Infectious diseases in large-scale cat hoarding investigations.
Animal hoarders accumulate animals in over-crowded conditions without adequate nutrition, sanitation, and veterinary care. As a result, animals rescued from hoarding frequently have a variety of medical conditions including respiratory infections, gastrointestinal disease, parasitism, malnutrition, and other evidence of neglect. The purpose of this study was to characterize the infectious diseases carried by clinically affected cats and to determine the prevalence of retroviral infections among cats in large-scale cat hoarding investigations. Records were reviewed retrospectively from four large-scale seizures of cats from failed sanctuaries from November 2009 through March 2012. The number of cats seized in each case ranged from 387 to 697. Cats were screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) in all four cases and for dermatophytosis in one case. A subset of cats exhibiting signs of upper respiratory disease or diarrhea had been tested for infections by PCR and fecal flotation for treatment planning. Mycoplasma felis (78%), calicivirus (78%), and Streptococcus equi subspecies zooepidemicus (55%) were the most common respiratory infections. Feline enteric coronavirus (88%), Giardia (56%), Clostridium perfringens (49%), and Tritrichomonas foetus (39%) were most common in cats with diarrhea. The seroprevalence of FeLV and FIV were 8% and 8%, respectively. In the one case in which cats with lesions suspicious for dermatophytosis were cultured for Microsporum canis, 69/76 lesional cats were culture-positive; of these, half were believed to be truly infected and half were believed to be fomite carriers. Cats from large-scale hoarding cases had high risk for enteric and respiratory infections, retroviruses, and dermatophytosis. Case responders should be prepared for mass treatment of infectious diseases and should implement protocols to prevent transmission of feline or zoonotic infections during the emergency response and when transferring the rescued cats to other shelters or to adopters.


Effects of fentanyl on isoflurane minimum alveolar concentration in New Zealand White rabbits (Oryctolagus cuniculus).
To determine effects of increasing plasma fentanyl concentrations on the minimum alveolar concentration (MAC) of isoflurane in rabbits. 6 adult female New Zealand White rabbits (Oryctolagus cuniculus). Rabbits were anesthetized with isoflurane in oxygen; ventilation was controlled and body temperature maintained between 38.5° and 39.5°C. Fentanyl was administered IV by use of a computer-controlled infusion system to achieve 6 target plasma concentrations. Isoflurane MAC was determined in duplicate by use of the bracketing technique with a supramaximal electrical stimulus. Blood samples were collected for measurement of plasma fentanyl concentration at each MAC determination. The MAC values were analyzed with a repeated-measures ANOVA followed by Holm-Sidak pairwise comparisons. Mean ± SD plasma fentanyl concentrations were 0 ± 0 ng/mL (baseline), 1.2 ± 0.1 ng/mL, 2.2 ± 0.3 ng/mL, 4.4 ± 0.4 ng/mL, 9.2 ± 0.4 ng/mL, 17.5 ± 2.6 ng/mL, and 36.8 ± 2.4 ng/mL. Corresponding mean values for isoflurane MAC were 1.92 ± 0.16%, 1.80 ± 0.16%, 1.60 ± 0.23%, 1.46 ± 0.22%, 1.12 ± 0.19%, 0.89 ± 0.14%, and 0.70 ± 0.15%, respectively. Isoflurane MAC for plasma fentanyl concentrations ≥ 2.2 ng/mL differed significantly from the baseline value. In 3 rabbits, excessive spontaneous movement prevented MAC determination at the highest plasma fentanyl concentration. Fentanyl reduced isoflurane MAC by approximately 60% in New Zealand White rabbits. Further studies will be needed to investigate the cardiorespiratory effects of isoflurane and fentanyl combinations in rabbits; however, fentanyl may prove to be a useful adjunct to inhalation anesthesia in this species.


Molecular basis of levodopa-induced dyskinesias.
A series of experiments were performed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism for the purpose of understanding the mechanism of dopaminergic dyskinesias. Dyskinesias can be induced in this model by de novo treatment with levodopa, or selective D1 or D2 agonists, provided the drugs are short acting and administered in the pulsatile mode. Biochemical analysis of the brains revealed several alterations in dopamine receptor-binding and messenger RNA message following denervation and dopaminergic treatment, but none that clearly correlated with the presence of dyskinesias. On the other hand, gamma-aminobutyric acid (GABA)A binding was increased in the internal segment of the globus pallidus of dyskinetic MPTP monkeys. This was observed consistently and could be associated with an exaggerated response to GABAergic inhibitory inputs in this strategic structure. Increased preproenkephalin message was also found to correlate with dyskinesias and may be linked to changes in GABA receptors. Treatments that caused dyskinesias induced, in the striatum, chronic Fos proteins of the deltaFosB family which, when coupled with Jun-D, form AP-1 complexes that can affect several genes, including enkephalin and N-methyl-D-aspartate receptor. We suggest that levodopa-induced dyskinesias represent a form of pathological learning, which results from deficient gating of glutamatergic inputs to the striatum by dopamine.


Prophylactic Effects of Lidocaine or Beclomethasone Spray on Post-Operative Sore Throat and Cough after Orotracheal Intubation.
Post-operative sore throat and cough are common complications of endotracheal intubation. These conditions may be very distressing for the patient and may lead to unpleasant memories. This study was performed in order to determine whether beclomethasone and lidocaine spray could reduce the frequency of post-operative sore throat and hoarseness after tracheal extubation. Ninety women (18-60 years of age) with an American Society of Anesthesiologists (ASA) physical status I or II and undergoing elective mastoidectomy were randomized into three groups of 30 patients. The endotracheal tubes in each group were sprayed with 50% beclomethasone, 10% lidocaine hydrochloride, or normal saline (control group) before endotracheal intubation. Patients were examined for sore throat (none, mild, moderate, or severe), cough, and hoarseness at 1 and 24 h after extubation. There was a significantly lower incidence and severity of post-operative sore throat in the beclomethasone group than the lidocaine and control groups (P<0.05) at each observation time point. At 24 h after extubation, the incidence and severity of sore throat and cough was significantly lower in the lidocaine compared with the control group. The incidence of hoarseness was not significantly different among the three groups. Spraying beclomethasone and lidocaine on the endotracheal tube is a simple and effective method to reduce the incidence and severity of post-operative sore throat.


Human listeriosis in England, 2001-2007: association with neighbourhood deprivation.
Listeriosis is a rare but severe food-borne disease that predominantly affects pregnant women, the unborn, newborns, the elderly and immunocompromised people. Despite the high mortality rate of the disease, its socio-economic determinants have not been studied in detail, meaning that health inequalities that might exist in relation to this disease are not apparent. Laboratory surveillance data on listeriosis cases reported in England between 2001 and 2007 were linked to indices of deprivation and denominator data using patients' postcodes. Incidence relative to increasing quintiles of deprivation was calculated by fitting generalised linear models while controlling for population size. Patient food purchasing and consumption data were scrutinised and compared with commercial food purchasing denominator data to further quantify the observed differences in disease incidence. For all patient groups, listeriosis incidence was highest in the most deprived areas of England when compared with the most affluent, and cases were more likely to purchase foods from convenience stores or from local services (bakers, butchers, fishmongers and greengrocers) than the general population were. Patients' risk profile also changed with increasing neighbourhood deprivation. With increased life expectancy and rising food prices, food poverty could become an increasingly important driver for foodborne disease in the future. While United Kingdom Government policy should continue to focus on small food businesses to ensure sufficient levels of food hygiene expertise, tailored and targeted food safety advice on the avoidance of listeriosis is required for all vulnerable groups. Failure to do so may enhance health inequality across socio-economic groups.


