Effect of ascorbic acid on stimulatory status of activated mouse peritoneal phagocytes.
Mouse peritoneal macrophages (MPM) when elicited by the antioxidant ascorbic acid have been found to be significantly stimulatory, exhibiting marked alteration at the cellular and enzyme levels. Alterations recorded were as follows--cellular yield per mouse, their protein content, lysosomal acid hydrolase levels and capability to phagocyte, all were significantly enhanced. The new stimulant was observed to produce no synergistic action on MPM when thioglycollate, BCG or endotoxin along with the same stimulated the latter. Levels of antioxidants like ascorbic acid and glutathione were found to be enhanced in elicited macrophages whereas superoxide dismutase levels varied when the three above stimulators were administered. However, the ascorbic acid elicited cells showed an increase in glutathione levels and a decrease in SOD levels but no change in total intracellular ascorbic acid levels. Further, though ascorbic acid interaction enhanced the phagocytic capability of MPM as compared to resident cells, no significant boosting of phagocytic process could be observed when each of three stimulators coupled with ascorbic acid was used for macrophage elicitation.


Correlation between PKB/Akt, GSK-3β expression and tubular epithelial-mesenchymal transition in renal allografts with chronic active antibody-mediated rejection.
Chronic antibody-mediated rejection (ABMR) is a major cause of the transplant renal interstitial fibrosis and transplanted kidney epithelial cell transdifferentiation is one of the main mechanisms. The transforming growth factor (TGF)-β1/integrin-linked kinase (ILK) signaling pathway has a significant role in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells; however, the molecular mechanisms of this process have remained elusive. The present study confirmed that Akt and glycogen synthase kinase (GSK)-3β, as TGF-β1 downstream signaling factors, are involved in fibrotic processes caused by kidney disease, which, however, has been rarely reported in the kidney transplant field. Based on the Banff 2009 standard, transplanted kidney specimens were classified according to the fibrosis level. The results showed that with the reduction of the interstitial fibrosis level, E-cadherin expression was gradually reduced, while α-smooth muscle actin expression progressively increased. The expression of Akt and GSK-3β in normal human kidney tissue was not obvious but showed a marked increase with the aggravation of the interstitial fibrosis level, which confirmed the occurrence of EMT during the fibrosis process, and that phosphorylated (p)-Akt and GSK-3β have an important role in the EMT process in the transplanted kidney. A correlation analysis of p-Akt, GSK-3β, TGF-β1 and ILK suggested that overexpression of p-Akt and GSK-3β may induce and mediate the transdifferentiation of renal tubular epithelial cells to myofibroblasts and that this proceeds via TGFβ1/ILK signaling pathways.


Severe platelet dysfunction in hairy cell leukemia with improvement after splenectomy.
A patient with hairy cell leukemia developed purpura not attributable to thrombocytopenia. We found markedly reduced platelet aggregation responses and malondialdehyde production, decreased serotonin uptake, and depleted dense granule contents. Ultrastructural studies showed that most platelets had few or nor granules. All of the clinical and laboratory studies of platelet function and morphology improved after splenectomy. These findings indicate that qualitative defects in platelet function occurring in hairy cell leukemia may cause clinically important bleeding and that the bleeding diathesis may be ameliorated by splenectomy.


Does increased prescribed exercise alter non-exercise physical activity/energy expenditure in healthy adults? A systematic review.
Prescribed physical activity/exercise training may reduce non-exercise physical activity resulting in no change in total daily energy expenditure and no or minimal exercise-induced weight loss. This systematic review evaluated cross-sectional, short-term (2-14 d), randomized and non-randomized trials which reported on the effect of prescribed physical activity/exercise on non-exercise physical activity/energy expenditure in healthy adults. PubMed and Embase were searched (from January 1990 to March 2013) for articles that presented data on the change in non-exercise physical activity/energy expenditure in response to prescribed physical activity/exercise training. Thirty-one articles were included in this review. One-hundred per cent of cross-sectional studies (n = 4), 90% of short-term studies (n = 10), 50% of non-randomized trials (n = 10) and 100% of randomized trials (n = 7) reported no reductions in non-exercise physical activity/energy expenditure in response to prescribed physical activity/exercise training. We found minimal evidence to support the hypothesis that prescribed physical activity/exercise training results in decreased non-exercise physical activity/energy expenditure in healthy adults. However, this literature is limited by the lack of adequately powered trials designed specifically to evaluate this hypothesis which have included assessments of both the energy expenditure of prescribed exercise and non-exercise energy expenditure using state-of-the-art techniques, i.e. indirect calorimetry and doubly labelled water, respectively.


Purine nucleoside analog--sulfinosine modulates diverse mechanisms of cancer progression in multi-drug resistant cancer cell lines.
Achieving an effective treatment of cancer is difficult, particularly when resistance to conventional chemotherapy is developed. P-glycoprotein (P-gp) activity governs multi-drug resistance (MDR) development in different cancer cell types. Identification of anti-cancer agents with the potential to kill cancer cells and at the same time inhibit MDR is important to intensify the search for novel therapeutic approaches. We examined the effects of sulfinosine (SF), a quite unexplored purine nucleoside analog, in MDR (P-gp over-expressing) non-small cell lung carcinoma (NSCLC) and glioblastoma cell lines (NCI-H460/R and U87-TxR, respectively). SF showed the same efficacy against MDR cancer cell lines and their sensitive counterparts. However, it was non-toxic for normal human keratinocytes (HaCaT). SF induced caspase-dependent apoptotic cell death and autophagy in MDR cancer cells. After SF application, reactive oxygen species (ROS) were generated and glutathione (GSH) concentration was decreased. The expression of key enzyme for GSH synthesis, gamma Glutamyl-cysteine-synthetase (γGCS) was decreased as well as the expression of gst-π mRNA. Consequently, SF significantly decreased the expression of hif-1α, mdr1 and vegf mRNAs even in hypoxic conditions. SF caused the inhibition of P-gp (coded by mdr1) expression and activity. The accumulation of standard chemotherapeutic agent--doxorubicin (DOX) was induced by SF in concentration- and time-dependent manner. The best effect of SF was obtained after 72 h when it attained the effect of known P-gp inhibitors (Dex-verapamil and tariquidar). Accordingly, SF sensitized the resistant cancer cells to DOX in subsequent treatment. Furthermore, SF decreased the experssion of vascular endothelial growth factor (VEGF) on mRNA and protein level and modulated its secretion. In conclusion, the effects on P-gp (implicated in pharmacokinetics and MDR), GSH (implicated in detoxification) and VEGF (implicated in tumor-angiogenesis and progression) qualify SF as multi-potent anti-cancer agent, which use must be considered, in particular for resistant malignancies.


Characterization of AlgMsp, an alginate lyase from Microbulbifer sp. 6532A.
Alginate is a polysaccharide produced by certain seaweeds and bacteria that consists of mannuronic acid and guluronic acid residues. Seaweed alginate is used in food and industrial chemical processes, while the biosynthesis of bacterial alginate is associated with pathogenic Pseudomonas aeruginosa. Alginate lyases cleave this polysaccharide into short oligo-uronates and thus have the potential to be utilized for both industrial and medicinal applications. An alginate lyase gene, algMsp, from Microbulbifer sp. 6532A, was synthesized as an E.coli codon-optimized clone. The resulting 37 kDa recombinant protein, AlgMsp, was expressed, purified and characterized. The alginate lyase displayed highest activity at pH 8 and 0.2 M NaCl. Activity of the alginate lyase was greatest at 50°C; however the enzyme was not stable over time when incubated at 50°C. The alginate lyase was still highly active at 25°C and displayed little or no loss of activity after 24 hours at 25°C. The activity of AlgMsp was not dependent on the presence of divalent cations. Comparing activity of the lyase against polymannuronic acid and polyguluronic acid substrates showed a higher turnover rate for polymannuronic acid. However, AlgMSP exhibited greater catalytic efficiency with the polyguluronic acid substrate. Prolonged AlgMsp-mediated degradation of alginate produced dimer, trimer, tetramer, and pentamer oligo-uronates.


Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes.
In contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D. A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices. There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported. Linagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.


Peripheral and mesenteric serum levels of CEA and cytokeratins, staging and histopathological variables in colorectal adenocarcinoma.
To evaluate the differences that exist between peripheral and mesenteric serum levels of carcinoembryonic antigen (CEA) and cytokeratins in patients with colorectal adenocarcinoma. One hundred and thirty-eight patients with colorectal adenocarcinoma who underwent surgery at Hospital Sao Paulo (Discipline of Surgical Gastroenterology of UNIFESP-EPM) between December 1993 and March 2000 were retrospectively analyzed. Differences between CEA and cytokeratin (TPA-M) levels in peripheral blood (P) and in mesenteric blood (M) were studied. Associations were investigated between peripheral and mesenteric levels and the staging and histopathological variables (degree of cell differentiation, macroscopic appearance, tumor dimensions and presence of lymphatic and venous invasion). Differences were observed in the numerical values of the marker levels: CEA (M) (39.10 mg/L +/- 121.19 mg/L) vs CEA (P) (38.5 mg/L +/- 122.55 mg/L), P < 0.05; TPA-M (M) (325.06 U/L +/- 527.29 U/L) vs TPA-M (P) (279.48 U/L +/- 455.81 U/L), P < 0.01. The mesenteric CEA levels were higher in more advanced tumors (P < 0.01), in vegetating lesions (34.44 mg/L +/- 93.07 mg/L) (P < 0.01) and with venous invasion (48.41 mg/L +/- 129.86 mg/L) (P < 0.05). Peripheral CEA was higher with more advanced staging (P < 0.01) and in lesions with venous invasion (53.23 mg/L +/- 158.57 mg/L) (P < 0.05). The patients demonstrated increased mesenteric and peripheral TPA-M levels with more advanced tumors (P < 0.01 and P < 0.01) and in non-ulcerated lesions [530.45 U/L +/- 997.46 U/L (P < 0.05) and 457.95 U/L +/- 811.36 U/L (P < 0.01)]. The mesenteric levels of the tumor markers CEA and cytokeratins were higher than the peripheral levels in these colorectal adenocarcinoma patients. Higher levels of these biologic tumor markers are associated with an advanced state of cancerous dissemination.


