Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer.
Sirtuins are NAD+-dependent deacylases that play crucial roles in the regulation of cellular metabolism, and as a result, are implicated in several diseases. The mitochondrial sirtuin Sirt4, for a long time considered as mainly a mono-ADP-ribosyltransferase, recently has shown a robust deacylase activity in addition to the already accepted substrate-dependent lipoamidase and deacetylase properties. Through these and likely other enzymatic and non-enzymatic activities, Sirt4 closely controls various metabolic events, and its dysregulation is linked to various aging-related disorders, including type 2 diabetes, cardiac hypertrophy, non-alcoholic fatty liver disease, obesity, and cancer. For its capability to inhibit glutamine catabolism and for the modulation of genome stability in cancer cells in response to different DNA-damaging conditions, Sirt4 is proposed as either a mitochondrial tumor suppressor or a tumor-promoting protein in a context-dependent manner. In addition to what is already known about the roles of Sirt4 in different biological settings, further studies are certainly still needed in order to validate this enzyme as a new potential target for various aging diseases.


Current state of knowledge on porcine circovirus type 2-associated lesions.
Porcine circovirus type 2 (PCV2), a small single-stranded DNA virus, was initially discovered in 1998 and is highly prevalent in the domestic pig population. Disease manifestations associated with PCV2 include postweaning multisystemic wasting disease (PMWS), enteric disease, respiratory disease, porcine dermatitis and nephropathy syndrome (PDNS), and reproductive failure. Although these clinical manifestations involve different organ systems, there is considerable overlap in clinical expression of disease and presence of lesions between pigs and within herds. It is now widely accepted that PCV2 can be further subdivided into different types, of which PCV2a and PCV2b are present worldwide and of greatest importance. This review will focus on PCV2-associated lesions in different organ systems.


Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans.
Innate immunity in Caenorhabditis elegans requires a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway that regulates the basal and pathogen-induced expression of immune effectors. The mechanisms by which PMK-1 p38 MAPK regulates the transcriptional activation of the C. elegans immune response have not been identified. Furthermore, in mammalian systems the genetic analysis of physiological targets of p38 MAPK in immunity has been limited. Here, we show that C. elegans ATF-7, a member of the conserved cyclic AMP-responsive element binding (CREB)/activating transcription factor (ATF) family of basic-region leucine zipper (bZIP) transcription factors and an ortholog of mammalian ATF2/ATF7, has a pivotal role in the regulation of PMK-1-mediated innate immunity. Genetic analysis of loss-of-function alleles and a gain-of-function allele of atf-7, combined with expression analysis of PMK-1-regulated genes and biochemical characterization of the interaction between ATF-7 and PMK-1, suggest that ATF-7 functions as a repressor of PMK-1-regulated genes that undergoes a switch to an activator upon phosphorylation by PMK-1. Whereas loss-of-function mutations in atf-7 can restore basal expression of PMK-1-regulated genes observed in the pmk-1 null mutant, the induction of PMK-1-regulated genes by pathogenic Pseudomonas aeruginosa PA14 is abrogated. The switching modes of ATF-7 activity, from repressor to activator in response to activated PMK-1 p38 MAPK, are reminiscent of the mechanism of regulation mediated by the corresponding ancestral Sko1p and Hog1p proteins in the yeast response to osmotic stress. Our data point to the regulation of the ATF2/ATF7/CREB5 family of transcriptional regulators by p38 MAPK as an ancient conserved mechanism for the control of innate immunity in metazoans, and suggest that ATF2/ATF7 may function in a similar manner in the regulation of mammalian innate immunity.


An Approach to Speed up Single-Frequency PPP Convergence with Quad-Constellation GNSS and GIM.
The single-frequency precise point positioning (PPP) technique has attracted increasing attention due to its high accuracy and low cost. However, a very long convergence time, normally a few hours, is required in order to achieve a positioning accuracy level of a few centimeters. In this study, an approach is proposed to accelerate the single-frequency PPP convergence by combining quad-constellation global navigation satellite system (GNSS) and global ionospheric map (GIM) data. In this proposed approach, the GPS, GLONASS, BeiDou, and Galileo observations are directly used in an uncombined observation model and as a result the ionospheric and hardware delay (IHD) can be estimated together as a single unknown parameter. The IHD values acquired from the GIM product and the multi-GNSS differential code bias (DCB) product are then utilized as pseudo-observables of the IHD parameter in the observation model. A time varying weight scheme has also been proposed for the pseudo-observables to gradually decrease its contribution to the position solutions during the convergence period. To evaluate the proposed approach, datasets from twelve Multi-GNSS Experiment (MGEX) stations on seven consecutive days are processed and analyzed. The numerical results indicate that the single-frequency PPP with quad-constellation GNSS and GIM data are able to reduce the convergence time by 56%, 47%, 41% in the east, north, and up directions compared to the GPS-only single-frequency PPP.


Assessment of renal function in geriatric palliative care patients - comparison of creatinine-based estimation equations.
Renal function impairment is common in geriatric palliative care patients. Accurate assessment of renal function is necessary for appropriate drug dosage. Several equations are used to estimate kidney function. 1) To investigate the differences (Δ) in kidney function assessed with simplified Modifi-cation of Diet in Renal Disease (MDRD), Berlin Initiative Study (BIS1), and Cockcroft-Gault (C-G) formulas in geriatric palliative care patients, and 2) to assess factors that may influence these differences. A retrospective analysis of data of patients aged ≥70 years admitted to a palliative care in-patient unit. The agreement between C-G, MDRD, and BIS1 equations was assessed with Bland-Altman analysis. Partial correlation analysis was used to analyze factors influencing the discordance. A total of 174 patients (67 men; mean age 77.9±5.8 years) were enrolled. The mean Δ MDRD and C-G was 18.6 (95% limits of agreement 55.3 and -18.2). The mean Δ BIS1 and C-G was 6.1 (25.7 and -13.5), and the mean Δ MDRD and BIS1 was 12.5 (40.6 and -15.6). According to the National Kidney Foundation classification, 61 (35.1%) patients were differently staged using MDRD and C-G, whilê20% of patients were differently staged with BIS1 and C-G and MDRD and BIS1. Serum creatinine (SCr) and body mass index (BMI) had the most important influence on variability of Δ MDRD and C-G (partial R2 37.7% and 28.4%). Variability of Δ BIS1 and C-G was mostly influenced by BMI (34.8%) and variability of Δ MDRD and BIS1 by SCr (42.2%). Age had relatively low influence on differences between equations (3.1%-9.5%). There is a considerable disagreement between renal function estimation formulas, especially MDRD and C-G in geriatric palliative care patients, which may lead to errors in drug dosage adjustment. The magnitude of discrepancy increases with lower SCr, lower BMI, and higher age.


Venous thromboembolism in morbid obesity and trauma. A review of literature.
Deep venous thromboembolism (DVT) is common and leads to disability, economic loss and even death. The aims of this paper are to start from the basic knowledge that we have about DVT and to tailor our knowledge to the treatment and diagnosis of thromboembolism in obese patients and trauma patients, which are among the patients who have a high risk of developing DVT and pulmonary embolism. Venous thromboembolism is a common complication in patients with major trauma, and effective, safe prophylactic regimens are needed. The patients are treated effectively with heparin and low molecular weight heparins, which are shown to be safe and effective. Morbid obesity is a disease that affects 10% of Americans and increases the incidence of DVT. Forty mg of enoxaparin subcutaneously twice a day seems to be a better DVT prophylaxis than the 30 mg twice a day. Many patients admitted to the hospital are morbidly obese; therefore, we suggest they start on low molecular heparin. The high morbidity of these patients is because most of them are bedridden, which increases the chance of DVT and death from pulmonary embolism. Trauma increases the chance of having DVT. Low molecular weight heparin or heparin is a safe and extremely effective method of preventing DVT in high-risk trauma patients.


Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies.
Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) is a common neuropathological subtype of frontotemporal dementia. Although this subtype of frontotemporal dementia is defined by the presence of ubiquitin-positive but tau- and alpha-synuclein-negative inclusions, it is unclear whether all cases of FTLD-U have the same underlying pathogenesis. Examination of tissue sections from FTLD-U brains stained with anti-ubiquitin antibodies revealed heterogeneity in the morphological characteristics of pathological inclusions among subsets of cases. Three types of FTLD-U were delineated based on morphology and distribution of ubiquitin-positive inclusions. To address the hypothesis that FTLD-U is pathologically heterogeneous, novel monoclonal antibodies (mAbs) were generated by immunization of mice with high molecular mass (Mr > 250 kd) insoluble material prepared by biochemical fractionation of FTLD-U brains. Novel mAbs were identified that immunolabeled all of the ubiquitin-positive inclusions in one subset of FTLD-U cases, whereas other mAbs stained the ubiquitin-positive inclusions in a second subset of cases. These novel mAbs did not stain inclusions in other neurodegenerative disorders, including tauopathies and alpha-synucleinopathies. Therefore, ubiquitin immunohistochemistry and the immunostaining properties of the novel mAbs generated here suggest that FTLD-U is pathologically heterogeneous. Identification of the disease proteins recognized by these mAbs will further advance understanding of molecular substrates of FTLD-U neurodegenerative pathways.


The minimum information required for a glycomics experiment (MIRAGE): reporting guidelines for capillary electrophoresis.
The Minimum Information Required for a Glycomics Experiment (MIRAGE) is an initiative to standardize the reporting of glycoanalytical methods and to assess their reproducibility. To date, the MIRAGE Commission has published several reporting guidelines that describe what information should be provided for sample preparation methods, mass spectrometry methods, liquid chromatography analysis, exoglycosidase digestions, glycan microarray methods, and nuclear magnetic resonance methods. Here, we present the first version of reporting guidelines for glyco(proteo)mics analysis by capillary electrophoresis (CE) for standardized and high-quality reporting of experimental conditions in the scientific literature. The guidelines cover all aspects of a glyco(proteo)mics CE experiment including sample preparation, CE operation mode (CZE, CGE, CEC, MEKC, cIEF, cITP), instrument configuration, capillary separation conditions, detection, data analysis, and experimental descriptors. These guidelines are linked to other MIRAGE guidelines and are freely available through the project website https://www.beilstein-institut.de/en/projects/mirage/guidelines/#ce_analysis (doi:10.3762/mirage.7).


