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  • Paediatric antiretroviral programmes have been implemented globally for more than a decade, yet information on long-term treatment outcomes in perinatally HIV-infected adolescents is limited. Published literature on long-term treatment outcomes was reviewed, including virologic, immunologic and growth outcomes, as well as drug resistance and factors associated with drug resistance. Outcomes were compared between high-income countries and low- and middle-income countries (LMIC), with additional focus on South Africa, the country with the biggest HIV epidemic in the world and the largest treatment programme. Treatment outcomes varied but viral suppression results globally were generally concerning. No studies from LMIC have reported on outcomes after >10 years follow-up, demonstrating that further studies are needed.OBJECTIVE Traditionally, popliteal artery aneurysms (PPAs) were treated via open repair (OR). However, more recently endovascular repair (EVR) approaches have become more common for the treatment of PPAs. The present meta-analysis therefore sought to conduct an up-to-date review of studies comparing the relative safety and efficacy of these 2 repair strategies. To that end, patient outcomes including primary patency, operating time, hospital stay duration, and re-intervention, amputation, and graft occlusion within 30 days were compared for these OR and EVR approaches. METHODS Studies in which OR and EVR were compared as treatments for PPAs were identified through systematic searching of the PubMed and Embase databases. Any studies either analyzing only one of these treatments in isolation or analyzing less then 5 patients were not included in this analysis. For all relevant studies, patient demographic information and outcome details were compiled. Risk of bias was analyzed using a modified Newcastle-Ottawaeatments with respect to rates of patient amputation (OR = 1.01; 95% CI 0.55-1.85; P = .98). CONCLUSIONS The available data suggest that PPA repair via EVR is a safe alternative to OR, but that short-term graft thrombosis and reintervention rates are significantly greater for the former approach. Moreover, few studies to date have compared these techniques and those that were largely retrospective in nature with relatively low-quality evidence, making it difficult to make definitive statements regarding the relative safety and efficacy of these 2 repair strategies. Additional population-based large-scale studies are therefore essential in order to conduct a robust evaluation of the safety and utility of EVR as an alternative to OR for PPA repair.This paper examines responses to the 2015 terror attack on Charlie Hebdo, a French satirical magazine, amongst students in a secondary school in Berlin-Neukölln, Germany. The Charlie Hebdo attack occurred in the final weeks of a 19-month ethnographic study in the community. By analyzing the responses in the school to this critical event, we identify what is at stake for Muslim students. Students presented many explanations for why the attack happened, and opinions on whether the attackers' actions were justified. Staff were alarmed about students' viewpoints that they considered "extreme". These dynamics resulted in conflicts and misunderstandings amongst students, and between students and staff. Yet, we show that, rather than the violence itself, or questions about its legitimacy, it was everyday processes in students' lives - e.g., bullying, peer pressure and discrimination, and feelings of being misrepresented and misunderstood - that were central to students' reactions to the event. We suggest that to understand students' reactions, both the immediate and the broader socio-political contexts must be considered, particularly rising xenophobia and processes of polarization in Germany and Europe at large. We thus conclude that to understand young people's reactions to terrorist acts, we need to look beyond initial statements and explore ethnographically how wider contexts shape the actions, reactions, and future orientations of young Muslims in Europe.Spatio-temporal data in sport is increasing rapidly, however suitable statistical methods for analysing this data are underdeveloped. The current study establishes the need for spatial statistical methods, propose a Bayesian hierarchical model as an appropriate method for comparing spatial variables, and test this model across three spatial scales. The need for spatial statistical methods was established through the identification of spatial autocorrelation. This necessitated the use of a Bayesian hierarchical model to test for an association between spatial ball movement entropy and spatial effectiveness. Posterior distribution results showed a generally positive association such that increases in entropy were associated with increases in effectiveness. The strength and confidence of the associations were impacted by the spatial scale, with the 6 × 6 grid showing the most conclusive evidence of a positive relationship; the 4 × 4 grid was mostly positive, however with a large variation; and finally, the basket-centric scale results were less conclusive. The results of the current study demonstrate the suitability of a Bayesian hierarchical model for testing for associations or differences between spatial variables. With the increase in spatial analyses in sport, this study presents an appropriate statistical method for dealing with complex problems associated with spatial analyses.Mouth rinsing has been proposed as a strategy to minimize performance decrements during Ramadan. We investigated the effect of 4 weeks of Ramadan on kicking performance in 27 Taekwondo athletes performing weekly Taekwondo Anaerobic Intermittent Kick Tests (TAIKT). https://www.selleckchem.com/products/mdl-800.html The effects of a placebo, 6.4% glucose and 6-mg/kg caffeine mouth rinses on TAIKT performance and perceived exertion were investigated before, during weekly training sessions, and after Ramadan in a counterbalanced, crossover design. Ramadan had a significant negative impact on the percentage of successful kicks in Week 1 of Ramadan (pre 76.7±0.4%, Week 1 69.9±3.2%). The percentage of successful kicks was significantly greater in the caffeine mouth rinse condition compared to the glucose and placebo conditions during the first 3 weeks of Ramadan (caffeine 38.3±6.8%, glucose 36.4±6.9%, placebo 36.0±6.5%). Caffeine decreased perceived exertion during Ramadan (0.74-1.15 AU, p>0.05). Our results showed that Ramadan had a significant negative effect on repeated high-intensity kicking efforts that should be considered when training and competing.
    Paediatric antiretroviral programmes have been implemented globally for more than a decade, yet information on long-term treatment outcomes in perinatally HIV-infected adolescents is limited. Published literature on long-term treatment outcomes was reviewed, including virologic, immunologic and growth outcomes, as well as drug resistance and factors associated with drug resistance. Outcomes were compared between high-income countries and low- and middle-income countries (LMIC), with additional focus on South Africa, the country with the biggest HIV epidemic in the world and the largest treatment programme. Treatment outcomes varied but viral suppression results globally were generally concerning. No studies from LMIC have reported on outcomes after >10 years follow-up, demonstrating that further studies are needed.OBJECTIVE Traditionally, popliteal artery aneurysms (PPAs) were treated via open repair (OR). However, more recently endovascular repair (EVR) approaches have become more common for the treatment of PPAs. The present meta-analysis therefore sought to conduct an up-to-date review of studies comparing the relative safety and efficacy of these 2 repair strategies. To that end, patient outcomes including primary patency, operating time, hospital stay duration, and re-intervention, amputation, and graft occlusion within 30 days were compared for these OR and EVR approaches. METHODS Studies in which OR and EVR were compared as treatments for PPAs were identified through systematic searching of the PubMed and Embase databases. Any studies either analyzing only one of these treatments in isolation or analyzing less then 5 patients were not included in this analysis. For all relevant studies, patient demographic information and outcome details were compiled. Risk of bias was analyzed using a modified Newcastle-Ottawaeatments with respect to rates of patient amputation (OR = 1.01; 95% CI 0.55-1.85; P = .98). CONCLUSIONS The available data suggest that PPA repair via EVR is a safe alternative to OR, but that short-term graft thrombosis and reintervention rates are significantly greater for the former approach. Moreover, few studies to date have compared these techniques and those that were largely retrospective in nature with relatively low-quality evidence, making it difficult to make definitive statements regarding the relative safety and efficacy of these 2 repair strategies. Additional population-based large-scale studies are therefore essential in order to conduct a robust evaluation of the safety and utility of EVR as an alternative to OR for PPA repair.This paper examines responses to the 2015 terror attack on Charlie Hebdo, a French satirical magazine, amongst students in a secondary school in Berlin-Neukölln, Germany. The Charlie Hebdo attack occurred in the final weeks of a 19-month ethnographic study in the community. By analyzing the responses in the school to this critical event, we identify what is at stake for Muslim students. Students presented many explanations for why the attack happened, and opinions on whether the attackers' actions were justified. Staff were alarmed about students' viewpoints that they considered "extreme". These dynamics resulted in conflicts and misunderstandings amongst students, and between students and staff. Yet, we show that, rather than the violence itself, or questions about its legitimacy, it was everyday processes in students' lives - e.g., bullying, peer pressure and discrimination, and feelings of being misrepresented and misunderstood - that were central to students' reactions to the event. We suggest that to understand students' reactions, both the immediate and the broader socio-political contexts must be considered, particularly rising xenophobia and processes of polarization in Germany and Europe at large. We thus conclude that to understand young people's reactions to terrorist acts, we need to look beyond initial statements and explore ethnographically how wider contexts shape the actions, reactions, and future orientations of young Muslims in Europe.Spatio-temporal data in sport is increasing rapidly, however suitable statistical methods for analysing this data are underdeveloped. The current study establishes the need for spatial statistical methods, propose a Bayesian hierarchical model as an appropriate method for comparing spatial variables, and test this model across three spatial scales. The need for spatial statistical methods was established through the identification of spatial autocorrelation. This necessitated the use of a Bayesian hierarchical model to test for an association between spatial ball movement entropy and spatial effectiveness. Posterior distribution results showed a generally positive association such that increases in entropy were associated with increases in effectiveness. The strength and confidence of the associations were impacted by the spatial scale, with the 6 × 6 grid showing the most conclusive evidence of a positive relationship; the 4 × 4 grid was mostly positive, however with a large variation; and finally, the basket-centric scale results were less conclusive. The results of the current study demonstrate the suitability of a Bayesian hierarchical model for testing for associations or differences between spatial variables. With the increase in spatial analyses in sport, this study presents an appropriate statistical method for dealing with complex problems associated with spatial analyses.Mouth rinsing has been proposed as a strategy to minimize performance decrements during Ramadan. We investigated the effect of 4 weeks of Ramadan on kicking performance in 27 Taekwondo athletes performing weekly Taekwondo Anaerobic Intermittent Kick Tests (TAIKT). https://www.selleckchem.com/products/mdl-800.html The effects of a placebo, 6.4% glucose and 6-mg/kg caffeine mouth rinses on TAIKT performance and perceived exertion were investigated before, during weekly training sessions, and after Ramadan in a counterbalanced, crossover design. Ramadan had a significant negative impact on the percentage of successful kicks in Week 1 of Ramadan (pre 76.7±0.4%, Week 1 69.9±3.2%). The percentage of successful kicks was significantly greater in the caffeine mouth rinse condition compared to the glucose and placebo conditions during the first 3 weeks of Ramadan (caffeine 38.3±6.8%, glucose 36.4±6.9%, placebo 36.0±6.5%). Caffeine decreased perceived exertion during Ramadan (0.74-1.15 AU, p>0.05). Our results showed that Ramadan had a significant negative effect on repeated high-intensity kicking efforts that should be considered when training and competing.
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  • Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B is an H3K36me3 reader that forms a stable complex with HDAC1/2. We used CAGE-seq to profile all transcription initiation sites in wild-type mESCs and cells lacking PWWP2A/B. Loss of PWWP2A/B enhances spurious initiation from intragenic sites present in wild-type mESCs, and this effect is associated with increased levels of initiating Pol-II and histone acetylation. Spurious initiation events in Pwwp2a/b DKO mESCs do not overlap in genomic location or chromatin features with spurious sites that arise in Dnmt3b KO mESCs, previously reported to function in the suppression of intragenic transcriptional initiation, suggesting these pathways function cooperatively in maintaining the fidelity of transcription initiation in metazoans.In contrast to enormous progresses in electrode active materials, little attention has been paid to electrode sheets despite their crucial influence on practical battery performances. Here, as a facile strategy to address this issue, we demonstrate nanofibrous conductive electrode binders based on deoxyribonucleic acid (DNA)-wrapped single-walled carbon nanotubes (SWCNT) (denoted as DNA@SWCNT). DNA@SWCNT binder allows the removal of conventional polymeric binders and carbon powder additives in electrodes. As a proof of concept, high-capacity overlithiated layered oxide (OLO) is chosen as a model electrode active material. Driven by nanofibrous structure and DNA-mediated chemical functionalities, the DNA@SWCNT binder enables improvements in the redox reaction kinetics, adhesion with metallic foil current collectors, and chelation of heavy metal ions dissolved from OLO. The resulting OLO cathode exhibits a fast charging capability (relative capacity ratio after 15 min [versus 10 h] of charging = 83%), long cyclability (capacity retention = 98% after 700 cycles), and thermal stability.Aureochromes represent a unique type of blue light photoreceptors that possess a blue light sensing flavin-binding LOV-domain and a DNA-binding bZIP domain, thus being light-driven transcription factors. The diatom Phaeodactylum tricornutum, a member of the essential marine primary producers, possesses four aureochromes (PtAUREO1a, 1b, 1c, 2). Here we show a dramatic change in the global gene expression pattern of P. tricornutum wild-type cells after a shift from red to blue light. About 75% of the genes show significantly changed transcript levels already after 10 and 60 min of blue light exposure, which includes genes of major transcription factors as well as other photoreceptors. Very surprisingly, this light-induced regulation of gene expression is almost completely inhibited in independent PtAureo1a knockout lines. Such a massive and fast transcriptional change depending on one single photoreceptor is so far unprecedented. We conclude that PtAUREO1a plays a key role in diatoms upon blue light exposure.Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and to experimental observations of cellular signaling pathways of glia-neuron crosstalk. The model suggests that the onset of neurodegeneration can result as a compromise between two conflicting goals short-term resilience to stressors versus long-term prevention of tissue damage.
