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  • Antibiotic-loaded cement spacers are used in two- stage hip replacement. The aim of our study was to compare our results using a Spacer-G with previous results reported in the literature. From June 2002 to April 2010, all patients treated with a two-stage revision were retrospectively reviewed. On the basis of the results of the first-stage procedure, 52 patients underwent the second stage, six developed a dislocation, in eight the spacer was maintained, and five patients developed an acute infection of the spacer or the infection was not resolved. With regard to the second-stage procedure the revision was successful in 44 patients, a re-infection developed in four patients and the definitive prosthesis presented a mechanical complication in four more. The literature results reported that 97.5% of the spacers were reimplanted, although 12.09% of them developed a dislocation. Surgeons must assess several aspects so as to avoid mechanical complications like dislocation and re- infections during the two stages of the procedure.The aim of this study was to review the incidence, management and outcome of isolated iliac wing fractures and to compare them with other type A, B and C fractures. From 2004 to 2015, the data of 547 patient with a pelvic fracture regarding age, gender, RTS, ISS, treatment, complications and mortality were analyzed and a comparison was made between iliac wing fractures and the other pelvic fractures. We encountered 30 isolated iliac wing fractures. The ISS, shock class, transfusion rate, complications and mortality were comparable to those of patients with an unstable pelvic fracture. https://www.selleckchem.com/products/resigratinib.html Concomitant injuries were observed in 93% of the patients. None of the fractures were operatively stabilized. Isolated iliac wing fractures are rare, and operative stabilization of the fracture itself is often not necessary. However, these fractures are serious injuries with characteristics resembling those of patients with an unstable pelvic ring injury.We performed a prospective study on patients with acetabular fractures treated either with internal fixation either with arthroplasty comparing clinical outcomes, quality of life, economic resources and cost efficacy in the first five years after surgery. Demographic data, diagnosis, index treatment, costs and subsequent surgeries were recorded. Patients were requested to fulfill Merle d'Aubigné and EQ-5D-5L questionnaires. Clinical differences between treatments are significant only in discharge period. Comparing respectively group with fixation and arthroplasty, cost efficacy was 5483 and 10838 euros/quality-adjusted-life years, mean global costs 23965 and 16878 € and quality of life gained in five years 2.788 and 3.175. Group of arthroplasty showed better quality of life at discharge and at one year. If choice between fixation and arthroplasty should be based only on cost-efficacy, arthroplasty should be suggested but clinical outcomes suggest to consider fixation because results at five years are not different to arthroplasty.The aim of this study was to prospectively compare different delivery forms, doses and combined application forms of TXA for the reduction of blood loss and prevention of the allogeneic blood transfusion in patients with TKA and evaluate the results. The study included patients with knee joint osteoarthritis who were unresponsive to conservative management and 168 patients met the inclusion criteria. They were divided into 5 groups randomly as, Control (1), Local (2), Systemic+short infusion (3), Systemic+long infusion (4) and Systemic+oral TXA (5). When compared with the Control group, blood loss was significantly reduced in Groups 2, 3 and 4 (p=0.001, 0.001, 0.003) but not in Group 5. Twenty- four hour drainage output was lower in all treatment groups (p=0.001, 0.001, 0.001, 0.004). Although TXA groups had no difference in terms of blood loss, 24- hour drainage outputs of the local TXA group were less than Group 4 and 5 and it yielded similar amounts in comparison with group 3. It was determined that TXA use whether local or systemic gave rise to decreased blood loss and prevent allogeneic blood transfusion. But, regarding the results above, local TXA seemed to have favorable effects when compared with systemic+long infusion and systemic+oral TXA usage, whereas local use had similar results with systemic+short infusion. Additionally, there found no difference between systemic+short, systemic+long infusion and systemic+oral combined TXA usage with respect to blood loss, transfusion rates and drain follow-up. We recommend further prospective randomized controlled studies to make clear these differences. Systemic+oral combined TXA use have promising results when compared with other systemic multiple deliveries.The purpose of this study was to assess the factors associated with high fibular head in symptomatic discoid lateral meniscus (DLM). Eighty-seven patients with complete DLM (discoid group) and 80 normal subjects (control group) were included prospectively. Plain X-rays and MRI were analyzed for level and angle of the fibular head and thickness and type of Wrisberg ligament. Multivariate regression analysis was performed to find the factors associated with levels of the fibular head and DLM. The angle of the fibular head was the only factor associated with level of the fibula in the discoid group (odds ratio 3.0, p=0.007). The 13.6mm cut off value for fibular level had 70.5% sensitivity and 77.0% specificity for diagnosis of DLM. A high fibular head was associated with larger angle and type of fibular head. Level of evidence Level II.This study is aimed to compare the clinical and radiological differences between classic locked intra- medullary nailing (LIN) and blade expandable intra- medullary nailing (BEIN) at tibia shaft fractures. Operation time, exposing of radiation time and fracture healing times were recorded. Pain visual anolog scale (VAS), shortening of tibia and angulation of fracture line were compared. All patients healed. In LIN group operation time, exposing of radiation time was longer (statistically significant). Because of shorter operation time and lower radiation exposure we recommend the BEIN technique as a preferable technique in tibia intramedullary nailing.
    Antibiotic-loaded cement spacers are used in two- stage hip replacement. The aim of our study was to compare our results using a Spacer-G with previous results reported in the literature. From June 2002 to April 2010, all patients treated with a two-stage revision were retrospectively reviewed. On the basis of the results of the first-stage procedure, 52 patients underwent the second stage, six developed a dislocation, in eight the spacer was maintained, and five patients developed an acute infection of the spacer or the infection was not resolved. With regard to the second-stage procedure the revision was successful in 44 patients, a re-infection developed in four patients and the definitive prosthesis presented a mechanical complication in four more. The literature results reported that 97.5% of the spacers were reimplanted, although 12.09% of them developed a dislocation. Surgeons must assess several aspects so as to avoid mechanical complications like dislocation and re- infections during the two stages of the procedure.The aim of this study was to review the incidence, management and outcome of isolated iliac wing fractures and to compare them with other type A, B and C fractures. From 2004 to 2015, the data of 547 patient with a pelvic fracture regarding age, gender, RTS, ISS, treatment, complications and mortality were analyzed and a comparison was made between iliac wing fractures and the other pelvic fractures. We encountered 30 isolated iliac wing fractures. The ISS, shock class, transfusion rate, complications and mortality were comparable to those of patients with an unstable pelvic fracture. https://www.selleckchem.com/products/resigratinib.html Concomitant injuries were observed in 93% of the patients. None of the fractures were operatively stabilized. Isolated iliac wing fractures are rare, and operative stabilization of the fracture itself is often not necessary. However, these fractures are serious injuries with characteristics resembling those of patients with an unstable pelvic ring injury.We performed a prospective study on patients with acetabular fractures treated either with internal fixation either with arthroplasty comparing clinical outcomes, quality of life, economic resources and cost efficacy in the first five years after surgery. Demographic data, diagnosis, index treatment, costs and subsequent surgeries were recorded. Patients were requested to fulfill Merle d'Aubigné and EQ-5D-5L questionnaires. Clinical differences between treatments are significant only in discharge period. Comparing respectively group with fixation and arthroplasty, cost efficacy was 5483 and 10838 euros/quality-adjusted-life years, mean global costs 23965 and 16878 € and quality of life gained in five years 2.788 and 3.175. Group of arthroplasty showed better quality of life at discharge and at one year. If choice between fixation and arthroplasty should be based only on cost-efficacy, arthroplasty should be suggested but clinical outcomes suggest to consider fixation because results at five years are not different to arthroplasty.The aim of this study was to prospectively compare different delivery forms, doses and combined application forms of TXA for the reduction of blood loss and prevention of the allogeneic blood transfusion in patients with TKA and evaluate the results. The study included patients with knee joint osteoarthritis who were unresponsive to conservative management and 168 patients met the inclusion criteria. They were divided into 5 groups randomly as, Control (1), Local (2), Systemic+short infusion (3), Systemic+long infusion (4) and Systemic+oral TXA (5). When compared with the Control group, blood loss was significantly reduced in Groups 2, 3 and 4 (p=0.001, 0.001, 0.003) but not in Group 5. Twenty- four hour drainage output was lower in all treatment groups (p=0.001, 0.001, 0.001, 0.004). Although TXA groups had no difference in terms of blood loss, 24- hour drainage outputs of the local TXA group were less than Group 4 and 5 and it yielded similar amounts in comparison with group 3. It was determined that TXA use whether local or systemic gave rise to decreased blood loss and prevent allogeneic blood transfusion. But, regarding the results above, local TXA seemed to have favorable effects when compared with systemic+long infusion and systemic+oral TXA usage, whereas local use had similar results with systemic+short infusion. Additionally, there found no difference between systemic+short, systemic+long infusion and systemic+oral combined TXA usage with respect to blood loss, transfusion rates and drain follow-up. We recommend further prospective randomized controlled studies to make clear these differences. Systemic+oral combined TXA use have promising results when compared with other systemic multiple deliveries.The purpose of this study was to assess the factors associated with high fibular head in symptomatic discoid lateral meniscus (DLM). Eighty-seven patients with complete DLM (discoid group) and 80 normal subjects (control group) were included prospectively. Plain X-rays and MRI were analyzed for level and angle of the fibular head and thickness and type of Wrisberg ligament. Multivariate regression analysis was performed to find the factors associated with levels of the fibular head and DLM. The angle of the fibular head was the only factor associated with level of the fibula in the discoid group (odds ratio 3.0, p=0.007). The 13.6mm cut off value for fibular level had 70.5% sensitivity and 77.0% specificity for diagnosis of DLM. A high fibular head was associated with larger angle and type of fibular head. Level of evidence Level II.This study is aimed to compare the clinical and radiological differences between classic locked intra- medullary nailing (LIN) and blade expandable intra- medullary nailing (BEIN) at tibia shaft fractures. Operation time, exposing of radiation time and fracture healing times were recorded. Pain visual anolog scale (VAS), shortening of tibia and angulation of fracture line were compared. All patients healed. In LIN group operation time, exposing of radiation time was longer (statistically significant). Because of shorter operation time and lower radiation exposure we recommend the BEIN technique as a preferable technique in tibia intramedullary nailing.
