protein tyrosine phosphatase PTP1B as a case study. Using a combination of blind and targeted docking VSpipe identified both new and known functional ligand binding sites. Assessment of different binding clusters using the ligand efficiency plots created by VSpipe, defined a drug-like chemical space for development of PTP1B inhibitors with potential applications to other PTPs. In this study, we show that VSpipe can be deployed to identify and compare different modes of inhibition thus guiding the selection of initial hits for drug discovery.


Assuntos
Biologia Computacional/métodos , Descoberta de Drogas/métodos , Software , Regulação Alostérica , Sítios de Ligação , Domínio Catalítico , Humanos , Ligantes , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Proteínas Tirosina Fosfatases/química , Relação Quantitativa Estrutura-Atividade
20.
J Christ Nurs ; 35(3): 191-197, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29863515

RESUMO

African Americans have increased rates of overweight and obesity and are least likely to participate in family meals compared with other racial groups. A Family Meal Challenge (FMC) was developed with the objective of empowering individuals to eat healthy meals together as a family. The FMC was presented through four classes in three churches, two faith-based ministries, and two community service programs in health disparity zip codes. Surveys (N = 257) indicated a positive response. Engaging participants and teaching the benefits of eating healthy family meals in a faith-based environment are feasible and may increase the frequency of family meals. Information is provided to create and implement an FMC in any faith setting.


Assuntos
Cristianismo , Culinária , Família/psicologia , Refeições/psicologia , Poder Psicológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Currículo , Educação Continuada em Enfermagem/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
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