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1.
J Shoulder Elbow Surg ; 32(11): 2371-2375, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37327990

RESUMEN

BACKGROUND: Many factors contribute to the risk of surgical-site infection (SSI) following total shoulder arthroplasty (TSA). Operative time is a modifiable factor that may contribute to SSI occurrence after TSA. This study aimed to determine the correlation between operative time and SSI following TSA. MATERIALS AND METHODS: By use of the American College of Surgeons National Surgical Quality Improvement Program database, a total of 33,987 patient records were queried from 2006 to 2020 and sorted by operative time and the development of an SSI in the 30-day postoperative period. Odds ratios for the development of an SSI were calculated based on operative time. RESULTS: An SSI developed in the 30-day postoperative period in 169 of the 33,470 patients in this study, resulting in an overall SSI rate of 0.50%. A positive correlation was identified between operative time and the SSI rate. An inflection point was identified at an operative time of 180 minutes, with a significant increase in the rate of SSI occurrence for operative times >180 minutes. DISCUSSION AND CONCLUSION: Increased operative time was shown to be strongly correlated with an increased risk of SSI within 30 days following surgery, with a significant inflection point at 180 minutes. The target operative time for TSA should be <180 minutes to reduce the risk of SSI.

2.
Infect Immun ; 89(5)2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33558320

RESUMEN

Enterotoxigenic Escherichia coli (ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an "open-aperture" approach to capture all potential conserved ETEC surface antigens, in which we mined the genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n = 118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n = 52) and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens, including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children <2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (noncanonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings may inform vaccine design efforts to complement existing approaches.


Asunto(s)
Inmunidad Adaptativa , Antígenos Bacterianos/inmunología , Escherichia coli Enterotoxigénica/inmunología , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/inmunología , Interacciones Huésped-Patógeno/inmunología , Adhesinas Bacterianas/genética , Adhesinas Bacterianas/inmunología , Susceptibilidad a Enfermedades , Humanos , Virulencia , Factores de Virulencia/genética , Factores de Virulencia/inmunología
3.
Eur J Neurosci ; 54(2): 4528-4549, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34043854

RESUMEN

Rodent dams seek and gather scattered pups back to the nest (pup retrieval), an essential aspect of maternal care. Systematic analysis of the dynamic sequences of goal-related movements that comprise the entire behavioural sequence, which would be ultimately essential for understanding the underlying neurobiology, is not well-characterized. Here, we present such analysis across 3 days in alloparental female mice (Surrogates or Sur) of two genotypes; Mecp2Heterozygotes (Het), a female mouse model for Rett syndrome and their wild type (WT) siblings. We analysed CBA/CaJ and C57BL/6J WT surrogates for within-strain comparisons. Frame-by-frame analysis over different phases was performed manually using DataVyu software. We previously showed that surrogate Het are inefficient at pup retrieval, by end-point analysis such as latency index and errors. Here, the sequence of searching, pup-approach and successful retrieval streamlines over days for WT, while Het exhibits variations in this pattern. Goal-related movements between Het and WT are similar in other phases, suggesting context-driven atypical patterns in Het during the pup retrieval phase. We identified proximal pup approach and pup grooming as atypical tactile interactions between pups and Het. Day-by-day analysis showed dynamic changes in goal-related movements in individual animals across genotypes and strains. Overall, our approach (1) highlights natural variation in individual mice on different days, (2) establishes a "gold-standard" manually curated dataset to help build behavioural repertoires using machine learning approaches, and (3) suggests atypical tactile sensory processing and possible regression in a female mouse model for Rett syndrome.


