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Antibody-drug conjugates (ADCs) are an emerging class of anticancer agents that combine targeting antibodies with potent cytotoxic agents. Their molecular configuration allows for increased therapeutic efficacy and reduced adverse-effect profiles compared to monoclonal antibodies or cytotoxic chemotherapy alone. ADCs cause off-target toxicities through several mechanisms, including premature deconjugation of the cytotoxic agent in the serum and the presence of the targeted antigen on normal tissues. Given cutaneous adverse events comprise 31.3% of all-grade adverse events in clinical trials involving ADCs, dermatologists are increasingly called upon to manage the cutaneous toxicities caused by these drugs. In this review, we summarize known cutaneous toxicities of the ADCs that have been approved for use by the US Food and Drug Administration to date. Dermatologists can play a key role in recognizing cutaneous reactions associated with ADCs, contributing to guidelines for their management, and aiding during clinical trials to generate detailed morphologic and histopathologic descriptions of cutaneous toxicities caused by ADCs.
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Toxidermias , Imunoconjugados , Humanos , Imunoconjugados/efeitos adversos , Toxidermias/etiologia , Antineoplásicos/efeitos adversosRESUMO
The direct blockade of CB1 cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB1 negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB1. We recently reported that GAT358, a CB1-NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB1-allosteric mechanism of action. Whether a CB1-NAM dampens opioid-mediated therapeutic effects such as analgesia or alters other unwanted opioid side-effects remain unknown. Here, we characterized the effects of GAT358 on nociceptive behaviors in the presence and absence of morphine in male rats. We examined the impact of GAT358 on formalin-evoked pain behavior and Fos protein expression, a marker of neuronal activation, in the lumbar spinal cord. We also assessed the impact of GAT358 on morphine-induced slowing of colonic transit, tolerance, and withdrawal behaviors in male mice. GAT358 attenuated morphine antinociceptive tolerance without blocking acute antinociception and reduced morphine-induced slowing of colonic motility without impacting fecal boli production. GAT358 also produced antinociception in the presence and absence of morphine in the formalin model of inflammatory nociception and reduced the number of formalin-evoked Fos protein-like immunoreactive cells in the lumbar spinal cord. Finally, GAT358 mitigated the somatic signs of naloxone-precipitated, but not spontaneous, opioid withdrawal following chronic morphine dosing. Our results support the therapeutic potential of CB1-NAMs as novel drug candidates aimed at preserving opioid-mediated analgesia while preventing their unwanted side-effects. Our studies also uncover previously unrecognized antinociceptive properties associated with an arrestin-biased CB1-NAM.
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Analgésicos Opioides , Tolerância a Medicamentos , Morfina , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide , Síndrome de Abstinência a Substâncias , Animais , Receptor CB1 de Canabinoide/metabolismo , Masculino , Analgésicos Opioides/farmacologia , Tolerância a Medicamentos/fisiologia , Regulação Alostérica/efeitos dos fármacos , Camundongos , Morfina/farmacologia , Ratos , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
BACKGROUND: Naloxone is an effective and safe opioid reversal medication now approved by the U.S. Food and Drug Administration (FDA) for use with or without a prescription. Despite this, naloxone dissemination lags at a time when U.S. opioid-related mortality expands. The authors proposed distributing naloxone to all U.S. medical students using established statewide standing prescription orders for naloxone, eliminating the financial burden of over-the-counter costs on students and streamlining workflow for the pharmacy. By focusing naloxone distribution on medical students, we are able to capitalize on a group that is already primed on healthcare intervention, while also working to combat stigma in the emerging physician workforce. METHODS: Beginning August 2022, the authors established a partnership between Harvard Medical School (HMS) and the outpatient pharmacy at Brigham and Women's Hospital (BWH) to facilitate access to naloxone for HMS medical students. BWH developed a HIPAA-secure electronic form to collect individual prescription information. BWH pharmacists processed submissions daily, integrating the naloxone prescription requests into their workflow for in-person pick-up or mail-order delivery. The electronic form was disseminated to medical students through a required longitudinal addiction medicine curriculum, listserv messaging, and an extracurricular harm reduction workshop. RESULTS: Over the 2022-2023 academic year, 63 medical students obtained naloxone kits (two doses per kit) through this collaboration. CONCLUSIONS: We propose that medical schools advocate for a hospital pharmacy-initiated workflow focused on convenience and accessibility to expand naloxone access to medical students as a strategy to strengthen the U.S. emergency response and prevention efforts aimed at reducing opioid-related morbidity and mortality. Expansion of our program to BWH internal medicine residents increased our distribution to over 110 healthcare workers, and efforts to expand the program to other BWH training programs and clinical sites such as the emergency department and outpatient infectious disease clinics are underway. With more than 90,000 medical students in the U.S., we believe that widespread implementation of targeted naloxone training and distribution to this population is an accessible approach to combating the public health crisis of opioid-related overdoses.