Dorsal Hippocampal Actin Polymerization Is Necessary for Activation of G-Protein-Coupled Estrogen Receptor (GPER) to Increase CA1 Dendritic Spine Density and Enhance Memory Consolidation.
Activation of the membrane estrogen receptor G-protein-coupled estrogen receptor (GPER) in ovariectomized mice via the GPER agonist G-1 mimics the beneficial effects of 17β-estradiol (E2) on hippocampal CA1 spine density and memory consolidation, yet the cell-signaling mechanisms mediating these effects remain unclear. The present study examined the role of actin polymerization and c-Jun N-terminal kinase (JNK) phosphorylation in mediating effects of dorsal hippocampally infused G-1 on CA1 dendritic spine density and consolidation of object recognition and spatial memories in ovariectomized mice. We first showed that object learning increased apical CA1 spine density in the dorsal hippocampus (DH) within 40 min. We then found that DH infusion of G-1 increased both CA1 spine density and phosphorylation of the actin polymerization regulator cofilin, suggesting that activation of GPER may increase spine morphogenesis through actin polymerization. As with memory consolidation in our previous work (Kim et al., 2016), effects of G-1 on CA1 spine density and cofilin phosphorylation depended on JNK phosphorylation in the DH. Also consistent with our previous findings, E2-induced cofilin phosphorylation was not dependent on GPER activation. Finally, we found that infusion of the actin polymerization inhibitor, latrunculin A, into the DH prevented G-1 from increasing apical CA1 spine density and enhancing both object recognition and spatial memory consolidation. Collectively, these data demonstrate that GPER-mediated hippocampal spinogenesis and memory consolidation depend on JNK and cofilin signaling, supporting a critical role for actin polymerization in the GPER-induced regulation of hippocampal function in female mice.SIGNIFICANCE STATEMENT Emerging evidence suggests that G-protein-coupled estrogen receptor (GPER) activation mimics effects of 17β-estradiol on hippocampal memory consolidation. Unlike canonical estrogen receptors, GPER activation is associated with reduced cancer cell proliferation; thus, understanding the molecular mechanisms through which GPER regulates hippocampal function may provide new avenues for the development of drugs that provide the cognitive benefits of estrogens without harmful side effects. Here, we demonstrate that GPER increases CA1 dendritic spine density and hippocampal memory consolidation in a manner dependent on actin polymerization and c-Jun N-terminal kinase phosphorylation. These findings provide novel insights into the role of GPER in mediating hippocampal morphology and memory consolidation, and may suggest first steps toward new therapeutics that more safely and effectively reduce memory decline in menopausal women.


A Comparison of Social Robot to Tablet and Teacher in a New Script Learning Context.
This research occurred in a special context where Kazakhstan's recent decision to switch from Cyrillic to the Latin-based alphabet has resulted in challenges connected to teaching literacy, addressing a rare combination of research hypotheses and technical objectives about language learning. Teachers are not necessarily trained to teach the new alphabet, and this could result in a challenge for children with learning difficulties. Prior research studies in Human-Robot Interaction (HRI) have proposed the use of a robot to teach handwriting to children (Hood et al., 2015; Lemaignan et al., 2016). Drawing on the Kazakhstani case, our study takes an interdisciplinary approach by bringing together smart solutions from robotics, computer vision areas, and educational frameworks, language, and cognitive studies that will benefit diverse groups of stakeholders. In this study, a human-robot interaction application is designed to help primary school children learn both a newly-adopted script and also its handwriting system. The setup involved an experiment with 62 children between the ages of 7-9 years old, across three conditions: a robot and a tablet, a tablet only, and a teacher. Based on the paradigm-learning by teaching-the study showed that children improved their knowledge of the Latin script by interacting with a robot. Findings reported that children gained similar knowledge of a new script in all three conditions without gender effect. In addition, children's likeability ratings and positive mood change scores demonstrate significant benefits favoring the robot over a traditional teacher and tablet only approaches.


The impact of severe preeclampsia on maternal quality of life.
Preeclampsia (PE) is a serious life event that can change women's psychological profile. The aim of this study was to evaluate the physical and mental health-related quality of life (HR-QoL) in women after PE and the impact of contributing factors. Ninety-five women who had suffered from PE answered the Short-Form-12 Health Survey on general state of health. Comparison was made with the reference values and among the study cohorts, namely mild (14.7 %), severe (74.7 %) and superimposed PE (10.5 %). Medical parameters were evaluated as additional factors, and age served as covariate. Quality of mental life was significantly worse in all patients (p < 0.01), especially in those after severe PE (p < 0.01) compared to the reference range. These women demonstrated significantly worse results than those affected by the mild form (p = 0.03). Women who had had superimposed PE were neither physically nor mentally impaired compared to the standard population values (p = 0.94 and p = 0.90, respectively). After controlling for medical parameters and age, differences remained statistically significant. Multiparous women scored significantly worse on the mental scale than primiparous (p = 0.02), and pregnant women scored significantly worse than non-pregnant women on the physical level (p = 0.04). This study shows that women who have suffered from severe PE are substantially reduced in their mental quality of life. An extensive medical care including HR-QoL parameters might improve pregnancy outcome.


Hippocampal anatomy supports the use of context in object recognition: a computational model.
The human hippocampus receives distinct signals via the lateral entorhinal cortex, typically associated with object features, and the medial entorhinal cortex, associated with spatial or contextual information. The existence of these distinct types of information calls for some means by which they can be managed in an appropriate way, by integrating them or keeping them separate as required to improve recognition. We hypothesize that several anatomical features of the hippocampus, including differentiation in connectivity between the superior/inferior blades of DG and the distal/proximal regions of CA3 and CA1, work together to play this information managing role. We construct a set of neural network models with these features and compare their recognition performance when given noisy or partial versions of contexts and their associated objects. We found that the anterior and posterior regions of the hippocampus naturally require different ratios of object and context input for optimal performance, due to the greater number of objects versus contexts. Additionally, we found that having separate processing regions in DG significantly aided recognition in situations where object inputs were degraded. However, split processing in both DG and CA3 resulted in performance tradeoffs, though the actual hippocampus may have ways of mitigating such losses.


Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy: the experience of Japanese multi-institutions.
To investigate oncological outcomes and prognostic factors in patients with upper tract urothelial carcinoma (UTUC) who experienced disease recurrence after radical nephroureterectomy (RNU). Few studies have focused on the clinical courses of patients who experienced disease recurrence after RNU. A total of 204 UTUC patients who experienced disease recurrence from a retrospective multi-institutional cohort were included in the present study. Associated patient outcomes were analyzed using multivariate analysis. The mean time from RNU to first disease recurrence was 15.0 months and ≈90% of patients experienced disease recurrence within the first 3 years after RNU. During a median follow-up of 8.1 month after disease recurrence, 165 patients died from UTUC and five patients died from other causes. In the 204 cohorts, 1- and 3-year cancer-specific survival rates were 40.2% and 9.7%, respectively, and 1- and 3-year overall survival rates were 39.5% and 9.4%, respectively. After disease recurrence, 132 patients underwent systemic chemotherapy, and a subgroup analysis of patients who underwent systemic chemotherapy multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently prognostic of cancer-specific and overall survival after relapsing. According to three significant variables, 1- and 3-year cancer-specific survival rates were 72.7% and 20.8% in patients with no risk factors, 46.5% and 7.5% in patients with one risk factor, and 26.4% and 4.4% in patients with two or three risk factors, respectively (P < 0.001). Most patients died from UTUC within 3 years, even though systemic chemotherapies were administered after relapsing. Multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently related to poor survival after systemic chemotherapy.


