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1.
Eur Respir J ; 60(5)2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35728977

RESUMEN

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.


Asunto(s)
Bronquiectasia , Trastornos de la Motilidad Ciliar , Ciliopatías , Síndrome de Kartagener , Humanos , Mutación , Bronquiectasia/diagnóstico , Bronquiectasia/genética , Cilios , Trastornos de la Motilidad Ciliar/diagnóstico , Trastornos de la Motilidad Ciliar/genética , Ciliopatías/complicaciones , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética
2.
BJOG ; 127(4): 490-499, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31778255

RESUMEN

OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs. DESIGN: Prospective observational cohort study. SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia. POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT. METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records. MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile. RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile. CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy. TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.


Asunto(s)
Peso al Nacer , Macrosomía Fetal/sangre , Hiperlipidemias/sangre , Adulto , Pueblo Asiatico , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Macrosomía Fetal/epidemiología , Humanos , Hiperlipidemias/complicaciones , Recién Nacido , Malasia/epidemiología , Masculino , Obesidad/epidemiología , Embarazo , Estudios Prospectivos , Encuestas y Cuestionarios , Triglicéridos/sangre
3.
J Nucl Cardiol ; 22(6): 1262-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25698476

RESUMEN

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT. METHODS AND RESULTS: We undertook (123)I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups. CONCLUSION: Global and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.


Asunto(s)
3-Yodobencilguanidina , Enfermedades Cardiovasculares/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Prueba de Tolerancia a la Glucosa , Corazón/inervación , Sistema Nervioso Simpático/diagnóstico por imagen , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Corazón/diagnóstico por imagen , Historia Antigua , Humanos , Masculino , Persona de Mediana Edad , Cintigrafía/métodos , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
4.
Int J Oral Maxillofac Surg ; 53(8): 635-643, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38342749

RESUMEN

Glutamine metabolism, governed by enzymes including glutaminase (GLS1 and GLS2), has a pivotal role in cancer progression. The objective of this study was to determine whether GLS2 transcription levels are associated with oral squamous cell carcinoma (OSCC) when compared to matched adjacent normal tissues. Primary tumour and adjacent normal tissues were collected from 51 OSCC patients, and GLS2 mRNA expression analysis was conducted using real-time qPCR. Additionally, The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSCC) dataset was utilized to examine GLS2 expression in relation to clinicopathological features, the prognosis, and tumour immune cell infiltration. A significantly reduced expression of GLS2 mRNA was found in the OSCC tissues when compared to the matched adjacent normal tissue samples (P < 0.001), which aligned with the results from the TCGA-HNSCC dataset and immunohistochemistry. Moreover, GLS2 mRNA expression was associated with clinicopathological features including tumour stage, grade, and human papillomavirus status (all P < 0.05), predicted a poorer prognosis (P = 0.024), and was correlated with tumour immune cell infiltration (all P < 0.05) in head and neck squamous cell carcinoma. Functional pathway analysis indicated its involvement in cell proliferation and metabolic cycles. GLS2 dysregulation is linked to oral cancer, suggesting its potential as a predictive prognostic marker for OSCC. Furthermore, targeting glutaminases via GLS2 may represent a promising therapeutic strategy for OSCC treatment.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas , Glutaminasa , Neoplasias de la Boca , Humanos , Glutaminasa/metabolismo , Glutaminasa/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Anciano , Estadificación de Neoplasias , ARN Mensajero/metabolismo , Clasificación del Tumor , Inmunohistoquímica , Adulto , Reacción en Cadena en Tiempo Real de la Polimerasa
5.
Dent Res J (Isfahan) ; 20: 32, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37180688

