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OBJECTIVE: Around 30% of people with long-term physical health conditions (LTCs) experience comorbid anxiety and depression. For many, comorbid distress is linked to difficulties adjusting to the challenges of the LTC. The aims of this article are to present a transdiagnostic theoretical model of adjustment to LTCs (TMA-LTC), demonstrate the application of this model in clinical practice, and highlight the distinguishing features of treating LTC-related distress compared with treating primary anxiety and/or depression. METHODS: A systematic review (k = 21) was conducted to collate preexisting evidence-based models of adjustment across LTCs. Models of adjustment for a range of LTCs were extracted and synthesized into a new preliminary TMA-LTC. Two expert consensus meetings were held, where experts rated the relevance and importance of all concepts within the models. RESULTS: The TMA-LTC proposes that acute critical events or ongoing illness stressors can disrupt emotional equilibrium, and that whether a person returns to equilibrium and achieves good psychological adjustment depends on a number of cognitive and behavioral factors, as well as their interpersonal, intrapersonal, environmental, and illness-specific contexts. A case study is presented to demonstrate the clinical application of this model in treating illness-related distress, highlighting how it overcomes roadblocks that may be encountered when working primarily within traditional mental health paradigms. CONCLUSIONS: As an empirically and clinically informed model, TMA-LTC provides a useful guide for assessment, formulation, and treatment in the context of psychological adjustment to LTCs. Future studies are needed to test treatments that have been developed based on TMA-LTC.
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Ansiedad , Ajuste Emocional , Trastornos de Ansiedad , Comorbilidad , Humanos , Salud MentalRESUMEN
The perceived risk of CO2 leakage through wells has been considered a potential limitation to commercial scale deployment of geologic CO2 storage. However, chemical and mechanical alteration of cement can reduce the permeability of leakage pathways. We conducted 100s of simulations spanning realistic operating conditions and well-damage characteristics to understand (1) under what conditions and time frames do fractures seal and (2) for fractures that do not seal, how quickly and to what extent is the permeability reduced. For the conditions simulated, fractures with apertures in the tens of microns seal while those greater than hundreds of microns may exhibit long-term leakage. Fractures with apertures between 10 and 500 µm took a few days to a couple of years to seal. For non-sealing fractures mechanical deformation of altered asperities can rapidly reduce permeability. A sealing criterion was developed to relate fracture aperture with the cemented length required for self-sealing. Longer cemented intervals can seal large fractures; however, they take longer to seal and leak larger volumes before sealing. While the results presented here are subject to uncertainties, the manuscript provides a framework in which a model can be used to quantitatively answer questions regarding well integrity to facilitate decision making.
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Dióxido de Carbono , Pozos de Agua , Materiales de Construcción , Geología , Fenómenos MecánicosRESUMEN
Depleted oil reservoirs are considered a viable solution to the global challenge of CO2 storage. A key concern is whether the wells can be suitably sealed with cement to hinder the escape of CO2. Under reservoir conditions, CO2 is in its supercritical state, and the high pressures and temperatures involved make real-time microscopic observations of cement degradation experimentally challenging. Here, we present an in situ 3D dynamic X-ray micro computed tomography (µ-CT) study of well cement carbonation at realistic reservoir stress, pore-pressure, and temperature conditions. The high-resolution time-lapse 3D images allow monitoring the progress of reaction fronts in Portland cement, including density changes, sample deformation, and mineral precipitation and dissolution. By switching between flow and nonflow conditions of CO2-saturated water through cement, we were able to delineate regimes dominated by calcium carbonate precipitation and dissolution. For the first time, we demonstrate experimentally the impact of the flow history on CO2 leakage risk for cement plugging. In-situ µ-CT experiments combined with geochemical modeling provide unique insight into the interactions between CO2 and cement, potentially helping in assessing the risks of CO2 storage in geological reservoirs.
