Molecular structure of the rat bone Gla protein gene and identification of putative regulatory elements.
The rat bone Gla protein (BGP, osteocalcin) gene was isolated from a rat genomic library and sequenced. BGP is a 5.8-kD noncollagenous protein secreted by calcified tissues whose expression is regulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The BGP gene consists of 4 exons separated by 3 introns and spans almost 1 kb of DNA. The 5'-flanking region of the gene contains CCAAT and TATAAA elements common to eukaryotic genes. An analysis of approximately 600 bp of 5'-flanking sequence of this gene revealed sequences homologous to regulatory elements for glucocorticoids, metal ions, and cAMP. The latter is especially significant since recent evidence suggests that the rat BGP gene can be regulated by cAMP. This region of the gene also contains numerous pairs of inverted repeat sequences (imperfect palindromes). The sequence of the rat BGP gene was compared to that of the recently published human BGP gene (Celeste et al., EMBO J. 5, 1885, 1986). The coding regions of these two genes share 77% sequence identity, and several regions of the 5'-flanking sequences are also well conserved. Knowledge of the sequence of the rat BGP gene will allow studies of its regulation by 1,25(OH)2D3, cAMP, and other trans-acting transcriptional factors, and identification of the regulatory sequence elements involved.


[Acquired epidermolysis bullosa in Crohn's disease].
A case of epidermolysis bullosa acquisita associated with colitis granulomatosa (Crohn's disease) is reported. Although the cutaneous lesions of this unusual disease resemble in their clinical, histological and ultrastructural features to those of the hereditary epidermolysis bullosa dystrophica, the epidermolysis bullosa acquisita has to be regarded as a separate entity among the blistering epidermolysis because of its late manifestation in adults without evidence of hereditary disorders. The deposits of immunoglobulins in the involved skin of the acral areas demonstrated fluorescentmicroscopically are discussed in regard of a possible etiopathogenic relation with the primary irritated intestinal disease.


Investigation of the Role of Zn/Cu Index and its Correlation with Physiological Activity of SOD 1 and GRx in Males with Acne Vulgaris.
It has been approved that the normal physiology of skin can be adversely affected by acne vulgaris (AV). This disorder leads to impairment of stratum corneum hydration and causes trans epidermal water loss. The normal physiology of the males' skin is different from the normal physiology of females' skin. Therefore, in case of any skin disorder, choosing the best strategy and treatment should be investigated seriously in each gender. Therefore the current study was designed to investigate the effect of two important trace elements (i.e., zinc [Zn] and copper [Cu]) on skin health and the correlation of Zn/Cu index with the physiological activity of antioxidant enzymes superoxide dismutase (SOD1) and glutaredoxins (Grx) in males with AV. In total, 100 samples were obtained from 60 males (in the age range of 17-20 years) with a definite diagnosis of AV (AVM group) and 40 males (in the age range of 18-20 years) with normal skin as the control group (CON group). The blood samples were obtained from each participant. The blood samples were centrifuged for the measurements of Zn, Cu, Zn/Cu index, SOD1, and GRx, and serum samples were preserved at -20°C until use. Moreover, Zn, Cu, and Zn/Cu index were determined using spectrophotometric kits. The enzyme-linked immunosorbent assay, as the preferred method, was performed for SOD1 and GPx measurements. On the other hand, in this study, body mass index (BMI) and age were considered to have a possible association with the incidence of acne in males. The recorded data showed that there were no significant differences between the AVM group and controls in terms of BMI. The recorded data showed that Zn (AVM:151±10.7; CON:189±9.7) and Cu (AVM:55±5.2; CON: 77±4.8) concentration was significantly reduced (P<0.05) in the AVM group, compared to controls. On the other hand, the Zn/Cu index was significantly lower in the AVM group (1.05±0.19), compared to the control group (1.78±0.08). The results of the SOD1 and GRx assay showed that the AVM group suffered from a significant reduction in the SOD1 and GRx concentration, compared to the group of control. Overall, it can be concluded that the improvement of the antioxidant enzyme activity and supplementation of trace elements may significantly reduce the incidence of AV in males.


Proteomic analysis of microparticles isolated from malaria positive blood samples.
Malaria continues to be a great public health concern due to the significant mortality and morbidity associated with the disease especially in developing countries. Microparticles (MPs), also called plasma membrane derived extracellular vesicles (PMEVs) are subcellular structures that are generated when they bud off the plasma membrane. They can be found in healthy individuals but the numbers tend to increase in pathological conditions including malaria. Although, various studies have been carried out on the protein content of specific cellular derived MPs, there seems to be paucity of information on the protein content of circulating MPs in malaria and their association with the various signs and symptoms of the disease. The aim of this study was therefore to carry out proteomic analyses of MPs isolated from malaria positive samples and compare them with proteins of MPs from malaria parasite culture supernatant and healthy controls in order to ascertain the role of MPs in malaria infection. Plasma samples were obtained from forty-three (43) malaria diagnosed patients (cases) and ten (10) healthy individuals (controls). Malaria parasite culture supernatant was obtained from our laboratory and MPs were isolated from them and confirmed using flow cytometry. 2D LC-MS was done to obtain their protein content. Resultant data were analyzed using SPSS Ver. 21.0 statistical software, Kruskal Wallis test and Spearman's correlation coefficient r. In all, 1806 proteins were isolated from the samples. The MPs from malaria positive samples recorded 1729 proteins, those from culture supernatant were 333 while the control samples recorded 234 proteins. The mean number of proteins in MPs of malaria positive samples was significantly higher than that in the control samples. Significantly, higher quantities of haemoglobin subunits were seen in MPs from malaria samples and culture supernatant compared to control samples. A great number of proteins were observed to be carried in the microparticles (MPs) from malaria samples and culture supernatant compared to controls. The greater loss of haemoglobin from erythrocytes via MPs from malaria patients could serve as the initiation and progression of anaemia in P.falciparum infection. Also while some proteins were upregulated in circulating MPs in malaria samples, others were down regulated.


Anisotropic effects in highly scattering media.
In this paper, we study anisotropic scattering and light propagation models applicable to diffuse optical tomography. We propose a model for anisotropic scattering in the radiative transfer framework and derive the corresponding anisotropic diffusion model. To verify the anisotropic diffusion model, we consider the case of a simple anisotropic scattering model also presentable within the diffusion approximation. For numerical computations, we present a three-dimensional (3D) anisotropic Monte Carlo model and 2D finite element and boundary element solutions of the anisotropic diffusion model, and compare the results of the simulations.


Changes in biochemical parameters on the first day after kidney transplantation: risk factors for nosocomial infection?
Nosocomial infection in early post-transplantation period is a tough problem for kidney transplantation. Few reports have explored the relations between biochemical parameters and nosocomial infection in kidney transplantation. This retrospective study was carried out to describe the characteristics of nosocomial infection in the very early period of kidney transplantation and to determine the risk factors in biochemical parameters and their alterations. Patients who underwent their first kidney transplantation from January 2001 to March 2009 in Beijing Chao-Yang Hospital were recruited and the nosocomial infectious episodes were collected for this study. Gender, age, donor type, delayed graft function (DGF) and biochemical parameters such as serum uric acid, lipids files and albumin on day 0 (before transplantation) and day 1 (24 hours after transplantation) and their changes were analyzed with Logistic regression models for nosocomial infection. A total of 405 patients (315 men and 90 women) were involved in this study. There were 80 patients experiencing 113 infection episodes and 105 strains of microorganism were identified. In univariate analysis, there were significant differences in DGF, albumin on day 0, lipoprotein (a) (Lp(a)) on day 1, change in low density lipoprotein-cholesterol (LDL-C, day 1-day 0) and change in uric acid (day 1-day 0) between nosocomial infection patients and noninfectious patients (P < 0.05). In multivariate analysis, change in uric acid (day 1-day 0) (OR 5.139, 95%CI 1.176-22.465, P < 0.05), change in LDL-C (day 1-day 0) (OR 4.179, 95%CI 1.375-12.703, P < 0.05) and DGF (OR 14.409, 95%CI 1.603-129.522, P < 0.05) were identified as independent risk factors for nosocomial infection in kidney transplantation. Most nosocomial infections in early postoperative period of kidney transplantation are bacterial, especially with Gram-negative bacteria. The most common infection sites are respiratory tract, urinary tract and surgical site. DGF, decrease of LDL-C and increase of uric acid could increase the risk for nosocomial infections.


Inhibition of ribonucleotide reductase in thymocytes of rats treated by ditiocarb sodium.
The i.p. administration of ditiocarb sodium (diethyldithiocarbamate, DDC) at doses of 500 and 1000 mg/kg body wt. decreased within 1 h and in a competitive manner the ribonucleotide reductase (RNR) activity of rat thymocytes by about 25 and 40%, respectively. Under the same conditions, scheduled DNA synthesis was inhibited by almost 30 and 75%, whereas RNA synthesis remained unchanged. 1000 mg DDC/kg body wt. resulted in a long-lasting diminution in thymus weight; the spleen revealed no significant drug effects. It is suggested that the decrease of RNR activity in thymocytes of DDC-treated rats is a major determinant in the (reversible) inhibition of DNA synthesis which, in turn, may be implicated in the radio- and chemoprotective effects of the drug.


Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome.
Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood. In this study, we shed more light on this aspect by performing a comprehensive analysis on the effects of variation in prenatal environment, neonatal methylome, and genotype on birth weight and adiposity in early childhood. In a prospective mother-offspring cohort (N = 987), we interrogated the effects of 30 variables that influence the prenatal environment, umbilical cord DNA methylation, and genotype on offspring weight and adiposity, over the period from birth to 48 months. This is an interim analysis on an ongoing cohort study. Eleven of 30 prenatal environments, including maternal adiposity, smoking, blood glucose and plasma unsaturated fatty acid levels, were associated with birth weight. Polygenic risk scores derived from genetic association studies on adult adiposity were also associated with birth weight and child adiposity, indicating an overlap between the genetic pathways influencing metabolic health in early and later life. Neonatal methylation markers from seven gene loci (ANK3, CDKN2B, CACNA1G, IGDCC4, P4HA3, ZNF423 and MIRLET7BHG) were significantly associated with birth weight, with a subset of these in genes previously implicated in metabolic pathways in humans and in animal models. Methylation levels at three of seven birth weight-linked loci showed significant association with prenatal environment, but none were affected by polygenic risk score. Six of these birth weight-linked loci continued to show a longitudinal association with offspring size and/or adiposity in early childhood. This study provides further evidence that developmental pathways to adiposity begin before birth and are influenced by environmental, genetic and epigenetic factors. These pathways can have a lasting effect on offspring size, adiposity and future metabolic outcomes, and offer new opportunities for risk stratification and prevention of obesity. This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .


Cerebral metabolic effects of strict versus conventional glycaemic targets following severe traumatic brain injury.
Optimal glycaemic targets for patients with severe traumatic brain injury remain unclear. The primary objective of this microdialysis study was to compare cerebral metabolism with strict versus conventional glycaemic control. We performed a prospective single-centre randomised controlled within-subject crossover study of 20 adult patients admitted to an academic neurointensive care unit with severe traumatic brain injury. Patients underwent randomised, consecutive 24-h periods of strict (4-7 mmol/L; 72-126 mg/dl) and conventional (<10 mmol/L; 180 mg/dl) glycaemic control with microdialysis measurements performed hourly. The first 12 h of each study period was designated as a 'washout' period, with the subsequent 12 h being the period of interest. Cerebral glucose was lower during strict glycaemia than with conventional control (mean 1.05 [95% CI 0.58-1.51] mmol/L versus 1.28 [0.81-1.74] mmol/L; P = 0.03), as was lactate (3.07 [2.44-3.70] versus 3.56 [2.81-4.30]; P < 0.001). There were no significant differences in pyruvate or the lactate/pyruvate ratio between treatment phases. Strict glycaemia increased the frequency of low cerebral glucose (< 0.8 mmol/L; OR 1.91 [95% CI 1.01-3.65]; P < 0.05); however, there were no differences in the frequency of critically low glucose (< 0.2 mmol/L) or critically elevated lactate/pyruvate ratio between phases. Compared with conventional glycaemic targets, strict blood glucose control was associated with lower mean levels of cerebral glucose and an increased frequency of abnormally low glucose levels. These data support conventional glycaemic targets following traumatic brain injury. ISRCTN, ISRCTN19146279 . Retrospectively registered on 2 May 2014.


Developing Functional Relationships between Soil Moisture Content and Corn Early-Season Physiology, Growth, and Development.
Drought is a severe threat to agriculture production that affects all growth stages of plants, including corn (Zea mays L.). Any factor affecting early seedling growth and development will significantly impact yield. Despite the recurrence of low rainfall during the growing seasons, corn responses to different early-season soil moisture content levels have not been investigated. In this study, we investigated how corn morpho-physiological and biomass traits responded to varied soil moisture content during the early vegetative stage. Two corn hybrids were grown in a pot-culture facility under five different soil moisture treatments (0.15, 0.12, 0.09, 0.06, and 0.03 m3 m-3 volumetric water content, VWC) to assess the growth and developmental responses to varied soil moisture content during early-season growth (V2 to V7) stage. Sub-optimal soil moisture content limited plant growth and development by reducing physiological and phenotypic expression. Stomatal conductance and transpiration were decreased by an average of 65% and 59% across stress treatments relative to optimum conditions. On average, soil moisture deficit reduced the total leaf area by 71% and 72% compared to the control in 'A6659VT2RIB' and 'P1316YHR', respectively. Shoot and root dry weights were reduced by 74% and 43% under 0.03 m3 m-3 VWC. An increase in the root-to-shoot ratio was noticed under low VWC conditions compared to the control. Based on the stress tolerance index, the physiology and leaf growth parameters were more sensitive to soil moisture deficit. Our results highlight the impact of sub-optimal soil moisture on physiology and morphological traits during early-season growth. 'P1316YHR' demonstrated better physiological performance under stress conditions, while 'A6659VT2RIB' produced relatively better root growth. The findings suggest that biomass partitioning between shoot and root components is dynamic and depends on stress intensity. The current findings can help to prioritize traits associated with the early-season drought tolerance in corn. The functional relationships developed between soil moisture content and growth and developmental responses can be integrated into corn crop modeling to allow better irrigation management decisions.


The application of molecular techniques to solid tumors.
Recent developments in the field of molecular biology including the sequencing of the human genome and related high throughput methodologies are presenting the diagnostic pathologist with new opportunities to expand our understanding of human disease. These techniques enable the comprehensive assessment of molecular alterations with cell populations of interest, including cancer. It will be necessary for the diagnostic pathologist to become familiar with these techniques to effectively translate their potential into the clinical environment.


Undisturbed water gastric emptying in patients of stomach cancer.
Gastric cancer is an infiltrative disease involving deep layers of the stomach. It is of interest whether the stomach motility in gastric cancer patients may be altered. We employed a homemade applied potential tomographic system to study the features of water gastric emptying in gastric cancer patients. Twelve electrodes were placed in a circular array around the upper abdomen of studied subjects. After drinking 500 mL of test water, paired electrodes injected an electrical current and another 9 paired electrodes recorded signals. This procedure was processed in a rotated order for 50 min while the serial changes in altered resistivity were constructed to display water gastric emptying curve. Before surgery, 27 histologically confirmed gastric cancer patients were enrolled to measure their gastric emptying parameters including half emptying time (T1/2) and area under the curve (AUC). Consequently, tumor parameters were obtained from their resected specimens. In addition, 28 healthy controls were recruited to compare water gastric emptying. The half emptying times of gastric cancer patients and controls were 15.51 +/- 2.21 (SE) and 16.82 +/- 2.13 min, respectively (NS). While their measured areas under the curve were also comparable (1719.5 +/- 169.4 vs. 1896.0 +/- 143.6 arbitrary unit, NS). Regarding with various patient factors to influence water gastric emptying among gastric cancer patients, those patients presenting nausea (T1/2: 8.3 +/- 1.44 vs. 18.5 +/- 2.8 min, P<0.05) or free of regional lymph node metastasis (9.98 +/- 2.53 vs. 22.7 +/- 3.84 min, P<0.05) had a rapid water gastric emptying. Other demographic and tumor characteristics including gender, age, smoking, body size, serum levels of tumor markers, cancer location/size, invasion layer, Helicobacter pylori colonization and histological subtype did not influence water gastric emptying. Water gastric emptying in non-obstructive gastric cancer patients is mainly undisturbed. However, some obvious dyspeptic symptom or tumor nature appears leading to a rapid water gastric emptying.


Realization and manipulation of ZnO nanorod arrays on sapphire substrates using a catalyst-free metalorganic chemical vapor deposition technique.
Single-crystalline ZnO nanorod arrays (ZNRs) were grown by metalorganic chemical vapor deposition on ZnO buffer/sapphire substrate without using any metal catalyst. The density of vertically aligned ZNRs was found to govern by the morphology and thickness of buffer layer. That is to say, the ZnO buffer layer can be used as the nucleation template to control the growth direction and density of the ZNRs. In addition, by controlling the diethyl zinc flow rate, we can manipulate the size, crystal, and optical quality of ZNRs. Finally, the possible growth mechanism of ZNRs was discussed in detail.


Iron Deficiency Leads to Chlorosis Through Impacting Chlorophyll Synthesis and Nitrogen Metabolism in Areca catechu L.
Deficiency of certain elements can cause leaf chlorosis in Areca catechu L. trees, which causes considerable production loss. The linkage between nutrient deficiency and chlorosis phenomenon and physiological defect in A. catechu remains unclear. Here, we found that low iron supply is a determinant for chlorosis of A. catechu seedling, and excessive iron supply resulted in dark green leaves. We also observed morphological characters of A. catechu seedlings under different iron levels and compared their fresh weight, chlorophyll contents, chloroplast structures and photosynthetic activities. Results showed that iron deficiency directly caused chloroplast degeneration and reduced chlorophyll synthesis in chlorosis leaves, while excessive iron treatment can increase chlorophyll contents, chloroplasts sizes, and inflated starch granules. However, both excessive and deficient of iron decreases fresh weight and photosynthetic rate in A. catechu seedlings. Therefore, we applied transcriptomic and metabolomic approaches to understand the effect of different iron supply to A. catechu seedlings. The genes involved in nitrogen assimilation pathway, such as NR (nitrate reductase) and GOGAT (glutamate synthase), were significantly down-regulated under both iron deficiency and excessive iron. Moreover, the accumulation of organic acids and flavonoids indicated a potential way for A. catechu to endure iron deficiency. On the other hand, the up-regulation of POD-related genes was assumed to be a defense strategy against the excessive iron toxicity. Our data demonstrated that A. catechu is an iron-sensitive species, therefore the precise control of iron level is believed to be the key point for A. catechu cultivation.


Effectiveness of indometacin to prevent ovulation in modified natural-cycle IVF: a randomized controlled trial.
Modified natural-cycle IVF has a lower pregnancy rate per started cycle as compared with IVF with ovarian stimulation due to, for example, premature ovulation. Indometacin administered before ovulation prevents follicle rupture. Therefore, addition of indometacin may improve the effectiveness of modified natural-cycle IVF. This double-blind, randomized, placebo-controlled trial with indometacin or placebo in 120 women aged 27-36 years compared the number of patients without premature ovulation as compared with the number of patients with one or more ovulations in a maximum of six cycles. Indometacin had no significant influence on the probability of a premature ovulation in patients during the six cycles (OR 2.38, 95% CI 0.94-6.04). A subgroup analysis showed a significant influence of indometacin in decreasing the probability of a premature ovulation in cycles without LH surge at the day of human chorionic gonadotrophin administration (OR 8.29, 95% CI 1.63-42.3, P=0.009). Although this study could not detect a significantly lower ovulation rate in the indometacin group versus the placebo group, the data suggest that a subgroup of patients without LH surge prior to oocyte retrieval might benefit from indometacin in modified natural-cycle IVF.


