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In Alzheimer's disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology. The Liver X receptor (LXR) family, consisting of LXRα and LXRß, was reported to inhibit angiogenesis and particularly LXRα was shown to secure BBB stability, suggesting a major role in vascular function. In this study, we unravel the regulatory mechanism exerted by LXRα to preserve BBB integrity in human brain endothelial cells (BECs) and investigate its role during pathological conditions. We report that LXRα ensures BECs identity via constitutive inhibition of the transcription factor SNAI2. Accordingly, deletion of brain endothelial LXRα is associated with impaired DLL4-NOTCH signalling, a critical signalling pathway involved in vessel sprouting. A similar response was observed when BECs were exposed to hypoxia, with concomitant LXRα decrease and SNAI2 increase. In support of our cell-based observations, we report a general increase in vascular SNAI2 in the occipital cortex of AD patients with and without capCAA. Importantly, SNAI2 strongly associated with vascular amyloid-beta deposition and angiopoietin-like 4, a marker for hypoxia. In hypoxic capCAA vessels, the expression of LXRα may decrease leading to an increased expression of SNAI2, and consequently BECs de-differentiation and sprouting. Our findings indicate that LXRα is essential for BECs identity, thereby securing BBB stability and preventing aberrant angiogenesis. These results uncover a novel molecular pathway essential for BBB identity and vascular homeostasis providing new insights on the vascular pathology affecting AD patients.

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Fat necrosis of the breast is a commonly encountered condition in daily practice. It is a benign pathology, but it can have variable manifestations and patterns that may sometimes mimic malignancy, depending on its stage of evolution and its underlying cause. This review demonstrates the wide spectrum of appearances of fat necrosis on mammography, digital breast tomosynthesis (DBT), ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron-emission tomography (PET). Sequential follow-up images are included in some cases to illustrate the temporal change of the findings. The typical location and distribution of fat necrosis from a comprehensive list of aetiologies are discussed. Improved knowledge of the multimodality imaging features of fat necrosis could enhance diagnostic accuracy and clinical management, thus avoiding unnecessary invasive investigations.

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Physiological and pathological processes arising from the breast and anterior chest wall may share similar clinical presentations because of the small volume of male breasts. Therefore, imaging is frequently required to localise and characterise the lesion and guide biopsy when radiological findings are equivocal or suspicious. Mammography or digital breast tomosynthesis (DBT) and ultrasound are the mainstays of breast imaging work-up. Other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography (PET) can sometimes augment the investigation and aid treatment planning. This article reviews the key imaging features of a wide spectrum of benign and malignant conditions that involve the male breast and anterior chest wall across various age groups. Familiarisation with the salient radiological findings is essential for reaching an accurate diagnosis and optimising management.

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The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. Aggravatingly, CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. Crucially, however, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions be it primary, secondary or tertiary. This complementing article focuses on outlining and analyzing measures that can beimplemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management and treatment are often lacking. Hence, there is an urgent need to increase the awareness of the importance of preventive measures throughout populations, professionals and policy makers.

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INTRODUCTION: A magnetic seed marker system (Magseed, Endomagnetics, Cambridge, United Kingdom) is used as a localisation method for non-palpable breast lesions in the United States, Europe, and Hong Kong. It overcomes many limitations of conventional techniques and allows scheduling flexibility. We sought to evaluate its efficacy and safety in the Chinese population. METHODS: We retrospectively reviewed all Chinese women who underwent magnetic seed marker-guided breast lesion excision from June 2019 to February 2020 at a single institution. Placement success (final target-to-seed distance <10 mm) was evaluated by imaging on the day of surgery. Specimen radiographs and pathology reports were reviewed for magnetic seed markers and target removal. Margin clearance and re-excision rates were analysed. RESULTS: Twenty two magnetic seed markers were placed in 21 patients under sonographic or stereotactic guidance to localise 21 target lesions. One target lesion required two magnetic seed markers for bracketing. There was no migration of nine markers placed 6 to 56 days before the day of surgery. Placement success was achieved in 20 (90.9%) cases. Mean final target-to-seed distance was 3.1 mm. Two out of 21 (9.5%) lesions required alternative localisation due to marker migration ≥10 mm, while 19 (90.5%) lesions underwent successful magnetic seed marker-guided excision. Three of these 19 lesions (15.8%) were excised with therapeutic intent, one of which (33%) required re-excision due to a close margin. All 22 magnetic seed markers were successfully removed. No complications were reported. CONCLUSION: Magnetic seed markers demonstrated safety and efficacy in Chinese women for breast lesion localisation and excision.