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Dióxido de Carbono , Carbonatos , Materiales de Construcción , Agua , Microtomografía por Rayos XRESUMEN
AIM: To: (1) provide greater insight into the psychological and social impact of a range of demyelinating disorders, (2) explore differences between disorders, and (3) provide direction for future research. METHOD: Studies were identified by searching online databases. Studies that explored the psychological, emotional, or social impact of a range of demyelinating disorders in childhood, including acute disseminated encephalomyelitis (ADEM), optic neuritis, transverse myelitis, and multiple sclerosis, were included and screened independently by three authors. Data on the design, sample characteristics, psychosocial measures, key findings, and methodological strengths and limitations were extracted. Twenty-five studies were included in the narrative synthesis. RESULTS: Demyelinating disorders are associated with lower quality of life, affecting young people's emotional, social, school, and behavioural functioning. There is a high prevalence of psychiatric disorders and fatigue, particularly in multiple sclerosis. Subtle differences exist in the psychological presentation between different demyelinating disorders, with clear gaps in the research for the long-term psychosocial impact of monophasic conditions. INTERPRETATION: The difference between the impact of monophasic and relapsing demyelinating disorders on psychosocial functioning is unclear. Future research should aim to identify the psychosocial impact across disorders and over time, ensure that services are capturing those patients who may benefit from tailored interventions. WHAT THIS PAPER ADDS: Prevalence of psychiatric diagnoses in paediatric demyelinating disorders is higher than controls. Depression and emotional concerns are elevated in paediatric demyelinating disorders. Demyelinating disorders impact children's quality of life across school, social, and physical functioning.
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Síntomas Conductuales , Enfermedades Autoinmunes Desmielinizantes SNC , Fatiga , Trastornos Mentales , Funcionamiento Psicosocial , Calidad de Vida , Síntomas Conductuales/etiología , Síntomas Conductuales/fisiopatología , Síntomas Conductuales/psicología , Niño , Enfermedades Autoinmunes Desmielinizantes SNC/complicaciones , Enfermedades Autoinmunes Desmielinizantes SNC/fisiopatología , Enfermedades Autoinmunes Desmielinizantes SNC/psicología , Fatiga/etiología , Fatiga/fisiopatología , Fatiga/psicología , Humanos , Trastornos Mentales/etiología , Trastornos Mentales/fisiopatología , Trastornos Mentales/psicología , Calidad de Vida/psicologíaRESUMEN
Aim: To assess real-world occurrence of common clinical trial-reported adverse events (AE) among patients with recurrent ovarian cancer initiating niraparib 200 mg/day. Materials & methods: This retrospective observational study used physician-extracted anonymized medical record data of eligible patients initiating niraparib 200 mg/day after platinum-based chemotherapy. Results: Of 153 patients, 57 (37%) experienced ≥1 of the three most common all-grade AEs within 3 months after niraparib initiation: nausea (16%; grade 3/4: 2%), thrombocytopenia (14%; grade 3/4: 3%) and fatigue (24%; grade 3/4: 3%). In the ENGOT-OV16/NOVA trial, these respective AEs occurred in 74, 61 and 59% of patients. Conclusion: Incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200 mg/day in real-world practice versus patients initiating niraparib 300 mg/day in ENGOT-OV16/NOVA.
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Antineoplásicos/uso terapéutico , Indazoles/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Piperidinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Femenino , Humanos , Indazoles/administración & dosificación , Indazoles/efectos adversos , Quimioterapia de Mantención , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Wells are considered to be high-risk pathways for fluid leakage from geologic CO2 storage reservoirs, because breaches in this engineered system have the potential to connect the reservoir to groundwater resources and the atmosphere. Given these concerns, a few studies have assessed leakage risk by evaluating regulatory records, often self-reported, documenting leakage in gas fields. Leakage is thought to be governed largely by initial well-construction quality and the method of well abandonment. The geologic carbon storage community has raised further concerns because acidic fluids in the CO2 storage reservoir, alkaline cement meant to isolate the reservoir fluids from the overlying strata, and steel casings in wells are inherently reactive systems. This is of particular concern for storage of CO2 in depleted oil and gas reservoirs with numerous legacy wells engineered to variable standards. Research suggests that leakage risks are not as great as initially perceived because chemical and mechanical alteration of cement has the capacity to seal damaged zones. Our work centers on defining the coupled chemical and mechanical processes governing flow in damaged zones in wells. We have developed process-based models, constrained