[Fungal population and distribution of aflatoxigenic fungi in commercial almond powder products].
The fungal population and distribution of aflatoxin-producing fungi in 30 samples of imported almond powder products purchased from retail markets were examined in this study. Total counts of fungi ranged from under 1.0 x 10 colony-forming units (CFU)/g to 8.5 x 10(3) CFU/g as determined with the dilution plating technique. The predominant fungi in the mould-contaminated almond samples were Aspergillus niger, A. flavus and the related species, Penicillium, Cladosporium and Rhizopus. Aflatoxin-producing ability in the isolates of A. flavus and related fungi were tested by thin layer chromatography using 2% yeast extract and 15% sucrose broth culture. Four different aflatoxigenic fungi were detected in the isolates; aflatoxins B1 and B2 were produced by some strains of A. flavus and A. parvisclerotigenus, and aflatoxins B1, B2, G1, G2 were produced by all tested strains of A. parasiticus and A. nomius. Identification of the strains was based on morphological and metabolic characters.


Non-Fourier bioheat model for bone grinding with application to skull base neurosurgery.
Bone grinding is used to remove the skull bone and access tumors through the nasal passage during cranial base neurosurgery. The generated heat of the spherical diamond tool propagates and could damage the nerves or coagulate the arteries blood. Little is known about the non-Fourier behavior of heat propagation during bone grinding. Therefore, this study develops an analytical model of the hyperbolic Pennes bioheat transfer equation (HPBTE) to calculate the three-dimensional temperature and necrosis in the grinding region. In vitro experimental investigations were carried out, and the contact zone temperature was measured using an infrared thermography system to validate the proposed thermal model. The results demonstrate that the HPBTE provides more reliable temperature evaluation and thermal damage than Fourier or parabolic heat transfer equation (PHTE). Due to the low thermal diffusivity of the bone, the lower grinding feed rate leads to higher temperature amplitude and a smaller radius of the affected zone in the surface and depth of the bone. Also, the intensity of bone necrosis decreases with the increase of the feed rate, and the shape of the damage zone becomes stretched. This analytical model can assess the potential risk of the surgery before clinical trials. Also, it could be used for comparing the different operating conditions to minimize bone necrosis and improve the control process in neurosurgeries.


A mouse model of urofacial syndrome with dysfunctional urination.
Urofacial syndrome (UFS) is an autosomal recessive disease with severe dysfunctional urination including urinary incontinence (UI). Biallelic mutations of HPSE2 are discovered from UFS patients, suggesting that HPSE2 is a candidate disease gene. Here, we show that deletion of Hpse2 is sufficient to cause the UFS-like phenotype in mice. Hpse2 knockout mutants display a distended bladder (megacystis) phenotype and abnormal voiding behavior similar to that found in patients. While Hpse2 is largely dispensable for detrusor smooth muscle and urothelial cell fate determination, the mutants have significantly lower rates of cell proliferation than wild-type littermate controls. All Hpse2 mutants have a growth retardation phenotype and die within a month after birth. Comprehensive blood chemistry and urinalysis indicate that Hpse2 mutants have renal dysfunction and malnutrition. We provide evidence that transforming growth factor beta (Tgfβ) signaling is attenuated at birth. However, Tgfβ activity is significantly enhanced at later stages when the urological phenotype is severe, and the mutant bladders have accumulated excessive amount of fibrotic tissue. Together, these findings strongly suggest that Hpse2 is a causative gene of human UFS and further uncover unexpected roles of Hpse2 in bladder physiology, tissue remodeling and Tgfβ signaling.


Chest physiotherapy for pneumonia in adults.
Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults. We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 2, 2012), EMBASE (1974 to November 2012), Physiotherapy Evidence Database (PEDro) (1929 to November 2012), CINAHL (2009 to November 2012) and CBM (1978 to November 2012). Randomised controlled trials (RCTs) assessing the efficacy of chest physiotherapy for treating pneumonia in adults. Two authors independently assessed trial eligibility, extracted data and appraised trial quality. Primary outcomes were mortality and cure rate. We used risk ratios (RR) and mean difference (MD) for individual trial results in the data analysis. We performed meta-analysis and measured all outcomes with 95% confidence intervals (CI). Six RCTs (434 participants) appraised four types of chest physiotherapy (conventional chest physiotherapy; osteopathic manipulative treatment (which includes paraspinal inhibition, rib raising and myofascial release); active cycle of breathing techniques (which include active breathing control, thoracic expansion exercises and forced expiration techniques); and positive expiratory pressure).None of the physiotherapies (versus no physiotherapy or placebo) improved mortality rates of adults with pneumonia.Conventional chest physiotherapy (versus no physiotherapy), active cycle of breathing techniques (versus no physiotherapy) and osteopathic manipulative treatment (versus placebo) did not increase the cure rate or chest X-ray improvement rate.Osteopathic manipulative treatment (versus placebo) and positive expiratory pressure (versus no physiotherapy) reduced the mean duration of hospital stay by 2.0 days (mean difference (MD) -2.0 days, 95% CI -3.5 to -0.6) and 1.4 days (MD -1.4 days, 95% CI -2.8 to -0.0), respectively. Conventional chest physiotherapy and active cycle of breathing techniques did not.Positive expiratory pressure (versus no physiotherapy) reduced fever duration (MD -0.7 day, 95% CI -1.4 to -0.0). Osteopathic manipulative treatment did not.Osteopathic manipulative treatment (versus placebo) reduced the duration of intravenous (MD -2.1 days, 95% CI -3.4 to -0.9) and total antibiotic treatment (MD -1.9 days, 95% CI -3.1 to -0.7).Limitations of this review are that the studies addressing osteopathic manipulative treatment were small, and that six published studies which appear to meet the inclusion criteria are awaiting classification. Based on current limited evidence, chest physiotherapy might not be recommended as routine additional treatment for pneumonia in adults.


Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE(∗)3Leiden mice.
Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stress- and chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis (NASH) under conditions relevant for human pathogenesis remains unclear. Therefore, we studied the effects of the standardised anthocyanin-rich extract Mirtoselect on diet-induced NASH in a translational model of disease. ApoE(∗)3Leiden mice were fed a Western-type cholesterol-containing diet without (HC) or with 0.1% (w/w) Mirtoselect (HCM) for 20weeks to study the effects on diet-induced NASH. Mirtoselect attenuated HC-induced hepatic steatosis, as observed by decreased macro- and microvesicular hepatocellular lipid accumulation and reduced hepatic cholesteryl ester content. This anti-steatotic effect was accompanied by local anti-inflammatory effects in liver, as demonstrated by reduced inflammatory cell clusters and reduced neutrophil infiltration in HCM. On a molecular level, HC diet significantly induced hepatic expression of pro-inflammatory genes Tnf, Emr1, Ccl2, Mpo, Cxcl1, and Cxcl2 while this induction was less pronounced or significantly decreased in HCM. A similar quenching effect was observed for HC-induced pro-fibrotic genes, Acta2 and Col1a1 and this anti-fibrotic effect of Mirtoselect was confirmed histologically. Many of the pro-inflammatory and pro-fibrotic parameters positively correlated with intrahepatic free cholesterol levels. Mirtoselect significantly reduced accumulation and crystallisation of intrahepatic free cholesterol, providing a possible mechanism for the observed hepatoprotective effects. Mirtoselect attenuates development of NASH, reducing hepatic lipid accumulation, inflammation and fibrosis, possibly mediated by local anti-inflammatory effects associated with reduced accumulation and crystallisation of intrahepatic free cholesterol.


Phloroglucinol Attenuates Ultraviolet B-Induced 8-Oxoguanine Formation in Human HaCaT Keratinocytes through Akt and Erk-Mediated Nrf2/Ogg1 Signaling Pathways.
Ultraviolet B (UVB) radiation causes DNA base modifications. One of these changes leads to the generation of 8-oxoguanine (8- oxoG) due to oxidative stress. In human skin, this modification may induce sunburn, inflammation, and aging and may ultimately result in cancer. We investigated whether phloroglucinol (1,3,5-trihydroxybenzene), by enhancing the expression and activity of 8-oxoG DNA glycosylase 1 (Ogg1), had an effect on the capacity of UVB-exposed human HaCaT keratinocytes to repair oxidative DNA damage. Here, the effects of phloroglucinol were investigated using a luciferase activity assay, reverse transcription-polymerase chain reactions, western blot analysis, and a chromatin immunoprecipitation assay. Phloroglucinol restored Ogg1 activity and decreased the formation of 8-oxoG in UVB-exposed cells. Moreover, phloroglucinol increased Ogg1 transcription and protein expression, counteracting the UVB-induced reduction in Ogg1 levels. Phloroglucinol also enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as Nrf2 binding to an antioxidant response element located in the Ogg1 gene promoter. UVB exposure inhibited the phosphorylation of protein kinase B (PKB or Akt) and extracellular signal-regulated kinase (Erk), two major enzymes involved in cell protection against oxidative stress, regulating the activity of Nrf2. Akt and Erk phosphorylation was restored by phloroglucinol in the UVB-exposed keratinocytes. These results indicated that phloroglucinol attenuated UVB-induced 8-oxoG formation in keratinocytes via an Akt/Erk-dependent, Nrf2/Ogg1-mediated signaling pathway.


"Internal root resorption: An endodontic challenge": A case series.
Management of internal root resorption is a challenge to the endodontists. It may occur in cases with chronic pulpal inflammation, following caries or due to trauma in the form of an accidental blow. Most cases of internal root resorption are seen in anterior teeth, due to their susceptibility to trauma. However, it may be seen in posterior teeth, most likely because of carious involvement of the pulp. Early diagnosis, removal of the cause, proper treatment of the resorbed root is mandatory for successful treatment outcome. This paper is an attempt to summarize the knowledge on internal root resorption and present various cases, which were successfully managed with different treatment modalities.


