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Control of algal blooms and associated biologically-induced water quality risks in drinking reservoirs is problematic. Copper sulphate (CuSO4) treatment is one intervention that has been utilised for >100 years. Evidence indicates a favourable short-term reduction in Cyanobacterial biomass (e.g. bloom termination), but here we indicate that it may also increase longer-term water quality risk. In 2022, we investigated the impacts of CuSO4 spraying on Cyanobacterial communities and nutrient levels within a drinking water supply reservoir using environmental DNA (eDNA) to assess community shifts, alongside monitoring nutrient fractions, orthophosphate (OP) and total phosphate (TP), post-treatment. CuSO4 application successfully reduced Cyanobacterial abundance, however elimination of Cyanobacteria resulted in a shift in bacterial dominance favouring Planctomycetota throughout the summer and a combination of Actinobacteriota and Verrucomicrobiota, throughout autumn. As Cyanobacterial abundance recovered post-treatment, Cyanobacterial genera demonstrated greater diversity compared to only three Cyanobacterial genera present across samples pre-treatment, and included taxa associated with water quality risk (e.g. taste and odour (T&O) metabolite and toxin producers). The increase in Cyanobacteria post-treatment was attributed to an increase in biologically available nutrients, primarily a significant increase in OP. Overall, findings suggest that the significant shift in biodiversity likely induces a less stable ecosystem with greater plasticity of response to changing environmental and biogeochemical variables. Legacy implications of CuSO4 spraying, in terms of shifts in ecosystem and nutrient balance over time, may have implications for drinking water quality, but importantly also for reservoir management options. As such, the effects of CuSO4 spraying should be considered carefully before consideration as a contender for in-reservoir biological control.
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Sulfato de Cobre , Cianobacterias , Calidad del Agua , Cianobacterias/efectos de los fármacos , EutrofizaciónRESUMEN
INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.
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Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Humanos , Anciano , Estudios Prospectivos , Estudios de Factibilidad , Australia , Paro Cardíaco Extrahospitalario/terapia , Hospitales , Reperfusión , Estudios RetrospectivosRESUMEN
Geosmin synthase (geoA) and 2-MIB cyclase (mic) are key biosynthetic genes responsible for the production of taste and odour (T&O) compounds, geosmin and 2-MIB. These T&O compounds are becoming an increasing global problem for drinking water supplies. It is thought that geosmin and 2-MIB may be linked to, or exacerbated by, a variety of different environmental and nutrient triggers. However, to the best of our knowledge, no studies to date have evaluated the combined effects of seasonality, temperature, and nutrient concentrations on geoA and mic copy numbers in conjunction with T&O concentrations. In this study, environmental triggers behind geosmin and 2-MIB production were investigated in nine reservoirs across Wales, U.K. between July 2019 - August 2020. The abundance of geoA and mic were quantified through quantitative Polymerase Chain Reaction (qPCR). Temporal changes in geoA and geosmin concentrations revealed geoA to be an indicator of monthly geosmin concentrations, although only when geosmin concentrations exceeded 100 ng L-1. Model analysis of a reservoir with elevated geosmin concentrations revealed geoA to be significantly associated with mean temperature (p < 0.001) and the nutrients dissolved reactive silicate (p < 0.001), dissolved iron (p < 0.001), total inorganic nitrogen to phosphorous ratio (TIN:TP) (p < 0.001) and ammonium to nitrate ratio (NH4+:NO3-) (p < 0.001). Sulphate also demonstrated a significant positive linear relationship with geoA (p < 0.001). For mic analysis, NH4+:NO3- was significantly associated with mic (p < 0.05) and an association with dissolved reactive silicate was also observed (p = 0.084). Within this study we also report extreme variance in gene copy numbers between the study seasons. No consistent relationship could be determined for mic copy numbers mL-1 and 2-MIB (ng L-1). The findings from this study indicate that TIN:TP and NH4+:NO3- serve as good predictors for elevated geoA and mic, along with negative linear relationships observed for mean temperature and dissolved reactive silicate. Overall, our findings demonstrate the importance of nutrient concentrations, nutrient ratios and temperature for evidence based predictive capacity of taste and odour events in drinking water reservoirs.
