Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases

INTRODUCTION: We explored how blood-brain barrier (BBB) leakage rate of gadolinium chelates (K trans) and BBB water exchange rate (k w) varied in cerebral small vessel disease (cSVD) subtypes. METHODS: Thirty sporadic cSVD, 40 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and 13 high-temperature requirement factor A serine peptidase 1 (HTRA) -related cSVD subjects were investigated parallel to 40 healthy individuals. Subjects underwent clinical, cognitive, and MRI assessment.RESULTS: In CADASIL, no difference in K trans, but lower k w was observed in multiple brain regions. In sporadic cSVD, no difference in k w, but higher K trans was found in the whole brain and normal-appearing white matter. In HTRA1-related cSVD, both higher K trans in the whole brain and lower k w in multiple brain regions were observed. In each patient group, the altered BBB measures were correlated with lesion burden or clinical severity. DISCUSSION: In cSVD subtypes, distinct alterations of k w and K trans were observed. The combination of K trans and k w can depict the heterogeneous BBB dysfunction. HIGHLIGHTS: We measured BBB leakage to gadolinium-based contrast agent (K trans) and water exchange rate (k w) across BBB in three subtypes of cSVD. CADASIL is characterized by lower k w, HTRA1-related cSVD exhibits both higher K trans and lower k w, while sporadic cSVD is distinguished by higher K trans. There are distinct alterations in k w and K trans among subtypes of cSVD, indicating the heterogeneous nature of BBB dysfunction. </p

Diagnosis of mixed infection and a primary immunodeficiency disease using next-generation sequencing: a case report

Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS

A MODIFIED FOUR-QUADRANT FREQUENCY DISCRIMINATOR FOR CARRIER FREQUENCY ACQUISITION OF GPS RECEIVERS

ITC/USA 2005 Conference Proceedings / The Forty-First Annual International Telemetering Conference and Technical Exhibition / October 24-27, 2005 / Riviera Hotel & Convention Center, Las Vegas, NevadaThe four-quadrant frequency discriminator (FQFD) plays an important role in GPS receivers for carrier synchronization. This paper presents a detailed study of the operating principle of the FQFD, and the acquisition performance degradation due to the gain fluctuation of the FQFD is discussed. A modified FQFD called the enveloped-four-quadrant frequency discriminator (Enveloped-FQFD) is proposed, which introduces an envelope calculator on the basis of the FQFD. Performance comparison of the FQFD and the Enveloped-FQFD is given through theoretical analysis and computer simulation. Simulation results show that by employing the Enveloped-FQFD, a quicker pull-in process and a wider threshold than the FQFD can be achieved, while the additional hardware costs are trivial.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

SOFT SEAMLESS SWITCHING IN DUAL-LOOP DSP-FLL FOR RAPID ACQUISITION AND TRACKING

International Telemetering Conference Proceedings / October 18-21, 2004 / Town & Country Resort, San Diego, CaliforniaFLL’s are extensively used for fast carrier synchronization. A common approach to meet the wide acquisition range and sufficiently small tracking error requirements is to adopt the wide or narrow band FLL loop in the acquisition and tracking modes and direct switching the loop. The paper analyze the influence of direct switching on performance, including the narrow band loop convergence, transition time etc. and propose applying the Kalman filtering theory to realize the seamless switching (SS) with time-varying loop gains between the two different loop tracking state. The SS control gains for the high dynamic digital spread spectrum receiver is derived. Simulation results for the SS compared to the direct switching demonstrate the improved performance.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

Study on Water Purification Effect and Operation Parameters of Various Units of Wastewater Circulation