Reproduction of a fish assemblage in the state of São Paulo, southeastern Brazil.
Fish reproductions were studied in two river basins (Corumbataí and Jacaré-Pepira basins) in the State of São Paulo, southeastern Brazil. In the Corumbataí basin, four sites were sampled: Cabeça River, Lapa Stream, Passa-Cinco River, and Corumbataí River; in the Jacaré-Pepira basin, three sites were sampled: Tamanduá Stream, Jacaré-Pepira River, and Agua Branca Stream. A total of 12 bimonthly samples were made. Fish equipment included gill nets, purse seines, sieves, and traps. The main objective of this study was to characterize the fish assemblage regarding their reproductive biology and to compare these reproductive traits between both river basins. Most individuals with gonads in stage C (mature) and in stage D (empty gonads) were captured in the spring and summer. Multiple spawn and parental care were common strategies, which guaranteed offspring survivorship in unstable conditions.


Stimulation of ACTH release by human interleukin-1 beta, but not by interleukin-1 alpha, in conscious, freely-moving rats.
Ever since two distinct molecules of human interleukin-1 (termed interleukin-1 alpha and interleukin-1 beta) were cloned, sequenced and expressed, it has been a matter of investigation whether these two forms of interleukin-1 possess an identical spectrum of biological activities. Our current studies of interleukin-1 and its involvement in the hypothalamic-pituitary-adrenal axis have indicated that there is a clear-cut differential response to interleukin-1 alpha and interleukin-1 beta. The intravenous injection of human recombinant interleukin-1 beta significantly increased the plasma levels of adrenocorticotropic hormone in a dose-related manner, whereas interleukin-1 alpha did not. This observation suggests for the first time that the two members of the interleukin-1 family may have a different spectrum of biological actions.


Argon plasma coagulation of hemorrhagic solitary rectal ulcer syndrome.
Solitary ulcer syndrome (SUS) is a rare disorder that may provoke hematochezia. Argon plasma coagulation (APC) is used in a wide range of gastrointestinal bleeding. We experienced APC in a patient with a bleeding gigantic SUS: a 64-year-old woman who developed a SUS at 60. After 3 years, recurrent hematochezia, secondary anemia, and rectal pain occurred. Endoscopy revealed a large rectal bleeding ulcer. Moreover, the pain led the patient to assume analgesics. These conditions stimulated us to treat this ulcer with APC within 4 sessions; each session spaced out at 30-day intervals. The patient experienced and maintained the following benefits: (1) resolution of bleeding and secondary anemia after the first session, (2) reduction of ulcer depth, disappearance of pain and analgesic withdrawal at the end of the cycle, (3) almost complete endoscopic healing of the ulcer after 9 months of follow-up. This experience suggests that APC may represent a therapeutic approach for bleeding SUS even if controlled studies are necessary before recommending it as acceptable treatment.


Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors.
Severe and prolonged stress is the main environmental factor that precipitates depression, anxiety and cognitive dysfunctions. On the other hand, exposure to environmental enrichment (EE) has been shown to induce progressive plasticity in the brain and improve learning and memory in various neurological and psychiatric disorders. It is not known whether exposure to enriched environment could ameliorate chronic immobilisation stress-induced cognitive deficits and altered molecular markers. Hence, in the present study we aimed to evaluate the effect of enriched environment on chronic immobilisation stress (CIS) associated changes in spatial learning and memory, behavioural measures of anxiety, depression and molecular markers as well as structural alterations. Male Wistar rats were subjected to chronic immobilisation stress for 2h/day/10days followed by 2weeks of exposure to EE. CIS resulted in weight loss, anhedonia, increased immobility, spatial learning and memory impairment, enhanced anxiety, and reduced expression of BDNF, VEGF, GFAP and glucocorticoid receptors (GR) in discrete brain regions. Interestingly, stressed rats exposed to enrichment ameliorated behavioural depression, spatial learning and memory impairment and reduced anxiety behaviour. In addition, EE restored BDNF, VEGF, GFAP and GR expression and normalized hypotrophy of dentate gyrus and hippocampus in CIS rats. In contrast, EE did not restore hypertrophy of the amygdalar complex. Thus, EE ameliorates stress-induced cognitive deficits by modulating the neurotrophic factors, astrocytes and glucocorticoid receptors in the hippocampus, frontal cortex and amygdala.


Association of Vitamin D Levels and type 2 Diabetes Mellitus in Asian Indians is Independent of Obesity.
A large proportion of subjects with type 2 diabetes mellitus (T2DM) in India are non-obese. Asian-Indian subjects with diabetes have been shown to have low vitamin D levels. Whether low vitamin D levels and T2DM in Asian-Indians is attributable to the associated obesity as in caucasians is unclear. Hence we studied the association of vitamin D levels and T2DM in Asian-Indians with or without obesity. Total of 213 subjects were recruited in four groups, group 1-Non-obese diabetic, group 2-Non-obese non-diabetic, group 3-Obese diabetic and group 4-Obese non-diabetic. Subjects recruited under various groups were matched for age and sex. Anthropometry, skin-fold thickness, fasting and postprandial plasma glucose, HbA1c, fasting insulin, lipids and vitamin D levels were measured in all study subjects and were compared between the groups. Mean age of study population was 41.23±7.43 years. Mean BMI in groups 1,2,3 and 4 was 21.34±1.41, 20.53±2.27, 27.72±2.94 and 27.62±3.37 kg/m2 respectively. Overall 64.3% study subjects had vitamin D deficiency and 27.7% had insufficient vitamin D levels. Significantly lower vitamin D levels were found in diabetic groups 1 and 3 compared to non-diabetic groups 2 and 4. No significant difference was observed in vitamin D levels between groups 1 and 3. Similarly, no significant difference was observed in vitamin D levels between groups 2 and 4. Vitamin D levels did not show any significant correlation with BMI, waist or body fat. Vitamin D levels do not appear to be related to obesity in diabetic as well non-diabetic Asian-Indian individuals.


Coordination networks with flexible ligands based on silver(I) salts: complexes of 1,3-bis(phenylthio)propane with silver(I) salts of PF6-, CF3COO-, CF3CF2COO-, CF3CF2)CF2COO-, p-TsO-, and CF3SO3-.
The synthesis and characterization of nine coordination networks based on 1,3-bis(phenylthio)propane, L(3), and silver(I) salts of PF(6)(-) (1), CF(3)COO(-) (2), CF(3)CF(2)COO(-) (3), CF(3)CF(2)CF(2)COO(-) (4), p-TsO(-) (5, 6), and CF(3)SO(3)(-) (7-9) are reported. Only 1 and other "isostructural" complexes with weakly coordinating anions such as ClO(4)(-) and SbF(6)(-) are of the host-guest type. In all the other complexes, the anions and the acetone molecules, when present, are coordinated to the metal. Most of the complexes studied here form a 2D-coordination network. Only 4 and 5 adopt a polymer-like chain structure. The packing of the chains of 4 is pseudohexagonal compact, while that of 5 is of the centered type. In complex 1, the silver atom is tetrahedrally coordinated to the sulfur atoms of four different ligands. The PF(6)(-) anions and acetone molecules, sandwiched between silver-ligand cationic sheets, are held through van der Waals interactions. In each of the three perfluorocarboxylates (2-4), two silver atoms are joined by the anions in a diatomic bridging mode. The Ag...Ag distances are sufficiently short to indicate weak metal...metal interactions. The dimeric units in 2 and 3 are interconnected through the ligands, thereby generating a 2D-network of neutral sheets, while, in 4, the dimeric units are bound to four ligands and a 1D-coordination polymer is generated. In the case of the sulfonate anions (p-TsO(-) and CF(3)SO(3)(-)), the crystallization solvent influences the structure adopted. Thus, in 5, 7, and 9 obtained from petroleum ether, or other nonpolar solvents, two silver atoms are bound in a double-bridge fashion, while a monobridge mode is noted for 6 and 8, both recrystallized from diethyl ether. In 8, both bridging types are observed. The thermogravimetric investigation, in the room temperature-450 degrees C interval, of complexes 1, 3, and 7, which incorporate acetone molecules in their crystal structures, reveals a two-step weight loss for 1 (the acetone molecules are lost first followed by the ligands, leaving behind the silver salt), while complexes 3 and 7 decompose in a single step to metallic silver.


An update on primary findings and new designs in biotherapy studies for acute myocardial infarction.
Treatment of acute myocardial infarction in the future should focus not only on improving acute treatment, as it has been done over the past decades, but also on secondary prevention of left ventricular dysfunction and/or progression to heart failure by preserving left ventricular shape, avoiding left ventricular remodeling and stimulating cardiac regeneration. Biotherapies with adult stem cells and bone marrow-derived endothelial cell progenitors, combined or not with biomaterials, and new drugs are under investigation and will probably be part of routine clinical practice for patients suffering from myocardial infarction in the near future.