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Agua Potable , Gusto , Canfanos , Agua Potable/análisis , Naftoles/análisis , Nutrientes/análisis , Odorantes/análisisRESUMEN
Objective: Tracheostomy is a common procedure that requires management by a multidisciplinary team of health care providers across a range of surgical and nonsurgical specialties. Nonsurgical health care providers have demonstrated a lack of knowledge and confidence in tracheostomy care, which improve with tracheostomy education programs. However, tracheostomy care is rarely included in preresidency medical education. The purpose of this study is to evaluate the effectiveness of a tracheostomy care video on third-year medical students' knowledge of and confidence in performing tracheostomy care. Methods: Prior to beginning clinical rotations, third-year medical students completed a 10-question tracheostomy care knowledge test (100 points total) and 11-question confidence survey (110 points total). After watching an 18-minute teaching video on tracheostomy care, students repeated the knowledge test and confidence survey. Results: An overall 147 medical students completed the educational module. After they watched the tracheostomy education video, their average score on the knowledge test improved from 57.8 to 88.9 out of 100 (P < .0001), and their average rating in confidence improved from 12.7 to 49.1 out of 110 (P < .0001). Students rated the helpfulness of the video a 7.4 out of 10. Discussion: Medical students' knowledge of tracheostomy care and confidence in caring for patients with tracheostomies improved after watching the video. Tracheostomy education should be included in early medical education so that future physicians of various specialties can better care for this patient population. Implications for Practice: Internet-published videos are an accessible educational resource with great potential application to various topics within otolaryngology, including tracheostomy care.
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Accelerated soil-nitrifier activity and rapid nitrification are the cause of declining nitrogen-use efficiency (NUE) and enhanced nitrous oxide (N2O) emissions from farming. Biological nitrification inhibition (BNI) is the ability of certain plant roots to suppress soil-nitrifier activity, through production and release of nitrification inhibitors. The power of phytochemicals with BNI-function needs to be harnessed to control soil-nitrifier activity and improve nitrogen-cycling in agricultural systems. Transformative biological technologies designed for genetic mitigation are needed, so that BNI-enabled crop-livestock and cropping systems can rein in soil-nitrifier activity, to help reduce greenhouse gas (GHG) emissions and globally make farming nitrogen efficient and less harmful to environment. This will reinforce the adaptation or mitigation impact of other climate-smart agriculture technologies.
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Agricultura/métodos , Gases de Efecto Invernadero , Productos Agrícolas/metabolismo , Productos Agrícolas/fisiología , Nitrificación , Óxido Nitroso/metabolismo , Sorghum/genética , Sorghum/metabolismo , Triticum/genética , Triticum/metabolismoRESUMEN
Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABAA receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic doses of ketamine. Thus GABAergic deficits may causally contribute to depressive disorders, while antidepressant therapies may enhance GABAergic synaptic transmission. Here we tested the hypothesis that sustained enhancement of GABAergic transmission alone is sufficient to elicit antidepressant-like behavior, using disinhibition of GABAergic interneurons. We focused on somatostatin-positive (SST+) GABAergic interneurons because of evidence that their function is compromised in MDD. To disinhibit SST+ interneurons, we inactivated the γ2 subunit gene of GABAA receptors selectively in these neurons (SSTCre:γ2f/f mice). Loss of inhibitory synaptic input resulted in increased excitability of SST+ interneurons. In turn, pyramidal cell targets of SST+ neurons showed an increased frequency of spontaneous inhibitory postsynaptic currents. The behavior of SSTCre:γ2f/f mice mimicked the effects of anxiolytic and antidepressant drugs in a number of behavioral tests, without affecting performance in a spatial learning- and memory-dependent task. Finally, brain extracts of SSTCre:γ2f/f mice showed decreased phosphorylation of the eukaryotic elongation factor eEF2, reminiscent of the effects of ketamine. Importantly, these effects occurred without altered activity of the mammalian target of rapamycin pathway nor did they involve altered expression of SST. However, they were associated with reduced Ca2+/calmodulin-dependent auto-phosphorylation of eEF2 kinase, which controls the activity of eEF2 as its single target. Thus enhancing GABAergic inhibitory synaptic inputs from SST+ interneurons to pyramidal cells and corresponding chronic reductions in the synaptic excitation:inhibition ratio represents a novel strategy for antidepressant therapies that reproduces behavioral and biochemical end points of rapidly acting antidepressants.