[Prognostic factors of stage IB and IIA carcinoma of the cervix treated by surgery].
To evaluate prognostic factors in patients with stage IB-IIA of cervical carcinoma treated by surgery. Between December 1992 and December 2001, 111 patients with stage IB-IIA cervical cancer surgically treated were analyzed. Median age 40 years. According to 1994 FIGO Staging System: IB 80 (IB1 40, IB2 40) and IIA 31. There were 93 cases of squamous cell carcinoma (83.5%), 17 cases of adenocarcinoma (15.3%) and one case of small cell carcinoma. All patients were treated by radical hysterectomy and pelvic lymphadenectomy, 74 patients had preoperative adjuvant radiotherapy, 24 patients had postoperative adjuvant treatment. Kaplan-Meier method was used to evaluate the survival, the related prognostic factors were assessed by Cox regression and chi(2) test. The overall 5-year survival rate was 85.9%, being 89.1%, 90.7% and 78.4% for stage IB1, IB2 and IIA, respectively. Univariate analysis showed that tumor size (hazards ratio [HR] = 1.479, P = 0.152), tumor type (HR = 1.440, P = 0.264), clinical stage (HR = 1.380, P = 0.354), adjuvant treatment (HR = 1.210, P = 0.450), lymph node metastasis (HR = 1.432, P = 0.540), endocervical involvement (HR = 2.244, P = 0.036), depth of myometrial invasion (HR = 3.295, P = 0.06) and multiple sexual partners during pregnancy (HR = 10.172, P = 0.000) were of prognostic significance. The latter two were the most important factors indicative of poor prognosis. The depth of myometrial invasion and multi-partners combined with pregnancy are closely related to the prognosis while the pre- and/or postoperative adjuvant therapy should be considered for stage IB-IIA cervical cancer with deep myometrial invasion and in pregnant patients with multiple sexual partners.


On the regulation of the plasminogen activator inhibitor-1 gene expression.
Plasminogen activators and their inhibitors play a pivotal role in maintaining the hemostatic balance in blood and also in other proteolytic processes such as cell migration and tumor invasion. The main physiological inhibitor of the plasminogen activators is plasminogen activator inhibitor-1 (PAI-1). The effect of PMA on the endogenous PAI-1 production and on the expression of transfected promoter/reporter gene constructs was studied in HUVEC and in the HT1080 and HeLa cell lines. Addition of PMA (> or = 10 nM) to monolayer cell cultures induced a 2- to 5.5-fold increase of PAI-1 antigen production within 8-24 h. In HUVEC, PMA (160 nM) induced both the 2.4 kb and 3.4 kb mRNA species of PAI-1: 3.1 +/- 1.1 and 1.7 +/- 0.8-fold (n = 6), respectively, within 8 h. Run-on experiments confirmed that this increase is at least partially mediated by increased gene transcription. When HUVEC, HT1080 and HeLa, transfected with an 826 bp or a 336 bp PAI-1 gene promoter fragment, were stimulated with 160 nM phorbol 12-myristate 13-acetate (PMA), the CAT activity was induced 4-, 3.5- and 10-fold respectively for both constructs, revealing that PMA responsive sequences are present in the proximal 336 bp of the PAI-1 promoter. Substitution mutations in the regions encompassing nucleotides -78 to -69 (TGGGTGGGGC) or -61 to -54 (TGAGTTCA), but not in the regions -155 to -149 (TGCCTCA) or -84 to -76 (AGTGAGTGG) reduced this induction. Gel electrophoresis of double stranded -65 to -50 oligonucleotides of the PAI-1 promoter region and nuclear extracts from HeLa cells produced a gel shift pattern, similar to that obtained with a AP-1 consensus oligomer, and excess unlabeled AP-1 oligomer reverted binding suggesting that this region of the PAI-1 promoter is an AP-1-like binding site. Gel electrophoresis of double stranded -82 to -65 oligonucleotide with HeLa nuclear extracts revealed a gel shift pattern of three bands. Sp1 consensus oligomer competed with the binding of two of these bands and AP-2 consensus sequence oligomer with the binding to the third band. The -82 to -65 oligomer also bound to purified AP-2 and Sp1 proteins. Southwestern blotting of HeLa nuclear extracts revealed that the labeled oligomer covering region -82 to -65 bound the proteins with molecular weights of 52 kD and 72 kD.(ABSTRACT TRUNCATED AT 400 WORDS)


Studies on carbon nanotubes and fullerenes under extreme conditions.
Ion beam irradiation of materials can cause defect creation as well as defect annealing depending on the ion beam parameters such as ion fluence and the energy loss of ions in materials. In present review, we report the behaviour of carbon nanotubes under exteme conditions such as laser irradiation and ion irradiation. The reorientation of the crystalline planes in confined single crystal nickel nanorods inside carbon nano tube, induced by heavy ion irradiation, is reported. Axial buckling of nickel nanorods as well as walls of carbon nano tubes in nickel encapsulated carbon nano tubes under swift heavy ion irradiation at high fluence is observed. At high fluence, amorphization of nickel nanorods inside carbon nanotubes is also observed. Axial buckling and amorphization under ion irradiation at high fluence are dependent on the number of walls in carbon nanotubes. High resolution transmission electron microscopy was used to investigate the reorientations, buckling and amorphization of metal filled nanotubes. Synthesis of carbon nanowires by ion irradiation of fullerene and their field emission properties with comparison to that of unirradiated and irradiated carbon nanotubes are reported. An international scenario with future prospects of ion beam studies in carbon nanotube is briefed.


Positive schizotypy and negative schizotypy are associated with differential patterns of episodic memory impairment.
Cognitive impairment is a hallmark of schizophrenia; however, studies have not comprehensively examined such impairments in non-clinically ascertained schizotypic young adults. The present study employed a series of measures to assess episodic memory in high positive schizotypy, high negative schizotypy, and comparison groups (each group n = 25). Consistent with diminished cognitive functioning seen in negative symptom schizophrenia, the negative schizotypy group exhibited deficits on free recall, recognition, and source memory tasks. The positive schizotypy group did not demonstrate deficits on the above mentioned tasks. However, in contrast to the other groups, the positive schizotypy group showed an unexpected set-size effect on the cued-recall task. Set-size effect, which refers to the finding that words that have smaller networks of associates tend to have a memory advantage, is usually found in associative-cuing, but not cued-recall, tasks. The finding for the positive schizotypy group is consistent with heightened spreading activation and reduced executive control suggested to underlie psychotic symptoms. The findings support a multidimensional model of schizotypy and schizophrenia, and suggest that positive and negative schizotypy involve differential patterns of cognitive impairment.


Osimertinib: A third-generation tyrosine kinase inhibitor for treatment of epidermal growth factor receptor-mutated non-small cell lung cancer with the acquired Thr790Met mutation.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for the treatment of metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) in patients failing previous TKI therapy. The T790M mutation is an acquired resistance mechanism found in over half of patients with NSCLC progressing on first-generation TKIs. First- and second-generation TKIs do not inhibit the T790M mutation at clinically relevant concentrations. Osimertinib is selective for mutated forms of EGFR, including the TKI-sensitizing mutations L858R and exon 19 deletions, as well as the acquired T790M resistance mutation. In a trial comparing osimertinib to platinum doublet therapy among patients with the T790M mutation progressing on first-line TKI therapy, median progression-free survival was significantly longer in patients receiving osimertinib. Osimertinib has a favorable safety profile compared to platinum-doublet chemotherapy. Common adverse events include diarrhea, skin rash, dry skin, and paronychia; however, because it spares wild-type EGFR, these toxicities appear to occur with less frequency and severity compared to other TKIs. Serious, but rare, adverse events include pneumonitis, interstitial lung disease-like events, QT interval prolongation, and reduced ejection fraction. Osimertinib has the unique ability to distribute readily into brain tissue compared with other TKIs, giving it a potential role in the treatment and/or prevention of CNS metastases; future studies are warranted in this area. An ongoing study evaluating osimertinib versus first-generation TKIs as first-line treatment for patients with EGFR mutation-positive NSCLC may help to define the role of osimertinib as front-line therapy.


Sensorimotor Peak Alpha Frequency Is a Reliable Biomarker of Prolonged Pain Sensitivity.
Previous research has observed that the speed of alpha band oscillations (8-12 Hz range) recorded during resting electroencephalography is slowed in chronic pain patients. While this slowing may reflect pathological changes that occur during the chronification of pain, an alternative explanation is that healthy individuals with slower alpha oscillations are more sensitive to prolonged pain, and by extension, more susceptible to developing chronic pain. To test this hypothesis, we examined the relationship between the pain-free, resting alpha oscillation speed of healthy individuals and their sensitivity to two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two visits separated by 8 weeks on average (n = 61 Visit 1, n = 46 Visit 2). We observed that the speed of an individual's pain-free alpha oscillations was negatively correlated with sensitivity to both models and that this relationship was reliable across short (minutes) and long (weeks) timescales. Furthermore, the speed of pain-free alpha oscillations can successfully identify the most pain sensitive individuals, which we validated on data from a separate, independent study. These results suggest that alpha oscillation speed is a reliable biomarker of prolonged pain sensitivity with potential for prospectively identifying pain sensitivity in the clinic.


Cutaneous anthrax: an overview.
The recent acts of bioterrorism have raised new questions about this uncommon disease. Clinicians are puzzled as to why some of the victims exposed to Bacillus anthracis spores developed the cutaneous form of the disease and others the inhalational form. Despite these questions, cutaneous anthrax remains relatively simple to treat effectively. The real clinical challenge lies in the diagnosis, especially being able to distinguish it from a spider bite.