by experiments, to better understand and forecast leakage risk. Leakage pathways can be sealed by precipitation of carbonate minerals in the fractures and deformation of the reacted cement. High reactivity of cement hydroxides releases excess calcium that can precipitate as carbonate solids in the fracture network under low brine flow rates. If the flow is fast, then the brine remains undersaturated with respect to the solubility of calcium carbonate minerals, and zones depleted in calcium hydroxides, enriched in calcium carbonate precipitates, and made of amorphous silicates leached of original cement minerals are formed. Under confining pressure, the reacted cement is compressed, which reduces permeability and lowers leakage risks. The broader context of this paper is to use our experimentally calibrated chemical, mechanical, and transport model to illustrate when, where, and in what conditions fracture pathways seal in CO2 storage wells, to reduce their risk to groundwater resources. We do this by defining the amount of cement and the time required to effectively seal the leakage pathways associated with peak and postinjection overpressures, within the context of oil and gas industry standards for leak detection, mitigation, and repairs. Our simulations suggest that for many damage scenarios chemical and mechanical processes lower leakage risk by reducing or sealing fracture pathways. Leakage risk would remain high in wells with a large amount of damage, modeled here as wide fracture apertures, where fast flowing fluids are too dilute for carbonate precipitation and subsurface stress does not compress the altered cement. Fracture sealing is more likely as reservoir pressures decrease during the postinjection phase where lower fluxes aid chemical alteration and mechanical deformation of cement. Our results hold promise for the development of mitigation framework to avoid impacting groundwater resources above any geologic CO2 storage reservoir by correlating operational pressures and barrier lengths.
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PURPOSE: The optimal management of early squamous cell carcinoma of the anal canal (AC) is yet to be determined. This study investigated current practice in the management of early AC. METHODS: A patterns of care survey was completed by Australian surgeons and radiation oncologists. Specific topics addressed were as follows: geographical location of practice, staging of disease, treatment approaches to T1N0 tumours and grade 3 anal intra-epithelial neoplasia (AIN3) lesions, radiotherapy planning, toxicities, follow-up and clinical trial involvement. RESULTS: Sixty-four responses were obtained. For the management of T1N0 disease, half the respondents recommended standard dose chemo-radiotherapy (CRT) and one third recommended wide local excision (WLE). For the management of AIN3, half recommended WLE while a quarter advocated observation. CONCLUSIONS: This study reveals a significant variation in the management of early AC. The development of guidelines specific to the treatment of early AC could standardise treatment while further research is required to define the optimal management of T1N0 AC and AIN.
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Neoplasias del Ano/terapia , Carcinoma in Situ/terapia , Carcinoma de Células Escamosas/terapia , Disparidades en Atención de Salud/normas , Guías de Práctica Clínica como Asunto/normas , Pautas de la Práctica en Medicina/normas , Oncólogos de Radiación/normas , Cirujanos/normas , Neoplasias del Ano/diagnóstico por imagen , Neoplasias del Ano/patología , Australia , Carcinoma in Situ/diagnóstico por imagen , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Ensayos Clínicos como Asunto/normas , Adhesión a Directriz/normas , Encuestas de Atención de la Salud , Humanos , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
During breast radiotherapy treatment, the contralateral breast receives radiation doses to the skin and subcutaneous tissue caused mainly from incident electron contamination and low energy photon scatter radiation. Measurements have shown that for a typical hybrid tangential treatment, these dose levels can be up to 17% of maximum applied prescription dose if no shielding is used during the treatment process. This work examined the use of different shielding metals, aluminum, copper, and lead to reduce peripheral radiation dose to evaluate the optimal metal to form the basis of a contralateral breast radiation shield. This work also shows a simple but novel method to substantially reduce this unwanted radiation dose with the use of a copper scale maille sheet which can be easily and accurately draped over a patient's contralateral breast during treatment. The copper scale maille is flexible and can thus conform around typical breast shapes. It can also form irregular shaped edges to match those outlined by typical tangential treatment fields. As the shield is made from copper, it is nontoxic and can potentially be used directly on patients for treatment. The designed copper scale maille has shown to reduce contralateral breast skin and subcutaneous dose by up to 80% for typical radiation fields used in breast radiotherapy.