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Estudantes de Medicina , Feminino , Estados Unidos , Humanos , Epidemia de Opioides , Analgésicos Opioides/uso terapêutico , Instituições de Assistência Ambulatorial , CurrículoRESUMO
BACKGROUND: Physician malpractice lawsuits are climbing, and the reasons underlying litigation against dermatologists are unclear. OBJECTIVE: To determine the reasons patients pursue litigation against dermatologists or dermatology practices. MATERIALS AND METHODS: A retrospective analysis of all state and federal cases between 2011 and 2022 was performed after a query using "Dermatology" and "dermatologist" as search terms on 2 national legal data repositories. RESULTS: The authors identified a total of 48 (37 state and 11 federal) lawsuits in which a practicing dermatologist or dermatology group practice was the defendant. The most common reason for litigation was unexpected harm (26 cases, 54.2%), followed by diagnostic error (e.g. incorrect or delayed diagnoses) (16 cases, 33.3%). Six cases resulted from the dermatologist failing to communicate important information, such as medication side effects or obtaining informed consent. Male dermatologists were sued at a rate 3.1 times higher than female dermatologists. CONCLUSION: Although lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed diagnoses and ensure critical information is shared with patients to safeguard against easily avoidable litigation.
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Dermatologistas , Imperícia , Humanos , Estudos Retrospectivos , Estados Unidos , Imperícia/legislação & jurisprudência , Imperícia/estatística & dados numéricos , Masculino , Feminino , Dermatologistas/estatística & dados numéricos , Dermatologistas/legislação & jurisprudência , Dermatologia/legislação & jurisprudência , Dermatologia/estatística & dados numéricos , Erros de Diagnóstico/legislação & jurisprudência , Erros de Diagnóstico/estatística & dados numéricos , Consentimento Livre e Esclarecido/legislação & jurisprudênciaRESUMO
The direct blockade of CB 1 cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB 1 negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB 1 . We recently reported that GAT358, a CB 1 -NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB 1 -allosteric mechanism of action. Whether a CB 1 -NAM dampens opioid-mediated therapeutic effects such as analgesia or alters other unwanted side-effects of opioids remain unknown. Here, we characterized the effects of GAT358 on nociceptive behaviors in the presence and absence of morphine. We examined the impact of GAT358 on formalin-evoked pain behavior and Fos protein expression, a marker of neuronal activation, in the lumbar dorsal horn. We also assessed the impact of GAT358 on morphine-induced slowing of colonic transit, tolerance, and withdrawal behaviors. GAT358 attenuated morphine antinociceptive tolerance without blocking acute antinociception. GAT358 also reduced morphine-induced slowing of colonic motility without impacting fecal boli production. GAT358 produced antinociception in the presence and absence of morphine in the formalin model of inflammatory nociception and reduced the number of formalin-evoked Fos protein-like immunoreactive cells in the lumbar spinal dorsal horn. Finally, GAT358 mitigated the somatic signs of naloxone-precipitated, but not spontaneous, opioid withdrawal following chronic morphine dosing in mice. Our results support the therapeutic potential of CB 1 -NAMs as novel drug candidates aimed at preserving opioid-mediated analgesia while preventing their unwanted side-effects. Our studies also uncover previously unrecognized antinociceptive properties associated with an arrestin-biased CB 1 -NAMs. Highlights: CB 1 negative allosteric modulator (NAM) GAT358 attenuated morphine tolerance GAT358 reduced morphine-induced slowing of colonic motility but not fecal productionGAT358 was antinociceptive for formalin pain alone and when combined with morphineGAT358 reduced formalin-evoked Fos protein expression in the lumbar spinal cordGAT358 mitigated naloxone precipitated withdrawal after chronic morphine dosing.