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The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. Aggravatingly, CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplant consume up to 3% of the annual healthcare budget in high-income countries. However, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions - be they primary, secondary or tertiary. This complementing article focuses on outlining and analyzing measures that can be implemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney, urinary tracts, as well as the exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycaemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, the management of co-morbidities such as uraemia and cardiovascular disease is a highly recommended preventive intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate this preventive approach. While national policies and strategies for non-communicable diseases might be in place in all or every country. Also, specific policies directed toward education and awareness about CKD screening, management and treatment are often lacking. Hence, there is an urgent need to increase the awareness and importance of preventive measures among populations, professionals and policy makers.

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PURPOSE: Transfusion is associated with increased perioperative morbidity and mortality in patients undergoing total knee arthroplasty (TKA). Patient blood management (PBM) is an evidence-based approach to maintain blood mass via haemoglobin maintenance, haemostasis optimisation, and blood loss minimisation. The aim of the present study was to assess the effectiveness of a multimodal PBM approach in our centre. METHODS: This was a single-centre retrospective study of patients who underwent primary TKA in Queen Mary Hospital in Hong Kong in 2013 or 2018, using data from the Clinical Data Analysis and Reporting System and a local joint registry database. Patient demographics, preoperative haemoglobin, length of stay, readmission, mean units of transfusion, postoperative prosthetic joint infection, and mortality data were compared between groups. RESULTS: In total, 262 and 215 patients underwent primary TKA in 2013 and 2018, respectively. The mean transfusion rate significantly decreased after PBM implementation (2013: 31.3%; 2018: 1.9%, P<0.001); length of stay after TKA also significantly decreased (2013: 14.49±8.10 days; 2018: 8.77±10.14 days, P<0.001). However, there were no statistically significant differences in readmission, early prosthetic joint infection, or 90-day mortality rates between the two groups. CONCLUSION: Our PBM programme effectively reduced the allogeneic blood transfusion rate in patients undergoing TKA in our institution. Thus, PBM should be considered in current TKA protocols to reduce rates of transfusions and related complications.

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The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. However, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions - be it primary, secondary, or tertiary. This article focuses on outlining and analyzing measures that can be implemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management, and treatment are often lacking. Hence, there is an urgent need to increase the awareness of preventive measures throughout populations, professionals, and policy makers.

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The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. However, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions - be it primary, secondary, or tertiary. This article focuses on outlining and analyzing measures that can be implemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management, and treatment are often lacking. Hence, there is an urgent need to increase the awareness of preventive measures throughout populations, professionals, and policy makers.

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BACKGROUND: Mendelian randomization (MR) analyses have been increasingly used to seek evidence of causal associations. This systematic review aims at characterizing and evaluating the reporting of MR analyses in oncological studies. METHODS: The PubMed database was searched to identify MR cancer studies until December 31, 2017. Two of the authors independently selected and evaluated reporting quality of the studies. Reporting quality in MR studies before 2016 and in 2016/17 was compared. RESULTS: Cancer studies with MR analyses in 2016 and 2017 accounted for 55.8% of the total number of studies identified. In the 77 eligible articles, 39 (50.6%) did not report subjects' characteristics, 53 (68.8%) did not conduct power estimation, 40 (51.9%) did not state all of the first three MR assumptions (i.e., genetic instrument is associated with exposure, is not associated with confounders, and acts on outcome only through exposure), and 31 (40.3%) did not exclude SNPs that diverged from Hardy-Weinberg equilibrium. More studies estimated power in 2016/2017 than before 2016 (p = 0.028). CONCLUSIONS: Some MR cancer studies did not sufficiently report essential information, posing obstacles for critical appraisal. This study proposes for MR analysis a guideline/checklist for future publications in cancer and other biomedical research.