Time series analysis of onchocerciasis data from Mexico: a trend towards elimination.
In Latin America, there are 13 geographically isolated endemic foci distributed among Mexico, Guatemala, Colombia, Venezuela, Brazil and Ecuador. The communities of the three endemic foci found within Mexico have been receiving ivermectin treatment since 1989. In this study, we predicted the trend of occurrence of cases in Mexico by applying time series analysis to monthly onchocerciasis data reported by the Mexican Secretariat of Health between 1988 and 2011 using the software R. A total of 15,584 cases were reported in Mexico from 1988 to 2011. The data of onchocerciasis cases are mainly from the main endemic foci of Chiapas and Oaxaca. The last case in Oaxaca was reported in 1998, but new cases were reported in the Chiapas foci up to 2011. Time series analysis performed for the foci in Mexico showed a decreasing trend of the disease over time. The best-fitted models with the smallest Akaike Information Criterion (AIC) were Auto-Regressive Integrated Moving Average (ARIMA) models, which were used to predict the tendency of onchocerciasis cases for two years ahead. According to the ARIMA models predictions, the cases in very low number (below 1) are expected for the disease between 2012 and 2013 in Chiapas, the last endemic region in Mexico. The endemic regions of Mexico evolved from high onchocerciasis-endemic states to the interruption of transmission due to the strategies followed by the MSH, based on treatment with ivermectin. The extremely low level of expected cases as predicted by ARIMA models for the next two years suggest that the onchocerciasis is being eliminated in Mexico. To our knowledge, it is the first study utilizing time series for predicting case dynamics of onchocerciasis, which could be used as a benchmark during monitoring and post-treatment surveillance.


Kock pouch urinary diversion: follow-up by ultrasound.
In the post-operative follow-up of 24 patients who received a continent Kock pouch for urinary diversion, several complications were encountered, including hydronephrosis, stone formation and valve dysfunction, resulting in reflux and/or urinary incontinence. After comparing findings on ultrasound with those obtained by Koch pouch cystography, intravenous urography, plain abdominal radiography, Kock pouch endoscopy and operation, we consider ultrasound to be an important technique in the follow-up, especially in non-symptomatic patients. All cases of hydronephrosis and pouch calculi were detected by ultrasound and no false positive findings were encountered in either group. A good correlation is demonstrated between nipple length, as measured by ultrasound, and valve dysfunction, clinically important only for the afferent nipple.


Perception of small animal cardiopulmonary resuscitation of owners presenting to a small animal teaching clinic including a large first opinion service.
To gather information from veterinary clients to better understand and gauge the knowledge level and perception of small animal cardiopulmonary resuscitation (CPR) in an academic veterinary hospital. Prospective cross-sectional survey. A veterinary teaching hospital including a large first opinion service. None. An anonymous survey was developed to gauge the knowledge of veterinary clients on a variety of CPR related topics at a university veterinary hospital. Surveys were randomly distributed to a convenience sample of clients in the waiting room through the client services staff between October 2017 and March 2018. Of the 451 surveys distributed, 296 were used for the statistical analysis. The majority of respondents (92%) knew the appropriate definition of CPR but only 11% knew how to perform CPR on a dog or cat. Most respondents (82%) wanted to discuss their pet's CPR status at a veterinary visit. The mean ± SD estimate of rate of discharge from hospital after cardiac arrest was 39.4 ± 25.6% and the majority of respondents (202 [68%]) got their estimate from an educated guess. The respondents who elected CPR that day provided an estimated cost of 257 ± 365 USD while the respondents who elected not to have CPR provided an estimated cost of 491 ± 875 USD; P = 0.019. The respondents that watched television medical dramas estimated a higher rate of survival to discharge at 42 ± 25%, while people who did not watch television medical dramas provided an estimated survival rate of 35 ± 26%; P = 0.034. Inaccurate perceptions regarding CPR and survival rates exist among the general public; however, respondents are interested in becoming better informed.


Pneumonias - a dynamic relationship between the human organism and the etiologic agent.
Pneumonias are usually acute infectious processes of the pulmonary parenchyma, being the result of the overcome of the natural defence mechanisms of the human organism, which lead to the penetration, persistence and multiplication of a biologic agent (which has become a pathogen agent) within the lungs. This is a phenomena which generates local manifestations (inflammation) and systemic manifestations, their variable dimension (which is conditioned by the state of the host and/or the virulence of the pathogen agent) explaining the clinical, paraclinical and biological dimensions of the phenomena. The current material deals on one hand with the phenomena which takes part in the formation of the heterogeneous spectrum of the pneumonias and, on the other hand, we will demonstrate the manner in which the expansion and the severity of the infectious phenomena depend on the virulence of the etiologic agent, on the manner in which the defence mechanisms have been overcome, and also on the biological state of the invaded organism.


Deep Characterization of a Greek Patient with Desmin-Related Myofibrillar Myopathy and Cardiomyopathy.
Desmin is a class III intermediate filament protein highly expressed in cardiac, smooth and striated muscle. Autosomal dominant or recessive mutations in the desmin gene (DES) result in a variety of diseases, including cardiomyopathies and myofibrillar myopathy, collectively called desminopathies. Here we describe the clinical, histological and radiological features of a Greek patient with a myofibrillar myopathy and cardiomyopathy linked to the c.734A>G,p.(Glu245Gly) heterozygous variant in the DES gene. Moreover, through ribonucleic acid sequencing analysis in skeletal muscle we show that this variant provokes a defect in exon 3 splicing and thus should be considered clearly pathogenic.


Isolation of polysaccharides from Malva aegyptiaca and evaluation of their antioxidant and antibacterial properties.
This study investigated the antioxidant and antibacterial properties of crude water-soluble polysaccharides extracted from the mallow (Malva aegyptiaca) by precipitation with cetylpyridinium chloride (P1) or ethanol (P2). The Polysaccharides fractions were characterized by FTIR spectroscopy, a monosaccharide composition, and antioxidant and antibacterial activities. P1 showed the highest total sugars (81.2%) and sulfated groups (2.9%) contents but with the lowest total proteins content (8.7%). The infrared spectroscopic spectra exhibited the typical bands and peak characteristic of polysaccharides. Monosaccharides analysis revealed the dominance of galactose (40.3-43.7%) and glucuronic acid (25.9-30.9%). Interestingly, P1 displayed an important antioxidant activity as evaluated by the (Fe2+) chelating activity (IC50=1.15mg/ml), (Fe3+) reducing power (EC50=1.22mg/ml), β-carotene bleaching inhibition capacity (IC50=1.56mg/ml) and DPPH-radical scavenging activity (IC50=1.94mg/ml). Furthermore, P1 at 10mg/ml was highly active than P2 against several bacterial strains and especially the Gram-positive bacteria, where the inhibition rate ranged between 84.2 and 90.3%. Obtained results suggest that M. aegyptiaca polysaccharides precipitated by cetylpyridinium chloride could be used as a naural antioxidant and antibacterial agent.


Liquid-Phase Synthesis of Ba2V2O7 Phosphor Powders and Films Using Immiscible Biphasic Organic-Aqueous Systems.
A liquid-phase synthesis of inorganic phosphor materials at a moderate temperature was proposed by using immiscible liquid-liquid biphasic systems. A self-activated Ba2V2O7 phosphor was actually synthesized from vanadium alkoxide dissolved in an organic solution and barium acetate in an aqueous solution. A mild hydrolysis reaction of the alkoxide started at the organic-inorganic interface, and an intermediate compound, Ba(VO3)2·H2O, was initially formed. Ba2V2O7 powders were then obtained by the conversion from Ba(VO3)2·H2O promoted in the aqueous solution. Ba2V2O7 films were obtained on surface-modified silica glass substrates through the similar chemical reactions. Factors such as the surface state of substrates, the kind of organic solvents, and the volume of aqueous solutions were examined to improve the film deposition behavior. The resultant Ba2V2O7 materials showed broad-band visible photoluminescence upon irradiation with ultraviolet light based on the charge transfer transition in the VO4(3-) units existing as dimers.


Office-Based Intraosseous Infiltrations of PRGF as an Effective Treatment for Knee Osteoarthritis: A Retrospective Observational Clinical Study.
The aim of this study was to explore and assess office-based ultrasound-guided intraosseous and intra-articular infiltrations of plasma rich in growth factors (PRGF) in patients with moderate and severe knee osteoarthritis (KOA). Seventy-nine patients (30 women and 49 men) with grade 3-4 KOA according to the Kellgren-Lawrence classification participated in the study. All patients were treated with a minimally invasive technique using local anesthesia WALANT (wide-awake local anesthesia no tourniquet) in the ambulatory setting. A PRGF intra-articular infiltration and two intraosseous infiltrations in the tibial plateau and femoral condyle were performed weekly for a total of three sessions. The evaluation of the results was carried out using knee injury and osteoarthritis outcome score (KOOS) at baseline and post-treatment. After a follow-up period of 11 months (median) [interquartile range, 7-14], all the KOOS domains showed statistically significant improvement (p < 0.001). Moreover, 88% of the patients showed a pain reduction of at least 10 points (minimally clinically important improvement) from pre- to post-treatment. Our retrospective study using the in-office procedure of ultrasound-guided combination of intra-articular and intraosseous infiltrations of PRGF is a safe and efficacious approach for the treatment of grade 3-4 knee osteoarthritis.


Volatile Organic Compounds in the Breath of Oral Squamous Cell Carcinoma Patients: A Pilot Study.
Objective To assess the feasibility of detecting signature volatile organic compounds in the breath of patients with oral squamous cell carcinoma. Study Design Prospective cohort pilot study. Setting University hospital. Subjects and Methods Using gas chromatography and mass spectrometry, emitted volatile organic compounds in the breath of patients before and after curative surgery (n = 10) were compared with those of healthy subjects (n = 4). It was hypothesized that certain volatile organic compounds disappear after surgical therapy. A characteristic signature of these compounds for diseased patients was compiled and validated. Results Breath analyses revealed 125 volatile organic compounds in patients with oral cancer. A signature of 8 compounds that were characteristic for patients with oral cancer could be detected: 3 from this group presented were absent after surgery. Conclusion The presented results confirmed the hypothesis of an absence of cancer-associated volatile organic compounds in the breath after therapy. In this pilot study, we proved the feasibility of this test approach. Further studies should be initiated to establish protocols for usage in a clinical setting.