Asunto(s)
Síndrome de Rett , Animales , Femenino , Objetivos , Humanos , Conducta Materna , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Síndrome de Rett/genética
4.
Stem Cells ; 38(10): 1332-1347, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32535942

RESUMEN

Osteoblast differentiation of bone marrow-derived human mesenchymal stem cells (hMSC) can be induced by stimulation with canonical Notch ligand, Jagged1, or bone morphogenetic proteins (BMPs). However, it remains elusive how these two pathways lead to the same phenotypic outcome. Since Runx2 is regarded as a master regulator of osteoblastic differentiation, we targeted Runx2 with siRNA in hMSC. This abrogated both Jagged1 and BMP2 mediated osteoblastic differentiation, confirming the fundamental role for Runx2. However, while BMP stimulation increased Runx2 and downstream Osterix protein expression, Jagged1 treatment failed to upregulate either, suggesting that canonical Notch signals require basal Runx2 expression. To fully understand the transcriptomic profile of differentiating osteoblasts, RNA sequencing was performed in cells stimulated with BMP2 or Jagged1. There was common upregulation of ALPL and extracellular matrix genes, such as ACAN, HAS3, MCAM, and OLFML2B. Intriguingly, genes encoding components of Notch signaling (JAG1, HEY2, and HES4) were among the top 10 genes upregulated by both stimuli. Indeed, ALPL expression occurred concurrently with Notch activation and inhibiting Notch activity for up to 24 hours after BMP administration with DAPT (a gamma secretase inhibitor) completely abrogated hMSC osteoblastogenesis. Concordantly, RBPJ (recombination signal binding protein for immunoglobulin kappa J region, a critical downstream modulator of Notch signals) binding could be demonstrated within the ALPL and SP7 promoters. As such, siRNA-mediated ablation of RBPJ decreased BMP-mediated osteoblastogenesis. Finally, systemic Notch inhibition using diabenzazepine (DBZ) reduced BMP2-induced calvarial bone healing in mice supporting the critical regulatory role of Notch signaling in BMP-induced osteoblastogenesis.


Asunto(s)
Proteínas Morfogenéticas Óseas/metabolismo , Diferenciación Celular , Osteoblastos/citología , Osteoblastos/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Adulto , Fosfatasa Alcalina/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Dibenzazepinas/farmacología , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Proteína Jagged-1/metabolismo , Ratones Endogámicos C57BL , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Unión Proteica/genética , Cráneo/patología , Factor de Transcripción Sp7/genética , Factor de Transcripción Sp7/metabolismo , Adulto Joven
5.
N Z Vet J ; 68(2): 101-106, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31645214

RESUMEN

Aims: To determine the presence of infection and co-infection of Plasmodium lineages in introduced birds at translocation sites for the North Island saddleback (Philesturnus rufusater), to investigate their role as Plasmodium spp. reservoirs.Methods: Blood samples were collected from introduced bird species, with a special focus on blackbirds (Turdus merula) and song thrushes (Turdus philomelos), at six locations in the North Island of New Zealand that were the origin, or translocation sites, for North Island saddleback. Where available, blood smears were examined, and blood samples were tested using nested PCR with subsequent sequence analysis, for the presence of Plasmodium spp.Results: Of the 55 samples tested using PCR analysis, 39 (71%) were positive for Plasmodium spp., and 28/40 (62%) blood smears were positive for Plasmodium spp. Overall, 31 blood samples were from blackbirds with 28/31 (90%) samples positive for Plasmodium spp. Six distinct avian Plasmodium lineages were identified, including three cosmopolitan lineages; Plasmodium vaughani SYAT05 was detected in 16 samples, Plasmodium matutinum Linn1 in 10 samples and Plasmodium elongatum GRW6 in eight samples. Mixed infections with more than one lineage were detected in 12 samples. Samples from two Australian magpies (Gymnorhina tibicen) were positive for Plasmodium. sp. lineage MYNA02, previously not identified in New Zealand.Conclusions and clinical relevance: This is the first report from New Zealand in which specific Plasmodium spp. mixed infections have been found in introduced birds. Co-infections with several cosmopolitan Plasmodium lineages were identified, as well as the first report in New Zealand of an exotic avian Plasmodium sp. lineage, in Australian magpies. Whilst the role of introduced birds in maintaining and spreading pathogenic avian malaria in New Zealand is unclear, there is a potential infection risk to native birds, especially where distributions overlap.