The discharge of wastewater from aquaculture ponds causes a certain degree of damage to the environment. It is necessary to continuously improve the treatment efficiency of wastewater treatment devices. The purpose of this study is to obtain an optimal ratio of wastewater circulation devices in order to obtain the best operating parameters and to reduce the discharge of polluted water. We constructed an experimental wastewater circulation device consisting of three units. The primary unit contained modified attapulgite (Al@TCAP-N), volcanic stone, and activated carbon for precipitation. The secondary and tertiary units used biological methods to enhance removal rates of nitrogen and phosphorus. Water quality indicators of total phosphorus (TP), total nitrogen (TN), ammonia (NH3-N), permanganate (CODMn), and total suspended solids (TSS) were detected. Water quality was tested under different matching ratios for three units of different hydraulic retention time (HRT) and load Results showed that the removal rate of TP, TN, NH3-N, and TSS reached 20–60%, 20%, 30–70%, and 10–80%, respectively. The average reduction efficiencies of secondary module chlorella and filler on TP, TN, NH3-N, CODMn, and TSS were 56.88%, 30.09%, 0.43%, 46.15%, and 53.70%, respectively. The best removal rate can be achieved when the matching ratio of each unit becomes 2:1:1 and the hydraulic retention time is maintained within 2 h in the high-concentration load. Finally, the average removal rates of TP, TN, NH3-N, and TSS reached 58.87%, 15.96%, 33.99%, and 28.89%, respectively. The second unit obtained the enhanced removal effect in this wastewater treatment system when adding microorganisms and activated sludge

Study on Water Purification Effect and Operation Parameters of Various Units of Wastewater Circulation

The discharge of wastewater from aquaculture ponds causes a certain degree of damage to the environment. It is necessary to continuously improve the treatment efficiency of wastewater treatment devices. The purpose of this study is to obtain an optimal ratio of wastewater circulation devices in order to obtain the best operating parameters and to reduce the discharge of polluted water. We constructed an experimental wastewater circulation device consisting of three units. The primary unit contained modified attapulgite (Al@TCAP-N), volcanic stone, and activated carbon for precipitation. The secondary and tertiary units used biological methods to enhance removal rates of nitrogen and phosphorus. Water quality indicators of total phosphorus (TP), total nitrogen (TN), ammonia (NH3-N), permanganate (CODMn), and total suspended solids (TSS) were detected. Water quality was tested under different matching ratios for three units of different hydraulic retention time (HRT) and load Results showed that the removal rate of TP, TN, NH3-N, and TSS reached 20&ndash;60%, 20%, 30&ndash;70%, and 10&ndash;80%, respectively. The average reduction efficiencies of secondary module chlorella and filler on TP, TN, NH3-N, CODMn, and TSS were 56.88%, 30.09%, 0.43%, 46.15%, and 53.70%, respectively. The best removal rate can be achieved when the matching ratio of each unit becomes 2:1:1 and the hydraulic retention time is maintained within 2 h in the high-concentration load. Finally, the average removal rates of TP, TN, NH3-N, and TSS reached 58.87%, 15.96%, 33.99%, and 28.89%, respectively. The second unit obtained the enhanced removal effect in this wastewater treatment system when adding microorganisms and activated sludge

Homozygous IL37 mutation associated with infantile inflammatory bowel disease.

Interleukin (IL)-37, an antiinflammatory IL-1 family cytokine, is a key suppressor of innate immunity. IL-37 signaling requires the heterodimeric IL-18R1 and IL-1R8 receptor, which is abundantly expressed in the gastrointestinal tract. Here we report a 4-mo-old male from a consanguineous family with a homozygous loss-of-function IL37 mutation. The patient presented with persistent diarrhea and was found to have infantile inflammatory bowel disease (I-IBD). Patient cells showed increased intracellular IL-37 expression and increased proinflammatory cytokine production. In cell lines, mutant IL-37 was not stably expressed or properly secreted and was thus unable to functionally suppress proinflammatory cytokine expression. Furthermore, induced pluripotent stem cell-derived macrophages from the patient revealed an activated macrophage phenotype, which is more prone to lipopolysaccharide and IL-1β stimulation, resulting in hyperinflammatory tumor necrosis factor production. Insights from this patient will not only shed light on monogenic contributions of I-IBD but may also reveal the significance of the IL-18 and IL-37 axis in colonic homeostasis