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The effectiveness and treatment conditions of FeCl3- and AlCl3-coagulated municipal sewage sludge from chemically enhanced primary treatment (CEPT) using anaerobic digestion (AD) and the structure of microbial community were investigated. The results based on 297 measurements under different operational conditions demonstrate good average AD performance of CEPT sludge, that is, percent volatile solid reduction of 58 %, specific biogas production (or biogas yield) of 0.92 m(3)/kg volatile solids (VS) destroyed, and methane content of 65.4 %. FeCl3 dosing, organic loading rate, temperature, and hydraulic retention time all significantly affected AD performance. FeCl3 dosing greatly improved specific methane production (methane yield) by 38-54 % and significantly reduced hydrogen sulfide (H2S) content in biogas (from up to 13,250 to <200 ppm), contributing to higher methane recovery and simplified biogas cleaning for power generation. Metagenomic analysis suggested that anaerobic digesters of both CEPT sludge and combined primary and secondary sludge were dominated by Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, Thermotogae, and Chloroflexi. However, Methanomicrobia methanogens were better enriched in the anaerobic digesters of CEPT sludge than in the combined sludge. Further, different sources of CEPT sludge with various chemical properties nurtured shared and unique microbial community composition. Combined, this study supports AD as an efficient technology for CEPT sludge treatment and poses first insights into the microbial community structure.

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In their recent article in Pharmacopsychiatry Verhoeven and Egger report a case series of 28 patients and state that "treatment of psychotic symptoms in patients with 22q11.2 deletion syndrome (22q11.2DS) with quetiapine or clozapine in combination with valproic acid appears likely to be more effective than with other psychotropic compounds". In this letter, we discuss the limitations of their case series and the lack of evidence for such a sweeping conclusion. In lieu of strong evidence to the contrary, standard pharmacological treatments of psychotic illness in 22q11.2DS remains recommended, with attention to 22q11.2DS-related issues. The latter would include management strategies to help ameliorate the elevated risk of seizures (e. g. when using clozapine), and vigilance for Parkinson's disease or other potential movement disorders.

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Conventional membrane bioreactor (MBR) systems have increasingly been studied in recent decades. However, their applications have been limited due to their drawbacks such as low flux, membrane fouling, and high operating cost. In this study, a compact macro-filtration MBR (MfMBR) process was developed by using a large pore size membrane to mitigate the membrane fouling problem. A pilot trial of MfMBR process was set up and operated to treat 10 m(3)/day of saline wastewater within 4 h. The system was operated under an average permeate flux of 13.1 m(3)/(m(2)·day) for 74 days. The average total suspended solids, total chemical oxygen demand, biological oxygen demand, total Kjeldahl nitrogen, and total nitrogen removal efficiencies achieved were 94.3, 83.1, 98.0, 93.1, and 63.3%, respectively, during steady-state operation. The confocal laser scanning microscopy image indicated that the backwash could effectively remove the bio-cake and dead bacteria. Thus, the results showed that the MfMBR process, which is essentially a primary wastewater treatment process, had the potential to yield the same high quality effluent standards as the secondary treatment process; thereby suggesting that it could be used as an option when the economic budget and/or land space is limited.

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OBJECTIVES: Delirium is common in older patients admitted to hospital. Information obtained from patient's relatives or caregivers may contribute to improved detection. Our aim was to develop a caregiver based questionnaire, the Informant Assessment of Geriatric Delirium (I-AGeD), to assist in better recognition of delirium in elderly patients. METHODS: A cross-sectional observational study using a scale construction patient cohort and two validation cohorts was conducted at geriatric departments of two teaching hospitals in The Netherlands. Delirium status, based on DSM-IV criteria, was assessed directly on admission by a geriatric resident and evaluated within the first 48 h of admission. Caregivers filled out a 37-item questionnaire of which 10 items were selected reflecting delirium symptoms, based on their discriminatory abilities, internal consistency and inter-item correlations. RESULTS: A total of 88 patients with complete study protocols in the construction cohort were included. Average age was 86.4 (SD 8.5), and 31/88 patients had delirium on admission. Internal consistency of the 10-item I-AGeD was high (Cronbach's alpha = 0.85). At a cut-off score of >4 sensitivity was 77.4% and specificity 63.2%. In patients without dementia, sensitivity was 100% and specificity 65.2%. Validation occurred by means of two validation cohorts, one consisted of 59 patients and the other of 33 patients. Sensitivity and specificity in these samples ranged from 70.0% to 88.9% and 66.7% to 100%, respectively. CONCLUSION: The newly constructed caregiver based I-AGeD questionnaire is a valid screening instrument for delirium on admission to hospital in geriatric patients.

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