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Introduction: Aryl-alcohol oxidase (AAO) shows a pronounced duality as oxidase and dehydrogenase similar to that described for other glucose-methanol-choline (GMC) oxidase/dehydrogenase superfamily proteins involved in lignocellulose decomposition. In this work, we detail the overall mechanism of AAOs from Pleurotus eryngii and Bjerkandera adusta for catalyzing the oxidation of natural aryl-alcohol substrates using either oxygen or quinones as electron acceptors and describe the crystallographic structure of AAO from B. adusta in complex with a product analogue. Methods: Kinetic studies with 4-methoxybenzyl and 3-chloro-4- methoxybenzyl alcohols, including both transient-state and steady-state analyses, along with interaction studies, provide insight into the oxidase and dehydrogenase mechanisms of these enzymes. Moreover, the resolution of the crystal structure of AAO from B. adusta allowed us to compare their overall folding and the structure of the active sites of both AAOs in relation to their activities. Results and Discussion: Although both enzymes show similar mechanistic properties, notable differences are highlighted in this study. In B. adusta, the AAO oxidase activity is limited by the reoxidation of the flavin, while in P. eryngii the slower step takes place during the reductive half-reaction, which determines the overall reaction rate. By contrast, dehydrogenase activity in both enzymes, irrespective of the alcohol participating in the reaction, is limited by the hydroquinone release from the active site. Despite these differences, both AAOs are more efficient as dehydrogenases, supporting the physiological role of this activity in lignocellulosic decay. This dual activity would allow these enzymes to adapt to different environments based on the available electron acceptors.
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OBJECTIVE: Over the past 4 decades, discrepant research findings have emerged in the juror-confession literature, prompting the need for a systematic review and meta-analysis that assesses the effect of confession evidence (coerced or noncoerced) on conviction rates and the efficacy of trial safeguards. HYPOTHESES: We did not predict any directional hypotheses. Some studies show increased convictions when a confession is present (vs. not), regardless of whether that confession was coerced; other studies demonstrate that jurors are able to discount coerced confessions. Studies have also demonstrated sensitivity effects (safeguards aided jurors in making appropriate decisions), skepticism effects (safeguards led jurors to indiscriminately disregard confession evidence), or null effects with regard to expert testimony and jury instructions. METHOD: We identified 83 independent samples (N = 24,860) that met our meta-analytic inclusion criteria. Using extracted Hedges' g effect sizes, we conducted both network meta-analysis and metaregression to address key research questions. RESULTS: Coerced and noncoerced confessions (vs. no confession) increased convictions (network gs = 0.34 and 0.70, respectively), yet coerced (vs. noncoerced) confessions reduced convictions (network g = -0.36). When jury instructions were employed (vs. not), convictions in coerced confession cases were reduced (this difference did not emerge for noncoerced confessions; a sensitivity effect). Expert testimony, however, reduced conviction likelihood regardless of whether a confession was coerced (a skepticism effect). CONCLUSION: Confession evidence is persuasive, and although jurors appear to recognize the detrimental effect of coercive interrogation methods on confession reliability, they do not fully discount unreliable confessions. Educational safeguards are therefore needed, but more research is encouraged to identify the most effective forms of jury instructions and expert testimony. One potential reform could be in the interrogation room itself, as science-based interviewing approaches could provide jurors with more reliable defendant statement evidence that assists them in reaching appropriate verdict decisions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Subject(s)
Decision Making , Humans , Coercion , Criminal Law , Expert Testimony , Truth DisclosureABSTRACT
OBJECTIVE: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. METHODS: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). RESULTS: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. CONCLUSION: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.
