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BACKGROUND: The aim of this study was to assess the accuracy of clinical screening examination in newborns with dislocated hips compared with ultrasound scan (USS). METHODS: Newborns, up to 3 months of age, with confirmed hip dislocations on USS were prospectively enrolled in a multinational observational study. Data from 2010 to 2016 were reviewed to determine pretreatment clinical examination findings of the treating orthopaedic surgeon as well as baseline ultrasound indices of developmental dysplasia of the hip (DDH). All infants had been referred to specialist centres with expertise in DDH, due to abnormal birth examination or risk factor. RESULTS: The median age of the study population was 2.3 weeks and 84% of patients were female. Of the total 515 USS-confirmed dislocated hips included in the study, 71 (13.8%) were incorrectly felt to be reduced on clinical examination by the treating orthopaedist (P<0.001). Full hip abduction was documented in 106 hips. Of the hips correctly identified as dislocated, 322 hips were further analyzed based on clinical reducibility. Thirty-three of 322 (10.2%) were incorrectly thought to be reducible when in fact they were irreducible or vice versa. CONCLUSIONS: Expert examiners missed a significant number of frankly dislocated hips on clinical examination and their ability to classify hips based on clinical reducibility was only moderately accurate. This study provides evidence that, even in experienced hands, physical examination findings in DDH are often too subtle to elicit clinically in the first few months of life. This may explain the persistent and measurable rate of late presenting dislocations in countries with screening programmes reliant on clinical examination. LEVEL OF EVIDENCE: Level 1-testing of previously developed diagnostic criteria in series of consecutive patients (with universally applied reference "gold" standard).
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Diagnóstico Tardío/prevención & control , Luxación Congénita de la Cadera , Examen Físico/métodos , Ultrasonografía/métodos , Precisión de la Medición Dimensional , Femenino , Luxación Congénita de la Cadera/diagnóstico , Luxación Congénita de la Cadera/terapia , Humanos , Lactante , Recién Nacido , Masculino , Tamizaje Neonatal/métodos , Tamizaje Neonatal/normas , Reproducibilidad de los ResultadosRESUMEN
Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism.
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Guanidinas/síntesis química , Leishmania infantum/efectos de los fármacos , Poríferos/química , Trypanosoma cruzi/efectos de los fármacos , Alcaloides/farmacología , Animales , Guanidinas/química , Guanidinas/farmacología , Biología Marina , Estructura Molecular , Óxido Nítrico/metabolismoRESUMEN
HPLC-UV-ELSD-MS-guided fractionation of the anti-parasitic extract obtained from the marine sponge Monanchora arbuscula, collected off the southeastern coast of Brazil, led to the isolation of a series of guanidine and pyrimidine alkaloids. The pyrimidines monalidine A (1) and arbusculidine A (7), as well as the guanidine alkaloids batzellamide A (8) and hemibatzelladines 9-11, represent new minor constituents that were identified by analysis of spectroscopic data. The total synthesis of monalidine A confirmed its structure. Arbusculidine A (7), related to the ptilocaulin/mirabilin/netamine family of tricyclic guanidine alkaloids, is the first in this family to possess a benzene ring. Batzellamide A (8) and hemibatzelladines 9-11 represent new carbon skeletons that are related to the batzelladines. Evaluation of the anti-parasitic activity of the major known metabolites, batzelladines D (12), F (13), L (14), and nor-L (15), as well as of synthetic monalidine A (1), against Trypanosoma cruzi and Leishmania infantum is also reported, along with a detailed investigation of parasite cell-death pathways promoted by batzelladine L (14) and norbatzelladine L (15).
