Association of renal function with clinical parameters and conditions in a longitudinal population-based epidemiological study.
The aim of the present study was to examine the association of renal function with clinical parameters and conditions in the general population. Study subjects comprised 6,027 community-dwelling individuals who were recruited to the Inabe Health and Longevity Study: A longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The cutoff value, which was used to divide the subjects into those with normal and those with low estimated glomerular filtration rate (eGFR), was 60 ml/min/1.73 m2. Bonferroni's correction was applied to establish the statistical significance of the association. Longitudinal analysis using the generalized linear mixed-effect model, following adjustments for age and gender, revealed that the eGFR was significantly associated (P<0.0017) with serum levels of triglycerides, low-density lipoprotein cholesterol, uric acid, blood glycosylated hemoglobin content, fasting plasma glucose and body mass index. These parameters decreased curvilinearly with increases in eGFR. Furthermore, eGFR correlated positively with serum levels of high-density lipoprotein (HDL) cholesterol. Longitudinal analysis using the generalized estimating equation following adjustment for age and gender indicated a significant association (P<0.0024) between eGFR and prevalence of hypertension, type 2 diabetes mellitus, hypo-HDL cholesterolemia, hyperuricemia and obesity. Thus, low eGFR results in detrimental effects on various clinical parameters and conditions, resulting in increased risk of hypertension, dyslipidemia, type 2 diabetes mellitus, hyperuricemia and obesity.


AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat.
The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed. The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months. As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade. The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.


Twenty years after childhood-onset symptomatic generalized epilepsy the social outcome is usually dependency or death: a population-based study.
To document the adult social outcome for childhood onset symptomatic generalized epilepsies (SGE). Using the Nova Scotia population-based epilepsy cohort we identified children who developed SGE between 1977 and 1985. Social outcome for those >18 years old was assessed in 2003-5 by semi-structured interview with patients and/or caretakers. Eighty children developed SGE, 12% of childhood epilepsy. Syndromes at onset were: SGE undefined 32 (37%), West 32 (42%), Lennox-Gastaut 4, myoclonic astatic 9, other 3. Nineteen (24%) died. Fifty-two survivors (22 women, 30 men) were 23.7 SD 3.6 years old: 46 (88%) had mental retardation; 34 (65%) continued AEDs; and 27 (51%) were unable to walk. Social outcome was good (live independently) in 7 (13%), moderate (unable to live independently but independent for most daily activities) in 15 (29%) and poor (dependent for nearly all activities) in 30 (58%). Twenty-nine (56%) remained at home, 40% in group homes or institutions. Financial dependency was marked - complete dependence on parents/state in 90%. Eleven (20%) were socially isolated, and only 7 (13%) had significant social interaction in community activities. Health was satisfactory in 49 (94%). There were no pregnancies. Only 2 were seizure-free, off AEDs, living independently and financially independent. The social outcome of children with SGE 20 years after diagnosis is usually disappointing. One quarter die and nearly all survivors have mental retardation and are highly dependent.


HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients.
Routine HEV testing of blood products has recently been implemented in Great Britain and the Netherlands. The relevance of transfusion-transmitted HEV infections is still controversially discussed in Europe. All blood donations at the University Medical Center Hamburg-Eppendorf were prospectively tested for HEV RNA by pooled PCR from October 2016 to May 2017. Reactive samples were individually retested. Additionally, stored samples from previous donations of positive donors were tested to determine the duration of HEV viraemia. HEV RNA-positive donors and a control cohort were asked to answer a questionnaire. Twenty-three out of 18,737 HEV RNA-positive donors were identified (0.12%). Only two of the positive donors (8.7%) presented with elevated aminotransferases at time of donation (alanine aminotransferase: 192 and 101 U/L). The retrospective analysis of all positive donors revealed that four asymptomatic donors had been HEV viraemic for up to three months with the longest duration of HEV viraemia exceeding four months. Despite the HEV-testing efforts, 14 HEV RNA-positive blood products were transfused into 12 immunocompromised and two immunocompetent patients. One recipient of these products developed fatal acute-on-chronic liver failure complicated by Pseudomonas septicemia. The questionnaire revealed that HEV RNA-positive donors significantly more often consumed raw pork meat (12 out of 18; 67%) than controls (89 out of 256; 35%; p = 0.01). In two donors, undercooked pork liver dishes were identified as the source of infection. HEV genotyping was possible in 7 out of 23 of HEV viraemic donors and six out of seven isolates belonged to HEV Genotype 3, Group 2. Prolonged HEV viraemia can be detected at a relatively high rate in Northern German blood donors, leading to transfusion-transmitted HEV infections in several patients with the risk of severe and fatal complications. Eating raw pork tartare represented a relevant risk for the acquisition of HEV infection. The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.


Disentangling Conscience Protections.
Earlier this year, the U.S. Department of Health and Human Services announced its intent to strengthen enforcement of legal protections for health care providers' conscience rights. It proposed regulations that would give the DHHS Office of Civil Rights greater authority to ensure that recipients of federal funding comply with federal conscience laws. This recent development creates an opportunity for scholars and policy-makers to revisit the perennial debate about whether and how law should protect health care providers' rights of conscience. Arguments about who should be protected, what actions should be protected, and whether there should be any limitations on the exercise of conscience rights have brought us no closer to a resolution. However, there is one remaining avenue for analysis that has, surprisingly, received very little attention-the question of how providers are protected, and from what consequences. Existing U.S. conscience laws immunize health care providers from a wide range of adverse consequences-including civil liability, criminal prosecution, administrative penalties, adverse action by employers, and discrimination by private actors, among others. However, academic and public policy debates rarely acknowledge the breadth of these protections. It is essential to disentangle this network of possible protections.


Synthesis of globin mRNA in relation to the cell cycle during induced murine erythroleukemia differentiation.
The relationship between the synthesis of globin mRNA and the phase of cell cycle was examined in synchronized murine erythroleukemia cells. Cells were synchronized with respect to the cell division cycle either by culture with 2 mM thymidine or 2 mM thymidine followed by 0.5 mM hydroxyurea, which caused cells to accumulate in late G1 or early S (referred to as G1/S boundary). Cells were induced to erythroid differentiation by culture with 280 mM dimethyl sulfoxide or 4 mM hexamethylene bisacetamide. These inducers do not alter the progression of cells from the G1/S boundary through S, G2, and M, but do cause prolongation of the subsequent G1 phase. Accumulation of newly synthesized globin mRNA is first detected when cells are in this G1 phase.


Isolation and partial characterization of allergen C from Kentucky blue grass pollen.
An allergenic component, designated as Allergen C, was isolated from the retentate (R) of the aqueous extract of defatted Kentucky blue grass (KBG) pollen by a combination of preparative isoelectrofocussing and gel filtration. Allergen C was found to be a glycoprotein with molecular size of the order of 11,000 daltons and had a pI value of approximately 9.7. It possessed all the allergenic determinants collectively present in R. The allergenic activity was found to be associated with the protein moiety of the molecule. Allergen C was one of the 15 antigenic components detectable in R by crossed immunoelectrophoresis with a hyperimmune sheep antiserum to R. Observations based on enzymatic degradation of the molecule suggested that the determinants recognized by murine IgE antibodies were different from those which combined with rabbit precipitating antibodies.


Automated analysis of thiamine, ascorbic acid, and vitamin A.
Methods currently used in most nutrient analysis laboratories are the classical AOAC methods. One of the major challenges facing the analytical chemist is the need for new or modified quantitative and reliable nutrient assay methods, which are rapid and less labor intensive. Recently, numerous vitamin assays have been published which use continuous flow and high pressure liquid chromatographic techniques. This paper deals with some of the recent methods reported for analysis of thiamine and ascorbic acid, using continuous flow wet chemistry, and high pressure liquid chromatography for vitamin A in food products.


Psychiatric disorders among older prisoners: a systematic review and comparison study against older people in the community.
Despite emerging evidence that older prisoners experience poor mental health, literature in this area is still limited. In the present systematic review and meta-analysis, we report on the prevalence of psychiatric disorders among older prisoners and compare our findings against community studies on older people. We searched on Assia, PsycInfo, MedLine, Embase, Web of Science, Google and Gov.uk. We carried out bias assessments, rated studies for quality and ran a heterogeneity test. We meta-analysed prevalence rates of psychiatric disorders through an aggregate weighted mean and calculated relative risk (RR) and statistical significance against community studies. Sensitivity analyses were further performed. We reviewed nine studies and obtained the following prevalence: 'Any psychiatric disorder' 38.4%, depression 28.3%, schizophrenia/psychoses 5.5%, bipolar disorder 4.5%, dementia 3.3%, cognitive impairment 11.8%, personality disorder 22.9%, alcohol abuse 15.9%, anxiety disorders 14.2%, PTSD 6.2%. Older prisoners were found to have higher RR for every single psychiatric disorder against older people in the community, with the sole exception of alcohol abuse (RR = 1) and dementia (RR = .75). The prevalence rates were statistically significantly higher (p < .05) among the prisoners for 'Any psychiatric disorder', depression and personality disorder. Overall, the sensitivity analyses confirmed our original results. Our findings point at a high prevalence of every single psychiatric disorder among older prisoners, who also experience rates of dementia and alcohol abuse comparable to those reported in the community. Our results have relevant implications for policy and practice in this area. Further research is crucial to confirm findings from this study.


A Life Course Theory Approach to Understanding Eritrean Refugees' Perceptions of Preventive Health Care in the United States.
Thousands of Eritreans flee their homes each month, embarking on dangerous journeys. With these extreme life experiences in mind, this qualitative study aimed to better understand Eritrean resettled refugees' perceptions of United States (US) preventive health care through the lens of the Life Course Theory. Through secondary thematic analysis of narrative data, two over-arching themes emerged: 1) a thirst for information, understanding and affordable health care and 2) attitudes of gratitude and hope despite lack of information and funding. Health promotion programs should focus on enhancing community engagement while nurturing protective factors of resiliency and hope to improve information dissemination and access to affordable health-care services.