Subject(s)
COVID-19 , Intensive Care Units , Respiration, Artificial , Survivors , Humans , COVID-19/epidemiology , COVID-19/therapy , Male , Female , Middle Aged , Prospective Studies , Aged , Survivors/statistics & numerical data , SARS-CoV-2 , Muscle Strength , Hand Strength , Respiratory Muscles/physiopathology , Physical Functional PerformanceABSTRACT
BACKGROUND: Decentralization of a health system is a complex and multidimensional phenomenon that demands thorough investigation of its process logistics, predisposing factors and implementation mechanisms, within the broader socio-political environment of each nation. Despite its wide adoption across both high-income countries (HICs) and low-and-middle-income countries (LMICs), empirical evidence of whether decentralization actually translates into improved health system performance remains inconclusive and controversial. This paper aims to provide a comprehensive description of the decentralization processes in three countries at different stages of their decentralization strategies - Pakistan, Brazil and Portugal. MAIN BODY: This study employed a systematic analysis of peer-reviewed academic journals, official government reports, policy documents and publications from international organizations related to health system decentralization. A comprehensive search was conducted using reputable databases such as PubMed, Google Scholar, the WHO repository and other relevant databases, covering the period up to the knowledge cutoff date in June 2023. Information was systematically extracted and organized into the determinants, process mechanics and challenges encountered during the planning, implementation and post-decentralization phases. Although decentralization reforms have achieved some success, challenges persist in their implementation. Comparing all three countries, it was evident that all three have prioritized health in their decentralization reforms and aimed to enhance local decision-making power. Brazil has made significant progress in implementing decentralization reforms, while Portugal and Pakistan are still in the process. Pakistan has faced significant implementation challenges, including capacity-building, resource allocation, resistance to change and inequity in access to care. Brazil and Portugal have also faced challenges, but to a lesser extent. The extent, progress and challenges in the decentralization processes vary among the three countries, each requiring ongoing evaluation and improvement to achieve the desired outcomes. CONCLUSION: Notable differences exist in the extent of decentralization, the challenges faced during implementation and inequality in access to care between the three countries. It is important for Portugal, Brazil and Pakistan to address these through reinforcing implementation strategies, tackling inequalities in access to care and enhancing monitoring and evaluation mechanism. Additionally, fostering knowledge sharing among these different countries will be instrumental in facilitating mutual learning.
Subject(s)
Delivery of Health Care , Health Care Reform , Health Policy , Politics , Humans , Brazil , Delivery of Health Care/organization & administration , Developing Countries , Health Care Reform/organization & administration , Pakistan , PortugalABSTRACT
Albright's hereditary osteodystrophy is a rare hereditary disease due to a mutation of the complex guanine nucleotide-binding protein, alpha-stimulating activity polypeptide. This condition is commonly associated with type 1A and 1C pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism due to resistance of parathyroid hormone. Patients present with specific characteristics such as brachydactyly, short stature, round facies, subcutaneous ossifications, developmental delay, and obesity, associated with hypocalcemia and hyperphosphatemia. This case presents a 55-year-old woman with short stature and neurocognitive impairment, who was admitted to the emergency department with acute decompensated heart and respiratory failure. On admission, hypocalcemia and hyperphosphatemia were noted, which in combination with the patient's clinical history led to an etiological investigation. This case stresses the importance of not only treating the acute disease but also looking at the patient and their clinical and analytical features to diagnose this disease and prevent its complications.
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Sheehan syndrome is a rare cause of hypopituitarism characterized by pituitary gland necrosis after postpartum hemorrhage. It is a pertinent cause of maternal morbidity and mortality in developing countries with deficient obstetrical care but is frequently overlooked in developed countries where its occurrence is uncommon. We present the case of a 66-year-old female diagnosed with Sheehan syndrome more than 30 years after her last delivery complicated by postpartum hemorrhage. Although the patient presented several symptoms and signs of pituitary hormonal deficiencies, a diagnosis had never been established before. The complete laboratory analysis revealed a deficiency in the pituitary axis, and the cranial imaging showed an empty sella turcica. Hormonal replacement therapy resolved several impairments in terms of general energy, physical capacity, temperature regulation, skin characteristics, and sexual function. It also improved her cardiovascular and osteoporosis risk, and, most importantly, prevented a potential life-threatening adrenal crisis. This report highlights the subtle manifestations of Sheehan syndrome to help clinicians establish a prompt diagnosis. Even in developed countries such as Portugal, this condition should be regarded as a potential cause of hypopituitarism.