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Rheumatoid arthritis (RA) is the most common inflammatory arthritis affecting 0.5-1.0% of the general population worldwide and although RA is properly considered a disease of the joints, it can cause a variety of extra-articular manifestations. This study was performed to find out any discrepancy in fracture risk estimates with and without bone mineral density (BMD) in rheumatoid arthritis (RA) patients. This observational cross-sectional study was carried out in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from July 2013 to July 2015. Total 65 consecutive patients with RA fulfilling ACR/EULAR criteria aged 40-90 year were recruited. Ten year fracture risk of these patients was evaluated by the FRAX score with and without BMD and differences were observed. FRAX score without BMD revealed that major fracture risk was low in 58(89.2%) patients, moderate in 7(10.8%) patients but re-estimation with BMD revealed that 55(84.6%) patients remained in low risk group, 8(12.3%) patients in moderate risk group and 2(3.1%) patients went to the high risk group. In case of hip fracture risk without BMD, risk was low in 58(89.2%) patients, high in 7(10.8%) patients; but with BMD, 50(76.9%) patients remained in low risk group but risk of 15(23.1%) patients became high. Almost all the high risk patients (93.3%) were ≥55 years of age. Increasing age, female sex, disease duration and use of steroid were positively correlated with increased FRAX score where as high BMI and high BMD were associated with low FRAX score. But in multivariate analysis it was found that only relation with age was at statistically significant level. Significant numbers of patients with rheumatoid arthritis have high risk of fracture especially hip fracture. The mean of FRAX score increased in both major & hip osteoporotic fracture risk after adding BMD. More than half of the patients above fifty five years or more had high risk of fracture. So, BMD should be done in patients aged more than fifty five.
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Artrite Reumatoide , Fraturas do Quadril , Fraturas por Osteoporose , Humanos , Feminino , Pessoa de Meia-Idade , Densidade Óssea , Medição de Risco , Artrite Reumatoide/complicações , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/complicações , Fatores de Risco , Fraturas do Quadril/etiologia , Fraturas do Quadril/complicações , Absorciometria de Fóton/efeitos adversosRESUMO
Glutamate signalling through the N-methyl-d-aspartate receptor (NMDAR) activates the enzyme neuronal nitric oxide synthase (nNOS) to produce the signalling molecule nitric oxide (NO). We hypothesized that disruption of the protein-protein interaction between nNOS and the scaffolding protein postsynaptic density 95 kDa (PSD95) would block NMDAR-dependent NO signalling and represent a viable therapeutic route to decrease opioid reward and relapse-like behaviour without the unwanted side effects of NMDAR antagonists. We used a conditioned place preference (CPP) paradigm to evaluate the impact of two small-molecule PSD95-nNOS inhibitors, IC87201 and ZL006, on the rewarding effects of morphine. Both IC87201 and ZL006 blocked morphine-induced CPP at doses that lacked intrinsic rewarding or aversive properties. Furthermore, in vivo fast-scan cyclic voltammetry (FSCV) was used to ascertain the impact of ZL006 on morphine-induced increases in dopamine (DA) efflux in the nucleus accumbens shell (NAc shell) evoked by electrical stimulation of the medial forebrain bundle (MFB). ZL006 attenuated morphine-induced increases in DA efflux at a dose that did not have intrinsic effects on DA transmission. We also employed multiple intravenous drug self-administration approaches to examine the impact of ZL006 on the reinforcing effects of morphine. Interestingly, ZL006 did not alter acquisition or maintenance of morphine self-administration, but reduced lever pressing in a morphine relapse test after forced abstinence. Our results provide behavioural and neurochemical support for the hypothesis that inhibition of PSD95-nNOS protein-protein interactions decreases morphine reward and relapse-like behaviour, highlighting a previously unreported application for these novel therapeutics in the treatment of opioid addiction.
