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1.
Fam Process ; 63(1): 1-16, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38129316

RESUMO

Couple therapists have the unique and challenging opportunity of helping people find deeper connection in their intimate relationships. These clinicians apply therapeutic models and interventions designed to help couples. However, many of these models are derived from theoretical, scientific, and sociocultural traditions that conceptualize human phenomena as individualistic and reductionistic, and the language in these theories may not match clients' experiences, which include deeply relational phenomena such as love and loss. We review how Western scientific and sociocultural traditions have shaped conceptualization of problems and clinical intervention in couple therapy. In contrast, we provide an alternative, strongly relational framework for couple therapy that draws upon philosophical perspectives asserting that relational, rather than individual, experience is fundamental in human interaction. These ideas provide relational language which can influence how couple therapy is viewed and enacted. Specifically, we discuss how a strongly relational approach changes how therapists understand and intervene with conflict, abuse, love, and deception. This relational framework can help couples in their own goals to become more unified. Implications for the therapeutic relationship, interventions, and scholarship are provided.


Assuntos
Terapia de Casal , Relações Interpessoais , Humanos , Amor , Comportamento Sexual , Parceiros Sexuais
2.
J Nerv Ment Dis ; 211(6): 460-466, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37252882

RESUMO

ABSTRACT: Kernberg and McWilliams have spawned differing conceptualizations of the relationship between depressive and masochistic (self-defeating) personalities. Kernberg describes these personality styles as largely overlapping in features, whereas McWilliams accentuates important clinical differences that make up two distinct personalities. In this article, their theoretical perspectives are discussed and framed as more complementary than competitive. The malignant self-regard (MSR) construct is introduced and reviewed as an integrative self-representation that is shared by both depressive and masochistic personalities, as well as those often referred to as vulnerably narcissistic. We investigate developmental conflicts, motivations for perfectionism, countertransference patterns, and overall level of functioning as four primary clinical features through which a therapist may differentiate a depressive from a masochistic personality. We argue that depressive personalities tend to have more dependency-related conflicts and perfectionistic strivings motivated by lost object reunification, elicit more insidiously positive countertransference reactions in session, and are generally higher-functioning individuals. Masochistic personalities have more oedipal-related conflicts and perfectionistic strivings motivated by object control, elicit more aggressive countertransference reactions, and are relatively lower functioning. MSR is positioned as a bridge between Kernberg's and McWilliam's ideas. We close with a discussion of treatment implications for both disorders as well as how to understand and treat MSR.


Assuntos
Perfeccionismo , Personalidade , Humanos , Transtornos da Personalidade/terapia , Narcisismo , Motivação
3.
J Infect Dis ; 223(5): 843-847, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32702082

RESUMO

To explore whether glycosuria induces virulence of uropathogens, in turn facilitating urinary tract infection (UTI), we exposed group B Streptococcus (GBS) strain 10/84 to human urine plain or with 300 mg/dL glucose (mimicking moderate glycosuria). Exposure to moderate glycosuria significantly augmented bacterial growth, kidney bacterial burden in a mouse model of ascending UTI, and virulence characteristics and expression of corresponding genes. Exposure to glycosuria increased GBS adherence to human bladder epithelial cell line and expression of corresponding PI2a fimbrial gene, antimicrobial peptide LL-37 resistance and bacterial surface charge modulating dltA, and GBS hemolytic ability and expression of genes encoding pore-forming toxins.


Assuntos
Glicosúria , Infecções Estreptocócicas , Infecções Urinárias , Animais , Peptídeos Antimicrobianos , Aderência Bacteriana , Linhagem Celular , Glicosúria/complicações , Humanos , Camundongos , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Infecções Urinárias/microbiologia , Virulência
4.
Soft Matter ; 17(15): 4180-4190, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881039