RESUMEN

Background: The burden of oral diseases is increasing, which constitute a major public health problem. The use of probiotics as an adjuvant, along with routine dental care practice by an individual, can produce additional benefits in the maintenance of one's oral health. The study aimed to investigate the effect of Bifidobacterium as a probiotic on oral health. Material and Methods: Six databases and registers were searched from the start of the database to December 2021 without any restrictions. Randomized controlled trials (RCTs) evaluating the clinical effects of Bifidobacterium as a probiotic on oral health were included in the study. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed to conduct this systematic review. The included studies were analyzed for the risk of bias using the Cochrane risk-of-bias tool for randomized trial (RoB 2) tool as well as quality of available evidence using GRADE criteria. Results: From the 22 qualified studies, four studies showed non-significant results. There was a high risk of bias in 13 studies and some concerns of bias in nine studies. No adverse effects were reported, and the quality of available evidence was moderate. Conclusion: The effect of Bifidobacterium on oral health is questionable. Further high-quality RCTs are required on the clinical effects of bifidobacteria and also the optimum level of probiotic needed, and ideal mode of administration to provide oral health benefits. Furthermore, synergistic effects of the combined use of various strains of probiotics need to be studied.

6.
Sci Adv ; 9(17): eade2675, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-37115922

RESUMEN

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Glioma/genética , Glioma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Genómica , Predisposición Genética a la Enfermedad , Secuenciación Completa del Genoma , Proteínas de Unión al Calcio/genética , Proteínas de Unión al ADN/genética , Proteínas Supresoras de Tumor/genética
7.
Zootaxa ; 5219(1): 65-71, 2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-37044880

RESUMEN

Thyone neofusus Deichmann, 1941, Thyone adinopoda Pawson & Miller, 1981and Havelockia obunca (Lampert, 1885) are referred to the genus Sclerothyone Thandar, 1989, and a taxonomic key is provided to all species currently contained in the family Sclerothyonidae Thandar (sensu Smirnov 2012). Since the nomen Neothyone in the family Thyonidae (sensu Smirnov 2012), is preoccupied [(having been used by Hampson (1914) for a group of moths belonging to the family Arctiidae)], the name Lisacucumis nomen nov. is here proposed, with Stolus gibber Selenka as type species, as designated for Neothyone by Deichmann (1941).


Asunto(s)
Lepidópteros , Pepinos de Mar , Animales , Equinodermos , Derivación y Consulta
8.
Ann Burns Fire Disasters ; 34(4): 351-359, 2021 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-35035329

RESUMEN

Electrical burn injuries result in significant mortality and morbidity. Most of these injuries are preventable. We conducted a retrospective analysis of various aspects of electrical injuries presenting to our center over a period of 1 year from September 2018 to August 2019. Demographic characteristics of patients along with burn characteristics and associated injuries were analysed. Outcomes including length of hospital stay, need for fasciotomy, amputation, renal failure and mortality were also analysed. A total of 6380 patients presented to our center during the study period, of which 471 (7.38%) had electrical burns. Total burn admissions were 1530, of which 283 (18.49%) patients were admitted with electrical burns. The mean age in our cohort was 25.31±12.76 years and mean TBSA was 29.22±23.81%. The most common cause of electrical burns was occupational (33.3%), followed by those that occurred on the rooftop of houses (31%). A historical comparison with data published from our center in 2011 showed a significant increase in occupational burns (18.72% vs. 33.3%) and rooftop electrical burns (8.21% vs. 31%), and a decrease in agriculture-related (42.46% vs. 9.1%) and domestic electrical burns (26.02% vs. 6.7%). There was also a significant rise in proportion of high voltage injuries (71.23% vs. 86.90%). Logistic regression analysis showed electric contact burn to be a risk factor for fasciotomy and limb gangrene. Risk factors for renal failure were age, percentage burn, electric contact burn and rural residence, and those for mortality were percentage burn and renal failure. Emphasis on preventive strategies, especially against occupational injuries and injuries occurring on rooftops, is necessary to prevent such devastating injuries.


