Post-receptor-mediated increases in adenylate cyclase activity after chronic antidepressant treatment: relationship to receptor desensitization.
Administration to rats of chronic electroconvulsive shock (ECS) or chronic desipramine (DMI, 10 mg/kg daily i.p. for 3 weeks) did not affect either basal or forskolin-stimulated adenylate cyclase activity in membranes prepared from the caudate nucleus. In cerebellar membranes prepared from rats which had received chronic ECS, forskolin-stimulated activity was significantly increased compared to activity in sham- or single ECS treated rats. Forskolin-stimulated adenylate cyclase was increased in both hippocampal and cerebellar membranes from rats which received chronic DMI, compared to saline-treated animals. In cerebellar membranes, increases comparable to those with forskolin were also obtained with guanylyl-5'-imidodiphosphate (GppNHp) after both treatments, while with Mn2+ ions, either alone or in the additional presence of forskolin, the changes observed were similar to those previously reported in cortical membranes. A possible mechanism for these effects was investigated by studying antidepressant-induced and in vitro desensitization of the cyclic AMP response in slice preparations from the various brain areas. In slices from caudate nucleus, chronic DMI did not alter stimulation of cyclic AMP formation by either noradrenaline or forskolin, while in cerebellar slices the noradrenaline response was significantly reduced, and in hippocampal slices both responses were reduced (heterologous desensitization). In vitro incubation of cortical slices with noradrenaline also resulted in a reduction in the response to both agents. However, in membranes prepared from the desensitized cortical slices, there was no change in the degree of activation of adenylate cyclase by either NaF or forskolin. Thus, the increase in these activities, observed in certain brain areas after chronic antidepressant treatment may not necessarily be related to beta-adrenoceptor desensitization.


Inflammation and lipid metabolism as potential biomarkers of memory impairment across type 2 diabetes mellitus and severe mental disorders.
Neurocognitive impairment is a transdiagnostic feature across several psychiatric and cardiometabolic conditions. The relationship between inflammatory and lipid metabolism biomarkers and memory performance is not fully understood. This study aimed to identify peripheral biomarkers suitable to signal memory decline from a transdiagnostic and longitudinal perspective. Peripheral blood biomarkers of inflammation, oxidative stress and lipid metabolism were assessed twice over a 1-year period in 165 individuals, including 30 with schizophrenia (SZ), 42 with bipolar disorder (BD), 35 with major depressive disorder (MDD), 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls (HCs). Participants were stratified by memory performance quartiles, taking as a reference their global memory score (GMS) at baseline, into categories of high memory (H; n = 40), medium to high memory (MH; n = 43), medium to low memory (ML; n = 38) and low memory (L; n = 44). Exploratory and confirmatory factorial analysis, mixed one-way analysis of covariance and discriminatory analyses were performed. L group was significantly associated with higher levels of tumor necrosis factor-alpha (TNF-α) and lower levels of apolipoprotein A1 (Apo-A1) compared to those from the MH and H groups (p < 0.05; η2p = 0.06-0.09), with small to moderate effect sizes. Moreover, the combination of interleukin-6 (IL-6), TNF-α, c-reactive protein (CRP), Apo-A1 and Apo-B compounded the transdiagnostic model that best discriminated between groups with different degrees of memory impairment (χ2 = 11.9-49.3, p < 0.05-0.0001). Inflammation and lipid metabolism seem to be associated with memory across T2DM and severe mental illnesses (SMI). A panel of biomarkers may be a useful approach to identify individuals at greater risk of neurocognitive impairment. These findings may have a potential translational utility for early intervention and advance precision medicine in these disorders.


Resource utilization in management of spontaneous intracerebral hemorrhage without systemic risk factors. Does early surgical decompression matter?
Even though different subtypes of spontaneous ICH are frequently linked to a poor prognosis, their causes, pathological features, and prognoses vary. Atypical intracerebral hemorrhage is the subtype of spontaneous ICH that usually occurs due to an underlying localized vascular lesion. It is unrelated to systemic vascular risk factors, mostly affects children and young adults and is associated with a relatively good outcome. This fact should be considered when planning the evaluation and treatment. Investigating the cause of this subtype is fundamental to providing optimal management. However, if resources do not allow completing the investigations, the cause will be more difficult to discover. Treatment decisions will be made under stress to save the patient's life, especially with rapidly deteriorating patients. We described three cases of spontaneous ICH without systemic risk factors where the bleeding source could not be determined before surgery due to a lack of resources, preventing preoperative vascular investigation. Knowing that the atypical ICH has a distinct identity, regarding etiology and prognosis, encouraged the surgeons to resort to early surgical decompression as an alternative plan. We reviewed the literature searching for supporting evidence. The results of treatment of the presented cases were satisfactory. The lack of reported similar cases was brought to light by a literature analysis that sought to provide backing for the proposed management strategy. In the end, we supplied two graphic organizers to help readers remember the different types and treatment of hemorrhagic stroke. There isn't enough evidence to show that there are other ways to treat atypical intracerebral haemorrhage when resources are limited. The presented cases highlight the importance of decisionmaking in resource-constrained situations when patient outcomes can be improved.


Evolution of drug delivery system from viewpoint of controlled intracellular trafficking and selective tissue targeting toward future nanomedicine.
Due to the rapid changes that have occurred in the field of drug discovery and the recent developments in the early 21st century, the role of drug delivery systems (DDS) has become increasingly more important. For the past 20 years, our laboratory has been developing gene delivery systems based on lipid-based delivery systems. One of our efforts has been directed toward developing a multifunctional envelope-type nano device (MEND) by modifying the particle surface with octaarginine, which resulted in a remarkably enhanced cellular uptake and improved intracellular trafficking of plasmid DNA (pDNA). When we moved to in vivo applications, however, we were faced with the PEG-dilemma and we shifted our strategy to the incorporation of ionizable cationic lipids into our system. This resulted in some dramatic improvements over our original design and this can be attributed to the development of a new lipid library. We have also developed a mitochondrial targeting system based on a membrane fusion mechanism using a MITO-Porter, which can deliver nucleic acids/pDNA into the matrix of mitochondria. After the appearance of antibody medicines, Opdivo, an immune checkpoint inhibitor, has established cancer immunology as the 4th strategy in cancer therapy. Our DDS technologies can also be applied to this new field of cancer therapy to cure cancer by controlling our immune mechanisms. The latest studies are summarized in this review article.


A new chromone functionalized isoqunoline derived chemosensor with fluorogenic switching effect for selective detection of Zn2+ in real water samples and living cells.
In this work, a selective chemosensor, (E)-N'-((4-oxo-4H-chromen-3-yl)methylene)isoquinoline-1-carbohydrazide (ENO), was rationally developed for colorimetric and fluorogenic detection of Zn2+ ions. It was readily synthesized from 4-oxo-4H-chromene-3-carbaldehyde and isoquinoline-1-carbohydrazide via one-step Schiff reaction. ENO exhibited excellent fluorescent response performances toward Zn2+ over a wide pH range in EtOH/H2O media, including a distinguished color change from colorless to gold, a low limit of detection (LOD) value (34 nM), strong complexation ability (1.36 × 105 M-1) and rapid identification (2 min). The sensing mechanism of ENO toward Zn2+ was proposed on the basis of the chelation-enhanced fluorescence (CHEF) process, which was further supported by IR studies and the density functional theory (DFT) calculation. Moreover, ENO presented here demonstrated outstanding capability in monitoring trace level of Zn2+ ions in real water samples, living cells as well as the on-site assay kit.


Health management of malnourished elderly in primary health care: a scoping review.
The aim of this study, as the first review directed at Primary Health Care, is to identify the screening practices and health outcomes related to the care provided by Family Health Teams to the malnourished elderly people/population. Following PRISMA and PICO strategies, searches were conducted in four electronic databases (PubMed, Web of Science, Scopus & EMBASE) on observational, qualitative, quantitative, or mixed studies, written in Portuguese, Spanish and English language, with participants of 65 years old or older at a community setting. The literature selected for this study ranges from the period 2011 to 2021; additional articles were included through reference lists. From the 483 studies identified, 16 were considered eligible to use in this work. The Mini Nutritional Assessment (MNA) score appears as the main criteria of choice, however, a standardized practice in the health systems regarding the use of screening methods has not been demonstrated. Studies are more oriented towards the analysis of the relationship of mortality/morbidity and malnutrition than towards the relationship of the cost and quality of life and malnutrition of the elderly. Malnutrition is one of the modifiable risk factors which contributes to the vulnerable condition of the elderly, with serious effects, especially when related to other comorbidities. Yet, several authors argue that the Primary Health Care intervention can minimize the negative impacts and improve the health outcomes.


Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid.
Changes in reduced glutathione (GSH) and pyridine nucleotide phosphate levels as well as in the activities of the glutathione peroxidase-reductase system and glucose-6-phosphate dehydrogenase have been studied in rats after a single i.p. administration of various doses of valproic acid (VPA). GSH level decreased in a dose-dependent relation. At the end of 180 min GSH levels either returned to control limits (lower doses) or showed a tendency to normalize (higher doses). GSH loss was paralleled by the reduction in glutathione reductase activity. A significant NADPH reduction was also seen after animal exposure to high VPA doses. At the end of 180 min a maximal NADPH decrease was reached. The activities of both glutathione peroxidase and glucose-6-phosphate dehydrogenase were suppressed irrespective of whether animals were given low or high VPA doses.


Abscisic acid and stress treatment are essential for the acquisition of embryogenic competence by carrot somatic cells.
Studies of carrot embryogenesis have suggested that abscisic acid (ABA) is involved in somatic embryogenesis. A relationship between endogenous ABA and the induction of somatic embryogenesis was demonstrated using stress-induced system of somatic embryos. The embryonic-specific genes C-ABI3 and embryogenic cell proteins (ECPs) were expressed during stress treatment prior to the formation of somatic embryos. The stress-induction system for embryogenesis was clearly distinguished by two phases: the acquisition of embryogenic competence and the formation of a somatic embryo. Somatic embryo formation was inhibited by the application of fluridone (especially at 10(-4) M), a potent inhibitor of ABA biosynthesis, during stress treatment. The inhibitory effect of fluridone was nullified by the simultaneous application of fluridone and ABA. The level of endogenous ABA increased transiently during stress. However, somatic embryogenesis was not significantly induced by the application of only ABA to the endogenous level, in the absence of stress. These results suggest that the induction of somatic embryogenesis, in particular the acquisition of embryogenic competence, is caused not only by the presence of ABA but also by physiological responses that are directly controlled by stresses.