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  • Lymphomatoid granulomatosis (LYG) is a rare, extranodal B-cell lymphoproliferative disorder. The disease commonly presents with nonspecific symptoms and imaging features, making the diagnosis and therapeutic response assessment difficult. While histopathology is the mainstay of diagnosis, different imaging modalities such as computed tomography (CT), magnetic resonance imaging, or F18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) can help in identifying the different organs involved. We present a case of LYG, post chemotherapy in remission for the past 5 years, presenting with symptoms of disease recurrence. Copyright © 2020 Indian Journal of Nuclear Medicine.We present fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) findings in an extremely rare case of penile metastasis from renal cell carcinoma. A 66-year-old male, a known case of renal cell carcinoma, underwent FDG PET-CT. The scan showed metabolically active cervical lymph nodes, lytic skeletal lesions, deposit in the left adrenal gland, and nodules in the bilateral lungs, indicating metastatic disease. In addition, a hypermetabolic lesion was seen in the corpus cavernosum of the shaft of the penis, suggestive of penile metastasis. Follow-up PET-CT after tyrosine kinase inhibitor therapy showed reduction in size and metabolic activity of all previously seen lesions including penile lesion, suggestive of favorable response to therapy. Copyright © 2020 Indian Journal of Nuclear Medicine.Extraskeletal tracer uptake in methylene diphosphonate (MDP) bone scan is not a common finding. There have been several case reports in the literature showing diffuse splenic uptake in MDP bone scan. We present a case of sickle cell disease, which showed diffuse splenic uptake on MDP whole-body bone scan. Copyright © 2020 Indian Journal of Nuclear Medicine.Melanomas are usually cutaneous in origin but rarely can also arise from the mucosal linings in the body. Sinonasal melanomas arise from the mucosa of the nasal cavity and paranasal sinuses, which account for approximately 50% of mucosal melanomas in the body. 18F fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has proven its role in malignant melanoma in staging especially in stage III and IV disease, restaging, assessing response to therapy and had affected in treatment change in significant number of cases. We present a case of sinonasal melanoma who underwent FDG PET/CT for staging and showed cervical lymph node and marrow metastases. Copyright © 2020 Indian Journal of Nuclear Medicine.Gated imaging, as a technically demanding procedure, requires special attention and effort to fulfill the technical adequacy and accuracy of the study, based on the available standard guidelines. One of the essential requirements to be met by both technologists and physicians, in nuclear cardiology, is triggering and synchronization as a fundamental subject of gating. There are many sources of gating errors that produce imaging artifacts and, in some occasions, render the images uninterpretable or the quantitative analyses less accurate. Sufficient knowledge of recognition of these artifacts and understanding of their related mechanisms (from physical and technical perspectives) enable the technologists and physicians to promote their performance in daily practice. https://www.selleckchem.com/products/olprinone.html In this article, intended as a readily practical technical review for nuclear medicine practitioners, it is aimed to present the technical and computer aspects of triggering and synchronization as well as the related errors during imaging. Copyright © 2020 Indian Journal of Nuclear Medicine.Myocardial perfusion single-photon emission computed tomography (SPECT) as a common imaging procedure in nuclear medicine laboratories may encompass findings in the heart or beyond it, in the thorax or abdomen, which may be related or unrelated to the symptoms of the patients. Sometimes, these findings may be discovered incidentally. In the present article, it is aimed to present some less frequent cardiac and extracardiac findings including radiolabeled emboli, transposition of great arteries, breast prosthesis, breast tissue uptake, pericardial effusion, hiatal hernia, hepatocellular carcinoma, ascites, aortic aneurysm, splenomegaly, and polycystic kidney disease during 99mTc-methoxyisobutylisonitrile myocardial perfusion SPECT with their radiological correlates. Copyright © 2020 Indian Journal of Nuclear Medicine.Objective The objective of this study is to assess the efficacy of Yttrium-90 (Y-90) radiation synovectomy in decreasing the recurrent bleeding episodes in hemophilic joints. Subjects and Methods A retrospective analysis of patients who had Y-90 synovectomy from January 2001 to January 2016 was done. Among them, patients with minimum follow-up of 6 months were selected. The response in terms of decrease in the number of bleeding episodes was evaluated. Results A total of 167 patients (243 joints) with hemophilia had radiation synovectomy over 15 years. Those with a minimum follow-up of 6 months were 155 joints (115 patients). The age ranged from 5 to 43 years and included 113 male and two female patients. Data for 11 joints were unavailable as these patients were lost to follow-up. The assessment of response for the remaining 144 joints was done based on the data available for different follow-up periods. They were divided into the following - 7 months to 2 years (89 joints), 3-5 years (6 joints), 6-10 years (39 joints), and above 11 years (10 joints). Overall, 37.4% of the joints had complete response, 56% had partial response, and 6% of the joints had no response. Conclusion Radiation synovectomy is a noninvasive and effective modality which decreases the bleeding episodes in hemophiliac joints and improves the quality of life remarkably. Copyright © 2020 Indian Journal of Nuclear Medicine.Background Coronary artery calcification (CAC) can be visually estimated on computed tomography (CT) attenuation correction (CTAC) of positron emission tomography (PET). The visual estimation of CAC from CTAC scans performed for PET/CT is comparable to the standard CAC score scan. Myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) is commonly performed for risk stratification before oncologic surgery. Objective We investigated the value of visual estimation of CAC from CTAC of PET/CT as well as other factors such as coronary artery disease (***) risk factors and type of cancer as predictors of MPI ischemia. Methods Retrospectively, we identified 268 patients who underwent PET/CT and MPI for preoperative cardiac evaluation. Visual estimation of CAC was performed and classified into four categories. Results The results of visual CAC were as follows 47.8% - zero CAC, 32.8% - mild CAC, 14.2% - moderate CAC, and 5.2% - severe CAC. The majority of patients (85.8%) had normal MPI, whereas 14.2% were abnormal.
    Lymphomatoid granulomatosis (LYG) is a rare, extranodal B-cell lymphoproliferative disorder. The disease commonly presents with nonspecific symptoms and imaging features, making the diagnosis and therapeutic response assessment difficult. While histopathology is the mainstay of diagnosis, different imaging modalities such as computed tomography (CT), magnetic resonance imaging, or F18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) can help in identifying the different organs involved. We present a case of LYG, post chemotherapy in remission for the past 5 years, presenting with symptoms of disease recurrence. Copyright © 2020 Indian Journal of Nuclear Medicine.We present fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) findings in an extremely rare case of penile metastasis from renal cell carcinoma. A 66-year-old male, a known case of renal cell carcinoma, underwent FDG PET-CT. The scan showed metabolically active cervical lymph nodes, lytic skeletal lesions, deposit in the left adrenal gland, and nodules in the bilateral lungs, indicating metastatic disease. In addition, a hypermetabolic lesion was seen in the corpus cavernosum of the shaft of the penis, suggestive of penile metastasis. Follow-up PET-CT after tyrosine kinase inhibitor therapy showed reduction in size and metabolic activity of all previously seen lesions including penile lesion, suggestive of favorable response to therapy. Copyright © 2020 Indian Journal of Nuclear Medicine.Extraskeletal tracer uptake in methylene diphosphonate (MDP) bone scan is not a common finding. There have been several case reports in the literature showing diffuse splenic uptake in MDP bone scan. We present a case of sickle cell disease, which showed diffuse splenic uptake on MDP whole-body bone scan. Copyright © 2020 Indian Journal of Nuclear Medicine.Melanomas are usually cutaneous in origin but rarely can also arise from the mucosal linings in the body. Sinonasal melanomas arise from the mucosa of the nasal cavity and paranasal sinuses, which account for approximately 50% of mucosal melanomas in the body. 18F fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has proven its role in malignant melanoma in staging especially in stage III and IV disease, restaging, assessing response to therapy and had affected in treatment change in significant number of cases. We present a case of sinonasal melanoma who underwent FDG PET/CT for staging and showed cervical lymph node and marrow metastases. Copyright © 2020 Indian Journal of Nuclear Medicine.Gated imaging, as a technically demanding procedure, requires special attention and effort to fulfill the technical adequacy and accuracy of the study, based on the available standard guidelines. One of the essential requirements to be met by both technologists and physicians, in nuclear cardiology, is triggering and synchronization as a fundamental subject of gating. There are many sources of gating errors that produce imaging artifacts and, in some occasions, render the images uninterpretable or the quantitative analyses less accurate. Sufficient knowledge of recognition of these artifacts and understanding of their related mechanisms (from physical and technical perspectives) enable the technologists and physicians to promote their performance in daily practice. https://www.selleckchem.com/products/olprinone.html In this article, intended as a readily practical technical review for nuclear medicine practitioners, it is aimed to present the technical and computer aspects of triggering and synchronization as well as the related errors during imaging. Copyright © 2020 Indian Journal of Nuclear Medicine.Myocardial perfusion single-photon emission computed tomography (SPECT) as a common imaging procedure in nuclear medicine laboratories may encompass findings in the heart or beyond it, in the thorax or abdomen, which may be related or unrelated to the symptoms of the patients. Sometimes, these findings may be discovered incidentally. In the present article, it is aimed to present some less frequent cardiac and extracardiac findings including radiolabeled emboli, transposition of great arteries, breast prosthesis, breast tissue uptake, pericardial effusion, hiatal hernia, hepatocellular carcinoma, ascites, aortic aneurysm, splenomegaly, and polycystic kidney disease during 99mTc-methoxyisobutylisonitrile myocardial perfusion SPECT with their radiological correlates. Copyright © 2020 Indian Journal of Nuclear Medicine.Objective The objective of this study is to assess the efficacy of Yttrium-90 (Y-90) radiation synovectomy in decreasing the recurrent bleeding episodes in hemophilic joints. Subjects and Methods A retrospective analysis of patients who had Y-90 synovectomy from January 2001 to January 2016 was done. Among them, patients with minimum follow-up of 6 months were selected. The response in terms of decrease in the number of bleeding episodes was evaluated. Results A total of 167 patients (243 joints) with hemophilia had radiation synovectomy over 15 years. Those with a minimum follow-up of 6 months were 155 joints (115 patients). The age ranged from 5 to 43 years and included 113 male and two female patients. Data for 11 joints were unavailable as these patients were lost to follow-up. The assessment of response for the remaining 144 joints was done based on the data available for different follow-up periods. They were divided into the following - 7 months to 2 years (89 joints), 3-5 years (6 joints), 6-10 years (39 joints), and above 11 years (10 joints). Overall, 37.4% of the joints had complete response, 56% had partial response, and 6% of the joints had no response. Conclusion Radiation synovectomy is a noninvasive and effective modality which decreases the bleeding episodes in hemophiliac joints and improves the quality of life remarkably. Copyright © 2020 Indian Journal of Nuclear Medicine.Background Coronary artery calcification (CAC) can be visually estimated on computed tomography (CT) attenuation correction (CTAC) of positron emission tomography (PET). The visual estimation of CAC from CTAC scans performed for PET/CT is comparable to the standard CAC score scan. Myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) is commonly performed for risk stratification before oncologic surgery. Objective We investigated the value of visual estimation of CAC from CTAC of PET/CT as well as other factors such as coronary artery disease (CAD) risk factors and type of cancer as predictors of MPI ischemia. Methods Retrospectively, we identified 268 patients who underwent PET/CT and MPI for preoperative cardiac evaluation. Visual estimation of CAC was performed and classified into four categories. Results The results of visual CAC were as follows 47.8% - zero CAC, 32.8% - mild CAC, 14.2% - moderate CAC, and 5.2% - severe CAC. The majority of patients (85.8%) had normal MPI, whereas 14.2% were abnormal.