Applicant attraction to organizations and job choice: a meta-analytic review of the correlates of recruiting outcomes.
Attracting high-performing applicants is a critical component of personnel selection and overall organizational success. In this study, the authors meta-analyzed 667 coefficients from 71 studies examining relationships between various predictors with job-organization attraction, job pursuit intentions, acceptance intentions, and job choice. The moderating effects of applicant gender, race, and applicant versus nonapplicant status were also examined. Results showed that applicant attraction outcomes were predicted by job-organization characteristics, recruiter behaviors, perceptions of the recruiting process, perceived fit, and hiring expectancies, but not recruiter demographics or perceived alternatives. Path analyses showed that applicant attitudes and intentions mediated the predictor-job choice relationships. The authors discuss the implications of these findings for recruiting theory, research, and practice.


Adenosine induces prolonged anti-beta-adrenergic effects in guinea-pig papillary muscle.
A sustained anti-beta-adrenergic effect of adenosine has been reported. This study was initiated to investigate this topic and especially elucidate the role of protein kinase C (PKC). Contractile force amplitude and action potential duration at 90% repolarization (APD90) were measured in guinea-pig papillary muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols contained 30 min exposure to the test agents adenosine 33 microm (ado), adenosine + PKC-inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC-activator 1,2-dioctanoyl-sn-glycerol 10 microm (DOG) and alpha-agonist phenylephrine 5 microm (phe). Isoproterenol was given at the end of test exposure and after 15 min washout. Results are mean +/- SEM of percentage-change, P < or = 0.05 considered significant and labelled *. The first isoproterenol challenge significantly increased contractile force (27 +/- 7%*) in the control group. Responses in the test groups were 2 +/- 4 (ado), 1 +/- 5 (ado + BIM), 14 +/- 4* (DOG), 0 +/- 2% (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3 +/- 8 (ado), 23 +/- 5* (ado + BIM), 13 +/- 5* (DOG), 15 +/- 7% (phe) increase in test groups compared with 22 +/- 5%* increase in contractile force in the control group. After 45 min washout of adenosine the inotropic response was still significantly reduced compared with control (29 +/- 4 vs. 79 +/- 8%*). Isoproterenol stimulation shortened APD90 in controls at both time points (5 +/- 1%* and 4 +/- 1%*), with no significant shortening in test groups. Adenosine induces sustained anti-beta-adrenergic effects on contractile force as well as APD90. A role for PKC in signal transduction is supported with respect to contractile force.


Epidemiology and control of trachoma: systematic review.
Trachoma is the commonest infectious cause of blindness. Recurrent episodes of infection with serovars A-C of Chlamydia trachomatis cause conjunctival inflammation in children who go on to develop scarring and blindness as adults. It was estimated that in 2002 at least 1.3 million people were blind from trachoma, and currently 40 million people are thought to have active disease and 8.2 million to have trichiasis. The disease is largely found in poor, rural communities in developing countries, particularly in sub-Saharan Africa. The WHO promotes trachoma control through a multifaceted approach involving surgery, mass antibiotic distribution, encouraging facial cleanliness and environmental improvements. This has been associated with significant reductions in the prevalence of active disease over the past 20 years, but there remain a large number of people with trichiasis who are at risk of blindness.


Social-economic costs and quality of life of Alzheimer disease in the Canary Islands, Spain.
To examine the economic burden (direct and indirect costs) of Alzheimer disease (AD) and to analyze the impact on health-related quality of life (HRQOL) for patients with AD and caregivers in 2001 in the Canary Islands, Spain. Two hundred thirty-seven patients (61% of those contacted) were recruited from the Alzheimer's Disease Association in the Canary Islands. Demographic, health resources utilization, informal care, indirect costs, and quality of life data were collected from primary caregivers of patients as proxy respondents. HRQOL was measured for patients and caregivers with the generic questionnaire EQ-5D. The average annual cost per patient with AD was 28,198 (36,144 US dollars). The most important categories of costs were for informal care and drugs. Costs increased with cognitive impairment with an average annual cost of 14,956 (19,171 US dollars) for mild, 25,562 (32,765 US dollars) for moderate, and 41,669 (53,411 US dollars) for severe patients. The total cost of patients with AD in Canary Islands was 259 (332 US dollars) million. The HRQOL with the EQ-5D social tariff was 0.29 for patients and 0.67 for caregivers. The EQ-5D VAS (thermometer) score was 42 for patients and 62 for caregivers. Direct health care costs of AD represented 2.4% of the total public health care expenditure in the Canary Islands. Across all severity levels, we estimated a total annual cost of 10 (13 US dollars) billion for AD patients older than 65 years in Spain. The degree of severity of the patients with AD substantially influenced the quality of life of the patients but not that of the caregivers.


Preparation of a cross-linked porous protein crystal containing Ru carbonyl complexes as a CO-releasing extracellular scaffold.
Protein crystals generally are stable solid protein assemblies. Certain protein crystals are suitable for use as nanovessels for immobilizing metal complexes. Here we report the preparation of ruthenium carbonyl-incorporated cross-linked hen egg white lysozyme crystals (Ru·CL-HEWL). Ru·CL-HEWL retains a Ru carbonyl moiety that can release CO, although a composite of Ru carbonyl-HEWL dissolved in buffer solution (Ru·HEWL) does not release CO. We found that treatment of cells with Ru·CL-HEWL significantly increased nuclear factor kappa B (NF-κB) activity as a cellular response to CO. These results demonstrate that Ru·CL-HEWL has potential for use as an artificial extracellular scaffold suitable for transport and release of a gas molecule.


Worldwide Prevalence of Mandibular Second Molar C-Shaped Morphologies Evaluated by Cone-Beam Computed Tomography.
The aim of this study was to evaluate and compare the C-shaped mandibular second molar prevalence in different regions around the world with the aid of cone-beam computed tomography technology. Nine field observers from 9 different geographic regions were calibrated. A total of 400 samples were collected in each region. The prevalence of C-shaped anatomy was calculated. The number of roots and the configuration of the C-shaped canals at 3 different axial levels were also evaluated. The z-test was used to analyze the difference between the means of each independent group. Intrarater reliability was also tested. A total of 3600 teeth from 2735 patients were included in this research; 499 teeth presented C-shaped root canal configuration, representing a global prevalence of 13.9%. China had a prevalence of 44.0%, which was significantly higher than any other region. The C-shape prevalence in women was 16.5%, which was significantly higher than the 10.4% prevalence found in men. No difference between sides (37 or 47) was evident in the global sample. Cone-beam computed tomography is a valuable tool to evaluate the C-shaped root canal configuration in vivo. In the present study, China presented the highest prevalence of C-shaped mandibular second molars when compared with other regions. Women exhibited a higher prevalence than men.


Pegylated versus standard interferon plus ribavirin in chronic hepatitis C genotype 4: A systematic review and meta-analysis.
Treatment of hepatitis C genotype 4 (HCV-G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta-analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR). We searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta-analysis was used to pool the risk ratio (RR) of achieving SVR across trials. Five RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR = 1.51, 95% confidence interval [CI] = 1.08-2.10). SVR was significantly higher in PEG IFN-α-2a compared to the -α-2b group (P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR (P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity. In treatment-naive patients with HCV-G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.


2018-2022 Southern Resident killer whale presence in the Salish Sea: continued shifts in habitat usage.
The fish-eating Southern Resident killer whales (Orcinus orca) of the northeastern Pacific are listed as Endangered in both the USA and Canada. The inland waters of Washington State and British Columbia, a region known as the Salish Sea, are designated as Southern Resident critical habitat by both countries. The whales have historically had regular monthly presence in the Salish Sea, with peak abundance occurring from May through September. In recent years, at least partially in response to shifting prey abundance, habitat usage by the Southern Residents has changed. As conservation measures aim to provide the best possible protection for the whales in their hopeful recovery, it is key that policies are based both on historic trends and current data. To this aim, our study shares 2018-2022 daily occurrence data to build upon and compare to previously published whale presence numbers and to demonstrate more recent habitat shifts. Based on reports from an extensive network of community scientists as well as online streaming hydrophones, every Southern Resident occurrence was confirmed either visually or acoustically. Documented here are the first-ever total absence of the Southern Residents in the Salish Sea in the months of May, June, and August, as well as their continued overall declining presence in the spring and summer, while fall and winter presence remains relatively high. It is key that management efforts consider these shifting presence patterns when setting both seasonal and regional protection measures aimed at supporting population recovery.


Systemic side effects of glaucoma medications.
Glaucoma is a progressive loss of retinal ganglion cells leading to visual field loss. Lowering intraocular pressure is currently the only modifiable risk factor to slow glaucoma progression. Intraocular pressure-lowering options include topical and systemic medications, lasers, and surgical procedures. Glaucoma eye drops play a major role in treating this blinding disease. Similar to all medications, the glaucoma medications have their own adverse effects. The majority of glaucoma medications work by stimulating or inhibiting adrenergic, cholinergic, and prostaglandin receptors, which are distributed all over the body. Therefore, the glaucoma medications can affect organs other than the eye. This review will discuss the systemic adverse effects of carbonic anhydrase inhibitors, sympathomimetics, para-sympathomimetics, beta blockers, prostaglandin analogs, hyperosmotic agents, and novel glaucoma medications with a stress on pregnant patients, breastfeeding mothers, and paediatric patients.


Effects of Hot Pixels on Pixel Performance on Backside Illuminated Complementary Metal Oxide Semiconductor (CMOS) Image Sensors.
Effects of hot pixels on pixel performance in light and dark environments have been investigated in pinned photodiode 0.18 μm backside illuminated CMOS image sensors irradiated by 10 MeV protons. After exposure to protons, hot pixels and normal pixels are selected from the whole pixel array, and their influences on key parameters are analyzed. Experimental results show that radiation-induced hot pixels have a significant impact on pixel performance in dark environments, such as dark signal nonuniformity, long integration time, and random telegraph signal. Hot pixels are caused by defects with complex structures, i.e., cluster defects. Furthermore, the dark current activation energy result confirms that the defects causing the hot pixels have defect energy levels close to mid-gap.