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Neoplasias de la Mama/radioterapia , Mama/efectos de la radiación , Protección Radiológica/instrumentación , Dispersión de Radiación , Electrones , Femenino , Humanos , Fotones , Dosificación RadioterapéuticaRESUMEN
Selective serotonin reuptake inhibitors (SSRIs) were designed to treat depression by increasing serotonin levels throughout the brain via inhibition of clearance from the extracellular space. Although increases in serotonin levels are observed after acute SSRI exposure, 3-6 weeks of continuous use is required for relief from the symptoms of depression. Thus, it is now believed that plasticity in multiple brain systems that are downstream of serotonergic inputs contributes to the therapeutic efficacy of SSRIs. The onset of antidepressant effects also coincides with desensitization of somatodendritic serotonin autoreceptors in the dorsal raphe nucleus (DRN), suggesting that disrupting inhibitory feedback within the serotonin system may contribute to the therapeutic effects of SSRIs. Previously, we showed that chronic SSRI treatment caused a frequency-dependent facilitation of serotonin signaling that persisted in the absence of uptake inhibition. In this work, we use in vivo fast-scan cyclic voltammetry in mice to investigate a similar facilitation after a single treatment of the SSRI citalopram hydrobromide. Acute citalopram hydrobromide treatment resulted in frequency-dependent increases of evoked serotonin release in the substantia nigra pars reticulata. These increases were independent of changes in uptake velocity, but required SERT expression. Using microinjections, we show that the frequency-dependent enhancement in release is because of SERT inhibition in the DRN, demonstrating that SSRIs can enhance serotonin release by inhibiting uptake in a location distal to the terminal release site. The novel finding that SERT inhibition can disrupt modulatory mechanisms at the level of the DRN to facilitate serotonin release will help future studies investigate serotonin's role in depression and motivated behavior. In this work, stimulations of the dorsal raphe nucleus (DRN) evoke serotonin release that is recorded in the substantia nigra pars reticulata (SNpr) using in vivo fast-scan cyclic voltammetry. Systemic administration of a selective serotonin reuptake inhibitor (SSRI) causes both an increase in t1/2 and an increase in [5-HT]max in the SNpr. Local application of SSRI to the DRN recapitulates the increase in [5-HT]max observed in the SNpr without affecting uptake. Thus, SSRIs increase serotonin signaling via two distinct SERT-mediated mechanisms.
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AIM: Fatigue in children and adolescents with multiple sclerosis (caMS) is currently poorly understood. This review aimed to provide greater insight into this area and direction for future research by evaluating evidence of associations between fatigue and clinical, psychological, and social factors in caMS. METHOD: Studies were identified by searching online databases, hand-searching reference lists, and requesting unpublished literature from key authors. Studies that examined fatigue in relation to at least one clinical, psychological, or social factor in caMS were included. Data on design, sample characteristics, measures of fatigue, clinical, psychological, and social variables, and key findings were extracted. Twelve studies were narratively synthesized. RESULTS: Clinical factors appeared largely unrelated to fatigue, whereas associations between fatigue and tests of neurocognitive functioning, and fatigue and diagnosable psychiatric disorders, were mixed. However, fatigue and depressed mood consistently correlated. A small number of studies indicated associations between fatigue and reduced quality of life and school performance. INTERPRETATION: A sufficient explanatory model of fatigue in caMS is lacking as studies in this area are few and diverse. Future research should endeavour to identify potentially modifiable clinical and psychosocial factors that are associated with fatigue in caMS so that interventions targeting such factors may be developed.
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Fatiga , Esclerosis Múltiple , Adolescente , Niño , Fatiga/complicaciones , Fatiga/fisiopatología , Fatiga/psicología , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/psicologíaRESUMEN
PURPOSE: This pilot study aimed to obtain feedback on the feasibility, safety and acceptability of a psychosexual rehabilitation booklet developed for women undergoing pelvic radiation therapy (PRT) and to explore women's sexual, informational and supportive care needs post-PRT rehabilitation. METHODS: Twenty women treated with PRT for gynaecological or anorectal cancer within the last 5 years, who had received vaginal dilators, provided feedback on the format, content and utility of the booklet and discussed their post-treatment information needs, via a semi-structured phone interview. Women completed standardized (HADS, IES-R) and study-specific scales to characterize psychological status of the sample and to assess participants' booklet knowledge and feedback, respectively. RESULTS: The booklet was perceived as very helpful, informative and not distressing, providing additional information to that discussed with clinicians. After reading the booklet, women had good understanding of strategies to reduce the sexual impact of PRT. Many women reported that discussion of sexuality was often avoided during consultations, despite them experiencing distressing sexual experiences and difficulties post-PRT. CONCLUSIONS: This novel resource which addresses an important component of post-pelvic radiation care appears acceptable and highly valued. Findings have highlighted a need for sexual health communication training for clinicians who treat this population so that they can initiate conversations about vaginal health and sexual health in an informed and comfortable manner. The impact of the revised booklet on psychosexual and clinical outcomes is being evaluated in a multicentre RCT.