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  • Following publication of the original article [1], we have been notified that the author Joan Calzada should not have been included to the team of authors. The authors' team, thus, should be as follows.BACKGROUND During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients. CASE PRESENTATION We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML. CONCLUSIONS The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.BACKGROUND Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patients. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. OBJECTIVE The objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients. METHODS This is a double-blind, randomized controlled trial. Block randomization will be used. An intervention group will receive pycnogenol supplementation of 150 mg for 10 days and a control group will receive a placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (malondialdehyde, total antioxidant capacity), at the baseline, at the 5th day, and at the end of the study (10th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. The Sequential Organ Failure Assessment (SOFA) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index, and body composition will be measured. All analyses will be conducted by an initially assigned study arm in an intention-to-treat analysis. DISCUSSION We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients. TRIAL REGISTRATION This trial is registered at clinicaltrials.gov (ref NCT03777683) at 12/13/2018.BACKGROUND Current there are different screws fixation methods used for fixation of the talar neck fracture. However, the best method of screws internal fixation is still controversial. Few relevant studies have focused on this issue, especially by finite element analysis. The purpose of this study was to explore the mechanical stability of dual screws internal fixation methods with different approaches and the best biomechanical environment of the fracture section, so as to provide reliable mechanical evidence for the selection of clinical internal fixation. METHODS The computed tomography (CT) image of the healthy adult male ankle joint was used for three-dimensional reconstruction of the ankle model. Talus neck fracture and screws were constructed by computer-aided design (***). Then, 3D model of talar neck fracture which fixed with antero-posterior (AP) parallel dual screws, antero-posterior (AP) cross dual screws, postero-anterior (PA) parallel dual screws, and postero-anterior (PA) cross dual screws werparallel double screws fixation is better than that of cross double screws fixation. Thus, for the talar neck fracture, the use of posterior to anterior parallel double screws fixation is recommended in clinical surgery.BACKGROUND Ketamine is a widely used anesthetic in experimental medicine. We have also used ketamine for surgical interventions and imaging in rats and found significantly impaired ossification between identically performed experiments, which only differed in the number of anesthetic events. In order to investigate this phenomenon, we estimated the absorbed ionizing radiation and also studied whether ketamine administration has disadvantageous effect on bone cell viability. METHODS Spongious bone chips and parietal bone disks were harvested from rats. Explants were incubated in stem cell media containing 0.02, 0.2 and 2 mM ketamine. After 3 days of incubation, tetrazolium-based spectrophotometric assay was performed to measure cell viability. Size-specific dose estimation was used to calculate ionizing radiation of computed tomography imaging. RESULTS We found that ketamine supplementation with 0.2 mM slightly decreased cell viability, while 2 mM caused significant reduction both in the spongious and cortical explants. The cumulative ionizing radiation was found to be negligible compared to irradiation dosages used to impair ossification. CONCLUSIONS We conclude that multiple ketamine administration was responsible for the diminished regenerative potential of bone tissue in the present experimental setup. For this reason, we suggest that ketamine anesthesia should be avoided in studies investigating bone regeneration.BACKGROUND The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), the mechanisms underlying extra-choroidal CSF production remain elusive. We here investigated the distributions of aquaporin 1 (AQP1) and Na+/K+/2Cl- cotransporter 1 (NKCC1), key proteins for choroidal CSF production, in the adult rodent brain and spinal cord. METHODS We have accessed AQP1 distribution in the intact brain using uDISCO tissue clearing technique and by Western blot. AQP1 and NKCC1 cellular localization were accessed by immunohistochemistry in brain and spinal cord obtained from adult rodents. Imaging was performed using light-sheet, confocal and bright field light microscopy. RESULTS We determined that AQP1 is widely distributed in the leptomeningeal vasculature of the intact brain and that its glycosylated isoform is the most prominent in different brain regions. https://www.selleckchem.com/products/tradipitant.html Moreover, AQP1 and NKCC1 show specific distributions in the smooth muscle cell layer of penetrating arterioles and veins in the brain and spinal cord, and in the endothelia of capillaries and venules, restricted to the SAS vasculature.
    Following publication of the original article [1], we have been notified that the author Joan Calzada should not have been included to the team of authors. The authors' team, thus, should be as follows.BACKGROUND During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients. CASE PRESENTATION We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML. CONCLUSIONS The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.BACKGROUND Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patients. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. OBJECTIVE The objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients. METHODS This is a double-blind, randomized controlled trial. Block randomization will be used. An intervention group will receive pycnogenol supplementation of 150 mg for 10 days and a control group will receive a placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (malondialdehyde, total antioxidant capacity), at the baseline, at the 5th day, and at the end of the study (10th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. The Sequential Organ Failure Assessment (SOFA) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index, and body composition will be measured. All analyses will be conducted by an initially assigned study arm in an intention-to-treat analysis. DISCUSSION We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients. TRIAL REGISTRATION This trial is registered at clinicaltrials.gov (ref NCT03777683) at 12/13/2018.BACKGROUND Current there are different screws fixation methods used for fixation of the talar neck fracture. However, the best method of screws internal fixation is still controversial. Few relevant studies have focused on this issue, especially by finite element analysis. The purpose of this study was to explore the mechanical stability of dual screws internal fixation methods with different approaches and the best biomechanical environment of the fracture section, so as to provide reliable mechanical evidence for the selection of clinical internal fixation. METHODS The computed tomography (CT) image of the healthy adult male ankle joint was used for three-dimensional reconstruction of the ankle model. Talus neck fracture and screws were constructed by computer-aided design (CAD). Then, 3D model of talar neck fracture which fixed with antero-posterior (AP) parallel dual screws, antero-posterior (AP) cross dual screws, postero-anterior (PA) parallel dual screws, and postero-anterior (PA) cross dual screws werparallel double screws fixation is better than that of cross double screws fixation. Thus, for the talar neck fracture, the use of posterior to anterior parallel double screws fixation is recommended in clinical surgery.BACKGROUND Ketamine is a widely used anesthetic in experimental medicine. We have also used ketamine for surgical interventions and imaging in rats and found significantly impaired ossification between identically performed experiments, which only differed in the number of anesthetic events. In order to investigate this phenomenon, we estimated the absorbed ionizing radiation and also studied whether ketamine administration has disadvantageous effect on bone cell viability. METHODS Spongious bone chips and parietal bone disks were harvested from rats. Explants were incubated in stem cell media containing 0.02, 0.2 and 2 mM ketamine. After 3 days of incubation, tetrazolium-based spectrophotometric assay was performed to measure cell viability. Size-specific dose estimation was used to calculate ionizing radiation of computed tomography imaging. RESULTS We found that ketamine supplementation with 0.2 mM slightly decreased cell viability, while 2 mM caused significant reduction both in the spongious and cortical explants. The cumulative ionizing radiation was found to be negligible compared to irradiation dosages used to impair ossification. CONCLUSIONS We conclude that multiple ketamine administration was responsible for the diminished regenerative potential of bone tissue in the present experimental setup. For this reason, we suggest that ketamine anesthesia should be avoided in studies investigating bone regeneration.BACKGROUND The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), the mechanisms underlying extra-choroidal CSF production remain elusive. We here investigated the distributions of aquaporin 1 (AQP1) and Na+/K+/2Cl- cotransporter 1 (NKCC1), key proteins for choroidal CSF production, in the adult rodent brain and spinal cord. METHODS We have accessed AQP1 distribution in the intact brain using uDISCO tissue clearing technique and by Western blot. AQP1 and NKCC1 cellular localization were accessed by immunohistochemistry in brain and spinal cord obtained from adult rodents. Imaging was performed using light-sheet, confocal and bright field light microscopy. RESULTS We determined that AQP1 is widely distributed in the leptomeningeal vasculature of the intact brain and that its glycosylated isoform is the most prominent in different brain regions. https://www.selleckchem.com/products/tradipitant.html Moreover, AQP1 and NKCC1 show specific distributions in the smooth muscle cell layer of penetrating arterioles and veins in the brain and spinal cord, and in the endothelia of capillaries and venules, restricted to the SAS vasculature.