RESUMO

Tubular structures in nature have the ability to respond to their environment-for example, blood vessels can constrict or dilate, thereby regulating flow velocity and blood pressure. These tubes have multiple concentric layers, with each layer having a distinct composition and properties. Inspired by such natural structures, we have synthesized responsive multilayer tubes in the laboratory without resorting to complex equipment such as a 3-D printer. Each layer of our tubes is a polymer gel formed by free-radical polymerization of water-soluble monomers. We can precisely control the inner diameter of the tube, the number of layers in the tube wall, and the thickness and chemistry of each layer. Tubes synthesized in this manner are robust, flexible, and stretchable. Moreover, our technique allows us to incorporate stimuli-responsive polymers into distinct regions of these tubes, and the resulting tubes can change their shape in response to external stimuli such as pH or temperature. In the case of laterally patterned tubes, the tube can be made to constrict or dilate over a particular segment-a behavior that is reminiscent of blood vessels. In the case of longitudinally patterned tubes, a straight tube can be induced to systematically curl into a coil. The versatility of our technique is further shown by constructing complex tubular architectures, including branched networks. On the whole, the polymeric tubes shown in this paper exhibit remarkable properties that cannot be realized by other techniques. Such tubes could find utility in biomedical engineering to construct anatomically realistic mimics of various tissues.


Assuntos
Polímeros , Água , Polimerização
5.
Am J Orthod Dentofacial Orthop ; 159(2): 210-216.e2, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33342673

RESUMO

INTRODUCTION: This study aimed to evaluate market trends on the demographics most likely to select direct to consumer orthodontics and the reasoning behind their decisions. METHODS: An internet-based cross-sectional survey was conducted. Data analysis was carried out using logistic regression models. RESULTS: Total of 1573 surveys were completed. While 32.2% of those surveyed selected direct to consumer orthodontics over conventional orthodontics, 10.8% would select direct to consumer orthodontics for their children. Among parents who would seek direct to consumer orthodontics, only 27.8% would consider the same treatment for their children. The odds of seeking direct to consumer orthodontic treatment for divorced participants was 2.52 times higher than that for single participants, for participants with 4 children or more was 2 times higher than that for participant with no children, and in age group 46-59 years was 2.23 times higher than that for age group 18-26 years. Seventy three percent of consumers who selected direct to consumer orthodontics selected cost as an influencing factor. Convenience was also a major determining factor at 69.6%. CONCLUSIONS: Cost, convenience, and perceived simplicity all appear to factor into a consumer's consideration of direct to consumer orthodontics. As annual household income, age, and education increases consumers are more likely to consider direct to consumer orthodontic treatment.


Assuntos
Ortodontia , Adolescente , Adulto , Criança , Estudos Transversais , Demografia , Assistência Odontológica , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
6.
Langmuir ; 36(26): 7268-7276, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32543183

RESUMO

Hydrogels of biopolymers such as agar and gelatin are widely used in many applications, and in many cases, the gels are loaded with nanoparticles. The polymer chains in these gels are cross-linked by physical bonds into three-dimensional networks, with the mesh size of these networks typically being 10-100 nm. One class of "soft" nanoparticles are liposomes, which have an aqueous core surrounded by a lipid bilayer. Solutes encapsulated in the liposomal core can be delivered externally over time. In this paper, we create liposomes with diameters ∼150 nm from an unsaturated phospholipid (lecithin) and embed them in agar gels (the aqueous phase also contains 0-50% of glycerol, which is an active ingredient in cosmetic products). Upon placing this gel in quiescent water, we find that the liposomes release out of the gel into the water over a period of 1-3 days, even though the gel remains intact. This is a surprising result that runs contrary to our expectation that the liposomes would simply remain immobilized in the gel. We show that the release rate of liposomes can be tuned by several variables: for example, the release rate increases as the agar concentration is lowered and the rate increases steadily with temperature. In addition to agar, release of liposomes also occurs out of other physical gels including those of agarose and gelatin. However, liposomes made from a saturated phospholipid do not release out of any gels. We discuss a possible mechanism for liposomal release, which involves intact liposomes deforming and squeezing through transient large pores that arise in physical networks such as agar. Our findings have relevance to transdermal delivery: they suggest the possibility of systematically delivering liposomes loaded with actives out of an intact matrix.