Ethics, evidence, and public policy.
The growth of evidence-based medicine (EBM) raises a number of ethical issues that have too often been overlooked. These include issues that arise when clinicians make judgments under uncertainty, new challenges for the clinician-patient relationship, new duties for institutional review boards, issues in physician autonomy and reimbursement, and challenges for disclosure and informed consent. Ethics and EBM must be addressed by policy makers and integrated into medical education.


Antagonizing Peroxisome Proliferator-Activated Receptor α Activity Selectively Enhances Th1 Immunity in Male Mice.
Females exhibit more robust Th1 responses than males. Our previous work suggested that this sex disparity is a consequence of higher activity of the androgen-induced gene peroxisome proliferator-activated receptor α (PPARα) in male CD4(+) T cells. The objective of this study was to elucidate the cellular and molecular mechanism of how PPARα inhibits Th1 responses in male mice. In this study, we found that PPARα functions within CD4(+) and CD8(+) T lymphocytes and NKT cells to negatively regulate IFN-γ responses in male mice and identified Ifng as the gene target of PPARα repression. Treatment of male CD4(+) T cells with the PPARα agonist fenofibrate induced the recruitment of PPARα and the nuclear receptor-interacting protein, nuclear receptor corepressor 1, to specific cis-regulatory elements in the Ifng locus. This recruitment associated with reduced histone acetylation at these sites. Knockdown of nuclear receptor corepressor 1 in primary male T cells abolished the effect of fenofibrate in reducing IFN-γ production. In contrast, treatment of male T cells with IS001, a novel antagonist of PPARα, increased Ifng gene expression and histone acetylation across the Ifng locus. Finally, we investigated the effects of IS001 on IFN-γ responses in mice during infection with the Th1-associated pathogen Listeria monocytogenes and observed that IS001 enhanced IFN-γ production by NKT, CD4(+), and CD8(+) T cells and improved the survival of male, but not female, mice. Our findings provide a novel mechanism of why IFN-γ responses are more robust in females and introduce a small-molecule IS001 that can be used to enhance Th1 immunity in males.


Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized, double-blind, clinical trials.
To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials. Adult patients with CAP eligible for oral therapy (Study 1, n = 448; Study 2, n = 575) received telithromycin 800 mg once daily for 10 (Study 1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500 mg twice daily for 10 days. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use, as well as CAP-related length of hospital stay and hospitalization costs, were compared by treatment group (intent to treat populations) up until the late post-therapy visit (Days 31-36). Study investigators blinded to treatment regimen assessed whether hospital admissions were CAP related. Despite equivalent clinical efficacy for telithromycin vs clarithromycin in the clinically evaluable per-protocol populations (n = 784) (88.8% [428/482] vs 90.1% [272/302]--difference: -1.3%; 95% CI: -6.0, 3.4), telithromycin treatment for 5, 7, or 10 days was associated with significantly fewer CAP-related hospitalizations (p = 0.023) and CAP-related hospital days (p = 0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital days per 100 patients). Accordingly, estimated CAP-related hospitalization costs were significantly lower (p = 0.025) for telithromycin recipients (30,231 US dollars less per 100 patients). CAP-related hospitalizations, duration of hospital stay, and hospitalization costs for 7- to 10-day telithromycin--the approved dosing regimen for CAP--were significantly lower (p = 0.023, 0.025, and 0.025, respectively) than for clarithromycin. Data from this study indicate that telithromycin 800 mg once daily for 5, 7, or 10 days provides an effective therapy for patients with CAP, and may be associated with fewer CAP-related hospitalizations and hospital days than clarithromycin 500 mg twice daily for 10 days. Treatment with telithromycin could, therefore, potentially translate into cost savings in the management of CAP.


Tularaemia - a diagnostic challenge.
Tularaemia is an infrequently occurring disease in Poland. It has therefore rarely been taken into account in the differential diagnosis of skin lesions, lymphadenitis, or soft tissue abscesses. This fact, accompanied by non-specific initial presentation, may lead to a delay in diagnosis and a more severe course of the disease. Objective. The aim of the study is to present the current state of knowledge on tularaemia and convince medical professionals to take it into consideration in the diagnosis of skin lesions, lymphadenitis, and tissue abscesses. A literature review using PubMed and other online resources, using terms including 'tularaemia', 'lymphadenitis', etc., was undertaken. Papers were reviewed for relevance and scientific merit. Tularaemia, also known as 'rabbit fever', is a zoonotic infection caused by Francisella tularensis, an aerobic, facultative intracellular, gram-negative bacteria. In Europe, it is mainly spread via tick bites and contact with wild animals such as lagomorphs and rodents. Clinical presentation may differ depending on the transmission route; the ulceroglandular and glandular forms of disease predominate. An early diagnosis and implementation of appropriate antibiotic therapy are the cornerstones of successful treatment and make it possible to avoid a surgical incision and drainage of suppurative complications. Raised awareness and knowledge on tularaemia among health care professionals are required for timely diagnosis and treatment. Arrival from endemic areas, contact with wild animals, tick bites, and exclusion of more common etiologies of presenting signs should prompt consideration of tularaemia. More research is needed for a better understanding of the burden of the disease and its impact on public health in Poland.


Extrusion-Based 3D Printing of Poly(ethylene glycol) Diacrylate Hydrogels Containing Positively and Negatively Charged Groups.
Hydrogels are an interesting class of materials used in extrusion-based 3D printing, e.g., for drug delivery or tissue engineering. However, new hydrogel formulations for 3D printing as well as a detailed understanding of crucial formulation properties for 3D printing are needed. In this contribution, hydrogels based on poly(ethylene glycol) diacrylate (PEG-DA) and the charged monomers 3-sulfopropyl acrylate and [2-(acryloyloxy)ethyl]trimethylammonium chloride are formulated for 3D printing, together with Poloxamer 407 (P407). Chemical curing of formulations with PEG-DA and up to 5% (w/w) of the charged monomers was possible without difficulty. Through careful examination of the rheological properties of the non-cured formulations, it was found that flow properties of formulations with a high P407 concentration of 22.5% (w/w) possessed yield stresses well above 100 Pa together with pronounced shear thinning behavior. Thus, those formulations could be processed by 3D printing, as demonstrated by the generation of pyramidal objects. Modelling of the flow profile during 3D printing suggests that a plug-like laminar flow is prevalent inside the printer capillary. Under such circumstances, fast recovery of a high vicosity after material deposition might not be necessary to guarantee shape fidelity because the majority of the 3D printed volume does not face any relevant shear stress during printing.


Aldolase A Promotes Colorectal Cancer Progression through Targeting COPS6 and Regulating MAPK Signaling Pathway.
Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms remain to be further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the role and mechanisms of ALDOA in CRC are still unclear. In the current study, high expression levels and enzymatic activity of ALDOA were detected in CRC tissues and cell lines, indicating the clinical significance of ALDOA in human CRC. In addition, silencing ALDOA significantly impaired the proliferation and metastasis of CRC cells in vitro and in vivo. Mechanistically, immunoprecipitation assays and mass spectrometry analysis identified the binding protein COPS6 of ALDOA. Furthermore, the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by COPS6 depletion, demonstrating COPS6 was required for ALDOA in mediating CRC progress. Moreover, the epithelial-mesenchymal transition (EMT) program and MAPK signaling pathway were found to be activated by ALDOA overexpression as well. In summary, our findings suggested that ALDOA facilitated the proliferation and metastasis of CRC by binding and regulating COPS6, inducing EMT, and activating the mitogen-activated protein kinase (MAPK) signaling pathway. The present study provided evidence for ALDOA as a promising potential biomarker for CRC.


Cerebrospinal fluid chitinase-3-like protein 1 level is not an independent predictive factor for the risk of clinical conversion in radiologically isolated syndrome.
Younger age, male sex and presence of spinal cord lesion(s) increase the risk of conversion from radiologically isolated syndrome (RIS) to relapsing-remitting multiple sclerosis (RRMS). Elevated cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) levels predict conversion from clinically isolated syndrome (CIS) to RRMS. To evaluate the prognostic value of CSF CHI3L1 in RIS patients for conversion to RRMS. We compared CSF CHI3L1 concentrations in RIS, CIS, RRMS and symptomatic controls (SCs). We analysed the influence of epidemiological, radiological and CSF parameters on the risk of clinical event. A total of 211 patients (71 RIS, 48 CIS, 50 RRMS and 42 SC) were included. CSF CHI3L1 levels were lower in RIS than in RRMS and higher in RIS with positive CSF versus negative CSF and SC. The presence of at least one spinal cord lesion was the only independent predictor of faster conversion to RRMS. Association of high CSF CHI3L1 levels, positive CSF (presence of oligoclonal bands and/or an elevated IgG index) or four Barkhof criteria with any spinal cord lesion showed a tendency for reduced mean conversion time. CSF CHI3L1 correlates with positive CSF but is not an independent predictor of the risk of conversion from RIS to RRMS.


Comparison of SPECT/CT and Planar Lympho-scintigraphy in Sentinel Node Biopsies of Oral Cavity Squamous Cell Carcinomas.
Evidence supporting the use of Sentinel node biopsy (SNB) for nodal staging of early oral squamous cell carcinomas (OSCC) appears to be very promising. Pre-operative lymphatic mapping using planar lymphoscinitigraphy (PL) with or without SPECT/CT in the SNB procedure is useful in sentinel node localization and for planning appropriate surgery. Recently, a large prospective multi-centric study evaluating SNB in cutaneous melanoma, breast and pelvic malignancies, demonstrated that adding SPECT to PL leads to surgical adjustments in a considerable number of patients. Our aim of this study was to evaluate the incremental value of additional SPECT/CT over PL alone in SNB for OSCC. This was a retrospective analysis of 44 patients (40- tongue, 4- buccal mucosa) with T1-T2, clinically N0 oral cavity SCC who underwent sentinel node biopsy procedure. PL and SPECT lymphoscinitigraphy images were compared for pre-operative mapping of sentinel nodes. Using a handheld gamma probe, a total of 179 sentinel nodes were harvested, with a mean of 4.06 per patient. PL revealed 75 hotspots with a mean of 1.70 per patient, and SPECT/CT revealed 92 hotspots with a mean of 2.09 per patient. Additional hotpots were identified in 14 patients on SPECT/CT, which included 4 patients, where PL did not detect any sentinel nodes. Pre-operative SPECT/CT in addition to planar lympho-scinitigraphy in sentinel node biopsies of oral cavity SCC detects more number of sentinel nodes compared to planar imaging alone. The higher sensitivity of SPECT combined with better anatomical localization using diagnostic CT may further improve the precision of SNB procedure.