[Apoptotic deregulation of endothelial cells and intimal proliferation in pulmonary hypertension of congenital heart disease].
To assess the cellular and histological basis of irreversible pulmonary hypertension (PHT) in the clinical setting of congenital heart disease (CHD). Although many children with CHD develop pulmonary vascular disease, it is unclear why this complication is reversible after complete repair in some cases but irreversible in others. As failure of endothelial cell apoptosis might lead to intimal proliferation and lack of reversibility of PHT, we investigated this and other key markers of vasoactivity and angiogenesis, in subjects with PHT and CHD. We assessed anti- and pro-apoptotic markers in vascular and perivascular cells in lung biopsies from 18 patients with CHD; 7 with reversible and 11 with irreversible PHT, and from 6 controls. Immunostaining for eNOS, VEGF and CD34 (markers of vasoactivity and neoangiogenesis) was also performed. The anti-apoptotic protein Bcl-2 was highly expressed by pulmonary endothelial cells in all cases of irreversible PHT but in no cases of reversible PHT, nor in controls (p<0.001). Intimal proliferation was present in 10/11 irreversible PHT cases but never observed in reversible PHT (p<0.001). Similarly, perivascular inflammatory T-cells expressed more anti-apoptotic proteins in irreversible PHT (p<0.01). Irreversible PHT cases were also more likely to show compensatory up-regulation of VEGF and new small vessel formation at the sites of native vessel stenosis or occlusion (p<0.001). Irreversible PHT is strongly associated with impaired endothelial cell apoptosis and anti-apoptotic signalling from perivascular inflammatory cells. These changes are associated with intimal proliferation and vessel narrowing and thereby may contribute to clinical outcomes associated with pulmonary hypertension. Markers of apoptosis and angiogenesis were assessed in lung biopsies of subjects with pulmonary hypertension (PHT) due to congenital heart disease (CHD). The anti-apoptotic protein Bcl-2 was strongly expressed by pulmonary endothelial cells in irreversible PHT (n=11) but never in reversible PHT (n=7) (p<0.01). Irreversible PHT was also associated with up-regulation of VEGF and new vessel formation around occluded native vessels (p<0.01).


Gallbladder epithelial cells that engraft in mouse liver can differentiate into hepatocyte-like cells.
We tested the hypothesis that well-differentiated gallbladder epithelial cells (GBECs) are capable of engrafting and surviving in murine liver and acquire phenotypic characteristics of hepatocytes. GBECs isolated from transgenic mice that constitutively express green fluorescent protein (GFP) were either cultured before transplantation or transplanted immediately following isolation. Recipient mice with severe-combined immunodeficiency underwent retrorsine treatment and either partial hepatectomy before transplantation or carbon tetrachloride treatment following transplantation. From 1 to 4 months following transplantation, the livers of recipient mice contained discrete colonies of GFP(+) cells. Most GFP(+) cells surrounded vesicles, were epithelial cell-like in morphology, and expressed the biliary epithelial markers cytokeratin 19 and carbonic anhydrase IV. Subpopulations of GFP(+) cells resembled hepatocytes morphologically and expressed the hepatocyte-specific markers connexin-32 and hepatic nuclear factor-4alpha, but not cytokeratin 19 or carbonic anhydrase IV. At 4 months, cells in GFP(+) colonies were not actively proliferating as determined by proliferating cell nuclear antigen expression. Thus, GBECs are capable of engrafting and surviving in damaged mouse livers, and some can differentiate into cells with hepatocyte-like features. These findings suggest that environmental cues in the recipient liver are sufficient to allow a subpopulation of donor GBECs to differentiate into hepatocyte-like cells in the absence of exogenous transcriptional reprogramming. GBECs might be used as donor cells in a cell transplantation approach for the treatment of liver disease.


[Intestinal transplantation--an experimental therapy which has become a realistic alternative].
Outcome after intestinal transplantation has improved dramatically since the introduction of novel immunosuppressive agents and refined surgical techniques. Small bowel transplantation is now considered to be the best treatment modality for patients with life threatening complications of intestinal failure and parenteral nutrition. We hereby review the international experience as well as the first ten cases of intestinal transplantation performed in Sweden.


Crk associates with a multimolecular Paxillin/GIT2/beta-PIX complex and promotes Rac-dependent relocalization of Paxillin to focal contacts.
We have previously demonstrated that the CrkII and CrkL adapter proteins are required for the spreading of epithelial colonies and the breakdown of adherens junctions in response to hepatocyte growth factor. When overexpressed, CrkII and CrkL promote lamellipodia formation, cell spreading, and the loss of epithelial adherens junctions in the absence of hepatocyte growth factor. The exact mechanism by which Crk proteins elicit these changes is unclear. We show that the overexpression of CrkII or CrkL, but not Src homology 2 or amino-terminal Src homology 3 domain mutant Crk proteins, promotes the relocalization of Paxillin to focal contacts throughout the cell and within lamellipodia in a Rac-dependent manner. In stable cell lines overexpressing CrkII, enhanced lamellipodia formation and cell spreading correlate with an increased association of CrkII with Paxillin, GIT2 (an ARF-GAP) and beta-PIX (a Rac1 exchange factor). Mutants of Paxillin that fail to associate with Crk or GIT2, or do not target to focal adhesions inhibit Crk-dependent cell spreading and lamellipodia formation. We conclude from these studies that the association of Crk with Paxillin is important for the spreading of epithelial colonies, by influencing the recruitment of Paxillin to focal complexes and promoting the enhanced assembly of Paxillin/GIT2/beta-PIX complexes.


Working memory deficits in neuronal nitric oxide synthase knockout mice: potential impairments in prefrontal cortex mediated cognitive function.
Neuronal nitric oxide synthase (nNOS) forms nitric oxide (NO), which functions as a signaling molecule via S-nitrosylation of various proteins and regulation of soluble guanylate cyclase (cGC)/cyclic guanosine monophosphate (cGMP) pathway in the central nervous system. nNOS signaling regulates diverse cellular processes during brain development and molecular mechanisms required for higher brain function. Human genetics have identified nNOS and several downstream effectors of nNOS as risk genes for schizophrenia. Besides the disease itself, nNOS has also been associated with prefrontal cortical functioning, including cognition, of which disturbances are a core feature of schizophrenia. Although mice with genetic deletion of nNOS display various behavioral deficits, no studies have investigated prefrontal cortex-associated behaviors. Here, we report that nNOS knockout (KO) mice exhibit hyperactivity and impairments in contextual fear conditioning, results consistent with previous reports. nNOS KO mice also display mild impairments in object recognition memory. Most importantly, we report for the first time working memory deficits, potential impairments in prefrontal cortex mediated cognitive function in nNOS KO mice. Furthermore, we demonstrate Disrupted-in-Schizophrenia 1 (DISC1), another genetic risk factor for schizophrenia that plays roles for cortical development and prefrontal cortex functioning, including working memory, is a novel protein binding partner of nNOS in the developing cerebral cortex. Of note, genetic deletion of nNOS appears to increase the binding of DISC1 to NDEL1, regulating neurite outgrowth as previously reported. These results suggest that nNOS KO mice are useful tools in studying the role of nNOS signaling in cortical development and prefrontal cortical functioning.


Interaction of Salmonella enterica serotype Typhimurium with dendritic cells is defined by targeting to compartments lacking lysosomal membrane glycoproteins.
Dendritic cells (DCs) play a central role in the generation of acquired immunity to infections by pathogenic microorganisms. Salmonella enterica serotype Typhimurium is known to survive and proliferate intracellularly within macrophages and nonphagocytic cells, but no data exist on how this pathogen interacts with DCs. In this report, we show the capacity of serotype Typhimurium to survive within the established mouse DC line CB1. In contrast to the case for the macrophage model, the compartments of DCs containing serotype Typhimurium are devoid of lysosomal membrane glycoproteins and the PhoPQ two-component regulatory system is not essential for pathogen intracellular survival.


Obesity, Cardiovascular Disease, and the Promising Role of Semaglutide: Insights from the SELECT Trial.
Cardiovascular disease (CVD) is a leading global cause of death, with preventable risk factors like obesity contributing most to it. Obesity's association with CVD originate from factors like inflammation, insulin resistance, and altered lipid profiles. Obesity also raises the risk of atrial fibrillation (AF) and sudden cardiac death. Semaglutide, a GLP-1 receptor agonist, initially used for weight loss and diabetes, emerged as a breakthrough in CVD prevention. The SELECT trial assessed semaglutide's impact on major adverse cardiovascular events (MACE). In this double-blind, placebo-controlled trial, 17,604 adults with CVD and obesity were given a weekly 2.4 mg dose of semaglutide or placebo. The trial observed a significant 20% reduction in MACE risk for those receiving semaglutide, demonstrating its potential in obesity-associated CVD prevention. This shift marks a transformative approach to obesity management and CVD prevention. However, further research is needed to fully comprehend semaglutide's cardiovascular benefits and potential risks.