Intramedullary spinal cord germinoma: case report and review of the literature.
A 33-year-old man with an intramedullary spinal cord germinoma was treated successfully with partial resection, combined chemotherapy with carboplatin and etoposide, and reduced-dose local-field radiation therapy. The authors believe this is the first case without syncytiotrophoblastic giant cells so treated. The literature is reviewed, and the appearance, radiologic and histopathologic features, and treatment of germinomas are discussed.


[Breast-feeding during the first month of life in Cordoba city, Argentina].
In the foregoing investigation breast-feeding during the first 30 days of life was studied in a representative sample of 620 babies born and settled down in the city of Cordoba Argentina. To analyse this information, the classification of breastfeeding suggested by the WHO/UNICEF was used. The results reveal that being a month old, 26% of the babies had complete breastfeeding 60% had partial breastfeeding and the remaining 14% did not have it at all. Among the children with complete breast-feeding, 21% was exclusive and 5% was prevailing. 18% of the babies were exposed to breastfeeding before an hour and a half after they were born, the average number of nursings a day was 7.3 (D.S. 1.9) taking less than 15 minutes to reach the 57%; and with a free-demanding timetable in 44%. The children with partial breast-feeding were classified into low, medium, and high being 20%, 54%, 22% respectively. The average age in which another milk was introduced was 3.7 days, and the main reasons were "insufficient mother milk", and "the child's hunger". Among the children with artificial lactation, 87% were once exposed to breastfeeding, the weaning took place during the 4 days in average (D.S. 5.6) and in an abrupt way in 55% of them. The Health personnel helped supporting the introduction of lacteal formula in 68% of the children with partial lactation and in 42% of the cases of complete abandon of natural breastfeeding.


Swallowing problems in Parkinson disease: frequency and clinical correlates.
Changes to the efficiency and integrity of swallowing mechanisms are inevitable in Parkinson disease (PD); however, it remains unclear how many people with PD are at risk of dysphagia. The aim of this study was to establish the frequency of impaired swallowing in people with PD and the relationship between swallowing performance and indicators of disease progression. A community-based and hospital-based cohort of 137 individuals with PD were asked to drink 150 ml of water as quickly as possible while in an 'off drug' state. Thirty-one (23%) patients could not completely drink the full 150 ml. Swallowing rate (ml/sec) fell to more than 1 SD below published norms for 115 (84%) patients and to more than 2SD below for 44 (32%) individuals. There were moderate correlations between rate of swallowing and disease severity, depression and cognition, but not between swallowing speed and disease duration. There was poor correlation between subjective reports of dysphagia and performance on the water swallow test. Swallowing problems are frequent in PD. Self-report of 'no difficulty' is not a reliable indicator of swallowing ability. Studies employing more-objective assessment of aspiration risk to compare with water swallow test performance are advocated.


The application of computer color matching techniques to the matching of target colors in a food substrate: a first step in the development of foods with customized appearance.
A predictive color matching model based on the colorimetric technique was developed and used to calculate the concentrations of primary food dyes needed in a model food substrate to match a set of standard tile colors. This research is the first stage in the development of novel three-dimensional (3D) foods in which color images or designs can be rapidly reproduced in 3D form. Absorption coefficients were derived for each dye, from a concentration series in the model substrate, a microwave-baked cake. When used in a linear, additive blending model these coefficients were able to predict cake color from selected dye blends to within 3 ΔE*(ab,10) color difference units, or within the limit of a visually acceptable match. Absorption coefficients were converted to pseudo X₁₀, Y₁₀, and Z₁₀ tri-stimulus values (X₁₀(P), Y₁₀(P), Z₁₀(P)) for colorimetric matching. The Allen algorithm was used to calculate dye concentrations to match the X₁₀(P), Y₁₀(P), and Z₁₀(P) values of each tile color. Several recipes for each color were computed with the tile specular component included or excluded, and tested in the cake. Some tile colors proved out-of-gamut, limited by legal dye concentrations; these were scaled to within legal range. Actual differences suggest reasonable visual matches could be achieved for within-gamut tile colors. The Allen algorithm, with appropriate adjustments of concentration outputs, could provide a sufficiently rapid and accurate calculation tool for 3D color food printing. The predictive color matching approach shows potential for use in a novel embodiment of 3D food printing in which a color image or design could be rendered within a food matrix through the selective blending of primary dyes to reproduce each color element. The on-demand nature of this food application requires rapid color outputs which could be provided by the color matching technique, currently used in nonfood industries, rather than by empirical food industry methods.


A sterilizing tail stump sperm defect in a Holstein-Friesian bull.
A case of sterility in an 18-month-old bull of the Holstein-Friesian breed was investigated. A semen sample sent to the laboratory showed a very low sperm concentration and abnormal sperm morphology. On the preliminary examination, the major sperm defect (60-70%) seemed to be tailless heads. When higher manification was used it was found that most of the defective heads had a short tail rudiment, a tail stump 2-3 mu long. Loose sperm tails were seldom seen in the smears. The defect has been described previously from Canada where it has occurred in different breeds, including Holstein-Friesians. The dam of the Danish bull in question was inseminated with imported American semen, and the sire is one of the most demanded Holstein-Friesian bulls at present. The possible heredity of the defect is discussed.


Assembly of Ultrathin Gold Nanowires: From Polymer Analogue to Colloidal Block.
Ultrathin nanowires (NWs) are considered to be ideal building blocks for the assembly of complex nanostructures toward future nanodevices. The polymer/particle duality of ultrathin NWs plays an important role in the study of solution phase self-assembly behavior of ultrathin NWs; yet it has not been fully exploited. Herein, we demonstrate the effects of the polymer/particle duality of ultrathin NWs on the morphologies of assembled complex nanostructures. The length of ultrathin AuNWs directly correlates with the flexibility of NWs and affects the polymer-like assembly of NWs, while the concentration of surfactants determines interfacial tension and ligand-solvent interactions and affects both polymer-like and colloidal assembly of NWs. By fine-tuning these two factors, ultrathin AuNWs can swing between "soft" and "hard" building blocks, and highly uniform nanorings, nanograins, nanobundles, and superlattice-like nanospheres are obtained. The different assembly behavior of long and short NWs can be considered as two components to construct anisotropic complex nanostructures, in analogy with the fabrication of polymer-inorganic nanoparticle hybrid nanostructures. We synthesized anisotropic structures of Au nanodiamond rings and nanonecklaces by the coassembly of polymer-like long NWs with particle-like short NWs or Au nanoparticles. This strategy could potentially be extended to the organization of anisotropic complex nanostructures with other ultrathin NW systems in the future.


Elevated hematocrit enhances platelet accumulation following vascular injury.
Red blood cells (RBCs) demonstrate procoagulant properties in vitro, and elevated hematocrit is associated with reduced bleeding and increased thrombosis risk in humans. These observations suggest RBCs contribute to thrombus formation. However, effects of RBCs on thrombosis are difficult to assess because humans and mice with elevated hematocrit typically have coexisting pathologies. Using an experimental model of elevated hematocrit in healthy mice, we measured effects of hematocrit in 2 in vivo clot formation models. We also assessed thrombin generation, platelet-thrombus interactions, and platelet accumulation in thrombi ex vivo, in vitro, and in silico. Compared with controls, mice with elevated hematocrit (RBCHIGH) formed thrombi at a faster rate and had a shortened vessel occlusion time. Thrombi in control and RBCHIGH mice did not differ in size or fibrin content, and there was no difference in levels of circulating thrombin-antithrombin complexes. In vitro, increasing the hematocrit increased thrombin generation in the absence of platelets; however, this effect was reduced in the presence of platelets. In silico, direct numerical simulations of whole blood predicted elevated hematocrit increases the frequency and duration of interactions between platelets and a thrombus. When human whole blood was perfused over collagen at arterial shear rates, elevating the hematocrit increased the rate of platelet deposition and thrombus growth. These data suggest RBCs promote arterial thrombosis by enhancing platelet accumulation at the site of vessel injury. Maintaining a normal hematocrit may reduce arterial thrombosis risk in humans.


A simple method for removing initial irregularity of an electrocardiogram during a transient state of a power supply in a defibrillator.
The defibrillator is a device that instantaneously discharges the high energy stored in the capacitor to the human body to help revitalize the heart. The circuit for charging the capacitor uses the same power source as the biosignal measurement unit. Therefore, variation in main power supply voltage, ground noise, and electromagnetic interference from the charging circuit can induce distortion into the biosignal at the initial stage of charging. In this study, a simple method is proposed for removing the initial irregularity of an electrocardiogram due to the transient state of a power supply. To evaluate the method, a 1-channel electrocardiogram measurement unit and peripheral units were separated from the main control module using galvanic isolation. An isolated push-pull converter was designed to power the secondary side. The method was tested under steady-state and transient conditions. The obtained results proved that biosignal distortion can be significantly reduced. This method could be another simple implementation approach for solving signal distortions due to the transient status of power supplies used in medical devices.


Matrix effect on the analysis of oligonucleotides by using a mass spectrometer with a sonic spray ionization source.
Matrix or impurities remaining in a DNA sample solution after various sample treatment procedures may influence a subsequent DNA analysis. In this work, several matrices were investigated concerning their effects on the analysis of oligonucleotide by using an ion-trap mass spectrometer equipped with a sonic spray ionization source. Inorganic salts of sodium chloride and magnesium chloride depressed the signal intensity by about 50% when the content of the salts was about 10 microM. dNTPs and Taq showed more severe depression on the oligonucleotide. However, Tris, or (hydroxymethyl)aminomethane, intensified the signal intensity, if its content was within an appropriate range. When the content of Tris was about 500 microM, the signal intensity was enhanced by factors of 3 and 5 for the 6-mer and the 20-mer oligonucleotides, respectively. With the existence of Tris, matrix effects from the inorganic salts, dNTPs and Taq were reduced.