Current condition of genetic medicine for hereditary breast cancer.
BRCA1 or BRCA2 (BRCA1/2) germline mutations, which cause hereditary breast and ovarian cancer syndrome, have been studied to develop targeted therapies for these associated cancer types. The BRCA1/2 test has been implemented in more than one hundred medical facilities in a clinical setting in Japan. The purpose of the current study is to document the prevalence and the awareness of genetic medicine for all hereditary breast cancer (HBC) including the BRCA1/2 test in Japan. The self-administered questionnaire was sent to 120 medical facilities where the BRCA1/2 test was provided, and 83 health care professionals participated (response rate, 69.2%). Of the all respondents, 33.7% (N=42) were clinical geneticists, 31.3% (N=26) other physicians, 15.7% (N=13) genetic counselors and 2.4% (N=2) nurses. In the most recent one-year period, in 83.1% of the 69 facilities the number of patients who underwent genetic testing for HBC was <10 and only 4 facilities provided multigene panel testing for HBC. In order to facilitate the access to genetic medicine, the majority of the genetic counselors (58.3%) recognized the need for education of healthcare professionals. Although the awareness of and interests in HBC have increased gradually, the equitable access to precision medicine is considered to be a challenging issue in Japan.


Peierls transitions in ionic organic charge-transfer crystals with spin and charge degrees of freedom.
The quasi-one-dimensional electronic structure of organic charge-transfer (CT) salts rationalizes Peierls transitions in mixed or segregated stacks of pi-electron donors (D) and acceptors (A). A microscopic Peierls-Hubbard model, HCT, is presented for CT salts with mixed stacks (Drho+Arho-)n and ionicity rho > 0.7. Dimerization opens a Peierls gap that, due to electron correlation, is the singlet-triplet gap, EST. In contrast to spin-Peierls systems, such as Heisenberg spin chains with rho = 1 and TSP < 20 K, Peierls transitions in CT salts with rho < 1 occur at higher TP and involve both spin and charge degrees of freedom. Linear electron-phonon coupling and an adiabatic approximation for a harmonic lattice are used to model the dimerization amplitude deltaT for T < TP, the magnetic (spin) susceptibility chiT, and the relative infrared intensity of totally symmetric molecular modes. Exact thermodynamics of HCT for stacks up to N = 12 sites are applied to two CT salts with TP approximately 50 and 120 K whose magnetism and infrared have not been modeled previously and to CT salts with inaccessibly high TP > 350 K whose description has been difficult. Ionic CT salts are correlated Peierls systems with a degenerate ground state (GS) at T = 0 whose elementary excitations are spin solitons, while dimerized ion-radical stacks that support triplet-spin excitons have nondegenerate GS. In less ionic CT salts, modulation of HCT parameters on cooling or under pressure leads to Peierls and/or neutral-ionic transitions of the GS, without appreciable thermal population of excited states. Correlations change the gap equation that relates EST at T = 0 to TP compared to free electrons, and size convergence is fast in stacks with large delta0 and high TP.


A retrospective study of treatment efficacy of 65 children with ametroic amblyopia.
To investigate relationship between treatment efficacy and the severity of ametropic amblyopia, the type of anisometropia and patient age. A total of 65 children with ametropic amblyopia undergoing clinical treatment in the ophthalmology department of Shaoguan Hygienic Hospital of Women and Children between June 2005 and November 2011 were enrolled in this study. The treatment efficacy for those subjects with different severities of ametropic amblyopia, types of anisometropia and ages was recorded. The near-recovery/recovery rate, improvement rate and ineffectiveness rate were 70.8%, 16.9% and 12.3%, respectively. The recovery rates in mild-, moderate- and severe amblyopia groups were 97.1%, 61.1% and 8.3% respectively (P<0.05). The recovery rate for patients with hyperopic-, astigmatic- and myopic anisometropia were 75.8%, 78.3% and 33.3% respectively. The recovery rates did not differ between hyperopic- and astigmatic- anisometropia children (P>0.05), whereas a statistically significant difference was noted between myopic children compared with their hyperopic and myopic-anisometropia counterparts (all P<0.05). The recovery rate for patients aged 3 to 6 years was 86.8% and 48.1% for those aged between 7 and 10 years (P<0.05). The treatment efficacy in ametropic amblyopia is associated with the severity of amblyopia, type of anisometropia and patient's age. Older patients with more severe amblyopia had poorer treatment efficacy. The efficacy in patients with hyperopic and astigmatic anisometropia was better than that for myopic anisometropia subjects.


[The bioutilization of thiodiglycol (a breakdown product of mustard gas): isolation of degraders and investigation of degradation conditions].
The Alcaligenes xylosoxydans subsp. denitrificans strain TD1 capable of degrading thiodiglycol (TDG), a breakdown product of mustard gas, was isolated from soil contaminated with breakdown products of this chemical warfare agent. The selected stable variant of TD1 (strain TD2) can grow on TDG with a lag phase of 4-8 h and a specific growth rate of 0.04-0.045 h-1. Optimal conditions for the biodegradation of TDG (pH, the concentration of TDG in the medium, and its relative content with respect to the bacterial biomass) were determined. TDG was found to be degraded with the formation of diglycolsulfoxide and thiodiglycolic acid. The data obtained can be used to develop approaches to the bioremediation of mustard gas-contaminated soils.


Electrographic recording from bovine vomeronasal capsule under spontaneous and stimulated conditions.
The vomeronasal organ ( VNO ) is an accessory olfactory system which in many vertebrates seems to be involved in reproductive behavior, particularly in permitting males to detect estrus in conspecific females. We postulated that EEG-like field potentials could be recorded from the VNO because the organ has a sensory epithelium that can discharge in response to odorants, and because VNO receptor cells are structurally similar to cells in the olfactory mucosa that produce field potentials (the "electro- olfactogram "). We examined this postulate in male cattle by surgically implanting recording/perfusion cannulae into the ducts leading to each VNO . Both bipolar (between VNOs ) and reference recording revealed continuous spontaneous voltage fluctuations that were similar to an EEG, except that amplitudes were larger and frequencies slower. Simultaneous recording of the EEG and VNO , using the same nasal reference electrode revealed that neither signal was "contaminated" by voltages from the other. Perfusions of one VNO with whole urine, urine condensate, or aqueous reconstituted urine extracts, whether from females in estrus or in anestrus, produced massive transient electrical responses from both VNOs . Perfusion with penicillin or local anesthetics caused more sustained large electrical responses from both VNOs , except that activity became quiescent about 15 min after local anesthesia. These results suggest that it is feasible to use direct recording of VNO responses to stimulation to investigate the behavioral physiology of the VNO .(ABSTRACT TRUNCATED AT 250 WORDS)


Description and Factors Affecting the Referral of Presumptive Tuberculosis Patients in China.
To describe and analyze the factors affecting the referral of presumptive tuberculosis patients between health-care facilities that are not affiliated with the National TB Control Program (NTP) and NTP-designated medical facilities in China, we carried out a retrospective study based on data collected in the Tuberculosis Information Management System in 2015. Out of 324,221 presumptive pulmonary tuberculosis (PTB) cases reported by non-NTP health-care facilities, 302,006 (93.1%) reported cases successfully arrived at designated medical facilities and 22,215 cases (6.9%) were lost to follow-up. The arrival rate of presumptive cases among male patients (92.9%) was slightly lower than that among female ones (93.7%), and this difference is statistically significant. The majority (73.3%) of reported cases were local permanent residents. Migrants have a higher risk of being lost to follow-up compared with local residents (adjusted odds ratios 4.126 and 5.003, respectively). Compared with farmers and herdsmen, pre-school children, unemployed laborers, retirees, and people with other occupations (adjusted odds ratios 2.361, 1.274, 1.068, and 1.993, respectively) had higher rates of loss to follow-up during the referral and tracing processes. In conclusion, this study demonstrates that the high referral rate of presumptive TB cases from non-NTP health-care facilities to designated medical facilities in China is due to implementation of effective active case identification strategies. In addition, migrant populations, pre-school children, unemployed laborers, and retirees were identified as high-risk groups that contribute to the loss to follow-up.


The pathogenesis of group A streptococcal cell wall-induced polyarthritis in the rat. Comparative studies in arthritis resistant and susceptible inbred rat strains.
This report addresses the host mechanisms which regulate susceptibility and resistance to group A streptococcal cell wall-induced polyarthritis in the rat. We have compared cell wall tissue distribution and persistence following a single intraperitoneal injection of an aqueous suspension of the cell walls into arthritis susceptible LEW/N and resistant F344/N female rats. Selected aspects of the induced inflammatory reaction were also compared. Our results suggest that development of chronic erosive polyarthritis in this model is dependent, in variable degrees, upon 1) deposition and persistence of the cell walls in synovial tissues, and 2) a relative inability of arthritis susceptible rats to neutralize the proinflammatory properties of the cell walls.


Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep.
Transmissible spongiform encephalopathies (TSEs) are zoonotic fatal neurodegenerative diseases in animals and humans. TSEs are commonly known as bovine spongiform encephalopathy in cattle, scrapie in sheep and goats, chronic wasting disease in cervids, and Creutzfeldt-Jakob disease in humans. The putative transmissible agents are infectious prion proteins (PrP(Sc)), which are formed by the conversion of the normal prion protein on the glycoprotein cell surface in the presence of other PrP(Sc). Reports of the transmission of TSEs through blood raised considerable concern about the safety of blood and blood products. To address this issue, many laboratories attempted to develop a sensitive and accurate blood diagnostic test to detect PrP(Sc). Previously, we reported that, compared to normal controls, the multimer detection system (MDS) was more efficient in detecting PrP(Sc) in infected hamster brain homogenate, mouse plasma spiked with purified PrP(Sc) from scrapie mouse brain, and scrapie-infected hamster plasmas. MDS differentiates prion multimers from the cellular monomer through the multimeric expression of epitopes on prion multimers, in contrast to the monomeric form. In this study, MDS detected PrP(Sc) in plasma samples from scrapie-infected sheep expressing clinical symptoms, demonstrating 100% sensitivity and specificity in these samples. Plasma samples from asymptomatic lambs at the preclinical stage (8-month-old naturally infected offspring of scrapie-infected parents expressing a highly susceptible genotype) tested positive with 50% sensitivity and 100% specificity. In the first of two coded analyses using clinical scrapie-infected sheep and normal healthy samples, MDS successfully identified all but one of the clinical samples with 92% sensitivity and 100% specificity. Similar results were obtained in the second coded analysis using preclinical samples. MDS again successfully identified all but one of the samples with 87% sensitivity and 100% specificity. The false-negative sample was subjected to a protease pretreatment. In conclusion, MDS could accurately detect scrapie in plasma samples at both preclinical and clinical stages. From these studies, we conclude that MDS could be a promising tool for the early diagnosis of TSEs from blood samples.