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Morfina , Recompensa , Animais , Proteína 4 Homóloga a Disks-Large , Morfina/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Núcleo Accumbens/metabolismo , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , RecidivaRESUMO
Individuals living with disabilities are underrepresented in the physician workforce, despite benefits of inclusion. This article describes how both ableism in admissions processes and expectations set by technical standards can perpetuate harm. The authors advocate for active attention to disability diversity and equity in medical school admissions.
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Pessoas com Deficiência , Médicos , Humanos , Faculdades de Medicina , Discriminação SocialRESUMO
Thin films of polymer coatings have important industrial applications ranging from paints and coatings to pharmaceuticals. In many applications, the coatings are obtained by applying thin films of dilute polymer solutions, wherein the solvent evaporates to leave behind a thin polymer film. In some cases, the thin films may crack due to shrinkage stresses developed during drying. While a number of studies have focused on the stress development, the phenomenon of cracking in polymer films is not fully investigated. In the present work, thin films of a silicone polymer solution were cast on substrates of varying Young's moduli and investigated for cracking as a function of film thickness and substrate modulus. Micro-Raman spectroscopy measurements show that thin films dry uniformly while thick films form a skin at the top surface leading to slow drying rates. Transverse stresses were measured using the cantilever technique and related to the extent of cracking in the film. We investigated the influence of substrate rigidity on the cracking behavior and found that decreasing the stiffness of the substrate increases the extent of cracking.
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BACKGROUND AND OBJECTIVES: White blood cells (WBCs) differential counting yields valued information about human health and disease. The current developed automated cell morphology equipments perform differential count which is based on blood smear image analysis. Previous identification systems for WBCs consist of successive dependent stages; pre-processing, segmentation, feature extraction, feature selection, and classification. There is a real need to employ deep learning methodologies so that the performance of previous WBCs identification systems can be increased. Classifying small limited datasets through deep learning systems is a major challenge and should be investigated. METHODS: In this paper, we propose a novel identification system for WBCs based on deep convolutional neural networks. Two methodologies based on transfer learning are followed: transfer learning based on deep activation features and fine-tuning of existed deep networks. Deep acrivation featues are extracted from several pre-trained networks and employed in a traditional identification system. Moreover, a novel end-to-end convolutional deep architecture called "WBCsNet" is proposed and built from scratch. Finally, a limited balanced WBCs dataset classification is performed through the WBCsNet as a pre-trained network. RESULTS: During our experiments, three different public WBCs datasets (2551 images) have been used which contain 5 healthy WBCs types. The overall system accuracy achieved by the proposed WBCsNet is (96.1%) which is more than different transfer learning approaches or even the previous traditional identification system. We also present features visualization for the WBCsNet activation which reflects higher response than the pre-trained activated one. CONCLUSION: a novel WBCs identification system based on deep learning theory is proposed and a high performance WBCsNet can be employed as a pre-trained network.
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Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Leucócitos/citologia , Redes Neurais de Computação , Basófilos/citologia , Eosinófilos/citologia , Humanos , Linfócitos/citologia , Informática Médica , Monócitos/citologia , Neutrófilos/citologia , Reprodutibilidade dos TestesRESUMO
