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Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.
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Anticuerpos Monoclonales Humanizados , Penfigoide Ampolloso , Prurito , Humanos , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/diagnóstico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Prurito/tratamiento farmacológico , Prurito/etiología , Prurito/diagnóstico , Adulto , Reacción en el Punto de Inyección/etiología , Reacción en el Punto de Inyección/diagnósticoRESUMEN
Ethyl 2-[(2-oxo-2H-chromen-6-yl)-oxy]acetate, C13H12O5, a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C2/c space group in the form of sheets, within which mol-ecules are related by inversion centers and 21 axes. Multiple C-Hâ¯O weak hydrogen-bonding inter-actions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Inter-sheet inter-actions are a combination of coumarin system π-π stacking and additional C-Hâ¯O weak hydrogen bonds between ethyl acet-oxy groups.
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Here we test a method of incorporating of plant extracts into popular snack foods to help control diabetes. Since some fresh vegetables contain antidiabetic compounds, ultrasound-assisted extraction was used to optimize their extraction of from spring onions, bunching onions, and celery for later incorporation into crackers. We compared various concentrations of ethanol used during extraction, after which they were exposed to an ultrasound processor whose amplitude and sonication time were also varied. The optimal extraction conditions were found to be an ethanol concentration of 44.08%, an amplitude of 80%, and a sonication time of 30 min. This resulted in the highest level of α-glucosidase inhibitory activity (i.e., 1,449.73 mmol ACE/g) and the highest extraction yield (i.e., 24.16%). The extract produced from these optimum conditions was then used as a constituent component of crackers at 0.625%, 1.25%, or 2.5% w/w. These biscuits were then produced at baking temperatures of 140°C, 150°C, or 160°C. We then measured the physical characteristics and bioactivities of sample biscuits from each treatment. We found that biscuits containing 2.5% vegetable combination extract and baked at 140°C had the highest total phenolic content, the strongest antioxidant performance, and showed the most substantial antidiabetic and antiobesity effects. Here we establish conditions for the effective extraction of antidiabetic functional ingredients via ultrasound from green leafy vegetables. We also provide a method of using these ingredients to prepare crackers with the aim of developing a functional antidiabetic snack food.
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Factor XIIa (FXIIa) functions as a plasma serine protease within the contact activation pathway. Various animal models have indicated a substantial role for FXIIa in thromboembolic diseases. Interestingly, individuals and animals with FXII deficiency seem to maintain normal hemostasis. Consequently, inhibiting FXIIa could potentially offer a viable therapeutic approach for achieving effective and safer anticoagulation without the bleeding risks associated with the existing anticoagulants. Despite the potential, only a limited number of small molecule inhibitors targeting human FXIIa have been documented. Thus, we combined a small library of 32 triazole and triazole-like molecules to be evaluated for FXIIa inhibition by using a chromogenic substrate hydrolysis assay under physiological conditions. Initial screening at 200 µM involved 18 small molecules, revealing that 4 molecules inhibited FXIIa more than 20%. In addition to being the most potent inhibitor identified in the first round, inhibitor 8 also exhibited a substantial margin of selectivity against related serine proteases, including factors XIa, Xa, and IXa. However, the molecule also inhibited thrombin with a similar potency. It also prolonged the clotting time of human plasma, as was determined in the activated partial thromboplastin time and prothrombin time assays. Subsequent structure-activity relationship studies led to the identification of several inhibitors with submicromolar activity, among which inhibitor 22 appears to demonstrate significant selectivity not only over factors IXa, Xa, and XIa, but also over thrombin. In summary, this study introduces novel triazole-based small molecules, specifically compounds 8 and 22, identified as potent and selective inhibitors of human FXIIa. The aim is to advance these inhibitors for further development as anticoagulants to provide a more effective and safer approach to preventing and/or treating thromboembolic diseases.
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BACKGROUND: Developments in digital health have the potential to create new opportunities for healthcare professionals support delivery of palliative care. Globally, many palliative care professionals used digital health innovations to support communication with staff, patients and caregivers, during COVID-19 pandemic. However, there is limited data about the views of palliative care professionals of using digital health to support communication during the pandemic. We aimed to describe how palliative care professionals used technology to support communication (multidisciplinary team working, education and with patients and family caregivers) during the COVID-19 pandemic. METHOD(S): UK based palliative care healthcare professionals completed an electronic questionnaire to describe their use of digital health, during the COVID-19 pandemic, to support (1) communication within the multidisciplinary team (MDT), (2) education and (3) to support communication with patients and carers. RESULTS: Two hundred and thirty-four palliative care professionals participated. Most (n = 227, 97%) described an increase in their use of digital health, to support communication, since the start of the COVID-19 pandemic. We identified benefits and challenges for digital health communication, which we summarised into themes, including 'a new way of working', 'developing a new approach to learning' and 'impacting care'. CONCLUSION(S): Since the pandemic, palliative care professionals have increased their use of digital health to support communication in clinical practice. We have identified facilitators and barriers for future practice. Further work should identify the levels of support needed for organisations to ensure that digital health interventions are meaningfully used to help palliative care professionals effectively communicate with patients, caregivers and staff.