The number of loci that affect milk production traits in dairy cattle.
We have used the results of an experiment mapping quantitative trait loci (QTL) affecting milk yield and composition to estimate the total number of QTL affecting these traits. We did this by estimating the number of segregating QTL within a half-sib daughter design using logic similar to that used to estimate the "false discovery rate" (FDR). In a half-sib daughter design with six sire families we estimate that the average sire was heterozygous for approximately 5 QTL per trait. Also, in most cases only one sire was heterozygous for any one QTL; therefore at least 30 QTL were likely to be segregating for these milk production traits in this Holstein population.


Dataset on Women's empowerment, land and donor-driven agricultural interventions in Eastern Zambia.
A survey was conducted with 235 randomly selected households to investigate women's empowerment, land and donor-driven agricultural interventions in Eastern Zambia [1] for aid programmes with (Norwegian) and without (Chinese) women empowerment goals. The survey was complemented by six focus group discussions (FGDs) and 12 key informant interviews. A triple-stream approach for focus discussions was used (i.e. women-only, men-only, and mixed gender). The results suggest that despite differing aid programme modalities, there was increased access to, and control over, productive resources by women farmers. At least 60% of the respondents reported joint ownership of all types of livestock and poultry, including large livestock such as cattle. Within households, decisions on cotton, groundnuts, and maize were made jointly by the husband and wife. Greater than 70% of the respondents in both Norwegian and Chinese aided households reported joint decision making by the husband and wife. Although both men and women farmers attended training sessions, the percentage of attending respondents was lower for Chinese-aid affiliated farmers. The majority (81% - Norwegian aid; 89% - Chinese aid) jointly earned and owned the income from cotton. When women entered into contract farming with the cotton company, operations management was performed by the entire household, and the applicable income was considered jointly earned.


Economic growth and industrial expansion and renewal as instruments to achieve full employment.
Institutional changes have weakened the capacity of market economies to adjust with sufficient speed to change in factor prices and in the available technology. As a consequence of this lower flexibility traditional economic policy instruments are no longer effective in creating growth and employment. This is the overall theme of the analysis presented in this paper concerning the reasons for our current long-term employment problems.


Lower survival after right-sided versus left-sided colon cancers: Is an extended lymphadenectomy the answer?
Tumour location may affect oncologic outcomes for colon adenocarcinoma due to different levels of vascular ligation and nodal harvest, but the data are equivocal. The objective of this study is to determine the effect of tumor location and lymph node yield on overall survival(OS) in stage I-III colon adenocarcinoma. The 2004-2014 National Cancer Database was queried for colectomies for non-metastatic colon adenocarcinoma, excluding transverse colon and rectal cancer. Patients were grouped based on left/right tumor location. Main outcome measure was 5-year OS. Propensity score matching created balanced cohorts. Multilevel survival analysis determined the independent effect of tumor location and nodal harvest on OS. There were 504,958 patients (273,198 right; 231,760 left) in the entire cohort: 26.4% stage-I, 37.3% stage-II, and 36.3% stage-III (equal distribution left/right). After 1:1 matching(n = 297,080), right cancers were associated with worse 5-year overall survival for stage-II (66% vs. 70%, p < 0.001) and -III (56% vs. 60%, p < 0.001) despite similar nodal harvest and proportion receiving systemic therapy. On multivariate analysis, right-sided cancers (HR 1.12, 95%CI 1.06-1.19) had worse OS, independent of stage and nodal harvest. Nodal harvest ≥22 nodes had the highest OS (HR 0.71, 95%CI 0.68-0.75). There was an interaction between right-sided cancer and >22 lymph node harvest towards increased survival (HR 0.86, 95%CI 0.80-0.92). Right-sided cancers are associated with worse oncologic outcomes compared to left-sided tumors but a higher lymph node yield improves survival. These data provide indirect evidence for a higher lymphatic harvest to improve survival.


A t(3;5) in blastic phase of a Philadelphia chromosome-negative chronic myeloid leukemia.
Serial cytogenetic analyses from the bone marrow of a patient with blastic phase of a Philadelphia chromosome-negative chronic myeloid leukemia revealed a t(3;5)(p21;q31). The literature on translocations involving chromosome 3 and the long arm of chromosome 5 is reviewed. The importance of breakpoints in band 5q31 is discussed.


[A comparison of measurements made with Goldmann's application tonometer and Draeger's hand applanation tonometer (author's transl)].
The hand held applanationstonometer Draeger gives reliable measurements of intraocular pressure, they correspond of those from Goldmann applanationstonometer. The eventual value deviations of i. o. pressure at the beginning of the tests are not caused by the instrument but mainly by the effect of repeated applanation tonometry.


Chemoselective hydrogenation of nitroarenes with carbon nanofiber-supported platinum and palladium nanoparticles.
Platinum and palladium nanoparticles supported on three types of carbon nanofibers (CNFs) are synthesized and used as catalysts in the hydrogenation of nitroarenes. Nanosized platinum particles dispersed on platelet-type CNF efficiently catalyze the reduction of functionalized nitroarenes to the corresponding substituted anilines in high turnover numbers with other functional groups remaining intact.


Value of 3.0 T diffusion-weighted imaging in discriminating thecoma and fibrothecoma from other adnexal solid masses.
To investigate the value of diffusion-weighted imaging (DWI) at 3.0 T (3T), and especially the apparent diffusion coefficient (ADC), in discriminating ovarian thecoma from other adnexal solid masses. Eighteen thecomas or fibrothecomas, 14 ligamentous leiomyomas, and 24 other ovarian solid tumors underwent prospective DWI magnetic resonance imaging (MRI) in addition to routine MRI on a 3T MRI machine. The baseline characteristics, components, and conventional MRI and DWI-MRI signals for the thecomas were recorded. The ADC values (ADCs) were measured for each group and compared. The thecomas often appeared as homogeneous isointensity (17/18) on T1-weighted images (T1WI; 11/18) or T2WI (11/18) on DWI-MRI, with minor (9/18) or mild (6/18) enhancement. The mean ADC value for thecoma (1.20 ± 0.45 × 10-3 mm2/s) was almost equal to that of the other solid ovarian masses (1.26 ± 0.51 × 10-3 mm2/s), but lower than that for leiomyoma (1.48 ± 0.42 × 10-3 mm2/s), although not significantly so. There was a significant difference (p = 0.043) in the ADCs of the benign ovarian solid masses (1.16 ± 0.47 × 10-3 mm2/s) and leiomyomas (1.48 ± 0.42 × 10-3 mm2/s). There is no significant difference in ADC between thecoma and other adnexal solid masses, but the ADCs of thecomas are lower than those of leiomyomas.


Changing climate, changing minds? The effects of natural disasters on public perceptions of climate change.
The frequency and intensity of natural disasters such as hurricanes, wildfires, and floods are predicted to change as greenhouse gas concentrations increase. These disasters may represent sources of information for individuals as they update their beliefs related to climate change. Using a dataset that includes climate beliefs of respondents, we examine the effect of natural disasters on climate change beliefs and find that hurricanes significantly increase the probability that survey respondents from a given county believe that climate change is occurring and that it is human caused. We find that past experience with certain types of natural disasters (e.g., hurricanes) impacts beliefs regarding whether climate change is occurring and if it is human caused. The research contributes to the literature evaluating climate change attitudes by using spatially disaggregate information on climate change beliefs and exposure to a set of natural disasters over time. Characterizing beliefs and attitudes toward climate change and related policies is important since these beliefs are a determinant of individual adaptation and support for policies related to reducing carbon emissions.


Determination of natural and artificial radioactivity in soil at North Lebanon province.
The concentrations of natural and artificial radionuclides at 57 sampling locations along the North Province of Lebanon are reported. The samples were collected from uncultivated areas in a region not previously reported. The samples were analyzed by gamma spectrometers with High Purity Germanium detectors of 30% and 40% relative efficiency. The activity concentrations of primordial naturally occurring radionuclides of (238)U, (232)Th, and (40)K varied between 4-73 Bq kg(-1), 5-50 Bq kg(-1), and 57-554 Bq kg(-1) respectively. The surface activity concentrations due to the presence of these radionuclides were calculated and Kriging-geostatistical method was used to plot the obtained data on the Lebanese radioactive map. The results for (238)U, (232)Th, and (40)K ranged from 0.2 kBq m(-2) to 9 kBq m(-2), from 0.2 kBq m(-2) to 3 kBq m(-2), and from 3 kBq m(-2) to 29 kBq m(-2) respectively. For the anthropogenic radionuclides, the activity concentrations of (137)Cs founded in soil ranged from 2 Bq kg(-1) to 113 Bq kg(-1), and the surface activity concentration from 0.1 kBq m(-2) to 5 kBq m(-2). The total absorbed gamma dose rates in air from natural and artificial radionuclides in these locations were calculated. The minimum value was 6 nGy h(-1) and the highest one was 135 nGy h(-1) with an average of 55 nGy h(-1) in which the natural terrestrial radiation contributes in 99% and the artificial radionuclides mainly (137)Cs contributes only in 1%. The total effective dose calculated varied in the range of 7 μSv y(-1) and 166 μSv y(-1) while the average value was 69 μSv y(-1) which is below the permissible limit 1000 μSv y(-1).


Use of dilute drug solutions for routine cycloplegia and mydriasis.
Clinic patients and students were given several regular drops of commercial 10% phenylephrine HCl, and 1.0% cyclopentolate HCl or 1.0% tropicamide HCl. The drops were given three times at five-minute intervals. Mydriasis and cycloplegia were determined and compared with the results obtained by using one of the following: microdrops (0.005 or 0.01 ml) of a mixture of 5% phenylephrine HCl and 0.5% tropicamide HCl, or regular drops of mixtures of 1% phenylephrine HCl, or 0.4% hydroxyamphetamine hydrobromide with 0.1% cyclopentolate HCl, or 0.1% tropicamide in a vehicle of 1.6% or 1.0% methylcellulose 400, or artificial tears or lubricants (Absorbobase, Contique, Isopto Tears, Liquifilm, Lyteers, Ultra Tears). Except for an initial lag in the production of mydriasis with the diluted mixtures, the results were similar for all preparations. The diluted solutions produced little ocular irritation or tearing.