Mesenteric Teratoma in Elderly Female: A Rare Case Report.
Dermoid cysts rarely present as mesenteric cysts. Mesenteric cysts are rare pathologic entities, with a reported incidence of approximately 1 of 27 000 to 1 of 100 000 admissions. Mesenteric cyst was first described by Florentine anatomist Benevieni in 1507, while performing an autopsy on an eight-year-old boy. Most commonly, teratoma occurs in the early age group. Mature mesenteric teratoma in adulthood is extremely rare. Teratoma are germ cell tumours commonly composed of multiple cell types derived from one or more of the 3 germ layers. We present the case of a 69-year-old elderly female who presented with abdomen pain for nine months with right lumbar and right iliac fossa mass. Computed Tomography (CT) abdomen revealed bilocular cystic lesion with possibility of mucinous cystadenoma with no definitive organ of origin. She underwent explorative laparotomy and total excision of the cystic mass. Histopathologic examination confirmed diagnosis of mature cystic teratoma of mesentery. This case report highlights the need to maintain high index of suspicion while evaluating abdominal mass.


Design and development of an automated and non-contact sensing system for continuous monitoring of plant health and growth.
An automated system was designed and built to continuously monitor plant health and growth in a controlled environment using a distributed system approach for operational control and data collection. The computer-controlled system consisted of a motorized turntable to present the plants to the stationary sensors and reduce microclimate variability among the plants. Major sensing capabilities of the system included machine vision, infrared thermometry, time domain reflectometry, and micro-lysimeters. The system also maintained precise growth-medium moisture levels through a computer-controlled drip irrigation system. The system was capable of collecting required data continuously to monitor and to evaluate the plant health and growth.


ACL rupture and joint laxity progression: a quantitative in vivo analysis.
Benefits of an early reconstruction and the optimal time lapse between injury and surgery to reduce the effects of altered kinematics in ACL-deficient knees are still controversial. The aim of this study was to clarify, through a quantitative in vivo evaluation, the effects of the time lapse between ACL injury and surgery in terms of changes in the pre-operative knee laxity. An in vivo study was performed on 99 patients who underwent ACL surgery. Just before the graft fixation, six laxity tests were performed for all the subjects at manual-maximum load: anterior-posterior displacement and internal-external rotation at 30° and 90° of knee flexion (AP30, AP90, IE30, IE90) as well as varus-valgus rotation (VV0, VV30) at 0° and 30° of flexion. Kinematics data were acquired by a navigation system. The Spearman rank correlation was used to assess correlation between rank and continuous data. Significance was set at P = 0.05. The analysis highlighted a significant influence of the injury-to-surgery time lapse on VV0 and AP90 compared with pre-operative laxity levels. Meniscus status also significantly affected the pre-operative laxity in the VV0 (Spearman's ρ = 0.203, P = 0.038; GLM with meniscal correction partial η = 0.27, P = 0.007) and AP90 (Spearman's ρ = 0.329, P = 0.001; GLM with meniscal correction partial η = 0.318, P = 0.017) tests. The main finding of this study is that patients with ACL rupture and a higher injury-to-surgery time present higher values of knee laxity involving AP90 displacement and VV30 rotation. Clinical relevance of the study is that ACL-deficient joint laxity, involving anterior-posterior displacement at 90° of knee flexion and varus-valgus rotation at 0° of flexion, is significantly affected by the lapse of injury-to-surgery time. This highlights the importance of considering the effects of delaying surgery when managing patients with such deficiency.


Epidemiology of intestinal helminth infestations among schoolchildren in southern Uganda.
To determine the prevalence and intensity of intestinal helminth species among school children in southern Uganda. A cross-sectional survey using a randomly selected sample. Eighteen districts of southern Uganda. Two thousand and four school children aged two to twenty years (93.3%, aged 5-10 years) selected from classes 1 and 2 in 26 randomly selected primary schools. Overall, 55.9% of children were infected with either hookworm, Ascanis lumbricoides or Trichuris trichiura. The prevalence of A. lumbricoides was 17.5% ( range 0-66.7% by school), T. trichiura was 7.3% (0-45.0%) and hookworm 44.5% (15.6-86.0%). The prevalence of A. lumbricoides and T. trichiura was greatest in western districts while hookworm infection was more evenly distributed across the country. Mass antihelminthic treatment of school children was warranted in 13 of the 18 districts as more than 50% of the children were infected with an intestinal nematode. It is likely that pre-school children are similarly infected.


The Association Between Facial Dermatosis and Face-Mask Wearing During COVID-19 in Saudi Arabia.
During the coronavirus pandemic of 2019, there has been an upsurge in the number of reported cases of facial dermatosis caused by face masks wearing within the general population. Face mask-induced facial dermatosis has been investigated previously in healthcare workers without involving the general population. However, as a precautionary measure against the coronavirus disease 2019 (COVID-19) pandemic, wearing a face mask has become mandatory for the general population, similar to healthcare workers. Objective: To measure the prevalence of COVID-19 pandemic-induced facial dermatosis. Also, to determine the type of face mask used that causes the most facial dermatosis and the association between prolonged usage of face masks and facial dermatosis in Western Saudi Arabia's population. The study covers the Western region of Saudi Arabia. A self-administered Google survey was shared on social media. The study used prior surveys from similar studies. The data collection included participants' demographic information, pre-existing skin conditions, mask type, and mask-related skin conditions. The data were analyzed using the statistical package for the social sciences (SPSS) version 20.0 (IBM Corp., Armonk, NY). The median age was 30 years (interquartile range {IQR} 23-43). Females represented 65.5% of our sample. Face mask-wearing was associated with skin changes in 41.7% of the population. The most common skin condition associated with mask use was pimples and pustules representing 28.7%, of which the most common site was on the cheeks 31.4%. Acne vulgaris was the most common pre-existing skin condition, affecting 8.7% of the total population. Of the total, 46.2% experienced an exacerbation of their pre-existing skin condition with or after wearing masks. Skin changes were significantly associated with skin type and duration of wearing the mask (P<0.001). The prevalence of facial mask-induced facial dermatosis is 41.7% of the general population in which surgical mask was responsible for most cases. In addition, there is a strong association between the duration of wearing the mask and facial dermatosis.


Overt versus covert assessment of observer reliability.
This study examined the tendency of observers to make less reliable recordings of behavioral events when a calibrating observer is absent. Experienced observers in 4 different research sites coded videotapes of family interaction using the multicategory system developed at each site. 60 tapes were coded simultaneously by randomly selected observer pairs (overt reliability assessment) and 40 tapes were coded independently by 2 observers who did not know that their entries could be compared (covert assessment). Within site, intraclass correlations (ICCs) were computed separately for both forms of reliability assessment and a variety of behaviors. Overt ICCs were very high for most behaviors in all 4 systems. The corresponding covert reliabilities were significantly lower. Covert decline was conspicuous in the first 10 min of a 1-hour coding session. Hence, observer fatigue was not its principal cause. Apparently, observers lapse into a less attentive "set" prior to coding without a partner. This tendency is most discernible when a highly complex system is employed.


Effect of dose of behavioral weight loss treatment on glycemic control in adults with prediabetes.
This study examined the effects of three doses of behavioral weight loss treatment, compared with a nutrition education control group, on changes in glycemic control in individuals with obesity and prediabetes. The study included 287 adults (77% female, 81% White; mean (SD) age=54.1 (10.5) years, body mass index=36.3 (3.9) kg/m2, and hemoglobin A1c (HbA1c)=5.9 (0.2%)). Participants were randomized to one of three behavioral treatment doses (high=24 sessions, moderate=16 sessions, or low=8 sessions) or to an education group (control=8 sessions). Changes in HbA1c, fasting glucose, and body weight were assessed from baseline to 6 months. Mean (99.2% credible interval (CI)) reductions in HbA1c were 0.11% (0.07% to 0.16%), 0.08% (0.03% to 0.13%), 0.03% (-0.01% to 0.07%), and 0.02% (-0.02% to 0.07%), for the high, moderate, low, and control conditions, respectively. Mean (CI) reductions in fasting blood glucose were 0.26 mmol/L (0.14 to 0.39), 0.09 mmol/L (0 to 0.19), 0.01 mmol/L (-0.07 to 0.09), and 0.04 mmol/L (-0.03 to 0.12) for the high, moderate, low, and control conditions, respectively. The high-dose treatment produced significantly greater reductions in HbA1c and fasting blood glucose than the low-dose and control conditions (posterior probabilities (pp)<0.001); no other significant between-group differences were observed. Mean (CI) reductions in body weight were 10.91 kg (9.30 to 12.64), 10.08 kg (8.38 to 11.72), 6.35 kg (5.19 to 7.69), and 3.82 kg (3.04 to 4.54) for the high, moderate, low, and control conditions, respectively. All between-group differences in 6-month weight change were significant (pps<0.001) except for the high-dose versus moderate-dose comparison. For adults with obesity and prediabetes a high dose of behavioral treatment involving 24 sessions over 6 months may be needed to optimize improvements in glycemic control. NCT00912652.