Medicine donations: a review of policies and practices.
To help promote the effective delivery of drug donations, the World Health Organization (WHO) developed the Guidelines for Medicine Donations. The need for revisions is timely given the large-scale influx of medicine donations since the start of the COVID-19 pandemic. This study analyses current policies of donors and recipients that are commensurate with the recommendations in the Guidelines and examines current practices, challenges, and revision suggestions. A search for medicine donation policies of donors and recipients was conducted in May/June 2022 and repeated in January 2023. Potential donor countries were identified from the high-income countries on the United Nation's (UN) List of G20 Countries. Potential pharmaceutical company donors were selected from those with 2021 revenue of $30 billion or greater. Potential non-government organization donors came from the WHO list of non-governmental organizations (NGOs) and two other sources. Potential recipient countries were those on the UN List of Least Developed Countries. These four lists were supplemented with actual donors and recipients identified from the literature. All policies retrieved were screened to identify which of the 12 recommendations from the WHO Guidelines were incorporated. We identified 38 policies from 1 donor country, 6 brand-name multinational pharmaceutical companies, 6 NGOs and 25 recipient countries. Most policies incorporated all 12 recommendations. Twenty-five of the 38 policies were developed in 2010 or later. The majority of actual donors and recipients did not have policies that were publicly available. A rapid literature review for publications from 2010 onwards identified challenges in implementing the WHO Guidelines and suggested for revisions. Challenges included: (1) information management; (2) medication presentation; (3) influence from the pharmaceutical industry; (4) donation sustainability; and (5) the belief that donations are inherently good. Our findings suggest that both donors and recipients could further align their policies with the existing Guidelines and both groups should be consulted on any revisions to ensure that their experiences are reflected and their needs are addressed. While the current WHO Guidelines for Medicine Donations are a solid base for medical humanitarian efforts, evidence points to the need for an update to meet current challenges.


Hyaluronate-Peanut Agglutinin Conjugates for Target-Specific Bioimaging of Colon Cancer.
Colon cancer is one of the most common death-related cancers in the world. For treating colon cancer, it is crucial to detect and remove malignant lesions early. Here, we developed hyaluronate (HA)-peanut agglutinin (PNA) conjugates for the bioimaging of colon cancer. The HA-PNA conjugates were successfully synthesized by the coupling reaction between aldehyde-modified HA and the N-terminal amine group of PNA. For diagnostic imaging, rhodamine B (RhoB) was chemically conjugated onto PNA in HA-PNA conjugates. After intraluminal injection of HA-PNA-RhoB conjugates into tumor-bearing mice, small-sized colon cancers could be effectively visualized by ex vivo imaging with an in vivo imaging system (IVIS) and a two-photon microscope. With these results taken together, we could confirm the feasibility of HA-PNA-RhoB conjugates as a bioimaging agent for detecting colon cancers.


MicroRNAs synergistically regulate milk fat synthesis in mammary gland epithelial cells of dairy goats.
Synergistic regulation among microRNAs (miRNAs) is important to understand the mechanisms underlying the complex molecular regulatory networks in goats. Goat milk fat synthesis is driven by a gene network that involves many biological processes in the mammary gland. These biological processes are affected by several miRNAs rather than a single miRNA. Therefore, identifying synergistic miRNAs is necessary to further understand the functions of miRNAs and the metabolism of goat milk fat synthesis. Using qRT-PCR, we assessed the expression of 11 miRNAs that have the potential to regulate milk fat synthesis in the goat mammary gland. Six of these miRNAs exhibited expression during the lactation cycle. Additionally, we also found that prolactin, the key hormone that regulates lactation, promotes the expression of four miRNAs (miR-23a, miR-27b, miR-103, and miR-200a). Further functional analysis showed that overexpression of all four miRNAs by using recombinant adenovirus in goat mammary gland epithelial cells can affect gene mRNA expression associated with milk fat synthesis. Specifically, elevated miR-200a expression suppressed the mRNA expression of genes involved in fat droplet formation. To analyze the synergistic regulation among these four miRNAs (miR-23a, miR-27b, miR-103, and miR-200a), we used the Pearson correlation coefficient to evaluate the correlation between their expression levels in 30 lactating goats. As a result, we found a strong correlation and mutual regulation between three miRNA pairs (miR-23a and miR-27b, miR-103 and miR-200a, miR-27b and miR-200a). This study provides the first experimental evidence that miRNA expression is synergistically regulated in the goat mammary gland and has identified the potential biological role of miRNAs in goat milk fat synthesis. The identification of synergistic miRNAs is a crucial step for further understanding the molecular network of milk fat synthesis at a system-wide level.


Stress management: MHC class I and class I-like molecules as reporters of cellular stress.
The evolutionarily ancient intracellular stress response protects cells from the effects of external and internal forces which perturb cellular metabolism. Members of the major histocompatibility complex (MHC) class I-like superfamily act as cell surface indicators of the intracellular stress response. Cellular immunity employs these indicators as a cue for elimination of damaged, infected, and malignant cells, promoting the health of the individual and the evolutionary success of the species.


Observations on the transmissibility of lentogenic strains of Newcastle disease virus: significance of variables.
Virus strain and age of chicken influenced the transmissibility of lentogenic strains of Newcastle disease virus (NDV). The ability of LaSota, B1, V4, CT, F, and Ulster strains to spread from cages of oronasally inoculated chickens to adjacent cages of susceptible chickens was assessed by virus isolation, serology, and immunity to challenge with virulent NDV. Although all inoculated chickens were immune to challenge, the immunity of contact chickens ranged from 100% for LaSota and CT strains to 0% for Ulster strain. The transmissibility of B1 and V4 strains for chickens 1, 4, 8, and 16 weeks old was assessed by within-cage contact infection, exposure to contaminated food and water containers, and exposure to air from infected chickens. Serology and immunity to challenge with virulent virus were used as criteria. Differences in transmissibility were observed for the strain of virus used, route of exposure, and age of chickens. Care must be used in interpreting the significance of strain differences until the effect of variables can be minimized by further improvements in design of the test procedure.


Denatured state effects and the origin of nonclassical phi values in protein folding.
Analysis of the phi value is one of the most powerful tools to understand the transition state for protein folding. In principle, phi values are expected to fall in the range of 0 to 1. However, a noticeable number of phi values have been observed which are either less than 0 or greater than 1. The origin of such phi values, sometimes referred to as noncanonical or nonclassical phi values, has been controversial. Here we show that mutational effects upon denatured state energetics can lead to nonclassical phi values.


The influence of specific chronic somatic conditions on the care for co-morbid depression in general practice.
Limited information exists on the relationship between specific chronic somatic conditions and care for co-morbid depression in primary care settings. Therefore, the present prospective, general practice-based study examined this relationship. Longitudinal data on morbidity, prescribing and referrals concerning 991 patients newly diagnosed with depression by their general practitioner (GP) were analysed. The influence of a broad range of 13 specific chronic somatic conditions on the initiation of any depression care, as well as the prescription of continuous antidepressant therapy for 180 days, was examined. Multilevel logistic regression analysis was used to control for history of depression, psychiatric co-morbidity, sociodemographics and interpractice variation. Multilevel analysis showed that patients with pre-existing ischaemic heart disease (72.1%) or cardiac arrhythmia (59.3%) were significantly less likely to have any depression care being initiated by their GP than patients without chronic somatic morbidity (88.0%). No other specific condition had a significant influence on GP initiation of any care for depression. Among the patients being prescribed antidepressant treatment by their GP, none of the conditions was significantly associated with being prescribed continuous treatment for 180 days. Our study indicates that patients with ischaemic heart disease or cardiac arrhythmia have a lower likelihood of GP initiation of any care for depression after being newly diagnosed with depression by their GP. This finding points to the importance of developing interventions aimed at supporting GPs in the adequate management of co-morbid depression in heart disease patients to reduce the negative effects of this co-morbidity.


Limbic Encephalitis Associated with Human Herpesvirus-7 (HHV-7) in an Immunocompetent Adult: The First Reported Case in Japan.
A 35-year-old male who had not previously suffered any major illnesses was admitted to our hospital because of general fatigue, fever, headache, vomiting, consciousness disturbance, and seizures. A neurological examination showed that he was in a semi-comatose state and exhibited neck stiffness. Brain magnetic resonance imaging detected high-intensity areas in the bilateral hippocampi and periventricular white matter. A cerebrospinal fluid examination revealed mononuclear pleocytosis, an elevated protein level, and positivity for human herpesvirus-7 (HHV-7) DNA. The patient's condition improved after the administration of methylprednisolone, intravenous immunoglobulins, and acyclovir. This is the first known case of limbic encephalitis associated with HHV-7 in an immunocompetent Japanese adult.