Incidence and predictive factors for malignancies with dermatomyositis: a cohort from southern China.
We aimed to explore the incidence of malignancy in dermatomyositis and assess the potential risk factors of occurrence of malignancy in DM from southern China. A retrospective cohort study of patients admitted in the 1st affiliated university hospital between 2003 and 2012 was performed. Demographic information, clinical symptoms, laboratory findings, medications were documented. The endpoint of the study was defined as occurrence of malignancy or death. For this approximately 10-year retrospective study, 60 out of 246 dermatomyositis patients developed malignancies with the overall incidence of 24.4%. Nasopharyngeal carcinoma (NPC) and ovarian carcinoma were the most common malignant disease, accounting for 35% (21/60) and 15% (9/60) of malignancies, respectively. Lung and colon were followed as the third most common carcinoma (5 out of 60, 8.3%). Among these 60 patients with malignancies, 39 (65.0%, 39/60) cases occurred within 1 year after DM diagnosis. Subsequently, malignancies were detected in 13 (21.7%, 13/60) patients during the second year and 8 (13.3%, 8/60) during the third year. One patient developed cancer at the 35th month after DM as the latest. The logistic regression multivariate analysis indicated that male gender [odds ratio (OR) = 3.76, 95% confidence interval (CI ) 1.86~7.61, p<0.01], dysphagia (OR= 2.21, 95%CI 1.10~4.48, p=0.03) and elevated erythrocyte sedimentation rate (ESR) (OR= 2.37, 95% CI 1.18~4.75, p=0.02) were risk factors for the occurrence of malignancies, while interstitial lung disease (ILD) acted as a protective factor (OR=0.13, 95%CI 0.06~0.28, p<0.01). It was necessary to carry out routine malignancy screening for Chinese DM patients due to its high incidence. Nasopharyngeal carcinoma and ovarian cancer were the most common malignant disease. The risk of malignancy was highest in the first year after DM diagnosis and reduced thereafter. Extensive work-ups for malignancy screening should be carried out at the first year. Male gender, dysphagia and elevated ESR were risk factors for occurrence of malignancy. The presence of ILD could diminish the risk of coexisting of malignancy.


Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic-neurohypophysial explants.
Glucocorticoids inhibit and glucocorticoid deficiency increases vasopressin (AVP) release in vivo. To determine whether the effect of glucocorticoids is hypothalamic and mediated via a glucocorticoid receptor, explants of the hypothalamic-neurohypophysial system were used to measure AVP release during agonist and antagonist exposure. Explants from adult rats, which contained AVP neurons of the supraoptic nucleus with axonal projections terminating in the neural lobe but excluded the paraventricular nucleus, were perifused with an osmotic stimulus (increase of 5 mosmol/h over 6 h) in the absence or presence of corticosterone (100 micrograms/dl) or with corticosterone (100 micrograms/dl) in the absence or presence of the glucocorticoid antagonist RU-486 (10 microM). AVP release was not increased during osmotic stimulation in the presence of corticosterone (Cort) and was 20-30% lower than osmotically stimulated release observed in the absence of Cort. RU-486 reversed the inhibitory effect of corticosterone on AVP release. No changes in AVP mRNA content were detected. These results suggest that Cort inhibits osmotically stimulated AVP release by a direct effect within the hypothalamus and/or neurohypophysis. This effect is mediated by the glucocorticoid receptor through either genomic or nongenomic mechanisms.


Interleukin 1beta and progesterone stimulate activin a expression and secretion from cultured human endometrial stromal cells.
Steroid hormones, cytokines, and growth factors have a major role in evoking local endometrial changes needed for trophoblast implantation. In the present study, the effect of interleukin-1beta (IL-1beta), 17-beta estradiol (E2), and progesterone (Pr) on activin A and follistatin (FS) secretion from cultured human endometrial stromal cells (HESCs) is evaluated. HESCs were obtained from healthy human endometrial samples (n = 8) collected from healthy women. The cells were cultured and stimulated with E2 (10(-7) M, 10(-6)M), Pr (10(-7)M, 10(-6)M), IL-1beta (500 pg/mL), IL-1beta (500 pg/mL) + E2 (10(-6)M), and IL-1beta (500 pg/mL) + Pr (10(-6)M). Activin A and FS secretion and mRNA expression were assayed by enzyme-linked immunosorbent assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. Pr (10(-7) M, 10(-6) M) significantly increased activin A secretion and mRNA expression from HESCs, but E2 did not show remarkable effects. The addition of IL-1beta (P< .001), IL- 1beta + E2 (P < .01), and IL-1beta + Pr (P< .001). significantly stimulated activin A secretion and mRNA expression, compared to untreated cells. Activin A expression and secretion after the coincubation of IL-1beta+ Pr were significantly higher than after IL-1betaand IL-1beta+ E2 stimuli ( P< .01 and P< .001, respectively). Neither Pr nor E2 and IL-1beta had a significant effect on FS secretion and expression. IL-1betaand Pr stimulated activin A but not FS secretion from cultured HESCs, and the effect of IL-1betawas augmented by Pr. These findings, together with the evidence that activin A is involved in trophoblast implantation, suggest the existence of a complex cross-talk by which the ovary, through Pr secretion, and the embryo, through IL-1beta production, may trigger the endometrial induction of activin A and consequently timing implantation.


[Changes in the tempo parameters of speech in the dynamics of depressions].
The paper is devoted to study of methods for evaluation of the state of depressive patients by the parameters characterizing the rate of their speech. It is found that elongation of mean durations of pauses and decrease of mean durations of clear speech at the height of pathologic process testify to the presence of depressive affect of anguish. Short pauses with long portions of clear speech are typical for the patients with affects of alarm. In the study of psychomotor disturbances of depressive patients it was shown that the motor component was the most reflected in such characteristic of the speech rate as mean duration of clear speech and the ideatory one--in mean duration of pauses. Analysis of speech rate characteristics confirmed the significance of the ideatory inhibition in diagnostics of alarm endogenous depressions and ideatory excitation at psychogenic variants.


Bioactivity and efficacy of a hyperimmune bovine colostrum product- Travelan, against shigellosis in a non-Human primate model (Macaca mulatta).
Infectious diarrhea is a World Health Organization public health priority area due to the lack of effective vaccines and an accelerating global antimicrobial resistance crisis. New strategies are urgently needed such as immunoprophylactic for prevention of diarrheal diseases. Hyperimmune bovine colostrum (HBC) is an established and effective prophylactic for infectious diarrhea. The commercial HBC product, Travelan® (Immuron Ltd, Australia) targets multiple strains of enterotoxigenic Escherichia coli (ETEC) is highly effective in preventing diarrhea in human clinical studies. Although Travelan® targets ETEC, preliminary studies suggested cross-reactivity with other Gram-negative enteric pathogens including Shigella and Salmonella species. For this study we selected an invasive diarrheal/dysentery-causing enteric pathogen, Shigella, to evaluate the effectiveness of Travelan®, both in vitro and in vivo. Here we demonstrate broad cross-reactivity of Travelan® with all four Shigella spp. (S. flexneri, S. sonnei, S. dysenteriae and S. boydii) and important virulence factor Shigella antigens. Naïve juvenile rhesus macaques (NJRM) were randomized, 8 dosed with Travelan® and 4 with a placebo intragastrically twice daily over 6 days. All NJRM were challenged with S. flexneri 2a strain 2457T on the 4th day of treatment and monitored for diarrheal symptoms. All placebo-treated NJRM displayed acute dysentery symptoms within 24-36 hours of challenge. Two Travelan®-treated NJRM displayed dysentery symptoms and six animals remained healthy and symptom-free post challenge; resulting in 75% efficacy of prevention of shigellosis (p = 0.014). These results strongly indicate that Travelan® is functionally cross-reactive and an effective prophylactic for shigellosis. This has positive implications for the prophylactic use of Travelan® for protection against both ETEC and Shigella spp. diarrheal infections. Future refinement and expansion of pathogens recognized by HBC including Travelan® could revolutionize current management of gastrointestinal infections and outbreaks in travelers' including military, peacekeepers, humanitarian workers and in populations living in endemic regions of the world.