HLA-DQB1 genotyping by a modified PCR-RFLP method combined with group-specific primers.
We previously reported a simple technique for HLA-DQB genotyping by digestion of polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP method). However, this method has some problems in that some heterozygotes cannot be discriminated from each other. Furthermore, concomitantly amplified product derived from the DQB2 gene by the primers used previously also obstructs precise DQB1 genotyping. To resolve these problems, we have developed two different pairs of specific primers for selective amplification of the DQB1 gene and also used restriction endonucleases which have either a single cleavage site or, alternatively, no cleavage site in the amplified DNA region, depending on the HLA-DQB1 alleles, making reading of RFLP band patterns much easier. The second exon of the DQB1 gene was selectively amplified by DQw1 group-specific primers and/or DQw2,3,4 group-specific primers using genomic DNAs from 70 HLA-homozygous B-cell lines and 50 healthy Japanese. Of the seven DQw1-associated DQB1 alleles, six alleles could be defined by digestion of 6 restriction enzymes, although DQB1*0602 and DQB1*0603 could not be discriminated from each other because of unavailability of suitable enzymes. Similarly, all of the six DQw2,3,4-associated DQB1 alleles could be defined by digestion of 5 restriction enzymes. Using this modified PCR-RFLP method, complete DQB1 genotyping of all heterozygotes is possible except for discrimination between DQB1*0602 and 0603. Thus this method is simpler and more practical for a routine DNA typing than the PCR-SSO method or our previous PCR-RFLP method.


[Diffuse alveolar hemorrhage as a complication in patients with hematologic malignancies after chemotherapy: report of two cases and literature review].
To study diffuse alveolar hemorrhage (DAH) in patients with hematologic malignancies after chemotherapy and discuss the possible etiology and appropriate therapy. Symptoms, physical examinations, laboratory examination, chest radiographs or computed tomographic (CT) scans, treatments and outcomes of two patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) each after chemotherapy were presented. Both of the patients developed cough, progressive dyspnea, a drop of hemoglobin level, hypoxemia and widespread pulmonary infiltrate on chest radiographs or CT scans after chemotherapy. Moreover, case 1 (ALL) had high fever and bloody fluid drained from the intubation of mechanical ventilation, case 2 (NHL) developed continual hemoptysis. They were diagnosed as DAH and improved significantly after intermediate- or high-dose corticosteroid therapy. DAH is a rare fatal acute noninfectious pulmonary complication in patients with hematologic malignancies after chemotherapy. Early accurate diagnosis, identifying the underlying cause and appropriate treatment are critical for the management of DAH.


SPRTN and TDP1/TDP2 Independently Suppress 5-Aza-2'-deoxycytidine-Induced Genomic Instability in Human TK6 Cell Line.
DNA-protein cross-links (DPCs) are generated by internal factors such as cellular aldehydes that are generated during normal metabolism and external factors such as environmental mutagens. A nucleoside analog, 5-aza-2'-deoxycytidine (5-azadC), is randomly incorporated into the genome during DNA replication and binds DNA methyltransferase 1 (DNMT1) covalently to form DNMT1-DPCs without inducing DNA strand breaks. Despite the recent progress in understanding the mechanisms of DPCs repair, how DNMT1-DPCs are repaired is unclear. The metalloprotease SPRTN has been considered as the primary enzyme to degrade protein components of DPCs to initiate the repair of DPCs. In this study, we showed that SPRTN-deficient (SPRTN-/-) human TK6 cells displayed high sensitivity to 5-azadC, and the removal of 5-azadC-induced DNMT1-DPCs was significantly slower in SPRTN-/- cells than that in wild-type cells. We also showed that the ubiquitination-dependent proteasomal degradation, which was independent of the SPRTN-mediated processing, was also involved in the repair of DNMT1-DPCs. Unexpectedly, we found that cells that are double deficient in tyrosyl DNA phosphodiesterase 1 and 2 (TDP1-/-TDP2-/-) were also sensitive to 5-azadC, although the removal of 5-azadC-induced DNMT1-DPCs was not compromised significantly. Furthermore, the 5-azadC treatment induced a marked accumulation of chromosomal breaks in SPRTN-/- as well as TDP1-/-TDP2-/- cells compared to wild-type cells, strongly suggesting that the 5-azadC-induced cell death was attributed to chromosomal DNMT1-DPCs. We conclude that SPRTN protects cells from 5-azadC-induced DNMT1-DPCs, and SPRTN may play a direct proteolytic role against DNMT1-DPCs and TDP1/TDP2 also contributes to suppress genome instability caused by 5-azadC in TK6 cells.


Interleukin-15 receptor is essential to facilitate GABA transmission and hippocampal-dependent memory.
Interleukin-15 (IL15) is a cytokine produced by normal brain, but the functions of the IL15 system in normal adults are not yet clear. The hypothesis that the hippocampal IL15 system is essential for memory consolidation was tested by use of IL15Ralpha knock-out mice in behavioral, biochemical, immunohistological, and electron microscopic analyses. The knock-out mice showed deficits in memory, determined by the Stone T-maze and fear conditioning. In their hippocampi, the concentration of GABA was significantly lower. There were region-specific changes of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), with increased GAD-67-immunopositive interneurons in the stratum oriens of the CA1 region of the hippocampus, accompanied by nonsignificant reduction of GAD-67 synapses in the CA3 region. Western blotting showed an increase of GAD-65, but not GAD-67, in the hippocampal homogenate. The ultrastructure of the hippocampus remained intact in the knock-out mice. To further test the hypothesis that IL15 directly modulates GABA turnover by reuptake mechanisms, the dose-response relationship of IL15 on (3)H-GABA uptake was determined in two neuronal cell lines. The effective and nontoxic dose was further used in the synaptosomal uptake studies. IL15 decreased the uptake of (3)H-GABA in synaptosomes from the forebrain of wild-type mice. Consistent with this, IL15Ralpha knock-out mice had increased synaptosomal uptake of (3)H-GABA. Overall, the results show novel functions of a unique cytokine in normal hippocampal activity by regulating GABA transmission.


A novel 'leadless' dielectrophoresis chip with dot matrix electrodes for patterning nanowires.
In this paper, we present a novel 'leadless' dielectrophoresis chip with dot matrix electrodes (LDME-DEP chip) fabricated by stacking three different functional layers. Our LDME-DEP chip excels mainly in two aspects: we for the first time applied the technique of separating the lead and the electrode pattern into two different layers to patterning nanowires which achieves continuous-area manipulation of nanowires without interference from the lead; the use of dot matrix electrodes makes the manipulation more flexible. We firstly detail the fabrication and working principle of our LDME-DEP chip and propose the scheme for washing away the nanowires with unsatisfactorily positioned postures. Then, nanowire patterning applications (e.g., letter E, square and long chain) under the combination of dielectrophoretic force and hydrodynamic force are carried out and the effect of frequency of the electric signal on assembling accuracy of nanowires is discussed.


A Markov model for the temporal dynamics of balanced random networks of finite size.
The balanced state of recurrent networks of excitatory and inhibitory spiking neurons is characterized by fluctuations of population activity about an attractive fixed point. Numerical simulations show that these dynamics are essentially nonlinear, and the intrinsic noise (self-generated fluctuations) in networks of finite size is state-dependent. Therefore, stochastic differential equations with additive noise of fixed amplitude cannot provide an adequate description of the stochastic dynamics. The noise model should, rather, result from a self-consistent description of the network dynamics. Here, we consider a two-state Markovian neuron model, where spikes correspond to transitions from the active state to the refractory state. Excitatory and inhibitory input to this neuron affects the transition rates between the two states. The corresponding nonlinear dependencies can be identified directly from numerical simulations of networks of leaky integrate-and-fire neurons, discretized at a time resolution in the sub-millisecond range. Deterministic mean-field equations, and a noise component that depends on the dynamic state of the network, are obtained from this model. The resulting stochastic model reflects the behavior observed in numerical simulations quite well, irrespective of the size of the network. In particular, a strong temporal correlation between the two populations, a hallmark of the balanced state in random recurrent networks, are well represented by our model. Numerical simulations of such networks show that a log-normal distribution of short-term spike counts is a property of balanced random networks with fixed in-degree that has not been considered before, and our model shares this statistical property. Furthermore, the reconstruction of the flow from simulated time series suggests that the mean-field dynamics of finite-size networks are essentially of Wilson-Cowan type. We expect that this novel nonlinear stochastic model of the interaction between neuronal populations also opens new doors to analyze the joint dynamics of multiple interacting networks.


Ion mobility spectrometry: the diagnostic tool of third millennium medicine.
Ion mobility spectrometry (IMS) is a fast, low cost, portable, and sensitive technique that separates ions in a drift tube under the influence of an electric field according to their size and shape. IMS represents a non-invasive and reliable instrumental alternative for the diagnosis of different diseases through the analysis of volatile metabolites in biological samples. IMS has applications in medicine in the study of volatile compounds for the non-invasive diagnose of bronchial carcinoma, chronic obstructive pulmonary disease, and other diseases analysing breath, urine, blood, faeces, and other biological samples. This technique has been used to study complex mixtures such as proteomes, metabolomes, complete organisms like bacteria and viruses, monitor anaesthetic agents, determine drugs, pharmaceuticals, and volatile compounds in human body fluids, and others. Pharmaceutical applications include analysis of over-the-counter-drugs, quality assessment, and cleaning verification. Medical practice needs non-invasive, robust, secure, fast, real-time, and low-cost methods with high sensitivity and compact size instruments to diagnose different diseases and IMS is the diagnostic tool that meets all these requirements of the Medicine of the future.


The effect of selection on the phenotypic variance.
We consider the within-generation changes of phenotypic variance caused by selection w(x) which acts on a quantitative trait x. If before selection the trait has Gaussian distribution, its variance decreases if the second derivative of the logarithm of w(x) is negative for all x, while if it is positive for all x, the variance increases.


Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action.
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key 'known unknowns' that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.


Palliative Care Unit at Home: Impact on Quality of Life in Cancer Patients at the End of Life in a Rural Environment.
Advanced cancer is accompanied by a substantial burden of symptoms, and palliative care (PC) plays an essential role, especially at the end of life (EOL). In fact, a comprehensive PC through Home Palliative Care Units (HPCU) has been associated with reducing potentially aggressive care at the EOL. We aim to study the impact of HPCU on the quality of assistance of cancer patients at Alcoy Health Department. A retrospective study was conducted including patients diagnosed with terminal cancer at the Medical Department of Hospital Virgen de los Lirios who died between January 2017 and December 2018. The Multivariate Cox regression model was used to assess the impact of HPCU assistance on the quality of life indicators. 388 patients were included. The median age was 71 years; 65% patients were male, and 68% presented with a 0-2 score on the ECOG scale. On the multivariate analysis, a lack of assistance by HPCU was associated with a higher risk of consulting in the emergency department (OR = 1.29, 95% CI: 1.02-1.67), of hospital admissions (OR = 4.72, 95% CI: 2.45-9.09), a higher probability of continuing active treatment (OR = 2.59, 95% CI: 1.44-4.67), and a greater probability of dying in hospital (OR = 6.52, 95% CI: 3.78-11.27). Patients receiving HPCU assistance have a lower number of emergency room visits and hospital admissions, and are more likely to die at home. Taken together, these results support the relevance of HPCU providing a high quality attention of cancer patients.