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OBJECTIVE: Neurovascular coupling (NVC) represents the increase in regional blood flow associated with neural activity. The aim here was to describe a new approach to non-invasive measurement of NVC by spectral analysis of the cerebral blood flow velocity (CBFV) with transcranial Doppler. METHODS: In a sample of 20 healthy participants, we monitored systolic CBFV in the left posterior cerebral artery (PCA) during off (eyes closed) and on (flickering checkerboard) periods. The contralateral middle cerebral artery was simultaneously monitored as a control. Each participant was submitted to three experiments, each having five cycles, with increasing duration of the cycles, from 10 s (0.1 Hz) to 20 s (0.05 Hz) and lastly 40 s (0.025 Hz), half the time for on and for off periods, constituting a total of 6 min. The successive cycles were expected to cause oscillation in CBFV in a sinusoidal pattern that could be characterized by spectral analysis. We also measured the classic CBFV overshoot as the relative increase in percentage of systolic CBFV from baseline. The relationship and agreement between the two methods were analyzed by linear regression and Bland-Altman plots. In every participant, a clear peak of amplitude in the PCA CBFV spectrum was discernible at 0.1, 0.05 and 0.025 Hz of visual stimulation. RESULTS: On average, this amplitude was 7.1 ± 2.3%, 10.9 ± 3.5% and 17.3 ± 6.5%, respectively. This response contrasted significantly with an absent peak in middle cerebral artery monitoring (p < 0.0001). The spectral amplitude and classic overshoot were highly correlated and linearly related (p < 0.0001). CONCLUSION: NVC can be quantified by the spectral amplitude of PCA CBFV at slower and higher frequencies of visual stimulation. This method represents an alternative to classic overshoot without the need for stimulus marking or synchronization.
Subject(s)
Neurovascular Coupling , Humans , Neurovascular Coupling/physiology , Middle Cerebral Artery/diagnostic imaging , Blood Flow Velocity/physiology , Ultrasonography, Doppler, Transcranial/methods , Healthy Volunteers , Cerebrovascular Circulation/physiologyABSTRACT
A novel trypsin inhibitor from Cajanus cajan (TIC) fresh leaves was partially purified by affinity chromatography. SDS-PAGE revealed one band with about 15 kDa with expressive trypsin inhibitor activity by zymography. TIC showed high affinity for trypsin (Ki = 1.617 µM) and was a competitive inhibitor for this serine protease. TIC activity was maintained after 24 h of treatment at 70 °C, after 1 h treatments with different pH values, and ß-mercaptoethanol increasing concentrations, and demonstrated expressive structural stability. However, the activity of TIC was affected in the presence of oxidizing agents. In order to study the effect of TIC on secreted serine proteases, as well as on the cell culture growth curve, SK-MEL-28 metastatic human melanoma cell line and CaCo-2 colon adenocarcinoma was grown in supplemented DMEM, and the extracellular fractions were submitted salting out and affinity chromatography to obtain new secreted serine proteases. TIC inhibited almost completely, 96 to 89%, the activity of these serine proteases and reduced the melanoma and colon adenocarcinoma cells growth of 48 and 77% respectively. Besides, it is the first time that a trypsin inhibitor was isolated and characterized from C. cajan leaves and cancer serine proteases were isolated and partial characterized from SK-MEL-28 and CaCo-2 cancer cell lines. Furthermore, TIC shown to be potent inhibitor of tumor protease affecting cell growth, and can be one potential drug candidate to be employed in chemotherapy of melanoma and colon adenocarcinoma.