    To assess the impact of MRI findings on management of symptomatic patients following RFA of OO.

    Retrospective review of 43 patients with RFA for OO between June 2010 and June 2017 was performed. Patient, nidus and ablation data were reviewed. Pre- and 6-8 weeks post-procedural MRI (n=32) were compared for coverage of nidus by ablation zone, bone marrow edema, nidus hyperintensity and other findings. Baseline pain levels and analgesic use were compared with post-procedural follow-up visit at 6-8 weeks. Three groups of clinical and MRI outcomes of complete (CR), partial (PR) and no response (NR) were defined. A weighted-kappa statistic was used to assess for agreement.

    Clinical responses were CR in 34/43 (79.1%, 95%CI 64.0-90.0%), PR in 8/43 (18.6%) and NR in 1/43 (2.3%) patients. All 19/32 patients with MRI CR experienced clinical CR. One patient with MRI NR had clinical NR. All 7/32 patients with clinical PR had MRI PR. https://www.selleckchem.com/products/ulk-101.html All 4/43 complications were in MRI PR or NR groups. Substantial agreement was observed between MRI and clinical outcomes (kappa0.69, 95%CI0.45-0.95). MRI helped determine etiologies in all symptomatic patients and their management (n=8).

    MRI is recommended for symptomatic patients after ablation.
    MRI is recommended for symptomatic patients after ablation.Myocardial involvement has been described during previous SARS and MERS outbreaks. Infection by SARS-CoV-2 (COVID-19) can range from asymptomatic to life-threatening multi-system disease. Heart involvement most commonly occurs during severe COVID-19 infection. Myocardial injury, based on elevated levels of myocardial enzymes, has been noted in up to 30% of patients with COVID-19 infection and could be a marker for worse prognosis. A few cases of possible myocarditis due to SARS-CoV-2 have been described, providing variable degree of evidence of direct myocardial involvement. We reviewed in detail those cases in comparison to relevant literature on SARS and MERS and attempted to draw initial conclusions in regard to clinical presentation, treatment and prognosis.
    Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B is an H3K36me3 reader that forms a stable complex with HDAC1/2. We used CAGE-seq to profile all transcription initiation sites in wild-type mESCs and cells lacking PWWP2A/B. Loss of PWWP2A/B enhances spurious initiation from intragenic sites present in wild-type mESCs, and this effect is associated with increased levels of initiating Pol-II and histone acetylation. Spurious initiation events in Pwwp2a/b DKO mESCs do not overlap in genomic location or chromatin features with spurious sites that arise in Dnmt3b KO mESCs, previously reported to function in the suppression of intragenic transcriptional initiation, suggesting these pathways function cooperatively in maintaining the fidelity of transcription initiation in metazoans.In contrast to enormous progresses in electrode active materials, little attention has been paid to electrode sheets despite their crucial influence on practical battery performances. Here, as a facile strategy to address this issue, we demonstrate nanofibrous conductive electrode binders based on deoxyribonucleic acid (DNA)-wrapped single-walled carbon nanotubes (SWCNT) (denoted as DNA@SWCNT). DNA@SWCNT binder allows the removal of conventional polymeric binders and carbon powder additives in electrodes. As a proof of concept, high-capacity overlithiated layered oxide (OLO) is chosen as a model electrode active material. Driven by nanofibrous structure and DNA-mediated chemical functionalities, the DNA@SWCNT binder enables improvements in the redox reaction kinetics, adhesion with metallic foil current collectors, and chelation of heavy metal ions dissolved from OLO. The resulting OLO cathode exhibits a fast charging capability (relative capacity ratio after 15 min [versus 10 h] of charging = 83%), long cyclability (capacity retention = 98% after 700 cycles), and thermal stability.Aureochromes represent a unique type of blue light photoreceptors that possess a blue light sensing flavin-binding LOV-domain and a DNA-binding bZIP domain, thus being light-driven transcription factors. The diatom Phaeodactylum tricornutum, a member of the essential marine primary producers, possesses four aureochromes (PtAUREO1a, 1b, 1c, 2). Here we show a dramatic change in the global gene expression pattern of P. tricornutum wild-type cells after a shift from red to blue light. About 75% of the genes show significantly changed transcript levels already after 10 and 60 min of blue light exposure, which includes genes of major transcription factors as well as other photoreceptors. Very surprisingly, this light-induced regulation of gene expression is almost completely inhibited in independent PtAureo1a knockout lines. Such a massive and fast transcriptional change depending on one single photoreceptor is so far unprecedented. We conclude that PtAUREO1a plays a key role in diatoms upon blue light exposure.Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and to experimental observations of cellular signaling pathways of glia-neuron crosstalk. The model suggests that the onset of neurodegeneration can result as a compromise between two conflicting goals short-term resilience to stressors versus long-term prevention of tissue damage. To assess the impact of MRI findings on management of symptomatic patients following RFA of OO. Retrospective review of 43 patients with RFA for OO between June 2010 and June 2017 was performed. Patient, nidus and ablation data were reviewed. Pre- and 6-8 weeks post-procedural MRI (n=32) were compared for coverage of nidus by ablation zone, bone marrow edema, nidus hyperintensity and other findings. Baseline pain levels and analgesic use were compared with post-procedural follow-up visit at 6-8 weeks. Three groups of clinical and MRI outcomes of complete (CR), partial (PR) and no response (NR) were defined. A weighted-kappa statistic was used to assess for agreement. Clinical responses were CR in 34/43 (79.1%, 95%CI 64.0-90.0%), PR in 8/43 (18.6%) and NR in 1/43 (2.3%) patients. All 19/32 patients with MRI CR experienced clinical CR. One patient with MRI NR had clinical NR. All 7/32 patients with clinical PR had MRI PR. https://www.selleckchem.com/products/ulk-101.html All 4/43 complications were in MRI PR or NR groups. Substantial agreement was observed between MRI and clinical outcomes (kappa0.69, 95%CI0.45-0.95). MRI helped determine etiologies in all symptomatic patients and their management (n=8). MRI is recommended for symptomatic patients after ablation. MRI is recommended for symptomatic patients after ablation.Myocardial involvement has been described during previous SARS and MERS outbreaks. Infection by SARS-CoV-2 (COVID-19) can range from asymptomatic to life-threatening multi-system disease. Heart involvement most commonly occurs during severe COVID-19 infection. Myocardial injury, based on elevated levels of myocardial enzymes, has been noted in up to 30% of patients with COVID-19 infection and could be a marker for worse prognosis. A few cases of possible myocarditis due to SARS-CoV-2 have been described, providing variable degree of evidence of direct myocardial involvement. We reviewed in detail those cases in comparison to relevant literature on SARS and MERS and attempted to draw initial conclusions in regard to clinical presentation, treatment and prognosis.
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  • Introduction Induction of collagen and elastin remodeling in the human skin can be achieved by non-ablative fractional laser (NAFXL) and ablative fractional laser (AFXL). Our objective was to compare the safety, efficacy, tolerability, and ability to induce collagen and elastin remodeling of NAFXL versus AFXL in a series of treatments over time.Materials and Methods In this prospective, proof of principle, single-case study, the safety, tolerability and efficacy of the laser systems were assessed via histopathology and clinical evaluations including photographs. Optical biopsies by means of multiphoton tomography (MPT) were used to evaluate the induction of collagen and elastin remodeling.Results Treatments by both NAFXL and AFXL were well tolerated. The NAFXL system was found to be less painful and resulted in a shorter down- and healing times. MPT findings showed the superior capability of the AFXL procedure to induce collagen; on the other hand, elastin induction was more pronounced after NAFXL treatments.Conclusions While NAFXL is as effective and safe as the traditional AFXL, it is better tolerated and has a shorter downtime. Serial optical biopsies over time over time can be a useful tool to assess the induction of collagen and elastin remodeling in the human skin.Objectives. There is limited knowledge of atrial fibrillation (AF) incidence among the very old. Data from longitudinal cohort studies may give us a better insight. The aim of the study was to investigate the incidence rate and prevalence of AF, as well as the impact of AF on mortality, in the general population, from 70 to 100 years of age. Design. This was a population-based prospective cohort study where three representative samples of 70-year-old men and women (n = 2,629) from the Gerontological and Geriatric Populations Studies in Gothenburg (H-70) were included between 1971 and 1982. The participants were examined at age 70 years and were re-examined repeatedly until 100 years of age. AF was diagnosed according to a 12-lead electrocardiogram (ECG) recording at baseline and follow-up examinations, from the Swedish National Patient Register (NPR), or from the Cause of Death Register. Results. The cumulative incidence of AF from 70 to 100 years of age was 65.6% for men and 52.8% for women. Mortality was significantly higher in participants with AF compared with those without, rate ratio (RR) 1.92 (95% CI 1.73-2.14). In a subgroup analysis comprising only participants with AF diagnosed by ECG at screening, the RR for death was 1.29 (95% C.I 1.03-1.63). Conclusions. Among persons surviving to age 70, the cumulative incidence of AF was over 50% during follow-up. Mortality rate was twice as high in participants with AF compared to participants without AF. Among participants with AF first recorded at a screening examination, the increased risk was only 29%.Aim To identify intestinal microbiota compositions in elderly functional constipation (FC) patients. Materials & methods Fecal samples from 61 FC patients and 48 healthy age-matched volunteers were analyzed through 16S rRNA gene sequencing. Results The intestinal microbiota compositions of FC patients were significantly different from healthy controls. Additionally, the species diversity of healthy controls was greater than that of FC patients. Indeed, the abundance of Firmicutes and Proteobacteria was significantly decreased, whereas that of Bacteroides, Prevotella, Lactococcus, Ruminococcus and Butyricimonas was remarkably increased in FC patients. Conclusion Elderly FC patients appear to have a unique intestinal microbiota profile. Our findings should provide insight regarding the pathogenic mechanism of FC and evidence for exploring new therapeutic strategies in elderly FC patients.Context Ketoprofen is widely used to remove pain. A steady increase on allergic reactions and photoallergic contact dermatitis related to ketoprofen has been reported when there is topical use. However, there are few documented cases of hypersensitivity when it is administered systemically.Objective Present a case of hypersensitivity reaction after systemic administration of ketoprofen for pain control in nephritis crisis.Case description A 43-years-old Caucasian man diagnosed with renal colic (kidney lithiasis), who was initially treated with 100 mg of tramadol (IV), followed by 4 mg of thiocolchicoside (IM) which caused no relief. Then 100 mg of ketoprofen was administered (IV). Right after the patient began to show hypersensitivity reaction type I characterized by intense coughing, rhinitis, angioedema, periorbital edema, rash, and scleral jaundice.Discussion and conclusion Maybe it was a case of drug-induced liver disease, however therapeutic dosages of all administered drugs only once. The mechanisms involved were not investigated, but may be the result of allergic and immunologic aspects caused by ketoprofen and facilitated by a history of hypersensitivity to other NSAIDs as reported by the patient. https://www.selleckchem.com/products/tpx-0046.html As for jaundice can be attributed to drug toxicity since laboratory parameters did not reveal any evidence of liver disease.Shift nurses are prone to sleep problems and impaired nighttime alertness, with risk for reduced health status plus decreased performance, handling errors, and workplace accidents. Attention to and improvements in the situation of shift nurses are urgent. Shimian granules (SMG), an improved formula of Jieyuanshen with liver qingre and yangxin tranquilizing effects, for more than a decade has been used in China as a herbal treatment of sleep disorders in clinical practice. However, clinical data on SMG have rarely been reported. This double-blinded, randomized, placebo-controlled, pilot clinical trial (ChiCTR-IOR-17013031) aimed to explore whether Shimian granules (SMG) improves sleep and affective state in shift nurses and in association with changes in concentrations of salivary cytokines. Fifty-three rotating-shift female nurses with a Pittsburgh Sleep Quality Index (PSQI) score ≥8 were orally treated with 10.0 g SMG or placebo 2 times daily (30 min after breakfast and 30 min before bed) for 1 month. The Insomnia Severity Index (ISI), a psychomotor vigilance task, Hospital Anxiety and Depression Scale (HADS-A/HADS-D), and levels of four salivary cytokines were evaluated by single time-of-day sampling at baseline and after 1 month of treatment.