Asunto(s)
Aves , Especies en Peligro de Extinción , Variación Genética , Especies Introducidas , Malaria Aviar/parasitología , Plasmodium/clasificación , Animales , Malaria Aviar/epidemiología , Nueva Zelanda/epidemiología
6.
Hum Reprod ; 33(7): 1247-1253, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29788136

RESUMEN

STUDY QUESTION: Does the provision of fertility (compared to control) information affect fertility-related knowledge, perceived threat of infertility, anxiety, physical stress and fertility plans in adolescents and emerging adults? SUMMARY ANSWER: The provision of fertility information was associated with increased fertility knowledge (emerging adults) and greater infertility threat (adolescents and emerging adults). WHAT IS KNOWN ALREADY: According to fertility education research, adolescents and emerging adults know less than they should know about fertility topics. Fertility knowledge can be improved through the provision of information in older adults. STUDY DESIGN, SIZE, DURATION: Experimental design. Secondary and university students completed pre-information questionnaires, were randomly assigned via computer to an experimental group, read either fertility (FertiEduc group) or healthy pregnancy information (Control group), and completed post-information questionnaires. Data were collected in group sessions via an online portal. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible participants were aged 16-18 (adolescents) or 21-24 years (emerging adults), childless, not currently pregnant (for men, partner not pregnant) or trying to conceive, presumed fertile and intending to have a child in the future. Of the 255 invited, 208 (n = 93 adolescents, n = 115 emerging adults) participated. The FertiEduc group received 'A Guide to Fertility', four online pages of information about fertility topics (e.g. 'When are men and women most fertile?') and the Control group received four online pages from the National Health Service (NHS) pregnancy booklet 'Baby Bump and Beyond'. Participants completed a questionnaire (fertility knowledge, perceived threat of infertility, anxiety, physical stress and fertility plans, moderators) prior to and after the provision of information. Mixed factorial analysis of variance was used to examine the effects of information provision and hierarchical multiple regression to assess potential moderators of knowledge. MAIN RESULTS AND THE ROLE OF CHANCE: The FertiEduc and Control groups were equivalent on age, gender, disability, relationship status and orientation at baseline. Results showed that fertility information significantly increased fertility knowledge for emerging adults only (P < 0.001) and threat of infertility for emerging adults and adolescents (P = 0.05). The moderators were not significant. Participation in the study was associated with an increase in feelings of anxiety but a decrease in physical stress reactions. Adolescents had more optimal fertility plans compared to emerging adults due to being younger. LIMITATIONS, REASONS FOR CAUTION: This was an experimental study on a self-selected sample of men and women from selected educational institutions and only short term effects of information were studied. WIDER IMPLICATIONS OF THE FINDINGS: Provision of fertility information can have benefits (increased fertility knowledge) but also costs (increase potential threat of infertility). Adolescents find fertility information positive but do not learn from it. Fertility education should be tailored according to age groups and created to minimise negative effects. Longitudinal examination of the effects of fertility information in multi-centre studies is warranted and should include measures of perceived threat of infertility. STUDY FUNDING/COMPETING INTEREST(S): Cardiff University funded this research. All authors have no conflicts of interest to declare.


Asunto(s)
Fertilidad , Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Parejas Sexuales , Adulto Joven
7.
Mol Psychiatry ; 22(5): 647-655, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28348382

RESUMEN

Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.


Asunto(s)
Cerebelo/fisiopatología , Lóbulo Frontal/fisiopatología , Esquizofrenia/fisiopatología , Adulto , Anciano , Animales , Estudios de Casos y Controles , Cerebelo/patología , Cognición/fisiología , Modelos Animales de Enfermedad , Electroencefalografía/métodos , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Neuronas/patología , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , Ratas , Ratas Long-Evans , Esquizofrenia/patología , Esquizofrenia/terapia , Tálamo/fisiopatología , Estimulación Transcraneal de Corriente Directa/métodos
8.
Mol Psychiatry ; 20(9): 1085-90, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25349162

RESUMEN

The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.