Assuntos
Hidrogéis , Lipossomos , Biopolímeros , Gelatina , Géis , Fosfatidilcolinas
7.
J Med Internet Res ; 22(10): e16802, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33112254

RESUMO

BACKGROUND: Adolescent depression carries a high burden of disease worldwide, but access to care for this population is limited. Prevention is one solution to curtail the negative consequences of adolescent depression. Internet interventions to prevent adolescent depression can overcome barriers to access, but few studies examine long-term outcomes. OBJECTIVE: This study compares CATCH-IT (Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training), an internet-based intervention, to a general health education active control for depression onset at 12 and 24 months in adolescents presenting to primary care settings. METHODS: A 2-site randomized trial, blinded to the principal investigators and assessors, was conducted comparing Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training to health education to prevent depressive episodes in 369 adolescents (193 youths were randomly assigned to Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training and 176 to health education) with subthreshold depressive symptoms or prior depressive episodes. Participants were recruited from primary care settings in the United States. The primary outcome was the occurrence of a depressive episode, determined by the Depression Symptom Rating. The secondary outcome was functioning, measured by the Global Assessment Scale. RESULTS: In intention-to-treat analyses, the adjusted hazard ratio favoring Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training for first depressive episode was not statistically significant at 12 months (hazard ratio 0.77, 95% CI 0.42-1.40, P=.39) and 24 months (hazard ratio 0.87, 95% CI 0.52-1.47, P=.61). Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training provided preventive benefit for first depressive episode for those with mild hopelessness or at least moderate paternal monitoring at baseline. Global Assessment Scale scores improved comparably in both groups (intention-to-treat). CONCLUSIONS: A technology-based intervention for adolescent depression prevention implemented in primary care did not have additional benefit at 12 or 24 months. Further research is necessary to determine whether internet interventions have long-term benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT01893749; http://clinicaltrials.gov/ct2/show/NCT01893749.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Depressão/terapia , Intervenção Baseada em Internet/tendências , Atenção Primária à Saúde/métodos , Adolescente , Feminino , Humanos , Internet , Masculino , Fatores de Tempo , Resultado do Tratamento
8.
Ir Med J ; 112(7): 969, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642643

RESUMO

Aims To explore the integration and delivery of oncology led referrals to palliative care (PC) by examining physician attitudes and referral practices. Methods An online survey was circulated to oncologists and PC physicians in Ireland. Results The study (N = 100) comprised sixty-nine oncologists (69%) and thirty-one PC physicians (31%). Ninety-two(92%) believe patients with advanced cancer should receive concurrent treatment, however only 53% of oncologists(N = 37) routinely refer. Regarding end-of-life (EOL) care: 81% of oncologists (N = 55) are directly involved in its administration, despite 84% (N = 53) agreeing patients benefit when PC specialists coordinate EOL care. Conclusion The gulf between positive attitudes and limited implementation suggests the need for interdisciplinary changes to facilitate integration of PC in clinical practice in Ireland.


Assuntos
Gerenciamento Clínico , Neoplasias , Oncologistas/estatística & dados numéricos , Cuidados Paliativos/estatística & dados numéricos , Encaminhamento e Consulta , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Oncologistas/psicologia , Cuidados Paliativos/psicologia
9.
Telemed J E Health ; 24(1): 37-44, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28657881

RESUMO

BACKGROUND: Internet Support Groups (ISGs) offer people easy access to information regarding depression as well as support from others who are either currently suffering from depression or have previously suffered from depression. The safety and efficacy of ISGs for people with depression have not been thoroughly studied. INTRODUCTION: The safety and helpfulness of a depression ISG were assessed by analyzing pre- and postintervention depressive symptoms, other psychological outcomes, and participant ratings of helpfulness. MATERIALS AND METHODS: Participants were recruited through self-referral from six primary care offices. Participants were given access to a depression ISG and participated in an ISG for 6 weeks. RESULTS: Thirty-four (n = 34) participants enrolled in the study (mean age = 32.53, standard deviation [SD] = 16.10). Depressive symptoms approached significance for decreasing over time and self-efficacy increased over time. No self-harm occurred over the course of the study, but two participants developed self-harm ideation. Ratings of ISG helpfulness were mixed. DISCUSSION: Primary care patients participating in depression ISGs reported few adverse experiences directly related to the ISG. Depressive symptoms and self-efficacy have beneficial findings while ratings of helpfulness were mixed. CONCLUSIONS: Primary care patients can benefit from the use of an ISG. This could be particularly pertinent to people in rural settings where mental health resources are not as available. An ISG offers a low-cost and easily accessible resource for primary care patients with depression.