Remediation of water and wastewater by using engineered nanomaterials: A review.
Nanotechnology is currently a fast-rising socioeconomic and political knowledge-based technology owing to the unique characteristics of its engineered nanomaterials. This branch of technology is useful for water and wastewater remediation. Many scientists and researchers have been conducting different studies and experiments on the applications of engineered nanomaterials at the local to international level. This review mainly aims to provide a current overview of existing knowledge on engineered nanomaterials and their applications in water and wastewater remediation. Furthermore, the present risks and challenges of nanotechnology are examined.


Effects of 33% stable xenon/O2 mixture on somatosensory evoked potentials.
The influences of 30% stable xenon/O2 mixture on somatosensory evoked potentials were investigated in 8 patients with and without Diamox application. Changes of the amplitude of the primary cortical response occurred frequently and correlated well with the psychotropical effect of xenon. They usually normalized within 2 to 3 minutes after ending xenon inhalation. There were no significant changes of the latency of the N20.


[Studies on the antibacterial activity of the combination sulfamoxole/trimethoprim (CN 3123) (author's transl)].
After giving a survey on the situation of antibiotic resistance in the region of Northern Bavaria during 1973/74 and comparing the activity of a sulfamethoxazole (SMZ) trimethoprim (TMP) combination to other commonly used antibiotics and chemotherapeutic agents, the results of tests with the new combination of N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide) (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) at a ratio of 5:1 (CN 3123; Nevin, Supristol) are compared to those of tests with TMP/SMZ. This was done by correlating the inhibition zone diameters and, on the other hand, by referring to a great number of sensitivity evaluations in routine diagnostic tests. According to the size of the inhibition zone, CN 3123 showed a somewhat greater activity on Enterococcus (fecal streptococci), Escherichia coli, and Klebsiella aerogenes, whereas the TPM/SMZ combination had apparently a stronger antibacterial effect in vitro against Proteus mirabilis, Staphylococcus aureus, and the Achromobacter-group. Analysis of sensitivity readings from routine diagnosis demonstrated accordance of CN 3123 with TMP/SMZ in 92.6% (first series) and 94.2% (second series), respectively. These results should be considered critically in view of the manifold factors which influence sensitivity tests in the agar diffusion method.


Effects of vasoactive agents on isolated human umbilical arteries in preeclamptic women treated with magnesium sulfate: a preliminary report.
Increased vascular reactivity has been noted in preeclampsia. It is uncertain whether this increased reactivity extends to the umbilical circulation. Helical strips of human umbilical arteries from 12 preeclamptic and 17 control patients were set up isometrically in physiological solution. Four preeclamptics who had not received magnesium were included. The resting tensions of the strips, amplitudes, frequencies, and times of onset of spontaneous contractions during the incubation period were noted and did not differ between the groups. When logarithmic dose contractile-response curves were made for serotonin, bradykinin, and KCl for each group, differences were noted only for KCl. The threshold dose for KCl was higher in tissues from the preeclamptic group (8.52 +/- 0.96 mM) compared to the controls (4.09 +/- 0.59 mM) regardless of magnesium therapy. Also, the ED50 for KCl was higher for preeclamptics given magnesium (12.45 +/- 1.21 mM) compared to controls (9.17 +/- 1.05 mM). There were no significant differences between maximal tensions obtained, but a trend was noted for preeclamptics who did not receive magnesium to develop less tension than either controls or preeclamptics who did receive magnesium, regardless of the agonist tested. Relaxation times differed only for KCl, where there was a shortening of the time for the preeclamptics (8.76 +/- 0.64 min) compared to controls (14.53 +/- 2.46 min). These results do not support other studies in which an increased peripheral vascular reactivity in preeclamptics was noted. An explanation for the decreased reactivity to KCl awaits further investigation.


Preoperative Planning in the Surgical Correction of Tibial Nonunions and Malunions.
Three typical cases demonstrate the achievement of precision in the reconstruction of ununited fractures of the tibia by preliminary planning with the aid of tracings on roentgenograms, templates, and goniometer measurements.


A report of two cases of pigmented purpuric dermatoses treated with PUVA therapy.
This is a report of 2 patients with pigmented purpuric dermatosis treated successfully with Psoralen photochemotherapy (PUVA). Treatment for pigmented purpuric dermatosis is generally unsatisfactory, and we believe this to be the first report of successful response of this condition to PUVA.


Discovery of novel photocaged ERK1/2 inhibitors as light-controlled anticancer agents.
Although extracellular regulated protein kinases (ERKs) are considered important targets for the treatment of various cancers, the occurrence of severe side effects in clinical trials restricts the development of ERK inhibitors. Here, we developed the first series of photocaged ERK inhibitors, which can be selectively activated by UV irradiation to release a highly potent ERK inhibitor in multiple cancer cell lines including A375, A549 and HCT116, and Compound 2 demonstrated clear anticancer activity in a zebrafish xenograft model. In conclusion, photocaged ERK inhibitor 2 provides a new strategy for precise cancer therapy.


Some reactions of an eta3-tetracyanobutadienyl-ruthenium complex.
In the eta(3)-butadienyl complex Ru{eta(3)-C(CN)(2)CPhC=C(CN)(2)}(PPh(3))Cp 1, which is formed from Ru(C[triple bond]CPh)(PPh(3))(2)Cp and tcne, a CN group reacts with MeO(-) to give the methoxy-amide Ru{NH=C(OMe)C(CN)=CCPh=C(CN)(2)}(PPh(3))Cp 2, in which the NH has displaced the C=C from the Ru centre with formation of a RuC(3)N ring. "Click addition" of azide to a CN group in 1 gives the oligomeric tetrazolato complex Ru{N(3)N[Na(OEt(2))]=CC(CN)=CCPh=C(CN)(2)}(PPh(3))Cp 3, also containing a RuC(3)N ring. Salt-elimination reactions of 3 with MeOTf, FeCl(dppe)Cp, RuCl(dppe)Cp* and trans-PtCl(2){P(tol)(3)}(2) result in selective substitution at one nitrogen atom of the RuC(3)N ring. Geometries of 1 and the anion in 3 were computed by DFT methods. Preferences for CN groups attacked in the nucleophilic and cycloaddition reactions of 1 are supported by NBO calculations. Alkylation of 1 in reactions with 1,2-dimethoxyethane gave two isomers of Ru{N(3)[CH(CH(2)OMe)(OMe)]N=CC(CN)=CCPh=C(CN)(2)}(PPh(3))Cp 8 and 9, differing in the sites of attachment of the alkyl group, likely by radical processes. The molecular structures of eight complexes are reported, including a re-determination of 1. Computed NMR chemical shifts are used to reassign the butadienyl carbon resonances in the (13)C NMR spectrum of 1.


Periodontal manifestations of von Recklinghausen neuro fibromatosis.
Neurofibroma is an uncommon benign tumor of the oral cavity derived from the cells that constitute the nerve sheath neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is the most common type of neurofibromatosis and accounts for about 90% of all cases. It is one of the most frequent human genetic diseases, with the prevalence of one case in 3,000 births. Neurofibroma is seen either as a solitary lesion or as part of the generalized syndrome of neurofibromatosis. The solitary form does not differ from the disseminated form or the multiple form of the disease, except that systemic and hereditary factors present in the disseminated form are absent in the solitary type. Oral cavity involvement by a solitary and peripheral plexiform neurofibroma in patients with no other signs of neurofibromatosis is uncommon. The expressivity of NF1 is extremely variable, with manifestations ranging from mild lesions to several complications and functional impairment. Oral manifestations can be found in almost 72% of NF1 patients. This is a case report of a 40-year-old lady with a history of multiple faint rounded densities in the skin, chest pain occasionally since 8 months and breathlessness since 1 year and swelling of the right side of the angle of the mandible with limited mouth opening.


Cerebral Venous Sinus Thrombosis Successfully Treated with Mechanical Thrombectomy under Intracranial Pressure Monitoring: A Case Report.
A 54-year-old man with no medical history presented to our hospital with vomiting, left hemiplegia, and seizures. On arrival, he was experiencing generalized tonic-clonic seizures, which required him to be intubated and deeply sedated. Contrast-enhanced computed tomography revealed extensive venous sinus obstruction from the superior sagittal sinus to the bilateral sigmoid sinus and cerebral edema with intracranial hemorrhage. An intracranial pressure (ICP) monitor was immediately placed intracranially, and mechanical thrombectomy (MT) was performed under ICP monitoring. MT was immediately terminated when the venous sinus was partially recanalized enough to decrease the ICP; then, anticoagulation therapy was initiated. Postoperative follow-up angiography revealed that venous sinus obstruction and intracranial venous perfusion improved over time. Although he had intracranial hemorrhage-induced left hemiplegia and sensory deficits, his condition improved with rehabilitation, and the patient was eventually discharged home. The indication criteria and techniques for MT for cerebral venous sinus thrombosis are yet to be established. As in this case, in patients with impaired consciousness due to intracranial hemorrhage or epilepsy, preoperative ICP monitor placement is deemed useful to evaluate venous perfusion during MT and decide the treatment goal.


Bone-targeting dendrimer for the delivery of methotrexate and treatment of bone metastasis.
We developed a bone-targeting dendrimer for the delivery of anti-tumour agents and effective treatment of bone metastasis, in which alendronate (ALN), a bone-targeting moiety, is covalently bonded to a polyethylene glycol (PEG)-conjugated polyamidoamine (PAMAM) dendrimer (PEG-PAMAM-ALN). Approximately 7.0 and 21.9% of the administered doses of [111In]PAMAM and PEG-PAMAM-ALN accumulated in the bones within 180 min after intravenous injection in mice, respectively. [3H]-labelled methotrexate (MTX) rapidly disappeared from the blood, and bone distribution was found to be only 1.1% of the administered dose at 180 min. In contrast, 21.5% of the administered dose of [3H]MTX-loaded PEG-PAMAM-ALN accumulated in the bones at 180 min after intravenous injection in mice, which was approximately 20-fold higher than that of [3H]MTX. In a bone metastatic tumour mouse model, in which B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice, the growth of metastatic tumour in the bones was significantly inhibited by intravenous injection of MTX-loaded PEG-PAMAM-ALN. These findings indicate that PEG-PAMAM-ALN is a promising bone-targeting carrier for the delivery of anti-tumour agents and treatment of bone metastasis.