Stop Preaching to the Choir, Publish Outside the Box: A Discussion.
In this article, I comment on Normand's, Vyse's, Friman's, Schlinger's, and Reed's articles on publishing books, journal articles, letters to the editor, and columns outside of behavior analysis, that is, "outside the box," as well as communicating with editors, authors, and journalists. Among the topics I address are the prerequisite repertoires and these authors' guidance (e.g., task analyses), as well as technical terms and language and the many opportunities available to us, yet also caveats about how, whether, and when we should publish outside the box. In the process, I include lessons I have learned from submitting my own manuscripts outside the box and suggestions I have gleaned from my failures and successes. In conclusion, if the field values publishing outside the box, then, it should analyze the necessary repertoires and provide systematic instruction in them.


Asymptomatic bacteriuria in antenatal patients in ilorin, Nigeria.
To determine the prevalence of asymptomatic bacteriuria, bacteriology and sensitivity pattern in Ilorin using the gold standard of urine culture. A prospective study was carried out from 1st July to 31st October 2007, at the University of Ilorin Teaching Hospital (UITH) on 125 consenting asymptomatic pregnant women. A structured proforma was used to collect information from the women and a midstream urine specimen collected for bacteriological culture. Of the 125 pregnant women, 50 had bacteriuria on urine culture giving a prevalence of 40%. The mean age of the women was 28.5 years with a standard deviation of 4.95. The age ranged between 14 and 40 years. Staphylococcus aureus was the commonest pathogen isolated (72%), followed by Proteus spp (14%). Most of the organisms showed good sensitivity to Nitrofurantoin and gentamicin. The prevalence of asymptomatic bacteriuria in Ilorin is high and routine urine culture is advocated for all pregnant women at booking.


Prevalence of the optrA gene among Streptococcus suis isolates from diseased pigs and identification of a novel integrative conjugative element ICESsu988S.
Aim of this study was to investigate the prevalence and genetic environment of the oxazolidinone resistance gene optrA in Streptococcus suis (S. suis) isolates from diseased pigs in China. A total of 178 S. suis isolates were screened for the optrA gene by PCR. The phenotypes and genotypes of optrA-positive isolates were investigated by antimicrobial susceptibility testing, core genome Multilocus Sequence Typing (cgMLST), capsular serotypes determination and whole-genome sequencing (WGS). Fifty-one (28.7%) S. suis isolates were positive for optrA. Phylogenetic analysis indicated that the spread of the optrA among S. suis isolates was primarily due to horizontal transfer. Analysis of S. suis serotypes from diseased pigs revealed substantial diversity. The genetic environment of optrA was complex and diverse and could be divided into 12 different types. Interestingly, we identified a novel integrative and conjugative element ICESsu988S, carrying optrA and erm(T) genes. This is to the best of our knowledge the first report of the optrA and erm(T) co-located on an ICE in S. suis. Our results showed a high prevalence of optrA gene in S. suis isolates in China. Further research is needed to evaluate the importance of ICEs, as they horizontally propagate important clinical resistance genes.


Evaluation of linked cancer registry and hospital records of breast cancer.
Information on the treatment of women with breast cancer in Australia is generally available only from special surveys. Analysis of routinely collected datasets may be more timely and cost effective, if the data are sufficiently accurate and complete. To evaluate the accuracy and completeness of data on treatment in linked records of breast cancer from two routinely collected datasets. The NSW Department of Health linked NSW Central Cancer Registry (CCR) records for 2,636 women diagnosed with breast cancer in NSW in 1992 to all hospital admission records in the NSW In-patient Statistics Collection (ISC) from January 1991 to June 1994. We queried the original paper records of subsets of women to identify missing or miscoded information and cases not notified to the CCR. We also compared the treatment data with data collected independently from the medical records of 19% of the women. ISC records linked to 89% of the CCR records. The CCR had identified 94.9% of women with breast cancer treated as hospital in-patients and 83% of these women had surgical treatment recorded in the ISC. The linked dataset under-estimated the percentage of women having breast-conserving therapy (-4%) and slightly over-estimated the percentage having mastectomy (+1%). We estimated that 42% of women treated surgically for breast cancer had actually had breast-conserving surgery, compared with 39% in the original dataset. There was no evident bias by age or by urban or rural residence in the under-recording of breast conservation. There was 94% agreement on the type of surgery between the linked dataset and the independent dataset.


Distribution of GnRH in the brain of the freshwater teleost Astyanax altiparanae.
GnRH is well known as a key decapeptide neurohormone involved in reproduction, stimulating the pituitary gland to release gonadotropins (LH and FSH), which, in turn, regulate steroidogenesis and gametogenesis. However, in addition to its reproductive functions, GnRH displays neuromodulatory roles with implications for sexual behavior. The pattern of distribution in the brain of GnRH may help reveal GnRH specific functions. Therefore, the main emphasis of this study is to detect the presence and distribution of GnRH in the brain of the freshwater teleost Astyanax altiparanae ("lambari"). The immunohistochemical method of peroxidase with an antibody raised against GnRH3 was used to detect the location of GnRHs in the brain and pituitary gland. Immunoreactivity to GnRH was found in the following encephalic areas: olfactory bulb, terminal nerve ganglion, preoptic area, nucleus of midbrain tegmentum, but also in torus longitudinalis, glomerular nucleus, and central and dorsal posterior nuclei of dorsal thalamus. In addition, cell bodies from neurons in the parvocellular and magnocellular periventricular nuclei and ventral tuberal nucleus along with many fibers including ones innervating the neurohypophysis were immunoreactive to a GnRH antiserum that detects all known eight GnRH peptides in teleosts. This is the first study describing the distribution of the complete GnRH system in the brain of A. altiparanae, which has great importance for aquaculture and ecology, and represents one of the major orders of South American teleosts--the Characiformes.


Prevalence of hypertension in patients with type II diabetes in referral versus primary care clinics.
We compared the prevalence of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM) in referral and primary care practices using definitions of The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), while controlling for other risk factors such as hypertension, obesity, smoking, and age. Patients (n = 1443) were enrolled consecutively from a large referral practice at the Jackson Diabetes Center and four primary care clinics in the vicinity. Blood pressures were measured at three clinic visits after a 5-min rest in a sitting position using a standard clinical sphygmomanometer. Charts were reviewed to determine diabetes duration, insulin usage, height, weight, smoking history, use of antihypertensive and oral hypoglycemic medications, socioeconomic status, and race. Patients were classified as hypertensive based on JNC-V definitions or if they were on antihypertensive medication. Hypertension was termed uncontrolled if blood pressure was JNC-V Stage 2 or higher while on antihypertensive medication. Seventy-eight percent of referral clinic and 55% of primary care clinic patients had either JNC-V State 1 or higher hypertension or were on antihypertensive medication. Actual blood pressures indicated that more patients had JNC-V Stage 1 (mild) or higher hypertension in referral compared to primary care clinics (62% versus 48% p = 0.01) but fewer had JNC-V Stage 2 or higher (moderate-severe) hypertension (12% versus 19% p = 0.002). Patients seen in the referral clinic were significantly more likely to have greater age, greater duration of diabetes, higher insulin dosage, longer smoking history, antihypertensive medication, and live outside the metropolitan area. By logistic regression, the odds of hypertension were significantly increased with age (OR 1.51/decade), BMI greater than 27 (OR 2.17), diabetes duration (OR 1.04/year), and insulin dosage (OR 1.74/U/kg). Current smoking and attending a referral clinic were not significantly related. The odds of moderate-severe hypertension were significantly increased with age (OR 1.23/ decade), decreased by attending a referral clinic (OR 0.45), and not significantly related to other confounders in the model. The prevalence of hypertension among patients with NIDDM was higher in referral than primary care clinics. The higher prevalence in the referral practice can be accounted for by the greater severity of associated risk factors in the referral practice patients; however, most patients will be diagnosed and treated for hypertension prior to referral. More patients in the referral practice were on hypertensive medication, which lowered the stage or severity of hypertension but still not to the normal range. The results suggest that the primary detection of hypertension in patients with type II diabetes resides with the primary care physician. Management of hypertension will require both a delineation and acceptance of responsibilities between the primary care physician and diabetes specialists.


Limno-ecological assessment of lentic ecosystems in the western Mediterranean basin (Turkey) using phytoplankton indices.
Great attention has been given to freshwater ecosystems worldwide due to the increased exploitation of water resources and the degradation of water quality. This study was aimed to demonstrate the phytoplankton-stressor interactions using multivariate approaches and assess the ecological conditions of 28 sampling stations of 12 lentic ecosystems (five lakes and seven reservoirs) in the western Mediterranean basin using phytoplankton indices in dry and rainy seasons 2018. Freshwater and brackish water systems were separately ordinated by canonical correspondence analysis. The brackish ecosystems were under pressures of Ar (arsenic), N-N[Formula: see text] (nitrite), Ca (calcium), EC (electrical conductivity), Cl (chloride), B (boron), etc., whereas shallow freshwater ecosystems were associated with total organic carbon. These factors had significant effects on phytoplankton distribution among lentic ecosystems on the basin. Ecological associations of phytoplankton assemblages varied in the western Mediterranean basin during the study. Pseudanabaena catenata and Palatinus apiculatus, considered tolerant taxa, are associated with higher Ar, EC, and V (vanadium) while Desmodesmus abundans and Microcystis flos-aquae are related to total organic carbon. The modified PTI (phytoplankton trophic index) had the highest correlation coefficient value. Scores of the PTI varied from 2.02 in Çavdır Reservoir to 2.59 in Lake Kocagöl. Results of phytoplankton indices indicated that two (Gölhisar and Yazır) lakes and two (Yapraklı and Çavdır) reservoirs were classified as Good, and three lakes and five reservoirs were classified as Moderate condition. Other predicted classifications (high, poor, and bad) by phytoplankton metrics were not represented. The modified PTI could be a suitable phytoplankton metric for assessing the ecological status of lentic ecosystems in the Mediterranean system according to its highest correlation coefficient value. Overall, the results of this limno-ecological study demonstrated that responses of phytoplankton taxa to explanatory factors provide crucial ecological information about their ecology and to estimate the ecological status of lentic ecosystems.


Management of endocrine orbitopathy.
Endocrine ophthalmopathy remains the most common cause of proptosis in adults. In a small but significant percentage of patients, vision can be threatened, requiring prompt intervention. In the patients who fail to respond to medical management with high-dose steroids, surgical decompression is indicated. The Walsh-Ogura antral-ethmoidal decompression is the most widely used approach at this time. Radiation therapy is a therapeutic modality that is probably best reserved for patients who fail to respond to steroids or surgery, or in whom these two approaches are not possible. The management of endocrine orbitopathy continues to be directed toward relief of symptoms. A multidisciplinary approach, involving the endocrinologist, ophthalmologist, otolaryngologist-head and neck surgeon, and oculoplastic surgeon is often required to achieve the best outcome.