Subject(s)
Cajanus , Plant Leaves , Humans , Cajanus/chemistry , Plant Leaves/chemistry , Caco-2 Cells , Cell Proliferation/drug effects , Cell Line, Tumor , Trypsin Inhibitors/pharmacology , Trypsin Inhibitors/chemistry , Trypsin Inhibitors/isolation & purification , Plant Proteins/pharmacology , Plant Proteins/chemistry , Plant Proteins/isolation & purification , Serine Proteases/chemistry , Serine Proteases/isolation & purification , Serine Proteases/metabolismABSTRACT
Vaccine hesitancy tends to exhibit geographical patterns and is often associated with social deprivation and migrant status. We aimed to estimate COVID-19 vaccination hesitancy in a high-vaccination-acceptance country, Portugal, and determine its association with sociodemographic risk factors. We used the Registry of National Health System Users to determine the eligible population and the Vaccination Registry to determine individuals without COVID-19 vaccine doses. Individuals older than five with no COVID-19 vaccine dose administered by 31 March 2022 were considered hesitant. We calculated hesitancy rates by municipality, gender, and age group for all municipalities in mainland Portugal. We used the spatial statistical scan method to identify spatial clusters and the Besag, Yorke, and Mollié (BYM) model to estimate the effect of age, gender, social deprivation, and migrant proportion across all mainland municipalities. The eligible population was 9,852,283, with 1,212,565 (12%) COVID-19 vaccine-hesitant individuals. We found high-hesitancy spatial clusters in the Lisbon metropolitan area and the country's southwest. Our model showed that municipalities with higher proportions of migrants are associated with an increased relative risk (RR) of vaccine hesitancy (RR = 8.0; CI 95% 4.6; 14.0). Social deprivation and gender were not associated with vaccine hesitancy rates. We found COVID-19 vaccine hesitancy has a heterogeneous distribution across Portugal and has a strong association with the proportion of migrants per municipality.
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Frequent droughts have led to an expansion of irrigated common bean (Phaseolus vulgaris L.) cultivation areas. An effective strategy to enhance water use efficiency and optimize crop growth is the application of silicon (Si) and potassium (K). However, the interaction between Si dosage, water regimes, and plant potassium status, as well as the underlying physiological mechanisms, remains unknown. This study aimed to assess the effects of Si doses applied via fertigation under various water regimes, in the presence and absence of potassium fertilization, on gas exchange, water use efficiency, and growth of Common beans in field conditions. Two experiments were conducted, one with and one without K supply, considering that the potassium content in the soil was 6.4 mmolc dm-3 in both experiments and a replacement dose of 50 kg ha was applied in the with K treatment, with the same treatments evaluated in both potassium conditions. The treatments comprised a 3 × 4 factorial design, encompassing three water regimes: 80% (no deficit), 60% (moderate water deficit), and 40% (severe water deficit) of soil water retention capacity, and four doses of Si supplied via fertigation: 0, 4, 8, and 12 kg ha-1. Where it was evaluated, content of photosynthetic pigments, fluorescence of photosynthesis, relative water content, leaf water potential and electrolyte extravasation, dry mass of leaves, stems and total. The optimal doses of Si for fertigation application, leading to increased Si absorption in plants, varied with decreasing soil water content. The respective values were 6.6, 7.0, and 7.1 kg ha-1 for the water regimes without deficit, with moderate water deficit, and with severe water deficit. Fertigation application of Si improved plant performance, particularly under severe water deficit, regardless of potassium status. This improvement was evident in relative water content, leaf water potential, and membrane resistance, directly impacting pigment content and gas exchange rates. The physiological effects resulted in enhanced photosynthesis in water-deficient plants, mitigating dry mass production losses. This research demonstrates, for the first time in common bean, the potential of Si to enhance irrigation efficiency in areas limited by low precipitation and water scarcity.