Les brûlures électriques sont responsables d'une morbidité et d'une mortalité significatives, quand la plupart d'entre elles peuvent être prévenues. Nous avons étudié rétrospectivement les brûlures électriques vues dans notre service entre septembre 2018 et août 2019 inclus (données démographiques, caractéristiques de la brûlure, lésions associées, durée d'hospitalisation, aponévrotomies, amputations, défaillances rénales, mortalité). Quatre cent soixante et onze des 6 380 (7,38%) patients s'étant présentés souffraient de brûlures électriques. Deux cent quatre- vingt- trois des 1 530 (18,49%) hospitalisés l'étaient en raison de brûlures électriques. L'âge moyen était de 25,31 +/- 12,76 ans, la surface brûlée de 29,22 +/- 23,81%. La brûlure survenait au travail dans 1/3 des cas, au domicile (sur le toit) dans 31% des cas. Comparativement aux données historiques de notre CTB (datant de 2011), on constate une recrudescence des accidents de travail (qui passent de 18,72 à 33,3%) et de ceux survenant sur le toit du domicile (de 8,21 à 31%) alors que ceux chez les agriculteurs (de 42,46% à 9,1%) et les accidents domestiques (de 26,02 à 6,7%) baissent. La proportion des accidents à haut voltage a augmenté de 71,23 à 86,9%. En régression logistique, la brûlure électrothermique est un facteur de risque d'aponévrotomie et de gangrène de membre. Les facteurs de risque d'insuffisance rénale étaient l'âge, la surface brûlée, la brûlure électrothermique et la ruralité. Les facteurs de risque de mortalité étaient la surface brûlée et la défaillance rénale. Les mesures préventives doivent se focaliser sur les accidents de travail et le risque encouru sur les toits des habitations.

9.
Saudi J Biol Sci ; 27(12): 3249-3257, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33304130

RESUMEN

This context was investigated to determine in vitro antimicrobial, antioxidative, and anticancer traits of crude ethyl acetate extract of Streptomyces cangkringensis strain TSAS 04 isolated from soil sample of rhizosphere regions. The antimicrobial activity of ethyl acetate extract of strain TSAS 04 was determined against indicator pathogens using disc diffusion assay which exhibited maximum zones of inhibition of 20.6 ± 0.3 and 16.3 ± 0.6 mm against Bacillus subtilis and Trichoderma viride, respectively. In vitro antioxidant properties of the crude ethyl acetate extract were performed using standard methodologies. The extract revealed maximum DPPH and ABTS•+ radical scavenging activities of 51.1 ± 0.39 and 81.25 ± 0.33%, respectively. Likewise, maximum phosphomolybdenum reduction and Fe3+ reduction of the crude ethyl acetate extract of strain TSAS 04 were estimated 76.18 ± 0.10 and 89.01 ± 0.44%, respectively. In vitro anticancer trait of the extract was determined against HeLa cell line using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay which showed anticancer activities in a dose dependent manner with an IC50 value of 410.5 µg/mL. Fourier transform infrared spectroscopy (FT-IR) and Gas chromatography-mass spectrometry (GC-MS) analyses indicated the presence of distinct functional groups and bioactive components in the extract, respectively. In conclusion, S. cangkringensis strain TSAS 04 showed its effectiveness as ideal bioactive agent by exhibiting substantial antimicrobial, antioxidant, and anticancer properties.

10.
Ann Burns Fire Disasters ; 33(4): 293-298, 2020 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-33708018

RESUMEN

Adequate resuscitation of acute burn patients is important to ensure end organ perfusion and oxygenation. The ideal marker to the endpoint of burn resuscitation is still not established. We aimed to evaluate the role of blood lactate and lactate clearance in burn resuscitation and their association with mortality and sepsis in burn patients. The retrospective study included patients (18-50 years) with thermal and scald burns with total body surface area of 30% to 60% over a period of 9 months who had achieved target urine output of at least 0.5ml/kg/hr within 24 hours of resuscitation. Patients were divided based on their admission blood lactate levels (Group A < 2 mmol/L and Group B > 2 mmol/L). Group B was further subdivided into Group B1 in whom blood lactate levels reached less than 2 mmol/L within 24 hours of burn resuscitation and Group B2 in whom it did not. Total patients included were 203. Mortality (M) and sepsis (S) rates in subgroup B2 were higher (M=57.9%; S=43.5%) and rates in subgroup B1 (M=25.8%; S=27.4%) were comparable to Group A (M=27.8%; S=26.4%). Persistent lactic acidosis at 24 hours was independently associated with significantly increased mortality and sepsis. Our data suggests a correlation of blood lactate levels and lactate clearance within 24 hours of admission with mortality and sepsis related to burn injury.