Decision making under uncertainty in the diagnosis and management of Alzheimer's Disease in primary care: A study protocol applying concepts from neuroeconomics.
The current management of patients with Dementia, primarily with Alzheimer's Disease (AD) is rapidly evolving. However, limited information is available about the current gaps and decision-making in primary care. To evaluate factors associated with gaps, risk preferences regarding diagnostic and therapeutic choices in the management of patients with AD by primary care physicians (PCP) from across Canada. We propose a non-interventional, cross-sectional pilot study involving 120 primary care physicians referred from the College of Family Physicians of Canada to assess diagnostic and therapeutic decisions in the management of ten simulated AD-related case-scenarios commonly encountered in clinical practice. We initially describe the current landscape and gaps regarding diagnostic and therapeutic challenges in the management of patients with AD in primary care. Then, we provide concepts from behavioral economics and neuroeconomics applied to medical decision-making. Specifically, we include standardized tests to measure risk aversion, physicians' reactions to uncertainty, and questions related to risk preferences in different domains. Finally, we summarize the protocol to be implemented to address our goals. The primary study outcome is the proportion of participants that elect to defer initial investigations to the specialist and the associated factors. Secondary outcomes include the proportion of PCP willing to order cerebral spinal fluid studies, PET scans, or initiate treatment according to the simulated case-scenarios. The study will be conducted in English and French. The study findings will contribute a better understanding of relevant factors associated with diagnostic and therapeutic decisions of PCP in the management of AD, identifying participant's preferences and evaluating the role of behavioral aspects such tolerance to uncertainty, aversion to ambiguity, and therapeutic inertia.


Mastocytosis in Children.
In this review, we examine the current understanding of the pathogenesis, clinical presentations, diagnostic tools, and treatment options of pediatric mastocytosis as well as the natural history of the disease. We discuss the emerging concept of mast cell activation syndrome. Mastocytosis in children presents most commonly as isolated cutaneous lesions and is a relatively rare occurrence with excellent prognosis and spontaneous regression often occurring by adolescence. Systemic mastocytosis with organ system involvement is a more serious condition and is likely to persist into adulthood.


TssA from Burkholderia cenocepacia: expression, purification, crystallization and crystallographic analysis.
TssA is a core component of the type VI secretion system, and phylogenetic analysis of TssA subunits from different species has suggested that these proteins fall into three distinct clades. Whilst representatives of two clades, TssA1 and TssA2, have been the subjects of investigation, no members of the third clade (TssA3) have been studied. Constructs of TssA from Burkholderia cenocepacia, a representative of clade 3, were expressed, purified and subjected to crystallization trials. Data were collected from crystals of constructs of the N-terminal and C-terminal domains. Analysis of the data from the crystals of these constructs and preliminary structure determination indicates that the C-terminal domain forms an assembly of 32 subunits in D16 symmetry, whereas the N-terminal domain is not involved in subunit assocation.


[Accumulation of α-tocopherol and β-carotene in Euglena gracilis Cells under Autotrophic and Mixotrophic Culture Conditions].
The aim of the work was to find the mode of cultivation of unicellular flagellate Euglena gracilis, favorable for the simultaneous accumulation of α-tocopherol and β-carotene. Cells were grown either in photoautotrophic or photoheterotrophic conditions in the presence of 100 mM ethanol (variant Et) or 40 mM glutamate (variant Gt), or their combination (variant EtGt). The exogenous substrates significantly stimulated light-dependent growth of E. gracilis. The largest increase of biomass was recorded on the 20th day in the variant EtGt and exceeded the autotrophic control by 7 times. The content of β-carotene and chlorophyll (Chl) per cell in mixotrophic cultures exceeded the control by 2-3 and 1.6-2 times, respectively. At the same time, α-tocopherol accumulation in autotrophic cells was greater than in the cells of mixotrophic cultures by 2-7 times. Total yield of tocopherol per unit volume of culture medium, which depended not only on its intracellular content, but also on the amount of accumulated biomass was highest in EtGt variant. A correlation between the accumulation of the antioxidants and the equilibrium concentration of oxygen in the growth medium, which depended on the intensities of photosynthesis and respiration has been analyzed.


TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes.
Rapid induction of inflammatory genes by tumor necrosis factor (TNF) has been well studied, but little is known about delayed and chronic TNF responses. Here we investigated the kinetics of primary macrophage responses to TNF and discovered that TNF initiates an interferon-beta-mediated autocrine loop that sustains expression of inflammatory genes and induces delayed expression of interferon-response genes such as those encoding the transcription factors STAT1 and IRF7, which enhance macrophage responses to stimulation of cytokines and Toll-like receptors. TNF-induced interferon-beta production depended on interferon-response factor 1, and downstream gene expression was mediated by synergy between small amounts of interferon-beta and canonical TNF-induced signals. Thus, TNF activates a 'feed-forward' loop that sustains inflammation but avoids the potential toxicity associated with the high interferon production induced by stimulation of Toll-like receptors.


The isolation and immunogenicity of the cuticle of Dipetalonema viteae (Filarioidea).
The cuticle of the filaria Dipetalonema viteae was isolated by sonication in 1% sodiumdodecylsulphate (SDS) and in a mixture of 1% SDS and 5% B-mercaptoethanol (BME). Sonication in SDS removed all internal parts and left the cuticle intact; this was verified by light- and electronmicroscopy. Sonication and incubation of the cuticle in the mixture of SDS-BME at pH 6.8 dissolved the basal and part of the median zone of the cuticle. The epicuticle and the cortical zone remained intact. The extracts were investigated using SDS-polyacrylamide gel electrophoresis; the early extracts contained a wide variety of proteins, whereas the later steps showed a consistent pattern with a smaller number of bands. Cuticles after SDS-purification, the extract of cuticular material in SDS-BME, and the cuticles insoluble in SDS-BME were used to immunize mice; the antibodies produced were visualized by an indirect fluorescent antibody test on cryostat sections of female worms. When SDS-purified cuticles were used for immunization, antibodies directed against all organs in the filariae were found. The SDS-BME extract and the insoluble cuticular pellet stimulated the production of antibodies restricted to the cuticle of adult worms and microfilariae. The purification method opens up the possibility of further isolation and characterization of antigens from the cuticle.


Lack of correlation of ECV and outcome in an in vivo murine model of systemic fusariosis.
The efficacy of liposomal amphotericin B and voriconazole was evaluated against the systemic infection by Fusarium oxysporum species complex or Fusarium keratoplasticum. Although MIC values were within the epidemiological cutoff values (ECVs) recently stablished for Fusarium spp., no efficacy was obtained, indicating that ECVs for Fusarium are not relevant for in vivo efficacy.


Preventing the next event in the elderly: the PROSPER perspective.
Statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals but their efficacy and safety in elderly people has not been confirmed. Several clinical trials including the Cholesterol and Recurrent Events (CARE) and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), have sub-analysed their results for the 'elderly' cohort, but the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial is the first trial to specifically evaluate the benefits of statin therapy on vascular risk in elderly men and women. The results have shown that pravastatin, given for 3 years, reduced the risk of coronary heart disease in elderly individuals. Within this same time frame, there was no significant benefit on the risk reduction of stroke but there was a trend to reduce the risk of transient ischemic attacks. It was discovered that those patients with the lowest baseline high-density lipoprotein cholesterol gained the most benefit from the intervention. Drug interactions between pravastatin and the concomitant medications seen in this elderly cohort, was not a significant clinical issue. Therefore, PROSPER extends to elderly individuals the treatment strategy currently used in middle-aged people.


Real-time forecasting and early warning of bacillary dysentery activity in four meteorological and geographic divisions in China.
Accurate and timely forecasts of bacillary dysentery (BD) incidence can be used to inform public health decision-making and response preparedness. However, our ability to detect BD dynamics and outbreaks remains limited in China. This study aims to explore the impacts of meteorological factors on BD transmission in four representative regions in China and to forecast weekly number of BD cases and outbreaks. Weekly BD and meteorological data from 2014 to 2016 were collected for Beijing (Northern China), Shenyang (Northeast China), Chongqing (Southwest China) and Shenzhen (Southern China). A boosted regression tree (BRT) model was conducted to assess the impacts of meteorological factors on BD transmission. Then a real-time forecast and early warning model based on BRT was developed to track the dynamics of BD and detect the outbreaks. The forecasting methodology was compared with generalized additive model (GAM) and seasonal autoregressive integrated moving average model (SARIMA) that have been used to model the BD case data previously. Ambient temperature was the most important meteorological factor contributing to the transmission of BD (80.81%-92.60%). A positive effect of temperature was observed when weekly mean temperature exceeded 4 °C, -3 °C, 9 °C and 16 °C in Beijing (Northern China), Shenyang (Northeast China), Chongqing (Southwest China) and Shenzhen (Southern China), respectively. BD incidence (Beijing and Shenyang) in temperate cities was more sensitive to high temperature than that in subtropical cities (Chongqing and Shenzhen). The dynamics and outbreaks of BD can be accurately forecasted and detected by the BRT model. Compared to GAM and SARIMA, BRT model showed more accurate forecasting for 1-, 2-, 3-weeks ahead forecasts in Beijing, Shenyang and Shenzhen. Temperature plays the most important role in weather-attributable BD transmission. The BRT model achieved a better performance in comparison with GAM and SARIMA in most study cities, which could be used as a more accurate tool for forecasting and outbreak alert of BD in China.


Application of temperature-controlled micro planar chromatography for separation and quantification of testosterone and its derivatives.
Temperature-controlled micro thin-layer chromatography (TLC) was applied for separation and quantification studies of testosterone and its derivatives including methyltestosterone, testosterone propionate, isobutyrate, phenylpropionate, isocaproate, enanthate and caprate. Chromatographic studies were performed on silica-, octadecylsilica- and aluminum-coated plates working inside a small thermostated horizontal chamber unit allowing one-dimensional and two-dimensional developing modes with an elution distance of 45 mm. Retention properties of steroids were investigated across a whole range of binary mixtures such as methanol/water, acetonitrile/water, methanol/dichloromethane and acetone/hexane (0-100% v/v). Moreover, the effect of temperature ranging from -20 to +60 degrees C under saturated and unsaturated chamber conditions was also investigated. Our results revealed that depending on the mobile phase polarity the separation system based on the low carbon load wettable with water RP18W plates may work as a normal-phase (NP) or reversed-phase (RP) chromatographic system. It has been also demonstrated that micro TLC equipment can be applied as a fast retention screening device as well as simple and robust quantitative tool for determination of testosterone residue containing testosterone derivatives in complex samples.