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  • CONCLUSIONS Although the universal health insurance has largely removed financial barriers to health care, the urban-rural disparity in LEA prevalence still exists in Taiwan after nearly two decades of the NHI program.BACKGROUND The Objective Structured Clinical Examination (OSCE) has been used in pediatrics since the 1980s. Its main drawback is that large numbers of children are needed to make up for the fatigue factor inherent in prolonged testing periods. Also, examinations mainly include children between 7 and 16 years old. We describe the summative examination used in our institution to evaluate medical students' clinical competencies in pediatrics with realistic available resources and for a wider age-range. We also evaluated different factors known to influence medical students' performances. METHODS This retrospective, descriptive, observational study evaluated the 740 distinct pediatric examination results of fourth-year medical students over 5 years. Their summative examination combined two different assessment methods a structured real-patient examination (SRPE) using standardized assessment grids for the most frequent pediatric diagnoses, and a computer-based written examination (CBWE). RESULTS Our approach defined an appropriate setting for some key elements of the educational objectives of pediatrics training, such as balancing the child-parent-pediatrician triangle and the ability to interact with pediatric patients, from newborns to 16-year-old adolescents, in a child-friendly fashion in realistic scenarios. SRPE scores showed no associations with students' degrees of exposure to specific lecture topics, vignettes, or bedside teaching. The impacts of clinical setting, topic, and individual examiners on SRPE scores was quite limited. Setting explained 1.6%, topic explained 4.5%, and examiner explained 4.7% of the overall variability in SRPE scores. CONCLUSIONS By combining two different assessment methods, we were able to provide a best-practice approach for assessing clinical skills in Pediatrics over a wide range of real patients.BACKGROUND Resistance to antimicrobial agents has become a problem in modern society. Antibiotic resistant bacteria undermine the prevention and treatment of infections. Undergraduate dental students in Europe are required to receive information in aspects of microbiology relevant for dental practice, including oral microbial pathogens and resistance mechanisms against antimicrobial compounds. The objective of this study was to implement a research-based strategy to aid the understanding of the increase in antimicrobial resistance in undergraduate dental student training. The primary outcome of this project is the efficacious delivery of the learning objectives. METHODS Ten volunteer undergraduate student "ambassadors" were recruited to manage the project with assistance from lead academics. https://www.selleckchem.com/products/CX-3543.html Student ambassadors were a source of peer learning for their colleagues. The project consisted of three phases Pre-project preparation (in which the ambassadors received special instruction and training); Practical experie best of our knowledge, this the first instance of the application of project-based methodologies to the teaching of a traditionally non-laboratory component of a subject taught in the dentistry curriculum. Results from both students and ambassadors highlighted the increase in dental knowledge and an increased awareness of antimicrobial resistance as the key outcomes of this project.BACKGROUND The Ethiopian law on abortion was liberalized in 2005. However, as a strongly religious country, the new law has remained controversial from the outset. Many abortion providers have religious allegiances, which begs the question how to negotiate the conflicting demands of their jobs and their commitment to their patients on the one hand, and their religious convictions and moral values on the other. METHOD A qualitative study based on in-depth interviews with 30 healthcare professionals involved in abortion services in either private/non-governmental clinics or in public hospitals in Addis Ababa, Ethiopia. Transcripts were analyzed using systematic text condensation, a qualitative analysis framework. RESULTS For the participants, religious norms and the view that the early fetus has a moral right to life count against providing abortion; while the interests and needs of the pregnant woman supports providing abortion services. The professionals weighed these value considerations differently and reached different conclusions. One group appears to have experienced genuine conflicts of conscience, while another group attempted to reconcile religious norms and values with their work, especially through framing provision of abortion as helping and preventing harm and suffering. The professionals handle this moral balancing act on their own. In general, participants working in the private sector reported less moral dilemma with abortion than did their colleagues from public hospitals. CONCLUSIONS This study highlights the difficulties in reconciling tensions between religious convictions and moral norms and values, and professional duties. Such insights might inform guidelines and healthcare ethics education.BACKGROUND Massive hemoptysis is a serious complication in Cystic Fibrosis (CF), occurring commonly in older patients. Bronchial artery embolization (BAE) can be performed to stop the bleeding. BAE is generally safe and effective, but can sometimes lead to serious complications. We report the first case of temporary unilateral diaphragmatic paralysis associated to lung consolidation following BAE in a pediatric CF female patient. This complication worsened the lung function of the patient who underwent lung transplantation after 9 months. CASE PRESENTATION A 14 years old female CF patient followed by the CF center of Florence presented low-grade fever, cough increase and recurrent episodes of major hemorrhages such as to carry out a BAE. Within 24 h the patient started to complain of severe thoracic pain in the right hemithorax, increased dyspnea and fever. A computed tomographic angiography and a dynamic fluoroscopic evaluation revealed the right diaphragmatic paralysis, not present before the procedure. After 4 days the clinical condition and radiological imaging had improved with restored mobility of the right hemidiaphragm.
    CONCLUSIONS Although the universal health insurance has largely removed financial barriers to health care, the urban-rural disparity in LEA prevalence still exists in Taiwan after nearly two decades of the NHI program.BACKGROUND The Objective Structured Clinical Examination (OSCE) has been used in pediatrics since the 1980s. Its main drawback is that large numbers of children are needed to make up for the fatigue factor inherent in prolonged testing periods. Also, examinations mainly include children between 7 and 16 years old. We describe the summative examination used in our institution to evaluate medical students' clinical competencies in pediatrics with realistic available resources and for a wider age-range. We also evaluated different factors known to influence medical students' performances. METHODS This retrospective, descriptive, observational study evaluated the 740 distinct pediatric examination results of fourth-year medical students over 5 years. Their summative examination combined two different assessment methods a structured real-patient examination (SRPE) using standardized assessment grids for the most frequent pediatric diagnoses, and a computer-based written examination (CBWE). RESULTS Our approach defined an appropriate setting for some key elements of the educational objectives of pediatrics training, such as balancing the child-parent-pediatrician triangle and the ability to interact with pediatric patients, from newborns to 16-year-old adolescents, in a child-friendly fashion in realistic scenarios. SRPE scores showed no associations with students' degrees of exposure to specific lecture topics, vignettes, or bedside teaching. The impacts of clinical setting, topic, and individual examiners on SRPE scores was quite limited. Setting explained 1.6%, topic explained 4.5%, and examiner explained 4.7% of the overall variability in SRPE scores. CONCLUSIONS By combining two different assessment methods, we were able to provide a best-practice approach for assessing clinical skills in Pediatrics over a wide range of real patients.BACKGROUND Resistance to antimicrobial agents has become a problem in modern society. Antibiotic resistant bacteria undermine the prevention and treatment of infections. Undergraduate dental students in Europe are required to receive information in aspects of microbiology relevant for dental practice, including oral microbial pathogens and resistance mechanisms against antimicrobial compounds. The objective of this study was to implement a research-based strategy to aid the understanding of the increase in antimicrobial resistance in undergraduate dental student training. The primary outcome of this project is the efficacious delivery of the learning objectives. METHODS Ten volunteer undergraduate student "ambassadors" were recruited to manage the project with assistance from lead academics. https://www.selleckchem.com/products/CX-3543.html Student ambassadors were a source of peer learning for their colleagues. The project consisted of three phases Pre-project preparation (in which the ambassadors received special instruction and training); Practical experie best of our knowledge, this the first instance of the application of project-based methodologies to the teaching of a traditionally non-laboratory component of a subject taught in the dentistry curriculum. Results from both students and ambassadors highlighted the increase in dental knowledge and an increased awareness of antimicrobial resistance as the key outcomes of this project.BACKGROUND The Ethiopian law on abortion was liberalized in 2005. However, as a strongly religious country, the new law has remained controversial from the outset. Many abortion providers have religious allegiances, which begs the question how to negotiate the conflicting demands of their jobs and their commitment to their patients on the one hand, and their religious convictions and moral values on the other. METHOD A qualitative study based on in-depth interviews with 30 healthcare professionals involved in abortion services in either private/non-governmental clinics or in public hospitals in Addis Ababa, Ethiopia. Transcripts were analyzed using systematic text condensation, a qualitative analysis framework. RESULTS For the participants, religious norms and the view that the early fetus has a moral right to life count against providing abortion; while the interests and needs of the pregnant woman supports providing abortion services. The professionals weighed these value considerations differently and reached different conclusions. One group appears to have experienced genuine conflicts of conscience, while another group attempted to reconcile religious norms and values with their work, especially through framing provision of abortion as helping and preventing harm and suffering. The professionals handle this moral balancing act on their own. In general, participants working in the private sector reported less moral dilemma with abortion than did their colleagues from public hospitals. CONCLUSIONS This study highlights the difficulties in reconciling tensions between religious convictions and moral norms and values, and professional duties. Such insights might inform guidelines and healthcare ethics education.BACKGROUND Massive hemoptysis is a serious complication in Cystic Fibrosis (CF), occurring commonly in older patients. Bronchial artery embolization (BAE) can be performed to stop the bleeding. BAE is generally safe and effective, but can sometimes lead to serious complications. We report the first case of temporary unilateral diaphragmatic paralysis associated to lung consolidation following BAE in a pediatric CF female patient. This complication worsened the lung function of the patient who underwent lung transplantation after 9 months. CASE PRESENTATION A 14 years old female CF patient followed by the CF center of Florence presented low-grade fever, cough increase and recurrent episodes of major hemorrhages such as to carry out a BAE. Within 24 h the patient started to complain of severe thoracic pain in the right hemithorax, increased dyspnea and fever. A computed tomographic angiography and a dynamic fluoroscopic evaluation revealed the right diaphragmatic paralysis, not present before the procedure. After 4 days the clinical condition and radiological imaging had improved with restored mobility of the right hemidiaphragm.