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Neoplasias de los Genitales Femeninos/psicología , Neoplasias de los Genitales Femeninos/radioterapia , Aceptación de la Atención de Salud , Educación del Paciente como Asunto , Neoplasias del Recto/psicología , Neoplasias del Recto/radioterapia , Conducta Sexual/psicología , Adaptación Psicológica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Folletos , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Calidad de VidaRESUMEN
We experimentally demonstrate the direct coupling of silicate mineral dissolution with saline water electrolysis and H2 production to effect significant air CO2 absorption, chemical conversion, and storage in solution. In particular, we observed as much as a 10(5)-fold increase in OH(-) concentration (pH increase of up to 5.3 units) relative to experimental controls following the electrolysis of 0.25 M Na2SO4 solutions when the anode was encased in powdered silicate mineral, either wollastonite or an ultramafic mineral. After electrolysis, full equilibration of the alkalized solution with air led to a significant pH reduction and as much as a 45-fold increase in dissolved inorganic carbon concentration. This demonstrated significant spontaneous air CO2 capture, chemical conversion, and storage as a bicarbonate, predominantly as NaHCO3. The excess OH(-) initially formed in these experiments apparently resulted via neutralization of the anolyte acid, H2SO4, by reaction with the base mineral silicate at the anode, producing mineral sulfate and silica. This allowed the NaOH, normally generated at the cathode, to go unneutralized and to accumulate in the bulk electrolyte, ultimately reacting with atmospheric CO2 to form dissolved bicarbonate. Using nongrid or nonpeak renewable electricity, optimized systems at large scale might allow relatively high-capacity, energy-efficient (<300 kJ/mol of CO2 captured), and inexpensive (<$100 per tonne of CO2 mitigated) removal of excess air CO2 with production of carbon-negative H2. Furthermore, when added to the ocean, the produced hydroxide and/or (bi)carbonate could be useful in reducing sea-to-air CO2 emissions and in neutralizing or offsetting the effects of ongoing ocean acidification.
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Dióxido de Carbono/química , Secuestro de Carbono , Electrólisis/métodos , Hidrógeno/química , Silicatos/química , Cloruro de Sodio/química , Ácidos/química , Bicarbonatos/química , Compuestos de Calcio/química , Cloro/química , Electrólitos/química , Calentamiento Global , Minerales/química , Océanos y Mares , Agua de Mar/química , TermodinámicaRESUMEN
Human papillomavirus (HPV) causes most cases of anal cancers. In this study, we analyzed biopsy material from 112 patients with anal cancers in Australia for the presence of HPV DNA by the INNO LiPA HPV genotyping assay. There were 82% (92) males and 18% (20) females. The mean age at diagnosis was significantly (p = 0.006) younger for males (52.5 years) than females (66 years). HIV-infected males were diagnosed at a much earlier mean age (48.2 years) than HIV negative (56.3 years) males (p = 0.05). HPV DNA was detected in 96.4% (108) of cases. HPV type 16 was the commonest, at 75% (81) of samples and being the sole genotype detected in 61% (66). Overall, 79% (85) of cases had at least one genotype targeted by the bivalent HPV (bHPV) vaccine, 90% (97) by the quadrivalent HPV (qHPV) vaccine and 96% (104) by the nonavalent HPV (nHPV) vaccine. The qHPV vaccine, which is now offered to all secondary school students in Australia, may prevent anal cancers in Australia. However, given the mean age of onset of this condition, the vaccine is unlikely to have a significant impact for several decades. Further research is necessary to prove additional protective effects of the nHPV vaccine.