Tear lipocalin: potential for selective delivery of rifampin.
The potential of ligand binding proteins as drug carriers and delivery systems has recently sparked great interest. We investigated the potential of tear lipocalin (TL) to bind the antibiotic, rifampin, and the environmental conditions for controlled release. To determine if TL binds rifampin, gel filtration was used to isolate protein fractions of tears. Rifampin was detected by absorbance spectroscopy in the elution fractions containing TL. The bound complex of rifampin-TL generates optical activity at about 360 nm, indicating a unique conformation at the binding site. Rifampin has a higher affinity for TL (Kd=128 microM) than albumin. Rifampin is released from the TL calyx in acidic conditions and is displaced by palmitic acid. Autooxidation of free rifampin begins in minutes but is delayed by at least 3 h in the presence of TL. These properties are conducive to stabilization and delivery of rifampin to tubercles that are acidic and rich in fatty acids. These studies show the potential of TL as a carrier for rifampin with controlled release to a targeted environment.


Influence of diagnostic categories, age, and gender on antioxidative defense and lipid peroxidation in skeletal muscle of patients with neuromuscular diseases.
The influence of diagnostic categories, age, and gender on parameters of oxidative stress measured in 102 patients with neuromuscular diseases and 11 control subjects was assessed using a stepwise multiple linear regression model. Antioxidative enzyme activities, lipophilic antioxidants, and lipid peroxidation were analyzed in muscle biopsies. Mitochondrial myopathies and amyotrophic lateral sclerosis (ALS) are thought to be particularly susceptible to increased oxidative stress. In our study, mitochondrial myopathies emerged as a positive predictor of malondialdehyde (p < 0.05) and ALS as a negative predictor of alpha-tocopherol (p < 0.05). Although the primary atrophic process in ALS is not in muscle but in motoneurons, this finding could have therapeutic implications, as such patients might benefit from antioxidant supplementation. In our study age emerged as a negative predictor of the coenzyme Q10 concentration (p < 0.003), whereas the percentage of reduced coenzyme Q10 remained unchanged. Age emerged as a positive predictor of the activities of catalase (p < 0.01) and superoxide dismutase (p < 0.002), probably reflecting an enzymatic upregulation that compensates for the loss of coenzyme Q10. The increased activities of catalase and superoxide dismutase in females compared to males indicate a higher antioxidative potential in female muscle. Whether this increase contributes to a higher life expectancy of women remains to be investigated.


Micromonospora mangrovi sp. nov., isolated from mangrove soil.
A novel actinomycete strain 2803GPT1-18(T) was isolated from a composite mangrove soil sample collected from Beihai, Guangxi province, China. Phylogenetic analysis of the 16S rRNA gene sequence of strain 2803GPT1-18(T) indicated high similarity with 'Micromonospora harpali' NEAU-JC6(T) (99.2 %), Micromonospora haikouensis 232617(T) (99.1 %), Micromonospora wenchangensis 2602GPT1-05(T) (99.1 %), Micromonospora schwarzwaldensis HKI0641(T) (99.1 %). The gyrB gene sequence analysis also indicated that strain 2803GPT1-18(T) should be assigned to the genus Micromonospora but different from any established Micromonospora species. The strain harbored meso-DAP and glycine as major cell wall amino acids, MK-10(H6) (53.5 %), MK-9(H6) (25.1 %) and MK-9(H4) (13.4 %) as predominant menaquinones. The characteristic whole cell sugars are arabinose, xylose, glucose, galactose and mannose. The polar lipid profile comprises phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol and unidentified polar lipids. The major cellular fatty acids present are iso-C16:0 (44.2 %) and iso-C15:0 (12.4 %). The DNA G+C content is 71.2 mol%. Furthermore, a combination of DNA-DNA relatedness and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from the closely related species. On the basis of these phenotypic and genotypic data, strain 2803GPT1-18(T) represents a novel species of the genus Micromonospora, for which the name Micromonospora mangrovi sp. nov. is proposed. The type strain is 2803GPT1-18(T) (=CCTCC AA2012012(T) = DSM45761(T)).


Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 analogue, in Latino/Hispanic patients with type 2 diabetes: post hoc analysis of data from four phase III trials.
The aim of the present analysis was to evaluate the efficacy of the glucagon-like peptide-1 receptor agonist liraglutide in Latino/Hispanic individuals with type 2 diabetes, in addition to comparing its treatment effects with those observed in non-Latino/Hispanic individuals. Analyses were performed on patient-level data from a subset of individuals self-defined as Latino/Hispanic from four phase III studies, the LEAD-3, LEAD-4, LEAD-6 and 1860-LIRA-DPP-4 trials. Endpoints included change in glycated haemoglobin (HbA1c) and body weight from baseline. In Latino/Hispanic patients (n = 505; 323 treated with liraglutide) after 26 weeks, mean HbA1c reductions were significantly greater with both liraglutide 1.2 and 1.8 mg versus comparator or placebo in the LEAD-3 and LEAD-4 studies, and with 1.8 mg liraglutide in the 1860-LIRA-DPP-4 trial. In LEAD-3 both doses led to significant differences in body weight change among Latino/Hispanic patients versus the comparator. With 1.8 mg liraglutide, difference in weight change was significant only in the 1860-LIRA-DPP-4 trial versus sitagliptin. For both endpoints Latino/Hispanic and non-Latino/Hispanic patients responded to liraglutide similarly. In summary, liraglutide is efficacious for treatment of type 2 diabetes in Latino/Hispanic patients, with a similar efficacy to that seen in non-Latino/Hispanic patients.


Vertical angular momentum constraint on lunar formation and orbital history.
The Moon likely formed in a giant impact that left behind a fast-rotating Earth, but the details are still uncertain. Here, we examine the implications of a constraint that has not been fully exploited: The component of the Earth-Moon system's angular momentum that is perpendicular to the Earth's orbital plane is nearly conserved in Earth-Moon history, except for possible intervals when the lunar orbit is in resonance with the Earth's motion about the Sun. This condition sharply constrains the postimpact Earth orientation and the subsequent lunar orbital history. In particular, the scenario involving an initial high-obliquity Earth cannot produce the present Earth-Moon system. A low-obliquity postimpact Earth followed by the evection limit cycle in orbital evolution remains a possible pathway for producing the present angular momentum and observed lunar composition.


Delayed diagnosis, due to the associated radiological abnormalities, of spontaneous intracranial hypotension caused by cerebrospinal fluid leakage at C1-2.
Spontaneous intracranial hypotension (SIH) is an uncommon clinical entity that is often diagnosed after a delay, or it is misdiagnosed due to the variety of clinical presentations and the associated radiological findings. We present here a case of SIH associated with chronic subdural haematoma (SDH) and subarachnoid haemorrhage. Following the diagnosis of the SIH, the patient underwent injection of an epidural blood patch for the SIH and burr hole trephination was done for treating the chronic subdural haematoma.


[Quantitative ultrasonic integrated backscatter of the intima-media complex, serum level of matrix metalloprotease-9 and simvastatin in hyperlipemia patients].
To determine the diagnostic value of the integrated backscatter (IBS) technique for carotid artery atherosclerosis (AS), to investigate the correlation between IBS of carotid artery and the serum level of matrix metalloprotease-9(MMP-9), and to explore the effect of simvastatin on the IBS value of the carotid artery and serum MMP-9 level in hyperlipemia patients. Fifty-eight patients with hyperlipemia and 26 normal controls were enrolled in this study. Patients with hyperlipemia were randomly divided into 2 groups: a simvastatin treatment group (20 mg/d) and a control group (without simvastatin treatment). Twenty-six healthy people were served as normal control group(n=26).The corrected IBS values(C-IBS) in carotid arteries,the intima-media thickness (IMT), and the serum MMP-9 levels were measured in the normal control group and the patients with hyperlipemia before and 8 weeks after the simvastatin therapy. The C-IBS of the simvastatin treatment group and the control group was significantly lower than that in the normal control group (all P<0.05). The IMT and MMP-9 in the simvastatin treatment group and the control group were significantly higher than those in the normal control group (all P<0.05). There was a negative correlation between the C-IBS of carotid arteries and the serum MMP-9 levels in the patients with hyperlipemia (r=-0.76,P<0.05). Eight weeks after the simvastatin treatment, the serum MMP-9 levels decreased significantly(P<0.05). There is a negative correlation between the decreased C-IBS of carotid arteries and the increased serum MMP-9 levels in patients with hyperlipemia.The decreased C-IBS of carotid arteries and the increased serum MMP-9 levels may be the early indicators of atherosclerosis in hyperlipemia patients. The anti-atherosclerosis effect of simvastatin may partly attribute to its ability to lower the serum MMP-9.


Morphology, flow regimes, and filtering rates of Daphnia, Ceriodaphnia, and Bosmina fed natural bacteria.
Body size is the best overall indicator of the abilities of the cladocerans Daphnia magna, D. parvula, Ceriodaphnia lacustris and Bosmina longirostris to filter natural bacteria (<1.0 μm). However, species differences exist which cannot be inferred from differences in size, behavior, or morphology alone. The relationship between filtering rate (FR in ml animal-1h-1) and body length (L in mm) for the cladocerans studied can be described by the power function: [Formula: see text] In D. parvula, algal filtering rates are higher and increase more rapidly with increasing body size than do bacterial filtering rates which are 26 to 33% of algal rates. This suggests that different processes may be involved in the capture of these ultrafine particles and that ultrafine particle capture efficiency decreases with increasing body size within a species. Weight specific filtering rates (in μl μg dry wt-1h-1) have a strong negative relationship to body size and show species specific differences. Appendage beat rates intersetular distances, setule diameter, appendage, area, % open space on the filtering appendage, Reynolds number, and boundary layer thickness do not provide simple predictions of bacterial filtering rates for the cladocerans studied. Filtering rates on cultured laboratory bacteria and algae may not indicate filtering rates on natural bacterioplankton because of differences in bacterial size, motility, and surface properties. Uptake of ultrafine particles may be enhanced by the presence of larger, more readily filtered particles through a "piggybacking" phenomenon.