    Introduction Induction of collagen and elastin remodeling in the human skin can be achieved by non-ablative fractional laser (NAFXL) and ablative fractional laser (AFXL). Our objective was to compare the safety, efficacy, tolerability, and ability to induce collagen and elastin remodeling of NAFXL versus AFXL in a series of treatments over time.Materials and Methods In this prospective, proof of principle, single-case study, the safety, tolerability and efficacy of the laser systems were assessed via histopathology and clinical evaluations including photographs. Optical biopsies by means of multiphoton tomography (MPT) were used to evaluate the induction of collagen and elastin remodeling.Results Treatments by both NAFXL and AFXL were well tolerated. The NAFXL system was found to be less painful and resulted in a shorter down- and healing times. MPT findings showed the superior capability of the AFXL procedure to induce collagen; on the other hand, elastin induction was more pronounced after NAFXL treatments.Conclusions While NAFXL is as effective and safe as the traditional AFXL, it is better tolerated and has a shorter downtime. Serial optical biopsies over time over time can be a useful tool to assess the induction of collagen and elastin remodeling in the human skin.Objectives. There is limited knowledge of atrial fibrillation (AF) incidence among the very old. Data from longitudinal cohort studies may give us a better insight. The aim of the study was to investigate the incidence rate and prevalence of AF, as well as the impact of AF on mortality, in the general population, from 70 to 100 years of age. Design. This was a population-based prospective cohort study where three representative samples of 70-year-old men and women (n = 2,629) from the Gerontological and Geriatric Populations Studies in Gothenburg (H-70) were included between 1971 and 1982. The participants were examined at age 70 years and were re-examined repeatedly until 100 years of age. AF was diagnosed according to a 12-lead electrocardiogram (ECG) recording at baseline and follow-up examinations, from the Swedish National Patient Register (NPR), or from the Cause of Death Register. Results. The cumulative incidence of AF from 70 to 100 years of age was 65.6% for men and 52.8% for women. Mortality was significantly higher in participants with AF compared with those without, rate ratio (RR) 1.92 (95% CI 1.73-2.14). In a subgroup analysis comprising only participants with AF diagnosed by ECG at screening, the RR for death was 1.29 (95% C.I 1.03-1.63). Conclusions. Among persons surviving to age 70, the cumulative incidence of AF was over 50% during follow-up. Mortality rate was twice as high in participants with AF compared to participants without AF. Among participants with AF first recorded at a screening examination, the increased risk was only 29%.Aim To identify intestinal microbiota compositions in elderly functional constipation (FC) patients. Materials & methods Fecal samples from 61 FC patients and 48 healthy age-matched volunteers were analyzed through 16S rRNA gene sequencing. Results The intestinal microbiota compositions of FC patients were significantly different from healthy controls. Additionally, the species diversity of healthy controls was greater than that of FC patients. Indeed, the abundance of Firmicutes and Proteobacteria was significantly decreased, whereas that of Bacteroides, Prevotella, Lactococcus, Ruminococcus and Butyricimonas was remarkably increased in FC patients. Conclusion Elderly FC patients appear to have a unique intestinal microbiota profile. Our findings should provide insight regarding the pathogenic mechanism of FC and evidence for exploring new therapeutic strategies in elderly FC patients.Context Ketoprofen is widely used to remove pain. A steady increase on allergic reactions and photoallergic contact dermatitis related to ketoprofen has been reported when there is topical use. However, there are few documented cases of hypersensitivity when it is administered systemically.Objective Present a case of hypersensitivity reaction after systemic administration of ketoprofen for pain control in nephritis crisis.Case description A 43-years-old Caucasian man diagnosed with renal colic (kidney lithiasis), who was initially treated with 100 mg of tramadol (IV), followed by 4 mg of thiocolchicoside (IM) which caused no relief. Then 100 mg of ketoprofen was administered (IV). Right after the patient began to show hypersensitivity reaction type I characterized by intense coughing, rhinitis, angioedema, periorbital edema, rash, and scleral jaundice.Discussion and conclusion Maybe it was a case of drug-induced liver disease, however therapeutic dosages of all administered drugs only once. The mechanisms involved were not investigated, but may be the result of allergic and immunologic aspects caused by ketoprofen and facilitated by a history of hypersensitivity to other NSAIDs as reported by the patient. https://www.selleckchem.com/products/tpx-0046.html As for jaundice can be attributed to drug toxicity since laboratory parameters did not reveal any evidence of liver disease.Shift nurses are prone to sleep problems and impaired nighttime alertness, with risk for reduced health status plus decreased performance, handling errors, and workplace accidents. Attention to and improvements in the situation of shift nurses are urgent. Shimian granules (SMG), an improved formula of Jieyuanshen with liver qingre and yangxin tranquilizing effects, for more than a decade has been used in China as a herbal treatment of sleep disorders in clinical practice. However, clinical data on SMG have rarely been reported. This double-blinded, randomized, placebo-controlled, pilot clinical trial (ChiCTR-IOR-17013031) aimed to explore whether Shimian granules (SMG) improves sleep and affective state in shift nurses and in association with changes in concentrations of salivary cytokines. Fifty-three rotating-shift female nurses with a Pittsburgh Sleep Quality Index (PSQI) score ≥8 were orally treated with 10.0 g SMG or placebo 2 times daily (30 min after breakfast and 30 min before bed) for 1 month. The Insomnia Severity Index (ISI), a psychomotor vigilance task, Hospital Anxiety and Depression Scale (HADS-A/HADS-D), and levels of four salivary cytokines were evaluated by single time-of-day sampling at baseline and after 1 month of treatment.
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  • A head animation sub-system with graphical user interfaces was also developed. Model accuracy and system performances were analyzed. RESULTS The comparison with MRI-based model shows a very good accuracy level (distance deviation of ~1 mm in neutral position and an error range of [2-3 mm] for different facial mimic positions) for the generated model from our system. Moreover, the system speed can be optimized to reach a high framerate (up to 60 fps) during different head and facial mimic animations. CONCLUSIONS This study presents a novel computer vision system for tracking simultaneously subject-specific rigid head and non-rigid facial mimic movements in real time. In perspectives, serious game technology will be integrated into this system towards a full computer-aided decision support system for facial rehabilitation. V.Kinetic non-linear metabolic models are used extensively in medical research and increasingly for clinical diagnostic purposes. An example of such a model is the Glucose Minimal Model by Bergman and colleagues [1]. This model is similar to pharmacokinetic/pharmacodynamic models in that like pharmacokinetic/pharmacodynamic models, it is based on a small number of fairly simple ordinary differential equations and it aims to determine how the changing concentration of one blood constituent influences the concentration of another constituent. Although such models may appear prima facie, to be relatively simple, they have gained a reputation of being difficult to fit to data, especially in a consistent and repeatable fashion. Consequently, researchers and clinicians have generally relied on dedicated software packages to do this type of modeling. This article describes the use of statistical and spreadsheet software for fitting the Glucose Minimal Model to data from an insulin modified intravenous glucose tolerance test (IM-IVGTT). A novel aspect of the modeling is that the differential equations that are normally used to describe insulin action and the disposition of plasma glucose are first solved and expressed in their explicit forms so as to facilitate the estimation of Glucose Minimal Model parameters using the nonlinear (nl) optimization procedure within statistical and spreadsheet software. The most important clinical parameter obtained from the Glucose Minimal Model is insulin sensitivity (SI). Using IM-IVGTT data from 42 horses in one experiment and 48 horses in a second experiment, we demonstrate that estimates of SI derived from the Glucose Minimal Model fitted to data using STATA and Excel, are highly concordant with SI estimates obtained using the industry standard software, MinMod Millennium. This work demonstrates that there is potential for statistical and spreadsheet software to be applied to a wide range of kinetic non-linear modeling problems. https://www.selleckchem.com/products/pf-9366.html V.BACKGROUND Nanofluids are known for better heat transfer characteristics in many heat exchanger devices due to their enhanced heat transfer abilities. Recently, scientists give the idea of nanofluid which is the mixture of base fluid and solid nanoparticles having very small size. For physical phenomenon of conventional fluids by mean of suspensions of nanoparticles in base fluids and prompted produce a new composite known as "nanofluids". These composite contain the nanoparticles with 1-100 nm sized which are suspended in the base fluids. Here we have considered a subclass of non-Newtonian fluid called Oldroyd-B fluid. The fluid motion over the disk surface is produced due to the rotation as well as radially stretching of disk. Further, the impact of non-linear thermal radiation and heat generation/absorption is introduced to visualize the heat transfer behavior. The convective boundary is also taken into consideration in order to investigate the fluid thermal characteristics. The novel features of thermophosfer rate at the wall is noticed against thermoporesis and Brownian motion parameters, respectively. The concentration gradient at the wall reduces with an increment in mass transfer parameter. V.Sorption onto clays (montmorillonite and kaolinite), oxidation and sorption by manganese oxides (synthesized MnO and natural MnO), and coupled sorption-oxidation experiments were conducted for the removal of antibiotics sulfadiazine (SDZ) and ciprofloxacin (CIP) at pH 5 and 8. Individual sorption and oxidation modelling were carried out using the first-order kinetic model. A coupled sorption-oxidation kinetic model was developed to predict the simultaneous sorption and oxidation process. The coupled sorption-oxidation enhanced the antibiotic sorption, with the first-order sorption rate constants in the simultaneous presence of clays and manganese oxides (ksorp) being higher than those with clays only (ksorp0). In contrast, a depression was observed; the first-order oxidation and sorption combination rate constants in the simultaneous presence of manganese oxides and clays (kMnO) were lower than those with manganese oxides only (kMnO0). In the coupled sorption-oxidation reaction, 13.5-62.5% of SDZ and CIP removal was attributed to the sorption. The SDZ and CIP species distributions at pH 5 affected the coupled sorption and oxidation systems more than those at pH 8. The best removal efficiency was achieved by the montmorillonite-synthesized MnO combination, mainly due to the higher surface area (ABET) and pore size of montmorillonite and synthesized MnO combination compared to other clays and manganese oxides combinations. To investigate the effect of gestational and lactational nonylphenol (NP) exposure on airway inflammation in ovalbumin (OVA)-induced asthmatic pups. Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 7 to postnatal day 21. The results showed that the NP content in the lung tissues of pups in the 100 mg/kg NP group was significantly higher than that of the control group (P = 0.004). In the 100 mg/kg NP group, the infiltration of lymphocytes and eosinophils with thicken smooth muscle layer and inflammatory cells in the lumen were observed in the lung tissues of pups. Osmiophilic lamellar bodies were found in the cytoplasm of type II epithelial cells; mitochondria were clearly swollen. Compared with the control group, the levels of interleukin-4 (IL-4) in BALF (P = 0.042) and ovalbumin-specific serum immunoglobulin E (OVA-sIgE) (P = 0.005) in the OVA group were significantly higher.