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COVID-19 , Cuidados Paliativos , Humanos , Pandemias , Comunicación , Atención a la Salud , TecnologíaAsunto(s)
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Anciano , Estudios Retrospectivos , Rayos X , Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Radiografía , Carcinoma Basocelular/diagnóstico por imagen , Carcinoma Basocelular/cirugíaAsunto(s)
Enfermedades del Tejido Conjuntivo , Granuloma de Células Gigantes , Mucinosis , Enfermedades de la Piel , Humanos , Granuloma de Células Gigantes/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Enfermedades de la Piel/genética , Piel , Mucinosis/diagnóstico , Mucinosis/genéticaRESUMEN
As a potential means for smoking cessation and consequently prevention of smoking-related diseases and mortality, in this study, our goal was to investigate the inhibition of nicotine metabolism by P450 2A6. Smoking is the main cause of many diseases and disabilities and harms nearly every organ of the body. As reported by the Centers for Disease Control and Prevention (CDC), more than 16 million Americans are living with diseases caused by smoking. On average, the life expectancy of a smoker is about 10 years less than a nonsmoker. Smoking cessation can substantially reduce the incidence of smoking-related diseases, including cancer. At least, 70 of the more than 7000 cigarette smoke components, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are known carcinogens. Nicotine is the compound responsible for the addictive and psychopharmacological effects of tobacco. Cytochrome P450 enzymes are responsible for the phase I metabolism of many tobacco components, including nicotine. Nicotine is mainly metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism decreases the amount of available nicotine in the bloodstream, leading to increased smoking behavior and thus exposure to tobacco toxicants and carcinogens. Here, we report the syntheses and P450 2A6 inhibitory activities of a number of new flavone-based esters and acids. Three of the flavone derivatives studied were found to be potent competitive inhibitors of the enzyme. Docking studies were used to determine the possible mechanisms of the activity of these inhibitors.
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Flavonas , Nicotina , Humanos , Nicotina/farmacología , Nicotina/metabolismo , Citocromo P-450 CYP2A6/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Carcinógenos/metabolismo , Flavonas/farmacologíaRESUMEN
Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.
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Hipertensión , Hipotensión , Humanos , Vitaminas , Presión Sanguínea , Magnesio/farmacología , Magnesio/uso terapéutico , Calcio/farmacología , Suplementos Dietéticos , Hipertensión/epidemiología , Minerales/farmacología , Minerales/uso terapéutico , Hipotensión/tratamiento farmacológico , Calcio de la Dieta/farmacología , Potasio/farmacología , Antihipertensivos/farmacologíaRESUMEN
Sodium nitrite is a food additive commonly used in sausages, but legally, the unsafe levels of nitrite in sausage should be less than 80 mg/kg, since higher levels can be harmful to consumers. Consumers must rely on processors to conform to these levels. Therefore, the determination of nitrite content in chicken sausages using near infrared hyperspectral imaging (NIR-HSI) was investigated. A total of 140 chicken sausage samples were produced by adding sodium nitrite in various levels. The samples were divided into a calibration set (n = 94) and a prediction set (n = 46). Quantitative analysis, to detect nitrate in the sausages, and qualitative analysis, to classify nitrite levels, were undertaken in order to evaluate whether individual sausages had safe levels or non-safe levels of nitrite. NIR-HSI was preprocessed to obtain the optimum conditions for establishing the models. The results showed that the model from the partial least squares regression (PLSR) gave the most reliable performance, with a coefficient of determination of prediction (Rp) of 0.92 and a root mean square error of prediction (RMSEP) of 15.603 mg/kg. The results of the classification using the partial least square-discriminant analysis (PLS-DA) showed a satisfied accuracy for prediction of 91.30%. It was therefore concluded that they were sufficiently accurate for screening and that NIR-HSI has the potential to be used for the fast, accurate and reliable assessment of nitrite content in chicken sausages.