Opioid-based therapies remain a mainstay for chronic pain management, but unwanted side effects limit therapeutic use. We compared efficacies of brain-permeant and -impermeant inhibitors of fatty acid amide hydrolase (FAAH) in suppressing neuropathic pain induced by the chemotherapeutic agent paclitaxel. Paclitaxel produced mechanical and cold allodynia without altering nestlet shredding or marble burying behaviors. We compared FAAH inhibitors that differ in their ability to penetrate the central nervous system for antiallodynic efficacy, pharmacological specificity, and synergism with the opioid analgesic morphine. (3'-(aminocarbonyl)[1,1'-biphenyl]- 3-yl)-cyclohexylcarbamate (URB597), a brain-permeant FAAH inhibitor, attenuated paclitaxel-induced allodynia via cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) mechanisms. URB937, a brain-impermeant FAAH inhibitor, suppressed paclitaxel-induced allodynia through a CB1 mechanism only. 5-[4-(4-cyano-1-butyn-1-yl)phenyl]-1-(2,4-dichlorophenyl)-N-(1,1-dioxido-4-thiomorpholinyl)-4-methyl-1H-pyrazole-3-carboxamide (AM6545), a peripherally restricted CB1 antagonist, fully reversed the antiallodynic efficacy of N-cyclohexyl-carbamic acid, 3'-(aminocarbonyl)-6-hydroxy[1,1'- biphenyl]-3-yl ester (URB937) but only partially reversed that of URB597. Thus, URB937 suppressed paclitaxel-induced allodynia through a mechanism that was dependent upon peripheral CB1 receptor activation only. Antiallodynic effects of both FAAH inhibitors were reversed by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). Antiallodynic effects of URB597, but not URB937, were reversed by 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630). Isobolographic analysis revealed synergistic interactions between morphine and either URB597 or URB937 in reducing paclitaxel-induced allodynia. A leftward shift in the dose-response curve of morphine antinociception was observed when morphine was coadministered with either URB597 or URB937, consistent with morphine sparing. However, neither URB937 nor URB597 enhanced morphine-induced deficits in colonic transit. Thus, our findings suggest that FAAH inhibition may represent a therapeutic avenue to reduce the overall amount of opioid needed for treating neuropathic pain with potential to reduce unwanted side effects that accompany opioid administration.
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Amidoidrolases/metabolismo , Analgésicos Opioides/farmacologia , Antineoplásicos/efeitos adversos , Encéfalo/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Morfina/farmacologia , Nociceptividade/efeitos dos fármacos , Animais , Ácidos Araquidônicos/farmacologia , Benzamidas/farmacologia , Encéfalo/metabolismo , Canabinoides/farmacologia , Carbamatos/farmacologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Indóis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Morfolinas/farmacologia , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismoRESUMO
Objective The objective of this study was to describe the clinical and immunological pattern and disease outcome in Egyptian systemic lupus erythematosus patients. Patients and methods The medical records of 770 systemic lupus erythematosus patients who were followed from 2002-2015 at Kasr Alainy Hospital, Cairo University, were retrospectively reviewed. Results There were 707 (91.8%) females. The mean age at disease onset was 22.1 ± 8.6 and the disease duration was 6.1 ± 4.5 years. The main clinical manifestations were mucocutaneous (90.8% with oral ulcers affecting 52.5%), arthritis (80.3%), nephritis (67.8%), hematologic involvement (64.9%), serositis (55.2%) and neuropsychiatric manifestations (44.3%). The frequencies of antinuclear antibodies were 94.3%, anti-dsDNA 74.8%, anti-Smith 11%, anticardiolipin antibodies 29.5% and lupus anticoagulant 19.8%. Infections, predominantly bacterial, affected 337 (43.8%) patients. Thirty-three (4.3%) patients died. The main causes of death were sepsis and disease activity. The five- and 10-year survival rates for the total cohort were 97.4% and 96.3%, respectively, and were 96% and 92%, respectively for those with nephritis ( p = 0.008). Autoimmune hemolytic anemia, thrombocytopenia, elevated serum creatinine, a higher damage index, infections, a higher glucocorticoid dose and cyclophosphamide use ≥ six months were associated with an increased risk of mortality with odds ratios of 3.69, p < 0.01; 4.12, p < 0.001; 1.54, p < 0.001; 1.43, p < 0.001; 5.08, p < 0.001; 5.04, p < 0.001 and 2.25, p = 0.03, respectively. Conclusion Compared to other cohorts, a relatively lower mean age at systemic lupus erythematosus onset and higher frequencies of oral ulcers, serositis and nephritis were found.