    A head animation sub-system with graphical user interfaces was also developed. Model accuracy and system performances were analyzed. RESULTS The comparison with MRI-based model shows a very good accuracy level (distance deviation of ~1 mm in neutral position and an error range of [2-3 mm] for different facial mimic positions) for the generated model from our system. Moreover, the system speed can be optimized to reach a high framerate (up to 60 fps) during different head and facial mimic animations. CONCLUSIONS This study presents a novel computer vision system for tracking simultaneously subject-specific rigid head and non-rigid facial mimic movements in real time. In perspectives, serious game technology will be integrated into this system towards a full computer-aided decision support system for facial rehabilitation. V.Kinetic non-linear metabolic models are used extensively in medical research and increasingly for clinical diagnostic purposes. An example of such a model is the Glucose Minimal Model by Bergman and colleagues [1]. This model is similar to pharmacokinetic/pharmacodynamic models in that like pharmacokinetic/pharmacodynamic models, it is based on a small number of fairly simple ordinary differential equations and it aims to determine how the changing concentration of one blood constituent influences the concentration of another constituent. Although such models may appear prima facie, to be relatively simple, they have gained a reputation of being difficult to fit to data, especially in a consistent and repeatable fashion. Consequently, researchers and clinicians have generally relied on dedicated software packages to do this type of modeling. This article describes the use of statistical and spreadsheet software for fitting the Glucose Minimal Model to data from an insulin modified intravenous glucose tolerance test (IM-IVGTT). A novel aspect of the modeling is that the differential equations that are normally used to describe insulin action and the disposition of plasma glucose are first solved and expressed in their explicit forms so as to facilitate the estimation of Glucose Minimal Model parameters using the nonlinear (nl) optimization procedure within statistical and spreadsheet software. The most important clinical parameter obtained from the Glucose Minimal Model is insulin sensitivity (SI). Using IM-IVGTT data from 42 horses in one experiment and 48 horses in a second experiment, we demonstrate that estimates of SI derived from the Glucose Minimal Model fitted to data using STATA and Excel, are highly concordant with SI estimates obtained using the industry standard software, MinMod Millennium. This work demonstrates that there is potential for statistical and spreadsheet software to be applied to a wide range of kinetic non-linear modeling problems. https://www.selleckchem.com/products/pf-9366.html V.BACKGROUND Nanofluids are known for better heat transfer characteristics in many heat exchanger devices due to their enhanced heat transfer abilities. Recently, scientists give the idea of nanofluid which is the mixture of base fluid and solid nanoparticles having very small size. For physical phenomenon of conventional fluids by mean of suspensions of nanoparticles in base fluids and prompted produce a new composite known as "nanofluids". These composite contain the nanoparticles with 1-100 nm sized which are suspended in the base fluids. Here we have considered a subclass of non-Newtonian fluid called Oldroyd-B fluid. The fluid motion over the disk surface is produced due to the rotation as well as radially stretching of disk. Further, the impact of non-linear thermal radiation and heat generation/absorption is introduced to visualize the heat transfer behavior. The convective boundary is also taken into consideration in order to investigate the fluid thermal characteristics. The novel features of thermophosfer rate at the wall is noticed against thermoporesis and Brownian motion parameters, respectively. The concentration gradient at the wall reduces with an increment in mass transfer parameter. V.Sorption onto clays (montmorillonite and kaolinite), oxidation and sorption by manganese oxides (synthesized MnO and natural MnO), and coupled sorption-oxidation experiments were conducted for the removal of antibiotics sulfadiazine (SDZ) and ciprofloxacin (CIP) at pH 5 and 8. Individual sorption and oxidation modelling were carried out using the first-order kinetic model. A coupled sorption-oxidation kinetic model was developed to predict the simultaneous sorption and oxidation process. The coupled sorption-oxidation enhanced the antibiotic sorption, with the first-order sorption rate constants in the simultaneous presence of clays and manganese oxides (ksorp) being higher than those with clays only (ksorp0). In contrast, a depression was observed; the first-order oxidation and sorption combination rate constants in the simultaneous presence of manganese oxides and clays (kMnO) were lower than those with manganese oxides only (kMnO0). In the coupled sorption-oxidation reaction, 13.5-62.5% of SDZ and CIP removal was attributed to the sorption. The SDZ and CIP species distributions at pH 5 affected the coupled sorption and oxidation systems more than those at pH 8. The best removal efficiency was achieved by the montmorillonite-synthesized MnO combination, mainly due to the higher surface area (ABET) and pore size of montmorillonite and synthesized MnO combination compared to other clays and manganese oxides combinations. To investigate the effect of gestational and lactational nonylphenol (NP) exposure on airway inflammation in ovalbumin (OVA)-induced asthmatic pups. Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 7 to postnatal day 21. The results showed that the NP content in the lung tissues of pups in the 100 mg/kg NP group was significantly higher than that of the control group (P = 0.004). In the 100 mg/kg NP group, the infiltration of lymphocytes and eosinophils with thicken smooth muscle layer and inflammatory cells in the lumen were observed in the lung tissues of pups. Osmiophilic lamellar bodies were found in the cytoplasm of type II epithelial cells; mitochondria were clearly swollen. Compared with the control group, the levels of interleukin-4 (IL-4) in BALF (P = 0.042) and ovalbumin-specific serum immunoglobulin E (OVA-sIgE) (P = 0.005) in the OVA group were significantly higher.
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  • PURPOSE To evaluate the clinical value of intraoperative optical coherence tomography (iOCT) and prolonged overpressure in Descemet membrane endothelial keratoplasty for surgical safety, efficiency, and outcome. METHODS All Descemet membrane endothelial keratoplasties performed by the same surgeon from November 2016 through April 2018 at the University Medical Center Utrecht were included, including 6 months of follow-up. The primary outcome was the prevalence of adverse events, and the secondary outcomes included critical decision-making and surgery time. Surgeries that included prolonged (ca. 12 minutes) overpressurization of the globe were classified as group 1, and those without prolonged overpressurization of the globe were classified as group 2. In all cases, iOCT was used to determine the graft orientation, apposition, and assessment of interface fluid. RESULTS A total of 38 cases were included for analysis. In groups 1 and 2, 7 (43.6%) and 4 (18.1%) adverse events, respectively, were recorded (P = 0.29). Specifically, in groups 1 and 2, 4 and 3 cases, respectively, required rebubbling because of graft dislocation (P = 0.15). In 43% of surgeries, iOCT proved to be of value for surgical decision-making. Surgery time differed significantly between groups 1 and 2 (P less then 0.001) and was the result of a shortened pressurization time in group 2. CONCLUSIONS iOCT provides a direct assessment of the graft orientation and apposition, allowing the surgeon to refrain from prolonged pressurization of the globe after graft insertion. Optimizing the surgical protocol using iOCT can lead to a significant reduction in surgery time without compromising surgical safety or outcome.PURPOSE To report a case of corneal epithelial plaque formation associated with recombinant human nerve growth factor (cenegermin 0.002%; Oxervate, Dompe[Combining Acute Accent] US Inc., Boston, MA), an as-yet unreported adverse event. METHODS A case report and review of literature. RESULTS A 45-year-old woman presented with a nonhealing 3.25- × 4.25-mm corneal epithelial defect secondary to multifactorial neurotrophic keratitis in the right eye. The epithelial defect was resistant to maximal medical therapy, and so cenegermin 0.002% was initiated, resulting in resolution of the corneal epithelial defect. After 6.5 weeks of treatment, she developed an unusual corneal epithelial plaque, decreased visual acuity, and eye pain. Cenegermin was ceased, after which the lesion resolved, visual acuity improved, and eye pain resolved. CONCLUSIONS Cenegermin 0.002% has emerged as a promising treatment for neurotrophic keratitis. Reported adverse events with this agent have been minor and typically not vision threatening. Here, we describe corneal epithelial plaque formation as a visually significant adverse event that resolved with cessation of cenegermin 0.002%. Although the underlying mechanism is unknown, clinicians should be alerted to the possibility of epithelial plaque formation in patients being treated with recombinant human nerve growth factor for neurotrophic keratitis.PURPOSE To investigate the effects of an eye wash solution on the ocular surface damage induced by airborne carbon black (CB) exposure. METHODS Sprague-Dawley rats were exposed to ambient CB for 5 days. During the 5 days, a commercial eye wash solution (Eyebon-W) was used for irrigation twice daily on CB-exposed rat eyes; normal saline was used as the vehicle control. Lactic dehydrogenase (LDH) activity and matrix metallopeptidase (MMP)-9, histamine, and lactoferrin levels were measured in tears. The expression of inflammatory cytokines in the anterior segment of the eyeball was measured by Western blot analysis. RESULTS The ocular surface staining scores, tear LDH activity, tear MMP-9, histamine, and lactoferrin concentrations, and the expression of interleukin-4 and interferon-γ in the eye were significantly increased in the CB group versus the normal control group. When compared with CB group, the Eyebon-W eye wash treatment significantly reversed these elevations induced by CB, including ocular staining scores, tear LDH activity, histamine and MMP-9 concentrations in the tear fluid, and the expression of interleukin-4 in the eye. On the other hand, saline irrigation only reduced the concentrations of histamine and MMP-9 in tear fluid and the expression of interferon-γ in the eye. CONCLUSIONS Both Eyebon-W eye wash treatment and saline irrigation reversed CB-induced ocular surface injury, but the efficacy of Eyebon-W was more significant than that of the saline solution when compared with CB group. The use of an eye wash solution seems to play a protective role for the ocular surface when exposed to airborne particulate matter.PURPOSE To investigative the effects of sex steroids on hyperosmolar stress-induced proinflammatory cytokine expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, and IL-6, and on the mitogen-activated protein kinase pathway in immortalized human corneal epithelial cells (hCECs). METHODS Immortalized hCECs were cultured with keratinocyte-free medium until reaching 80% confluency with either 10 M dihidrotestosteron (DHT) or 10 M 17-β-estradiol, and then, the medium was changed to hyperosmolar for various time points. After hyperosmolar treatment, a real-time polymerase chain reaction was performed to show the TNF-α, IL-8, and IL-6 gene expression levels in hCECs. In addition, the treated cells were lysed, and Western blot analysis was applied for phosphorylated and nonphosphorylated forms of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 kinase, and c-Jun N-terminal kinase 1/2 (JNK1/2). hCECs viability was measured with Annexin V/propidium iodide. RESULTS Pretreatment with 10 M DHT or 17-β-estradiol inhibited the high osmolarity-induced expression of TNF-α, IL-8, and IL-6. The upregulation of p-ERK, p-JNK, and p-p38 with high osmolarity was inhibited partially by DHT, but 17-β-estradiol pretreatment only affected p-p38 for a short time interval. In addition, DHT increased cell viability of hCECs under hyperosmolar conditions. https://www.selleckchem.com/products/caerulein.html CONCLUSIONS Our results demonstrated that DHT and 17-β-estradiol decreased the proinflammatory cytokine gene expression levels which were stimulated by high osmolarity in immortalized hCECs. The mitogen-activated protein kinase signaling pathway is partially involved in the regulatory effects of DHT on hCECs. These findings may contribute to the etiologic role and therapeutic implications of sex steroids in certain ocular surface diseases.