A comparative clinical trial of two different regimens of artemether plus mefloquine in multidrug resistant falciparum malaria.
Plasmodium falciparum in Thailand is highly resistant to available antimalarial drugs. Artemether, a derivative of artemisinin, is a promising compound currently used to cope with this situation but the course of treatment has to be at least 5 d. An effective short treatment course of this drug is possible when used in combination with mefloquine. We now report a trial of different regimens of the combination artemether/mefloquine. Fifty-seven male Thai patients, admitted to the Bangkok Hospital for Tropical Diseases, were allocated at random to receive oral artemether 300 mg as an initial dose, followed by either the standard dose of mefloquine (750 mg) at 24 h or a higher dose of mefloquine (750 mg at 24 h, then 500 mg at 30 h). Patients were followed up in hospital for 42 d. Two patients, both in the high dose mefloquine group, were excluded as they failed to attend for follow-up. All patients had a rapid initial response to treatment with median parasite clearance times of 37 and 40 h, median fever clearance times of 33.5 and 30.5 h, and cure rates of 75 and 96% (P = 0.0248), for the standard and high doses of mefloquine respectively. No serious adverse effect was found; mild and transient dizziness, nausea, vomiting and diarrhoea were noted in half of the patients in each group. The results suggest that a 30 h short course of artemether plus mefloquine at high dose should be used in areas with documented mefloquine resistance.


Analysis of COVID-19 vaccine uptake among people with underlying chronic conditions in 2022: A cross-sectional study.
COVID-19 has been a global burden and vaccinations have proven to be the most effective measure to fight this pandemic. Since the approval and distribution of the vaccines, approximately 75% of District of Columbia residents have been fully vaccinated leaving a quarter of the population at risk. With the availability and approval of the booster doses to people with high-risk chronic conditions, it is important to understand the attitude of people towards vaccinations. The objective of this research study is to analyze the COVID-19 vaccination uptake among people with underlying chronic conditions residing in District of Columbia residents and to determine the reason for the hesitancy to perform targeted outreach to unvaccinated populations. In 2022, we conducted a cross sectional study via a short online survey that was distributed to the target populations via email and social media. Multivariable Regression Analyses were conducted to determine the factors associated with the acceptance of the vaccination across various demographics. The findings of the study demonstrate that the acceptance of COVID-19 vaccination was low among people with chronic conditions compared to those with no underlying chronic conditions, and vaccination rates strongly differ based on social determinants like education, employment, and area of residence across District of Columbia. The public health significance of this study is to understand the reason behind the vaccine hesitancy so that we can work towards building trust, extending outreach, creating targeted health education, and increasing access to vaccination to all communities across District of Columbia.


Significant change in air quality parameters during the year 2020 over 1st smart city of India: Bhubaneswar.
Prevention of Coronavirus results in lockdown in India from 24 March 2020 to 31 May 2020. Eastern India, which is having a dense cluster of coal-fired power plants and home to many mines, mineral industries, has not shutdown power plants and coal mines during this lockdown period, though other industrial and vehicular emissions were almost zero. The present study attempts to find the change in various atmospheric pollutants during this lockdown period over an eastern tropical Indian station-Bhubaneswar, which is the first smart city proposed in smart city mission of Government of India. The study analyses hourly concentrations of PM2.5, PM10, NO X , O3, and CO for March-May 2019 and 2020. The study shows a significant increase (rather than decrease) in PM2.5 and PM10, increase in O3 and a decrease in CO and NO X during the lockdown period. Results are advocating the impact of transported pollution over the study area for maintaining the PM2.5 and PM10 values even during the lockdown situation.


PCAF inhibits hepatocellular carcinoma metastasis by inhibition of epithelial-mesenchymal transition by targeting Gli-1.
The p300-CBP-associated factor (PCAF), other than its histone acetyltransferase (HAT) activity, possesses an intrinsic ubiquitination activity that is involved in various transcriptional regulators, including the transcription factor glioma-associated oncogene 1 (Gli1), a well-known regulator of epithelial-mesenchymal transition (EMT) in cancer. In present research, we detected that PCAF was down-regulated in hepatocellular carcinoma (HCC) tissues compared with the adjacent non-tumor tissues and significantly associated with malignant portal vein invasion (p < 0.05) and poor survival (p < 0.05) of HCC patients. Moreover, functional study demonstrated that downregulation of PCAF facilitated tumor cell migration, invasion via EMT. Further study found that Gli1 as a direct target of PCAF induced EMT and promoted tumor metastasis and invasion. PCAF is an anti-oncogene that plays an important role in the development of HCC by suppressing HCC cell metastasis and EMT by targeting Gli1, which indicates the potential therapeutic value of PCAF for suppression of metastasis of HCC.


Evolution of acute "black hole" lesions in patients with relapsing-remitting multiple sclerosis.
Gadolinium-enhanced T1-weighted lesions are a well-established marker of areas with acute inflammatory activity. A majority of these gadolinium-enhanced T1 lesions are isointense relative to the surrounding white matter, but 20-40% of such active lesions will evolve during one year into areas of low signal ("black hole"). This study sought to characterize evolution of "black hole" lesions in patients with relapsing-remitting multiple sclerosis (MS) using the magnetic resonance imaging (MRI), which measures active lesions via the count of new or enlarged T2 and gadolinium-enhanced T1-weighted lesions. This was a prospective, observational case-series study which utilized pre- and post-gadolinium contrast T1-weighted and Proton density MRI scans. Twenty-nine patients (8 males and 21 females) with average age of 38.86 ± 6.58 years and disease duration of 5.75 ± 7.00 years were used to analyze 196 acute demyelinating plaques detected on MRI images during the 24-month follow-up of post-gadolinium signal intensity enhancement of MS plaques. Significant difference in black hole development was found between the shapes of acute and chronic "black holes". Ring-shaped and patchy plaques were 4.09 (1.87-8.91) times more likely and 1.49 (0.71-3.12) times less likely to develop an acute "black holes" than homogeneous plaques, respectively. Acute plaques with higher lesion-to-CSF SI ratio and larger surface area showed a greater tendency to develop into acute and chronic "black holes". The value of lesion-to-CSF SI ratio and surface area were found as the predictors of the "black hole" formation.


Effects of methylprednisolone on concanavalin A-induced human lymphocyte blastogenesis: a comparative analysis by flow cytometry, volume determination and 3H-thymidine incorporation.
The inhibition of concanavalin A-induced human peripheral blood lymphocyte blastogenesis by methylprednisolone (MP) was studied by using flow cytometry and tritiated thymidine (3H-TdR) incorporation. Flow cytometric determinations of volume, low angle forward light scatter, and nucleic acid showed MP to be a potent inhibitor of blastogenesis. The effects were concentration-dependent and correlated with 3H-TdR uptake. By using the single cell analytic capability of flow cytometry, the target stages of the cell cycle where MP affects lymphocyte activation were determined. Evidence is presented that steroids can block both early and late phases of this process.


VCD studies on cyclic peptides assembled from L-α-amino acids and a trans-2-aminocyclopentane- or trans-2-aminocyclohexane carboxylic acid.
The increasing interest in peptidomimetics of biological relevance prompted us to synthesize a series of cyclic peptides comprising trans-2-aminocyclohexane carboxylic acid (Achc) or trans-2-aminocyclopentane carboxylic acid (Acpc). NMR experiments in combination with MD calculations were performed to investigate the three-dimensional structure of the cyclic peptides. These data were compared to the conformational information obtained by electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectroscopy. Experimental VCD spectra were compared to theoretical VCD spectra computed quantum chemically at B3LYP/6-31G(d) density functional theory (DFT) level. The good agreement between the structural features derived from the VCD spectra and the NMR-based structures underlines the applicability of VCD in studying the conformation of small cyclic peptides.


Clinical evaluation of optic atrophy in patients with neurological disorders.
Optic atrophy is a pathological term applied to optic nerve shrinkage from any process that produces degeneration of axons in the anterior visual system (the retino-geniculate pathway). The pathologist can make the diagnosis of optic atrophy by direct observation of the histopathological changes in the optic nerve. The clinician is restricted to indirect evidence by observing the optic nerve as it enters the eye and through testing its function. Fifty patients with bilateral or unilateral optic atrophy, were collected randomly from several teaching hospitals in Baghdad, Iraq, between August 1998 and June 1999. Those patients included in this study had ophthalmoscopic abnormalities of the optic disc in addition to defective visual function that could be localized to the optic nerve. The defects in visual function varied between patients according to the disease process and duration of illness. Eight-seven percent of patients had visual acuity impairment, 74.4% had visual field defect, 58.5% had impairment in color perception, 64% had defective pupillary response to light and 88.4% had prolonged visual evoked potential (VEP) responses. Patients who met the criteria for optic atrophy have different and unequal changes in optic nerve functions, ranging from 58.5% for color saturation test to 88.4% for VEP. Forty percent of patients with optic atrophy were discovered accidentally.


Intramitochondrial Ca(2+) Sensing by EMRE: The Matrix Outlook on Stimulus-Metabolism Coupling.
Mitochondrial Ca(2+) entry is an important process regulating cellular bioenergetics, redox responses, and apoptosis. The study by Vais and colleagues (Vais et al., 2016), recently published in Cell Reports, describes a novel mechanism of modulating Ca(2+) entry that involves mitochondrial matrix Ca(2+).


Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death.
Biodegraders are targeted protein degradation constructs composed of mini-proteins/peptides linked to E3 ligase receptors. We gained deeper insights into their utility by studying Con1-SPOP, a biodegrader against proliferating cell nuclear antigen (PCNA), an oncology target. Con1-SPOP proved pharmacologically superior to its stoichiometric (non-degrading) inhibitor equivalent (Con1-SPOPmut) as it had more potent anti-proliferative effects and uniquely induced DNA damage, cell apoptosis, and necrosis. Proteomics showed that PCNA degradation gave impaired mitotic division and mitochondria dysfunction, effects not seen with the stoichiometric inhibitor. We further showed that doxycycline-induced Con1-SPOP achieved complete tumor growth inhibition in vivo. Intracellular delivery of mRNA encoding Con1-SPOP via lipid nanoparticles (LNPs) depleted endogenous PCNA within hours of application with nanomolar potency. Our results demonstrate the utility of biodegraders as biological tools and highlight target degradation as a more efficacious approach versus stoichiometric inhibition. Once in vivo delivery is optimized, biodegraders may be leveraged as an exciting therapeutic modality.