[Simultaneous radio-chemotherapy of advanced epithelial ovarian cancer--results after three years (author's transl)].
An interdisciplinary prospective, non-randomized study was performed at the University Clinic for Radiotherapy and Radiobiology of Vienna in 26 patients with advanced epithelial ovarian cancers (FIGO stage III and IV) from February 1977 until February 1980. All patients underwent a combined radiotherapy-chemotherapy programme. In those 12 patients in whom at the time of the first operation only a biopsy was possible, the aim was to achieve early operability for a second-look operation (with removal of the internal reproductive organs, the omentum and remaining tumour masses). In 8 of theses 12 patients it was technically possible to perform radical surgery or to reduce tumour masses to under 2 cm. Of 20 evaluable patients 14 had stage III and 6 had stage IV cancer. In patients with stage III the response rate was 100% and the complete remission rate (with or without second-look operation) was above 70%. The duration of complete remission exceeded 10 months, median survival is at present 17 months. Patients with stage IV had a response rate of 66% (but mainly partial remissions), with significantly shorter survival times. Bowel complications occurred in one quarter of the patients and led to a revision of our therapeutic concept and the time sequence of the combined modality treatment. The importance of significant prognostic factors is stressed. The study indicated the superiority of the combined treatment approach in patients with stage III cancer. Patients with stage IV cancer, are, on the other hand, best managed primarily by chemotherapy; palliative irradiation and a second-look operation should be reserved only for selected patients.


Reaction-diffusion master equation in the microscopic limit.
Stochastic modeling of reaction-diffusion kinetics has emerged as a powerful theoretical tool in the study of biochemical reaction networks. Two frequently employed models are the particle-tracking Smoluchowski framework and the on-lattice reaction-diffusion master equation (RDME) framework. As the mesh size goes from coarse to fine, the RDME initially becomes more accurate. However, recent developments have shown that it will become increasingly inaccurate compared to the Smoluchowski model as the lattice spacing becomes very fine. Here we give a general and simple argument for why the RDME breaks down. Our analysis reveals a hard limit on the voxel size for which no local RDME can agree with the Smoluchowski model and lets us quantify this limit in two and three dimensions. In this light we review and discuss recent work in which the RDME has been modified in different ways in order to better agree with the microscale model for very small voxel sizes.


Odor and irritation thresholds for ammonia: a comparison between static and dynamic olfactometry.
Odor and lateralization (irritation) thresholds (LTs) for ammonia vapor were measured using static and dynamic olfactometry. The purpose of the study was to explore the test-retest reliability and comparability of dynamic olfactometry methodology, generally used to determine odor thresholds following European Committee for Standardization guidelines in the context of odor regulations to outside emissions, with static olfactometry. Within a 2-week period, odor and LTs for ammonia were obtained twice for each method for 24 females. No significant differences between methods were found: mean odor detection thresholds (ODTs) were 2.6 parts per million (ppm) for either method (P = 0.96), and mean LTs were 31.7 and 60.9 ppm for the static and dynamic method, respectively (P = 0.07). Test-retest reliability was higher for the dynamic than for the static method (r = 0.61 vs. 0.14 for ODTs and r = 0.86 vs. 0.45 for LTs). The choice of optimal method for any application, however, depends not only on psychometric factors but also on practical factors such as physicochemical properties of the compound, availability of equipment and expertise, task efficiency, and costs.


Erythrocyte lipid extraction in alcohol-chloroform systems: a comparative study.
Lipid extraction efficiency is variable when different methods are used on the same tissue. After a systematic comparison on erythrocytes, we found that this variability was due to several factors, such as the addition of alcohol and chloroform as a mixture, the use of repeated extractions or partition procedures after the extraction. Most important, however, was the uneven distribution of solvents and lipids in an apparently monophasic extraction system. This formation reduces lipid extraction and causes accumulation of lipids in the extract supernatant, which leads to an overestimation of the extracted lipid content. We recommend a one-step 18.75 volume of methanol-chloroform (1.5:1 v/v) method for lipid extraction from erythrocytes, with methanol added before chloroform. This method combines simplicity in the extraction procedure, complete extraction of cholesterol and total phospholipids, and reliability in the quantitation of the extracted lipids.


Multiphoton microscopic imaging of rabbit dorsal skin.
Rabbits are often preferred to be experimental animals during the skin research. The visualizing and understanding the full-thickness structure of rabbit skin has significance in biology, medicine, and animal husbandry. In this study, multiphoton microscopy (MPM) was employed to examine the rabbit skin on the back, which was based on second harmonic generation and two-photon excited fluorescence. High-resolution images were achieved from the fresh, unfixed, and unstained tissues, showing detailed microstructure of the skin without the administration of exogenous contrast agents. The morphology and distribution of the main components of epidermis and dermis, such as keratin, collagen fibers, elastic fibers, and hair follicles, can be distinctly identified in MPM images. Since the changes in these components are tightly related to skin diseases and wound healing, the noninvasive nature of MPM enables it become a valuable tool in skin research for detecting and monitoring.


Peripheral clock system circadian abnormalities in Cushing's disease.
In Cushing's syndrome, the cortisol rhythm is impaired and can be associated with the disruption in the rhythmic expression of clock genes. In this study, we evaluated the expression of CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3 genes in peripheral blood leukocytes of healthy individuals (n = 13) and Cushing's disease (CD) patients (n = 12). Participants underwent salivary cortisol measurement at 0900 h and 2300 h. Peripheral blood samples were obtained at 0900 h, 1300 h, 1700 h, and 2300 h for assessing clock gene expression by qPCR. Gene expression circadian variations were evaluated by the Cosinor method. In healthy controls, a circadian variation in the expression of CLOCK, BMAL1, CRY1, PER2, and PER3 was observed, whereas the expression of PER1 and CRY2 followed no specific pattern. The expression of PER2 and PER3 in healthy leukocytes presented a late afternoon acrophase, similarly to CLOCK, whereas CRY1 showed night acrophase, similarly to BMAL1. In CD patients, the circadian variation in the expression of clock genes was lost, along with the abolition of cortisol circadian rhythm. However, CRY2 exhibited a circadian variation with acrophase during the dark phase in patients. In conclusion, our data suggest that Cushing's disease, which is characterized by hypercortisolism, is associated with abnormalities in the circadian pattern of clock genes. Higher expression of CRY2 at night outlines its putative role in the cortisol circadian rhythm disruption.


The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel (review).
The ligand-gated ion channel superfamily of neurotransmitter receptors are proteins responsible for rapid transmission of nerve impulses at the synapse and have, therefore, been the subject of intensive research for many years. The cys-loop family, of which the 5-HT3 receptor is a member, includes the nicotinic acetylcholine receptor, the GABAA receptor and the glycine receptor. A diverse range of endogenous and artificial ligands activate these receptors, but, nevertheless, the family shares many similarities of structure and function. Several important questions, however, still remain to be determined, including the mechanism of agonist recognition at the binding site, the nature of the connection between the agonist binding and channel domains, the structure of the transmembrane regions and the mechanism of ion permeation and selectivity. This article reviews recent advances in the characterization of the molecular properties of the 5-HT3 receptor and their role in its function, and assesses its suitability as a model system for the study of the above questions.


An interaction between the human T cell leukemia virus type 1 basic leucine zipper factor (HBZ) and the KIX domain of p300/CBP contributes to the down-regulation of tax-dependent viral transcription by HBZ.
Activation of human T cell leukemia virus type 1 (HTLV-1) transcription is established through the formation of protein complexes on the viral promoter that are essentially composed of the cellular basic leucine zipper (bZIP) transcription factor cAMP-response element-binding protein (CREB (or certain other members of the ATF/CREB family), the HTLV-1-encoded transactivator Tax, and the pleiotropic cellular coactivators p300/CBP. HTLV-1 bZIP factor (HBZ) is a protein encoded by HTLV-1 that contains a bZIP domain and functions to repress HTLV-1 transcription. HBZ has been shown to repress viral transcription by dimerizing with CREB, which occurs specifically through the bZIP domain in each protein, and preventing CREB from binding to the DNA. However, we previously found that HBZ causes only partial removal of CREB from a chromosomally integrated viral promoter, and more importantly, an HBZ mutant lacking the COOH-terminal bZIP domain retains the ability to repress viral transcription. These results suggest that an additional mechanism contributes to HBZ-mediated repression of HTLV-1 transcription. In this study, we show that HBZ binds directly to the p300 and CBP coactivators. Two LXXLL-like motifs located within the NH(2)-terminal region of HBZ are important for this interaction and specifically mediate binding to the KIX domain of p300/CBP. We provide evidence that this interaction interferes with the ability of Tax to bind p300/CBP and thereby inhibits the association of the coactivators with the viral promoter. Our findings demonstrate that HBZ utilizes a bipartite mechanism to repress viral transcription.


Local CC2 electronic excitation energies for large molecules with density fitting.
A new local method for the computation of electronic excitation energies of singlet states in extended molecular systems is presented. It is based on the CC2 model and local approximations to the wave functions. In the proposed method the singles excitations are treated nonlocally and local restrictions are imposed on doubles amplitudes only. The accuracy of the new method was tested by calculating several lowest excited states for 14 molecules and comparing them with canonical CC2 values. Deviations of the local excitation energies from the canonical reference values do not exceed 0.05 eV for all test molecules and all states in the lower energy range investigated in this work. The method uses the density-fitting approximation for all two-electron integrals, which considerably simplifies the computational complexity of the individual diagrams. A combination of the local approximations and the powerful density-fitting technique leads to a low-scaling method, capable to treat molecular systems comprised of 100 atoms and more in a basis of a polarized double zeta quality. A test calculation for a system consisting of 127 atoms and 370 active electrons without symmetry is presented to show the efficiency of the new method.


Contamination of hypodermic needles in anaesthetic practice.
The study was undertaken to define and compare the incidence of bacterial contamination on opening three different types of hypodermic needle package. Four user groups were studied (anaesthetists, intensive care nurses, operating department assistants and medical laboratory scientific officers). Bacterial contamination was shown to occur and to be related to the type of needle packaging, the ratio of contamination incidence being similar in all four user groups. The results emphasize the importance of a careful opening technique when using sterile packaged hypodermic needles.