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  • Next, approximately half of RGCs display diverse forms of color opponency, including many that are driven by a pervasive and slow blue-Off system-far in excess of what would be required to satisfy traditional models of color vision. In addition, most information on spectral contrast was intermixed with temporal information. Taken together, our results suggest that zebrafish RGCs send a diverse and highly regionalized time-color code to the brain.Cambium drives the lateral growth of stems and roots, contributing to diverse plant growth forms. The root crop is one of the outstanding examples of the cambium-driven growth. To understand its molecular basis, we used radish to generate a compendium of root-tissue- and stage-specific transcriptomes from two contrasting inbred lines during root growth. Expression patterns of key cambium regulators and hormone signaling components were validated. https://www.selleckchem.com/products/icarm1.html Clustering and gene ontology (GO) enrichment analyses of radish datasets followed by a comparative analysis against the newly established Arabidopsis early cambium data revealed evolutionary conserved stress-response transcription factors that may intimately control the cambium. Indeed, an in vivo network consisting of selected stress-response and cambium regulators indicated ERF-1 as a potential key checkpoint of cambial activities, explaining how cambium-driven growth is altered in response to environmental changes. The findings here provide valuable information about dynamic gene expression changes during cambium-driven root growth and have implications with regard to future engineering schemes, leading to better crop yields.The ability to respond to unanticipated increases in volume is a fundamental property of cells, essential for cellular integrity in the face of osmotic challenges. Plants must manage cell swelling during flooding, rehydration, and pathogen invasion-but little is known about the mechanisms by which this occurs. It has been proposed that plant cells could sense and respond to cell swelling through the action of mechanosensitive ion channels. Here, we characterize a new assay to study the effects of cell swelling on Arabidopsis thaliana seedlings and to test the contributions of the mechanosensitive ion channel ****-like10 (MSL10). The assay incorporates both cell wall softening and hypo-osmotic treatment to induce cell swelling. We show that MSL10 is required for several previously demonstrated responses to hypo-osmotic shock, including a cytoplasmic calcium transient within the first few seconds, accumulation of ROS within the first 30 min, and increased transcript levels of mechano-inducible genes within 60 min. We also show that cell swelling induces programmed cell death within 3 h in a MSL10-dependent manner. Finally, we show that MSL10 is unable to potentiate cell swelling-induced death when phosphomimetic residues are introduced into its soluble N terminus. Thus, MSL10 functions as a phospho-regulated membrane-based sensor that connects the perception of cell swelling to a downstream signaling cascade and programmed cell death.Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.Understanding the adaptive function of conspicuous coloration has been a major focus of evolutionary biology for **** of the last century. Although considerable progress has been made in explaining how conspicuous coloration can be used in functions as diverse as sexual and social signaling, startling predators, and advertising toxicity [1], there remain a multitude of species that display conspicuous coloration that cannot be explained by existing theory. Here we detail a new "matador-like" divertive antipredator strategy based on conspicuous coloration in Trinidadian guppies (Poecilia reticulata). Guppies encountering predatory fish rapidly enhance the conspicuousness of their eyes by blackening their irises. By pitting biomimetic robotic guppies against real predatory fish, we show this conspicuous eye coloration diverts attacks away from the guppies' center of mass to their head. To determine the function of this seemingly counterintuitive behavior, we developed a method for simulating escape probabilities when live prey interact with ballistic attacking predators, and find this diversion effect significantly benefits black-eyed guppies because they evade capture by rapidly pivoting away from the predator once it has committed to its attack. Remarkably, this antipredator strategy reverses the commonly observed negative scaling relationship between prey size and evasive ability, with larger fish benefiting most from diverting predators. Taken together, our results introduce a new antipredator divertive strategy that may be widely used by conspicuously colored prey that rely on agility to escape their predators.
    Next, approximately half of RGCs display diverse forms of color opponency, including many that are driven by a pervasive and slow blue-Off system-far in excess of what would be required to satisfy traditional models of color vision. In addition, most information on spectral contrast was intermixed with temporal information. Taken together, our results suggest that zebrafish RGCs send a diverse and highly regionalized time-color code to the brain.Cambium drives the lateral growth of stems and roots, contributing to diverse plant growth forms. The root crop is one of the outstanding examples of the cambium-driven growth. To understand its molecular basis, we used radish to generate a compendium of root-tissue- and stage-specific transcriptomes from two contrasting inbred lines during root growth. Expression patterns of key cambium regulators and hormone signaling components were validated. https://www.selleckchem.com/products/icarm1.html Clustering and gene ontology (GO) enrichment analyses of radish datasets followed by a comparative analysis against the newly established Arabidopsis early cambium data revealed evolutionary conserved stress-response transcription factors that may intimately control the cambium. Indeed, an in vivo network consisting of selected stress-response and cambium regulators indicated ERF-1 as a potential key checkpoint of cambial activities, explaining how cambium-driven growth is altered in response to environmental changes. The findings here provide valuable information about dynamic gene expression changes during cambium-driven root growth and have implications with regard to future engineering schemes, leading to better crop yields.The ability to respond to unanticipated increases in volume is a fundamental property of cells, essential for cellular integrity in the face of osmotic challenges. Plants must manage cell swelling during flooding, rehydration, and pathogen invasion-but little is known about the mechanisms by which this occurs. It has been proposed that plant cells could sense and respond to cell swelling through the action of mechanosensitive ion channels. Here, we characterize a new assay to study the effects of cell swelling on Arabidopsis thaliana seedlings and to test the contributions of the mechanosensitive ion channel MscS-like10 (MSL10). The assay incorporates both cell wall softening and hypo-osmotic treatment to induce cell swelling. We show that MSL10 is required for several previously demonstrated responses to hypo-osmotic shock, including a cytoplasmic calcium transient within the first few seconds, accumulation of ROS within the first 30 min, and increased transcript levels of mechano-inducible genes within 60 min. We also show that cell swelling induces programmed cell death within 3 h in a MSL10-dependent manner. Finally, we show that MSL10 is unable to potentiate cell swelling-induced death when phosphomimetic residues are introduced into its soluble N terminus. Thus, MSL10 functions as a phospho-regulated membrane-based sensor that connects the perception of cell swelling to a downstream signaling cascade and programmed cell death.Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.Understanding the adaptive function of conspicuous coloration has been a major focus of evolutionary biology for much of the last century. Although considerable progress has been made in explaining how conspicuous coloration can be used in functions as diverse as sexual and social signaling, startling predators, and advertising toxicity [1], there remain a multitude of species that display conspicuous coloration that cannot be explained by existing theory. Here we detail a new "matador-like" divertive antipredator strategy based on conspicuous coloration in Trinidadian guppies (Poecilia reticulata). Guppies encountering predatory fish rapidly enhance the conspicuousness of their eyes by blackening their irises. By pitting biomimetic robotic guppies against real predatory fish, we show this conspicuous eye coloration diverts attacks away from the guppies' center of mass to their head. To determine the function of this seemingly counterintuitive behavior, we developed a method for simulating escape probabilities when live prey interact with ballistic attacking predators, and find this diversion effect significantly benefits black-eyed guppies because they evade capture by rapidly pivoting away from the predator once it has committed to its attack. Remarkably, this antipredator strategy reverses the commonly observed negative scaling relationship between prey size and evasive ability, with larger fish benefiting most from diverting predators. Taken together, our results introduce a new antipredator divertive strategy that may be widely used by conspicuously colored prey that rely on agility to escape their predators.
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  • Background This study examined the effect of a portable low-frequency electrostimulation (ES) device on patients diagnosed with chemotherapy-induced peripheral neuropathy (CIPN) immediately after chemotherapy for breast cancer. Methods A single-center, randomized, placebo-controlled trial was conducted. A total of 72 patients newly diagnosed with CIPN were enrolled and randomly placed into the ES (n = 36) or the sham ES group (SES; n = 36). Duloxetine or pregabalin was prescribed to all participants from the initial assessment. The devices for 14 days, at least twice a day, for at least 120 minutes. The primary outcomes were the overall intensities of the CIPN symptoms as assessed using Numerical Rating Scale (NRS). Secondary outcomes included Total Neuropathy Score (TNS), European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ), Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Instrument on Pattern Identification and Evaluation for CIPN (IPIE-CIPN). Results No differences in NRS scores were found between the patients in the ES and the SES group (P = 0.267). Patients in both groups showed significantly reduced CIPN intensities (ES P less then .001; SES P less then .001). No significant differences between the groups were found in TNS, EORTC-QLQ, CIPN20, and FACT-B. The general symptoms of CIPN diagnosed as cold arthralgia showed significance only in the ES group (P = .006). Conclusion Compared with a placebo, the effectiveness of the low-frequency ES device with pharmacological intervention was not significantly different, but a therapeutic effect was possible.Background/Aims Currently, the role of the microbiome GBA is being widely studied in the pathogenesis of visceral hypersensitivity in IBS. To investigate the role of fungus, the current study aimed to i) investigate the expression of Syk/CARD9-coupled Dectin-1 receptors in the ileocecal mucosa in D-IBS patients and (ii) explore the relationships between Dectin-1 and plasma MCT levels as well as anorectal sensory function in patients with D-IBS.Methods Thirty-eight D-IBS patients who met the Rome III criteria and 2 groups of age- and sex-matched asymptomatic healthy controls were recruited from March 2015 to January 2017. Anorectal sensory function was quantified by HR-ARM. Plasma MCT titers were identified by ELISA, while the expression of Syk/CARD9 Dectin-1 receptors in ileocecal mucosa was identified by RT-qPCR.Results (i) The expression of Syk/CARD9-coupled Dectin-1 receptors was significantly higher in D-IBS patients than in controls (p less then .001). ii) The threshold values of first sensation and desire to defecate were significantly lower in D-IBS patientsthan in controls (the P value was0.007 and 0.001 respectively). (iii) There were negative correlations between plasma MCT levels and first sensation thresholds in D-IBS patients (r = -0.513, p = .012) and the desire to defecate thresholds (r = -0.423, p = .044). https://www.selleckchem.com/products/pfi-2.html (iiii) There was a positive correlation between plasma MCT titers and the expression of Dectin-1 receptors in D-IBS patients (r = 0.565, p = .005).Conclusions These results suggested that fungi may partially participate in the genesis of visceral hypersensitivity by activating mast cells, which is mediated by activation of the Dectin-1 receptor-mediated Syk/CARD9 signaling pathway.)Several earlier studies have reported increased risk of bleeding in women with myocardial infarction, (MI) compared to men. The reasons for the observed difference are incompletely understood, but one suggested explanation has been excess dosing of antithrombotic drugs in women. The aim of this prospective observational study was to assess sex differences in platelet activity in patients treated with three different platelet inhibitors. We recruited 125 patients (37 women and 88 men) with MI, scheduled for coronary angiography. All patients received clopidogrel and aspirin. A subgroup of patients received glycoprotein (GP) IIb/IIIa-inhibitor. Platelet aggregation in whole blood was assessed at several time points, using impedance aggregometry. Soluble P-selectin was measured 3 days after admission. There were no significant differences between women and men in baseline features or comorbidities except higher frequency of diabetes, lower hemoglobin value, and lower estimated glomerular filtration rate, in women on admission. We observed significantly more in-hospital bleeding events in women compared to men (18.9% vs. 6.8%, p = .04). There were no differences in platelet aggregation using three different agonists, reflecting treatment effect of GPIIb/IIIa-inhibitors, clopidogrel, and aspirin, 6-8 hours, 3 days, 7-9 days, or 6 months after loading dose. Moreover, there was no significant difference in soluble P-selectin. The main finding of this study was a consistent lack of difference between the sexes in platelet aggregation, using three different agonists at several time-points. Our results do not support excess dosing of anti-platelet drugs as a major explanation for increased bleeding risk in women.Zygomaticomaxillary complex (ZMC) and orbital blow out fractures are commonly encountered midfacial fractures that may result in aesthetic and functional impairment. This retrospective study reports on the surgical treatment and associated postoperative complications in our patient collective. We evaluated 100 patients who underwent open reduction and internal fixation of midfacial fractures between 2010 and 2015. Preoperative clinical features, surgical technique and postoperative complications were analyzed. Surgery was performed with a mean latency of 7 days after trauma. We used titanium mesh and polydioxanone sheets to reconstruct the orbital floor. Most ZMC fractures were stabilized with two point fixation with titanium plates. Preoperative symptoms were present in 70 patients (70%). Infraorbital hypesthesia occurred in 49 patients, diplopia in 41 patients and ocular motility impairment in 24 patients. Postoperative symptoms persisted during a mean follow-up time of 4.5 months in 47 patients (47%) showing infraorbital hypesthesia in 24%, diplopia in 17%, ectropion in 7% and ocular motility impairment in 4%.