Nutritional risk factors in calcium stone disease in Japan.
The purpose of this study is to examine the nutritional environment affecting calcium stone disease in Japan. The following results were obtained. Renal stone disease in the late 1970s increased by about three times than that of the 1940s . Fats and oils, animal protein and calcium intake increased remarkably after the second World War and milk plus milk products, meat and animal products were increased surprisingly compared with 1950. The most ingested nutrients of calcium stone formers were not much different from the results of the National Nutritive Survey in Japan. But the ingested amount of calcium was unexpectedly small and did not reach the level of the daily nutritional requirement in Japanese (15 mmol). The ingested amount of total protein correlated with urinary calcium excretion and had the highest coefficient of determination to the urinary calcium excretion by multiple regression analysis. We have finished our research of individual dietary habits and suggest that the following individual dietary guidance is the primary treatment for the prophylaxis of renal stone disease.


Epiglottitis in infants less than two years of age.
A retrospective review of 41 children less than two years of age was conducted to characterize the clinical presentation of epiglottitis in this young age group. Up to 25% of all cases of epiglottitis occur in children less than two years of age. The clinical presentation of patients in this young age group is variable. Signs and symptoms not routinely described in children over two years of age with epiglottitis but often observed in infants with epiglottitis include the absence of fever, the presence of only low grade fever, a significant history of antecedent URI, and a prominent "croupy" cough. These same features are often noted in children with the viral croup syndrome. A diagnosis of this life-threatening illness may be made promptly through an awareness of the presenting findings observed in infants. Young infants with epiglottitis can be safely managed with short-term nasotracheal intubation.


To what extent are Arab pilgrims to Makkah aware of the middle east respiratory syndrome coronavirus and the precautions against it?
Approximately, 80% of the many cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) confirmed worldwide were diagnosed in the Kingdom of Saudi Arabia (KSA). The risk of the disease spreading internationally is especially worrying given the role of KSA as the home of the most important Islamic pilgrimage sites. This means the need to assess Arab pilgrims' awareness of MERS-CoV is of paramount importance. A cross-sectional study was carried out during Ramadan 2015 in the Holy Mosque in Makkah, Saudi Arabia. Self-administered questionnaires were distributed to 417 Arab participants at King Fahad Extension, King Abdullah Prayer Extension and, King Abdullah Piazza Extension after Taraweeh and Fajr prayers. The mean MERS-CoV knowledge score was 52.56. Majority of the respondents (91.3%) were familiar with MERS-CoV. Saudis had significantly higher knowledge of MERS-CoV than non-Saudis (56.92 ± 18.55 vs. 44.91 ± 25.46, p = 0.001). Females had significantly more knowledge about consanguineous MERS-CoV than males (55.82 ± 19.35 vs. 49.93 ± 23.66, p = 0.006). The average knowledge was significantly higher in respondents who had received health advice on MERS-CoV (56.08 ± 20.86 vs. 50.65 ± 22.51, p = 0.024). With respect to stepwise linear regression, knowledge of MERS-CoV tended to increase by 14.23 (B = 14.23%, p = 0.001) in participants who were familiar with MERS-CoV, and by 8.50 (B = 8.50, p = 0.001) in those who perceived MERS-CoV as a very serious disease. There is a great need for educational programs to increase awareness about MERS-CoV.


Image coding.
The digital representation of an image requires a very large number of bits. The goal of image coding is to reduce this number, as much as possible, and reconstruct a faithful duplicate of the original picture. Early efforts in image coding, solely guided by information theory, led to a plethora of methods. The compression ratio reached a saturation level around 10:1 a couple of years ago. Recent progress in the study of the brain mechanism of vision and scene analysis has opened new vistas in picture coding. Directional sensitivity of the neurones in the visual pathway combined with the separate processing of contours and textures has led to a new class of coding methods capable of achieving compression ratios as high as 100:1.


Potential key roles of tumour budding: a representative malignant pathological feature of non-small cell lung cancer and a sensitive indicator of prognosis.
To investigate the relationship between tumour budding, clinicopathological characteristics of patients and prognosis in non-small cell lung cancer. A retrospective study was used. We selected 532 patients with non-small cell lung cancer from China, including 380 patients with adenocarcinoma and 152 with squamous cell carcinoma. Tumour budding was visible using H&E staining as well as pancytokeratin staining. The count data and measurement data were compared using the χ2 test and the t-test, respectively. The overall survival rate was the follow-up result. The survival curves were drawn using the Kaplan-Meier method, and the differences between groups were analysed using the log-rank method. The independent prognostic factor of patients with lung cancer was determined using a multivariate Cox proportional hazard model. In patients with lung adenocarcinoma, there was a correlation between tumour budding and spread through air spaces (OR 36.698; 95% CI 13.925 to 96.715; p<0.001), and in patients with squamous cell carcinoma, tumour budding state was closely related to the peritumoural space (OR 11.667; 95% CI 4.041 to 33.683; p<0.001). On Cox regression analysis, multivariate analysis showed that tumour budding, pleural and vascular invasion, spread through air spaces, tumour size, lymph node metastasis, and tumour node metastasis stage were independent risk factors of prognosis for patients with non-small cell lung cancer. As an effective and simple pathological diagnostic index, it is necessary to establish an effective grading system in the clinical diagnosis of lung cancer to verify the value of tumour budding as a prognostic indicator. We hope that this analysis of Chinese patients with non-small cell lung cancer can provide useful reference material for the continued study of tumour budding.


Pathogen Stopping and Metabolism Modulation Are Key Points to Linum usitatissimum L. Early Response against Fusarium oxysporum.
Fusarium oxysporum is the one of the most common and impactful pathogens of flax. Cultivars of flax that show resistance to this pathogen have previously been identified. To better understand the mechanisms that are responsible for this resistance, we conducted time-lapse analysis of one susceptible and one resistant cultivar over a two-week period following infection. We also monitored changes in some metabolites. The susceptible cultivar showed a strong onset of symptoms from 6 to 8 days after inoculation, which at this time point, was associated with changes in metabolites in both cultivars. The resistant cultivar maintained its height and normal photosynthetic capacity but showed a reduced growth of its secondary stems. This resistance was correlated with the containment of the pathogen at the root level, and an increase in some metabolites related to the phenylpropanoid pathway.


Pulmonary hypertension and HIV.
People living with HIV have long had enough to worry about from the most common opportunistic infections and HIV-related conditions. There are, however, a number of less well-known illnesses for which HIV is considered a risk factor. When people afflicted with these conditions turn to general sources of HIV information, they often find little or no recognition of the connection with HIV. Consequently, they often feel isolated and alone in facing their new problem and can't get much help from their usual support mechanisms.


Taking the VITALS to Interrupt Microaggressions.
Microaggressions are subtle statements or actions that reinforce stereotypes. Medical students, residents, and faculty report experiences of microaggressions, with higher incidences among women and marginalized groups. An educational tool utilizing the acronym VITALS (validate, inquire, take time, assume, leave opportunities, speak up) provided a framework for processing and addressing microaggressions encountered in the academic health center environment. We developed a 60-minute workshop designed to raise awareness of microaggressions encountered by medical students and trainees. The workshop consisted of a didactic presentation and multiple interactive exercises shared in small- and large-group formats. Participants also completed pre- and postsurvey instruments to assess changes in their knowledge and attitudes about promoting an environment that prevents microaggressions from occurring. There were 176 participants who completed our workshop. In comparing anonymized pre- and postworkshop responses submitted by attendees, an increase in recognition of one's own potential stereotypical beliefs about social identity groups was observed. Participants also expressed a greater sense of empowerment to foster mutual respect in health care settings. After completing the workshop, attendees indicated a greater likelihood to engage in difficult conversations, including responding to microaggressions, which both peers and superiors encountered in both academic and clinical environments. The workshop provided an interactive format for medical students and trainees to gain awareness, knowledge, and tools for addressing microaggressions encountered in health care settings.


Spent media from immature seminiferous tubules and Sertoli cells inhibit adult rat Leydig cell aromatase activity.
Adult rat Leydig cell aromatase activity is stimulated 2.5 fold by LH or dbcAMP. Spent media prepared from seminiferous tubules or Sertoli cells of immature rats depress both the basal and the LH stimulated estradiol syntheses (25 and 20% decreases, respectively). These inhibitory effects are further enhanced when FSH is added to the culture medium of seminiferous tubules or Sertoli cells. Rat serum as well as culture media from other cell lines are ineffective while seminiferous tubule media from other immature animals (mouse, guinea-pig, calf) inhibit the aromatase activity. This Sertoli cell factor is a heat stable protein (molecular weight greater than 10 kDa), different from the LHRH-like Sertoli cell compound, which acts on the aromatase activity at a step beyond the adenylate cyclase.


Systematic Characteristic Exploration of the Chimeras Generated in Multiple Displacement Amplification through Next Generation Sequencing Data Reanalysis.
The chimeric sequences produced by phi29 DNA polymerase, which are named as chimeras, influence the performance of the multiple displacement amplification (MDA) and also increase the difficulty of sequence data process. Despite several articles have reported the existence of chimeric sequence, there was only one research focusing on the structure and generation mechanism of chimeras, and it was merely based on hundreds of chimeras found in the sequence data of E. coli genome. We finished data mining towards a series of Next Generation Sequencing (NGS) reads which were used for whole genome haplotype assembling in a primary study. We established a bioinformatics pipeline based on subsection alignment strategy to discover all the chimeras inside and achieve their structural visualization. Then, we artificially defined two statistical indexes (the chimeric distance and the overlap length), and their regular abundance distribution helped illustrate of the structural characteristics of the chimeras. Finally we analyzed the relationship between the chimera type and the average insertion size, so that illustrate a method to decrease the proportion of wasted data in the procedure of DNA library construction. 131.4 Gb pair-end (PE) sequence data was reanalyzed for the chimeras. Totally, 40,259,438 read pairs (6.19%) with chimerism were discovered among 650,430,811 read pairs. The chimeric sequences are consisted of two or more parts which locate inconsecutively but adjacently on the chromosome. The chimeric distance between the locations of adjacent parts on the chromosome followed an approximate bimodal distribution ranging from 0 to over 5,000 nt, whose peak was at about 250 to 300 nt. The overlap length of adjacent parts followed an approximate Poisson distribution and revealed a peak at 6 nt. Moreover, unmapped chimeras, which were classified as the wasted data, could be reduced by properly increasing the length of the insertion segment size through a linear correlation analysis. This study exhibited the profile of the phi29MDA chimeras by tens of millions of chimeric sequences, and helped understand the amplification mechanism of the phi29 DNA polymerase. Our work also illustrated the importance of NGS data reanalysis, not only for the improvement of data utilization efficiency, but also for more potential genomic information.