Relationship between apical periodontitis and marginal bone loss at individual level from a general population.
To study the relationship between the presence of apical periodontitis in root-filled teeth and marginal bone loss (MBL) in individual subjects from a general population. The study was conducted on a sample of 1,152 dentate individuals (participants in an epdemiological investigation) who were subjected to clinical and radiographic investigations. The presence of root fillings and apical periodontitis were registered. MBL was measured mesially and distally at all roots. The MBL index of the subject was defined as the mean MBL value at all measurable points in the same individual. Multiple regression analysis was adopted to calculate the influence of the presence of apical periodontitis and potential confounders on the dependent variable, MBL index. There was a significant correlation between MBL and the percentage of root-filled teeth and the percentage of root-filled teeth with apical periodontitis. The results of the multiple regression analysis showed that the relative frequency of root-filled teeth with apical periodontitis was significantly higher in subjects with more MBL, irrespective of age, number of remaining teeth, relative frequency of root-filled teeth and smoking habits. A significant association between the presence of apical and marginal periodontitis in individual subjects was found. The mechanisms behind the associations between these diseases are unknown and this cross-sectional observational study did not permit distinction between cause and effect. It is hoped that future cohort studies may provide more knowledge about the biological actions behind the relationship between apical and marginal disease.


Genetics of monoamine oxidase.
Evidence for the genetic control of human MAO is now well established. The relationships of MAO activities to neuropsychiatric disorders or response to psychopharmacologic treatments are relatively unstudied. Preliminary findings from our own studies suggest that (1) blood MAO activity is a polygenically controlled trait; (2) there may be a subgroup of depressed patients with high MAO activity who are more severe symptomatically and more resistant to treatment, and (3) that men with atypical and mixed depressions respond more favorably than women to treatment with an MAO inhibitory drug.


Applications of thin-layer chromatography in extraction and characterisation of ajoene from garlic bulbs.
Novel and inexpensive methods of thin-layer chromatography (TLC) were employed for the extraction, characterisation and mechanism of quorum sensing inhibition by ajoene, a component from toluene garlic bulb (Allium sativum L.) extract (TGE). TLC profiling of TGE was carried out using ethyl acetate as solvent. Out of total spots extracted from TLC, four spots exhibited quorum sensing inhibitory (QSI) potential. Among those, spot 5 was identified as Z-ajoene by TLC and confirmed by NMR and MS. HPLC analysis indicated 97.7% purity for purified ajoene. TLC densitometric analysis quantified 221.08 μmol/g of ajoene in TGE and indicated that ajoene is stable at 4°C and at acidic pH. HPTLC profiling showed that ajoene exhibits QSI effect by inhibiting the production of both long-chain acyl homoserine lactones and Pseudomonas quinolone signal (PQS) by P. aeruginosa and also by inactivating PQS molecules.


The defense mechanisms of coronary patients.
Tested 73 male inpatients with coronary heart disease on the Defense Mechanisms Inventory, State-Trait Anxiety Inventory, and a perception of health measure. Ss were followed for 5 years. Success of defenses was measured by lower anxiety, higher perception of health, and survival. Principalization was discovered to be the most successful and Projection the least successful defense. When a typology of patients was constructed using cluster analysis, those with high Principalization and low Reversal were judged to cope best. Although the efficacy of repressing defenses during crisis received support, both the type of repressing defense used and its relationship to other defenses were important in determining successful outcome.


Development of Carbon-Based Solid Acid Catalysts Using a Lipid-Extracted Alga, Dunaliella tertiolecta, for Esterification.
Novel carbon-based solid acid catalysts were synthesized through a sustainable route from lipid-extracted microalgal residue of Dunaliella tertiolecta, for biodiesel production. Two carbon-based solid acid catalysts were prepared by surface modification of bio-char with sulfuric acid (H₂SO₄) and sulfuryl chloride (SO₂Cl₂), respectively. The treated catalysts were characterized and their catalytic activities were evaluated by esterification of oleic acid. The esterification catalytic activity of the SO₂Cl₂-treated bio-char was higher (11.5 mmol Prod.∙h⁻¹∙g Cat. ⁻¹) than that of commercial catalyst silica-supported Nafion SAC-13 (2.3 mmol Prod.∙h⁻¹∙g Cat. ⁻¹) and H₂SO₄-treated bio-char (5.7 mmol Prod.∙h⁻¹∙g Cat. ⁻¹). Reusability of the catalysts was examined. The catalytic activity of the SO₂Cl₂-modified catalyst was sustained from the second run after the initial activity dropped after the first run and kept the same activity until the fifth run. It was higher than that of first-used Nafion. These experimental results demonstrate that catalysts from lipid-extracted algae have great potential for the economic and environment-friendly production of biodiesel.


A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis: Airleaf.
New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf™; NCT05238675) assessing the efficacy and safety of a novel CatC inhibitor, BI 1291583, in adult patients with bronchiectasis. This multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study has a screening period of at least 6 weeks, a treatment period of 24-48 weeks and a follow-up period of 4 weeks. ∼240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1 mg once daily, 2.5 mg once daily or 5 mg once daily in a 2:1:1:2 ratio, stratified by Pseudomonas aeruginosa infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose-response relationship for the three oral doses of BI 1291583 versus placebo on time to first pulmonary exacerbation up to Week 48 (the primary end-point). Efficacy will be assessed using exacerbations, patient-reported outcomes, measures of symptoms, sputum neutrophil elastase activity and pulmonary function testing. Safety assessment will include adverse event reporting, physical examination, monitoring of vital signs, safety laboratory parameters, 12-lead electrocardiogram, and periodontal and dermatological assessments. If efficacy and safety are demonstrated, results will support further investigation of BI 1291583 in phase 3 trials.


Movement disorders in catatonia.
Catatonia is a complex neuropsychiatric syndrome characterised by a broad range of motor, speech and behavioural abnormalities. 'Waxy flexibility', 'posturing' and 'catalepsy' are among the well-recognised motor abnormalities seen in catatonia. However, there are many other motor abnormalities associated with catatonia. Recognition of the full spectrum of the phenomenology is critical for an accurate diagnosis. Although controlled trials are lacking benzodiazepines are considered first-line therapy and N-Methyl-d-aspartate receptor antagonists also appears to be effective. Electroconvulsive therapy is used in those patients who are resistant to medical therapy. An underlying cause of the catatonia should be identified and treated to ensure early and complete resolution of symptoms.


Practical recommendations for managing hemolyzed samples in clinical chemistry testing.
We suggest here a pragmatic approach for managing results of clinical chemistry testing in hemolyzed samples collected from adults/older children, attempting to balance the need to produce quality laboratory data with clinical urgency of releasing test results. Automatic measurement of the hemolysis index (H-index) in serum or plasma is highly advisable, whilst low-quality assessment of this test remains less good than a visual inspection. Regarding its practical use, when the H-index value does not generate an analytically significant bias, results can be released, whilst when the value is associated with analyte variation in a range between analytically and clinically significant bias (i.e. variation does not exceed the reference change value [RCV]), results of hemolysis-sensitive tests can be released in association with a comment describing the direction in which data are potentially altered, suggesting the need to collect another sample. When the H-index is associated with analyte variation exceeding clinically significant bias (i.e. variation exceeds the RCV), results of hemolysis-sensitive tests should be suppressed and replaced with a comment that biased results cannot be released because the sample is preanalytically compromised and advising the recollection of another sample. If H-index values reach an even higher critical cut-off (i.e. H-index corresponding to a cell-free hemoglobin concentration ≥10 g/L), all laboratory data may be unreliable and should hence be suppressed and replaced with a comment that all data cannot be released because the sample is grossly hemolyzed, also suggesting the recollection of another sample. Due to inaccuracy and imprecision, the use of corrective formulas for adjusting data of hemolysis-sensitive tests is discouraged.


The readability of online breast cancer risk assessment tools.
Numerous breast cancer risk assessment tools that allow users to input personal risk information and obtain a personalized breast cancer risk estimate are available on the Internet. The goal of these tools is to increase screening awareness and identify modifiable health behaviors; however, the utility of this risk information is limited by the readability of the material. We undertook this study to assess the overall readability of breast cancer risk assessment tools and accompanying information, as well as to identify areas of suggested improvement. We searched for breast cancer risk assessment tools, using five search terms, on three search engines. All searches were performed on June 12, 2014. Sites that met inclusion criteria were then assessed for readability using the suitability assessment of materials (SAM) and the SMOG readability formula (July 1, 2014–January 31, 2015). The primary outcomes are the frequency distribution of overall SAM readability category (superior, adequate, or not suitable) and mean SMOG reading grade level. The search returned 42 sites were eligible for assessment, only 9 (21.4 %) of which achieved an overall SAM superior rating, and 27 (64.3 %) were deemed adequate. The average SMOG reading grade level was grade 12.1 (SD 1.6, range 9–15). The readability of breast cancer risk assessment tools and the sites that host them is an important barrier to risk communication. This study demonstrates that most breast cancer risk assessment tools are not accessible to individuals with limited health literacy skills. More importantly, this study identifies potential areas of improvement and has the potential to heighten a physician's awareness of the Internet resources a patient might navigate in their quest for breast cancer risk information.