Assuntos
Depressão/terapia , Internet , Atenção Primária à Saúde/organização & administração , Grupos de Autoajuda/organização & administração , Adulto , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Solidão , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Autoeficácia , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Apoio Social , Fatores Socioeconômicos
10.
Biotechnol Lett ; 39(6): 805-817, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28275884

RESUMO

New antibiotics are urgently required by human medicine as pathogens emerge with developed resistance to almost all antibiotic classes. Pioneering approaches, methodologies and technologies have facilitated a new era in antimicrobial discovery. Innovative culturing techniques such as iChip and co-culturing methods which use 'helper' strains to produce bioactive molecules have had notable success. Exploiting antibiotic resistance to identify antibacterial producers performed in tandem with diagnostic PCR based identification approaches has identified novel candidates. Employing powerful metagenomic mining and metabolomic tools has identified the antibiotic'ome, highlighting new antibiotics from underexplored environments and silent gene clusters enabling researchers to mine for scaffolds with both a novel mechanism of action and also few clinically established resistance determinants. Modern biotechnological approaches are delivering but will require support from government initiatives together with changes in regulation to pave the way for valuable, efficacious, highly targeted, pathogen specific antimicrobial therapies.


Assuntos
Antibacterianos , Biotecnologia , Técnicas de Cocultura , Descoberta de Drogas , Aspergillus , Metagenômica , Streptomyces
11.
Lett Appl Microbiol ; 63(2): 89-95, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27227694

RESUMO

UNLABELLED: Two Gram-negative Enterobacteriaceae, Gibbsiella quercinecans and Brenneria goodwinii, are frequently isolated from oak suffering from Acute Oak Decline. These two species are difficult to identify based on colony morphology, carbohydrate utilization or 16S rRNA gene sequence, and identification using gyrB gene sequencing is time-consuming and laborious. A rapid identification technique, based on high-resolution melt analysis of the atpD gene, was designed to efficiently process numerous isolates from an increasing number of affected woodlands and parks. Principal component analysis of the resulting melt curves from strains of G. quercinecans, B. goodwinii and their close phylogenetic relatives allowed differentiation into distinct clusters based on species or subspecies identity. SIGNIFICANCE AND IMPACT OF THE STUDY: Acute Oak Decline is an increasing threat to Britain's native oak population. Two novel bacterial species both belonging to the family Enterobacteriaceae, Gibbsiella quercinecans and Brenneria goodwinii, are thought to play an important role in symptom development. Here, we describe a rapid identification technique using high-resolution melt analysis of the atpD gene able to assign isolates to either G. quercinecans or B. goodwinii in a single assay, greatly reducing the time taken to identify if either or both of these species are present in symptomatic oak.


Assuntos
DNA Girase/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/isolamento & purificação , Doenças das Plantas/microbiologia , Quercus/microbiologia , Fatores de Transcrição/genética , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Enterobacteriaceae/genética , Desnaturação de Ácido Nucleico , Filogenia , Análise de Componente Principal , RNA Ribossômico 16S/genética , Reino Unido
12.
Surgeon ; 14(2): 82-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25444439

RESUMO

INTRODUCTION: There is an average of 25 cases of penile cancer in the Republic of Ireland each year. Due to the low volume of cases, the National Institute for Clinical Excellence recommends that treatment is centralised to allow the best standardised treatment for primary tumours and nodal disease. OBJECTIVES: To determine whether outcomes for patients with penile cancer differed significantly between secondary and tertiary referral centres in the Republic of Ireland. METHODS: Between 2001 and 2014, 36 patients were treated in the Mercy University Hospital (MUH) with penile cancer. Twenty patients were treated primarily in MUH and 16 patients underwent initial management in a secondary referral centre (SRC) with subsequent referral to the MUH. A retrospective matched case-control study was performed on this patient cohort. RESULTS: There were no significant differences in length of follow-up or risk factors for the development of penile cancer between both groups (p = 0.6 and p = 0.5 respectively) Ultimately, the incidence of high risk disease, nodal metasases, high grade disease and pelvic lymph node dissection were significantly greater in patients that were initially managed in a SRC (p = 0.02, p = 0.03, p = 0.004 and p = 0.028 respectively). Patients undergoing initial treatment in a SRC had a non-significantly reduced rate of cancer specific survival (88 Vs 66%, MUH Vs SRCs, p = 0.495) and recurrence free survival (85 Vs 46%, MUH Vs SRCs, p = 0.24). CONCLUSION: Our findings suggest that managing penile cancer in special interest centres may improve oncological outcome.