Un remplissage vasculaire adapté est nécessaire afin de préserver la perfusion et l'oxygénation tissulaires des brûlés. Le marqueur idéal de sa qualité reste à trouver. Nous avons évalué la lactatémie et l'élimination des lactates dans ce but, ainsi que leur corrélation avec la mortalité et le sepsis. Nous avons étudié rétrospectivement, sur 9 mois, 203 patients de 18 à 50 ans, brûlés sur 30 à 60% de SCT, ayant eu une diurèse horaire de plus de 0,5 mL/kg/h dans les 24 premières heures suivant leur brûlure. Le groupe A avait moins de 2 mmol/L de lactate à l'admission, le groupe B plus. Ce dernier groupe a été subdivisé en B1 (lactate redescendant à moins de 2 mmol/L dans les 24 premières heures) et B2 ne le faisant pas. La mortalité de B2 était plus élevée (57,8%) que A (27,8%) et B1 (25,8%), ces 2 derniers groupes étant comparables. De même, un sepsis survenait chez 43,5% des patients de B2 contre 27,4% pour B1 et 26,4% pour A. Plus que leur valeur initiale, c'est l'absence de décroissance dans les 24 premières heures des lactates qui est un marqueur de mauvais pronostic chez le brûlé.

11.
Environ Toxicol Pharmacol ; 26(1): 92-5, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21783894

RESUMEN

Anti-inflammatory effects of four solvent fractions of ethanol extract of Mentha spicata were evaluated in acute and chronic inflammation induced in Wistar albino rats. Lipid peroxidation (LPO) and some antioxidants produced during chronic inflammation were quantitated. Hexane (320mg/kg of body weight in 25% DMSO), chloroform (320mg/kg body weight in 25% DMSO), ethyl acetate (160mg/kg body weight in 25% DMSO), aqueous (320mg/kg of body weight in ddH(2)O) fractions, two negative control groups (25% DMSO and ddH(2)O) and two anti-inflammatory drugs (Diclofenac: 25mg/kg of body weight; Indomethacin: 10mg/kg of body weight both in ddH(2)O) were administered by oral intubations to the eight groups of rats consisting six animals, each. In acute study, 1% carrageenan was injected subcutaneously in the sub-plantar region of the right hind paw after 1h of administration of test doses. The increased paw edema was measured at 0.5, 1, 2, 4, 8, 16 and 24h intervals. In the chronic study, the oral administration was carried out for seven consecutive days. On eighth day, four sterile cotton pellets (50mg each) were implanted subcutaneously in the dorsal region of the rats. On the sixteenth day, the rats were sacrificed and the cotton pellets with granulomatous tissue were dissected out and weighed (fresh and dry). Both in chronic and acute inflammation, ethyl acetate (EAF) and aqueous fraction (AF) were effective. EAF is comparable with the positive standards in chronic inflammation. The results indicate that EAF's anti-inflammatory activity is largely due to its ability to modulate in vivo antioxidants.

12.
Indian J Exp Biol ; 46(12): 831-5, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19245180

RESUMEN

A bioactive compound with antibacterial activity was isolated and purified from the extract of leaves of sunflower, Helianthus annuus. The bioactive compound was characterized using 1H and 13C NMR. The compound induced auxin, gibberellins and cytokinin in Oryza sativa and Phaseolus mungo. It also showed activity against Xanthomonas oryzae pv. oryzae.


Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Helianthus/química , Xanthomonas/efectos de los fármacos , Antibacterianos/química , Espectroscopía de Resonancia Magnética , Oryza/efectos de los fármacos , Oryza/crecimiento & desarrollo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo , Semillas/química
13.
J Clin Invest ; 100(5): 1123-36, 1997 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-9276729