Treatment of hepatic metastases of neuroendocrine malignancies: a 10-year experience.
Liver metastases from neuroendocrine tumours may give rise to symptoms due to hormone production or mass effect. Accepted management options include administration of somatostatin-analogues, selective chemoembolisation or hepatic resection. The aim of this study was to review the management of hepatic neuroendocrine metastases in our unit. Patients with neuroendocrine tumours presenting between 1989 and 1999 were identified from pathology, radiology and surgical databases. Case notes were retrospectively reviewed for demographic data, treatment modality and outcome. Response to treatment was based on biochemistry, radiology or symptoms, and response rates were defined accordingly. Thirty patients with a mean age of 55 years presented with, or later developed liver metastases. The most frequent presenting symptoms were abdominal pain (63%), diarrhoea (40%), weight loss (33%) and flushing (13%). Five patients underwent liver resection with complete symptomatic response, nine underwent chemoembolisation with a 75% response rate (either biochemically, radiologically or symptomatic) and fifteen were treated with a somatostatin-analogue, with a response rate of 86%. Median survival from detection of metastases was 45 months. Liver resection provides good symptomatic relief, but it is only indicated in a small proportion of patients with metastatic neuroendocrine tumours. Both chemoembolisation and somatostatin-analogues offer useful symptomatic control for these patients with good survival prospects.


Photosensitizing activity of advanced glycation endproducts on tryptophan, glucose 6-phosphate dehydrogenase, human serum albumin and ascorbic acid evaluated at low oxygen pressure.
A comparative study of the photosensitizing activity of advanced glycation endproducts (AGEs) prepared by incubating glucose (Glc), threose (Threo) and ascorbate (AH-) in the presence of lysine (Lys) was performed. Photochemical activity was evaluated under low oxygen pressure with the aim to simulate the conditions of the eye lens. AGE-sensitized tryptophan and AH- photodecomposition and glucose 6-phosphate dehydrogenase inactivation were studied. In all systems, glucose-derived AGEs showed the highest photosensitizing efficiency, followed by ascorbate and threose. The presence of different sensitizers in glycation products mixtures was investigated. For this purpose, Trp decomposition quantum yields were determined at 344 and 367 nm. The values obtained at 344 nm are between three and six times higher than those observed at 367 nm, confirming the presence of at least two compounds with different photosensitizing activities in the mixtures. The chemiluminescence associated with the AGE-mediated oxidation of free Trp and Trp residues in human serum albumin was also studied, and a good correlation between the emission of light and the extent of Trp decomposition was found. In conclusion, it is demonstrated that glucose derived AGEs, which can be formed in vivo in the eye lens of diabetic patients and are accumulated in elderly lenses, have a higher photosensitizing efficiency, at low oxygen pressure, than those arising from ascorbate and threose. This high efficiency is especially significant when proteins are employed as photochemical targets, indicating that protein-sensitizer interaction and the local environment around the sensitizers play an important role.


An Efficacy Predictive Method for Diabetic Ulcers Based on Higher-Order Markov Chain-Set Pair Analysis.
Clinical comprehensive decision-making of diabetic ulcers includes curative effect evaluation and curative effect prediction. Nevertheless, there are few studies on the prediction of diabetic ulcers. Set pair analysis (SPA) was used to assess the curative effect evaluation, and therapeutic effect was evaluated by connection degree (CD). The higher-order Markov chain-SPA curative effect prediction model was established to predict the future curative effect development. The predicted results with higher-order Markov chain-SPA and traditional first-order Markov-SPA model were compared with the actual results of the patients to verify the effectiveness of prediction. The connection degree of index levels I and II of 15 patients with diabetic ulcers after traditional Chinese medicine (TCM) treatment increased with time, while that of index levels IV and V decreased, indicating that the curative effect tends to improve. The higher-order Markov chain-SPA model was used to predict the curative effect. The results showed that the relative errors were fewer than the traditional first-order Markov-SPA model. The present study suggests that a method of SPA combined with higher-order Markov-SPA is relatively effective and can be applied to the clinical prediction of diabetic ulcers, which has higher accuracy than traditional first-order curative effect prediction model.


Calculation of photodetachment cross sections and photoelectron angular distributions of negative ions using density functional theory.
Recently, the development of photoelectron velocity map imaging makes it much easier to obtain the photoelectron angular distributions (PADs) experimentally. However, explanations of PADs are only qualitative in most cases, and very limited works have been reported on how to calculate PAD of anions. In the present work, we report a method using the density-functional-theory Kohn-Sham orbitals to calculate the photodetachment cross sections and the anisotropy parameter β. The spherical average over all random molecular orientation is calculated analytically. A program which can handle both the Gaussian type orbital and the Slater type orbital has been coded. The testing calculations on Li(-), C(-), O(-), F(-), CH(-), OH(-), NH2 (-), O2 (-), and S2 (-) show that our method is an efficient way to calculate the photodetachment cross section and anisotropy parameter β for anions, thus promising for large systems.


Genetic characterization of highly pathogenic avian influenza A H5N8 viruses isolated from wild birds in Egypt.
A newly emerged H5N8 influenza virus was isolated from green-winged teal in Egypt during December 2016. In this study, we provide a detailed characterization of full genomes of Egyptian H5N8 viruses and some virological features. Genetic analysis demonstrated that the Egyptian H5N8 viruses are highly pathogenic avian influenza viruses. Phylogenetic analysis revealed that the genome of the Egyptian H5N8 viruses was related to recently characterized reassortant H5N8 viruses of clade 126.96.36.199 isolated from different Eurasian countries. Multiple peculiar mutations were characterized in the Egyptian H5N8 viruses, which probably permits transmission and virulence of these viruses in mammals. The Egyptian H5N8 viruses preferentially bound to avian-like receptors rather than human-like receptors. Also, the Egyptian H5N8 viruses were fully sensitive to amantadine and neuraminidase inhibitors. Chicken sera raised against commercial inactivated avian influenza-H5 vaccines showed no or very low reactivity with the currently characterized H5N8 viruses in agreement with the genetic dissimilarity. Surveillance of avian influenza in waterfowl provides early warning of specific threats to poultry and human health and hence should be continued.


Differences in chemoselectivity in olefin oxidation by a series of non-porphyrin manganese(IV)-oxo complexes.
High valent metal-oxo intermediates are versatile oxidants known to facilitate both oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactions in nature. In addition to performing essential yet challenging biological reactions, these intermediates are known for their selectivity in favoring the formation of one oxidation product. To understand the basis for this selectivity, we explore the role of equatorial ligand field perturbations in MnIV-oxo complexes on chemoselectivity in cyclohexene oxidation. We also examine reactions of MnIV-oxo complexes with cyclohexene-d10, cyclooctene, and styrene. Within this series, the product distribution in olefin oxidation is highly dependent on the coordination environment of the MnIV-oxo unit. While MnIV-oxo complexes with sterically encumbered, and slightly tilted, MnO units favor CC epoxidation products in cyclohexene oxidation, a less encumbered analogue prefers to cleave allylic C-H bonds, resulting in cyclohexenol and cyclohexenone formation. These conclusions are drawn from GC-MS product analysis of the reaction mixture, changes in the UV-vis absorption spectra, and kinetic analyses. DFT computations establish a trend in thermodynamic properties of the MnIV-oxo complexes and their reactivity towards olefin oxidation on the basis of the MnO bond dissociation free energy (BDFE). The most reactive MnIV-oxo adduct from this series oxidizes cyclohexene-d10, cyclooctene, and styrene to give corresponding epoxides as the only detected products. Collectively, these results suggest that the chemoselectivity obtained in oxidation of olefins is controlled by both the coordination environment around the MnO unit, which modulates the MnO BDFE, and the BDFEs of the allylic C-H bond of the olefins.


4-Nitro-N-(4-nitro-benzo-yl)benzamide.
The central acetyl-acetamide moiety in the title compound, C(14)H(9)N(3)O(6), is buckled [e.g. the C-N-C-O torsion angle is 14.3 (6)°] but the r.m.s. deviation for the five atoms is 0.044 Å. The benzene rings lie on the same side of the central plane, forming dihedral angles of 37.17 (15) and 28.58 (19)° with it. The dihedral angle between the two rings is 17.8 (2)° indicating that the mol-ecule is curved. The carbonyl groups are syn to each other and anti to the amino H atom. This allows for the formation of N-H⋯O hydrogen bonds in the crystal, which leads to twisted chains along the b axis. Positional disorder (50:50) of the O atoms was modelled for both the nitro groups.


Utility of the cumulative stress and mismatch hypotheses in understanding the neurobiological impacts of childhood abuse and recent stress in youth with emerging mental disorder.
Childhood abuse has an enduring impact on the brain's stress system. Whether the effects of childhood abuse and adulthood stress are additive (cumulative stress hypothesis) or interactive (mismatch hypothesis) is widely disputed, however. The primary aim of this study was to test the utility of the cumulative stress and mismatch hypotheses in understanding brain and behaviour. We recruited 64 individuals (aged 14-26) from a specialised clinic for assessment and early intervention of mental health problems in young people. A T1-weighted MRI, a resting state fMRI and clinical assessment were acquired from each participant. Grey matter estimates and resting state functional connectivity (rsFC) of the hippocampus, amygdala and anterior cingulate cortex (ACC) were determined using segmentation and seed-to-voxel rsFC analyses. We explored the effects of childhood abuse and recent stress on the structure and function of the regions of interest within general linear models. Worse psychiatric symptoms were significantly related to higher levels of life time stress. Individuals with mismatched childhood and recent stress levels had reduced left hippocampal volume, reduced ACC-ventrolateral prefrontal cortex rsFC and greater ACC-hippocampus rsFC, compared to individuals with matched childhood and recent stress levels. These results show specific utility of the cumulative stress hypothesis in understanding psychiatric symptomatology and of the mismatch hypothesis in modelling hippocampal grey matter, prefrontal rsFC, and prefrontal-hippocampal rsFC. We provide novel evidence for the enduring impact of childhood abuse on stress reactivity in a clinical population, and demonstrate the distinct effects of stress in different systems. Hum Brain Mapp 38:2709-2721, 2017. © 2017 Wiley Periodicals, Inc.