Assuntos
Gerenciamento Clínico , Estadiamento de Neoplasias , Neoplasias Penianas/terapia , Idoso , Seguimentos , Humanos , Incidência , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Penianas/epidemiologia , Estudos Retrospectivos
13.
Surgeon ; 14(1): 18-21, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25151340

RESUMO

OBJECTIVES: To describe our experience of all patients presenting to a tertiary referral centre over a 3 year time period with blunt scrotal trauma and to describe a methodical approach for managing this group of patients. METHODS: A retrospective analysis was performed on all patients presenting to the Emergency Department (ED) of a level 1 trauma centre with blunt scrotal trauma from 2010 to 2013 inclusive. Inclusion criteria included a recent history of blunt scrotal trauma with associated pain and/or swelling of the affected testis on clinical examination. RESULTS: Twenty-seven male patients with a median age of 19 (range 8-65) years were included and all but 1 patient underwent scrotal ultrasonography upon presentation. Sixteen patients (59%) presented with scrotal trauma secondary to a sports related injury. Fifteen patients were managed conservatively and of the 12 who underwent urgent exploration 9 had a testicular rupture, including 1 who had an emergency orchidectomy due to a completely shattered testis. Four patients had >30% of the testis replaced by necrotic tissue/haematoma; of which 2 ultimately underwent orchidectomy and insertion of testicular prosthesis. CONCLUSION: Our findings demonstrate that the necessity for scrotal protection in sports that predispose to scrotal trauma should be reviewed. We also demonstrate the importance of scrotal ultrasonography for determining an appropriate management strategy (i.e., conservative versus surgical treatment) in this young patient cohort.


Assuntos
Diagnóstico por Imagem/métodos , Gerenciamento Clínico , Serviço Hospitalar de Emergência , Guias de Prática Clínica como Assunto , Escroto/lesões , Ferimentos não Penetrantes , Adolescente , Adulto , Idoso , Criança , Humanos , Islândia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/etiologia , Ferimentos não Penetrantes/terapia , Adulto Jovem
14.
Int Urogynecol J ; 26(3): 313-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25216630

RESUMO

INTRODUCTION AND HYPOTHESIS: Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data assessing the effectiveness of trigonal BoNT-A are limited. This study evaluates adverse events (AEs) and short-term efficacy associated with trigonal and extratrigonal BoNT-A. METHODS: Electronic databases (PubMed, EMBASE, and the Cochrane database) were searched for studies comparing trigonal and extratrigonal BoNT-A for DO. Meta-analyses were performed using the random effects model. Outcome measures included incidence of AEs and short-term efficacy. RESULTS: Six studies describing 258 patients met the inclusion criteria. The meta-analysis did not show significant differences between trigonal and extratrigonal BoNT-A for acute urinary retention (AUR; 4.2 vs 3.7 %; odds ratio [OR]: 1.068, 95 % confidence interval [CI]: 0.239-4.773; P = 0.931) or high post-void residual (PVR; 25.8 vs 22.2 %; OR: 0.979; 95 % CI: 0.459-2.088; P = 0.956). The incidence of urinary tract infection (UTI; 7.5 vs 21.0 %; OR: 0.670; 95 % CI: 0.312-1.439; P = 0.305), haematuria (15.8 vs 25.9 %; OR: 0.547; 95 % CI: 0.264-1.134; P = 0.105) and post-operative muscle weakness (9.2 vs 11.3 %; OR: 0.587; 95 % CI: 0.205-1.680, P = 0.320) was similar in both groups. Finally, differences in short-term cure rates between two study arms were not statistically significant (52.9 vs 56.9 %; OR: 1.438; 95 % CI: 0.448-4.610; P = 0.542). CONCLUSIONS: Although data are limited, no significant differences between trigonal and extratrigonal BoNT-A in terms of AEs and short-term efficacy were observed. Additional randomised controlled trials are required to define optimal injection techniques and sites for administering intra-vesical BoNT-A.


Assuntos
Inibidores da Liberação da Acetilcolina/administração & dosagem , Inibidores da Liberação da Acetilcolina/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Administração Intravesical , Humanos
15.
Ir Med J ; 108(4): 125-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26016309

RESUMO

Empathy is increasingly being recognized as a crucial component for an effective doctor-patient relationship. Using a mixed method approach, we surveyed 125 patients and 361 medical practitioners (doctors and medical students) views of the doctor-patient relationship. We qualitatively assessed patients' views of what constituted a good doctor and qualitatively measured empathy using a validated scale in medical practitioners. Patients desire a doctor that is both clinically proficient 66 (55%) and caring 32 (27%). Doctors who have a personal experience of illness have a statistically higher empathy score. These doctors may be well placed to help develop and foster empathy in our profession.