RESUMEN

The FimH subunit of type 1-fimbriated Escherichia coli has been implicated as an important determinant of bacterial adherence and colonization of the urinary tract. Here, we sought to localize the functionally important domain(s) within the FimH molecule and to determine if antibodies against this domain would block adherence of type 1-fimbriated E. coli to the bladder mucosa in situ and in vivo in an established mouse model of cystitis. We generated translational fusion proteins of disparate regions of the FimH molecule with an affinity tag MalE, and tested each of the fusion products in vitro for functional activity. The minimum region responsible for binding mouse bladder epithelial cells and a soluble mannoprotein, horseradish peroxidase, was contained within residues 1-100 of the FimH molecule. We validated and extended these findings by demonstrating that antibodies directed at the putative binding region of FimH or at synthetic peptides corresponding to epitopes within the binding domain could specifically block type 1 fimbriae-mediated bacterial adherence to bladder epithelial cells in situ and yeast cells in vitro. Next, we compared the ability of mice passively immunized intraperitoneally with antisera raised against residues 1-25 and 253-264 of FimH or 1-13 of FimA to resist bladder colonization in vivo after intravesicular challenge with type 1-fimbriated E. coli. Only the antibody directed at the putative binding region of FimH (anti- s-FimH1-25) significantly reduced E. coli bladder infections in the experimental mouse model of urinary tract infections. Similar results were obtained when the mice were actively immunized with synthetic peptides corresponding to residues 1-25 and 253-264 of FimH or 1-13 of FimA. The mechanism of protection was attributed, at least in part, to inhibition of bacterial adherence to the bladder surface by s-FimH1-25-specific antibody molecules that had filtered through the kidneys into the urine. The level of FimH antibodies entering the bladder from the circulatory system of the immunized mice was found to be markedly enhanced upon bacterial challenge. The potential broad spectrum activity of the protective FimH antibody was indicated from its serologic cross-reactivity with various urinary tract bacterial isolates bearing type 1 fimbriae. These findings could be relevant in the design of an efficacious and broadly reactive FimH vaccine against urinary tract infections.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Adhesinas Bacterianas/inmunología , Adhesinas de Escherichia coli , Anticuerpos Antibacterianos/inmunología , Proteínas de Escherichia coli , Escherichia coli/inmunología , Proteínas Fimbrias , Inmunización Pasiva , Proteínas de Transporte de Monosacáridos , Proteínas de Unión Periplasmáticas , Infecciones Urinarias/prevención & control , Animales , Adhesión Bacteriana , Proteínas Portadoras/metabolismo , Células Cultivadas , Reacciones Cruzadas , Femenino , Fimbrias Bacterianas/fisiología , Proteínas de Unión a Maltosa , Ratones , Ratones Endogámicos ICR , Vejiga Urinaria/microbiología
14.
J Biomol Struct Dyn ; 25(3): 311-20, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17937492

RESUMEN

Xylanases are glycosyl hydrolases that catalyze the hydrolysis of internal beta-1,4 glycosidic bonds of xylan, the major hemi-cellulose component of the plant cell wall. Enzymes such as xylanases are used considerably in industries. Their industrial usage is especially attractive since they can replace some of the environmental pollutants. We have earlier isolated a family 11-xylanase gene from Bacillus subtilis-AK1, which is active at high temperature as well as at alkaline pH. In order to understand the factors liable for the adaptation of this enzyme, three dimensional model of B. subtilis-AK1 xylanase has now been obtained by homology modeling. Modeling was carried out using Molecular Operating Environment (MOE) software developed by Chemical Computing Group Inc., running on Pentium IV workstation. The model showed that B. subtilis-AK1 xylanase having molecular weight around 20 kDa contains in its fold an alpha-helix and two beta-sheets packed against each other forming a beta-sandwich. The conserved active site amino acids E78R, Y80L were mutated in this novel B. subtilis-AK1 strain, but the protein folding and the function was maintained with high thermal stability. Several minor modifications appeared to be responsible for the increased thermo stability of AK1. Docking studies of the substrate xylan with -AK1 shows the possibility of the Arg 78 acting as the nucleophile instead of Glu 78.