Effects of Polychlorinated Biphenyls (PCBs) and Their Hydroxylated Metabolites (OH-PCBs) on Arabidopsis thaliana.
Plants metabolize polychlorinated biphenyls (PCBs) into hydroxylated derivatives (OH-PCBs), which are sometimes more toxic than the parent PCBs. The objective of this research was to compare the toxicity of a suite of PCBs and OH-PCBs toward the model plant, Arabidopsis thaliana. While parent PCBs and higher-chlorinated OH-PCBs exhibited a low or nondetectable toxicity, lower-chlorinated OH-PCBs significantly inhibited the germination rate and plant growth, with inhibition concentration 50% (IC50) ranging from 1.6 to 12.0 mg L-1. The transcriptomic response of A. thaliana to 2,5-dichlorobiphenyl (2,5-DCB), and its OH metabolite, 4'-OH-2,5-DCB, was then examined using whole-genome expression microarrays (Affymetrix). Exposure to 2,5-DCB and 4'-OH-2,5-DCB resulted in different expression patterns, with the former leading to enrichment of genes involved in response to toxic stress and detoxification functions. Exposure to 2,5-DCB induced multiple xenobiotic response genes, such as cytochrome P-450 and glutathione S-transferases, potentially involved in the PCB metabolism. On the contrary, exposure to both compounds resulted in the down-regulation of genes involved in stresses not directly related to toxicity. Unlike its OH derivative, 2,5-DCB was shown to induce a transcriptomic profile similar to plant safeners, which are nontoxic chemicals stimulating detoxification pathways in plants. The differentiated induction of detoxification enzymes by 2,5-DCB may explain its lower phytotoxicity compared to 4'-OH-2,5-DCB.


In vitro assessment of the acaricidal activity of Piper longum, Piper nigrum, and Zingiber officinale extracts against Hyalomma anatolicum ticks.
Ticks and tick-borne diseases are a major constraint for the sustainable cattle industry in the tropical and subtropical regions including the Indian subcontinent. The development of resistance to most of the commonly used acaricides leads to an attempt to screen plant extracts and their combinations for their possible acaricidal activity to develop an eco-friendly tick control alternative. An alcoholic and various aqueous extracts of Piper longum, Piper nigrum and Zingiber officinale and their combinations were evaluated for acaricidal activity against the three-host ixodid tick, Hyalomma anatolicum by larval immersion test using 14-21 days old unfed larvae. The efficacy was assessed by measuring larval mortality (%) and the lethal concentrations for 50% (LC50) and 95% (LC95) with their 95% confidence limits (CL) values were estimated by applying regression equation analysis to the probit transformed data of mortality. A concentration-dependent mortality response was recorded in all extracts prepared from seeds of P. longum and P. nigrum and their combinations. The highest acaricidal property was exhibited by the alcoholic extract of P. longum seeds with the minimum LC50 and LC95 (95% CL) values of 0.071% (0.07-0.072) and 0.135% (0.13-0.14), respectively, followed by alcoholic combinations. Interestingly, no acaricidal activity was recorded in extracts prepared from the rhizome of Z. officinale. The results indicated that the ethanolic extracts of P. longum and P. nigrum and their combinations can be used effectively for tick control in an integrated format.


Zika Virus, Elevation, and Transmission Risk.
Zika virus has appeared in the Americas in the form of a major outbreak, and is now known to cause birth defects when pregnant women are infected. As a result, the Centers for Disease Control and Prevention issued travel guidelines, in the form of an elevational risk definition: destinations below 2000m are considered as at-risk. We explored the distribution of known Zika virus vector mosquito species in relation to climatic conditions, elevation, latitude, and air traffic connections to the United States. In view of the tropical and subtropical nature of the mosquito species that are the primary Zika virus vectors, we point out that climate varies rather dramatically with respect to elevation and latitude, such that a single elevational criterion will be a poor predictor of potential for transmission. We suggest an initial adjustment would consider latitude in addition to elevation; a more definitive, quantitative analysis of risk would consider variables of ecology, climate, human condition, and connectivity of areas.


C-Terminally fused affinity Strep-tag II is removed by proteolysis from recombinant human erythropoietin expressed in transgenic tobacco plants.
C -terminally fused Strep -tag II is removed from rhuEPO expressed in tobacco plants. The finding suggests that direct fusion of purification tags at the C -terminus of rhuEPO should be avoided. Asialo-erythropoietin (asialo-EPO), a desialylated form of EPO, is a potent tissue-protective agent. Recently, we and others have exploited a low-cost plant-based expression system to produce recombinant human asialo-EPO (asialo-rhuEPO(P)). To facilitate purification from plant extracts, Strep-tag II was engineered at the C-terminus of EPO. Although asialo-rhuEPO(P) was efficiently expressed in transgenic tobacco plants, affinity purification based on Strep -tag II did not result in the recovery of the protein. In this study, we investigated the stability of Strep-tag II tagged asialo-rhuEPO(P) expressed in tobacco plants to understand whether this fused tag is cleaved or inaccessible. Sequencing RT-PCR products confirmed that fused DNA sequences encoding Strep-tag II were properly transcribed, and three-dimensional protein structure model revealed that the tag must be fully accessible. However, Western blot analysis of leaf extracts and purified asialo-rhuEPO(P) revealed that the Strep-tag II was absent on the protein. Additionally, no peptide fragment containing Strep-tag II was identified in the LC-MS/MS analysis of purified protein further supporting that the affinity tag was absent on asialo-rhuEPO(P). However, Strep-tag II was detected on asialo-rhuEPO(P) that was retained in the endoplasmic reticulum, suggesting that the Strep-tag II is removed during protein secretion or extraction. These findings together with recent reports that C-terminally fused Strep-tag II or IgG Fc domain are also removed from EPO in tobacco plants, suggest that its C-terminus may be highly susceptible to proteolysis in tobacco plants. Therefore, direct fusion of purification tags at the C-terminus of EPO should be avoided while expressing it in tobacco plants.


Combining sparse coding and time-domain features for heart sound classification.
This paper builds upon work submitted as part of the 2016 PhysioNet/CinC Challenge, which used sparse coding as a feature extraction tool on audio PCG data for heart sound classification. In sparse coding, preprocessed data is decomposed into a dictionary matrix and a sparse coefficient matrix. The dictionary matrix represents statistically important features of the audio segments. The sparse coefficient matrix is a mapping that represents which features are used by each segment. Working in the sparse domain, we train support vector machines (SVMs) for each audio segment (S1, systole, S2, diastole) and the full cardiac cycle. We train a sixth SVM to combine the results from the preliminary SVMs into a single binary label for the entire PCG recording. In addition to classifying heart sounds using sparse coding, this paper presents two novel modifications. The first uses a matrix norm in the dictionary update step of sparse coding to encourage the dictionary to learn discriminating features from the abnormal heart recordings. The second combines the sparse coding features with time-domain features in the final SVM stage. The original algorithm submitted to the challenge achieved a cross-validated mean accuracy (MAcc) score of 0.8652 (Se = 0.8669 and Sp = 0.8634). After incorporating the modifications new to this paper, we report an improved cross-validated MAcc of 0.8926 (Se = 0.9007 and Sp = 0.8845). Our results show that sparse coding is an effective way to define spectral features of the cardiac cycle and its sub-cycles for the purpose of classification. In addition, we demonstrate that sparse coding can be combined with additional feature extraction methods to improve classification accuracy.


[Schleimpflug photography detects alterations in corneal density and thickness in patients with dry eye disease].
Dry eye disease is a common ocular surface disease that significantly affects the quality of life. Little is known about a potential impact of the disease on corneal morphology. This study was carried out to investigate for the first time if dry eye disease induces changes in corneal density and thickness. In total 97 patients suffering from dry eye disease and 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and analyzed for central corneal thickness and corneal density in five anatomical layers (i.e. epithelium, Bowman membrane, corneal stroma, Descemet membrane and endothelium). Corneal density was significantly reduced in the epithelium (p = 0.0053), Bowman membrane (p = 0.0049) and Descemet's membrane (p = 0.0385) in patients with dry eye syndrome compared to healthy controls. This decrease was age-dependant. Furthermore, central corneal thickness was significantly reduced in patients with dry eye syndrome compared to the control group (p = 0.0495). The change was again dependent on age with lower values at higher age. Central corneal thickness increased with age in the control group. The results of this study indicate that corneal morphology is subject to significant alterations in patients with dry eye disease. Scheimpflug photography provides not only unique information in lens trials but is also able to detect changes of corneal anatomy. However, further investigations with other anterior segment imaging techniques, such spectral domain optical coherence tomography (SD OCT/Pentacam®) are necessary to further evaluate the clinical consequences of these findings.


TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading.
Neurofibrillary tangles (NFTs) composed of hyperphosphorylated and misfolded tau protein are a pathological hallmark of Alzheimer's disease and other tauopathy conditions. Tau is predominantly an intraneuronal protein but is also secreted in physiological and pathological conditions. The extracellular tau has been implicated in the seeding and propagation of tau pathology and is the prime target of the current tau immunotherapy. However, truncated tau species lacking the microtubule-binding repeat (MTBR) domains essential for seeding have been shown to undergo active secretion and the mechanisms and functional consequences of the various extracellular tau are poorly understood. We report here that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, plays an essential role in the lysosomal exocytosis of selected tau species. TFEB loss of function significantly reduced the levels of interstitial fluid (ISF) tau in PS19 mice expressing P301S mutant tau and in conditioned media of mutant tau expressing primary neurons, while the secretion of endogenous wild-type tau was not affected. Mechanistically we found that TFEB regulates the secretion of truncated mutant tau lacking MTBR and this process is dependent on the lysosomal calcium channel TRPML1. Consistent with the seeding-incompetent nature of the truncated tau and supporting the concept that TFEB-mediated lysosomal exocytosis promotes cellular clearance, we show that reduced ISF tau in the absence of TFEB is associated with enhanced intraneuronal pathology and accelerated spreading. Our results support the idea that TFEB-mediated tau exocytosis serves as a clearance mechanism to reduce intracellular tau under pathological conditions and that effective tau immunotherapy should devoid targeting these extracellular tau species.