Assuntos
Empatia , Pacientes/psicologia , Relações Médico-Paciente , Médicos/psicologia , Feminino , Humanos , Masculino , Satisfação do Paciente , Encaminhamento e Consulta , Inquéritos e Questionários
17.
Br J Cancer ; 109(2): 433-43, 2013 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-23807168

RESUMO

BACKGROUND: Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded protein response (UPR) and enhance cell death in combination with ER stress inducers. METHODS: Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting. RESULTS: Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells. CONCLUSION: Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/uso terapêutico , Catequina/análogos & derivados , Proteínas de Choque Térmico/metabolismo , Lignanas/uso terapêutico , Neoplasias/tratamento farmacológico , Antineoplásicos Fitogênicos/metabolismo , Compostos de Bifenilo/metabolismo , Catequina/metabolismo , Catequina/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico/antagonistas & inibidores , Humanos , Lignanas/metabolismo , Terapia de Alvo Molecular , Peso Molecular , Neoplasias/patologia , Ligação Proteica/efeitos dos fármacos
18.
Ir Med J ; 106(5): 149-51, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23914579

RESUMO

Since 2008, government funding of the Health Service Executive (HSE) has decreased significantly. Our hospital, Cork University Hospital (CUH), implemented "cost saving" measures including scheduled operating theatre closures. We studied their affect on urological surgical activity at the hospital. A retrospective review was performed using theatre log books and theatre records to determine the number, type and training status of procedures performed for years 2009 and 2011. Scheduled theatre closures in 2011 resulted in 33 more theatre session cancelations compared to 2009. There was a reduction in the total number of procedures performed from 555 cases in 2009 to 443 in 2011 a 20.2(%) reduction. The number of "training" cases reduced from 325 (58.9%) in 2009 to 216 (48.7%) in 2011 a 10.2% reduction (Table 2). Eight out of the nine "core urology training" procedures reduced in number from 2009 to 2011 (Table 1). We have shown that scheduled theatre closures have reduced the number of procedures performed and have impacted on urology training. Scheduled theatre closures are expected to become more frequent in the future. Potential solutions to lessen the impact include providing simulation training using the Royal College of Surgeons in Ireland (RCSI) mobile skills unit during these theatre closures.


Assuntos
Fechamento de Instituições de Saúde , Salas Cirúrgicas , Urologia/educação , Redução de Custos , Humanos , Irlanda , Estudos Retrospectivos
19.
Phys Rev Lett ; 109(24): 245006, 2012 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-23368336

RESUMO

A novel absorption mechanism for linearly polarized lasers propagating in relativistically underdense solids in the ultrarelativistic (a ~ 100) regime is presented. The mechanism is based on strong synchrotron emission from electrons reinjected into the laser by the space charge field they generate at the front of the laser pulse. This laser absorption, termed reinjected electron synchrotron emission, is due to a coupling of conventional plasma physics processes to quantum electrodynamic processes in low density solids at intensities above 10(22) W/cm(2). Reinjected electron synchrotron emission is identified in 2D QED-particle-in-cell simulations and then explained in terms of 1D QED-particle-in-cell simulations and simple analytical theory. It is found that between 1% (at 10(22) W/cm(2)) and 14% (at 8 × 10(23) W/cm(2)) of the laser energy is converted into gamma ray photons, potentially providing an ultraintense future gamma ray source.

20.
Phys Rev Lett ; 108(16): 165006, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22680729

RESUMO

In simulations of a 10 PW laser striking a solid, we demonstrate the possibility of producing a pure electron-positron plasma by the same processes as those thought to operate in high-energy astrophysical environments. A maximum positron density of 10(26) m(-3) can be achieved, 7 orders of magnitude greater than achieved in previous experiments. Additionally, 35% of the laser energy is converted to a burst of γ rays of intensity 10(22) W cm(-2), potentially the most intense γ-ray source available in the laboratory. This absorption results in a strong feedback between both pair and γ-ray production and classical plasma physics in the new "QED-plasma" regime.

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