Subject(s)
Phaseolus , Potassium , Silicon , Droughts , SoilABSTRACT
Objetivo: compreender as concepções e práticas dos profissionais da Atenção Primária à Saúde acerca dos cuidados paliativos. Método: estudo descritivo-exploratório, de abordagem qualitativa realizado com profissionais atuantes em três Unidades Básicas em município no sul do Brasil. Os dados foram coletados em junho de 2021, mediante entrevistas presenciais, audiogravadas junto a 36 profissionais de saúde selecionados por conveniência e submetidos à análise de conteúdo, modalidade temática. Resultados: muitos profissionais da Atenção Primária, sobretudo os agentes comunitários, técnicos e auxiliares de enfermagem, possuem pouco conhecimento ou uma visão distorcida a respeito de cuidados paliativos, mas em seu cotidiano assistem pacientes e familiares. Considerações finais: embora não suficientemente preparados, os profissionais de saúde precisam estar junto, orientar e assistir usuários e familiares que necessitam de cuidados paliativos, necessitam portanto serem sensibilizados quanto a importância e benefícios dos cuidados paliativos e serem devidamente intrumentalizados para prestar essa assistência que valorize seus princípios.
Objective: to understand the conceptions and practices of Primary Health Care professionals regarding palliative care. Method: descriptive-exploratory study, with a qualitative approach carried out with professionals working in three Basic Units in a city in southern Brazil. Data were collected in June 2021, through face-to-face, audio-recorded interviews with 36 health professionals selected for convenience and subjected to content analysis, thematic modality. Results: many Primary Care professionals, especially community workers, technicians and nursing assistants, have little knowledge or a distorted view of palliative care, but in their daily lives they assist patients and families. Final considerations: although not sufficiently prepared, health professionals need to be together, guide and assist users and families who need palliative care, they therefore need to be made aware of the importance and benefits of palliative care and be properly equipped to provide this assistance that values its principles.
Objetivos: comprender las concepciones y prácticas de los profesionales de la Atención Primaria de Salud sobre los cuidados paliativos. Método: estudio descriptivo-exploratorio, con enfoque cualitativo, realizado con profesionales de tres Unidades Básicas de una ciudad de Brasil. Los datos fueron recolectados en junio de 2021, mediante entrevistas presenciales, audio grabadas, a 36 profesionales seleccionados por conveniencia y sometidos a análisis de contenido, modalidad temática. Resultados: muchos profesionales, especialmente trabajadores comunitarios, técnicos y auxiliares de enfermería, tienen pocos conocimientos o una visión distorsionada de los cuidados paliativos, pero en su vida diaria asisten a pacientes y familiares. Consideraciones finales: aunque no están suficientemente preparados, los profesionales de la salud necesitan estar juntos, orientar y asistir a los usuarios y familias que necesitan cuidados paliativos, por lo que deben ser conscientes de la importancia y los beneficios de estes Cuidados y estar adecuadamente equipados para brindar esta asistencia que valora sus principios.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Continuity of Patient CareABSTRACT
ABSTRACT Objective: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. Methods: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). Results: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. Conclusion: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.
RESUMO Objetivo: Examinar a função física e a força muscular respiratória de pacientes que se recuperaram da COVID-19 grave após a alta da unidade de terapia intensiva para a enfermaria nos Dias 1 e 7 e investigar as variáveis associadas ao comprometimento funcional. Métodos: Trata-se de estudo de coorte prospectivo de pacientes adultos com COVID-19 que necessitaram de ventilação mecânica invasiva, ventilação mecânica não invasiva ou cânula nasal de alto fluxo e tiveram alta da unidade de terapia intensiva para a enfermaria. Os participantes foram submetidos aos testes Medical Research Council sum-score, força de preensão manual, pressão inspiratória máxima, pressão expiratória máxima e short physical performance battery. Os participantes foram agrupados em dois grupos conforme a necessidade de ventilação mecânica invasiva: o Grupo Ventilação Mecânica Invasiva (Grupo