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Neoplasias del Ano/epidemiología , Neoplasias del Ano/virología , Genotipo , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Adulto , Factores de Edad , Anciano , Australia , ADN Viral/análisis , Femenino , Genes Virales , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Análisis de Secuencia de ADN , Factores SexualesRESUMEN
The development of accurate, predictive models for use in determining wellbore integrity requires detailed information about the chemical and mechanical changes occurring in hardened Portland cements. X-ray computed tomography (XRCT) provides a method that can nondestructively probe these changes in three dimensions. Here, we describe a method for extracting subvoxel mineralogical and chemical information from synchrotron XRCT images by combining advanced image segmentation with geochemical models of cement alteration. The method relies on determining "effective linear activity coefficients" (ELAC) for the white light source to generate calibration curves that relate the image grayscales to material composition. The resulting data set supports the modeling of cement alteration by CO2-rich brine with discrete increases in calcium concentration at reaction boundaries. The results of these XRCT analyses can be used to further improve coupled geochemical and mechanical models of cement alteration in the wellbore environment.
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Materiales de Construcción/análisis , Tomografía Computarizada por Rayos X/métodos , Calcio/química , Calibración , Carbonatos/química , Difusión , Modelos Teóricos , Sales (Química)/química , Espectrometría por Rayos XRESUMEN
Background: Major depressive disorder (MDD) exhibits gender disparities, and emerging evidence suggests the involvement of the gut microbiome, necessitating exploration of sex-specific differences. Methods: A review was conducted, encompassing a thorough examination of relevant studies available in Medline via Ovid, Embase via OvidSP, CINAHL, and PsycINFO databases from their inception to June 2023. The search strategy employed specific keywords and Medical Subject Headings (MeSH) terms tailored to major depressive disorder in women, encompassing unipolar depression, depressive symptoms, and dysbiosis. Results: Five studies were included. Among the four studies, alterations in alpha (n=1) and beta diversity (n=3) in the gut microbiome of individuals with MDD were revealed compared to controls. Gender-specific differences were observed in four studies, demonstrating the abundance of specific bacterial taxa and highlighting potential sex-specific implications in MDD pathophysiology. Correlation analyses (n=4) indicated associations between certain bacterial taxa and the severity of depressive symptoms, with varying patterns between males and females. Studies (n=3) also highlighted promising findings regarding the potential utility of microbial markers in diagnosing MDD, emphasizing the crucial role of sex stratification in understanding the disease pathophysiology. Conclusions: The findings underscore the importance of recognizing gender-specific differences in the composition of the gut microbiome and its relationship with MDD. Further comprehensive robust studies are required to unravel the intricate mechanisms underlying these disparities.
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Heme trafficking is essential for cellular function, yet mechanisms of transport and/or heme interaction are not well defined. The System I and System II bacterial cytochrome c biogenesis pathways are developing into model systems for heme trafficking due to their functions in heme transport, heme stereospecific positioning, and mediation of heme attachment to apocytochrome c. Here we focus on the System II pathway, CcsBA, that is proposed to be a bi-functional heme transporter and holocytochrome c synthase. An extensive structure-function analysis of recombinantly expressed Helicobacter pylori and Campylobacter jejuni CcsBAs revealed key residues required for heme interaction and holocytochrome c synthase activity. Homologous residues were previously identified to be required for heme interaction in Helicobacter hepaticus CcsBA. This study provides direct, biochemical evidence that mechanisms of heme interaction are conserved, leading to the proposal that the CcsBA WWD heme-handling domain represents a novel target for therapeutics.
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Proteínas Bacterianas , Campylobacter jejuni , Helicobacter pylori , Hemo , Hemo/metabolismo , Helicobacter pylori/enzimología , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Campylobacter jejuni/enzimología , Campylobacter jejuni/genética , Campylobacter jejuni/metabolismo , Relación Estructura-Actividad , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Unión Proteica , Modelos Moleculares , LiasasRESUMEN
In this perspective paper, the findings of the recently published LUMINA study are critically evaluated, with an emphasis on the need for careful interpretation and a thoughtful approach in clinical practice. The LUMINA trial, which investigates the role of adjuvant endocrine therapy in low-risk breast cancer patients, is assessed for its limitations, including a highly selective patient cohort and an insufficient follow-up period. The importance of long-term data and further trials to inform clinical decisions effectively is emphasized. While the LUMINA study does not support an immediate change in practice, it is seen as a foundation for generating hypotheses to guide ongoing clinical trials. This important study has served as inspiration to develop this perspective paper, which takes into account ongoing studies and the toxicity profile of postoperative treatments in low-risk recurrence breast cancer. The need for a patient-cantered approach is stressed, considering individual wishes and desires in decision-making, despite the complexity of articulating these aspects in guidelines. A wise interpretation of available findings is essential to ensure sound clinical decision-making before broadly applying omission of radiation therapy.