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Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/fisiología , Potenciales Postsinápticos Inhibidores/fisiología , Animales , Ansiolíticos/farmacología , Antidepresivos/uso terapéutico , Encéfalo/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , GABAérgicos/metabolismo , GABAérgicos/uso terapéutico , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Interneuronas/fisiología , Ketamina/farmacología , Ratones , Ratones Transgénicos , Receptores de GABA-A/metabolismo , Somatostatina/metabolismo , Transmisión Sináptica/fisiología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The rice C-glycosyltransferase (OsCGT) is one of only a small number of characterised plant C-glycosyltransferases (CGT) known. The enzyme C-glucosylates a 2-hydroxyflavanone substrate with UDP-glucose as the sugar donor to produce C-glucosyl-2-hydroxyflavanones. We tested substrate specificity of the enzyme, using synthetic 2-hydroxyflavanones, and showed it has the potential to generate known natural CGFs that have been isolated from rice and also other plants. In addition, we synthesised novel, unnatural 2-hydroxyflavanone substrates to test the B-ring chemical space of substrate accepted by the OsCGT and demonstrated the OsCGT capacity as a synthetic reagent to generate significant quantities of known and novel CGFs. Many B-ring analogues are tolerated within a confined steric limit. Finally the OsCGT was used to generate novel mono-C-glucosyl-2-hydroxyflavanones as putative biosynthetic intermediates to examine the potential of Desmodium incanum biosynthetic CGTs to produce novel di-C-glycosylflavones, compounds implicated in the allelopathic biological activity of Desmodium against parasitic weeds from the Striga genus.
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Flavonas/metabolismo , Glicósidos/metabolismo , Glicosiltransferasas/metabolismo , Oryza , Raíces de Plantas/metabolismo , Flavonas/química , Glicósidos/química , Estructura Molecular , Oryza/química , Oryza/enzimología , Oryza/genéticaRESUMEN
The one-pot borylation/Suzuki reaction is a very efficient means of accessing cross-coupling products of two aryl-halide partners that generally requires the use of specific catalysts or ligands and/or relatively long reaction times. This new microwave-assisted method provides a quick one-pot borylation/Suzuki reaction protocol that we applied to the synthesis of various bi- or poly-aryl scaffolds, including a variety of aryl and heteroaryl ring systems and the core frameworks of kinase inhibitors vemurafenib and GDC-0879.
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Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas/metabolismo , Catálisis , Relación Dosis-Respuesta a Droga , Indenos/química , Indoles/química , Microondas , Estructura Molecular , Compuestos Organometálicos/química , Paladio/química , Inhibidores de Proteínas Quinasas/química , Pirazoles/química , Relación Estructura-Actividad , Sulfonamidas/química , VemurafenibRESUMEN
Plants from the genus Desmodium, in particular D. uncinatum, are used on sub-Saharan small-holder farms as intercrops to inhibit parasitism of cereal crops by Striga hermonthica and Striga asiatica via an allelopathic mechanism. The search for Desmodium species which are adapted to more arid conditions, and which show resilience to increased drought stress, previously identified D. intortum, D. incanum and D. ramosissimum as potential drought tolerant intercrops. Their potential as intercrops was assessed for resource poor areas of rain-fed cereal production where drought conditions can persist through normal meteorological activity, or where drought may have increasing impact through climate change. The chemical composition of the root exudates were characterised and the whole exudate biological activity was shown to be active in pot experiments for inhibition of Striga parasitism on maize. Furthermore, rain fed plot experiments showed the drought tolerant Desmodium intercrops to be effective for Striga inhibition. This work demonstrates the allelopathic nature of the new drought tolerant intercrops through activity of root exudates and the major compounds seen in the exudates are characterised as being C-glycosylflavonoid. In young plants, the exudates show large qualitative differences but as the plants mature, there is a high degree of convergence of the C-glycosylflavonoid exudate chemical profile amongst active Desmodium intercrops that confers biological activity. This defines the material for examining the mechanism for Striga inhibition.