Potential Therapeutic Targets in Energy Metabolism Pathways of Breast Cancer.
Mutations in proto-oncogenes and tumor suppressor genes make cancer cells proliferate indefinitely. As they possess almost all mechanisms for cell proliferation and survival like healthy cells, it is difficult to specifically target cancer cells in the body. Current treatments in most of the cases are harmful to healthy cells as well. Thus, it would be of great prudence to target specific characters of cancer cells. Since cancer cells avidly use glucose and glutamine to survive and proliferate by upregulating the relevant enzymes and their specific isoforms having important regulatory roles, it has been of great interest recently to target the energy-related metabolic pathways as part of the therapeutic interventions. This paper summarizes the isozymes overexpressed in breast cancer, their roles of energy metabolism and cross-talks with other important signaling pathways in regulating proliferation, invasion and metastasis in breast cancer. Information has been collected from recently published literature available on Google Scholar and PubMed. Where available, in vivo results were given more importance over in vitro works. Like many other cancers, breast cancer shows increased dependence on glycolysis rather than mitochondrial respiration, the main energy source in healthy cells. Cancer cells alter the cellular energy system in a way that helps minimize level of reactive oxygen species and simultaneously produce enough macromolecules- proteins, lipids and nucleotides for cellular proliferation. The altered system enables the cells to grow, proliferate, metastasize and to develop drug resistance. Certain isozymes of metabolic enzymes are overexpressed in breast cancer and the degree of expression of these enzymes vary among subtypes. A clear understanding of the variations of energy metabolism in different molecular subtypes of breast cancer would help in treating each type with a very customized, safer and efficient treatment regimen. Anti-cancer drugs or RNAi or combination of both targeting cancer cell specific isozymes of metabolic enzymes mentioned in this article could offer a great treatment modality for breast cancer.


Ketamine Use for Successful Resolution of Post-ERCP Acute Pancreatitis Abdominal Pain.
We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute pancreatitis.


Web-assisted tobacco interventions: empowering change in the global fight for the public's (e)Health.
Tobacco control in the 21(st) century faces many of the same challenges as in the past, but in different contexts, settings and enabled by powerful new tools including those delivered by information and communication technologies via computer, videocasts, and mobile handsets to the world. Building on the power of electronic networks, Web-assisted tobacco interventions (WATI) provide a vehicle for delivering tobacco prevention, cessation, social support and training opportunities on-demand and direct to practitioners and the public alike. The Framework Convention on Tobacco Control, the world's first global public health treaty, requires that all nations develop comprehensive tobacco control strategies that include provision of health promotion information, population interventions, and decision-support services. WATI research and development has evolved to provide examples of how eHealth can address all of these needs and provide exemplars for other areas of public health to follow. This paper discusses the role of WATI in supporting tobacco control and introduces a special issue of the Journal of Medical Internet Research that broadens the evidence base and provides illustrations of how new technologies can support health promotion and population health overall, empowering change and ushering in a new era of public eHealth.


Production of the polysaccharide curdlan by an Agrobacterium strain grown on a plant biomass hydrolysate.
Production of the commercially available polysaccharide curdlan by Agrobacterium sp. strain ECP-1, isolated as a mutant strain from ATCC 31749, on a medium containing a hydrolysate of the plant prairie cordgrass with selected ammonium phosphate concentrations was investigated for a period of 144 h. Although several ammonium phosphate concentrations supported curdlan production by the strain, the optimal concentration after 120 or 144 h was 3.3 mmol·L⁻¹. Only ammonium phosphate concentrations of 1.1 or 8.7 mmol·L⁻¹ failed to support curdlan production by the strain after 120 or 144 h. Biomass production by strain ECP-1 on the hydrolysate-containing medium after 120 or 144 h was comparable, independent of the ammonium phosphate concentration present. The curdlan yield from the cordgrass hydrolysate indicated that the grass was an effective plant biomass substrate for polysaccharide production.


Coronary changes in the Atlantic salmon Salmo salar L: characterization and impact of dietary fatty acid compositions.
Consumption of fatty acids from fishes is widely regarded as beneficial for preventing cardiovascular disorders. Nevertheless, salmonids themselves are victims of vascular diseases. As the pathogenesis and nature of these changes are elusive, they are here addressed using novel morphological and transcriptional approaches. Coronary arteries of wild Atlantic salmon Salmo salar L., (n = 12) were investigated using histological and immunohistochemical techniques, and RT-qPCR was employed to investigate expression of stretch-induced genes. In an experimental trial, fish were fed diets with different fatty acids composition, and histological features of the coronary arteries (n = 36) were investigated. In addition, the heart fatty acid profile (n = 60) was analysed. There were no differences in morphological or immunological features between wild fish and groups of experimental fish. Arteriosclerotic lesions consisted of smooth muscle cells in dissimilar differential stages embedded in considerable amounts of extracellular matrix in a similar fashion to what is seen in early stages of human atherosclerosis. No fat accumulations were observed, and very few inflammatory cells were present. In affected arteries, there was an induction of stretch-related genes, pointing to a stress-related response. We suggest that salmon may have a natural resistance to developing atherosclerosis, which corresponds well with their high investment in lipid metabolism.


Urinary 11-Dehydro-Thromboxane B2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study.
Urinary 11-dehydro-thromboxane (TX)B2 has been described as a potential predictive biomarker of major adverse cardiovascular events (MACEs) in high cardiac risk patients. This part of LTIMI (Leukotrienes and Thromboxane In Myocardial Infarction) study aimed to evaluate the relationship between 11-dehydro-TXB2 and MACEs in patients with acute myocardial infarction (AMI). LTIMI was an observational, prospective study in 180 consecutive patients with AMI type 1 referred for primary percutaneous coronary intervention. On admission and at follow-up visits (1 month, 1 year), 11-dehydro-TXB2 was measured in urinary samples by using high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was occurrence of composite MACEs during 1-year after AMI. Left ventricular ejection fraction was assessed in echocardiography on admission and at 1-year follow-up. Analyses of 11-dehydro-TXB2 (pg/mg creatinine) were performed on log-transformed data and expressed as median with IQR (Q1-Q3). 11-Dehydro-TXB2 level on admission was 7.39 (6.85-8.01) and decreased at 1 month (6.73, 6.27-7.12; P<0.001) and 1-year follow-up (6.37, 5.91-6.94; P<0.001). In univariate analysis, baseline 11-dehydro-TXB2 was higher in patients with MACEs (n=60; 7.73, 7.07-8.60) compared with those without MACEs (n=119; 7.28, 6.68-7.79; P=0.002). In multivariate regression model, 11-dehydro-TXB2 and 3 other variables (diabetes, multivessel disease, and left ventricular ejection fraction) were found to be best 1-year cumulative MACE predictors with odds ratio for 11-dehydro-TXB2 of 1.58 (95% CI 1.095-2.33; P=0.017) and area under the curve (in receiver operating characteristic analysis of 0.8). Baseline 11-dehydro-TXB2 negatively correlated with both left ventricular ejection fraction on admission (R=-0.21; P=0.006) and after 1 year (R=-0.346; P<0.001). 11-Dehydro-TXB2 predicts 1-year cumulative MACEs in AMI patients and provides prognostic information on the left ventricular performance.


[Studies on perfecting Polish-made linen threads for surgical use].
Although many varieties of synthetic surgical threads exist there is still much demand for linen threads, due to their good resistance parameters and surgical suitability. In biological studies there is found, yet, a more increased reaction around linen threads than around synthetic ones, but the reaction is smaller than that around silk or catgut threads. The increase in the reaction around linen threads is mainly due to the differences - characteristic of natural polymers - in their chemical composition, high absorbability and coarseness. These adverse properties many be reduced by proper handling of raw thread and proper selection of the preparations put on their surface. This study was the find cut how to refine linen surgical threads by bettering some parameters of raw material and by replacing the preparations used in Poland, consisting mainly of wax and paraffin, with preparations of synthetic polymers of acknowledged suitability for medical use. For the study 12 varieties of flaxen thread, of surgical thickness "0", were used, including 3 groups of raw thread of various twists, 3 groups of cleaned thread, 2 groups of mercerized thread, 4 groups of threads covered with specially prepared preparations on the basis od silicon polymers and polyurethanes. Linen threads by the Ethicon manufacture were used as the basis for comparison. The investigations concerned: --physical and mechanical properties, including tensile strength, friction coefficient, vettability, and evaluation of surface by scanning electron microscope; --biological study in vitro, including evaluation of haemolitic action on human erythrocytes, and toxic action on bull spermatozoa, using water solutions of the studies threads. The water solutions were also studied laboratorily; --biological study in vivo, including evaluation of surgical suitability for muscle implantation, estimation of durability in tissues and macroscopic and microscopic estimate of tissue reaction around the grafts. The threads were implanted into dorsal muscles of rats and into the peritoneal cavity. The results were estimated and the following conclusions were formed: 1. Thread cleaning by continuous extraction in ethyl alcohol only insignificantly improves their properties in comparison with raw material. 2. The optimum twist for flax surgical threads No "0" is 480 twists/m. 3. Mercerization of linen threads for surgical use does not improve their properties. 4. The selected types of silicon polymer and polyurethane preparations, put on raw linen threads, significantly improved their surgical suitability. Biological properties of such threads were better than those in model threads.(ABSTRACT TRUNCATED AT 400 WORDS)


Molten uranium dioxide structure and dynamics.
Uranium dioxide (UO2) is the major nuclear fuel component of fission power reactors. A key concern during severe accidents is the melting and leakage of radioactive UO2 as it corrodes through its zirconium cladding and steel containment. Yet, the very high temperatures (>3140 kelvin) and chemical reactivity of molten UO2 have prevented structural studies. In this work, we combine laser heating, sample levitation, and synchrotron x-rays to obtain pair distribution function measurements of hot solid and molten UO2. The hot solid shows a substantial increase in oxygen disorder around the lambda transition (2670 K) but negligible U-O coordination change. On melting, the average U-O coordination drops from 8 to 6.7 ± 0.5. Molecular dynamics models refined to this structure predict higher U-U mobility than 8-coordinated melts.