    PURPOSE To evaluate the clinical value of intraoperative optical coherence tomography (iOCT) and prolonged overpressure in Descemet membrane endothelial keratoplasty for surgical safety, efficiency, and outcome. METHODS All Descemet membrane endothelial keratoplasties performed by the same surgeon from November 2016 through April 2018 at the University Medical Center Utrecht were included, including 6 months of follow-up. The primary outcome was the prevalence of adverse events, and the secondary outcomes included critical decision-making and surgery time. Surgeries that included prolonged (ca. 12 minutes) overpressurization of the globe were classified as group 1, and those without prolonged overpressurization of the globe were classified as group 2. In all cases, iOCT was used to determine the graft orientation, apposition, and assessment of interface fluid. RESULTS A total of 38 cases were included for analysis. In groups 1 and 2, 7 (43.6%) and 4 (18.1%) adverse events, respectively, were recorded (P = 0.29). Specifically, in groups 1 and 2, 4 and 3 cases, respectively, required rebubbling because of graft dislocation (P = 0.15). In 43% of surgeries, iOCT proved to be of value for surgical decision-making. Surgery time differed significantly between groups 1 and 2 (P less then 0.001) and was the result of a shortened pressurization time in group 2. CONCLUSIONS iOCT provides a direct assessment of the graft orientation and apposition, allowing the surgeon to refrain from prolonged pressurization of the globe after graft insertion. Optimizing the surgical protocol using iOCT can lead to a significant reduction in surgery time without compromising surgical safety or outcome.PURPOSE To report a case of corneal epithelial plaque formation associated with recombinant human nerve growth factor (cenegermin 0.002%; Oxervate, Dompe[Combining Acute Accent] US Inc., Boston, MA), an as-yet unreported adverse event. METHODS A case report and review of literature. RESULTS A 45-year-old woman presented with a nonhealing 3.25- × 4.25-mm corneal epithelial defect secondary to multifactorial neurotrophic keratitis in the right eye. The epithelial defect was resistant to maximal medical therapy, and so cenegermin 0.002% was initiated, resulting in resolution of the corneal epithelial defect. After 6.5 weeks of treatment, she developed an unusual corneal epithelial plaque, decreased visual acuity, and eye pain. Cenegermin was ceased, after which the lesion resolved, visual acuity improved, and eye pain resolved. CONCLUSIONS Cenegermin 0.002% has emerged as a promising treatment for neurotrophic keratitis. Reported adverse events with this agent have been minor and typically not vision threatening. Here, we describe corneal epithelial plaque formation as a visually significant adverse event that resolved with cessation of cenegermin 0.002%. Although the underlying mechanism is unknown, clinicians should be alerted to the possibility of epithelial plaque formation in patients being treated with recombinant human nerve growth factor for neurotrophic keratitis.PURPOSE To investigate the effects of an eye wash solution on the ocular surface damage induced by airborne carbon black (CB) exposure. METHODS Sprague-Dawley rats were exposed to ambient CB for 5 days. During the 5 days, a commercial eye wash solution (Eyebon-W) was used for irrigation twice daily on CB-exposed rat eyes; normal saline was used as the vehicle control. Lactic dehydrogenase (LDH) activity and matrix metallopeptidase (MMP)-9, histamine, and lactoferrin levels were measured in tears. The expression of inflammatory cytokines in the anterior segment of the eyeball was measured by Western blot analysis. RESULTS The ocular surface staining scores, tear LDH activity, tear MMP-9, histamine, and lactoferrin concentrations, and the expression of interleukin-4 and interferon-γ in the eye were significantly increased in the CB group versus the normal control group. When compared with CB group, the Eyebon-W eye wash treatment significantly reversed these elevations induced by CB, including ocular staining scores, tear LDH activity, histamine and MMP-9 concentrations in the tear fluid, and the expression of interleukin-4 in the eye. On the other hand, saline irrigation only reduced the concentrations of histamine and MMP-9 in tear fluid and the expression of interferon-γ in the eye. CONCLUSIONS Both Eyebon-W eye wash treatment and saline irrigation reversed CB-induced ocular surface injury, but the efficacy of Eyebon-W was more significant than that of the saline solution when compared with CB group. The use of an eye wash solution seems to play a protective role for the ocular surface when exposed to airborne particulate matter.PURPOSE To investigative the effects of sex steroids on hyperosmolar stress-induced proinflammatory cytokine expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, and IL-6, and on the mitogen-activated protein kinase pathway in immortalized human corneal epithelial cells (hCECs). METHODS Immortalized hCECs were cultured with keratinocyte-free medium until reaching 80% confluency with either 10 M dihidrotestosteron (DHT) or 10 M 17-β-estradiol, and then, the medium was changed to hyperosmolar for various time points. After hyperosmolar treatment, a real-time polymerase chain reaction was performed to show the TNF-α, IL-8, and IL-6 gene expression levels in hCECs. In addition, the treated cells were lysed, and Western blot analysis was applied for phosphorylated and nonphosphorylated forms of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 kinase, and c-Jun N-terminal kinase 1/2 (JNK1/2). hCECs viability was measured with Annexin V/propidium iodide. RESULTS Pretreatment with 10 M DHT or 17-β-estradiol inhibited the high osmolarity-induced expression of TNF-α, IL-8, and IL-6. The upregulation of p-ERK, p-JNK, and p-p38 with high osmolarity was inhibited partially by DHT, but 17-β-estradiol pretreatment only affected p-p38 for a short time interval. In addition, DHT increased cell viability of hCECs under hyperosmolar conditions. https://www.selleckchem.com/products/caerulein.html CONCLUSIONS Our results demonstrated that DHT and 17-β-estradiol decreased the proinflammatory cytokine gene expression levels which were stimulated by high osmolarity in immortalized hCECs. The mitogen-activated protein kinase signaling pathway is partially involved in the regulatory effects of DHT on hCECs. These findings may contribute to the etiologic role and therapeutic implications of sex steroids in certain ocular surface diseases.
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  • With the age the risks of comorbidities increases multidisease syndrome. Elderly patients suffer from frailty syndrome. All these factors make the elderly patient a major challenge for a laparoscopy treatment. CONCLUSION The laparoscopic approach is an effective method for treatment of perforated peptic ulcer in the elderly with a great diagnostic and therapeutic role. Nowadays more prospective randomized studies are needed to evaluate the effectiveness of laparoscopic versus open repair.INTRODUCTION Red cell distribution width (RDW) is a parameter that reflects the heterogeneity in the size of the circulating erythrocytes. Elevated levels of RDW have been found related to various pathologic conditions including cancers. We hypothesized that elevated RDW levels might correspond to advanced stages of pancreatic cancer. METHODS The medical files and pathology reports of patients who underwent Whipple procedure were evaluated in a retrospective casecontrol study. The relationship of RDW to age, gender, cancer antigen 19-9 (CA 19-9), blood hemoglobin levels, stage of the tumor, tumor size, tumor grade, number of lymph nodes with metastasis, the status of lymphovascular and perineural invasion were investigated. A oneto-two, age- and- gender matched group of seemingly healthy patients was used to compare the levels of RDW between the patients of pancreatic head malignancy and healthy people. ROC (receiver operating characteristics) curves analysis was conducted to define a threshold to discriminate malignant pancreatic head tumors from healthy control subjects. Then, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. RESULTS The median age was 61 years (IRQ 54.75-69). The median RDWs were 15.20% (IQR 13.20-19.50) vs 13.00 (IQR 12.60-13.48) in the pancreas adenocancer and the control group, respectively, p=0.000). There was significant relationship between RDW and the grade of the tumor, p=0.026. An RDW level of 14% was obtained as a result of the ROC curves analysis and the positive predictivity about malignancy was 70.73% with a negative predictive rate of 89.95% compared with the healthy group of patients. CONCLUSION The elevated levels of RDW in patients with a pancreatic mass may point to a possible malignancy; however, an elevated RDW in a patient with a malignant pancreatic head mass is related to the grade of the disease, not the stage.BACKGROUND Retroperitoneal sarcoma is a rare malignancy arising from mesenchymal cells, most commonly presented as an abdominal mass and is associated with poor prognosis. The most effective treatment modality for retroperitoneal sarcomas is complete surgical resection, including sometimes adjacent organs infiltrated by the tumor. Radiotherapy is frequently applied and has shown some benefit, while the role of chemotherapy and molecular-targeted agents is still not clear. Local recurrence is common for retroperitoneal sarcomas and still remains the main cause of death. The major factors associated with the overall survival are tumor grade, histological subtype, complete macroscopic excision and multifocality. AIM To report our experience via the presentation of patients with retroperitoneal sarcomas managed in our department during the period 2014-18; and to review the current literature. PATIENTS AND METHODS Eight patients appeared with chronic non-specific complaints including abdominal distension and changllance for early detection of recurrence or metastases.Bariatric surgery was introduced in 1953, but during the last 20 years its popularity has increased after the development of significant Romaevidenced based breakthroughs in the field. Currently, approximately 150 long-term randomized clinical trials and 40 meta-analyses support and give credibility to the surgical approaches for the treatment of obesity and its related metabolic disturbances. https://www.selleckchem.com/products/pf-9366.html Bariatric surgery has demonstrated improved outcomes compared to medical treatment, conduct therapy, and endoscopic procedures. Roux-en-Y gastrojejunostomy (RYGB) and Sleeve gastrectomy (SG) are the surgical procedures most frequently performed, due to their satisfactory results and security profile. There is sufficient evidence in medical literature to perform these procedures when indicated; however, there are still several controversies regarding technical aspects that need to be further explored.The present study aimed to examine the taxonomic relationship between two species, Paracoccus bengalensis Ghosh et al. 2006 and Paracoccus versutus (Harrison 1983) Katayama et al. 1996. Comparison of 16S rRNA gene sequences revealed that P. bengalensis JJJT was highly similar (99.9 %) to P. versutus A2T. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the two strains formed a tight cluster within the genus Paracoccus. Whole genomic comparison between the two strains showed a digital DNA-DNA hybridization estimate of 82. 0 % and an average nucleotide identity value of 98.2 %, clearly indicating that the two strains were members of the same species. Moreover, the type strains of both species shared similar physiological and biochemical properties and fatty acids profiles. Based on genotypic and phenotypic evidence, we conclude that Paracoccus bengalensis Ghosh et al. 2006 is a later heterotypic synonym of Paracoccus versutus (Harrison 1983) Katayama et al. 1996 according to the priority of publication and validation of the name.A novel Gram-negative, obligately aerobic, rod-shaped and non-motile bacterium, designated strain K13M18T, was isolated from the intestinal tract of a Korean indigenous fish, oily bitterling (Acheilognathus koreensis). Strain K13M18T formed creamy-pink colonies on a marine agar plate. Results of phylogenetic analysis based on the 16S rRNA gene sequence similarity indicated that strain K13M18T was most closely related to Tabrizicola sediminis DRYC-M-16T, sharing 97.62 % similarity with that strain. Strain K13M18T belonged to the genus Tabrizicola, which formed a cluster with Tabrizicola aquatica RCRI19T, Tabrizicola fusiformis SY72T, Tabrizicola sediminis DRYC-M-16T and Tabrizicola alkalilacus DJCT in a phylogenetic tree based on the 16S rRNA gene sequences. Strain K13M18T grown optimally in 0 % (w/v) NaCl, at pH 7 and 30 °C, in a marine broth medium. The predominant cellular fatty acids were C18 1 ω7c and C18 1 ω6c. The major respiratory isoprenoid quinone was ubiquinone Q-10. Polar lipids of strain K13M18T contained phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, diphosphatidylglycerol, six unidentified aminophospholipids, one unidentified aminolipid and an unidentified lipid.