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Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Femenino , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/tratamiento farmacológico , Terapia CombinadaRESUMEN
Delineation of cardiac substructures is crucial for a better understanding of radiation-related cardiotoxicities and to facilitate accurate and precise cardiac dose calculation for developing and applying risk models. This review examines recent advancements in cardiac substructure delineation in the radiation therapy (RT) context, aiming to provide a comprehensive overview of the current level of knowledge, challenges and future directions in this evolving field. Imaging used for RT planning presents challenges in reliably visualising cardiac anatomy. Although cardiac atlases and contouring guidelines aid in standardisation and reduction of variability, significant uncertainties remain in defining cardiac anatomy. Coupled with the inherent complexity of the heart, this necessitates auto-contouring for consistent large-scale data analysis and improved efficiency in prospective applications. Auto-contouring models, developed primarily for breast and lung cancer RT, have demonstrated performance comparable to manual contouring, marking a significant milestone in the evolution of cardiac delineation practices. Nevertheless, several key concerns require further investigation. There is an unmet need for expanding cardiac auto-contouring models to encompass a broader range of cancer sites. A shift in focus is needed from ensuring accuracy to enhancing the robustness and accessibility of auto-contouring models. Addressing these challenges is paramount for the integration of cardiac substructure delineation and associated risk models into routine clinical practice, thereby improving the safety of RT for future cancer patients.
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Over the last several decades, fast-scan cyclic voltammetry (FSCV) has proved to be a valuable analytical tool for the real-time measurement of neurotransmitter dynamics in vitro and in vivo. Indeed, FSCV has found application in a wide variety of disciplines including electrochemistry, neurobiology, and behavioral psychology. The maturation of FSCV as an in vivo technique led users to pose increasingly complex questions that require a more sophisticated experimental design. To accommodate recent and future advances in FSCV application, our lab has developed High Definition Cyclic Voltammetry (HDCV). HDCV is an electrochemical software suite that includes data acquisition and analysis programs. The data collection program delivers greater experimental flexibility and better user feedback through live displays. It supports experiments involving multiple electrodes with customized waveforms. It is compatible with transistor-transistor logic-based systems that are used for monitoring animal behavior, and it enables simultaneous recording of electrochemical and electrophysiological data. HDCV analysis streamlines data processing with superior filtering options, seamlessly manages behavioral events, and integrates chemometric processing. Furthermore, analysis is capable of handling single files collected over extended periods of time, allowing the user to consider biological events on both subsecond and multiminute time scales. Here we describe and demonstrate the utility of HDCV for in vivo experiments.
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Técnicas Electroquímicas/métodos , Programas Informáticos , Animales , HumanosRESUMEN
The Mount Simon sandstone and Eau Claire shale formations are target storage and cap rock formations for the Illinois Basin-Decatur Geologic Carbon Sequestration Project. We reacted rock samples with brine and supercritical CO(2) at 51 °C and 19.5 MPa to access the reactivity of these formations at storage conditions and to address the applicability of using published kinetic and thermodynamic constants to predict geochemical alteration that may occur during storage by quantifying parameter uncertainty against experimental data. Incongruent dissolution of iron-rich clays and formation of secondary clays and amorphous silica will dominate geochemical alterations at this CO(2) storage site in CO(2)-rich brines. The surrogate iron-rich clay in the model required significant adjustments to its thermodynamic constants and inclusion of incongruent reaction terms to capture the change in solution composition under acid CO(2) conditions. This result emphasizes the need for experiments that constrain the conceptual geochemical model, calibrate mean parameter values, and quantify parameter uncertainty in reactive-transport simulations that will be used to estimate long-term CO(2) trapping mechanisms and changes in porosity and permeability.