A Critical Thinking Activity on Drug Tolerance for Undergraduate Neuroscience Courses.
Active teaching techniques that involve critical thinking and analysis lead to better learning and retention, and there is growing need for learner-centered classroom activities in the neurosciences. This article presents a critical thinking activity that offers context and meaning to basic principles of synaptic pharmacology. Students analyze fictional datasets to identify major characteristics of drug tolerance. Students' self-reported perceptions and ungraded quiz scores suggest that this activity was an enjoyable and impactful way to deepen students' understanding and engage them with the course material. This activity was developed for a 300-level psychopharmacology course that included majors from various science departments, but could be used and/or modified for specialized seminars or other undergraduate courses in psychology or biology.


[Cytomegaloviruses--clinical aspects and therapy].
Human cytomegalovirus (HCMV) is an important pathogen for the fetus, recipients of solid organ transplants, bone marrow allograft patients, individuals infected with human immunodeficiency virus and other immunosuppressed patients. The clinical features of congenital cytomegalovirus infection as well as HCMV infection and HCMV disease in immunosuppressed transplant recipients are described. Diagnostic methods for HCMV monitoring are discussed from a clinical perspective. Antivirals as Ganciclovir and Foscarnet are used for induction and maintenance regimes for the treatment of HCMV-associated retinitis, pneumonitis, hepatitis, gastrointestinal involvement and neurological disorders. Drug resistance both to Ganciclovir and Foscarnet of HCMV strains isolated from immunosuppressed patients has already been reported. The development of rapid diagnostic tools for the detection of HCMV drug resistance is urgently required.


Vibration Response Analysis of the Tail Beam of Hydraulic Support Impacted by Coal Gangue Particles with Different Shapes.
The existing research on coal gangue identification based on vibration usually assumes that coal gangue particles are ideal shapes. To understand the vibration response difference in hydraulic support caused by coal and gangue with real shapes, this paper uses a three-dimensional (3D) scanning technology to determine the real shape of coal particles. The process of coal and gangue impacting the tail beam at different angles was simulated in the LS-DYNA software package, and the effects of shape parameters, velocity, and coal strength on the difference in vibration signals caused by the two were analyzed statistically. The conclusions are as follows: the vibrational response of the tail beam is concentrated mainly in the area between the ribs. The regularity of the velocity signal caused by gangue is better than the regularity of the velocity signal caused by coal, and the attenuation speed of the acceleration signal of gangue is slower than the attenuation speed of the acceleration signal of coal. The probability distributions of the velocity and acceleration responses were analyzed statistically, and the results show that the results from coal can be well fitted by a logarithmic normal function, and the standard deviations of velocity and acceleration are 0.05591 and 489.8, respectively. The gangue results are fitted by the gamma function and the Weibull function, and the standard deviations are 0.13531 and 737.9, respectively, showing that the fitting function has the potential to be used as the basis for coal gangue identification. The change in coal strength has little effect on the vibration response of the tail beam. With increasingly falling velocity, the vibration signal intensity of the tail beam increases, but the discrimination between coal and gangue weakens; therefore, measures should be taken to reduce the falling velocity of the rock mass. The research results of this paper can provide a reference for further study of coal gangue identification methods based on vibration.


Oncolytic bluetongue viruses: promise, progress, and perspectives.
Humans are sero-negative toward bluetongue viruses (BTVs) since BTVs do not infect normal human cells. Infection and selective degradation of several human cancer cell lines but not normal ones by five US BTV serotypes have been investigated. We determined the susceptibilities of many normal and human cancer cells to BTV infections and made comparative kinetic analyses of their cytopathic effects, survival rates, ultra-structural changes, cellular apoptosis and necrosis, cell cycle arrest, cytokine profiles, viral genome, mRNAs, and progeny titers. The wild-type US BTVs, without any genetic modifications, could preferentially infect and degrade several types of human cancer cells but not normal cells. Their selective and preferential BTV-degradation of human cancer cells is viral dose-dependent, leading to effective viral replication, and induced apoptosis. Xenograft tumors in mice were substantially reduced by a single intratumoral BTV injection in initial in vivo experiments. Thus, wild-type BTVs, without genetic modifications, have oncolytic potentials. They represent an attractive, next generation of oncolytic viral approach for potential human cancer therapy combined with current anti-cancer agents and irradiation.


Left Ventricular Myocardial Contractile Reserve during Exercise Stress in Healthy Adults: A Two-Dimensional Speckle-Tracking Echocardiographic Study.
The aims of the present study were to determine left ventricular (LV) myocardial contractile reserve during exercise stress testing in healthy adults and to evaluate the effects of gender and age on exercise LV global longitudinal strain (GLS). The study population consisted of 67 healthy adults (age range, 23-80 years; 49% women). Subjects were analyzed with respect to gender and predefined age groups (age < 35 years, n = 18; age 35-55 years, n = 24; age > 55 years, n = 25). All subjects underwent comprehensive echocardiographic assessment at rest and during symptom-limited semisupine exercise test. LV GLS was determined using two-dimensional speckle-tracking echocardiography. LV GLS magnitude during peak stress was 25.4 ± 2.0%. The average absolute numeric LV GLS increase was 5.3%, equivalent to a relative 26.7% increase of LV GLS. LV GLS magnitude at peak exercise was without clinically significant differences between age groups (P = .07). No significant difference was found in peak exercise LV GLS between genders (P = .48). Linear regression analysis revealed a significant but weak correlation between peak LV GLS and age (r = -0.30, P = .02), whereas peak LV GLS was independent of maximal heart rate (r = 0.23, P = .07), peak mean arterial blood pressure (r = -0.11, P = .38), body mass index (r = 0.15, P = .22), and peak pulsed Doppler-derived cardiac index (r = -0.06, P = .67). LV GLS increases significantly during exercise stress in a healthy population. A dose-response relationship was found between LV GLS and exercise level independent of gender, and the influence of age appeared marginal. The technique is feasible, with low intra- and interobserver variability.


Dysregulation of mRNA profile in cisplatin-resistant gastric cancer cell line SGC7901.
To explore novel therapeutic target of cisplatin resistance in human gastric cancer. The sensitivity of SGC7901 cells and cisplatin-resistant SGC7901 cells (SGC7901/DDP) for cisplatin were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. High-quality total RNA which isolated from SGC7901/DDP cells and SGC7901 cells were used for mRNA microarray analysis. Results were analyzed bioinformatically to predict their roles in the development of cisplatin resistance and the expression of 13 dysregulated mRNAs we selected were validated by quantitative real-time polymerase chain reaction (qRT-PCR). SGC7901/DDP cells highly resistant to cisplatin demonstrated by MTT assay. A total of 1308 mRNAs (578 upregulated and 730 downregulated) were differentially expressed (fold change ≥ 2 and P-value < 0.05) in the SGC7901/DDP cells compared with SGC7901 cells. The expression of mRNAs detected by qRT-PCR were consistent with the microarray results. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis demonstrated that the differentially expressed mRNAs were enriched in PI3K-Akt, Notch, MAPK, ErbB, Jak-STAT, NF-kappaB signaling pathways which may be involved in cisplatin resistance. Several genes such as PDE3B, VEGFC, IGFBP3, TLR4, HIPK2 and EGF may associated with drug resistance of gastric cancer cells to cisplatin. Exploration of those altered mRNAs may provide more promising strategy in diagnosis and therapy for gastric cancer with cisplatin resistance.


Early acute kidney injury after liver transplantation: Predisposing factors and clinical implications.
To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI) following liver transplantation. This was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation (OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT (> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration (CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase (AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor (< 1000 IU/L), moderate (1000-5000 IU/L) or severe (> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications (AKI and HIRI) alone and then as a combined outcome. Out of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustained moderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation (P < 0.001) and intensive care length of stay (P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication (P = 0.049). HIRI has an important role in the development of AKI post-OLT and has a negative impact on patient outcomes, especially when occurring alongside AKI.


Quantitative analysis of functional filtering bleb size using Mask R-CNN.
Deep learning has had a large effect on medical fields, including ophthalmology. The goal of this study was to quantitatively analyze the functional filtering bleb size with Mask R-CNN. This observational study employed eighty-three images of post-trabeculectomy functional filtering blebs. The images were divided into training and test groups and scored according to the Indiana Bleb Appearance Grading Scale (IBAGS) system. Then, 70 images from the training group were used to train an automatic detection system based on Mask R-CNN and perform a quantitative analysis of the function bleb size. Thirteen images from the test group were used to evaluate the model. During the training process, left and right image-flipping algorithms were used for data augmentation. Finally, the correlation between the functional filtering bleb area and the intraocular pressure (IOP) was analyzed. The 83 functional filtering blebs have similar morphological features. According to IBAGS, the functional filtering blebs have a high incidence of E1/E2, H1/H2, and V0/V1. Our Mask R-CNN-based model using the selected parameters achieves good results on the training group after a 200-epoch training process. All the Intersection over Union (IoU) scores exceeded 93% on the test group. The Spearman correlation coefficient between the area of functional filtering blebs and the IOP value was -0.757 (P<0.05). Deep learning is a powerful tool for quantitatively analyzing the functional filtering bleb size. This technique is suitable for use in monitoring post-trabeculectomy filtering blebs in the future.