Texture analysis and machine learning to characterize suspected thyroid nodules and differentiated thyroid cancer: Where do we stand?
In thyroid imaging, "texture" refers to the echographic appearence of the parenchyma or a nodule. However, definition of the image characteristics is operator dependent and influenced by the operator's experience. In a more objective texture analysis, a variety of mathematical methods are used to describe image inhomogeneity, allowing assessment of an image by means of quantitative parameters. Moreover, this approach may be used to develop an efficient computer-aided diagnosis (CAD) system to yield a second opinion when differentiating malignant and benign thyroid lesions. The aim of this review is to summarize the available literature data on texture analysis, with and without CAD, in patients with suspected thyroid nodules or differentiated thyroid cancer, and to assess the current state of the approach.


Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery.
Cardiac surgery may be associated with significant perioperative and postoperative morbidity and mortality. Underlying pathology, surgical technique, and postoperative complications may all influence outcome. These factors may be reflected as a rise in postoperative troponin levels. Interpretation of troponin levels in this setting may therefore be complex. This study assessed the prognostic significance of such measurements, taking into account potential confounding variables. One-thousand three hundred sixty-five patients undergoing cardiac surgery underwent measurement of cardiac troponin I (cTnI) at 2 and 24 hours after surgery. The relationship of these measurements to subsequent mortality was established. After taking into account all other variables, cTnI levels measured at 24 hours were independently predictive of mortality at 30 days (odds ratio [OR] 1.14 per 10 microg/L, 95% confidence interval [CI] 1.05 to 1.24, P=0.002), 1 year (OR 1.10 per 10 microg/L, 95% CI 1.03 to 1.18, P=0.006), and 3 years (OR 1.07 per 10 microg/L, 95% CI 1.00 to 1.15, P=0.04). Cardiac TnI levels in the highest quartile at 24 hours were associated with a particularly poor outcome. cTnI levels measured 24 hours after cardiac surgery predict short-, medium-, and long-term mortality and remain independently predictive when adjusted for all other potentially confounding variables, including operation complexity.


Determination of endocrine disruptors and endogenic androgens and estrogens in rat serum by high-performance liquid chromatography-tandem mass spectrometry.
To simultaneously measure some targeted endocrine disruptors and several forms of sex hormones in rat serum, an accurate analytical procedure was developed. First, a comparison between a polymeric-based solid-phase extraction (SPE) and a micro-extraction by packed sorbent was performed to choose the optimal method to extract and concentrate the analytes: bisphenol A, atrazine, vinclozolin metabolite, testosterone, androstenedione, estrone, estradiol, estrone-sulfate and glucuronide and estradiol-sulfate and glucuronide. The analyses were then performed by high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with electrospray ionisation in positive and negative modes. The protocol based on SPE was validated using the ICH/2005 guidelines. The validation demonstrated good performance in terms of linearity (R(2)>0.99), recovery (71-90%) and repeatability (relative standard deviation: 1-18%). The method was sensitive with LOQ comprised between 0.1 and 0.4 ng/ml for androgens and between 0.098 and 10.2 ng/ml for estrogens. The results obtained on the serum of rats exposed to the targeted endocrine disruptors showed the suitability of this analytical strategy.


Validation of Spanish Language Evaluation Instruments for Body Dysmorphic Disorder and the Dysmorphic Concern Construct.
Dysmorphic concern (DC) refers to excessive preoccupation with a slight or imagined defect in physical appearance with social avoidance and behavior directed at controlling the defect in appearance. This study attempted to adapt the factor structure of two instruments that cover the DC construct, the Dysmorphic Concern Questionnaire (DCQ) and the Body Dysmorphic Disorder Examination Self-Report (BDDE-SR), to Spanish and establish their psychometric properties. A total of 920 subjects (62.7% women, Mage = 32.44 years) participated. Exploratory and Confirmatory Factor Analysis of both scales found adequate goodness of fit indices. A one-dimensional structure was found for the DCQ and two first-order factors (dissatisfaction/preoccupation with body image (BI) and BI avoidance behavior) were identified for the BDDE-SR. The psychometric test-retest reliability and validity properties (content, convergent, and discriminant) were satisfactory. It is suggested that the DC construct includes both cognitive and behavioral aspects and may represent a continuum of severity with Body Dysmorphic Disorder at the end.


Cognitive-enhancing and antioxidant activities of the aqueous extract from Markhamia tomentosa (Benth.) K. Schum. stem bark in a rat model of scopolamine.
Plants of the genus Markhamia have been traditionally used by different tribes in various parts of West African countries, including Cameroun. Markhamia tomentosa (Benth.) K. Schum. (Bignoniaceae) is used as an antimalarial, anti-inflammatory, analgesic, antioxidant and anti-Alzheimer agent. The current study was undertaken in order to investigate its anti-amnesic and antioxidant potential on scopolamine-induced cognitive impairment and to determine its possible mechanism of action. Rats were pretreated with the aqueous extract (50 and 200 mg/kg, p.o.), for 10 days, and received a single injection of scopolamine (0.7 mg/kg, i.p.) before training in Y-maze and radial arm-maze tests. The biochemical parameters in the rat hippocampus were also assessed to explore oxidative status. Statistical analyses were performed using two-way ANOVA followed by Tukey's post hoc test. F values for which p < 0.05 were regarded as statistically significant. In the scopolamine-treated rats, the aqueous extract improved memory in behavioral tests and decreased the oxidative stress in the rat hippocampus. Also, the aqueous extract exhibited anti-acetylcholinesterase activity. These results suggest that the aqueous extract ameliorates scopolamine-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.


Influence of dietary lipids on iron and copper levels of rats administered oral contraceptives.
Interrelationships between oral contraceptives and dietary lipids on iron and copper levels in plasma and tissues were investigated in rats. Diets containing either 20% (by weight) safflower oil or hydrogenated coconut oil with and without cholesterol (0.5%) were fed to weanling, female, Wistar-strain rats for a period of 19 weeks. Three types of oral contraceptive agents differing in estrogen/progesterone ratios were administered during weeks 16 through 19 of the experiment. Control rats received the dietary treatment without oral contraceptives. Hemoglobin concentration, hematocrit, red blood cell counts, mean cell hemoglobin and hemoglobin concentration, and mean cell volume values were similar among the various dietary and drug-treatment groups. Elevated levels of copper were found in livers of drug-treated animals fed diets containing cholesterol and safflower oil, whereas levels of copper or iron in spleen and kidney were not influenced by oral contraceptives. Dietary safflower or coconut oil had no influence on levels of iron or copper in plasma. However, iron levels were higher in liver, spleen, and kidneys of rats fed coconut oil compared with those fed safflower oil. Cholesterol-fed rats had reduced levels of iron in plasma and tissues and increased levels of copper in plasma and liver. Iron deficiency in cholesterol-fed rats was indicated by low levels of iron in plasma, liver, spleen, and kidney. In experiment 2, animals were fed the 20% safflower oil diet, with and without sodium glycocholate or cholesterol, to determine whether the apparent malabsorption of iron resulted from sodium glycocholate or cholesterol. Sodium glycocholate resulted in a marked increase in the absorption of iron, whereas cholesterol depressed absorption.


Emerging Adults Riding With Marijuana-, Alcohol-, or Illicit Drug-Impaired Peer and Older Drivers.
The purpose of this study was to examine the prevalence and covariates among emerging adults of riding with an impaired peer or older adult driver (RWI) because of marijuana (MJ), alcohol (ALC), or illicit drugs (ID). Data were from Waves 4 (W4, N = 2,085) and 5 (W5, N = 2,116) of the NEXT Generation Health Study, collected in 2013-2014, 1 and 2 years after high school. W5 RWI was specified for substance-specific impaired peer and older adult (peer/older adult) drivers. Multinomial logistic regressions estimated W5 association of substance-specific RWI with W4 RWI, and W5 heavy episodic drinking, MJ use, and school/residence/work status. At W5, 33% of the participants reported RWI in the past year, including riding with ALC- (21%), MJ- (17%), and ID- (5%) impaired peer drivers and ALC- (2%), MJ- (4%), and ID- (0.7%) impaired older adult drivers. W4 RWI was associated with W5 RWI with impaired peer/older adult drivers for ALC- (adjusted odds ratio [AOR] = 4.28, 2.69) and MJ-RWI (AOR = 2.34, 3.56). W5 heavy episodic drinking was positively associated with W5 peer ALC-related RWI (AOR = 2.16) and peer/older adult MJ-related RWI (AOR = 2.38, 5.45). W5 MJ use was positively associated with W5 peer ALC-related RWI (AOR = 2.23), peer/older adult MJ-related (AOR = 10.89, 2.98), and peer/older adult ID-related (AOR = 9.34, 4.26) RWI. ID-related RWI was higher among those not attending 4-year college (AOR = 3.38), attending technology school (AOR = 16.23), living on their own (AOR = 6.85), or living on campus (AOR = 11.50). The high prevalence of RWI among emerging adults occurred mostly with ALC- or MJ-impaired peer drivers. The findings support the need for precisely tailored programs to prevent impaired driving according to substance use and age.


Topoisomerases as anticancer targets.
Many cancer type-specific anticancer agents have been developed and significant advances have been made toward precision medicine in cancer treatment. However, traditional or nonspecific anticancer drugs are still important for the treatment of many cancer patients whose cancers either do not respond to or have developed resistance to cancer-specific anticancer agents. DNA topoisomerases, especially type IIA topoisomerases, are proved therapeutic targets of anticancer and antibacterial drugs. Clinically successful topoisomerase-targeting anticancer drugs act through topoisomerase poisoning, which leads to replication fork arrest and double-strand break formation. Unfortunately, this unique mode of action is associated with the development of secondary cancers and cardiotoxicity. Structures of topoisomerase-drug-DNA ternary complexes have revealed the exact binding sites and mechanisms of topoisomerase poisons. Recent advances in the field have suggested a possibility of designing isoform-specific human topoisomerase II poisons, which may be developed as safer anticancer drugs. It may also be possible to design catalytic inhibitors of topoisomerases by targeting certain inactive conformations of these enzymes. Furthermore, identification of various new bacterial topoisomerase inhibitors and regulatory proteins may inspire the discovery of novel human topoisomerase inhibitors. Thus, topoisomerases remain as important therapeutic targets of anticancer agents.