    Background This study examined the effect of a portable low-frequency electrostimulation (ES) device on patients diagnosed with chemotherapy-induced peripheral neuropathy (CIPN) immediately after chemotherapy for breast cancer. Methods A single-center, randomized, placebo-controlled trial was conducted. A total of 72 patients newly diagnosed with CIPN were enrolled and randomly placed into the ES (n = 36) or the sham ES group (SES; n = 36). Duloxetine or pregabalin was prescribed to all participants from the initial assessment. The devices for 14 days, at least twice a day, for at least 120 minutes. The primary outcomes were the overall intensities of the CIPN symptoms as assessed using Numerical Rating Scale (NRS). Secondary outcomes included Total Neuropathy Score (TNS), European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ), Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Instrument on Pattern Identification and Evaluation for CIPN (IPIE-CIPN). Results No differences in NRS scores were found between the patients in the ES and the SES group (P = 0.267). Patients in both groups showed significantly reduced CIPN intensities (ES P less then .001; SES P less then .001). No significant differences between the groups were found in TNS, EORTC-QLQ, CIPN20, and FACT-B. The general symptoms of CIPN diagnosed as cold arthralgia showed significance only in the ES group (P = .006). Conclusion Compared with a placebo, the effectiveness of the low-frequency ES device with pharmacological intervention was not significantly different, but a therapeutic effect was possible.Background/Aims Currently, the role of the microbiome GBA is being widely studied in the pathogenesis of visceral hypersensitivity in IBS. To investigate the role of fungus, the current study aimed to i) investigate the expression of Syk/CARD9-coupled Dectin-1 receptors in the ileocecal mucosa in D-IBS patients and (ii) explore the relationships between Dectin-1 and plasma MCT levels as well as anorectal sensory function in patients with D-IBS.Methods Thirty-eight D-IBS patients who met the Rome III criteria and 2 groups of age- and sex-matched asymptomatic healthy controls were recruited from March 2015 to January 2017. Anorectal sensory function was quantified by HR-ARM. Plasma MCT titers were identified by ELISA, while the expression of Syk/CARD9 Dectin-1 receptors in ileocecal mucosa was identified by RT-qPCR.Results (i) The expression of Syk/CARD9-coupled Dectin-1 receptors was significantly higher in D-IBS patients than in controls (p less then .001). ii) The threshold values of first sensation and desire to defecate were significantly lower in D-IBS patientsthan in controls (the P value was0.007 and 0.001 respectively). (iii) There were negative correlations between plasma MCT levels and first sensation thresholds in D-IBS patients (r = -0.513, p = .012) and the desire to defecate thresholds (r = -0.423, p = .044). https://www.selleckchem.com/products/pfi-2.html (iiii) There was a positive correlation between plasma MCT titers and the expression of Dectin-1 receptors in D-IBS patients (r = 0.565, p = .005).Conclusions These results suggested that fungi may partially participate in the genesis of visceral hypersensitivity by activating mast cells, which is mediated by activation of the Dectin-1 receptor-mediated Syk/CARD9 signaling pathway.)Several earlier studies have reported increased risk of bleeding in women with myocardial infarction, (MI) compared to men. The reasons for the observed difference are incompletely understood, but one suggested explanation has been excess dosing of antithrombotic drugs in women. The aim of this prospective observational study was to assess sex differences in platelet activity in patients treated with three different platelet inhibitors. We recruited 125 patients (37 women and 88 men) with MI, scheduled for coronary angiography. All patients received clopidogrel and aspirin. A subgroup of patients received glycoprotein (GP) IIb/IIIa-inhibitor. Platelet aggregation in whole blood was assessed at several time points, using impedance aggregometry. Soluble P-selectin was measured 3 days after admission. There were no significant differences between women and men in baseline features or comorbidities except higher frequency of diabetes, lower hemoglobin value, and lower estimated glomerular filtration rate, in women on admission. We observed significantly more in-hospital bleeding events in women compared to men (18.9% vs. 6.8%, p = .04). There were no differences in platelet aggregation using three different agonists, reflecting treatment effect of GPIIb/IIIa-inhibitors, clopidogrel, and aspirin, 6-8 hours, 3 days, 7-9 days, or 6 months after loading dose. Moreover, there was no significant difference in soluble P-selectin. The main finding of this study was a consistent lack of difference between the sexes in platelet aggregation, using three different agonists at several time-points. Our results do not support excess dosing of anti-platelet drugs as a major explanation for increased bleeding risk in women.Zygomaticomaxillary complex (ZMC) and orbital blow out fractures are commonly encountered midfacial fractures that may result in aesthetic and functional impairment. This retrospective study reports on the surgical treatment and associated postoperative complications in our patient collective. We evaluated 100 patients who underwent open reduction and internal fixation of midfacial fractures between 2010 and 2015. Preoperative clinical features, surgical technique and postoperative complications were analyzed. Surgery was performed with a mean latency of 7 days after trauma. We used titanium mesh and polydioxanone sheets to reconstruct the orbital floor. Most ZMC fractures were stabilized with two point fixation with titanium plates. Preoperative symptoms were present in 70 patients (70%). Infraorbital hypesthesia occurred in 49 patients, diplopia in 41 patients and ocular motility impairment in 24 patients. Postoperative symptoms persisted during a mean follow-up time of 4.5 months in 47 patients (47%) showing infraorbital hypesthesia in 24%, diplopia in 17%, ectropion in 7% and ocular motility impairment in 4%.
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  • A set of 12 muscle transcripts, including ACSS3, FZD4, GNAI1 and IGF1, were differentially expressed before and after intervention (false discovery rate ⩽0.10, p ⩽0.001), and their corresponding bone transcripts were associated with BMD. Experimental data underline and describe the functionality of these genes in bone biology. OP women had 8% (p less then 0.01) higher proportion of type I fibres, but muscle fibre cross-sectional area did not differ. Muscle strength increased in both groups (p less then 0.01). Conclusions Postmenopausal healthy and OP women have distinct muscle transcriptomes [messenger ribonucleic acids (mRNAs) and microRNAs] that are modulated by strength training, translating into key protein alterations and muscle fibre changes. The function of common skeletal muscle and bone genes in postmenopausal OP is suggestive of a shared disease trait.Background The aim of this study was to evaluate disease-activity-guided stepwise tapering or discontinuation of rhTNFRFc, an etanercept biosimilar, in patients with ankylosing spondylitis (AS) in a prospective, randomized, open-label, multicentric study. Methods Active AS patients with AS disease activity score (ASDAS) ⩾2.1 recruited from 10 hospitals were treated with rhTNFRFc 50 mg weekly for 12 weeks, and further randomized into different tapering or discontinuation groups according to ASDAS at week 12. Patients who achieved clinical remission (ASDAS less then 1.3) were assigned randomly to stepwise tapering group or discontinuation group. Patients who achieved low disease activity (LDA, 1.3⩽ASDAS less then 2.1) were assigned randomly to stepwise tapering, delayed tapering, or discontinuation group. All patients were evaluated every 12 weeks until week 48. The primary endpoint was cumulative flare rates in different groups at week 48. Results A total of 311 patients were enrolled with an average ASDASpt discontinuation of rhTNFRFc even if patients achieved clinical remission should be avoided. Trial registration ClinicalTrials.gov NCT03880968,URL https//clinicaltrials.gov/ct2/show/NCT03880968.Background This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods A total of 1814 eligible patients with stage II-IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Results Nomograms were developed to predict OS, PFS and DMFS (C-index 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups (p = 0.040). https://www.selleckchem.com/products/sonrotoclax.html Conclusion IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), induction of signaling pathways, and angiogenesis. LncRNA-driven mechanisms of resistance to various antineoplastic agents have been studied extensively. There are unique mechanisms of resistance against different types of drugs, and each mechanism may have more than one contributing factor. We summarize the emerging strategies that can be used to overcome the technical challenges in studying and addressing lncRNA-mediated drug resistance.Background In the PACIFIC study, progression-free survival (PFS) and overall survival (OS) of patients with unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC) were prolonged by durvalumab as maintenance therapy after radical concurrent chemoradiotherapy using platinum-based antitumor agents. However, no data were obtained to reveal the efficacy of durvalumab after radiation monotherapy in patients unsuitable for chemoradiotherapy. Here, we describe an ongoing single-arm, prospective, open-label, multicenter phase II trial of durvalumab in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study). Methods Durvalumab at 10 mg/kg body weight is administered every 2 weeks after radiation therapy until individual patients meet the discontinuation criteria. The treatment duration is up to 12 months. The primary endpoint is the 1-year PFS rate. Secondary endpoints are response rate, PFS, OS, and safety. Durvalumab treatment after radiation monotherapy is expected to prolong 1-year PFS rate and have acceptable adverse events. Discussion We are conducting an intervention study to investigate the safety and efficacy of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy.