Asunto(s)
Ansiedad/sangre , Ansiedad/líquido cefalorraquídeo , Oxitocina/sangre , Oxitocina/líquido cefalorraquídeo , Adolescente , Adulto , Ansiedad/psicología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Estadística como Asunto , Adulto Joven
9.
Indoor Air ; 26(4): 634-41, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26126994

RESUMEN

Occupants of former methamphetamine laboratories, often residences, may experience increased exposure through the accumulation of the methamphetamine in the organic films that coat skin and indoor surfaces. The objectives of this study were to determine equilibrium partition coefficients of vapor-phase methamphetamine with artificial sebum (AS-1), artificial sebum without fatty acids (AS-2), and real skin surface films, herein called skin oils. Sebum and skin oil-coated filters were exposed to vapor-phase methamphetamine at concentrations ranging from 8 to 159 ppb, and samples were analyzed for exposure time periods from 2 h to 60 days. For a low vapor-phase methamphetamine concentration range of ~8-22 ppb, the equilibrium partition coefficient for AS-1 was 1500 ± 195 µg/g/ppb. For a high concentration range of 98-112 ppb, the partition coefficient was lower, 459 ± 80 µg/g/ppb, suggesting saturation of the available absorption capacity. The low partition coefficient for AS-2 (33 ± 6 µg/g/ppb) suggests that the fatty acids in AS-1 and skin oil are responsible for much high partition coefficients. We predict that the methamphetamine concentration in skin lipids coating indoor surfaces can exceed recommended surface remediation standards even for air concentrations well below 1 ppb.


Asunto(s)
Exposición a Riesgos Ambientales/análisis , Ácidos Grasos/química , Metabolismo de los Lípidos , Metanfetamina/farmacocinética , Absorción Cutánea , Humanos , Metanfetamina/análisis
10.
Indoor Air ; 25(4): 405-14, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25244432

RESUMEN

UNLABELLED: To better understand methamphetamine exposure and risk for occupants of former residential clandestine methamphetamine laboratories, we measured the dynamic accumulation of methamphetamine in skin oil, cotton and polyester (PE) clothing, upholstery, and toy fabric (substrates) exposed to 15-30 ppb (91-183 µg/m(3)) neutral methamphetamine in air for up to 60 days. The average equilibrium partition coefficients at 30% RH, in units of µg of methamphetamine per gram of substrate per ppb, are 3.0 ± 0.2 for a PE baby blanket, 5.6 ± 3.5 for a PE fabric toy, 3.7 ± 0.2 for a PE shirt, 18.3 ± 8.0 for a PE/cotton upholstery fabric, and 1200 ± 570 in skin oil. The partition coefficients at 60% RH are 4.5 ± 0.4, 5.2 ± 2.1, 4.5 ± 0.6, 36.1 ± 3.6, and 1600 ± 1100 µg/(g ppb), respectively. There was no difference in the partition coefficient for a clean and skin-oil-soiled cotton shirt [15.3 ± 2.1 µg/(g ppb) @ 42 days]. Partition coefficients for skin oil may be sensitive to composition. 'Mouthing' of cloth is predicted to be the dominant exposure pathway [60 µg/(kg body weight*ppb)] for a toddler in former meth lab, and indoor air concentrations would have to be very low (0.001 ppb) to meet the recommended reference dose for children. PRACTICAL IMPLICATIONS: Gas-phase methamphetamine transfers to and accumulates on clothing, toys and other fabrics significantly increases risk of ingestion of methamphetamine. Current remediation methods should consider measurement of postremediation gas-phase air concentrations of methamphetamine in addition to surface wipe samples.


Asunto(s)
Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Metanfetamina/análisis , Absorción Cutánea , Textiles/análisis , Humanos , Metanfetamina/química
11.
Artículo en Inglés | MEDLINE | ID: mdl-38218567