Multitest system for biochemical identification of Salmonella, Escherichia coli, and other Enterobacteriaceae isolated from foods: collaborative study.
Nine laboratories evaluated the ability of the MICRO-ID test system to correctly identify members of the Enterobacteriaceae. A total of 78 isolates representing 11 genera of enterics that had been previously isolated from foods were used in the collaborative study. The collaborators streaked each isolate on plate count agar and incubated the plates overnight at 35 degrees C to check purity of the isolates. Then they proceeded with the method in which an isolated colony is transferred to a plate count agar slant and is incubated 18-24 h at 35 degrees C. Growth from the slant is emulsified in 3.5 mL physiological saline to a density comparable to a McFarland No. 2 tube and is then used to inoculate the test (MICRO-ID) strip. The strip is incubated 4 h at 35 degrees C and the reactions are read and recorded. Isolates are identified by using an octal code and the test kit manual. The system correctly identified 98.8% of the Salmonella isolates, 97.7% of the E. coli isolates, and 84.6% of the other 9 enteric genera tested. The system has been approved interim official first action as an alternative to conventional biochemical tests (1) for presumptive generic identification of food-borne Salmonella and for screening and elimination of non-Salmonella isolates; (2) for identification of E. coli from foods; and (3) for presumptive generic identification of other Enterobacteriaceae isolated from foods.


Rebound and overshoot after plasma exchange in humans.
On the basis of animal experiments, some authors recommend a routine combination of therapeutic plasma exchange in patients with immunologically mediated disorders, such as autoimmune and immune complex diseases, with administration of cytotoxic drugs to prevent overshoot in plasma levels of pathogenic components after plasma exchange. We examined one healthy volunteer, seven patients with nonimmunologic diseases, and seven patients with immunologically mediated disorders (six with non-organ specific and one with organ-specific autoantibodies) to test whether plasma exchange is succeeded by an overshoot in levels of immunoglobulins, isohemagglutinins, autoantibodies, and antibodies after booster immunization with diphtheria and tetanus toxoid combined with poliomyelitis vaccine. Our data indicate that overshoot is not a generally occurring phenomenon in humans. We also confirmed the capability of corticosteroids, administered immediately after a period of plasma exchange, to reduce autoantibody levels. We found no arguments to support the suggestions in the literature that plasma exchange be combined with cytotoxic drugs in treatment of immunologically mediated diseases to prevent stimulation of potentially pathogenic components such as autoantibodies.


Genetic polymorphisms of IL-6 promoter in cancer susceptibility and prognosis: a meta-analysis.
IL-6 is critical for tumorigenesis. However, previous studies on the association of IL-6 promoter polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed this meta-analysis regarding the relationship between IL-6 promoter single nucleotide polymorphisms and cancer susceptibility and prognosis. Up to April 2017, 97 original publications were identified covering three IL-6 promoter SNPs. Our results showed statistically significant association between IL-6 promoter and cancer risk and prognosis. Subgroup analysis indicated that rs1800795 was significantly associated with increased risk of cervical cancer, colorectal cancer, breast cancer, prostate cancer, lung cancer, glioma, non-Hodgkin's lymphoma and Hodgkin's lymphoma but not gastric cancer and multiple myeloma. Furthermore, rs1800796 was significantly associated with increased risk of lung cancer, prostate cancer and colorectal cancer but not gastric cancer. Additionally, rs1800797 was significantly association with breast cancer, non-Hodgkin's lymphoma, B-cell lymphoma and diffuse large B-cell lymphoma but not gastric cancer. Simultaneously, rs1800795 and rs1800796 were associated with a significantly higher risk of cancer in Asia and Caucasian, rs1800797 was associated with a significantly risk of cancer in Caucasian but not in Asia. Furthermore, IL-6 promoter polymorphisms were significantly associated with the prognosis of cancer. Considering these promising results, IL-6 promoter including rs1800795, rs1800796 and rs1800797 may be a tumor marker for cancer therapy.


Multivariate analysis of prognostic factors in patients with pulmonary actinomycosis.
There have been few studies of pulmonary actinomycosis, which is an uncommon anaerobic infection. Consequently, the optimal therapeutic regimen, appropriate duration of treatment, long-term prognosis, and factors predicting prognosis are not well established. We retrospectively reviewed the medical records of histopathologically confirmed cases of pulmonary actinomycosis seen between November 2003 and December 2012. The study included 68 patients with a mean age of 58.4 ± 11.6 years. Of the 68, initial surgery was performed in 15 patients (22.1%), while the remaining 53 (77.9%) received antibiotic therapy initially. In the initial antibiotic group, 45/53 (84.9%) were cured without relapse (median antibiotic duration 5.3 months). 5/53 (9.4%) patients were refractory medically (median antibiotic duration 9.7 months), and 3/53 (5.7%) experienced a recurrence (median time to relapse 35.3 months). In the initial surgery group, 14/15 (93.3%) were cured and treatment failure occurred in one (6.7%). In the multivariate analysis, the absence of an antibiotic response at 1 month was the only independent factor associated with a poor treatment outcome, with an adjusted odds ratio of 49.2 (95% CI, 3.34-724.30). There was no significant difference in treatment outcome based on the size of the parenchymal lesion, comorbidities, whether intravenous antibiotics were used, antibiotic therapy duration, or whether the initial treatment was surgical. Antibiotic treatment with or without surgery was effective for treatment of pulmonary actinomycosis. Nevertheless, treatment failure or recurrence occurred in a considerable proportion of patients, especially those resistant to the initial antibiotic treatment.


New Solid Forms of the Antiviral Drug Arbidol: Crystal Structures, Thermodynamic Stability, and Solubility.
Salts of the antiviral drug Arbidol (umifenovir) with pharmaceutically relevant benzoate and salicylate anions were obtained, and their crystal structures were described. For Arbidol salicylate, an unstable solvate with acetonitrile was also found and characterized. Analysis of the conformational preferences of the Arbidol molecule in the crystal structures showed that it adopts two types of conformations, namely "open" and "closed", both of which correspond to local conformational energy minima of the isolated molecule. Thermal stability of the Arbidol salicylate solvates with chloroform and acetonitrile was analyzed by means of differential scanning calorimetry and thermogravimetric analysis. The standard thermodynamic functions of the salt formation were determined. The Gibbs energy change of the process was found to be negative, indicating that the formation of the salts from individual components is a spontaneous process. The dissolution study of the Arbidol salts performed in aqueous buffer solutions with pH 1.2 and 6.8 showed that both salts dissolve incongruently to form an Arbidol hydrochloride monohydrate at pH 1.2 and an Arbidol base at pH 6.8, respectively.


Al(n)Bi clusters: transitions between aromatic and jellium stability.
An experimental and theoretical study of bismuth-doped aluminum clusters in the gas phase has revealed two particularly stable clusters, namely, Al(3)Bi and Al(5)Bi. We show that their electronic structure can be understood in terms of the aromatic and "Jellium" models, respectively. Negative ion photodetachment spectra provide a fingerprint of the electronic states in Al(n)Bi(-) (n = 1-5) anions, while theoretical investigations reveal the nature of the electronic orbitals involved. Together, the findings reveal that the all-metal Al(3)Bi cluster with 14 valence electrons is a cyclic, planar structure with a calculated large ionization potential of 7.08 eV, a low electron affinity of 1.41 eV, and a large gap of 1.69 eV between the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gap). The Al(3)Bi cluster has molecular orbitals reminiscent of aromatic systems and is a neutral cluster with no need for counterion or ligand support. A slightly larger cluster, Al(5)Bi, has 20 valence electrons and is another highly stable compact structure with a calculated large ionization potential of 6.51 eV and a large HOMO-LUMO gap of 1.15 eV. This cluster's stability is rooted in a Jellium electronic shell closing. The formation of stable species using aromatic bonding allows us to extend the idea of cluster-assembled materials built out of stable clusters with Jellium shell closings (superatoms) to include ones involving aromatic building blocks.


Reduction in adverse effect on pulmonary function after exposure to filtered diesel exhaust.
A statistically significant temporary reduction on pulmonary function was measured with spirometry in stevedores on a roll-on-roll-off ro-ro ship who were exposed to diesel exhausts from trucks during a work shift. When all trucks were equipped with specially designed microfilters mounted on the exhaust pipes, this impairment in pulmonary function was reduced. Removal of the particulate fraction of the exhausts by filtering is an important factor in reducing the adverse effect of diesel exhaust on pulmonary function. The particle fraction should be considered when designing an indicator of the biological effects of diesel exhausts.


Speciation gradients and the distribution of biodiversity.
Global patterns of biodiversity are influenced by spatial and environmental variations in the rate at which new species form. We relate variations in speciation rates to six key patterns of biodiversity worldwide, including the species-area relationship, latitudinal gradients in species and genetic diversity, and between-habitat differences in species richness. Although they sometimes mirror biodiversity patterns, recent rates of speciation, at the tip of the tree of life, are often highest where species richness is low. Speciation gradients therefore shape, but are also shaped by, biodiversity gradients and are often more useful for predicting future patterns of biodiversity than for interpreting the past.