    A set of 12 muscle transcripts, including ACSS3, FZD4, GNAI1 and IGF1, were differentially expressed before and after intervention (false discovery rate ⩽0.10, p ⩽0.001), and their corresponding bone transcripts were associated with BMD. Experimental data underline and describe the functionality of these genes in bone biology. OP women had 8% (p less then 0.01) higher proportion of type I fibres, but muscle fibre cross-sectional area did not differ. Muscle strength increased in both groups (p less then 0.01). Conclusions Postmenopausal healthy and OP women have distinct muscle transcriptomes [messenger ribonucleic acids (mRNAs) and microRNAs] that are modulated by strength training, translating into key protein alterations and muscle fibre changes. The function of common skeletal muscle and bone genes in postmenopausal OP is suggestive of a shared disease trait.Background The aim of this study was to evaluate disease-activity-guided stepwise tapering or discontinuation of rhTNFRFc, an etanercept biosimilar, in patients with ankylosing spondylitis (AS) in a prospective, randomized, open-label, multicentric study. Methods Active AS patients with AS disease activity score (ASDAS) ⩾2.1 recruited from 10 hospitals were treated with rhTNFRFc 50 mg weekly for 12 weeks, and further randomized into different tapering or discontinuation groups according to ASDAS at week 12. Patients who achieved clinical remission (ASDAS less then 1.3) were assigned randomly to stepwise tapering group or discontinuation group. Patients who achieved low disease activity (LDA, 1.3⩽ASDAS less then 2.1) were assigned randomly to stepwise tapering, delayed tapering, or discontinuation group. All patients were evaluated every 12 weeks until week 48. The primary endpoint was cumulative flare rates in different groups at week 48. Results A total of 311 patients were enrolled with an average ASDASpt discontinuation of rhTNFRFc even if patients achieved clinical remission should be avoided. Trial registration ClinicalTrials.gov NCT03880968,URL https//clinicaltrials.gov/ct2/show/NCT03880968.Background This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods A total of 1814 eligible patients with stage II-IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Results Nomograms were developed to predict OS, PFS and DMFS (C-index 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups (p = 0.040). https://www.selleckchem.com/products/sonrotoclax.html Conclusion IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), induction of signaling pathways, and angiogenesis. LncRNA-driven mechanisms of resistance to various antineoplastic agents have been studied extensively. There are unique mechanisms of resistance against different types of drugs, and each mechanism may have more than one contributing factor. We summarize the emerging strategies that can be used to overcome the technical challenges in studying and addressing lncRNA-mediated drug resistance.Background In the PACIFIC study, progression-free survival (PFS) and overall survival (OS) of patients with unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC) were prolonged by durvalumab as maintenance therapy after radical concurrent chemoradiotherapy using platinum-based antitumor agents. However, no data were obtained to reveal the efficacy of durvalumab after radiation monotherapy in patients unsuitable for chemoradiotherapy. Here, we describe an ongoing single-arm, prospective, open-label, multicenter phase II trial of durvalumab in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study). Methods Durvalumab at 10 mg/kg body weight is administered every 2 weeks after radiation therapy until individual patients meet the discontinuation criteria. The treatment duration is up to 12 months. The primary endpoint is the 1-year PFS rate. Secondary endpoints are response rate, PFS, OS, and safety. Durvalumab treatment after radiation monotherapy is expected to prolong 1-year PFS rate and have acceptable adverse events. Discussion We are conducting an intervention study to investigate the safety and efficacy of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy.
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  • At the protein level, both D1 removal and replacement, as well as PS II biogenesis, were accelerated in the ∆PsbT strain. Our results demonstrate that PsbT plays a key role in optimizing the electron acceptor complex of the acceptor side of PS II and support the view that repair and biogenesis of PS II share an assembly pathway that incorporates both de novo synthesis and recycling of the assembly modules associated with the core membrane-spanning proteins.Background The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays. Methods Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers' and optimized thresholds. Results Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen's kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen's kappa = 0.962 and SE = 0.126) for ELISA. Conclusions The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.Ethylmalonic encephalopathy (EE) is a rare and devastating neurodegenerative disease caused by mutations in the ETHE1 gene. It is characterized by early-onset encephalopathy, chronic diarrhea, petechiae, orthostatic acrocyanosis, and high levels of methylsuccinic, lactic, and ethylmalonic acids in body fluids. In this study, we report a patient with EE, who was identified through newborn screening, and the diagnosis was confirmed by targeted next-generation sequencing (NGS). The patient displayed recurrent petechiae, intermittent jaundice, protracted diarrhea, and extensive developmental regression. Genetic testing identified a homozygous nonsense variant, c.295C > T (p. Q99*), in the ETHE1 gene. A review of all known ETHE1 variants observed in other EE patients was conducted. This revealed the current difficulties in EE diagnosis. Besides, it also showed that patients with truncated variants of ETHE1 might exhibit pathological symptoms earlier and present more severe manifestations. Finally, a novel nonsense variant was identified, which supported and expanded our current knowledge of the variant spectrum for ETHE1. https://www.selleckchem.com/products/avelumab.html This novel variant also deepened our understanding of the genotype-phenotype associations that occur in EE patients.Background Here, we report on a head-to-head comparison of the fully-automated Elecsys® Anti-SARS-CoV-2 immunoassay with the EDITM enzyme linked immunosorbent assays (ELISA) for the detection of SARS-CoV-2 antibodies in human plasma. Methods SARS-CoV-2 antibodies were measured with the Elecsys® assay and the EDITM ELISAs (IgM and IgG) in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n = 104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. Results In COVID-19 patients, the percentage of positive results rose with time from symptom onset, peaking to positivity rates after 15-22 days of 100% for the Elecsys® assay, of 94% for the EDITM IgM-ELISA and of 100% for the EDITM IgG ELISA. In the 104 blood samples, the agreement between positive/negative classifications of the Elecsys® assay and the EDITM ELISAs (IgM or IgG) was 90%. The false positivity rates in the healthy blood donors and the ICU patients were less then 1% for the Elecsys® assay and less then 3% for the EDITM ELISAs. Conclusions Our results indicate a high sensitivity and specificity for the Elecsys® assay and an acceptable agreement with the EDITM ELISAs.Iron is essential for all the lives on earth but may trigger a switch toward ferroptosis, a novel form of regulated necrosis. Carbonic anhydrases (CAs) are ubiquitous enzymes from microbes to humans. The primary function of CAs is to regulate cellular pH by hydrating carbon dioxide (CO2) to protons (H+) and bicarbonate ions (HCO3-). Furthermore, CAs play roles in biosynthetic reactions, such as gluconeogenesis, lipogenesis, ureagenesis and are also associated with tumor metabolism, suggesting that CAs may be a potential target for the treatment of cancers. We have recently revealed a novel function of CA IX in ferroptosis-resistance by using human malignant mesothelioma cells. Herein, we aim to review the potential molecular association between ferroptosis and CAs, from the viewpoint of iron-metabolism, lipogenesis and signaling pathways both under physiological and pathological contexts.Actinoporins are a family of pore-forming toxins produced by sea anemones as part of their venomous cocktail. These proteins remain soluble and stably folded in aqueous solution, but when interacting with sphingomyelin-containing lipid membranes, they become integral oligomeric membrane structures that form a pore permeable to cations, which leads to cell death by osmotic shock. Actinoporins appear as multigenic families within the genome of sea anemones several genes encoding very similar actinoporins are detected within the same species. The Caribbean Sea anemone Stichodactyla helianthus produces three actinoporins (sticholysins I, II and III; StnI, StnII and StnIII) that differ in their toxic potency. For example, StnII is about four-fold more effective than StnI against sheep erythrocytes in causing hemolysis, and both show synergy. However, StnIII, recently discovered in the S. helianthus transcriptome, has not been characterized so far. Here we describe StnIII's spectroscopic and functional properties and show its potential to interact with the other Stns.
    At the protein level, both D1 removal and replacement, as well as PS II biogenesis, were accelerated in the ∆PsbT strain. Our results demonstrate that PsbT plays a key role in optimizing the electron acceptor complex of the acceptor side of PS II and support the view that repair and biogenesis of PS II share an assembly pathway that incorporates both de novo synthesis and recycling of the assembly modules associated with the core membrane-spanning proteins.Background The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays. Methods Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers' and optimized thresholds. Results Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen's kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen's kappa = 0.962 and SE = 0.126) for ELISA. Conclusions The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.Ethylmalonic encephalopathy (EE) is a rare and devastating neurodegenerative disease caused by mutations in the ETHE1 gene. It is characterized by early-onset encephalopathy, chronic diarrhea, petechiae, orthostatic acrocyanosis, and high levels of methylsuccinic, lactic, and ethylmalonic acids in body fluids. In this study, we report a patient with EE, who was identified through newborn screening, and the diagnosis was confirmed by targeted next-generation sequencing (NGS). The patient displayed recurrent petechiae, intermittent jaundice, protracted diarrhea, and extensive developmental regression. Genetic testing identified a homozygous nonsense variant, c.295C > T (p. Q99*), in the ETHE1 gene. A review of all known ETHE1 variants observed in other EE patients was conducted. This revealed the current difficulties in EE diagnosis. Besides, it also showed that patients with truncated variants of ETHE1 might exhibit pathological symptoms earlier and present more severe manifestations. Finally, a novel nonsense variant was identified, which supported and expanded our current knowledge of the variant spectrum for ETHE1. https://www.selleckchem.com/products/avelumab.html This novel variant also deepened our understanding of the genotype-phenotype associations that occur in EE patients.Background Here, we report on a head-to-head comparison of the fully-automated Elecsys® Anti-SARS-CoV-2 immunoassay with the EDITM enzyme linked immunosorbent assays (ELISA) for the detection of SARS-CoV-2 antibodies in human plasma. Methods SARS-CoV-2 antibodies were measured with the Elecsys® assay and the EDITM ELISAs (IgM and IgG) in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n = 104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. Results In COVID-19 patients, the percentage of positive results rose with time from symptom onset, peaking to positivity rates after 15-22 days of 100% for the Elecsys® assay, of 94% for the EDITM IgM-ELISA and of 100% for the EDITM IgG ELISA. In the 104 blood samples, the agreement between positive/negative classifications of the Elecsys® assay and the EDITM ELISAs (IgM or IgG) was 90%. The false positivity rates in the healthy blood donors and the ICU patients were less then 1% for the Elecsys® assay and less then 3% for the EDITM ELISAs. Conclusions Our results indicate a high sensitivity and specificity for the Elecsys® assay and an acceptable agreement with the EDITM ELISAs.Iron is essential for all the lives on earth but may trigger a switch toward ferroptosis, a novel form of regulated necrosis. Carbonic anhydrases (CAs) are ubiquitous enzymes from microbes to humans. The primary function of CAs is to regulate cellular pH by hydrating carbon dioxide (CO2) to protons (H+) and bicarbonate ions (HCO3-). Furthermore, CAs play roles in biosynthetic reactions, such as gluconeogenesis, lipogenesis, ureagenesis and are also associated with tumor metabolism, suggesting that CAs may be a potential target for the treatment of cancers. We have recently revealed a novel function of CA IX in ferroptosis-resistance by using human malignant mesothelioma cells. Herein, we aim to review the potential molecular association between ferroptosis and CAs, from the viewpoint of iron-metabolism, lipogenesis and signaling pathways both under physiological and pathological contexts.Actinoporins are a family of pore-forming toxins produced by sea anemones as part of their venomous cocktail. These proteins remain soluble and stably folded in aqueous solution, but when interacting with sphingomyelin-containing lipid membranes, they become integral oligomeric membrane structures that form a pore permeable to cations, which leads to cell death by osmotic shock. Actinoporins appear as multigenic families within the genome of sea anemones several genes encoding very similar actinoporins are detected within the same species. The Caribbean Sea anemone Stichodactyla helianthus produces three actinoporins (sticholysins I, II and III; StnI, StnII and StnIII) that differ in their toxic potency. For example, StnII is about four-fold more effective than StnI against sheep erythrocytes in causing hemolysis, and both show synergy. However, StnIII, recently discovered in the S. helianthus transcriptome, has not been characterized so far. Here we describe StnIII's spectroscopic and functional properties and show its potential to interact with the other Stns.