Asunto(s)
Bacillus subtilis/enzimología , Endo-1,4-beta Xilanasas/química , Secuencia de Aminoácidos , Endo-1,4-beta Xilanasas/clasificación , Endo-1,4-beta Xilanasas/genética , Estabilidad de Enzimas , Calor , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Alineación de Secuencia , Homología de Secuencia , Termodinámica
15.
J Health Organ Manag ; 21(1): 54-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17455812

RESUMEN

PURPOSE: Cancelled operations are a major drain on health resources: 8 per cent of scheduled elective operations are cancelled nationally, within 24 hours of surgery. The aim of this study is to define the extent of this problem in one Trust, and suggest strategies to reduce the cancellation rate. DESIGN/METHODOLOGY/APPROACH: A prospective survey was conducted over a 12-month period to identify cancelled day case and in-patient elective operations. A dedicated nurse practitioner was employed for this purpose, ensuring that the reasons for cancellation and the timing in relation to surgery were identified. The reasons for cancellation were grouped into patient-related reasons, hospital clinical reasons and hospital non-clinical reasons. FINDINGS: In total, 13,455 operations were undertaken during the research period and 1,916 (14 per cent) cancellations were recorded, of which 615 were day cases and 1,301 in-patients: 45 per cent (n = 867) of cancellations were within 24 hours of surgery; 51 per cent of cancellations were due to patient-related reasons; 34 per cent were cancelled for non-clinical reasons; and 15 per cent for clinical reasons. The common reasons for cancellation were inconvenient appointment (18.5 per cent), list over-running (16 per cent), the patients thought that they were unfit for surgery (12.2 per cent) and emergencies and trauma (9.4 per cent). PRACTICAL IMPLICATIONS: This study demonstrates that 14 per cent of elective operations are cancelled, nearly half of which are within 24 hours of surgery. The cancellation rates could be significantly improved by directing resources to address patient-related causes and hospital non-clinical causes. ORIGINALITY/VALUE: This paper is of value in that it is demonstrated that most cancellations of elective operations are due to patient-related causes and several changes are suggested to try and limit the impact of these cancellations on elective operating lists.


Asunto(s)
Citas y Horarios , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Quirófanos/estadística & datos numéricos , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Revisión de Utilización de Recursos , Anestesiología , Ocupación de Camas , Eficiencia Organizacional , Urgencias Médicas , Falla de Equipo , Femenino , Cirugía General , Hospitales de Distrito , Hospitales Generales , Humanos , Masculino , Observación , Quirófanos/organización & administración , Pacientes Desistentes del Tratamiento/psicología , Estudios Retrospectivos , Listas de Espera , Gales , Recursos Humanos
16.
J Visc Surg ; 154(4): 303-305, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28688775

RESUMEN

Peritoneal encapsulation (PE) is a rare congenital anomaly that is formed due to an accessory peritoneal layer encapsulating the small bowel. Kinking of bowel within the accessory peritoneal layer or adhesions between the bowel loops and the peritoneal layer causes symptoms ranging from colicky abdominal pain to rarely intestinal obstruction. Cleland was the first person to have reported this condition as early as 1868 and since then only around 30 cases have been reported. Here, we present a case of acute intestinal obstruction in a 22-year-old woman. Imaging showed dilated bowel loops confined to the centre of the peritoneal cavity. Intraoperatively it was seen to be a case of peritoneal encapsulation. The small intestine was freed and accessory layer excised. This report is to demonstrate this rare congenital anomaly.


Asunto(s)
Enfermedades del Íleon/etiología , Obstrucción Intestinal/etiología , Peritoneo/anomalías , Enfermedad Aguda , Femenino , Humanos , Enfermedades del Íleon/diagnóstico , Enfermedades del Íleon/cirugía , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/cirugía , Peritoneo/cirugía , Adulto Joven
17.
Hernia ; 9(3): 248-51, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15891810