Endothelial Dysfunction of Conduit Arteries in Patients with Repaired Coarctation of the Aorta.
Adult patients with repaired coarctation of the aorta (r-CoA) show high prevalence of late hypertension, but the exact mechanisms of this phenomenon are unknown. Endothelial dysfunction has been implicated in this paradoxical hypertension. We evaluated the endothelial function of both conduit and resistance arteries by using flow-mediated dilation (FMD) and digital peripheral artery tonometry (PAT).Seventeen patients with r-CoA and one patient with repaired interrupted aortic arch (r-CoA group) aged 22.0 ± 6.9 years (5 females) underwent FMD of the right brachial artery, PAT of the right finger, blood marker tests, ambulatory blood pressure monitoring, echocardiography, carotid ultrasonography, and brachio-ankle pulse wave velocity measurement. The median age at aortic arch reconstruction was 2.0 months (interquartile range: 15 days to 7.0 years). Results were compared with 17 age-matched healthy subjects (control group).Eight (44%) patients of the r-CoA group were hypertensive (5 received antihypertensive drugs). Patients in the r-CoA group showed significantly lower FMD (3.8 ± 1.5 versus 6.6 ± 2.5%, P < 0.001), larger intima-media thickness (0.63 ± 0.17 versus 0.47 ± 0.09 mm, P = 0.001), and higher left ventricular mass index (91.4 ± 24.6 versus 73.4 ± 17.3 g/m2, P = 0.017) than those in the control group. There were no significant differences in PAT (refractory hyperemia index, 1.86 ± 0.43 versus 1.99 ± 0.59, P = 0.48) and brachio-ankle pulse wave velocity between the two groups.Vascular dysfunction in r-CoA patients, particularly endothelial dysfunction, tends to occur more significantly in conduit arteries than in resistance arteries.


Understanding the pathophysiology of typical acute respiratory distress syndrome and severe COVID-19.
Typical acute respiratory distress syndrome (ARDS) and severe coronavirus-19 (COVID-19) pneumonia share complex pathophysiology, a high mortality rate, and an unmet need for efficient therapeutics. This review discusses the current advances in understanding the pathophysiologic mechanisms underlying typical ARDS and severe COVID-19 pneumonia, highlighting specific aspects of COVID-19-related acute hypoxemic respiratory failure that require attention. Two models have been proposed to describe the mechanisms of respiratory failure associated with typical ARDS and severe COVID-19 pneumonia. ARDS is defined as a syndrome rather than a distinct pathologic entity. There is great heterogeneity regarding the pathophysiologic, clinical, radiologic, and biological phenotypes in patients with ARDS, challenging clinicians, and scientists to discover new therapies. COVID-19 has been described as a cause of pulmonary ARDS and has reopened many questions regarding the pathophysiology of ARDS itself. COVID-19 lung injury involves direct viral epithelial cell damage and thrombotic and inflammatory reactions. There are some differences between ARDS and COVID-19 lung injury in aspects of aeration distribution, perfusion, and pulmonary vascular responses.


Membrane synthesis in synchronous cultures of Bacillus subtilis 168.
Synthesis of bacterial membranes has been investigated in Bacillus subtilis by examining incorporation of amino acids and glycerol into the protein and lipid of membranes of synchronous cultures. A simple reproducible fractionation scheme divides cellular proteins into three classes (i) truly cytoplasmic, (ii) loosely membrane bound, released by chelating agents, and (iii) tightly membrane bound. These comprise approximately 75, 10, and 15%, respectively, of cellular proteins in this organism. Incorporation of radioactivity into these fractions, using steady-state and pulse labeling has been followed during the cell cycle. Cytoplasmic proteins and the loosely membrane-bound proteins are labeled at an exponential rate throughout the cell cycle. The membrane fraction is labeled discontinuously in the cell cycle, with periods of rapid synthesis over the latter part of the cycle and a period with no net synthesis during the early part of the cycle. Pulse labeling indicates that synthesis of membrane occurs at a linear rate that doubles at a fixed time in each cycle, which coincides with the period of zero net synthesis. Rates of membrane synthesis measured by pulse labeling during the period of rapid membrane synthesis are significantly less than indicated by steady-state labeling. These discrepancies are consistent with the hypothesis that during the cell cycle certain proteins are added to the membrane from the cytoplasm and that during the period of zero net synthesis there is an efflux of proteins from the membrane. Evidence in favor of this has been presented. The activity of succinic dehydrogenase (a representative of class c) varies in a step-wise manner with periods of rapid increase, approximately coincident with bursts of membrane protein synthesis, alternating with periods without any increase in activity. The activities of malate dehydrogenase (class a) and reduced nicotinamide adenine dinucleotide dehydrogenase (class b) increased throughout the cell cycle. Phospholipid synthesis is continuous throughout the cell cycle.


A Highly Sensitive Fiber-Optic Fabry-Perot Interferometer Based on Internal Reflection Mirrors for Refractive Index Measurement.
In this study, a new type of highly sensitive fiber-optic Fabry-Perot interferometer (FFPI) is proposed with a high sensitivity on a wide refractive index (RI) measurement range based on internal reflection mirrors of micro-cavity. The sensor head consists of a single-mode fiber (SMF) with an open micro-cavity. Since light reflections of gold thin films are not affected by the RI of different measuring mediums, the sensor is designed to improve the fringe visibility of optical interference through sputtering the gold films of various thicknesses on the inner surfaces of the micro-cavity, as a semi-transparent mirror (STM) and a total-reflection mirror (TRM). Experiments have been carried out to verify the feasibility of the sensor's design. It is shown that the fabricated sensor has strong interference visibility exceeding 15 dB over a wide measurement range of RI, and the sensor sensitivity is higher than 1160 nm/RIU, and RI resolution is better than 1.0 × 10(-6) RIU.


Phoenix dactylifera (Ajwa Dates) Alleviate LPS-Induced Sickness Behaviour in Rats by Attenuating Proinflammatory Cytokines and Oxidative Stress in the Brain.
Traditional medicine claims that various components of the Phoenix dactylifera (date plant) can be used to treat memory loss, fever, inflammation, loss of consciousness, and nerve disorders. The present study aims to evaluate the effectiveness of Phoenix dactylifera fruit extracts (PDF) against rat sickness behaviour caused by lipopolysaccharide (LPS) by assessing behavioural and biochemical parameters. PDF was prepared by extracting dry fruits of P. dactylifera with a methanol:water (4:1, v/v) mixture. The PDF was evaluated for phenolic and flavonoid content and HPLC analysis of quercetin estimation. Adult Wistar rats were treated with LPS, PDF + LPS and dexamethasone + LPS. Water and food intake, behavioural tests such as locomotor activity, tail suspension and forced swim tests were conducted. Furthermore, alanine transaminase (ALT) and aspartate transaminase (AST) were estimated in plasma and malondialdehyde (MDA), reduced glutathione (GSH), nitrite, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were estimated in the brain. PDF ameliorated LPS-induced sickness behaviour by reducing MDA, nitrite, IL-6, and TNF-α levels and improving GSH, behavioural alteration, water and food intake in the treated rats. In the plasma of the treated rats, PDF also decreased the levels of ALT and AST. The outcomes demonstrated the efficacy of PDF in reducing the sickness behaviour caused by LPS in rats. The authors believe that this study will provide the groundwork for future research to better understand the underlying mechanisms of action and therapeutic efficacy.


Amino-acid composition of the covalent rigid-layer lipoprotein in cell walls of Proteus mirabilis.
Cell walls of Proteus mirabilis in the stationary phase of growth contain a lipoprotein in covalent linkage to peptidoglycan and probably also in free form in the outer membrane. The protein moiety of this lipoprotein is composed of about 50 amino acids and has an approximate molecular weight of 5500. The Proteus lipoprotein has glycine and phenylalanine as specific components which are not present in lipoproteins of other enteric bacteria. Treatment of the peptidoglycan-lipoprotein complex of Proteus with trypsin leaves lysine as the only lipoprotein amino acid attached to the peptidoglycan. This suggests that in P. mirabilis, as in Escherichia coli, the lipoprotein is linked to the peptidoglycan by its C-terminal lysine residue.


Deconstructing emotion regulation in schizophrenia: The nature of abnormalities at the selection and implementation stages.
Difficulties with emotion regulation are observed across psychiatric diagnoses, including psychotic disorders. Past studies using trait self-report indicate that people with schizophrenia (SZ) are less likely to use adaptive emotion regulation strategies and more likely to use maladaptive emotion regulation strategies than controls (CN). However, more recent evidence using ecological momentary assessment (EMA) indicates that regulation effectiveness and adaptiveness may vary across strategies. The present study aimed to systematically understand abnormalities in state-level emotion regulation strategy selection, effectiveness, and adaptiveness in SZ compared to CN using EMA. Participants (n = 50 SZ; n = 53 CN) completed 6 days of EMA surveys assessing emotional experience, emotion regulation, and symptoms. Results indicated that SZ selected interpersonal emotion regulation and avoidance more often than CN, while both groups selected reappraisal and distraction more often than avoidance and suppression. Overall, strategies were effective at reducing negative emotion and adaptive for reducing delusions over time. Reappraisal, avoidance, and suppression all significantly down-regulated delusions over time. Although some selection abnormalities were present in terms of rate of selection and effort exertion, people with SZ select strategies which are effective and adaptive in the short term. The present results have implications for how cognitive therapy for psychosis may target delusions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).