Effect of ethanolic extract of propolis as an alternative to antibiotics as a growth promoter on broiler performance, serum biochemistry, and immune responses.
An in vivo experiment was conducted to investigate the effect of different levels of ethanolic extract of propolis, on growth performance, carcass traits, serum biochemistry, and humoral immune responses of chickens, as compared with the antibiotic flavophospholipol. 312 1-day-old as-hatched broiler chicks (Ross 308) were randomly allotted to 6 treatments with 4 replicate pens per treatment. The 6 dietary treatments fed for 42 days consisted of a corn-soybean meal basal diet (control); control plus 4.5 mg/kg flavophospholipol, and control plus 50, 100, 200, and 300 mg/kg ethanol extracts of propolis, respectively. Neither propolis nor antibiotic affected the performance criteria; however, dietary treatments tended to enhance to enhance body weight and daily feed intake of broiler chickens compared with control group (p>0.05). None of the dietary treatments significantly altered feed: Gain though; broilers fed diet supplemented with 200 mg/kg propolis had better feed: gain values compared with other groups in starter, and grower phases as well as the whole experimental period (p>0.05). Carcass yield and internal organ relative weights were not affected by treatments on day 42, except for abdominal fat pad weight that decreased in broilers supplemented with antibiotic. None of the treatments significantly affected humoral immune function. Dietary treatments failed to induce any significant effect on serum biochemistry (p>0.05); though broilers receiving 100 mg/kg propolis had greater high-density lipoprotein-cholesterol and lower triglyceride concentrations compared with other groups. In conclusion, the results indicated that addition of ethanolic extract of propolis to routine dietary components of broilers, such as corn and soybean, seems not to have a positive influence on performance criteria.


Pulsed estrogen exposure selectively modulates tissue response: a hypothesis.
All postmenopausal hormone replacement therapies (HTs) aim to provide a steady mid-follicular serum concentration of estrogen, with the exception of pulsed estrogen therapy, which concentrates hormone exposure in the few hours following administration. This alteration in the kinetics of estradiol exposure does not change the beneficial effect of HT on climacteric symptoms or bone loss, but does reduce the stimulation of the breast and uterus leading to less mastalgia and bleeding. The following hypothesis provides a plausible pharmacological explanation as to how estradiol kinetics can selectively modify tissue response. Pulsed estradiol exposure influences the relative abundance of estrogen receptors (ERs) alpha and beta, via a tissue-dependent non-genomic signaling pathway, resulting in selective upregulation and activation of ERbeta in breast and endometrium, but not in bone. In addition, pulsed estrogen exposure also increases local concentration of 2-methoxyestradiol, a specific estradiol metabolite with proven anti-tumor properties.


Tandem mass spectrometry characterization of a conjugate between oleuropein and hydrated cis-diammineplatinum(II).
Oleuropein (Ole) has been claimed to mitigate cisplatin (CP)-induced acute injury in kidney and liver of mice. In vitro reactivity of hydrated CP species with Ole, and an Ole metabolite, hydroxytyrosol (HT), is of great interest as the preliminary step for gathering in vivo information on the possible physiological role of the Ole/HT-cis-diammineplatinum(II) (Ole/HT-cis-DAP) conjugate. Reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry using a linear ion trap instrument (RPLC/ESI-MS) and tandem mass (MS/MS) measurements, both in positive and negative ion mode, revealed the molecular identity of platinum-based conjugates. The Ole-cis-DAP conjugate (i.e., C25 H36 N2 O13 PtII ) features two cis-ammine non-leaving ligands and a bidentate catechol ligand moiety belonging to Ole; the coordination of the central Pt(II) is square-planar with non-equivalent bond angles compared with the ideal arrangement of 90°. HT, the free Ole metabolite excreted in human urine, acts as bidentate O,O-donor ligand of cis-DAP as well. The first evidence, together with structural information, is provided about the in vitro formation of a conjugate between cis-DAP and Ole or its urinary metabolite HT. Presuming that such conjugates are also generated in vivo, the mechanisms by which they might contribute to reduce CP toxicity remain to be elucidated.


Cutaneous side-effects of biologics in immune-mediated disorders: A histopathological perspective.
Advances in understanding molecular mechanisms and targets in immune regulation have led to the widespread use of biologic targeted therapies, and, as such, reformed the course of many disabling diseases. However, with their expanded use, various side-effects, including cutaneous, have emerged. Many times a clear-cut relationship exists between the drug and the clinical manifestations; however, when a biopsy is warranted, various histopathological patterns may be observed and may cause confusion to the dermatopathologist. The aim of this review is to shed light on the different histopathological patterns observed as a manifestation secondary to biologics.


BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders.
B cell-activating factor receptor (BAFF-R) is one of three known receptors for BAFF, a critical regulator of B- and T-cell function. In mice, BAFF-R is required for B-cell maturation and survival, and in mice and humans, the overproduction of BAFF is associated with autoimmune disease. We sought to determine the normal pattern of BAFF-R expression at specific stages of B- and T-cell development and whether this pattern of expression corresponds with related B- and T-cell neoplasms. Most circulating human B cells and a small subset of T cells are BAFF-R-positive. In reactive lymphoid tissues, BAFF-R is expressed by B cells colonizing the mantle zones, by a subset of cells within germinal centers, and rare cells in the interfollicular T-cell zone. BAFF-R is also expressed by B cells colonizing the splenic marginal zone. Seventy-seven (78%) of 116 cases of B-cell lymphoproliferative disorders were BAFF-R-positive by immunohistochemical and/or flow cytometric immunophenotypic analysis, including most cases of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and diffuse large B-cell lymphoma. In contrast, cases of precursor B lymphoblastic lymphoma, Burkitt lymphoma, and nodular lymphocyte-predominant Hodgkin lymphoma exhibit weak to negative staining for BAFF-R. All cases of classical Hodgkin lymphoma and T-cell lymphomas were BAFF-R-negative, including all cases of anaplastic large cell lymphoma, adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphoma, unspecified. These findings highlight BAFF-R as a marker of both normal and neoplastic B cells and raise the possibility that BAFF-R expression is necessary for the survival of a subset of neoplastic B lymphocytes analogous to its known role in promoting normal B-cell maturation and survival.


Provocation dose and discriminant analysis in histamine bronchoprovocation. Are the current predictive data satisfactory?
In 20 normal subjects (N) and 20 asthmatic patients (A) using bronchodilators as needed, the PD40, PD10, PD15, PD20, PD10T, and PD20C were measured (PD being provocation dose, subscript being -% delta in Gaw/VL for PD40, lowest FEV1 for PD20C, and best FEV1 for the remaining PDs; 10T means delta FEV1 greater than -10 percent). For discriminant analysis we used an ad hoc graphic (best case) method, a ceiling method based on highest PD in A and two methods (logistic and linear) which considered PDs in both N and A (PDN and PDA, respectively). The distribution of PDN and PDA had substantial overlap and appeared log normal. The PD15, PD20, and PD20C displayed the smallest mean misclassification error followed by PD10T, PD40, and PD10. The linear and logistic methods produced balanced sensitivity and specificity but, predictably, a misclassification error higher than that of the graphic method. The ceiling method proved unsatisfactory with 100 percent sensitivity but approximately equal to 60 percent specificity. Using linear and logistic methods, the posttest likelihood of asthma could be expressed as a function of its pretest likelihood and level of PD recorded. We concluded that: (1) the most discriminant PDs are PD20, PD15 and PD20c; and (2) new normative data for diagnostic bronchoprovocation are needed, because: (a) when PDA and PDN overlap, the currently used ceiling method leads to a high misclassification rate, while the linear and logistic method based on mathematical model have a better discriminant ability; (b) to separate PDA from PDN and allow the application of the ceiling method, "as-needed bronchodilators" is not a reproducible criterion.


Exploring obesity, physical activity, and digital game addiction levels among adolescents: A study on machine learning-based prediction of digital game addiction.
Primary study aim was defining prevalence of obesity, physical activity levels, digital game addiction level in adolescents, to investigate gender differences, relationships between outcomes. Second aim was predicting game addiction based on anthropometric measurements, physical activity levels. Cross-sectional study design was implemented. Participants aged 9-14 living in Kirikkale were part of the study. The sample of the study consists of 405 adolescents, 231 girls (57%) and 174 boys (43%). Self-reported data were collected by questionnaire method from a random sample of 405 adolescent participants. To determine the physical activity levels of children, the Physical Activity Questionnaire for Older Children (PAQ-C). Digital Game addiction was evaluated with the digital game addiction (DGA) scale. Additionally, body mass index (BMI) status was calculated by measuring the height and body mass of the participants. Data analysis were performed using Python 3.9 software and SPSS 28.0 (IBM Corp., Armonk, NY, United States) package program. According to our findings, it was determined that digital game addiction has a negative relationship with physical activity level. It was determined that physical activity level had a negative relationship with BMI. In addition, increased physical activity level was found to reduce obesity and DGA. Game addiction levels of girl participants were significantly higher than boy participants, and game addiction was higher in those with obesity. With the prediction model obtained, it was determined that age, being girls, BMI and total physical activity (TPA) scores were predictors of game addiction. The results revealed that the increase in age and BMI increased the risk of DGA, and we found that women had a 2.59 times greater risk of DGA compared to men. More importantly, the findings of this study showed that physical activity was an important factor reducing DGA 1.51-fold. Our prediction model Logit (P) = 1/(1 + exp(-(-3.384 + Age*0.124 + Gender-boys*(-0.953) + BMI*0.145 + TPA*(-0.410)))). Regular physical activity should be encouraged, digital gaming hours can be limited to maintain ideal weight. Furthermore, adolescents should be encouraged to engage in physical activity to reduce digital game addiction level. As a contribution to the field, the findings of this study presented important results that may help in the prevention of adolescent game addiction.