RESUMEN

Polyvinylpyrrolidone-functionalized silver nanoparticles (nAgPVP) are popular in consumer products for their colloidal stability and antimicrobial activity. Whole lake additions of nAgPVP cause long term, ecosystem-scale changes in fish populations but the mechanisms underlying this effect are unclear. We have previously shown that in fish, nAgPVP impairs cardiac contractility and Na+/K+-ATPase (NKA) activity in vitro, raising the possibility that heart dysfunction could underlie population-level exposure effects. The goal of this study was to determine if nAgPVP influences the control of heart rate (fh), blood pressure, or cardiac NKA activity in vivo. First, a dose-response curve for the effects of 5 nm nAgPVP on contractility was completed on isometrically contracting ventricular muscle preparations from Arctic char (Salvelinus alpinus) and showed that force production was lowest at 500 µg L-1 and maximum pacing frequency increased with nAgPVP concentration. Stroke volume, cardiac output, and power output were maintained in isolated working heart preparations from brook char (Salvelinus fontinalis) exposed to 700 µg L-1 nAgPVP. Both fh and blood pressure were elevated after 24 h in brook char injected with 700 µg kg body mass-1 nAgPVP and fh was insensitive to modulation with blockers of ß-adrenergic and muscarinic cholinergic receptors. Na+/K+-ATPase activity was significantly lower in heart, but not gill of nAgPVP injected fish. The results indicate that nAgPVP influences cardiac function in vivo by disrupting regulation of the pacemaker and cardiomyocyte ionoregulation. Impaired fh regulation may prevent fish from appropriately responding to environmental or social stressors and affect their ability to survive.


Asunto(s)
Nanopartículas del Metal , Animales , Nanopartículas del Metal/toxicidad , Plata , Ecosistema , Trucha/fisiología , Sodio , Iones , Adenosina Trifosfatasas , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Branquias/metabolismo
12.
Diabetologia ; 56(9): 2021-33, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23760677

RESUMEN

AIMS/HYPOTHESIS: We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. METHODS: We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. RESULTS: pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. CONCLUSIONS/INTERPRETATION: pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.


Asunto(s)
Diabetes Gestacional/metabolismo , Insulina/metabolismo , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Adulto , Diabetes Mellitus Tipo 2/metabolismo , Hígado Graso/metabolismo , Femenino , Humanos , Resistencia a la Insulina/fisiología , Enfermedad del Hígado Graso no Alcohólico , Embarazo
13.
Am J Transplant ; 13(10): 2577-89, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23941128

RESUMEN

Reports have associated non-HLA antibodies, specifically those against angiotensin II type-1 receptor (AT1R), with antibody-mediated kidney graft rejection. However, association of anti-AT1R with graft failure had not been demonstrated. We tested anti-AT1R and donor-specific HLA antibodies (DSA) in pre- and posttransplant sera from 351 consecutive kidney recipients: 134 with biopsy-proven rejection and/or lesions (abnormal biopsy group [ABG]) and 217 control group (CG) patients. The ABG's rate of anti-AT1R was significantly higher than the CG's (18% vs. 6%, p < 0.001). Moreover, 79% of ABG patients with anti-AT1R lost their grafts (vs. 0%, CG), anti-AT1R levels in 58% of those failed grafts increasing posttransplant. With anti-AT1R detectable before DSA, time to graft failure was 31 months-but 63 months with DSA detectable before anti-AT1R. Patients with both anti-AT1R and DSA had lower graft survival than those with DSA alone (log-rank p = 0.007). Multivariate analysis showed that de novo anti-AT1R was an independent predictor of graft failure in the ABG, alone (HR: 6.6), and in the entire population (HR: 5.4). In conclusion, this study found significant association of anti-AT1R with graft failure. Further study is needed to establish causality between anti-AT1R and graft failure and, thus, the importance of routine anti-AT1R monitoring and therapeutic targeting.


Asunto(s)
Autoanticuerpos/sangre , Rechazo de Injerto/inmunología , Supervivencia de Injerto , Trasplante de Riñón , Receptor de Angiotensina Tipo 1/inmunología , Adulto , Autoanticuerpos/inmunología , Biopsia , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Rechazo de Injerto/sangre , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/mortalidad , Antígenos HLA/inmunología , Humanos , Terapia de Inmunosupresión , Enfermedades Renales/sangre , Enfermedades Renales/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Trasplante Homólogo
15.
Mol Cell Probes ; 27(2): 90-7, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23195601