RESUMEN

Adult umbilical and paraumbilical hernia repair is associated with a high recurrence rate of 10-30%. Mesh repair has been reported to be associated with low recurrence rates. This study aims to compare sutured repair with prosthetic mesh repair to evaluate recurrence and infection rates. A retrospective study was conducted over an 8-year period including all the umbilical and paraumbilical hernia repairs performed by one consultant surgeon. The hernias were repaired using interrupted suture, Mayo overlap, flat mesh and mesh plug techniques. The study was based on case-note review, telephone and postal questionnaire survey. A total of 100 patients were studied, of which 70 had paraumbilical hernias, 28 had umbilical hernias and 2 had both types of hernia. Median age was 56 years (range 19-90 years). A total of 61 patients had suture repair (50 interrupted suture repair, 11 Mayo) and 39 had prosthetic mesh repair (33 mesh plug, 6 flat mesh). The median body mass index (BMI) was 31.2 (range 23.4-44.5) in the suture repair group and 33.3 (range 24.1-59.1) in the mesh group, with no significant statistical difference in BMI between the two groups (P>0.05). Median follow-up was 4.5 years (range 1-8 years). Recurrence rates for the suture and mesh repair groups were 11.5 and 0%, respectively (P=0.007). Infection rates for the suture and mesh repair groups were 11.5 and 0%, respectively (P=0.007). Our data suggest that prosthetic mesh repair is ideal for managing primary and recurrent umbilical hernias in both obese and non-obese patients.


Asunto(s)
Hernia Umbilical/cirugía , Mallas Quirúrgicas , Suturas , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Infección de la Herida Quirúrgica
18.
Colorectal Dis ; 4(5): 345-347, 2002 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12780579

RESUMEN

INTRODUCTION: Biopsies of colonic lesions are often reported as showing dysplasia, though in reality some lesions may harbour invasive malignancy. AIM: To assess the risk of underlying invasive malignancy in sessile polyps where biopsies had shown severe dysplasia and also to attempt to define a management strategy in such patients. METHODS: Between 1997 and 2001, 30 patients were diagnosed as having severe dysplasia using Morson's criteria in colonic lesions not amenable for endoscopic polypectomy. Severely dysplastic lesions were completely excised by appropriate surgical measures. RESULTS: Out of 30 patients, 15 had invasive cancers. Surgical intervention involved anterior resections, endoanal excisions, sigmoid colectomies, or abdomino-perineal excisions as deemed appropriate. The lesions ranged in size from 0.5 cm to 13 cm (mean 3.4 cm). There were nine T1 lesions (one of which was T1N1) and two each of T2, T3, T4 lesions (10 Dukes' A, 3 Dukes' B, 2 Dukes' C). Complete resection was confirmed histologically in all cases. One patient had a leak following endoanal excision, which required intervention. There was no mortality. DISCUSSION: This study demonstrates that endoscopic sampling can be misleading and severely dysplastic sessile lesions should be managed along the same principles as followed for invasive cancers, rather than adopting a 'wait and watch' policy with repeated endoscopies, biopsies or piece-meal polypectomies.

19.
Hosp Med ; 64(2): 108-10, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12619340

RESUMEN

This study shows a targeted training for house officers relating to surgical procedures and consenting issues was helpful. The authors recommend that advice on obtaining consent should be a part of the induction programme for surgical house officers.


Asunto(s)
Competencia Clínica/normas , Cirugía General/normas , Consentimiento Informado/normas , Cuerpo Médico de Hospitales/normas , Humanos , Rol del Médico
20.
World J Nucl Med ; 13(3): 197-200, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25538493

RESUMEN

Incidental extracardiac findings are not uncommon in patients undergoing cardiac positron emission tomography/computed tomography (PET/CT) and some of these findings can have significant clinical impact. We report a case of a 74-year-old man who presented with dyspnea and left sided chest pain. 82-rubidium PET/CT imaging showed normal myocardial perfusion. Review of the low dose CT scan performed for attenuation correction purposes (CTAC) incidentally revealed a 4 cm mass in the left lung, which was histologically shown to be a squamous cell carcinoma. A subsequent staging CT showed chest wall metastases and rib destruction in the upper left thorax, which were outside the image reconstruction field of view of the CTAC. This report illustrates the importance of vigilant review of all acquired images by the PET/CT reader to look for extracardiac abnormalities that may explain symptoms in the absence of coronary artery disease. It also raises the question as to whether a larger field of CT image acquisition should be routinely performed to scan the entire chest during cardiac PET/CT imaging. However, the latter needs to be weighed against the increase in patient dose, which we estimated to be an additional 15%.

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