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Lúpus Eritematoso Sistêmico/mortalidade , Adolescente , Adulto , Antimaláricos/uso terapêutico , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Egito/epidemiologia , Feminino , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Adulto JovemRESUMO
The site preference for ligand substitution in the benzothiazolate-bridged cluster HOs3(CO)10(µ-1,2-N,C-η1,κ1-C7H4NS) (1) has been investigated using PPh3. 1 reacts with PPh3 in the presence of Me3NO to afford the mono- and bisphosphine substituted clusters HOs3(CO)9(PPh3)(µ-1,2-N,C-η1,κ1-C7H4NS) (2) and HOs3(CO)8(PPh3)2(µ-1,2-N,C-η1,κ1-C7H4NS) (3), respectively. 2 exists as a pair of non-interconverting isomers where the PPh3 ligand is situated at one of the equatorial sites syn to the edge-bridging hydride that shares a common Os-Os bond with the metalated heterocycle. The solid-state structure of the major isomer establishes the PPh3 regiochemistry at the N-substituted osmium center. DFT calculations confirm the thermodynamic preference for this particular isomer relative to the minor isomer whose phosphine ligand is located at the adjacent C-metalated osmium center. 2 also reacts with PPh3 to give 3. The locus of the second substitution occurs at one of the two equatorial sites at the Os(CO)4 moiety in 2 and gives rise to a pair of fluxional stereoisomers where the new phosphine ligand is scrambled between the two equatorial sites at the Os(CO)3P moiety. The molecular structure of the major isomer has been determined by X-ray diffraction analysis and found to represent the lowest energy structure of the different stereoisomers computed for HOs3(CO)8(PPh3)2(µ-1,2-N,C-η1,κ1-C7H4NS). The fluxional behavior displayed by 3 has been examined by VT NMR spectroscopy, and DFT calculations provide evidence for stereoselective tripodal rotation at the Os(CO)3P moiety that serves to equilibrate the second phosphine between the two available equatorial sites.
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BACKGROUND: White blood cells (WBCs) play a crucial role in the diagnosis of many diseases according to their numbers or morphology. The recent digital pathology equipments investigate and analyze the blood smear images automatically. The previous automated segmentation algorithms worked on healthy and non-healthy WBCs separately. Also, such algorithms had employed certain color components which leak adaptively with different datasets. METHODS: In this paper, a novel segmentation algorithm for WBCs in the blood smear images is proposed using multi-scale similarity measure based on the neutrosophic domain. We employ neutrosophic similarity score to measure the similarity between different color components of the blood smear image. Since we utilize different color components from different color spaces, we modify the neutrosphic score algorithm to be adaptive. Two different segmentation frameworks are proposed: one for the segmentation of nucleus, and the other for the cytoplasm of WBCs. Moreover, our proposed algorithm is applied to both healthy and non-healthy WBCs. in some cases, the single blood smear image gather between healthy and non-healthy WBCs which is considered in our proposed algorithm. Also, our segmentation algorithm is performed without any external morphological binary enhancement methods which may effect on the original shape of the WBC. RESULTS: Different public datasets with different resolutions were used in our experiments. We evaluate the system performance based on both qualitative and quantitative measurements. The quantitative results indicates high precision rates of the segmentation performance measurement A1 = 96.5% and A2 = 97.2% of the proposed method. The average segmentation performance results for different WBCs types reach to 97.6%. CONCLUSION: In this paper, a method based on adaptive neutrosphic sets similarity score is proposed in order to detect WBCs from a blood smear microscopic image and segment its components (nucleus and the cytoplasm). The proposed segmentation algorithm can be utilized for fully-automated classification systems, such systems can be either for the healthy WBCs or even for non-healthy WBCs specially the leukemia cells.
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BACKGROUND: The use of pegylated interferon alpha (IFN) has been of concern in chronic hepatitis C virus (HCV) patients with rheumatologic extrahepatic manifestations (EHM) due to the immunostimulatory effects of IFN. AIM: To study the efficacy and safety of sofosbuvir-based, IFN-free antiviral therapy in chronic HCV patients with rheumatologic EHM. MATERIAL AND METHODS: Group A included 24 patients with arthropathy (arthralgia or arthritis, n = 15) or vasculitis (n = 9) who received sofosbuvir and ribavirin (n = 17) or sofosbuvir and simeprevir (n = 7). Group B comprised 15 historical controls suffering from arthropathy who had received IFN and ribavirin. All patients were clinically evaluated and by detection of HCV viremia at baseline (V0), at the end of treatment (V1), 12 weeks after end of treatment (V2) and 24 weeks after end of treatment (V3). RESULTS: Sustained viral response was obtained in all patients of group A (100%) versus 12 out of 15 of group B (80%). In group A, the tender joint count (TJC) and visual analogue scale for pain (VAS) improved (p = 0.001 for both) while the swollen joint count (SJC) decreased at V1 (p = 0.001) but returned to baseline values at V3. All vasculitis patients improved. Purpura, arthralgia and leg ulcers disappeared, but peripheral neuropathy persisted. In group B, TJC, SJC and VAS increased from baseline values (p = 0.034, 0.03 and 0.001, respectively). Side effects in group A were generally mild, but one patient developed deterioration of arthralgia. CONCLUSION: The use of IFN-free regimens is safe and effective in the treatment of most HCV-related rheumatologic EHM.