RESUMEN

A nested PCR assay was employed to detect the presence of phytoplasmas in 127 blueberry plants exhibiting typical or a portion of blueberry stunt (BBS) syndrome collected in 2010 and 2011, from 11 commercial farms predominantly located in two counties in New Jersey, USA. Ninety plants exhibiting typical stunt syndrome tested positive for phytoplasma infection. Restriction fragment length polymorphism (RFLP) analysis indicated that two distinct phytoplasmas were associated with BBS-diseased plants. About 95% of phytoplasmas detected were very closely related to BBS phytoplasma strains BBS3-AR (subgroup 16SrI-E) and BBS1-MI (unidentified) identified previously, and 4.4% of phytoplasmas detected belonged to the pigeon pea witches'-broom phytoplasma group (16SrIX). Sequence and phylogenetic analysis of cloned 16S rDNA further indicated the subgroup 16SrI-E related phytoplasmas represented a variant of 16SrI-E reference strain BBS3-AR, while the 16SrIX related phytoplasmas were closely related to juniper witches'-broom (JunWB) phytoplasma (16SrIX-E), representing a 16SrIX-E variant. Ribosomal protein (rp) and secY gene-based phylogenies revealed that BBS3-AR and BBS-NJ 16SrI-E strains belonged to a closely related lineage, while BBS-NJ 16SrIX-E strains and JunWB strains represented two distinct lineages. Single nucleotide polymorphisms (SNPs) analyses of rp and secY gene sequences further revealed that no specific rp gene SNPs and only two specific secY gene SNPS were present between BBS-NJ 16SrI-E strains and BBS3-AR. In contrast, BBS-NJ 16SrIX-E strains/clones had 15 consensus rp SNPs and 28 consensus secY SNPs that separated them from JunWB strains/clones. For the first time, two distinct phytoplasmas that cause BBS-disease in the U.S. was revealed.


Asunto(s)
Arándanos Azules (Planta)/microbiología , Filogenia , Phytoplasma/clasificación , Phytoplasma/genética , Polimorfismo de Nucleótido Simple , Proteínas Bacterianas/genética , ADN Ribosómico , Datos de Secuencia Molecular , New Jersey , Enfermedades de las Plantas/microbiología , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , ARN Ribosómico 16S
16.
APL Bioeng ; 7(2): 026108, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37234844

RESUMEN

Light is recognized as an accurate and noninvasive tool for stimulating excitable cells. Here, we report on a non-genetic approach based on organic molecular phototransducers that allows wiring- and electrode-free tissue modulation. As a proof of concept, we show photostimulation of an in vitro cardiac microphysiological model mediated by an amphiphilic azobenzene compound that preferentially dwells in the cell membrane. Exploiting this optical based stimulation technology could be a disruptive approach for highly resolved cardiac tissue stimulation.

17.
Cells ; 12(13)2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37443709

RESUMEN

Oral cancer patients suffer pain at the site of the cancer. Calcitonin gene related polypeptide (CGRP), a neuropeptide expressed by a subset of primary afferent neurons, promotes oral cancer growth. CGRP also mediates trigeminal pain (migraine) and neurogenic inflammation. The contribution of CGRP to oral cancer pain is investigated in the present study. The findings demonstrate that CGRP-immunoreactive (-ir) neurons and neurites innervate orthotopic oral cancer xenograft tumors in mice. Cancer increases anterograde transport of CGRP in axons innervating the tumor, supporting neurogenic secretion as the source of CGRP in the oral cancer microenvironment. CGRP antagonism reverses oral cancer nociception in preclinical oral cancer pain models. Single-cell RNA-sequencing is used to identify cell types in the cancer microenvironment expressing the CGRP receptor components, receptor activity modifying protein 1 Ramp1 and calcitonin receptor like receptor (CLR, encoded by Calcrl). Ramp1 and Calcrl transcripts are detected in cells expressing marker genes for Schwann cells, endothelial cells, fibroblasts and immune cells. Ramp1 and Calcrl transcripts are more frequently detected in cells expressing fibroblast and immune cell markers. This work identifies CGRP as mediator of oral cancer pain and suggests the antagonism of CGRP to alleviate oral cancer pain.