Palladium-catalyzed oxidative aryltrifluoromethylation of activated alkenes at room temperature.
A palladium-catalyzed intramolecular oxidative aryltrifluoromethylation reaction of activated alkenes has been explored. The reaction allows for an efficient synthesis of a variety of CF(3)-containing oxindoles. Preliminary mechanistic study indicated that the reaction involves a C(sp(3))-Pd(IV)(CF(3)) intermediate, which undergoes reductive elimination to afford a C(sp(3))-CF(3) bond.


Effect of Beta-sitosterol on cholesterol-cholic acid-induced gallstone formation in mice.
Beta-sitosterol has been shown to prevent gallstone formation in mice fed 1.2% cholesterol and 0.5% cholic acid (lithogenic diet). The incidence of gallstone formation in the mouse by the addition of 2.5% sitosterol in the lithogenic diet is about 35.5% in male and 25% in female. The condition of the liver, whether fatty or normal, did not correlate with the presence or absence of cholelithiasis. The serum and liver cholesterol levels of mice fed either sitosterol and cholesterol or sitosterol and cholic acid is lower than those of mice fed cholesterol or cholic acid alone. Elevation of liver phospholipid concentration was noticed in mice fed sitosterol or a combination of sitosterol with cholesterol or cholic acid or both cholesterol and cholic acid.


The attributes of an effective teacher differ between the classroom and the clinical setting.
Most training programs use learners' subjective ratings of their teachers as the primary measure of teaching effectiveness. In a recent study we found that preclinical medical students' ratings of classroom teachers were associated with perceived charisma and physical attractiveness of the teacher, but not intellect. Here we explored whether the relationship between these variables and teaching effectiveness ratings holds in the clinical setting. We asked 27 Internal Medicine residents to rate teaching effectiveness of ten teachers with whom they had worked on a clinical rotation, in addition to rating each teacher's clinical skills, physical attractiveness, and charisma. We used linear regression to study the association between these explanatory variables and teaching effectiveness ratings. We found no association between rating of physical attractiveness and teaching effectiveness. Clinical skill and charisma were independently associated with rating of teaching effectiveness (regression coefficients [95 % confidence interval] 0.73 [0.60, 0.85], p < 0.001 and 0.12 [0.01, 0.23], p = 0.03, respectively). The variables associated with effectiveness of classroom and clinical teachers differ, suggesting context specificity in teaching effectiveness ratings. Context specificity may be explained by differences in the exposure that learners have to teachers in the classroom versus clinical setting-so that raters in the clinical setting may base ratings upon observed behaviours rather than stereotype data. Alternatively, since subjective ratings of teaching effectiveness inevitably incorporate learners' context-specific needs, the attributes that make a teacher effective in one context may not meet the needs of learners in a different context.


Biliary excretion of the halothane metabolite trifluoroacetic acid in infants.
In humans the biliary excretion of trifluoroacetic acid, the major halothane metabolite, has not been studied. We investigated the biliary excretion of trifluoroacetic acid in two infants aged five months and two months following halothane anaesthesia for the operation of choledocholithotomy. Bile, urine and faeces were collected continuously for five days after operation and trifluoroacetic acid excretion measured. Estimates of halothane uptake, daily bile flow and the proportion of daily bile flow collected via the T-tube drainage catheter were subject to percentage errors possibly as large as 50%. Of the total trifluoroacetic acid produced from halothane metabolism, it was estimated that 17% in the five-month-old infant and 20% in the two-month infant was excreted in bile. In the five-month-old infant where approximately 80% of the bile produced entered the duodenum in the normal way, no faecal trifluoroacetic acid was detected suggesting an enterohepatic circulation for this metabolite.


Atomistic real-space observation of the van der Waals layered structure and tailored morphology in VSe2.
Two-dimensional (2D) transition metal dichalcogenides with van der Waals gaps have attracted much attention due to their peculiarly distinctive physical properties from their bulk counterparts. Among them, vanadium diselenide (VSe2) has been considered to be a promising candidate for future spintronic devices, as room temperature ferromagnetism was reported recently. However, detailed crystallography and properties of VSe2 nanosheets have been less explored. Here, we report the atomistic real-space observation of the van der Waals layered structure of VSe2 for the first time. Furthermore, simply by controlling the carrier gas flow rate, a morphological variation of the surface area and thickness of VSe2 nanosheets was observed. The room temperature ferromagnetic feature of single VSe2 nanosheets was also revealed by magnetic force microscopy measurements. Our findings will play a significant role in the research of intrinsic 2D ferromagnetic materials.


Sites of symptomatic gas retention during intestinal lipid perfusion in healthy subjects.
Gas pooling within the gut may produce abdominal symptoms but the segment of the intestine responsible for gas retention is unknown. Our aim was to determine the role of the proximal and distal bowel in symptomatic gas accumulation using an experimental model of gas retention triggered by intraluminal lipids. Sixteen healthy subjects. A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the intestine at12 ml/min for three hours and gas evacuation was continuously measured via an anal cannula connected to a barostat. Abdominal perception and girth changes were measured at 10 minute intervals. Lipids (1 kcal/min) were simultaneously perfused either into the duodenum (n = 8) or into the ileum (n = 8). Each subject was studied twice on separate days, with gas infused into the jejunum or ileum. Duodenal lipids produced retention of gas infused into the jejunum (646 (62) ml) but the volume retained was much smaller when gas was infused directly into the ileum (262 (90) ml; p<0.05). The effects on gas retention were even more pronounced during ileal perfusion of lipids (1546 (184) ml during jejunal gas infusion and 847 (142) ml during ileal gas infusion; p<0.05). Abdominal distension correlated with the volume of gas retained (r = 0.87; p<0.001). Healthy subjects tolerated gas retention, and significant symptoms (score 3.7 (0.8)) developed only during jejunal gas infusion plus ileal lipid perfusion when gas retention was very large. Intraluminal lipids induce intestinal gas retention, predominantly acting on the proximal small bowel.


MS4--Multi-Scale Selector of Sequence Signatures: an alignment-free method for classification of biological sequences.
While multiple alignment is the first step of usual classification schemes for biological sequences, alignment-free methods are being increasingly used as alternatives when multiple alignments fail. Subword-based combinatorial methods are popular for their low algorithmic complexity (suffix trees ...) or exhaustivity (motif search), in general with fixed length word and/or number of mismatches. We developed previously a method to detect local similarities (the N-local decoding) based on the occurrences of repeated subwords of fixed length, which does not impose a fixed number of mismatches. The resulting similarities are, for some "good" values of N, sufficiently relevant to form the basis of a reliable alignment-free classification. The aim of this paper is to develop a method that uses the similarities detected by N-local decoding while not imposing a fixed value of N. We present a procedure that selects for every position in the sequences an adaptive value of N, and we implement it as the MS4 classification tool. Among the equivalence classes produced by the N-local decodings for all N, we select a (relatively) small number of "relevant" classes corresponding to variable length subwords that carry enough information to perform the classification. The parameter N, for which correct values are data-dependent and thus hard to guess, is here replaced by the average repetitivity kappa of the sequences. We show that our approach yields classifications of several sets of HIV/SIV sequences that agree with the accepted taxonomy, even on usually discarded repetitive regions (like the non-coding part of LTR). The method MS4 satisfactorily classifies a set of sequences that are notoriously hard to align. This suggests that our approach forms the basis of a reliable alignment-free classification tool. The only parameter kappa of MS4 seems to give reasonable results even for its default value, which can be a great advantage for sequence sets for which little information is available.