A New Area in Main-Group Chemistry: Zerovalent Monoatomic Silicon Compounds and Their Analogues.
Monoatomic zerovalent main-group element complexes emerged very recently and attracted increasing attention of both theoretical and experimental chemists. In particular, zerovalent silicon complexes and their congeners (metallylones) stabilized by neutral Lewis donors are of significant importance not only because of their intriguing electronic structure but also because they can serve as useful building blocks for novel chemical species. Featuring four valence electrons as two lone pairs at the central atoms, such complexes may form donor-acceptor adducts with Lewis acids. More interestingly, with the central atoms in the oxidation state of zero, they could pave a way to new classes of compounds and functional groups that are otherwise difficult to realize. In this Account, we mainly describe our contributions in the chemistry of monatomic zerovalent silicon (silylone) and germanium (germylone) supported by a chelate bis-N-heterocyclic carbene (bis-NHC) ligand in the context of related species developed by other groups in the meantime. Utilizing the bis-NHC stabilized chlorosilyliumylidene [:SiCl]+ and chlorogermyliumylidene [:GeCl]+ as suitable starting materials, we successfully isolated silylone (bis-NHC)Si and germylone (bis-NHC)Ge, respectively. The electronic structures of the latter complexes established by theoretical calculations and spectroscopic data revealed that they are genuine metallylone species with electron-rich silicon(0) and germanium(0) centers. Accordingly, they can react with 1 molar equiv of GaCl3 to form Lewis adducts (bis-NHC)E(GaCl3) (E = Si, Ge) and with 2 molar equiv of ZnCl2 to furnish (bis-NHC)Si(ZnCl2)2. Conversion of the metallylones with elemental chalcogens affords isolable monomeric silicon(II) and germanium(II) monochalcogenides (bis-NHC)EX(GaCl3) (X = Se, Te), representing molecular heavier congeners of CO. Moreover, their reaction with elemental chalcogens can also yield monomeric silicon(IV) and germanium(IV) dichalcogenides (bis-NHC)EX2 (X = S, Se, Te) as the first isolable complexes of the molecular congeners of CO2. Moreover, (bis-NHC)Si could even activate CO2 to afford the monomolecular silicon dicarbonate complex (bis-NHC)Si(CO3)2 via the formation of SiO and SiO2 complexes as intermediates. Furthermore, starting with a chelate bis-N-heterocyclic silylene supported [:GeCl]+, we developed two bis-N-heterocyclic silylene stabilized germylone→Fe(CO)4 complexes. Our achievements in the chemistry of metallylones demonstrate that the characteristic of monatomic zerovalent silicon and its analogues can provide novel reaction patterns for access to unprecedented species and even extends the series of functional groups of these elements. With this, we can envision that more interesting zerovalent complexes of the main-group elements with unprecedented reactivity will follow in the near future.


Expansion with transpalatal arch or continuous arch mechanics.
This study aimed to compare the 3-dimensional force system produced by transpalatal arch (TPA) mechanics with that produced by a continuous arch (CA) on the expansion of maxillary first molars. A patient's model with 2 molars in 4-mm crossbite had orthodontic appliances bonded to all teeth. The first and the second molars were connected to two 3-dimensional load cells to compare the forces in the transverse and anteroposterior planes (Fx and Fy) and the rotational moments (Mz) produced in both molars by the expanded TPA and by 0.016-in nickel-titanium CA. The data were evaluated using 6 independent t tests, and the net moment at the molar's center of resistance was also calculated. All forces and moments were different at both molars. At the first molar, CA produced Fx of 2.60 N, Fy of -0.08 N, Mz of -5.16 N·mm, and Net Mz of -5.68 N·mm, whereas the TPA produced Fx of 2.87 N, Fy of -0.60 N, Mz of -22.08 N·mm, and Net Mz of -25.09 N·mm. At the second molar, the TPA did not produce significant forces and moments, whereas the CA produced Fx of -1.00 N, Mz of 3.95 N·mm, Fy of -0.84 N, and Net Mz of -0.67 N·mm. Based on our findings in a clinical set up with the specific horseshoe TPA and archwire tested, with the TPA used only on the first molars and the CA used from one second molar to the other, the mechanics produced different expansion forces at the first molar. The TPA produced a larger rotational side effect on the first molar, whereas the CA produced side effects on the second molar.


Serial fine needle cytology in the diagnosis of esophageal cancer.
To describe a method of registering local spread of cancer in the esophageal wall through serial endoscopic fine needle aspiration (FNA), to evaluate FNA as a diagnostic tool as compared to histologic biopsies and brush cytology, and to investigate cytologic appearances of aspirates and correlate them with survival Fifty-two patients with esophageal cancer were investigated with serial FNA every second centimeter from the upper esophageal sphincter aborally down to the level of macroscopic tumor. Histologic biopsies and brush cytologies were then performed. Of investigated cases, 33% showed malignant or suspect malignant cells from macroscopic tumor, at > or = 4 cm orally, as did 3 of 12 patients at 14 cm. FNA was more sensitive than brush cytology in establishing the diagnosis. A high ratio between the numbers of benign and malignant cells in aspirates from gross tumor tissue correlated with shorter survival (P < .03). Serial FNA can demonstrate local microscopic tumor spread in the wall of the esophagus in vivo in esophageal cancer patients. FNA is also a useful adjunct in establishing the diagnosis. Finally, evaluations of tumor cytology may have prognostic value.


Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor.
Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options. Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques. Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery. Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.


Absence of major histocompatibility complex restriction in the interaction between processed basic protein and Ia of two rat strains.
Antigen fragments, biologically degraded by antigen-presenting cells (APC), combine with Ia positive moieties (IPM) to stimulate antigen-specific T lymphocyte lines. The main objective of this study was to evaluate whether this interaction was determined by the major histocompatibility complex (MHC) genotype of the APC, thus genetically restricting antigen-specific T lymphocyte proliferative responses. To do so, we assayed the capacity of processed basic protein, associated with IPM, to stimulate basic protein specific T lymphocyte lines derived from the Lewis (LW), Brown Norway (BN), and (LW x BN)F1 rat strains. Our findings are that: (a) IPM replaced the requirement for intact APC in proliferative responses of T lymphocytes to processed basic protein; (b) processed basic protein, irrespective of the genotype of APC from which it was prepared, was fully reconstituted by all IPM genotypes tested. Hence, the interaction between processed antigen and IPM was not found to be MHC-restricted. The possible implication of this conclusion is discussed.


Patient-Reported Outcome Measures in Takayasu Arteritis: A Systematic Review and Meta-Analysis.
We conducted a systematic review of patient-reported outcome measures (PROMs) regarding quality of life, disability, mood abnormalities (anxiety, depression), fatigue, illness perceptions and fibromyalgia in Takayasu arteritis (TAK). Wherever available, comparisons with healthy controls, disease controls or longitudinal changes in PROMs were noted. MEDLINE, EMBASE, Scopus, Web of Science and Pubmed Central databases, major recent international rheumatology conference abstracts, clinical trial databases and the Cochrane library were searched for relevant articles. Wherever possible, outcome measures across studies were pooled using the restricted maximum likelihood model. Inter-group differences were pooled and compared using standardized mean differences (SMD) with 95% confidence intervals (95% CI). Heterogeneity was assessed using the I2 statistic. Quality of randomized controlled trials was assessed using the Cochrane risk of bias tool. For cross-sectional and cohort studies, the Joana Briggs Institute checklist and Newcastle-Ottawa scale were used, respectively. GRADE methodology was used to determine the certainty of evidence for outcomes. Twenty-one studies (all but one observational) involving 1311 patients with TAK and 308 healthy controls were identified. Ten studies (559 TAK patients, 182 healthy controls were synthesized in a meta-analysis. Patients with TAK had worse quality of life (pooled SMD - 6.66, 95% CI - 10.08 to - 3.23 for individual domains; - 0.64, 95% CI - 1.19 to - 0.09 for pooled physical and mental component scores of 36-item Short Form Survey), depression (SMD 0.26, 95% 0.05-0.47) and anxiety (SMD 0.34, 95% CI - 0.06 to 0.75) scores and higher disability (SMD 0.64, 95% CI 0.43-0.84) than healthy controls. Patients with active TAK had worse quality of life, depression and work impairment when compared with those with inactive disease. Included studies were of moderate to high quality. Certainty of evidence for individual outcomes was low to very low. Literature on PROMs in TAK, albeit sparse, appears to indicate worse scores in patients with TAK compared to healthy individuals. These results, however, require cautious interpretation. Development of a TAK-specific PROM is an important focus of the research agenda.


Cadmium and zinc induced nuclear changes in the liver and kidney of rats.
When administered to animals cadmium is known to accumulate in the liver and kidney causing indentifiable toxicity. However, its binding with cell sap and nucleus and effects on their constituents are poorly known. Since nuclear changes reflect some of the metabolic disturbances and are of value in diagnosis, an attempt has been made to analyse their morphology and chemistry in the liver and kidney of rat after individual and combined treatment with Cd and Zn. Present observations clearly show that cadmium inhibits DNA synthesis by blocking the formation of the enzyme thymidine triphosphate which is prerequisite for DNA synthesis. Zinc exerted a stimulatory effect on DNA and RNA both by increasing the activity of thymidine kinase. Their combined effects were found to be less injurious to the cell. Though these changes could be a secondary or generalized response of nuclei to altered physiological conditions, specific reasons for these changes have been discussed.