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Eggs that are produced using organic methods retail at higher prices than those produced using conventional methods, but they cannot be differentiated reliably using visual methods. Eggs can therefore be fraudulently mislabeled in order to increase their wholesale and retail prices. The objective of this research was therefore to test near-infrared hyperspectral imaging (NIR-HSI) to identify whether an egg has been produced using organic or conventional methods. A total of 210 organic and 210 conventional fresh eggs were individually scanned using NIR-HSI to obtain absorbance spectra for discrimination analysis. The physical properties of each egg were also measured non-destructively in order to analyze the performance of discrimination compared with those of the NIR-HSI spectral data. Principal component analysis (PCA) showed variation for PC1 and PC2 of 57% and 23% and 94% and 4% based on physical properties and the spectral data, respectively. The best results of the classification using NIR-HSI spectral data obtained an accuracy of 96.03% and an error rate of 3.97% via partial least squares-discriminant analysis (PLS-DA), indicating the possibility that NIR-HSI could be successfully used to rapidly, reliably, and non-destructively differentiate between eggs that had been produced using organic methods from eggs that had been produced using conventional methods.
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This paper investigates a pursuit-evasion game with a single pursuer and evader in a bounded environment, inspired by observations of predation attempts by lionfish (Pterois sp.). The pursuer tracks the evader with a pure pursuit strategy while using an additional bioinspired tactic to trap the evader, i.e. minimize the evader's escape routes. Specifically, the pursuer employs symmetric appendages inspired by the large pectoral fins of lionfish, but this expansion increases its drag and therefore its work to capture the evader. The evader employs a bioinspired randomly-directed escape strategy to avoid capture and collisions with the boundary. Here we investigate the trade-off between minimizing the work to capture the evader and minimizing the evader's escape routes. By using the pursuer's expected work to capture as a cost function, we determine when the pursuer should expand its appendages as a function of the relative distance to the evader and the evader's proximity to the boundary. Visualizing the pursuer's expected work to capture everywhere in the bounded domain, yields additional insights about optimal pursuit trajectories and illustrates the role of the boundary in predator-prey interactions.
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Perciformes , Conducta Predatoria , AnimalesRESUMEN
It has been reported that some brands of roasted ground coffee, whose ingredients are labeled as 100% Arabica coffee, may also contain the cheaper Robusta coffee. Thus, the objective of this research was to test whether near-infrared spectroscopy hyperspectral imaging (NIR-HSI) or Fourier transform infrared spectroscopy (FTIRs) could be used to test whether samples of coffee were pure Arabica or whether they contained Robusta, and if so, what were the levels of Robusta they contained. Qualitative models of both the NIR-HSI and FTIRs techniques were established with support vector machine classification (SVMC). Results showed that the highest levels of accuracy in the prediction set were 98.04 and 97.06%, respectively. Quantitative models of both techniques for predicting the concentration of Robusta in the samples of Arabica with Robusta were established using support vector machine regression (SVMR), which gave the highest levels of accuracy in the prediction set with a coefficient of determination for prediction (Rp2) of 0.964 and 0.956 and root mean square error of prediction (RMSEP) of 5.47 and 6.07%, respectively. It was therefore concluded that the results showed that both techniques (NIR-HSI and FTIRs) have the potential for use in the inspection of roasted ground coffee to classify and determine the respective levels of Arabica and Robusta within the mixture.
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Síndrome del Nevo Basocelular , Carcinoma Basocelular , Fotoquimioterapia , Neoplasias Cutáneas , Humanos , Síndrome del Nevo Basocelular/tratamiento farmacológico , Estudios de Seguimiento , Carcinoma Basocelular/tratamiento farmacológico , Ácido Aminolevulínico/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/prevención & control , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Isolated optic neuropathy due to folate deficiency is rarely reported. Poor dietary practices, malabsorption, and tobacco/alcohol abuse are usually responsible. We examined a patient with blinding optic neuropathies and isolated folic acid deficiency. Visual acuity recovered after folate replacement. At the same time, serological investigation revealed high ferritin and iron saturation levels with negative genetic markers for haemochromatosis consistent with the diagnosis of iron overload syndrome. There are no reports of blindness associated with iron overload syndrome.
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Alcoholismo , Deficiencia de Ácido Fólico , Sobrecarga de Hierro , Enfermedades del Nervio Óptico , Ácido Fólico , Deficiencia de Ácido Fólico/complicaciones , Humanos , Sobrecarga de Hierro/complicaciones , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiologíaRESUMEN
Unexplained elevated intracranial pressure occasionally develops in individuals with Multiple Sclerosis (MS). Visual symptoms and signs are common to both conditions. An awareness of this association is particularly relevant due to the increased incidence of headache in MS and the frequent overlap of symptoms and signs in both conditions.