Bovine serum albumin adsorption onto immobilized organotrichlorosilane surface: influence of the phase separation on protein adsorption patterns.
Octadecyltrichlorosilane (OTS) and [2-(perfluorooctyl)ethyl]trichlorosilane (FOETS) monolayers and their mixed monolayer were polymerized on a water subphase and subsequently immobilized onto a silicon wafer surface by covalent bonding. Atomic force microscopic (AFM) observation of the mixed (OTS/FOETS) monolayer revealed the formation of a phase-separated structure. Protein-adsorption behavior onto the monolayers was investigated in situ on the basis of an attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopic flow cell method and the morphology of the monolayer surface-adsorbed bovine serum albumin (BSA) was observed by AFM. Protein adsorption behavior observed by ATR-FT-IR flow cell method revealed that the amount of BSA adsorption onto the OTS and FOETS monolayers increased remarkably at an initial experimental stage and attained a steady state within a few minutes at pH 7.5. The amount of steady state adsorption was c. 0.18-0.2 microgcm(-2). AFM observation of the monolayer after exposure to BSA solution suggested that BSA adsorbed in the end-on adsorption state on OTS monolayer and side-on one in the FOETS monolayer, respectively. However, in the case of the mixed (OTS/FOETS) monolayer, ATR-FT-IR flow cell experiment revealed that the amount of steady state adsorption of BSA was suppressed. Also, AFM observation revealed that at pH 7.5, BSA preferentially adsorbed onto the FOETS phase of the mixed (OTS/FOETS) monolayer, which had a higher interfacial free energy against water. On the other hand, BSA adsorbed homogeneously onto the OTS and FOETS phases at the isoelectric point of BSA (pH 4.7). These results indicate that the preferential adsorption of BSA onto the FOETS phase in the mixed (OTS/FOETS) monolayer system is due to: (1) the minimization of the interfacial free energy between a monolayer surface and an aqueous solution; and (2) the electrostatic repulsion between BSA molecules bearing negative charges.


Effect of triclosan on the formation of crystalline biofilms by mixed communities of urinary tract pathogens on urinary catheters.
The crystalline bacterial biofilms that encrust Foley catheters compromise the care of many elderly and disabled patients. The aim of this study was to examine whether the biocide triclosan can prevent encrustation by the mixed flora of uropathogens that commonly infect patients undergoing long-term catheterization. Models of the catheterized bladder were inoculated with communities of organisms isolated from patients who were experiencing catheter blockage. The catheter retention balloons were inflated with water or triclosan (3 g triclosan l(-1) in 0.1 M sodium carbonate) and urine was supplied to the models for up to 7 days. The effect of triclosan was recorded on the viable cell populations, the pH of the residual urine and the times that catheters took to block. The extent of encrustation of the catheters was visualized by scanning electron microscopy. In models inoculated with communities containing Proteus mirabilis, triclosan prevented the rise in urinary pH that drives crystalline biofilm formation and catheter blockage. The biocide had no effect on populations of Enterococcus faecalis and Pseudomonas aeruginosa, but Proteus mirabilis, Escherichia coli and Klebsiella pneumoniae were eliminated from the residual urine and the catheters drained freely for the 7-day experimental period. In models inoculated with a mixed community containing Providencia rettgeri, catheters inflated with triclosan continued to block rapidly. Although K. pneumoniae and Proteus vulgaris were eliminated from the residual urine, there was no effect on the viability of Providencia rettgeri. The results indicate that the triclosan strategy should be limited to the treatment of patients who are infected with Proteus mirabilis.


MoO3 nanoplates reinforced the structural, electrical, mechanical, and antibacterial characteristics of polyvinyl pyrrolidone/sodium alginate polymer blend for optoelectronics and biological applications.
Organic/Inorganic nanostructures enable the development of new functional materials for optoelectronics and biological applications. In this work, nanocomposite films of polyvinyl pyrrolidone (PVP) and sodium alginate (NaAlg) blend matrix (30/70 wt%) filled with molybdenum trioxide (MoO3) nanoplates were prepared using solution casting procedure. The effect of MoO3 nanoplates on structural, optical, electrical and antibacterial characteristics of pure PVP/NaAlg blend was investigated. The sizes of MoO3 nanoplates had dimensions between 90 and 420 nm with orthorhombic phase as indicated by the TEM and XRD techniques. Also, the XRD patterns of filled films suggested that the presence of crystalline phases of MoO3 within PVP/NaAlg matrix. FTIR analysis revealed the primary vibrational peaks of PVP and NaAlg, whose strength altered randomly after filling. The UV absorption increased gradually and shifted to the higher wavelength side. The alternating current (AC) conductivity and dielectric parameters were improved with increasing MoO3 concentration. The antibacterial activity against Staphylococcus aureus and Escherichia coli increased with increase of MoO3 nanoplates concentration. The filled PVP/NaAlg-MoO3 samples displayed considerable enhancements in the values of Young's modulus (Y), tensile stress (σt) and elongation at break (εB). The obtained results imply that these nanocomposite films can be potentially used in optoelectronics and biological applications.


Iron-catalyzed intermolecular [2π+2π] cycloaddition.
The bis(imino)pyridine iron dinitrogen compounds, ((iPr)PDI)Fe(N(2))(2) and [((Me)PDI)Fe(N(2))](2)(μ(2)-N(2)) ((R)PDI = 2,6-(2,6-R(2)-C(6)H(3)N═CMe)(2)C(5)H(3)N; R = (i)Pr, Me), promote the catalytic intermolecular [2π + 2π] cycloaddition of ethylene and butadiene to form vinylcyclobutane. Stoichiometric experiments resulted in isolation of a catalytically competent iron metallocycle intermediate, which was shown to undergo diene-induced C-C reductive elimination. Deuterium labeling experiments establish competitive cyclometalation of the bis(imino)pyridine aryl substituents during catalytic turnover.


High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict worse survival in human lung adenocarcinoma.
Background: Immunotherapy targeting PD-1/PD-L1 represents a breakthrough in the treatment of lung cancer. Pyruvate kinase M2 (PKM2) is not only a critical player in glycolysis, but also conducive to tumor progression and immune response. While both have been linked to lung adenocarcinoma (AC), the correlation and clinical significance of PKM2 and PD-L1 expression in human lung AC tissues remains not entirely explored. Methods: Expression of PKM2 and PD-L1 proteins were detected by immunohistochemistry in 74 lung AC cases and the corresponding noncancerous tissues. Simultaneously, multiplex immunofluorescence was used to detect PKM2, PD-L1, CK, CD3, and CD68 in the lung AC tissues. We measured expression patterns and co-localization of these markers, evaluating their association with clinicopathological features and overall survival. Validation of findings was conducted using mRNA expression data from The Cancer Genome Atlas (TCGA) of 515 lung AC cases. Results: High expression of PKM2 in tumor cells was significantly related with lymph node metastasis and TNM stage (p=0.035, p=0.017, respectively). Moreover, PKM2 expression in tumor cells was positively correlated with tumor PD-L1 expression. High expression of PKM2, PD-L1 in tumor cells and immune cells predicted high mortality rate and poorer survival rates, respectively. Additionally, multivariate Cox regression models indicated that high expression of PKM2 in tumor cells was an independent prognostic factor. Based on TCGA genomic data, high PKM2 mRNA expression was significantly associated with poorer survival (p=0.001). Conclusion: High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict poorer survival rates in patients with lung AC.


Cryotherapy for nodal metastasis in NSCLC with acquired resistance to immunotherapy.
Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8.6 cm right upper lobe lung lesion with local invasion, adenopathy, and a malignant pericardial effusion. This lesion was biopsied and identified to be cT3N3M1b squamous cell cancer of the lung without any recognizable PD-L1 expression on tumor cells. For her metastatic NSCLC, the patient underwent two lines of conventional chemotherapy before initiation of combination immunotherapy with an anti-PD-L1 and anti-CTLA-4 antibody. Though she initially achieved a response, she thereafter progressed and developed immunotherapy resistant lymph nodal metastasis. While cervical lymph nodes could be surgically removed, another metastasis in an aortocaval area required a more sensitive therapy like thermal ablation. The aortocaval node was partially treated with a single treatment of cryotherapy and demonstrated durable complete response. Cryotherapy for checkpoint immunotherapy resistant metastasis appears to be a safe and feasible treatment for treating metastatic disease in non-small cell lung cancer. The prospect of cryotherapy adjuvancy may enable local control of metastatic disease after initial response to immune checkpoint immunotherapy and may impact on overall outcomes.