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Exudados y Transudados/química , Feromonas/química , Raíces de Plantas/química , Striga/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Productos Agrícolas , Sequías , Fabaceae/química , Flavonoides/análisis , Flavonoides/química , Flavonoides/aislamiento & purificación , Espectrometría de Masas/métodos , Feromonas/aislamiento & purificación , Feromonas/farmacologíaRESUMEN
The catalytic hyperpolarisation of pyridine, 3-hydroxypyridine and oxazole by the Signal Amplification By Reversible Exchange (SABRE) process is achieved by a series of water soluble iridium phosphine and N-heterocyclic carbene dihydride complexes. While the efficiency of the SABRE process in methanol-d4 solution or ethanol-d6 solution is high, with over 400-fold (1)H polarisation of pyridine being produced by [Ir(H)2(NCMe)(py)(IMes)(monosulfonated-triphenylphosphine)]BF4, changing to a D2O or a D2O-ethanol solvent mixture leads to dramatically reduced activity which is rationalised in terms of low H2 solubility.
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AIMS: To determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL. METHODS: We conducted a case-control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations. RESULTS: Only one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs. 484 µg/l, P = 0.04). The mean fasting C-peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs. 50 pmol/l; P = 0.001). CONCLUSIONS: Lipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis-prone Type 2, rather than Type 1, diabetes.
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Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hiperlipidemias/genética , Lipoproteína Lipasa/genética , Adulto , Anciano , Apolipoproteína C-II/genética , Estudios de Casos y Controles , HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Cetoacidosis Diabética/metabolismo , Femenino , Genotipo , Humanos , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Hipertrigliceridemia/etiología , Hipertrigliceridemia/genética , Hipertrigliceridemia/metabolismo , Lipoproteína Lipasa/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Receptores de Lipoproteína/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
Reduction of adverse events depends on accurate detection. The utility of a Trigger Tool to detect and classify severity of adverse events in an intensive care unit of a paediatric university hospital was compared to voluntary reporting. Sixty patient records were randomly selected from 314 admissions over three months. Events detected by the Trigger Tool were classified by two independent investigators as insignificant, minor, moderate, major or catastrophic. Examination of each record required, on average, 40 minutes. Ninety-eight adverse events (1.66/patient) were detected in 59 available records. Mean admission was 2.77 days. The incidence of adverse events was 59.9 per 100 patient days or 0.60 events per patient per day. The number of events detected by the Trigger Tool was related to duration of admission (r=0.70, P <0.0001) and risk of mortality on admission (r=0.50, P=0.0001) but not to age. The inter-rater agreement on detection of adverse events was good. Investigator One detected 66 adverse events while Investigator Two detected 93 events (kappa 0.63). Of the 61 events detected by both investigators, the agreement of classification of severity was very good (kappa 0.89). Of the 56 events rated similarly by both investigators, 13 (23%) were insignificant, 19 (34%) were minor, 17 (30%) were moderate, 4 (7%) were major and 3 (6%) were catastrophic. Only four adverse events had been reported voluntarily, of which two were detected using the Trigger Tool. Whereas the Trigger Tool is a simple, efficient and robust method, voluntary reporting is inadequate and captures very few adverse events in the intensive care unit environment.