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Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Guanidinas/aislamiento & purificación , Guanidinas/farmacología , Poríferos/química , Pirimidinas/aislamiento & purificación , Pirimidinas/farmacología , Alcaloides/química , Animales , Brasil , Guanidinas/química , Leishmania infantum/efectos de los fármacos , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Pruebas de Sensibilidad Parasitaria , Pirimidinas/química , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Ellagitannins (ET) and ellagic acid (EA) are polyphenols, present in common foods, which may exhibit significant health benefits against inflammation, infection and cancer. EA is metabolised by the gut flora to produce urolithins, which are absorbed into the systemic circulation. Urolithins are widely documented to reduce oxidative stress associated with many diseases including cancer, heart disease and liver damage. In particular, Urolithin C and D have been shown to have high anti-oxidant properties through the inhibition of reactive oxygen species (ROS). The anti-inflammatory properties of EA have been demonstrated through the down-regulation of pro-inflammatory enzymes such as COX-2 and iNOS as well as decreasing the expression of adhesion molecules. EA also regulates the gut microflora and possesses antimicrobial activity against various strains of harmful bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Helicobacter pylori. Numerous studies have documented the anticarcinogenic benefits of EA and have been performed on, but not limited to, prostate, colon and breast cancer cell lines and in vivo models. Conventional treatments for cancer, such as chemotherapy, can often be associated with significant side effects such as fatigue, hair loss and alopecia. Naturally-occurring food substances such as ETs potentially offer a risk-free preventative measure against cancer and could perhaps be used in synergy with current treatments. More level 1 studies are required to inform the evidence-base on this topic.
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The management of benign prostatic obstruction (BPO) should involve a treatment algorithm that takes into account prostate size, and patient's symptoms and preference with the aim of helping with urinary symptoms and enhance quality of life. The diagnostic assessment for men with lower urinary tract symptoms (LUTS) should be comprehensive to help choose the best management strategy. Strategies from lifestyle modifications to medical treatment with alpha blockers and/or 5-alpha-reductase inhibitors to surgical procedures can all be used in the management algorithm. Surgical management ranges from transurethral resection of prostate (TURP) to minimally invasive surgical therapies (MIST) including laser therapies such as Holmium laser enucleation (HoLEP) and photoselective vaporisation (PVP), aquablation, Rezum system, prostate artery embolisation (PAE), prostatic urethral lift (PUL), temporary implantable nitinol device (iTind) and Optilume BPH catheter system. BPO is a common urological condition that has a significant impact on quality of life and economic burden globally and is likely to become increasingly prevalent with an ageing population. Selecting the most appropriate treatment modality will depend on the individual patient preferences, availability of resources, cost, anatomical factors and the goals of treatment.
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AIMS: The aim of this study was to assess screening costs in developmental dysplasia of the hip (DDH), to provide any clarity on the cost-effectiveness of various hip screening programmes internationally. METHODS: A PROSPERO-registered systematic review was performed by examining cost analysis studies of various DDH screening programmes, including those based around clinical examination, selective ultrasound and universal ultrasound. Costs were analysed using narrative synthesis. RESULTS: There were 14 studies included in this review. Two studies found that clinical hip screening is advantageous over no screening at all, both in terms of overall cost and favourable outcomes. When considering selective ultrasound imaging versus clinical screening, two studies found it to be more expensive, one found it cheaper and three studies calculated the overall programme costs to be similar. With universal ultrasound, four studies calculated this to be cheaper than clinical or selective ultrasound screening due to a reduced late detection and surgery rate. However, a comparable number of studies concluded that the increased financial costs of universal ultrasound were greater than the reduction in surgical costs. No studies included any long-term data. CONCLUSION: There is a dearth of information on DDH screening costs, with significant heterogeneity amongst the existing literature. Future research should include the cost analysis of long-term complications of DDH, including the social and psychological impact of early onset arthritis, as well as gender specific ultrasound screening programmes.
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Older lesbian, gay, bisexual, trans, queer and others (LGBTQ+) people living with dementia have specific needs related to their sexual orientation and identity that should be addressed to maintain their personhood. They may face challenges in health and social care settings, such as heteronormativity and lack of awareness of older LGBTQ+ needs. Service provision for older LGBTQ+ people with dementia is lacking. Healthcare professionals' attitudes towards older LGBTQ+ people with dementia are often poor and there is a clear need for better training, while increased knowledge and awareness would help to challenge the concept of heteronormativity. This article explores some of the needs of older LGBTQ+ people with dementia, the role of legislation and regulation and how healthcare professionals can provide support.