Long-Term Follow-Up of Men Invited to Participate in a Population-Based Abdominal Aortic Aneurysm Screening Program.
A screening program for abdominal aortic aneurysm (AAA), inviting 65-year-old men, was started in Stockholm in 2010 (2.3 million inhabitants). The aim was to present a long-term follow-up of men participating in screening, as well as AAA repair and ruptures among nonparticipants. Demographics were collected for men with screening detected with AAA 2010 to 2016 (n = 672) and a control group with normal aortas at screening (controls, n = 237). Medical charts and regional Swedvasc (Swedish Vascular registry) data were analyzed for aortic repair for men born 1945 to 1951. Ultrasound maximum aortic diameter (AD) as well as Aortic Size Index (ASI) was recorded. Participation was 78% and prevalence of AAA was 1.2% (n = 672). Aortic repair rates correlated with high ASI and AD. During the study period, 22% of the AAA patients were treated with the elective repair; 35 men in surveillance died (5.2%), non-AAA-related causes (82.9%) dominated, followed by unknown causes among 4 (11.4%), and 2 (5.7%) possibly AAA-related deaths. Abdominal aortic aneurysm rupture rate was higher among nonparticipants (0.096% vs 0.0036%, P < .001). The low dropout rate confirms acceptability of follow-up after screening. The efficacy is shown by the much higher rupture rate among the nonparticipating men.


Characterization of Microsatellites in the Akebia trifoliata Genome and Their Transferability and Development of a Whole Set of Effective, Polymorphic, and Physically Mapped Simple Sequence Repeat Markers.
Akebia trifoliata is a perennial climbing woody liana plant with a high potential for commercial exploitation and theoretical research. Similarly, microsatellites (simple sequence repeats, SSRs) also have dual roles: as critical markers and as essential elements of the eukaryotic genome. To characterize the profile of SSRs and develop molecular markers, the high-quality assembled genome of A. trifoliata was used. Additionally, to determine the potential transferability of SSR loci, the genomes of Amborella trichopoda, Oryza sativa, Vitis vinifera, Arabidopsis thaliana, Papaver somniferum, and Aquilegia coerulea were also used. We identified 434,293 SSRs with abundant short repeats, such as 290,868 (66.98%) single-nucleotide repeats (SNRs) and 113,299 (26.09%) dinucleotide repeats (DNRs) in the A. trifoliata genome. 398,728 (91.81%) SSRs on 344,283 loci were physically mapped on the chromosomes, and a positive correlation (r = 0.98) was found between the number of SSRs and chromosomal length. Additionally, 342,916 (99.60%) potential SSR markers could be designed from the 344,283 physically mapped loci, while only 36,160 could be viewed as high-polymorphism-potential (HPP) markers, findings that were validated by PCR. Finally, SSR loci exhibited broad potential transferability, particularly DNRs such as the "AT/AT" and "AG/CT" loci, among all angiosperms, a finding that was not related to the genetic divergence distance. Practically, we developed a whole set of effective, polymorphic, and physically anchored molecular markers and found that, evolutionarily, DNRs could be responsible for microsatellite origin and protecting gene function.


BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.
Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; p = 0.041). In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.


A Robust Machine Learning Algorithm for the Prediction of Methane Adsorption in Nanoporous Materials.
In the present study, we propose a new set of descriptors that, along with a few structural features of nanoporous materials, can be used by machine learning algorithms for accurate predictions of the gas uptake capacities of these materials. All new descriptors closely resemble the helium atom void fraction of the material framework. However, instead of a helium atom, a particle with an appropriately defined van der Waals radius is used. The set of void fractions of a small number of these particles is found to be sufficient to characterize uniquely the structure of each material and to account for the most important topological features. We assess the accuracy of our approach by examining the predictions of the random forest algorithm in the relative small dataset of the computation-ready, experimental (CoRE) MOFs (∼4700 structures) that have been experimentally synthesized and whose geometrical/structural features have been accurately calculated before. We first performed grand canonical Monte Carlo simulations to accurately determine their methane uptake capacities at two different temperatures (280 and 298 K) and three different pressures (1, 5.8, and 65 bar). Despite the high chemical and structural diversity of the CoRE MOFs, it was found that the use of the proposed descriptors significantly improves the accuracy of the machine learning algorithm, particularly at low pressures, compared to the predictions made based solely on the rest structural features. More importantly, the algorithm can be easily adapted for other types of nanoporous materials beyond MOFs. Convergence of the predictions was reached even for small training set sizes compared to what was found in previous works using the hypothetical MOF database.


Knock out of neuronal nitric oxide synthase exacerbates intestinal ischemia/reperfusion injury in mice.
Recent investigation of the intestine following ischemia and reperfusion (I/R) has revealed that nitric oxide synthase (NOS) neurons are more strongly affected than other neuron types. This implies that NO originating from NOS neurons contributes to neuronal damage. However, there is also evidence of the neuroprotective effects of NO. In this study, we compared the effects of I/R on the intestines of neuronal NOS knockout (nNOS(-/-)) mice and wild-type mice. I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the external muscle layers. Damage to the mucosa and muscle was more severe and greater infiltration by neutrophils occurred in the first 24 h in nNOS(-/-) mice. Immunohistochemistry for the contractile protein, α-smooth muscle actin, was used to evaluate muscle damage. Smooth muscle actin occurred in the majority of smooth muscle cells in the external musculature of normal mice but was absent from most cells and was reduced in the cytoplasm of other cells following I/R. The loss was greater in nNOS(-/-) mice. Basal contractile activity of the longitudinal muscle and contractile responses to nerve stimulation or a muscarinic agonist were reduced in regions subjected to I/R and the effects were greater in nNOS(-/-) mice. Reductions in responsiveness also occurred in regions of operated mice not subjected to I/R. This is attributed to post-operative ileus that is not significantly affected by knockout of nNOS. The results indicate that deleterious effects are greater in regions subjected to I/R in mice lacking nNOS compared with normal mice, implying that NO produced by nNOS has protective effects that outweigh any damaging effect of this free radical produced by enteric neurons.


Acute ethanol administration reduces the antidote effect of N-acetylcysteine after acetaminophen overdose in mice.
1. The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated. 2. Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N-acetylcysteine + ethanol i.p. (same doses as given individually) or saline i.p. (0.4 ml). Survival rates were determined after 24, 48, 72 and 96 h. 3. In the N-acetylcysteine group the survival rate was 85%. This rate was significantly reduced to 43% in the N-acetylcysteine + ethanol group (P = 0.0001). In the groups given ethanol or saline alone only 7% and 3%, respectively, survived 96 h. 4. The data suggest that the protective effect of N-acetylcysteine on acetaminophen-induced toxicity in fed mice is reduced by concomitant administration of ethanol. This may explain the clinical observation that ingestion of ethanol worsens the prognosis after acetaminophen intoxication.


Laboratory diagnosis of human immunodeficiency virus infection.
HIV infection and AIDS will continue to grow as a major medical and social problem. The incidence of heterosexual transmission is rising, and it will become increasingly difficult for physicians and counselors to assess an individual's risk of infection. In coming years, physicians can expect to see patients who are infected, but whose risk may not be apparent, and who may not present with conditions immediately suggestive of their infection. The majority of these patients may not even suspect they are infected. Many of the tests currently available for diagnosing HIV infection are very good. They are both highly sensitive and highly specific and their predictive values are good when their limits are understood. But, as HIV infection expands to an ever larger number of women and children and as the ability to sharply define risk groups fades, demand for a broader range of tests that can reliably confirm infection and are easy to perform can only increase. We have attempted to describe some of the common serologic tests currently used to diagnose HIV infection and some of the limitations of these tests. We also have pointed out that criteria used by laboratories for interpreting tests such as the Western blot may not always be uniform, and physicians should know the criteria used by their reference laboratory and the quality control measures taken. We also have attempted to describe some of the tests available to detect the virus, its genes, or its gene products. PCR and other rapidly evolving gene amplification techniques hold great promise as highly sensitive and specific tests for the diagnosis/confirmation of HIV infection. As with the serologic tests, it is important for those who may use these tests to understand their value as well as their limitations.


Role of c-Myb during prolactin-induced signal transducer and activator of transcription 5a signaling in breast cancer cells.
Implicated in the pathogenesis of breast cancer, prolactin (PRL) mediates its function in part through the prolactin receptor (PRLr)-associated Janus kinase 2 (Jak2)/signal transducer and activator of transcription 5 (Stat5) signaling complex. To delineate the mechanisms of Stat5a regulation in breast cancer, transcription factor-transcription factor (TF-TF) array analysis was employed to identify associated transcriptional regulators. These analyses revealed a PRL-inducible association of Stat5a with the transcription factor and protooncogene c-Myb. Confirmatory co-immunoprecipitation studies using lysates from both T47D and MCF7 breast cancer cells revealed a PRL-inducible association between these transcription factors. Ectopic expression of c-Myb enhanced the PRL-induced expression from both composite and synthetic Stat5a-responsive luciferase reporters. Chromatin immunoprecipitation assays also revealed a PRL-inducible association between c-Myb and endogenous Stat5a-responsive CISH promoter, which was associated with an enhanced expression of CISH gene product at the RNA and protein levels. Small interfering RNA-mediated c-Myb knockdown impaired the PRL-induced mRNA expression of five Stat5-responsive genes. DNA binding-defective mutants of c-Myb, incapable of activating expression from a c-Myb-responsive reporter, maintained their ability to enhance a Stat5a-responsive reporter. At a cellular level, ectopic expression of c-Myb resulted in an increase in T47D proliferation. Taken together, these results indicate that c-Myb potentiates Stat5a-driven gene expression, possibly functioning as a Stat5a coactivator, in human breast cancer.


Permeability of the blood-brain barrier for atenolol studied by positron emission tomography.
The permeability of the blood-brain barrier for atenolol, a hydrophilic beta-adrenergic blocking agent, has been assessed in dogs, by studying the distribution of [11C]atenolol in brain tissue with positron emission tomography. The passage of atenolol into the brain was very limited, but a measurable small net influx into the brain tissues did occur. Osmotic opening of the blood-brain barrier resulted in a marked increase of the atenolol concentrations in brain tissue. The approach described, with sequential non-invasive measurements in brain tissue, is applicable to pharmacokinetic studies of atenolol in man.