Awake transforaminal endoscopic lumbar facet cyst resection: technical note and case series.
The aim of this study was to describe a minimally invasive transforaminal surgical technique for treating awake patients presenting with lumbar radiculopathy and compressive facet cysts. Awake transforaminal endoscopic decompression surgery was performed in 645 patients over a 6-year period from 2014 to 2020. Transforaminal endoscopic decompression surgery utilizing a high-speed endoscopic drill was performed in 25 patients who had lumbar facet cysts. All surgeries were performed as outpatient procedures in awake patients. Nine of the 25 patients had previously undergone laminectomies at the treated level. A retrospective chart review of patient-reported outcome measures is presented. At the 2-year follow-up, the mean (± standard deviation) preoperative visual analog scale leg score and Oswestry Disability Index improved from 7.6 ± 1.3 to 2.3 ± 1.4 and 39.7% ± 8.1% to 13.0% ± 7.4%, respectively. There were no complications, readmissions, or recurrence of symptoms during the 2-year follow-up period. A minimally invasive awake procedure is presented for the treatment of lumbar facet cysts in patients with lumbar radiculopathy. Approximately one-third of the treated patients (9 of 25) had postlaminectomy facet cysts.


Simulated performance of flexible sigmoidoscopy-based screening for advanced neoplasia detection in a Greek population.
Flexible sigmoidoscopy (FS) is resource-conserving and may increase adherence to colorectal cancer (CRC) screening compared to total colonoscopy. We investigated the diagnostic performance of FS-based screening for advanced colorectal neoplasia (ACN), including advanced adenomatous neoplasms (AANs), advanced serrated lesions (ASLs) and CRCs. Data from 2005 subjects undergoing average-risk screening colonoscopy in a single center in Greece were retrospectively reviewed. Sensitivities of FS-based screening for detecting AANs, ASLs, CRCs or any ACN were simulated on a per-lesion basis, assuming: 1) FS up to the sigmoid-descending junction (FS-1) or splenic flexure (FS-2); 2) colonoscopy referral criteria according to the 4 screening FS trials conducted in UK, Italy, Norway, and USA. Overall, 114 ACNs (93 AANs, 17 ASLs, 4 CRCs) were detected in 102 (5.1%) subjects. The overall sensitivities of FS-1 and FS-2 alone for the detection of any ACN were 41.2% and 54.4%, respectively. Assuming different colonoscopy referral criteria, the estimated sensitivities for any ACN ranged from 48.2-50.9% for FS-1 and 60.5-64% for FS-2. The overall sensitivities were lower for ASLs (FS-1: 35.3-41.2%, FS-2: 41.2-52.9%) compared to those observed for AANs (FS-1: 48.4-51.6%, FS-2: 62.4-66.7%). The difference was particularly pronounced in women, in whom all 4 criteria led equally to a very low sensitivity for ASLs (30%). Implementation of FS-based screening in Greek subjects would have led to the detection of 48-64% of all ACNs. An alarmingly low detection of ASLs among women may call for gender-specific colonoscopy referral strategies.


Living kidney donors' experiences with the health care system.
The purpose of this study was to explore living kidney donors' perceived experiences with the health care system from the period prior to being tested as a potential donor, through to post donation discharge and follow-up. Qualitative methodology, using a phenomenological approach, explored the experiences, feelings, and ideas of 12 purposefully selected living kidney donors' interface with the health care system. Eight men and four women were interviewed four to 29 years post donation. Interviews were audio taped and transcribed verbatim. An iterative and interpretive analysis was conducted. Themes emerging from the data included factors influencing living kidney donors' decision to be tested as potential donors, the importance of emotional support, and humanistic care. This in turn impacted on their experience of: (1) the role of information in the decision-making process; (2) their tolerance of issues related to hospitalization and; (3) their perception of the quality of care. The findings of this study provide suggestions for the role of social work and improvement in the health care system to better address the needs of living kidney donors.


Distribution of twelve linear extrachromosomal DNAs in natural isolates of Lyme disease spirochetes.
We have analyzed a panel of independent North American isolates of the Lyme disease agent spirochete, Borrelia burgdorferi (sensu stricto), for the presence of linear plasmids with sequence similarities to the 12 linear plasmids present in the B. burgdorferi type strain, isolate B31. The frequency of similarities to probes from each of the 12 B31 plasmids varied from 13 to 100% in the strain panel examined, and these similarities usually reside on plasmids similar in size to the cognate B31 plasmid. Sequences similar to 5 of the 12 B31 plasmids were found in all of the isolates examined, and >66% of the panel members hybridized to probes from 4 other plasmids. Sequences similar to most of the B. burgdorferi B31 plasmid-derived DNA probes used were also found on linear plasmids in the related Eurasian Lyme agents Borrelia garinii and Borrelia afzelii; however, some of these plasmids had uniform but substantially different sizes from their B. burgdorferi counterparts.


The effects of COVID-19 stay-at-home orders on physical activity of people with obesity.
To verify the association of changes on physical activity levels during coronavirus disease 2019 (COVID-19) outbreak of individuals with normal weight and overweight/obesity, and the influence of sex in this relationship. This cross-sectional study (survey research) was conducted in Brazil between May 5 and May 17, 2020. Participants (n=1,828 / 1,062 women >18 years) were invited through social media to answer a structured questionnaire via Google Forms. The online assessment included self-reported responses to questions on physical activity, overall health, weight, and height. Binary logistic regression analyzed the relationship between overweight/obesity (body mass index ≥25kg/m2), the impact of COVID-19 on physical activity level, and the influence of sex. Compared to normal weight people, those with overweight/obesity practice less moderate to vigorous physical activity (p<0.001). There were associations between women and men with overweight/obesity and the impact of COVID-19 on the physical activity practice compared to normal weight people, adjusted by age, education level, social isolation, and previous physical activity level (p<0.017). The study found an association of weight and changes in physical activity levels. Individuals with overweight/obesity were more likely to have a lower physical activity level during COVID-19 pandemic, regardless of sex.


[The taxonomy and distribution of Nathalis (Lepidoptera: Pieridae) in Colombia].
In Colombia, Nathalis has two described species: N. iole and N. plauta. Previous authors did not make detailed descriptions of its distribution in meridional regions and failed to differentiate both species based on genitalic characters. Some wing marks have been enough to separate them, but co-specificity was a possibility. They inhabit Colombia above 2000 m in the paramo, and have a vicariant distribution from the remaining population of N. iole in the Antillean and Central and North America. An analysis focused on male and female genitalia, as well as the wing pattern of more than 100 specimens from the Colombian Andes (Sierra Nevada de Santa Marta and Sierra de Perijá) and Mexico, indicates that the two species differ in their genitalia, and considering their allopatric distribution, we support the specific distinction of N. iole and N. plauta. We describe a new endemic subspecies found exclusively in the paramo above 3000 m, an area where other endemics occur. It has phenotypic plasticity related to environmental factors.


Congenital cholesteatoma of occipital bone or intradiploic epidermoid cyst? One and the same disease.
We report an extremely rare case of congenital cholesteatoma affecting the occipital bone. We present a case report, plus a review of the world literature on similar lesions. This case report describes the presentation and treatment of a congenital cholesteatoma arising in an apparently unique location within the occipital bone, with no effect on middle-ear structure or function. The different imaging characteristics of this lesion are described and illustrated. The discussion centres on the differentiation of this lesion from intradiploic epidermoid cysts, more commonly described in the neurosurgical literature. The possible methods of pathogenesis are discussed, along with treatment suggestions. Congenital cholesteatomas and intradiploic epidermoid cysts are indistinguishable both histologically and radiologically, and would appear to be the same disease.