    With the age the risks of comorbidities increases multidisease syndrome. Elderly patients suffer from frailty syndrome. All these factors make the elderly patient a major challenge for a laparoscopy treatment. CONCLUSION The laparoscopic approach is an effective method for treatment of perforated peptic ulcer in the elderly with a great diagnostic and therapeutic role. Nowadays more prospective randomized studies are needed to evaluate the effectiveness of laparoscopic versus open repair.INTRODUCTION Red cell distribution width (RDW) is a parameter that reflects the heterogeneity in the size of the circulating erythrocytes. Elevated levels of RDW have been found related to various pathologic conditions including cancers. We hypothesized that elevated RDW levels might correspond to advanced stages of pancreatic cancer. METHODS The medical files and pathology reports of patients who underwent Whipple procedure were evaluated in a retrospective casecontrol study. The relationship of RDW to age, gender, cancer antigen 19-9 (CA 19-9), blood hemoglobin levels, stage of the tumor, tumor size, tumor grade, number of lymph nodes with metastasis, the status of lymphovascular and perineural invasion were investigated. A oneto-two, age- and- gender matched group of seemingly healthy patients was used to compare the levels of RDW between the patients of pancreatic head malignancy and healthy people. ROC (receiver operating characteristics) curves analysis was conducted to define a threshold to discriminate malignant pancreatic head tumors from healthy control subjects. Then, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. RESULTS The median age was 61 years (IRQ 54.75-69). The median RDWs were 15.20% (IQR 13.20-19.50) vs 13.00 (IQR 12.60-13.48) in the pancreas adenocancer and the control group, respectively, p=0.000). There was significant relationship between RDW and the grade of the tumor, p=0.026. An RDW level of 14% was obtained as a result of the ROC curves analysis and the positive predictivity about malignancy was 70.73% with a negative predictive rate of 89.95% compared with the healthy group of patients. CONCLUSION The elevated levels of RDW in patients with a pancreatic mass may point to a possible malignancy; however, an elevated RDW in a patient with a malignant pancreatic head mass is related to the grade of the disease, not the stage.BACKGROUND Retroperitoneal sarcoma is a rare malignancy arising from mesenchymal cells, most commonly presented as an abdominal mass and is associated with poor prognosis. The most effective treatment modality for retroperitoneal sarcomas is complete surgical resection, including sometimes adjacent organs infiltrated by the tumor. Radiotherapy is frequently applied and has shown some benefit, while the role of chemotherapy and molecular-targeted agents is still not clear. Local recurrence is common for retroperitoneal sarcomas and still remains the main cause of death. The major factors associated with the overall survival are tumor grade, histological subtype, complete macroscopic excision and multifocality. AIM To report our experience via the presentation of patients with retroperitoneal sarcomas managed in our department during the period 2014-18; and to review the current literature. PATIENTS AND METHODS Eight patients appeared with chronic non-specific complaints including abdominal distension and changllance for early detection of recurrence or metastases.Bariatric surgery was introduced in 1953, but during the last 20 years its popularity has increased after the development of significant Romaevidenced based breakthroughs in the field. Currently, approximately 150 long-term randomized clinical trials and 40 meta-analyses support and give credibility to the surgical approaches for the treatment of obesity and its related metabolic disturbances. https://www.selleckchem.com/products/pf-9366.html Bariatric surgery has demonstrated improved outcomes compared to medical treatment, conduct therapy, and endoscopic procedures. Roux-en-Y gastrojejunostomy (RYGB) and Sleeve gastrectomy (SG) are the surgical procedures most frequently performed, due to their satisfactory results and security profile. There is sufficient evidence in medical literature to perform these procedures when indicated; however, there are still several controversies regarding technical aspects that need to be further explored.The present study aimed to examine the taxonomic relationship between two species, Paracoccus bengalensis Ghosh et al. 2006 and Paracoccus versutus (Harrison 1983) Katayama et al. 1996. Comparison of 16S rRNA gene sequences revealed that P. bengalensis JJJT was highly similar (99.9 %) to P. versutus A2T. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the two strains formed a tight cluster within the genus Paracoccus. Whole genomic comparison between the two strains showed a digital DNA-DNA hybridization estimate of 82. 0 % and an average nucleotide identity value of 98.2 %, clearly indicating that the two strains were members of the same species. Moreover, the type strains of both species shared similar physiological and biochemical properties and fatty acids profiles. Based on genotypic and phenotypic evidence, we conclude that Paracoccus bengalensis Ghosh et al. 2006 is a later heterotypic synonym of Paracoccus versutus (Harrison 1983) Katayama et al. 1996 according to the priority of publication and validation of the name.A novel Gram-negative, obligately aerobic, rod-shaped and non-motile bacterium, designated strain K13M18T, was isolated from the intestinal tract of a Korean indigenous fish, oily bitterling (Acheilognathus koreensis). Strain K13M18T formed creamy-pink colonies on a marine agar plate. Results of phylogenetic analysis based on the 16S rRNA gene sequence similarity indicated that strain K13M18T was most closely related to Tabrizicola sediminis DRYC-M-16T, sharing 97.62 % similarity with that strain. Strain K13M18T belonged to the genus Tabrizicola, which formed a cluster with Tabrizicola aquatica RCRI19T, Tabrizicola fusiformis SY72T, Tabrizicola sediminis DRYC-M-16T and Tabrizicola alkalilacus DJCT in a phylogenetic tree based on the 16S rRNA gene sequences. Strain K13M18T grown optimally in 0 % (w/v) NaCl, at pH 7 and 30 °C, in a marine broth medium. The predominant cellular fatty acids were C18 1 ω7c and C18 1 ω6c. The major respiratory isoprenoid quinone was ubiquinone Q-10. Polar lipids of strain K13M18T contained phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, diphosphatidylglycerol, six unidentified aminophospholipids, one unidentified aminolipid and an unidentified lipid.
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  • Natural protection offered to living beings is the result of millions of years of biological revolution. The protections provided in fishes, armadillos, and turtles by unique hierarchal designs help them to survive in surrounding environments. Natural armors offer protections with outstanding mechanical properties, such as high penetration resistance and toughness to weight ratio. The mechanical properties are not the only key features that make scales unique; they are also highly flexible and breathable. In this study, we aim to review the structural and mechanical characteristics of the scales from ray-finned or teleost fishes, which can be used for new bio-inspired armor designs. It is also essential to consider the hierarchical structure of extinct and existing natural armors. The basic characteristics, as mentioned above, are the foundation for developing high-performance, well-structured flexible natural armors. Furthermore, the present review justifies the importance of interaction between toughness, hardness, and deformability in well-engineered bio-inspired body armor. At last, some suggestions are proposed for the design and fabrication of new bio-inspired flexible body armors.In efforts to achieve minimal systemic toxicity and high tumor delivery efficiencies in cancer therapy, various nanomedicine formulations having stealth polymer coatings have been developed for minimizing immune cell uptake and off-target macrophage phagocyte system (MPS) organ accumulation. Despite an initial reduction in immune cell uptake, stealth nanoparticles still initiate an antibody immune response. This response acts on subsequent administrations in treatment regimens resulting in accelerated blood clearance of particles into MPS organs, particularly the liver, where they are retained for prolonged periods. Consequently, doses after the first administration in treatment regimens have diminished tumor accumulation and increased MPS toxicity. Here, we present a strategy reducing antibody responses to each dose in a treatment regimen by alternating between polyethylene-glycol and polymethyloxazoline polymers as the nanoparticle coating between administrations. In a weekly dosing regimen, we find that the first dose of particles having either coating display similar favorable pharmacokinetics and biodistributions, thus allowing the polymers to be used interchangeably. However, when maintaining the same coating in subsequent administrations, we find that particles are in circulation at the height of the antibody immune response resulting in 50-60% decreases of circulation half-lives and tumor accumulation along with 50% increases in liver accumulation. By alternating the polymers used in the nanoparticle coating between administrations, we find each dose maintains favorable in vivo behaviors at the height of the antibody immune response to the previous administration. Furthermore, our strategy increases the clearance of particles uptaken by macrophages and hepatocytes, resulting in marked decreases in hepatotoxicity.Nanoparticles with longer blood circulation, high loading capacity, controlled release at the targeted site, and preservation of camptothecin (CPT) in its lactone form are the key characteristics for the effective delivery of CPT. In this regard, natural membrane-derived nanovesicles, particularly those derived from RBC membrane, are important. RBC membrane can be engineered to form vesicles or can be coated over synthetic nanoparticles, without losing their basic structural features and can have prolonged circulation time. Here, we developed a hybrid system to encapsulate CPT inside the amphiphilic micelle and coat it with RBC membrane. Thus, it uses the dual ability of polymeric micelles to preserve CPT in its active form, while maintaining its "stealth" effect due to conserved RBC membrane coating. The hybrid system stabilized 60% of the drug in its active form even after 30 h of incubation in serum, in contrast to 15% active form present in free drug formulation after 1 h of incubation. It showed strong retention inside the Ehrlich Ascites Carcinoma (EAC) **** models for at least 72 h, suggesting camouflaging ability conferred by RBC membrane. Additionally, the nano formulation retarded the tumor growth rate more efficiently than free drug, with no evident signs of necrotic skin lesions. Histopathological analysis showed a significant reduction in cardiac atrophy, hepato-renal degeneration, and lung metastasis, which resulted in the increased overall survival of **** treated with the nano formulation. Hence, CPT-loaded polymeric micelles when coated with RBC membrane can prove to be a better system for the delivery of poorly soluble drug camptothecin.Living cells are highly scalable biological actuators found in nature, and they are efficient technological solutions to actuate robotic systems. Recent advancements in biofabrication and tissue engineering have bridged the gap to interface muscle cells with artificial technology. https://www.selleckchem.com/products/super-tdu.html In this review, we summarize the recent progress in engineering the attributes of individual components for the development of fully functional biohybrid robots. First, we address the fabrication of biological actuators for biohybrid robots with muscle cells and tissues, including cardiomyocytes, skeletal muscles, insect tissues, and neuromuscular tissues, in well-organized pattern of 2D sheets and 3D constructs. Next, we discuss the performance of biohybrid robots for various biomimetic tasks such as swimming, walking, gripping, and pumping. Finally, the challenges and future directions in the development of biohybrid robots are described from different viewpoints of living material engineering, multiscale modeling, 3D printing for manufacturing, and multifunctional robotic system development.Transdermal drug delivery is an attractive route for dermatological disease therapy because it can directly target the lesion site on the skin, reduce adverse reactions associated with systemic administration, and improve patient compliance. However, the stratum corneum, as the main skin barrier, severely limits transdermal drug penetration, with compromised bioavailability. Microneedles (MNs), which are leveraged to markedly improve the penetration of therapeutic agents by piercing the stratum corneum and creating hundreds of reversible microchannels in a minimally invasive manner, have been envisioned as a milestone for effective transdermal drug delivery, especially for superficial disease therapy. Here, the emergence of versatile MNs for the transdermal delivery of various drugs is reviewed, particularly focusing on the application of MNs for the treatment of diverse skin diseases, including superficial tumors, scars, psoriasis, herpes, acne, and alopecia. Additionally, the promises and challenges of the widespread translation of MN-mediated transdermal drug delivery in the dermatology field are summarized.