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Unidades de Cuidado Intensivo Pediátrico , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Tiempo de Internación , Masculino , Registros Médicos , Errores de Medicación , Estudios Retrospectivos , Gestión de Riesgos , Administración de la SeguridadRESUMEN
Chinavia and Nezara spp. stink bugs (Heteroptera: Pentatomidae) include over100 species, with highest diversity in Afrotropical and Neotropical regions. Species thus far studied in these genera utilize trans-(Z)-(4 S)-bisabolene epoxide (BE) and cis-(Z)-(4 S)-BE as major sex pheromone components, with species specificity ensured by different ratios of the two compounds. Gas chromatography (GC) and coupled GC-mass spectrometry (GC-MS) analyses of a volatiles from C. ubica males revealed the presence of two BE isomers in approximately a 90:10 ratio, which were shown by microprobe (1) H NMR to be cis-(Z)-BE and trans-(Z)-BE isomers, respectively. Analyses of volatiles from C. impicticornis males suggested the presence of a single isomer, trans-(Z)-BE, in high purity (>90 %). The absolute configurations of the isomers produced by C. ubica and C. impicticornis were determined using chiral GC analysis (ß-DEX column). Oxidative microchemistry of synthetic standards of cis-(Z)-(4 S)-BE and trans-(Z)-(4R)-BE, and volatiles from male of C. ubica, revealed the absolute stereochemistry of the cis-(Z)-BE to be (1R,2 S,4 S) [cis-(Z)-(4 S) for short]. Similarly, analyses of trans-(Z)-(4 S)-BE and cis-(Z)-(4R)-BE standards, and volatiles from males of C. ubica and C. impicticornis, revealed the absolute stereochemistry of the trans-(Z)-BE to be (1 S,2R,4 S) [trans-(Z)-(4 S) for short]. Olfactometer bioassays with synthetic BEs confirmed attraction of female C. ubica and C. impicticornis to conspecific synthetic pheromone, but not to heterospecific synthetic pheromone. Chinavia impicticornis appeared not to discriminate behaviorally between the conspecific pheromone and its enantiomer. Coupled GC-electroantennography with antennae from females suggested that C. ubica and C. impicticornis possess olfactory receptors for both cis-(Z)-(4 S)-BE and trans-(Z)-(4 S)-BE. The results in this study confirm that C. ubica and C. impicticornis, as for other Chinavia and Nezara spp., utilize cis-(Z)-(4 S)-BE and trans-(Z)-(4 S)-BE as sex pheromone components, with different ratios guaranteeing species specificity. Furthermore, the results suggest that the absolute stereochemistry of BEs may be less important for conspecific recognition than the relative stereochemistry between the epoxide group and the alkyl substituent on the bisabolene ring.
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Comunicación Animal , Heterópteros/fisiología , Atractivos Sexuales/química , Animales , Antenas de Artrópodos/fisiología , Femenino , Isomerismo , Masculino , Atractivos Sexuales/fisiología , Especificidad de la EspecieRESUMEN
Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was approximately 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.
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Hiperlipoproteinemia Tipo I/enzimología , Hiperlipoproteinemia Tipo I/genética , Lipoproteína Lipasa/genética , Adulto , Anciano , Aminoácidos/genética , Niño , Femenino , Humanos , Hiperlipoproteinemia Tipo I/sangre , Lipoproteína Lipasa/metabolismo , Masculino , Persona de Mediana Edad , Mutación/genética , LinajeRESUMEN
Abetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)-containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat-soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB-30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in-frame deletion of MTP exon 15 (c.2076-39_2303 + 52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat-soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.
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Abetalipoproteinemia/genética , Apolipoproteínas B/genética , Proteínas Portadoras/genética , Hipobetalipoproteinemias/genética , Consanguinidad , Análisis Mutacional de ADN/métodos , Exones , Salud de la Familia , Femenino , Eliminación de Gen , Genotipo , Homocigoto , Humanos , Hígado/patología , Masculino , MutaciónRESUMEN
The enzyme beta-galactosidase, encoded by the bacterial gene lac-Z, is commonly used as a histochemical reporter to track transplanted cells in vivo or to analyze temporospatial gene expression patterns by coupling expression of specific target genes to beta-galactosidase activity. Previously, endogenous beta-galactosidase activity has been recognized as a confounding factor in the study of different soft tissues, but there is no description of the typical background on bone marrow sections when using the chromogenic substrate 5-Bromo-4-chloro-3-indolyl beta-D-Galactoside (X-Gal). In this report, we show that osteoclasts in bone marrow sections specifically and robustly stain blue with X-Gal. This leads to a typical background when bone marrow is examined that is present from the first day post partum throughout the adult life of experimental mice and can be confused with transgenic, bacterial beta-galactosidase expressing hematopoietic or stromal cells. Experimental variations in the X-Gal staining procedure, such as pH and time of exposure to substrate, were not sufficient to avoid this background. Therefore, these data demonstrate the need for strenuous controls when evaluating beta-galactosidase positive bone marrow cells. Verifiable bacterial beta-galactosidase positive bone marrow cells should be further identified using immunohistological or other approaches. Specifically, beta-galactosidase positive hematopoietic or stromal cells should be proven specifically not to be osteoclasts by co-staining or staining adjacent sections for specific markers of hematopoietic and stromal cells.