VMI) e o Grupo Não Ventilação Mecânica Invasiva (Grupo Não VMI). Resultados: Os pacientes do Grupo VMI (n = 31) eram mais jovens e tinham pontuações do Sequential Organ Failure Assessment mais altas do que os do Grupo VMI (n = 33). As pontuações do short physical performance battery (intervalo de zero a 12) nos Dias 1 e 7 foram 6,1 ± 4,3 e 7,3 ± 3,8, respectivamente para o Grupo Não VMI, e 1,3 ± 2,5 e 2,6 ± 3,7, respectivamente para o Grupo VMI. A prevalência de fraqueza adquirida na unidade de terapia intensiva no Dia 7 foi de 13% para o Grupo Não VMI e de 72% para o Grupo VMI. A pressão inspiratória máxima, a pressão expiratória máxima e a força de preensão manual aumentaram no Dia 7 em ambos os grupos, porém a pressão expiratória máxima e a força de preensão manual ainda eram fracas. Apenas a pressão inspiratória máxima foi recuperada (ou seja, > 80% do valor previsto) no Grupo Não VMI. As variáveis sexo feminino, e necessidade e duração da ventilação mecânica invasiva foram associadas de forma independente e negativa à pontuação do short physical performance battery e à força de preensão manual. Conclusão: Os pacientes que se recuperaram da COVID-19 grave e receberam ventilação mecânica invasiva apresentaram maior incapacidade do que aqueles que não foram ventilados invasivamente. No entanto, os dois grupos de pacientes apresentaram melhora funcional marginal durante a fase inicial de recuperação, independentemente da necessidade de ventilação mecânica invasiva. Esse resultado pode evidenciar a gravidade da incapacidade causada pelo SARS-CoV-2.
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In pregnant women, low molecular weight heparin is recommended as the preferred agent for venous thromboembolism prophylaxis and treatment. Despite their widespread application, heparin-induced skin lesions are probably under-reported and under-estimated. We present a case report of a primigravida treated with low molecular weight heparin for deep vein thrombosis, who developed a delayed-type hypersensitivity reaction to enoxaparin, tinzaparin and dalteparin. As the patient was pregnant, treatment options were restricted. Tolerance was achieved with dalteparin with adjuvant administration of prednisolone. An attempt to decrease prednisolone dose triggered delayed-type hypersensitivity reaction recurrence that was solved by keeping the initial prednisolone prescription. To the best of our knowledge, there are no described cases using this approach. In cases of delayed-type hypersensitivity reaction to low molecular weight heparin during pregnancy our case suggests that switching low molecular weight heparin and adjuvant administration of prednisolone can be an option.
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OBJECTIVE: In patients with large vessel occlusion, successful reperfusion is a predictor of favorable outcome. However, patients with underlying intracranial atherosclerotic disease (ICAD) show higher rates of immediate reocclusion, frequently requiring rescue stenting. We aimed to investigate the safety, efficacy, and outcome of acute stenting in acute stroke patients with underlying ICAD. METHODS: Prospective databases from two centers between 2012 and 2021 were reviewed. Adult patients who underwent ICAD-related acute intracranial stenting, after mechanical thrombectomy (MT) were included. Clinical and procedural data, technical success measured by Modified Thrombolysis in Cerebral Infarction score, periprocedural complications, stent restenosis, and follow up mRS at three months were evaluated. RESULTS: During a 10-year period, a total of 96 patients with acute stroke and intracranial atherosclerotic steno-occlusive lesions underwent stenting after MT. Mean age was 63 (SD 14) and 54 patients were male (56.3%). Successful reperfusion (TICI ≥ 2b) was achieved in 86 patients (89.6%) following rescue stenting; favorable clinical outcome (mRS < 3) was observed in 32 patients (37.6%). Symptomatic intracranial hemorrhage and mortality were observed in 9.5% and 22.4% of patients, respectively. Multivariate regression yielded older age (OR: 0.477, 95% CI: 0.933-0.999, p=0.046) as an independent negative predictor of favorable functional outcome after acute intracranial stenting. CONCLUSION: Our results suggest that acute intracranial stenting is safe and effective as a rescue treatment after MT in acute stroke patients with underlying ICAD. Younger age was found as an independent predictor of good outcome. Nevertheless, ICAD still carries a high mortality and poor functional clinical outcome.