    Natural protection offered to living beings is the result of millions of years of biological revolution. The protections provided in fishes, armadillos, and turtles by unique hierarchal designs help them to survive in surrounding environments. Natural armors offer protections with outstanding mechanical properties, such as high penetration resistance and toughness to weight ratio. The mechanical properties are not the only key features that make scales unique; they are also highly flexible and breathable. In this study, we aim to review the structural and mechanical characteristics of the scales from ray-finned or teleost fishes, which can be used for new bio-inspired armor designs. It is also essential to consider the hierarchical structure of extinct and existing natural armors. The basic characteristics, as mentioned above, are the foundation for developing high-performance, well-structured flexible natural armors. Furthermore, the present review justifies the importance of interaction between toughness, hardness, and deformability in well-engineered bio-inspired body armor. At last, some suggestions are proposed for the design and fabrication of new bio-inspired flexible body armors.In efforts to achieve minimal systemic toxicity and high tumor delivery efficiencies in cancer therapy, various nanomedicine formulations having stealth polymer coatings have been developed for minimizing immune cell uptake and off-target macrophage phagocyte system (MPS) organ accumulation. Despite an initial reduction in immune cell uptake, stealth nanoparticles still initiate an antibody immune response. This response acts on subsequent administrations in treatment regimens resulting in accelerated blood clearance of particles into MPS organs, particularly the liver, where they are retained for prolonged periods. Consequently, doses after the first administration in treatment regimens have diminished tumor accumulation and increased MPS toxicity. Here, we present a strategy reducing antibody responses to each dose in a treatment regimen by alternating between polyethylene-glycol and polymethyloxazoline polymers as the nanoparticle coating between administrations. In a weekly dosing regimen, we find that the first dose of particles having either coating display similar favorable pharmacokinetics and biodistributions, thus allowing the polymers to be used interchangeably. However, when maintaining the same coating in subsequent administrations, we find that particles are in circulation at the height of the antibody immune response resulting in 50-60% decreases of circulation half-lives and tumor accumulation along with 50% increases in liver accumulation. By alternating the polymers used in the nanoparticle coating between administrations, we find each dose maintains favorable in vivo behaviors at the height of the antibody immune response to the previous administration. Furthermore, our strategy increases the clearance of particles uptaken by macrophages and hepatocytes, resulting in marked decreases in hepatotoxicity.Nanoparticles with longer blood circulation, high loading capacity, controlled release at the targeted site, and preservation of camptothecin (CPT) in its lactone form are the key characteristics for the effective delivery of CPT. In this regard, natural membrane-derived nanovesicles, particularly those derived from RBC membrane, are important. RBC membrane can be engineered to form vesicles or can be coated over synthetic nanoparticles, without losing their basic structural features and can have prolonged circulation time. Here, we developed a hybrid system to encapsulate CPT inside the amphiphilic micelle and coat it with RBC membrane. Thus, it uses the dual ability of polymeric micelles to preserve CPT in its active form, while maintaining its "stealth" effect due to conserved RBC membrane coating. The hybrid system stabilized 60% of the drug in its active form even after 30 h of incubation in serum, in contrast to 15% active form present in free drug formulation after 1 h of incubation. It showed strong retention inside the Ehrlich Ascites Carcinoma (EAC) mice models for at least 72 h, suggesting camouflaging ability conferred by RBC membrane. Additionally, the nano formulation retarded the tumor growth rate more efficiently than free drug, with no evident signs of necrotic skin lesions. Histopathological analysis showed a significant reduction in cardiac atrophy, hepato-renal degeneration, and lung metastasis, which resulted in the increased overall survival of mice treated with the nano formulation. Hence, CPT-loaded polymeric micelles when coated with RBC membrane can prove to be a better system for the delivery of poorly soluble drug camptothecin.Living cells are highly scalable biological actuators found in nature, and they are efficient technological solutions to actuate robotic systems. Recent advancements in biofabrication and tissue engineering have bridged the gap to interface muscle cells with artificial technology. https://www.selleckchem.com/products/super-tdu.html In this review, we summarize the recent progress in engineering the attributes of individual components for the development of fully functional biohybrid robots. First, we address the fabrication of biological actuators for biohybrid robots with muscle cells and tissues, including cardiomyocytes, skeletal muscles, insect tissues, and neuromuscular tissues, in well-organized pattern of 2D sheets and 3D constructs. Next, we discuss the performance of biohybrid robots for various biomimetic tasks such as swimming, walking, gripping, and pumping. Finally, the challenges and future directions in the development of biohybrid robots are described from different viewpoints of living material engineering, multiscale modeling, 3D printing for manufacturing, and multifunctional robotic system development.Transdermal drug delivery is an attractive route for dermatological disease therapy because it can directly target the lesion site on the skin, reduce adverse reactions associated with systemic administration, and improve patient compliance. However, the stratum corneum, as the main skin barrier, severely limits transdermal drug penetration, with compromised bioavailability. Microneedles (MNs), which are leveraged to markedly improve the penetration of therapeutic agents by piercing the stratum corneum and creating hundreds of reversible microchannels in a minimally invasive manner, have been envisioned as a milestone for effective transdermal drug delivery, especially for superficial disease therapy. Here, the emergence of versatile MNs for the transdermal delivery of various drugs is reviewed, particularly focusing on the application of MNs for the treatment of diverse skin diseases, including superficial tumors, scars, psoriasis, herpes, acne, and alopecia. Additionally, the promises and challenges of the widespread translation of MN-mediated transdermal drug delivery in the dermatology field are summarized.
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  • The article will end by proposing some methodologies to facilitate patient-developed concepts of empowerment.Advances in genetic diagnostics lead to more patients being diagnosed with hereditary conditions. These findings are often relevant to patients' relatives. For example, the success of targeted cancer prevention is dependent on effective disclosure to relatives at risk. Without clear information, individuals cannot take advantage of predictive testing and preventive measures. Against this background, we argue that healthcare professionals have a duty to make actionable genetic information available to their patients' at-risk relatives. We do not try to settle the difficult question of how this duty should be balanced against other duties, such as the duty of confidentiality and a possible duty not to know one's genetic predisposition. Instead, we argue for the importance of recognising a general responsibility towards at-risk relatives, to be discharged as well as possible within the limits set by conflicting duties and practical considerations. According to a traditional and still dominant perspective, it is the patient's duty to inform his or her relatives, while healthcare professionals are only obliged to support their patients in discharging this duty. We argue that this perspective is a mistake and an anomaly. Healthcare professionals do not have a duty to ensure that their patients promote the health of third parties. It is often effective and desirable to engage patients in disseminating information to their relatives. However, healthcare professionals should not thereby deflect their own moral responsibility.Ethical discussions about medical treatment for seriously ill babies or children often focus on the 'value of life' or on 'quality of life' and what that might mean. In this paper, I look at the other side of the coin-on the value of death, and on the quality of dying. In particular, I examine whether there is such a thing as a good way to die, for an infant or an adult, and what that means for medical care. https://www.selleckchem.com/products/fluzoparib.html To do that, I call on philosophy and on personal experience. However, I will also make reference to art, poetry and music. That is partly because the topic of mortality has long been reflected on by artists as well as philosophers and ethicists. It is also because, as we will see, there may be some useful parallels to draw.Hospital systems commonly face the challenge of determining just ways to allocate scarce drugs during national shortages. There is no standardised approach of how this should be instituted, but principles of distributive justice are commonly used so that patients who are most likely to benefit from the drug receive it. As a result, clinical indications, in which the evidence for the drug is assumed to be established, are often prioritised over research use. In this manuscript, we present a case of a phase II investigational trial of intravenous thiamine for delirium prevention in patients undergoing haematopoietic stem cell transplantation to emphasise several shortcomings in the overarching prioritisation of clinical over research uses of scarce drugs. Specifically, we present the following considerations (1) clinical use may not have stronger evidence than research use; (2) a strong scientific rationale for research use may outweigh the claim for clinical indications in which there is weak evidence; (3) treatment within the context of a clinical trial may be the standard of care; and (4) research use may not only benefit patients receiving the treatment but also offers the prospect of improving future clinical care. In summary, we argue against allocation schemes that prohibit all research uses of scarce drugs and instead recommend that allocation schemes include a balanced approach that weighs risks and benefits of access to scarce drugs irrespective of the research versus clinical use designation.Where a person is unable to make medical decisions for themselves, law and practice allows others to make decisions on their behalf. This is common at the end of a person's life where decision-making capacity is often lost. A further, and separate, decision that is often considered at the time of death (and often preceding death) is whether the person wanted to act as an organ or tissue donor. However, in some jurisdictions, the lawful decision-maker for the donation decision (the 'donation decision-maker') is different from the person who was granted decision-making authority for medical decisions during the person's life. To date, little attention has been given in the literature to the ethical concerns and practical problems that arise where this shift in legal authority occurs. Such a change in decision-making authority is particularly problematic where premortem measures are suggested to maximise the chances of a successful organ donation. This paper examines this shift in decision-making authority and discusses the legal, ethical and practical implications of such frameworks.Pulmonary alveolar microlithiasis (PAM) is a fascinating rare lung disease that is associated with the accumulation of hydroxyapatite microliths within the lumen of the alveolar spaces. In most patients, PAM is discovered incidentally on radiographs performed for other purposes, and the typical disease course is characterised by slowly progressive respiratory insufficiency over decades. Recent genetic analyses that have revealed that the deficiency of the sodium-phosphate cotransporter NPT2B is the cause of PAM have enabled the development of powerful animal models that inform our approach to disease management and treatment. Here we review the epidemiology and molecular pathophysiology of PAM, as well as the diagnostic approach, clinical manifestations, radiographic and pathologic features, and clinical management of the disease. Although there are no proven treatments for PAM, progress in our understanding of disease pathogenesis is providing insights that suggest strategies for trials.Wheezing and asthma are a growing cause of morbidity in children and adults. Treatment is aimed at prevention of disease exacerbations and preservation of lung function. Respiratory viruses are involved in ∼40-60% of exacerbations. Bacterial lysates prevent recurrent respiratory tract infections and might reduce exacerbations. Moreover, immunomodulatory effects have been observed in human and animal studies. Here we aimed to assess the effects of bacterial lysate therapy on preschool wheezing episodes and asthma exacerbation frequency. We performed a systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and a meta-analysis using Cochrane Review Manager. Out of 2016 retrieved articles, 22 studies were included, of which five provided sufficient data for a meta-analysis.The use of bacterial lysates showed a decrease of both wheezing episodes (mean difference -2.35 (-3.03- -1.67), p less then 0.001) and asthma exacerbations in children (mean difference -0.
    The article will end by proposing some methodologies to facilitate patient-developed concepts of empowerment.Advances in genetic diagnostics lead to more patients being diagnosed with hereditary conditions. These findings are often relevant to patients' relatives. For example, the success of targeted cancer prevention is dependent on effective disclosure to relatives at risk. Without clear information, individuals cannot take advantage of predictive testing and preventive measures. Against this background, we argue that healthcare professionals have a duty to make actionable genetic information available to their patients' at-risk relatives. We do not try to settle the difficult question of how this duty should be balanced against other duties, such as the duty of confidentiality and a possible duty not to know one's genetic predisposition. Instead, we argue for the importance of recognising a general responsibility towards at-risk relatives, to be discharged as well as possible within the limits set by conflicting duties and practical considerations. According to a traditional and still dominant perspective, it is the patient's duty to inform his or her relatives, while healthcare professionals are only obliged to support their patients in discharging this duty. We argue that this perspective is a mistake and an anomaly. Healthcare professionals do not have a duty to ensure that their patients promote the health of third parties. It is often effective and desirable to engage patients in disseminating information to their relatives. However, healthcare professionals should not thereby deflect their own moral responsibility.Ethical discussions about medical treatment for seriously ill babies or children often focus on the 'value of life' or on 'quality of life' and what that might mean. In this paper, I look at the other side of the coin-on the value of death, and on the quality of dying. In particular, I examine whether there is such a thing as a good way to die, for an infant or an adult, and what that means for medical care. https://www.selleckchem.com/products/fluzoparib.html To do that, I call on philosophy and on personal experience. However, I will also make reference to art, poetry and music. That is partly because the topic of mortality has long been reflected on by artists as well as philosophers and ethicists. It is also because, as we will see, there may be some useful parallels to draw.Hospital systems commonly face the challenge of determining just ways to allocate scarce drugs during national shortages. There is no standardised approach of how this should be instituted, but principles of distributive justice are commonly used so that patients who are most likely to benefit from the drug receive it. As a result, clinical indications, in which the evidence for the drug is assumed to be established, are often prioritised over research use. In this manuscript, we present a case of a phase II investigational trial of intravenous thiamine for delirium prevention in patients undergoing haematopoietic stem cell transplantation to emphasise several shortcomings in the overarching prioritisation of clinical over research uses of scarce drugs. Specifically, we present the following considerations (1) clinical use may not have stronger evidence than research use; (2) a strong scientific rationale for research use may outweigh the claim for clinical indications in which there is weak evidence; (3) treatment within the context of a clinical trial may be the standard of care; and (4) research use may not only benefit patients receiving the treatment but also offers the prospect of improving future clinical care. In summary, we argue against allocation schemes that prohibit all research uses of scarce drugs and instead recommend that allocation schemes include a balanced approach that weighs risks and benefits of access to scarce drugs irrespective of the research versus clinical use designation.Where a person is unable to make medical decisions for themselves, law and practice allows others to make decisions on their behalf. This is common at the end of a person's life where decision-making capacity is often lost. A further, and separate, decision that is often considered at the time of death (and often preceding death) is whether the person wanted to act as an organ or tissue donor. However, in some jurisdictions, the lawful decision-maker for the donation decision (the 'donation decision-maker') is different from the person who was granted decision-making authority for medical decisions during the person's life. To date, little attention has been given in the literature to the ethical concerns and practical problems that arise where this shift in legal authority occurs. Such a change in decision-making authority is particularly problematic where premortem measures are suggested to maximise the chances of a successful organ donation. This paper examines this shift in decision-making authority and discusses the legal, ethical and practical implications of such frameworks.Pulmonary alveolar microlithiasis (PAM) is a fascinating rare lung disease that is associated with the accumulation of hydroxyapatite microliths within the lumen of the alveolar spaces. In most patients, PAM is discovered incidentally on radiographs performed for other purposes, and the typical disease course is characterised by slowly progressive respiratory insufficiency over decades. Recent genetic analyses that have revealed that the deficiency of the sodium-phosphate cotransporter NPT2B is the cause of PAM have enabled the development of powerful animal models that inform our approach to disease management and treatment. Here we review the epidemiology and molecular pathophysiology of PAM, as well as the diagnostic approach, clinical manifestations, radiographic and pathologic features, and clinical management of the disease. Although there are no proven treatments for PAM, progress in our understanding of disease pathogenesis is providing insights that suggest strategies for trials.Wheezing and asthma are a growing cause of morbidity in children and adults. Treatment is aimed at prevention of disease exacerbations and preservation of lung function. Respiratory viruses are involved in ∼40-60% of exacerbations. Bacterial lysates prevent recurrent respiratory tract infections and might reduce exacerbations. Moreover, immunomodulatory effects have been observed in human and animal studies. Here we aimed to assess the effects of bacterial lysate therapy on preschool wheezing episodes and asthma exacerbation frequency. We performed a systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and a meta-analysis using Cochrane Review Manager. Out of 2016 retrieved articles, 22 studies were included, of which five provided sufficient data for a meta-analysis.The use of bacterial lysates showed a decrease of both wheezing episodes (mean difference -2.35 (-3.03- -1.67), p less then 0.001) and asthma exacerbations in children (mean difference -0.