Asunto(s)
Dolor en Cáncer , Neoplasias de la Boca , Hormonas Peptídicas , Humanos , Ratones , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Calcitonina , Polipéptido alfa Relacionado con Calcitonina , Receptores de Péptido Relacionado con el Gen de Calcitonina/genética , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Dolor en Cáncer/tratamiento farmacológico , Células Endoteliales/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Microambiente Tumoral
18.
Int J Syst Evol Microbiol ; 62(Pt 9): 2279-2285, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22307512

RESUMEN

The pigeon pea witches'-broom phytoplasma group (16SrIX) comprises diverse strains that cause numerous diseases in leguminous trees and herbaceous crops, vegetables, a fruit, a nut tree and a forest tree. At least 14 strains have been reported worldwide. Comparative phylogenetic analyses of the highly conserved 16S rRNA gene and the moderately conserved rplV (rpl22)-rpsC (rps3) and secY genes indicated that the 16SrIX group consists of at least six distinct genetic lineages. Some of these lineages cannot be readily differentiated based on analysis of 16S rRNA gene sequences alone. The relative genetic distances among these closely related lineages were better assessed by including more variable genes [e.g. ribosomal protein (rp) and secY genes]. The present study demonstrated that virtual RFLP analyses using rp and secY gene sequences allowed unambiguous identification of such lineages. A coding system is proposed to designate each distinct rp and secY subgroup in the 16SrIX group.


Asunto(s)
Cytisus , Filogenia , Phytoplasma/clasificación , ADN Bacteriano/genética , Genes Bacterianos , Phytoplasma/genética , Polimorfismo de Longitud del Fragmento de Restricción , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
19.
Phys Med Biol ; 67(9)2022 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-35366658

RESUMEN

Major topics in medical ultrasound rest on the physics of wave propagation through tissue. These include fundamental treatments of backscatter, speed of sound, attenuation, and speckle formation. Each topic has developed its own rich history, lexicography, and particular treatments. However, there is ample evidence to suggest that power law relations are operating at a fundamental level in all the basic phenomena related to medical ultrasound. This review paper develops, from literature over the past 60 years, the accumulating theoretical basis and experimental evidence that point to power law behaviors underlying the most important tissue-wave interactions in ultrasound and in shear waves which are now employed in elastography. The common framework of power laws can be useful as a coherent overview of topics, and as a means for improved tissue characterization.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Sonido , Ultrasonografía
20.
Int J Syst Evol Microbiol ; 61(Pt 12): 2822-2826, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21216914

RESUMEN

A novel phytoplasma, designated strain SoyST1c1, associated with a newly emerging disease in soybean (Glycine max), known as soybean stunt (SoyST), was found in 2002 in a soybean plantation in Alajuela Province, Costa Rica. The same phytoplasma, or a very closely related strain, also infected sweet pepper (Capsicum annuum) with purple vein syndrome (SwPPV) and passion fruit vine (Passiflora edulis) with bud proliferation disease (PasFBP) in the same region. Sequence analysis of cloned 16S rRNA gene sequences (GenBank accession nos FJ226068-FJ226073 and HQ225624-HQ225635) indicated that all three affected plants were infected by phytoplasmas that shared <97.5% sequence similarity with previously described phytoplasmas. The SoyST-causing phytoplasma represents a new taxon, most closely related to phytoplasma group 16SrI and 16SrXII strains. Virtual RFLP analysis indicated that the SoyST-causing phytoplasma and its closely related strains represent a novel 16Sr group, designated 16SrXXXI. Phylogenetic analysis of 16S rRNA gene sequences from the new phytoplasma strains, those previously described as 'Candidatus Phytoplasma spp.' and other distinct, as yet unnamed, phytoplasmas indicated that the SoyST-causing phytoplasma represents a distinct lineage within the aster yellows/stolbur branch on the phylogenetic tree. On the basis of its unique 16S rRNA gene sequence and biological properties, strain SoyST1c1 represents a novel taxon, for which the name 'Candidatus Phytoplasma costaricanum' is proposed with SoyST1c1 as the reference strain.


Asunto(s)
Glycine max/microbiología , Phytoplasma/clasificación , Phytoplasma/aislamiento & purificación , Enfermedades de las Plantas/microbiología , ADN Bacteriano/genética , ADN Ribosómico/genética , Datos de Secuencia Molecular , Filogenia , Phytoplasma/genética , ARN Ribosómico 16S/genética
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