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Células de la Médula Ósea/citología , Histocitoquímica/métodos , Osteoclastos/metabolismo , beta-Galactosidasa/análisis , beta-Galactosidasa/metabolismo , Fosfatasa Ácida/metabolismo , Animales , Biomarcadores/metabolismo , Huesos/metabolismo , Fémur/metabolismo , Genes Reporteros , Sistema Hematopoyético/metabolismo , Concentración de Iones de Hidrógeno , Inmunohistoquímica , Isoenzimas/metabolismo , Operón Lac , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Radiografía Dental Digital , Coloración y Etiquetado , Células del Estroma/metabolismo , Especificidad por Sustrato , Fosfatasa Ácida Tartratorresistente , Factores de TiempoRESUMEN
The use of taping to modify pain and muscle activity has become common practice among musculoskeletal physiotherapists. The aim of this study was to evaluate the repeatability of two variables, skin displacement and pressure, produced by a standardized taping procedure designed to inhibit the vastus lateralis (VL) muscle in patellofemoral pain. Measurements were recorded in 10 healthy volunteers. The effects of the taping procedure were assessed on the two lower limbs of each individual, and on measurements taken on the same limb in five subjects on two different days. On two-way analysis of variance no significant variable or interaction effect (P<0.05) was found. The coefficient (limit) of repeatability demonstrated that 95% of the differences measured for skin displacement and pressure were less than 6% and 94% of their respective means. The absolute pressures found were without exception very small and not repeatable. The results demonstrated that the VL "inhibitory" taping procedure used produced a reproducible effect for skin displacement. The validity of this taping technique is discussed.
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Vendajes , Articulación de la Rodilla , Movimiento/fisiología , Músculo Esquelético/fisiología , Fenómenos Fisiológicos de la Piel , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Transductores de PresiónRESUMEN
A 26-year-old male, the index patient, presented with persecutory delusions and suicidal behavior. He had 10 paternal male relatives in two prior generations. Five of them died by violent suicide and one, of the five, also committed a double homicide. The index patient was found to be hypocholesterolemic due to being heterozygous for a novel mutation of apolipoprotein B (apoB-29.4). His mother and paternal grandmother were normocholesterolemic, whereas a surviving paternal uncle was hypocholesterolemic and heterozygous for the apoB-29.4 mutation. This indicated that the index patient's father and paternal grandfather, both of which died by violent suicide, were obligate heterozygotes for the apoB-29.4 mutation and that the index patient inherited the mutation from his paternal grandfather. The odds ratio for the association between hypocholesterolemia and violent behavior in this family, where cholesterol status was known, was 16.9 (95% confidence interval 1.1-239.3). Therefore, our results support an inheritable relationship between violent behavior and hypocholesterolemia.
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Agresión , Apolipoproteínas B/genética , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/fisiopatología , Mutación/genética , Adulto , Apolipoproteínas B/sangre , Western Blotting/métodos , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Humanos , Masculino , Oportunidad Relativa , Valores de ReferenciaRESUMEN
BACKGROUND: Achilles tendinopathy is a common condition, which can become chronic and interfere with athletic performance. The proteinase inhibitor aprotinin (as injection) has been found to improve recovery in patellar tendinopathy (evidence level 1b) and Achilles tendinopathy. Internationally this therapy is being used based on this limited knowledge base. AIM: To evaluate whether aprotinin injections decrease time to recovery in Achilles tendinopathy. METHOD: A prospective, randomised, double blind, placebo controlled trial was performed comparing saline (0.9%) plus local anaesthetic injections and eccentric exercises with aprotinin (30,000 kIU) plus local anaesthetic injection and eccentric exercise. Three injections were given, each a week apart. In total, 26 patients, with 33 affected tendons, were enrolled for this study. RESULTS: At no follow up point (2, 4, 12, or 52 weeks) was there any statistically significant difference between the treatment group and placebo. This included VISA-A scores and secondary outcome measures. However, a trend for improvement over placebo was noted. CONCLUSION: In this study on Achilles tendinopathy, aprotinin was not shown to offer any statistically significant benefit over placebo. Larger multicentre trials are needed to evaluate the efficacy of aprotinin in Achilles tendinopathy.