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BACKGROUND: The study aimed to evaluate the rate of endometrial sampling (ES) failure, predictive factors of success, and reliability as diagnostic methods of Endosampler versus Novak. METHODS: A retrospective single-center study was carried out with all patients who underwent ES via Endosampler or Novak in 2020 and 2021. Demographic data, personal background, and histopathologic results were evaluated. RESULTS: Eighty-six patients underwent ES by Novak and 90 by Endosampler. The failure rate of ES was 43.2% with lower values for Endosampler (33.3% vs. 53.5%, P<0.05). Age, biopsy device, menopausal status, indication for biopsy, and amount of sample collected were predictive factors of failure. Analyzing each device, Endosampler was only affected by menopausal status. Only 50% in Novak and 62.5% in the Endosampler group of endometrial neoplasia cases were detected by these methods. Analyzing the performance for endometrial neoplasia (EN), we obtained higher values of sensitivity and accuracy for Endosampler (62.5% vs. 50.0% and 83.3% vs. 72.7%), respectively. CONCLUSIONS: In our study, the failure rate obtained was in line with other previous studies. Menopausal status, age, type of biopsy device, indication for biopsy, and amount of sample collected affected ES performance. Analyzing diagnostic performance for EN, we found that these methods have better reliability for positive results than for negative ones, which may indicate the need for further evaluation in cases of high clinical suspicion. In short, we obtain a higher rate of success rate in Endosampler devices and better performance in diagnosing EN, which is the major objective of an ES.
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INTRODUCTION: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR's core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR's core capacities. METHODS: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR's core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. RESULTS: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. CONCLUSION: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.
Subject(s)
COVID-19 , International Health Regulations , Humans , Communicable Disease Control/methods , Pandemics/prevention & control , COVID-19/epidemiology , Portugal/epidemiology , Emergencies , SARS-CoV-2 , Global Health , World Health Organization , Disease OutbreaksABSTRACT
Intensive fertilization of vegetables can promote phosphorus (P) toxicity. However, it can be reversed using silicon (Si), although there is a lack of research clarifying its mechanisms of action. This research aims to study the damage caused by P toxicity to scarlet eggplant plants and whether Si can mitigate this toxicity. We evaluated the nutritional and physiological aspects of plants. Treatments were arranged in a 2 × 2 factorial design of two nutritional levels of adequate P (2 mmol L-1 of P) and toxic/excess P (8 to 13 mmol L-1 of P) combined with the absence or presence of nanosilica (2 mmol L-1 Si) in a nutrient solution. There were six replications. The excess P in the nutrient solution caused damage to scarlet eggplant growth due to nutritional losses and oxidative stress. We found that P toxicity can be mitigated by supplying Si, which decreases P uptake by 13%, improves C:N homeostasis, and increases iron (Fe), copper (Cu), and zinc (Zn) use efficiency by 21%, 10%, and 12%, respectively. At the same time, it decreases oxidative stress and electrolyte leakage by 18% and increases antioxidant compounds (phenols and ascorbic acid by 13% and 50%, respectively), and decreases photosynthetic efficiency and plant growth by 12% (by increasing 23% and 25% of shoot and root dry mass, respectively). These findings allow us to explain the different Si mechanisms used to reverse the damage caused by P toxicity to plants.