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  • In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.
    Campylobacter is the leading cause of bacterial gastroenteritis in the United States. We investigated the prevalence of postinfection irritable bowel syndrome (PI-IBS) in a cohort with culture-confirmed Campylobacter cases; risk factors for PI-IBS based on clinical factors; and shifts in IBS patterns postinfection in patients with pre-existing IBS.

    The Minnesota Department of Health collects data on symptoms and exposures upon notification of Campylobacter cases. From 2011 through 2019, we sent surveys (the Rome III and IBS symptom severity surveys) to 3586 patients 6 to 9 months after Campylobacter infection. The prevalence of PI-IBS was estimated and risk factors were assessed using multivariable logistic regression.

    There were 1667 responders to the survey, 249 of whom had pre-existing IBS. Of the 1418 responders without pre-existing IBS, 301 (21%) subsequently developed IBS. Most of these individuals had IBS-mixed (54%), followed by IBS-diarrhea (38%), and IBS-constipation (6%). The mean IBS symptomhenotype.
    In a cohort of patients with Campylobacter infection in Minnesota, 21% developed PI-IBS; most cases reported mixed IBS or diarrhea of moderate severity. Demographic and clinical factors during acute enterocolitis are associated with PI-IBS development. Campylobacter infection also can result in a switch of a pre-existing IBS phenotype.Vascular dementia (VaD) is one of the most common types of dementia followed by Alzheimer's disease (AD). Recent studies showed that approximately 30 %-35 % of patients with AD at post-mortem exhibited vascular pathologies, which suggested that mixed dementia may be the most common type of dementia. Permanent bilateral common carotid artery occlusion (2VO) is a well-characterized method for investigating cognitive functions and the histopathological consequences of chronic cerebral hypoperfusion (CCH) in rats. In the present study, we investigated the effects of environmental enrichment (EE) on cognitive impairment after CCH, as well as the effects of CCH-induced neurovascular damage on cognitive function. Wistar rats were randomly allocated to a sham group, a 2VO group, and a 2VO + EE group. https://www.selleckchem.com/products/Ilginatinib-hydrochloride.html The 2VO procedure was performed at 12 weeks, while EE was performed for 8 weeks before and 6 weeks after 2VO. The effect of EE on cognitive functions in 2VO rats was investigated using the radial-arm maze and Morris Water Maze tests. Neurovascular integrity was assessed based on immunoreactivity for glial fibrillary acidic protein (GFAP), morphological changes in microvessels, and the expression of matrix metalloproteinase-9 (MMP-9) and zonula occludens-1 (ZO-1) in the motor cortex and hippocampus. EE ameliorated microvessel fragmentation by sustaining the tight junction through increases of ZO-1 expression after CCH, resulting in preserving the neurovascular unit. In summary, EE mitigated cognitive impairment by restoring neurovascular integrity. These findings suggest that EE can be a valuable and meaningful environmental intervention for patients with cognitive impairment.Protein-mineral interaction is known to regulate biomineral stability and morphology. We hypothesise that fluid phases produce highly dynamic protein-mineral complexes involved in physiology and pathology of biomineralisation. Here, we specifically focus on calciprotein particles, complexes of vertebrate mineral-binding proteins and calcium phosphate present in the systemic circulation and abundant in extracellular fluids - hence the designation of the ensuing protein-mineral complexes as "mud in the blood". These complexes exist amongst other extracellular particles that we collectively refer to as "the particle zoo".
    High pneumococcal carriage density is a risk factor for invasive pneumococcal disease (IPD) and transmission, but factors that increase pneumococcal carriage density are still unclear.

    We undertook a cross-sectional study to evaluate the microbial composition, cytokine levels and pneumococcal carriage densities in samples from children presenting with an influenza-like illness (ILI) and asymptomatic healthy controls (HC).

    The proportion of children harbouring viral organisms (Relative risk (RR) 1.4, p = 0.0222) or ≥ 4 microbes at a time (RR 1.9, p < 0.0001), was higher in ILI patients than HC. ILI patients had higher IL-8 levels in nasal aspirates than HC (median [IQR], 265.7 [0 - 452.3] vs. 0 [0 - 127.3] pg/ml; p = 0.0154). Having an ILI was associated with higher pneumococcal carriage densities compared to HC (RR 4.2, p < 0.0001).

    These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community.
    These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community.
    To study the prevalence and distribution of HBV genotypes in Spain for the period 2000-2016.

    Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded.

    1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR 41-62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found.

    We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.
    We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.
    In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats. Campylobacter is the leading cause of bacterial gastroenteritis in the United States. We investigated the prevalence of postinfection irritable bowel syndrome (PI-IBS) in a cohort with culture-confirmed Campylobacter cases; risk factors for PI-IBS based on clinical factors; and shifts in IBS patterns postinfection in patients with pre-existing IBS. The Minnesota Department of Health collects data on symptoms and exposures upon notification of Campylobacter cases. From 2011 through 2019, we sent surveys (the Rome III and IBS symptom severity surveys) to 3586 patients 6 to 9 months after Campylobacter infection. The prevalence of PI-IBS was estimated and risk factors were assessed using multivariable logistic regression. There were 1667 responders to the survey, 249 of whom had pre-existing IBS. Of the 1418 responders without pre-existing IBS, 301 (21%) subsequently developed IBS. Most of these individuals had IBS-mixed (54%), followed by IBS-diarrhea (38%), and IBS-constipation (6%). The mean IBS symptomhenotype. In a cohort of patients with Campylobacter infection in Minnesota, 21% developed PI-IBS; most cases reported mixed IBS or diarrhea of moderate severity. Demographic and clinical factors during acute enterocolitis are associated with PI-IBS development. Campylobacter infection also can result in a switch of a pre-existing IBS phenotype.Vascular dementia (VaD) is one of the most common types of dementia followed by Alzheimer's disease (AD). Recent studies showed that approximately 30 %-35 % of patients with AD at post-mortem exhibited vascular pathologies, which suggested that mixed dementia may be the most common type of dementia. Permanent bilateral common carotid artery occlusion (2VO) is a well-characterized method for investigating cognitive functions and the histopathological consequences of chronic cerebral hypoperfusion (CCH) in rats. In the present study, we investigated the effects of environmental enrichment (EE) on cognitive impairment after CCH, as well as the effects of CCH-induced neurovascular damage on cognitive function. Wistar rats were randomly allocated to a sham group, a 2VO group, and a 2VO + EE group. https://www.selleckchem.com/products/Ilginatinib-hydrochloride.html The 2VO procedure was performed at 12 weeks, while EE was performed for 8 weeks before and 6 weeks after 2VO. The effect of EE on cognitive functions in 2VO rats was investigated using the radial-arm maze and Morris Water Maze tests. Neurovascular integrity was assessed based on immunoreactivity for glial fibrillary acidic protein (GFAP), morphological changes in microvessels, and the expression of matrix metalloproteinase-9 (MMP-9) and zonula occludens-1 (ZO-1) in the motor cortex and hippocampus. EE ameliorated microvessel fragmentation by sustaining the tight junction through increases of ZO-1 expression after CCH, resulting in preserving the neurovascular unit. In summary, EE mitigated cognitive impairment by restoring neurovascular integrity. These findings suggest that EE can be a valuable and meaningful environmental intervention for patients with cognitive impairment.Protein-mineral interaction is known to regulate biomineral stability and morphology. We hypothesise that fluid phases produce highly dynamic protein-mineral complexes involved in physiology and pathology of biomineralisation. Here, we specifically focus on calciprotein particles, complexes of vertebrate mineral-binding proteins and calcium phosphate present in the systemic circulation and abundant in extracellular fluids - hence the designation of the ensuing protein-mineral complexes as "mud in the blood". These complexes exist amongst other extracellular particles that we collectively refer to as "the particle zoo". High pneumococcal carriage density is a risk factor for invasive pneumococcal disease (IPD) and transmission, but factors that increase pneumococcal carriage density are still unclear. We undertook a cross-sectional study to evaluate the microbial composition, cytokine levels and pneumococcal carriage densities in samples from children presenting with an influenza-like illness (ILI) and asymptomatic healthy controls (HC). The proportion of children harbouring viral organisms (Relative risk (RR) 1.4, p = 0.0222) or ≥ 4 microbes at a time (RR 1.9, p < 0.0001), was higher in ILI patients than HC. ILI patients had higher IL-8 levels in nasal aspirates than HC (median [IQR], 265.7 [0 - 452.3] vs. 0 [0 - 127.3] pg/ml; p = 0.0154). Having an ILI was associated with higher pneumococcal carriage densities compared to HC (RR 4.2, p < 0.0001). These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community. These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community. To study the prevalence and distribution of HBV genotypes in Spain for the period 2000-2016. Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded. 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR 41-62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found. We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups. We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.
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