Development of a framework for resilience measurement: Suggestion of fuzzy Resilience Grade (RG) and fuzzy Resilience Early Warning Grade (REWG).
Resilience engineering (RE) can be an alternative technique to the traditional risk assessment and management techniques, to predict and manage safety conditions of modern socio-technical organizations. While traditional risk management approaches are retrospective and highlight error calculation and computation of malfunction possibilities, resilience engineering seeks ways to improve capacity at all levels of organizations in order to build strong yet flexible processes. Considering the resilience potential measurement as a concern in complex working systems, the aim of this study was to quantify the resilience by the help of fuzzy sets and Multi-Criteria Decision-Making (MCDM) techniques. In this paper, we adopted the fuzzy analytic hierarchy process (FAHP) method to measure resilience in a gas refinery plant. A resilience assessment framework containing six indicators, each with its own sub-indicators, was constructed. Then, the fuzzy weights of the indicators and the sub-indicators were derived from pair-wise comparisons conducted by experts. The fuzzy evaluating vectors of the indicators and the sub-indicators computed according to the initial assessment data. Finally, the Comprehensive Resilience Index (CoRI), Resilience Grade (RG), and Resilience Early Warning Grade (REWG) were established. To demonstrate the applicability of the proposed method, an illustrative example in a gas refinery complex (an instance of socio-technical systems) was provided. CoRI of the refinery ranked as "III". In addition, for the six main indicators, RG and REWG ranked as "III" and "NEWZ", respectively, except for C3, in which RG ranked as "II", and REWG ranked as "OEWZ". The results revealed the engineering practicability and usefulness of the proposed method in resilience evaluation of socio-technical systems.


Differences in EEG harmonic driving responses to photic stimulation between normal aging and Alzheimer's disease.
In order to investigate whether Alzheimer's disease (AD) is the end result of aging of the brain or the result of some other mechanism, we analyzed EEGs showing the absolute power of harmonic responses to photic stimulation (PS) in younger subjects, non-demented elderly subjects and AD patients. At rest, the AD patients generally showed less absolute power than the younger and elderly subjects, with significant differences found at 10 Hz and 20 Hz. Analysis of EEGs recorded during PS indicated that the elderly subjects generally demonstrated more absolute power than the younger subjects and AD patients. These findings suggest a failure of stimulation-related brain activation in AD patients, and provide further evidence that normal aging and AD employ different mechanisms for functional organization during PS.


Geriatric assessment tools.
In addition to medical diseases, psychological, social, cognitive, and functional issues influence the health of older persons. Therefore, the traditional medical assessment alone is often not enough to evaluate the older population with multiple comorbidities. Out of this recognized need, the geriatric assessment has been developed, which emphasizes a broader approach to evaluating contributors to health in older persons. Geriatric assessment uses specific tools to help determine patient's status across several different dimensions, including assessment of medical, cognitive, affective, social, economic, environmental, spiritual, and functional status. This article reviews specific tools that practitioners can use in their screening for the following geriatric syndromes: hearing impairment, vision impairment, functional decline, falls, urinary incontinence, cognitive impairment, depression, and malnutrition. This article also reviews spiritual, economic, and social assessment. By identifying conditions that are common in the elderly, geriatric assessment can provide substantial insight into the comprehensive care of older persons, from those who are healthy and high-functioning to those with significant impairments and multiple comorbidities.


[Adenopathies and anticonvulsants: Lymphoma or drug reaction?].
In this paper the authors present the clinical case of a nine years old girl with adenopathy, fever and important weight loss. 10 months after she begins with diphenidantoin the differential diagnosis was attempted between lymphoma and drug reaction. The authors reviewed the literature pointed out the development of lymphomas in patients on diphenidantoin therapy. They mention the different hipothesis to explain this drug-lymphoma interrelation concluding that there is necessary more studies and experience in future cases to clarify the certain role of the anticonvulsivants in the production of this abnormalities.


Microglial Function across the Spectrum of Age and Gender.
Microglia constitute the resident immunocompetent cells of the central nervous system. Although much work has focused on their ability to mount an inflammatory response in reaction to pathology, recent studies have delved into their role in maintaining homeostasis in the healthy brain. It is important to note that the function of these cells is more complex than originally conceived, as there is increasing evidence that microglial responses can vary greatly among individuals. Here, this review will describe the changing behavior of microglia from development and birth through to the aged brain. Further, it is not only age that impacts the state of the neuroimmune milieu, as microglia have been shown to play a central role in the sexual differentiation of the brain. Finally, this review will discuss the implications this has for the differences in the incidence of neurodegenerative disorders between males and females, and between the young and old.


Fatal hypersensitivity pneumonitis after chemical occupational exposure.
Hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis) is a rare non-immunoglobulin E (IgE)-mediated inflammatory lung disease caused by inhalation exposure (occupational, recreational or ordinary home exposure). A 36-year-old female patient, without significant medical history, is referred to an outpatient pulmonology clinic for dry cough, shortness of breath, fever, fatigue and weight loss. Chest high-resolution computed tomography (HRCT) was performed, and significant lung fibrosis (especially centrilobular and interlobular in bilateral "thick lines"), traction bronchiectasis and alveolitis in both superior lobes are described. Lung function tests showed severe restrictive dysfunction. Transfer factor of the lung for carbon monoxide (TLCO) being very low, the flexible bronchoscopy was contraindicated. Surgical lung biopsy was performed. Histopathological examination showed characteristic lesions of chronic bilateral hypersensitivity pneumonitis. The patient died four days after the surgical intervention due to post-operative complications. Exposure to various chemical substances can form bonds with human proteins molecules and induce an exaggerated immune response in susceptible individuals. A high index of suspicion of occupational exposure can determine an early diagnosis with a better outcome.


DFT calculations on molecular structures, HOMO-LUMO study, reactivity descriptors and spectral analyses of newly synthesized diorganotin(IV) 2-chloridophenylacetohydroxamate complexes.
The gas-phase-optimized geometry of newly synthesized and characterized diorganotin(IV) 2-chloridophenylacetohydroxamate complexes of composition [Me2 Sn(HL)2 ] (I) and [n-Bu2 Sn(HL)2 ] (II) (where KHL = potassium 2-chloridophenylacetohydroxamate (2-ClPhAHK); [Me2 Sn(2-ClC6 H4 CH2 CONHO)2 ] (I) and [n-Bu2 Sn(2-ClC6 H4 CH2 CONHO)2 ] (II) computed by B3LYP/6-311++G(d,p) method has shown these to be distorted octahedral. Bonding through carbonyl and hydroxamic oxygen atoms (O, O coordination) has been inferred from a comparison of computed important bond lengths (CO, CN, and NO) of complexes with that of free ligand. The SnO bond lengths in complexes are suggestive of weak coordinate (through carbonyl CO) and strong covalent (through hydroxamic NO) bonding of the ligand. The magnitude of CSnC bond angles involving two methyl/n-butyl groups is suggestive of cis-conformation at tin metal. The thermodynamic parameters (G, H, S, E, Cv, and U) of complexes have been computed. From the energies of frontier molecular orbitals (HOMO-LUMO), the reactivity descriptors, namely, ionization potential, electron affinity, chemical potential (μ), hardness (η), softness (S), electronegativity (χ), and electrophilicity index (ω) have been calculated. The computed vibrational frequencies and 1 H NMR chemical shifts have substantiated the molecular structure of complexes. © 2019 Wiley Periodicals, Inc.


Impact of influenza and other community-acquired viruses.
The incidence of community-acquired pneumonia peaks during the winter season each year. Increases in mortality from these pneumonias and influenza-like illnesses (P&I) above an "epidemic threshold" for 2 or more weeks generally signify increased numbers of influenza virus infections in the community, although peaks in P&I mortality typically lag a few weeks behind peaks in influenza virus activity. Most of the pneumonias cases found during influenza virus epidemics are due to secondary bacterial infections, with an increase in the frequency of Staphylococcus aureus over that seen in nonepidemic periods. One interaction between bacteria and influenza viruses that may increase disease severity by increasing growth of the virus is proteolytic cleaving of the hemagglutinin mediated directly or indirectly by bacterial products. Influenza virus infections also have many effects on the host that can enhance secondary bacterial infections; included are impairments of mucus clearance and T cell, polymorphonuclear cell and macrophage functions, as well as alterations in respiratory epithelium that can enhance adherence of bacteria. Recent studies indicate that the role of respiratory syncytial virus infections in causing acute pulmonary syndromes in elderly individuals, including secondary bacterial pneumonia, is essentially equivalent to that of influenza A viruses during years when there is not a severe influenza epidemic. Although other respiratory viruses can occasionally cause or facilitate the development of community-acquired pneumonia, currently available epidemiological data do not support significant roles for them relative to those of influenza and respiratory syncytial viruses.


Left ventricular aneurysm complicated by congestive heart failure: an analysis of long-term results and risk factors of surgical treatment.
The results of surgical treatment of post-infarction left ventricular aneurysms in 49 patients with congestive heart failure preoperatively were analyzed. Average patient age was 55 years. Preoperative total ejection fraction averaged 30.5 +/- 1.5% (mean +/- SEM), contractile segment ejection fraction was 42.5 +/- 1.1% and end-diastolic volume of aneurysm was 81.4 +/- 10.4 ml. Seventy eight percent of patients underwent coronary artery bypass grafting concomitantly with aneurysmectomy. Mean follow-up after operation was 41.5 +/- 3.5 months. Hospital mortality was 8.2%, the 5 year survival rate was 70 +/- 7% and the 5 year complication free rate was 52 +/- 8%. Mean functional class of dyspnea improved significantly from 2.9 +/- 0.1 preoperatively to 1.6 +/- 0.1 at late follow-up (p less than 0.001). Likewise, isotopic ejection fraction at rest increased from 13.7 +/- 1.3% preoperatively to 30.9 +/- 3.0% postoperatively (p less than 0.0001). Logistic regression analysis isolated two factors which influenced postoperative survival independently: contractile segment ejection fraction (p = 0.045) and myocardial score of left anterior descending coronary artery (p = 0.035). Combining these two risk factors, it was possible to identify a low risk group of patients with a 5 year survival probability of 93 +/- 6%, contrasting with a high risk group of patients having a 5 year survival of 57 +/- 9% (p less than 0.02). Thus, resection of left ventricular aneurysms complicated by congestive heart failure provides improvement in left ventricular function and clinical status.(ABSTRACT TRUNCATED AT 250 WORDS)


What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review.
Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.