A novel co-catalyzed system between persulfate and chlorite by sonolysis for removing triphenylmethane derivative.
Triphenylmethane (tpm) derivatives (e.g. tpmCV) have threatened the safety of the aquatic environment due to the potential toxicity and carcinogenicity. In this study, the novel ultrasonic/persulfate/chlorite (US/S2O82-/ClO2-) oxidation process was developed for the effective removal of tpmCV in wastewater. The apparent non-integer kinetics (n around 1.20) of tpmCV degradation under different factors (R2Adj > 0.990) were investigated, respectively. Inhibiting effects of anions were greater than those of cations (except Fe(II/III)). The adding of micromolecule organic acids could regulate degradation towards positive direction. The double response surface methodology (RSM) was designed to optimize tpmCV removal process, and the acoustic-piezoelectric interaction was simulated to determine the propagation process of acoustic wave in the reactor. The possible degradation pathway was explored to mainly include carbonylation, carboxylation, and demethylation. The estimated effective-mean temperature at the bubble-water interface was calculated from 721 to 566 K after introducing the ClO2-, however, the adsorption or partitioning capacity of tpmCV in the reactive zone was widened from 0.0218 to 0.0982. The proposed co-catalysis of US/S2O82-/ClO2- was based on the determined active species mainly including ClO2, SO4⋅-, and ⋅OH. Compared with other US-based processes, the operating cost (3.97 $/m3) of US/S2O82-/ClO2- with the EE/O value (16.8 kWh/m3) was relatively reduced.


SEOM-GEINO clinical guidelines for high-grade gliomas of adulthood (2022).
High-grade gliomas (HGG) are the most common primary brain malignancies and account for more than half of all malignant primary brain tumors. The new 2021 WHO classification divides adult HGG into four subtypes: grade 3 oligodendroglioma (1p/19 codeleted, IDH-mutant); grade 3 IDH-mutant astrocytoma; grade 4 IDH-mutant astrocytoma, and grade 4 IDH wild-type glioblastoma (GB). Radiotherapy (RT) and chemotherapy (CTX) are the current standard of care for patients with newly diagnosed HGG. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent high-grade gliomas is not well defined and decision-making is usually based on prior strategies, as well as several clinical and radiological factors. Whereas the prognosis for GB is grim (5-year survival rate of 5-10%) outcomes for the other high-grade gliomas are typically better, depending on the molecular features of the tumor. The presence of neurological deficits and seizures can significantly impact quality of life.


Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells.
1,25(OH)2-Vitamin D3 inhibits breast cancer cell proliferation through interaction with the vitamin D receptor (VDR). Regulation of VDR is under the influence of several factors which include the functional ligand for this receptor (1,25(OH)2-vitamin D3) as well as heterologous steroid hormones. We evaluated the nature of homologous regulation in T-47D human breast cancer cells with a radiolabelled ligand binding assay and a ribonuclease protection assay for VDR. Significant VDR up-regulation, as measured by hormone binding assays, occurred with pre-incubations with 10(-9)M through 10(-6)M 1,25(OH)2-vitamin D3 (P < 0.05). A 7-fold VDR up-regulation with 10(-8)M 1,25(OH)2-vitamin D3 occurred at 4 h treatment and was not associated with an increase in VDR mRNA expression on ribonuclease protection assay. This supports the hypothesis that up-regulation of VDR is probably the result of ligand-induced stabilization of pre-existing receptor. All-trans-retinoic acid, the progesterone analog R-5020, and prednisone were found to induce heterologous up-regulation of the VDR. We then determined with ligand binding assays whether 1,25(OH)2-vitamin D3 could influence receptor levels for another hormone in a manner analogous to the heterologous regulation of VDR. Regulation of estrogen receptor (ER) by 1,25(OH)2-vitamin D3 was studied in T-47D and MDA-MB-231 breast cancer cells. Incubation of T-47D cells, which are ER (+), with 10(-8)M 1,25(OH)2-vitamin D3 did not result in up-regulation of ER. Yet estrogen binding was significantly up-regulated in a cell line that is ER(-), MDA-MB-231. The increased estrogen binding was associated with a shift in binding affinity and ribonuclease protection assay showed absence of ER mRNA in these cells, suggesting an up-regulation of estrogen binding proteins and not of the ER itself.


Headgroup structure and fatty acid chain length of the acidic phospholipids modulate the interaction of membrane mimetic vesicles with the antimicrobial peptide protegrin-1.
The interaction of protegrin-1 (PG-1), a small beta-sheet antimicrobial peptide with acidic phospholipid model membranes was investigated by differential scanning calorimetry. We found that PG-1 can distinguish between liposomes of the anionic phospholipids DPPG, DPPS and DPPA, eventhough the headgroups of these phospholipids all have the same net charge and they carry the same hydrocarbon chains. Specifically, PG-1 had only a minor effect on the thermotropic phase behavior of DPPA liposomes, while it interacted preferentially with the fluid phase of DPPS. Furthermore, PG-1 could induce a phase separation in DPPG liposomes resulting in the formation of peptide-rich domains even at low concentrations of the peptide. However, this peptide-rich domain was not evident when the fatty acyl chains were longer or shorter by two carbon atoms. In addition, PG-1 can also form peptide-rich domains in DPPS vesicles but only at high concentrations of the peptide. These results suggest that in addition to an overall negative charge, the structural features of the phospholipid headgroups, lipid packing and thus membrane fluidity will influence the interaction with PG-1, thereby modulating its biological activity.


Treatment of post transfusion graft-versus-host disease.
In Japan, so many cases of post-transfusion graft-versus-host disease (PT-GVHD) have been reported, and no effective treatment has been reported. Totally 61 cases of PT-GVHD have been collected, and their background were analyzed. A serine protease inhibitor, nafamostat mesilate(N.M.) was examined as a drug for treatment of PT-GVHD using 4 patients. N.M. was confirmed to inhibit cytotoxic activities of established cytotoxic T cell (CTL) clones in vitro. Simultaneously it was confirmed that fever and skin rash disappeared and liver function tests were normalized soon after the administration of N.M. in all four cases. Leukopenia and thrombocytopenia simultaneously improved. The effects of N.M. seem to be limited to inhibit cytotoxic activity of CTL. In addition to this drug, how to remove the CTL from the patients will be the essentially important theme for the future.


Acquiring an understanding of design: evidence from children's insight problem solving.
The human ability to make tools and use them to solve problems may not be zoologically unique, but it is certainly extraordinary. Yet little is known about the conceptual machinery that makes humans so competent at making and using tools. Do adults and children have concepts specialized for understanding human-made artifacts? If so, are these concepts deployed in attempts to solve novel problems? Here we present new data, derived from problem-solving experiments, which support the following. (i) The structure of the child's concept of artifact function changes profoundly between ages 5 and 7. At age 5, the child's conceptual machinery defines the function of an artifact as any goal a user might have; by age 7, its function is defined by the artifact's typical or intended use. (ii) This conceptual shift has a striking effect on problem-solving performance, i.e. the child's concept of artifact function appears to be deployed in problem solving. (iii) This effect on problem solving is not caused by differences in the amount of knowledge that children have about the typical use of a particular tool; it is mediated by the structure of the child's artifact concept (which organizes and deploys the child's knowledge). In two studies, children between 5 and 7 years of age were matched for their knowledge of what a particular artifact "is for", and then given a problem that can only be solved if that tool is used for an atypical purpose. All children performed well in a baseline condition. But when they were primed by a demonstration of the artifact's typical function, 5-year-old children solved the problem much faster than 6-7-year-old children. Because all children knew what the tools were for, differences in knowledge alone cannot explain the results. We argue that the older children were slower to solve the problem when the typical function was primed because (i) their artifact concept plays a role in problem solving, and (ii) intended purpose is central to their concept of artifact function, but not to that of the younger children.


Site of lesion vestibular function testing.
The results of conventional electronystagmography (ENG) sometimes are confusing. The Hallpike alternate binaural bithermal (ABB) caloric test is helpful diagnostically except for the group of "sick patients that have a normal test." Conventional ENG tests also fall short in the area of objective confirmation of patient progress. What does each test tell us regarding site of lesion? 1. Alternate binaural bithermal stimulation gives us information about the semicircular canals -- particularly the horizontal semicircular canal -- pickup head. 2. Simultaneous binaural bithermal stimulation gives information brain stem connections -- switching and relay. 3. Rotation testing gives information about the processing by the brain -- central control.


Publication trends in knee surgery: a review of the last 16 years.
The trends in the publication of articles regarding knee arthroplasty and soft tissue surgery were analysed with regard to geographical authorship, institutional funding and number of authors. Over 7500 articles from relevant journals with the highest impact factors according to the Thomson Reuters Journal Citation Report (2010) were evaluated from 1995 to 2010. The rate of publication increased by 16.9 per year for arthroplasty articles and by 13.9 per year for soft tissue surgery articles. The relative supremacy of the USA has declined over the 16 years, its share dropping from 72.2% to 39.2% for arthroplasty articles and from 61.7% to 36.6% for soft tissue surgery articles. The UK, Japan, South Korea and smaller countries in Asia and South America have become increasingly prolific.


[Auditory threshold in professional divers not exposed to noise].
Otologic and audiometric evaluation of professional divers without noise exposure has been carried out to analyze the repercussions of this activity on their hearing. A total of 233 professional divers, working in a no noise environment, with an average experience of 9.6 years and 2074 lifetime dives, in a working depth between 10 m and 27 m, average 4.6 hours underwater time were evaluated. This atypical population of divers did not follow any decompression schedule and engaged in diving in a purely empirical and intuitive fashion. Eighty-nine point two per cent presented symptoms of decompression sickness (DCS). Only 19.7% presented a mean hearing threshold below 20 dB while 73.5% had a mild hearing loss. Significant differences (P < .0001) were found in hearing thresholds at 3, 4, and 6 kHz when hearing thresholds were grouped by years of experience and diver's age. No such increase was found when the sample was grouped by DCS symptoms, vestibular symptoms, number of dives, or patent foramen ovale. The presence of high-frequency sensorineural hearing loss in professional divers is related to their age and experience, even without a noisy working environment.


Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the biologically active metabolite of vitamin D and has been shown to regulate the growth of various cell types. There are two principal enzymes involved in the formation of circulating 1,25(OH)2D3 from vitamin D, the vitamin D 25-hydroxylase (25-OHase) and the 1alpha-hydroxylase (1alpha-OHase). Recently, extrarenal activity of 1alpha-OHase has been reported in various cell types. The aim of this study was to analyze expression of VDR and the main enzymes involved in the synthesis and metabolism of calcitriol in gynecological malignancies and corresponding normal tissue. Expression of VDR, 25-OHase, 1alpha-OHase, and 24-OHase was analyzed in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) and normal corresponding tissues using real-time PCR and specific hybridization probes as well as using immunohistochemistry. RNA for VDR, 1alpha-OHase, 24-OHase and 25-OHase was up-regulated in breast cervical and ovarian carcinomas as compared to normal tissue. VDR immunoreactivity was increased in breast and ovarian cancer and in cervix carcinomas as compared to normal corresponding tissue. Our findings indicate that cervical carcinomas, breast cancer and ovarian cancer may be considered as potential targets for prevention or therapy with new vitamin D analogs that exert little or no calcemic side effects or by pharmacological modulation of 1,25(OH)2D3 synthesis and metabolism in these tumor cells.


Inactivation of netilmicin by carbenicillin.
Netilmicin was added to human serum and stored at various temperatures and carbenicillin concentrations prior to bioassay. Inactivation of netilmicin increased with temperature and carbenicillin concentration. The order of inactivation of aminoglycosides was: tobramycin greater than gentamicin, netilmicin greater than amikacin.


Protective effects of pirfenidone on D-galactosamine and lipopolysaccharide-induced acute hepatotoxicity in rats.
To investigate the protective effects of pirfenidone on acute liver damage caused by D-galactosamine (GalN)/lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into five groups (five rats per group): normal control group, GalN/LPS-treated group, and three pirfenidone-treated group (100, 300 and 500 mg/kg i.p., respectively). All biochemical and histological indexes were determined at 12 h after GalN/LPS challenge. Severity of liver injury was assessed by determination of serum ALT, AST levels and histological analysis. SOD activity and MDA concentrations as well as TNF-alpha and IFN-gamma levels in the liver of rats were measured. The expression of iNOS and its product, NO concentration were also determined. Pretreatment with pirfenidone significantly attenuated GalN/LPS-induced severe hepatotoxicity, as evidenced by decreased ALT, AST levels and MDA content and improved histopathological changes. Pirfenidone inhibited the elevated levels of TNF-alpha and IFN-gamma and reduced the induction of iNOS/NO in a dose-dependent manner, which might be important mechanisms related to its protective effect. Pirfenidone can provide a definite protective effect against acute hepatic injury caused by GalN/LPS in rats, which may be mainly mediated through its anti-inflammatory effect.


Porcelain veneers.
The rise in popularity of the bonded porcelain laminate veneer has been nothing short of meteoric. Over the span of fifteen years, it has become the second most requested porcelain restoration in the United States. This article looks back at the short history of the bonded porcelain veneer and describes the most popular method for its fabrication.


Morroniside inhibits Beclin1-dependent autophagic death and Bax-dependent apoptosis in cardiomyocytes through repressing BCL2 phosphorylation.
Morroniside can prevent myocardial injury caused by ischemia and hypoxia, which can be used to treat acute myocardial infarction (AMI). Hypoxia can cause apoptosis and autophagic death of cardiomyocytes. Morroniside has the ability to inhibit apoptosis and autophagy. However, the relationship between Morroniside-protected cardiomyocytes and two forms of death is unclear. The effects of Morroniside on the proliferation, apoptosis level, and autophagic activity of rat cardiomyocyte line H9c2 under hypoxia were first observed. Next, the roles of Morroniside in the phosphorylation of JNK and BCL2, BCL2-Beclin1, and BCL2-Bax complexes as well as mitochondrial membrane potential in H9c2 cells were evaluated upon hypoxia. Finally, the significance of BCL2 or JNK in Morroniside-regulated autophagy, apoptosis, and proliferation in H9c2 cells was assessed by combining Morroniside and BCL2 competitive inhibitor (ABT-737) or JNK activator (Anisomycin). Our results showed that hypoxia promoted autophagy and apoptosis of H9c2 cells, and inhibited their proliferation. However, Morroniside could block the effect of hypoxia on H9c2 cells. In addition, Morroniside could inhibit JNK phosphorylation, BCL2 phosphorylation at the Ser70 and Ser87 sites, and the dissociation of BCL2-Beclin1 and BCL2-Bax complexes in H9c2 cells upon hypoxia. Moreover, the reduction of mitochondrial membrane potential in H9c2 cells caused by hypoxia was improved by Morroniside administration. Importantly, the inhibited autophagy, apoptosis, and promoted proliferation in H9c2 cells by Morroniside were reversed by the application of ABT-737 or Anisomycin. Overall, Morroniside inhibits Beclin1-dependent autophagic death and Bax-dependent apoptosis via JNK-mediated BCL2 phosphorylation, thereby improving the survival of cardiomyocytes under hypoxia.


[Post-dural (post-lumbar) puncture syndrome. Review and retrospective study at an emergency headache centre].
Post-lumbar puncture headache (PLPH) is a well-known syndrome resulting from spinal fluid leakage and delayed closure of a dural defect. The main symptom of PLPH is headache in upright posture relieved by lying down. Outcome is usually benign and complications are uncommon. The functional impact can however be important, leading to delayed discharge, sick leave and, if information delivery is ineffective, iterative consultations. Preventive measures have been published, but the prevalence of PLPH remains high (15 to 40% after diagnostic lumbar puncture). Needle size and type are probably the most important factors for reducing the risk of PLPH. Recovery can be rapid, within a few days. If PLPH persists after four days, an epidural blood patch should be discussed. The objective of this review is to summarize the literature on PLPH, and share the experience of our emergency headache center with an atraumatic 25-gauge needle (pencan, 0.5×90mm or 0.5×103mm, Braun, Germany).


Relevance of the test content of the Korean Nursing Licensing Examination to nursing job.
This study aimed at identifying if there is a relevance of content of the Korean Nursing Licensing Examination (KNLE) revised in 2014 to nursing job. It will be able to provide the validity of revised content of the KNLE. From October 13 to November 13, 2015, print version of 8 duties with 49-tasks, 155-job item questionnaires were distributed to 1,305 hospital nurses and 202 nursing faculties in Korea. Results were treated by descriptive statistics and comparison analysis. There were responses from 946 nurses or professors (72.5%). The relevance of test content of KNLE to nursing job was shown to be valid with over 3 points out of 4 point Likert scale in all items: from 3.23 at lowest to 3.64 at top. Above results showed that the revised version of KNLE in 2014 was valid to test the nursing students' knowledge for job performance.


Thickness dependence of the response of metal-dioxide-based micromechanical sensors for sensitive gamma-ray detection.
In this study, we investigated the effect of the thickness of metal-dioxide thin films on silicon (Si) micro-electromechanical systems (MEMS) for sensitive, accurate, and reproducible detection of gamma-radiation dose. Silicon wafers and microcantilevers were coated with various thicknesses of titanium dioxide (TiO2) thin films and controlled by the number of cycles in atomic layer deposition (ALD) under 17-mbar pressure and temperature of 200 °C. All samples were exposed to different doses of gamma (0, 10, and 20 kGy) using a60Co source. Before and after gamma irradiation, the optical and mechanical properties of the TiO2 thin films on Si wafers were studied by spectroscopic ellipsometry (SE) and atomic force microscopy (AFM). The resonance frequency shift (RFS) resulting from exposing different thicknesses of TiO2 thin films on MEMS-based cantilevers to gamma-radiation doses were evaluated by AFM. SE results revealed the film thicknesses of 11.91, 21.77, 62.91, and 218.23 nm at 250, 500, 1250, and 2500 coating cycles, respectively. Through SE, other optical constants, such as surface roughness (SR) and refractive index (n), were obtained. The root-mean-square (RMS) SR obtained from AFM images and SE measurements on Si wafers showed the same behavior under gamma radiation according to the TiO2 thin-films thicknesses. The RFS results show that the best film thickness for reproducible and sensitive gamma-radiation detection was 218.23 nm. The frequency shift as the gamma dose increase from 0 to 20 kGy was ∼60 Hz. It is a very palpable and linear shift; hence, it can be used as a dosimeter sensor. The results were verified by the statistical correlation coefficient method to find the correlation between RFS and the gamma dose at different film thicknesses. Correlation results are consistent with other results.


Low concentrations of nicotine differentially desensitize nicotinic acetylcholine receptors that include α5 or α6 subunits and that mediate synaptosomal neurotransmitter release.
Desensitization is a complex property of nicotinic acetylcholine receptors (nAChR). Several subtypes of nAChR have high sensitivity to nicotine and mediate effects of nicotine at concentrations found in blood of tobacco smokers. Desensitization of some of these receptor subtypes has been studied in model systems, however, other subtypes have been difficult to express heterologously in native forms. In addition, model systems may not have the same accessory molecules and post-translational modifications found in native populations. We have used wild-type and subunit null mutant mice to study desensitization properties of the high sensitivity α4β2-nAChRs including those that have α5 subunits at both GABAergic and dopaminergic nerve terminals. In addition, we have studied the desensitization of one subtype of α6β2-nAChRs at dopaminergic terminals using α4 subunit null mutant mice. Exposure to low nicotine concentrations, leads to rapid, but partial desensitization of activity mediated by these receptors. α4β2-nAChRs including α5 subunits show faster rates of recovery from desensitization than α4β2-nAChRs without α5. Inclusion of the α5 subunit significantly shifts the concentration response for desensitization to higher values, indicating that receptors with α5 subunits are less desensitized by a 10-min exposure to low concentrations of nicotine. Receptors with α6 subunits appear to desensitize to a lesser degree than those with α4 subunits, indicating that α6β2-nAChRs are somewhat resistant to desensitization by nicotine. These results highlight the importance of studying various receptor subtypes in native systems and how they may differentially respond to nicotine and to nicotinic drugs.


Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy.
NF-kappaB is an important transcription factor complex that appears to play a fundamental role in regulating acute inflammation through activation of the cytokine cascade and production of other pro-inflammatory mediators. There is increasing evidence that NF-kappaB is important in the pathobiology of disease states such as SIRS, MODS and ARDS; therefore, therapeutic interventions aimed at limiting NF-kappaB activation and down-regulating production of inflammatory mediators could prove to be beneficial in decreasing host-derived tissue injury and organ dysfunction. Specific interventions that hold promise for suppressing NF-kappaB activation include the use of antioxidants, inhibition of NIK and the IKK signalsome, treatment with proteasome inhibitors, induction of endotoxin tolerance and, possibly the use of corticosteroids in selected patients.