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  • 4%) or class C4 (35.6%) CVD. Sulodexide was associated with decreased symptom severity in 56.4% of patients and a decreased number of symptoms in 42.8%. Thus, improvements were observed in 99.2% overall, with the drug effects being apparent as early as 15-20 days after starting treatment. The highest rate of CVD symptom regression was observed in patients aged 30-40 years. There was a significant positive correlation between sulodexide efficacy and treatment duration and the use of capsules during follow-up. A negative correlation was found between treatment efficacy and patient age at diagnosis, CEAP class, the total number of symptoms, and a combination of risk factors. CONCLUSIONS Sulodexide was an effective, safe, well-tolerated, and pathogenetically substantiated pharmacologic agent for the treatment of patients with lower limb CVD, and therefore should be recommended in patients with early-stage CVD. https://www.selleckchem.com/products/4-hydroxynonenal.html Patients with venous trophic ulcers require higher doses and prolonged administration of the drug.BACKGROUND Patients with fibromyalgia syndrome (FMS) usually display a decrease in health-related quality of life (HRQoL). This decrease in HRQoL is related to clinical pain, anxiety, and depression. This cross-sectional study analyzes the mediating role of pain-coping strategies (especially catastrophizing) in the negative relationships of pain, anxiety, depression, and HRQoL in FMS. METHODS One hundred and thirteen women with FMS and 63 healthy women were assessed using the Short-Form Health Survey (SF-36). Participants completed self-report questionnaires to evaluate clinical pain, anxiety, depression, and pain-coping strategies. RESULTS Pain catastrophizing was inversely associated with the physical function, general health perception, vitality, emotional role, mental health, the physical and mental general components, and the global index of HRQoL, with percentages of variance explained ranging between 9 and 18%. Cognitive distraction showed a positive association with the physical function, general health perception, vitality, emotional role, mental health, physical component, and global index of HRQoL, with percentages of variance explained ranging between 4 and 7%. Mediation analysis showed that catastrophizing mediates the negative influence of clinical pain and trait-anxiety on the physical function, general health perception, vitality, mental health, and global index of HRQoL. No mediating effect of pain catastrophizing on the relation between depression and HRQoL was observed. CONCLUSIONS Patients with FMS exhibited markedly lower HRQoL than healthy individuals. While pain catastrophizing was inversely related to several domains of HRQL, associations were positive for cognitive distraction. Catastrophizing mediates the negative influence of clinical pain and trait-anxiety on HRQoL. Therefore, cognitive behavioral treatments focused on adaptive management and control of catastrophizing and negative emotional states may be helpful.PURPOSE This study aimed to investigate the level of fertility related quality of life (FertiQoL) in women with recurrent pregnancy loss (RPL), and to further examine moderated mediation effects of dispositional mindfulness and negative emotions on the relationship between perceived stress and FertiQoL. METHODS A cross-sectional study was conducted with 262 participants recruited from the infertility outpatient clinics. A self-administered, structured questionnaire including the Simplified Chinese version of FertiQoL tool, the Perceived Stress Scale-10 (PSS-10), the Chinese Version of the Hospital Anxiety and Depression Scale (HADS), and the Mindfulness Attention Awareness Scale (MAAS) was used to collect information in this research. The mediation model and moderated mediation model were conducted using the PROCESS macro for SPSS. RESULTS The mean score of Core FertiQoL was 64.59 (SD = 14.76) among women with RPL. Mediation analysis revealed that the association between perceived stress and FertiQoL was partially mediated by negative emotions (indirect effect = - 0.194 for anxiety, and - 0.151 for depression, all P  less then  0.001). Moderated mediation analysis indicated that the indirect effects of perceived stress on FertiQoL through negative emotions were significantly moderated by dispositional mindfulness. Specifically, the indirect effects of perceived stress on FertiQoL through negative emotions decreased were significant as dispositional mindfulness levels increased. CONCLUSION Overall, women with RPL experienced poor FertiQoL. The Moderated mediation model provides a better understanding of how perceived stress, negative emotions and dispositional mindfulness work together to affect FertiQoL. Interventions aiming to improve FertiQoL in women with RPL should consider targeting these aspects.PURPOSE Electronic patient-reported outcomes (ePROs) are increasingly being used for symptom monitoring during routine cancer care, but have rarely been evaluated in diverse patient populations. We assessed ePRO user experiences and perceived value among Black and White cancer patients. METHODS We recruited 30 Black and 49 White bladder and prostate cancer patients from a single institution. Participants reported symptoms using either a web-based or automated telephone interface over 3 months and completed satisfaction surveys and qualitative interviews focused on user experiences and value. Using a narrative mixed methods approach, we evaluated overall and race-specific differences in ePRO user experiences and perceived value. RESULTS Most participants selected the web-based system, but Blacks were more likely to use the automated telephone-based system than Whites. In satisfaction surveys, Whites more commonly reported ease in understanding and reporting symptoms compared with Blacks. Blacks more often reported that the ePRO system was helpful in facilitating symptom-related discussions with clinicians. During interviews, Blacks described how the ePRO helped them recognize symptoms, while Whites found value in better understanding and tracking symptoms longitudinally. Blacks also expressed preferences for paper-based ePRO options due to perceived ease in better understanding of symptom items. CONCLUSION Electronic patient-reported outcomes are perceived as valuable for variable reasons by Black and White cancer populations, with greater perceived value for communicating with clinicians reported among Blacks. To optimize equitable uptake of ePROs, oncology practices should offer several ePRO options (e.g., web-based, phone-based), as well as paper-based options, and consider the e-health literacy needs of patients during implementation.
    4%) or class C4 (35.6%) CVD. Sulodexide was associated with decreased symptom severity in 56.4% of patients and a decreased number of symptoms in 42.8%. Thus, improvements were observed in 99.2% overall, with the drug effects being apparent as early as 15-20 days after starting treatment. The highest rate of CVD symptom regression was observed in patients aged 30-40 years. There was a significant positive correlation between sulodexide efficacy and treatment duration and the use of capsules during follow-up. A negative correlation was found between treatment efficacy and patient age at diagnosis, CEAP class, the total number of symptoms, and a combination of risk factors. CONCLUSIONS Sulodexide was an effective, safe, well-tolerated, and pathogenetically substantiated pharmacologic agent for the treatment of patients with lower limb CVD, and therefore should be recommended in patients with early-stage CVD. https://www.selleckchem.com/products/4-hydroxynonenal.html Patients with venous trophic ulcers require higher doses and prolonged administration of the drug.BACKGROUND Patients with fibromyalgia syndrome (FMS) usually display a decrease in health-related quality of life (HRQoL). This decrease in HRQoL is related to clinical pain, anxiety, and depression. This cross-sectional study analyzes the mediating role of pain-coping strategies (especially catastrophizing) in the negative relationships of pain, anxiety, depression, and HRQoL in FMS. METHODS One hundred and thirteen women with FMS and 63 healthy women were assessed using the Short-Form Health Survey (SF-36). Participants completed self-report questionnaires to evaluate clinical pain, anxiety, depression, and pain-coping strategies. RESULTS Pain catastrophizing was inversely associated with the physical function, general health perception, vitality, emotional role, mental health, the physical and mental general components, and the global index of HRQoL, with percentages of variance explained ranging between 9 and 18%. Cognitive distraction showed a positive association with the physical function, general health perception, vitality, emotional role, mental health, physical component, and global index of HRQoL, with percentages of variance explained ranging between 4 and 7%. Mediation analysis showed that catastrophizing mediates the negative influence of clinical pain and trait-anxiety on the physical function, general health perception, vitality, mental health, and global index of HRQoL. No mediating effect of pain catastrophizing on the relation between depression and HRQoL was observed. CONCLUSIONS Patients with FMS exhibited markedly lower HRQoL than healthy individuals. While pain catastrophizing was inversely related to several domains of HRQL, associations were positive for cognitive distraction. Catastrophizing mediates the negative influence of clinical pain and trait-anxiety on HRQoL. Therefore, cognitive behavioral treatments focused on adaptive management and control of catastrophizing and negative emotional states may be helpful.PURPOSE This study aimed to investigate the level of fertility related quality of life (FertiQoL) in women with recurrent pregnancy loss (RPL), and to further examine moderated mediation effects of dispositional mindfulness and negative emotions on the relationship between perceived stress and FertiQoL. METHODS A cross-sectional study was conducted with 262 participants recruited from the infertility outpatient clinics. A self-administered, structured questionnaire including the Simplified Chinese version of FertiQoL tool, the Perceived Stress Scale-10 (PSS-10), the Chinese Version of the Hospital Anxiety and Depression Scale (HADS), and the Mindfulness Attention Awareness Scale (MAAS) was used to collect information in this research. The mediation model and moderated mediation model were conducted using the PROCESS macro for SPSS. RESULTS The mean score of Core FertiQoL was 64.59 (SD = 14.76) among women with RPL. Mediation analysis revealed that the association between perceived stress and FertiQoL was partially mediated by negative emotions (indirect effect = - 0.194 for anxiety, and - 0.151 for depression, all P  less then  0.001). Moderated mediation analysis indicated that the indirect effects of perceived stress on FertiQoL through negative emotions were significantly moderated by dispositional mindfulness. Specifically, the indirect effects of perceived stress on FertiQoL through negative emotions decreased were significant as dispositional mindfulness levels increased. CONCLUSION Overall, women with RPL experienced poor FertiQoL. The Moderated mediation model provides a better understanding of how perceived stress, negative emotions and dispositional mindfulness work together to affect FertiQoL. Interventions aiming to improve FertiQoL in women with RPL should consider targeting these aspects.PURPOSE Electronic patient-reported outcomes (ePROs) are increasingly being used for symptom monitoring during routine cancer care, but have rarely been evaluated in diverse patient populations. We assessed ePRO user experiences and perceived value among Black and White cancer patients. METHODS We recruited 30 Black and 49 White bladder and prostate cancer patients from a single institution. Participants reported symptoms using either a web-based or automated telephone interface over 3 months and completed satisfaction surveys and qualitative interviews focused on user experiences and value. Using a narrative mixed methods approach, we evaluated overall and race-specific differences in ePRO user experiences and perceived value. RESULTS Most participants selected the web-based system, but Blacks were more likely to use the automated telephone-based system than Whites. In satisfaction surveys, Whites more commonly reported ease in understanding and reporting symptoms compared with Blacks. Blacks more often reported that the ePRO system was helpful in facilitating symptom-related discussions with clinicians. During interviews, Blacks described how the ePRO helped them recognize symptoms, while Whites found value in better understanding and tracking symptoms longitudinally. Blacks also expressed preferences for paper-based ePRO options due to perceived ease in better understanding of symptom items. CONCLUSION Electronic patient-reported outcomes are perceived as valuable for variable reasons by Black and White cancer populations, with greater perceived value for communicating with clinicians reported among Blacks. To optimize equitable uptake of ePROs, oncology practices should offer several ePRO options (e.g., web-based, phone-based), as well as paper-based options, and consider the e-health literacy needs of patients during implementation.
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