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Antivirais , Hepatite C Crônica , Doenças Reumáticas , Sofosbuvir , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Adrenal infarction is a rare complication of antiphospholipid syndrome (APS). OBJECTIVES: The purpose of the current study is to detect and study the magnetic resonance imaging (MRI) findings of adrenal glands in APS patients. MATERIALS AND METHODS: In a cross-sectional study, the data of 20 patients with primary or secondary APS were compared to 20 SLE patients without antiphospholipid antibody (aPL) syndrome (controls). MRI of the abdomen showing the adrenal glands was performed. RESULTS: Of the patients, 80% were females with a mean age 32.45 ± 9.93 years, and mean disease duration of 46.65 ± 58.71 months. Adrenal gland abnormalities in the MRI study were detected in 35 % of APS patients vs. no abnormalities detected in the SLE controls. Adrenal gland enlargement was found in all patients (35 %). Capsular enhancement (infarction or hemorrhagic infarction) was found in 5 patients, increased stranding of the surrounding fat planes (inflammatory process) in 4 patients and increased signal on T1WI and T2WI (hemorrhage) in 3 patients. In patients with adrenal gland involvement, 71.4 % had triple aPL positivity compared to 23.1 % in patients with normal adrenal findings (p = 0.04). CONCLUSIONS: Adrenal gland abnormalities on MRI were detected in 35 % of the APS patients (whether primary or secondary); thus, increased focus on management is needed. This percentage is not small and needs to be focused on in terms of management.
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Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia , Síndrome Antifosfolipídica/diagnóstico por imagem , Síndrome Antifosfolipídica/epidemiologia , Infarto/diagnóstico por imagem , Infarto/epidemiologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Adulto , Causalidade , Comorbidade , Estudos Transversais , Diagnóstico Diferencial , Egito/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Distribuição por SexoAssuntos
Encéfalo/diagnóstico por imagem , Encefalite por Herpes Simples/diagnóstico , Neurossífilis/diagnóstico , Adulto , Diagnóstico Diferencial , Encefalite por Herpes Simples/líquido cefalorraquidiano , Encefalite por Herpes Simples/diagnóstico por imagem , Humanos , Masculino , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
The purposes of this study are to determine early detection practices performed by primary healthcare professionals, to compare medical and dental sub-groups, and to identify factors that influence the ability of medical and dental practitioners to recognize precancerous changes and clinical signs of oral cancer. A 28-item survey instrument was used to interview a total of 330 Jordanian primary health-care professionals (165 dental and 165 medical). An oral cancer knowledge scale (0 to 31) was generated from correct responses on oral cancer general knowledge. An early detection practice scale (0 to 24) was generated from the reported usage and frequency of procedures in oral cancer examination. Also, a diagnostic ability scale (0 to 100) was generated from correct selections of suspicious oral lesions. Only 17.8 % of the participants reported that they routinely performed oral cancer screening in practices. Their oral cancer knowledge scores ranged from 3 to 31 with a mean of 15.6. The early detection practice scores ranged from 2 to 21 with a mean of 11.6. A significant positive correlation was found between knowledge scores and early detection practice scores (r = 0.22; p < 0.001). The diagnostic ability scores ranged from 11.5 to 96 with a mean of 43.6. The diagnostic ability score was significantly correlated with knowledge scores (r = 0.39; p < 0.001), but not with early detection practice scores (r = 0.01; p = 0.92). Few significant differences were found between medical and dental primary care professionals. Continuous education courses on early diagnosis of oral cancer and oral mucosal lesions are needed for primary health-care professionals.