Plate-type acoustic metamaterials with strip masses.
Plate-type acoustic metamaterials (PAM) consist of a thin plate with periodically added masses. Similar to membrane-type acoustic metamaterials, PAM exhibit anti-resonances at low frequencies at which the transmission loss can be much higher than the mass-law without requiring a pretension. Most PAM designs previously investigated in literature require the addition of up to thousands of masses per square meter. This makes manufacturing of such PAM prohibitively expensive for most applications. In this contribution, a much simpler PAM design with strip masses is investigated. An analytical model is derived which can be used to estimate the modal properties, effective mass, and oblique incidence sound transmission loss of PAM with strip masses. For high strip masses (compared to the baseplate), this analytical model can be simplified to yield explicit expressions to directly calculate the resonance and anti-resonance frequencies of such PAM. The analytical model is verified using numerical simulations and laboratory measurement results are presented to demonstrate the performance of PAM with strip masses under diffuse field excitation and finite sample size conditions.


The Sensory Gating Inventory-Brief.
The Sensory Gating Inventory (SGI) is a 36-item measure used to assess an individual's subjective ability to modulate, filter, over-include, discriminate, attend to, and tolerate sensory stimuli. Due to its theoretical and empirical link with sensory processing deficits, this measure has been used extensively in studies of psychosis and other psychopathology. The current work fills a need within the field for a briefer measure of sensory gating aberrations that maintains the original measure's utility. For this purpose, large samples (total n = 1552) were recruited from 2 independent sites for item reduction/selection and brief measure validation, respectively. These samples reflected subgroups of individuals with a psychosis-spectrum disorder, at high risk for a psychosis-spectrum disorder, nonpsychiatric controls, and nonpsychosis psychiatric controls. Factor analyses and item-response models were used to create the SGI-Brief (SGI-B; 10 Likert-rated items), a unidimensional self-report measure that retains the original SGI's transdiagnostic (ie, present across disorders) utility and content breadth. Findings show that the SGI-B has excellent psychometric properties (alpha = 0.92) and demonstrates external validity through strong associations with measures of psychotic symptomatology, theoretically linked measures of personality (eg, perceptual dysregulation), and modest associations with laboratory-based sensory processing tasks in the auditory and visual domains on par with the original version. Accordingly, the SGI-B will be a valuable tool for dimensional and transdiagnostic examination of sensory gating abnormalities within clinical science research, while reducing administrator and participant burden.


The Impact of Intracoronary Imaging on PCI Outcomes in Cases Utilising Rotational Atherectomy: An Analysis of 8,417 Rotational Atherectomy Cases from the British Cardiovascular Intervention Society Database.
There is increasing evidence supporting the use of intracoronary imaging to optimize the outcomes of percutaneous coronary intervention (PCI). However, there are no studies examining the impact of imaging on PCI outcomes in cases utilising rotational atherectomy (RA-PCI). Our study examines the determinants and outcomes of using intracoronary imaging in RA-PCI cases including 12-month mortality. Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in the UK between 2007 and 2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural, and outcome associations with intravascular imaging. Intracoronary imaging was used in 1,279 out of 8,417 RA-PCI cases (15.2%). Baseline covariates associated with significantly more imaging use were number of stents used, smoking history, previous CABG, pressure wire use, proximal LAD disease, laser use, glycoprotein inhibitor use, cutting balloons, number of restenosis attempted, off-site surgery, and unprotected left main stem (uLMS) PCI. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (IH-MACCE), its individual components (death, peri-procedural MI, stroke, and major bleed), or 12-month mortality were not significantly altered by the use of imaging in RA-PCI. However, subgroup analysis demonstrated a signal towards reduction in 12-month mortality in uLMS RA-PCI cases utilising intracoronary imaging (OR 0.67, 95% CI 0.44-1.03). Intracoronary imaging use during RA-PCI is associated with higher risk of baseline and procedural characteristics. There were no differences observed in IH-MACCE or 12-month mortality with intracoronary imaging in RA-PCI.


Exploring Modified Rice Straw Biochar as a Sustainable Solution for Simultaneous Cr(VI) and Pb(II) Removal from Wastewater: Characterization, Mechanism Insights, and Application Feasibility.
This study aimed to investigate the efficacy of a rice straw biosorbent in batch adsorption for the removal of chromium (Cr(VI)) and lead (Pb(II)) heavy-metal ions from wastewater. The biosorbent was chemically synthesized and activated by using concentrated sulfuric acid. The produced biosorbent was then characterized by using Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analyses, which provided insights into surface morphology and functional groups. The study examined the effects of pH, rice straw dose, ion concentration, and contact time on metal ion adsorption. Optimal conditions for efficient removal (95.57% for Cr(VI) and 85.68% for Pb(II)) were achieved at a pH of 2.0, a biosorbent dose of 2 g/L, an initial concentration of 20 mg/L, and a contact time of 50 min in synthetic solutions. The isotherms and kinetics model fitting results found that both metal ion adsorption processes were multilayer on the hetero surface of rice straw biosorbent via rate diffusion kinetics. Thermodynamic investigations were conducted, and the results strongly indicate that the adsorption process is endothermic and spontaneous. Notably, the results indicated that the highest desorption rate was achieved by adding 0.3 N HCl to the system.


Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism.
Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18 805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). Site-specific and all solid-cancer mortality. A total of 18 805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14 671 [78.0%]), and most had a Graves disease diagnosis (17 615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P = .002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P = .04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P = .01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.


Sexual dysfunction in patients with polycystic ovary syndrome and its affected domains.
Polycystic Ovary Syndrome (PCOS) is presented with characteristic complications such as chronic an ovulation, obesity, and hyperandrogenism which can affect sexual function in women of reproductive age. Herein we evaluated the frequency and predisposing factors of sexual dysfunction in infertile PCOS patients. In this cross-sectional study, 130 married women with a definite diagnosis of PCOS who were referred due to infertility were recruited. They were evaluated concerning their sexual function in the domains of desire, arousal, lubrication, orgasm, satisfaction and pain with the female sexual function index (FSFI) questionnaire. The frequency of sexual dysfunction was verified 57.7% in PCOS patients with the domains of desire and arousal being commonly affected in 99.2% and 98.5%of cases respectively. BMI had a significant effect on sexual desire and arousal (p=0.02) while the effect of hirsutism was significant on all domains (p<0.001 for total FSFI score) except for dyspareunia. PCOS patients markedly suffer from sexual dysfunction as comorbidity. It seems appropriate to screen all PCOS patients for sexual function with a simple short questionnaire such as FSFI. Targeted interventions could be considered to help improve their quality of life along with other treatments.


Nuclear organization of centromeric domains is not perturbed by inhibition of histone deacetylases.
It is well established that modification of lysines in histone molecules correlates with gene expression and chromatin structure. It is not known whether this operates entirely at a local level, e.g. through the recruitment of specific proteins, or whether histone modifications might impact on more long-range aspects of chromatin organization. There is a distinctive organization of chromatin within the nucleus and the chromatin at the nuclear periphery of mammalian cells appears to be hypoacetylated. Previously it had been suggested that inhibition of histone deacetylases by TSA causes a gross remodeling of nuclear structure, specifically the recruitment of centromeric heterochromatin to the nuclear periphery. Here, we have quantified the nuclear organization of histone modifications and the localization of centromeric domains in human cells before and after TSA treatment. TSA alters the nuclear distribution of histone acetylation, but not that of histone methylation. TSA elevates levels of histone acetylation at the nuclear periphery but we see no alteration in the position of centromeric domains in the nuclei of treated cells. We conclude that the distinctive nuclear localization of centromeric domains is independent of histone acetylation.


Piloting Augmented Reality Technology to Enhance Realism in Clinical Simulation.
We describe a pilot study that incorporated an innovative hybrid simulation designed to increase the perception of realism in a high-fidelity simulation. Prelicensure students (N = 12) cared for a manikin in a simulation lab scenario wearing Google Glass, a wearable head device that projected video into the students' field of vision. Students reported that the simulation gave them confidence that they were developing skills and knowledge to perform necessary tasks in a clinical setting and that they met the learning objectives of the simulation. The video combined visual images and cues seen in a real patient and created a sense of realism the manikin alone could not provide.


The effect of counting system deadtime on thyroid uptake measurements.
Equations are derived and the results of numerical calculations shown that illustrate the effect of counting system deadtime on measured thyroid uptake of radioiodine. It is predicted that the observed uptake is higher than the true uptake due to system deadtime. This is shown for both paralyzing and nonparalyzing deadtime. The effect of increasing the administered activity is shown to increase the measured uptake, in a manner predicted by the paralyzable and nonparalyzable deadtime models.


Differentiating single and multiple victim child sexual abuse cases: a research note considering social disorganization theory.
This study examined the utility of social disorganization theory as an explanation for child sexual abuse with a focus on differentiating single and multiple victim cases. Drawing on 1,172 child sexual abuse cases (including 159 cases with multiple victims) in Orange County, Florida, from 2004 to 2006, the present study considered case characteristics and elements of social disorganization as potential predictors of child sexual abuse cases involving single and multiple victims. We found that social disorganization theory does not successfully predict the locations of multiple victim child sexual abuse incidents and is not useful for distinguishing between child sexual abuse incidents with single or multiple victims.


Biochemical and cellular effects of fish and fish oils.
The renewed interest in fish and fish oil has led to a re-examination of the biochemical and physiological basis of the preventive and therapeutic effects of fish and its components. Fatty acids are produced by a complex synthetic process. Unsaturated fatty acid derived from dietary sources are required for eicosanoid formation and are an integral part of cell wall and mitochondrial membranes. The beneficial role of fish oils is believed to stem from their being rich sources of omega-3 fatty acids. The dietary requirement of these fatty acids is a controversial issue but their essentiality for human health is being increasingly demonstrated and recognized. This review focusses on general aspects of lipid metabolism, biochemistry and physiological role of omega-3 fatty acids, and the unique characteristics of fatty acids found in fish. A subsequent review article will deal with metabolic and clinical aspects.