Subject(s)
Silicon , Solanum melongena , Silicon/pharmacology , Solanum melongena/metabolism , Oxidative Stress , Antioxidants/metabolism , PhotosynthesisABSTRACT
Aryl-alcohol oxidases (AAOs) are members of the glucose-methanol-choline oxidase/dehydrogenase (GMC) superfamily. These extracellular flavoproteins have been described as auxiliary enzymes in the degradation of lignin by several white-rot basidiomycetes. In this context, they oxidize fungal secondary metabolites and lignin-derived compounds using O2 as an electron acceptor, and supply H2O2 to ligninolytic peroxidases. Their substrate specificity, including mechanistic aspects of the oxidation reaction, has been characterized in Pleurotus eryngii AAO, taken as a model enzyme of this GMC superfamily. AAOs show broad reducing-substrate specificity in agreement with their role in lignin degradation, being able to oxidize both nonphenolic and phenolic aryl alcohols (and hydrated aldehydes). In the present work, the AAOs from Pleurotus ostreatus and Bjerkandera adusta were heterologously expressed in Escherichia coli, and their physicochemical properties and oxidizing abilities were compared with those of the well-known recombinant AAO from P. eryngii. In addition, electron acceptors different from O2, such as p-benzoquinone and the artificial redox dye 2,6-Dichlorophenolindophenol, were also studied. Differences in reducing-substrate specificity were found between the AAO enzymes from B. adusta and the two Pleurotus species. Moreover, the three AAOs oxidized aryl alcohols concomitantly with the reduction of p-benzoquinone, with similar or even higher efficiencies than when using their preferred oxidizing-substrate, O2. IMPORTANCE In this work, quinone reductase activity is analyzed in three AAO flavooxidases, whose preferred oxidizing-substrate is O2. The results presented, including reactions in the presence of both oxidizing substrates-benzoquinone and molecular oxygen-suggest that such aryl-alcohol dehydrogenase activity, although less important than its oxidase activity in terms of maximal turnover, may have a physiological role during fungal decay of lignocellulose by the reduction of quinones (and phenoxy radicals) from lignin degradation, preventing repolymerization. Moreover, the resulting hydroquinones would participate in redox-cycling reactions for the production of hydroxyl free radical involved in the oxidative attack of the plant cell-wall. Hydroquinones can also act as mediators for laccases and peroxidases in lignin degradation in the form of semiquinone radicals, as well as activators of lytic polysaccharide monooxygenases in the attack of crystalline cellulose. Moreover, reduction of these, and other phenoxy radicals produced by laccases and peroxidases, promotes lignin degradation by limiting repolymerization reactions. These findings expand the role of AAO in lignin biodegradation.
Subject(s)
Pleurotus , Quinone Reductases , Lignin/metabolism , Hydrogen Peroxide , Hydroquinones , Alcohol Oxidoreductases/metabolism , Peroxidases/genetics , Ethanol , Pleurotus/metabolism , BenzoquinonesABSTRACT
OBJECTIVES: to analyze the association between recurrence of emergency service visits due to lack of blood pressure and/or glycemic control with sociodemographic variables and disease registration in Primary Care. METHODS: quantitative study, which consulted medical records of people who attended these services two or more times for 26 months. Descriptive statistics and multiple logistic regression models were used in analysis. RESULTS: most people did not have hypertension and/or diabetes record in their Primary Care records. The absence of this record was more frequent in males, aged between 18 and 59 years, with low education and lack of blood pressure. There was association between greater number of people seeking these services in the same year and not monitoring the chronic condition in specialized care. CONCLUSIONS: people who do not follow up hypertension and/or diabetes in Primary Care are more likely to need assistance due to blood pressure and/or glycemic management.
Subject(s)
Diabetes Mellitus , Emergency Medical Services , Hypertension , Male , Humans , Adolescent , Young Adult , Adult , Middle Aged , Hypertension/complications , Hypertension/epidemiology , Hypertension/therapy , Blood Pressure , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Educational StatusABSTRACT
Pharmaceutical chemistry has many industrial processes that must be studied and adapted to a new reality where the environment must be the focus of all production chains. Thus, new technologies that are cleaner and use renewable sources of raw materials still need to be developed and applied to materials that go to the market, and they need to reach a level that is less harmful to the environment. This applies especially in areas related to the pharmaceutical industries since chemical products are used in the production of medicines and used in many other areas of everyday life and are included in the Sustainable Development Goals proposed by the United Nations. This article intends to provide insight into some relevant topics that can stimulate researchers toward medicinal chemistry that can contribute to a sustainable future of the biosphere. This article is structured around four interconnected themes that influence how green chemistry can be important for a future where science, technology and innovation are key to mitigating climate change and increasing global sustainability.