How "bad" does the pain have to be? A qualitative study examining adherence to pain medication in older adults with osteoarthritis.
To explore the experience of adherence to pain medication in older adults with osteoarthritis (OA). Individuals were recruited from an existing cohort (n = 1,300) of persons with disabling hip and knee OA. Twenty-seven individuals who reported previous physician visits for their arthritis, spoke English, were Toronto residents, and were receptive to in-depth interviews were approached by the cohort telephone interviewer to discuss their experiences with prescribed painkillers for OA. Semistructured face-to-face interviews were conducted by a qualitative researcher in participants' homes. Nineteen adults (10 women, 9 men) ages 67-92 years were interviewed for 1-3 hours. Participants varied in their socioeconomic status and education levels. Most had comorbidities, such as heart disease and diabetes, for which they were also being treated. Findings indicated that adherence to pain medication differed from that of other prescribed medications. Participants were reluctant to take painkillers, and when they did, they generally took them at a lower dose or frequency than prescribed. This behavior did not reflect their recommendations for others, who they expected to be treated appropriately for pain and to adhere to pain medication. Perceptions and attitudes to pain played an integral role in participants' adherence to painkillers. Despite obvious physical limitations, participants minimized their pain and claimed to have a high pain tolerance. These findings suggest that reevaluation of the prescription of pain medication for OA is warranted and that the effectiveness of pain management in OA needs to account for adherence behavior in older adults.


Accuracy of dermatoscopy for the diagnosis of nonpigmented cancers of the skin.
Nonpigmented skin cancer is common, and diagnosis with the unaided eye is error prone. To investigate whether dermatoscopy improves the diagnostic accuracy for nonpigmented (amelanotic) cutaneous neoplasms. We collected a sample of 2072 benign and malignant neoplastic lesions and inflammatory conditions and presented close-up images taken with and without dermatoscopy to 95 examiners with different levels of experience. The area under the curve was significantly higher with than without dermatoscopy (0.68 vs 0.64, P < .001). Among 51 possible diagnoses, the correct diagnosis was selected in 33.1% of cases with and 26.4% of cases without dermatoscopy (P < .001). For experts, the frequencies of correct specific diagnoses of a malignant lesion improved from 40.2% without to 51.3% with dermatoscopy. For all malignant neoplasms combined, the frequencies of appropriate management strategies increased from 78.1% without to 82.5% with dermatoscopy. The study deviated from a real-life clinical setting and was potentially affected by verification and selection bias. Dermatoscopy improves the diagnosis and management of nonpigmented skin cancer and should be used as an adjunct to examination with the unaided eye.


Out-of-step: brain-heart desynchronization in anxiety disorders.
Imaging studies in anxiety disorders (AD) show abnormal functional connectivity primarily in the salience network (SN), somatomotor network (SMN), and default mode network (DMN). However, it is not clear how precisely these network changes occur including their relation to psychopathological symptoms. Here, we show that the functional networks affected in AD overlap with cortical regions that receive visceral inputs (the so-called central/visceral autonomic network). Focusing on cardiac afferents, we suggest that network changes in AD may be due to reduced phase synchronization between ongoing neural and cardiac activity. This neuro-cardiac desynchronization occurs due to the abnormal phase resetting of neural activity at the onset of each heartbeat, as measured by a lower intertrial coherence and heartbeat-evoked potential. Biochemically, cardiac afferents reach subcortical serotonergic raphe nuclei and noradrenergic locus coeruleus (among others) which, in turn, are known to reciprocally modulate the DMN and SMN/SN on the cortical level. Consistent with the network changes in AD, decreases in serotonergic and noradrenergic activity are known to increase connectivity in both SMN and SN while, at the same time, they decrease DMN connectivity. SMN and SN increases, in turn, lead to increased emotional arousal/anxiety and bodily awareness whereas decreased DMN connectivity leads to an unstable sense-of-self in AD. Finally, we integrate our proposal with interoceptive predictive processing models suggesting neuro-cardiac desynchronization as a mechanism for "noisy" bottom-up information leading to a persistently uncertain bodily state in top-down models. In sum, integrating theories on active interference and hyperarousal, we propose a precise neuro-cardiac and biochemically -driven mechanisms for key psychopathological symptoms of AD.


Lower limb mechanics during moderate high-heel jogging and running in different experienced wearers.
The aim of this study is to investigate the differences in lower limb kinematics and kinetics between experienced (EW) and inexperienced (IEW) moderate high-heel wearers during jogging and running. Eleven experienced female wearers of moderate high-heel shoes and eleven matched controls participated in jogging and running tests. A Vicon motion analysis system was used to capture kinematic data and a Kistler force platform was used to collect ground reaction force (GRF). There were no significant differences in jogging and running speed respectively. Compared with IEW, EW adopted larger stride length (SL) with lower stride frequency (SF) at each corresponding speed. During running, EW enlarged SL significantly while IEW increased both SL and SF significantly. Kinematic data showed that IEW had generally larger joint range of motion (ROM) and peak angles during stance phase. Speed effect was not obvious within IEW. EW exhibited a significantly increased maximal vertical GRF (Fz2) and vertical average loading rate (VALR) during running, which was potentially caused by overlong stride. These suggest that both EW and IEW are at high risk of joint injuries when running on moderate high heels. For wearers who have to do some running on moderate high heels, it is crucial to control joint stability and balance SL and SF consciously.


Fear of re-injury: a hindrance for returning to sports after anterior cruciate ligament reconstruction.
Unrestricted participation in sports activities and return to the pre-injury level is often reported as an indicator of the success of ACL reconstruction. The athletes' choice not to return to their pre-injury level may depend on the knee function, but some times, social reasons or psychological hindrances such as fear of re-injury may influence their return to sports. The aim of this study was to investigate whether fear of re-injury due to movement is of significance for returning to previous level of activity in patients who have undergone anterior cruciate ligament reconstruction. The Tampa Scale of Kinesiophobia (TSK), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and some general questions were mailed to 87 patients who underwent ACL reconstruction 3-4 years before the study was conducted. Sixty-two patients (74%) answered the questionnaires (34 men and 28 women). Fifty-three percent of the patients returned to their pre-injury activity level. The patients who did not return to their pre-injury activity level had more fear of re-injury, which was reflected in the TSK. In addition, high fear of re-injury was correlated with low knee-related quality of life. Fear of re-injury must be considered in the rehabilitation and evaluation of the effects of an ACL reconstruction.


Role of TAAR1 within the Subregions of the Mesocorticolimbic Dopaminergic System in Cocaine-Seeking Behavior.
A novel G-protein coupled receptor, trace amine-associated receptor 1 (TAAR1), has been shown to be a promising target to prevent stimulant relapse. Our recent studies showed that systemic administration of TAAR1 agonists decreased abuse-related behaviors of cocaine. However, the role of TAAR1 in specific subregions of the reward system in drug addiction is unknown. Here, using a local pharmacological activation method, we assessed the role of TAAR1 within the subregions of the mesocorticolimbic system: that is, the VTA, the prelimbic cortex (PrL), and infralimbic cortex of medial prefrontal cortex, the core and shell of NAc, BLA, and CeA, on cue- and drug-induced cocaine-seeking in the rat cocaine reinstatement model. We first showed that TAAR1 mRNA was expressed throughout these brain regions. Rats underwent cocaine self-administration, followed by extinction training. RO5166017 (1.5 or 5.0 μg/side) or vehicle was microinjected into each brain region immediately before cue- and drug-induced reinstatement of cocaine-seeking. The results showed that microinjection of RO5166017 into the VTA and PrL decreased both cue- and drug priming-induced cocaine-seeking. Microinjection of RO5166017 into the NAc core and shell inhibited cue- and drug-induced cocaine-seeking, respectively. Locomotor activity or food reinforced operant responding was unaffected by microinjection of RO5166017 into these brain regions. Cocaine-seeking behaviors were not affected by RO5166017 when microinjected into the substantia nigra, infralimbic cortex, BLA, and CeA. Together, these results indicate that TAAR1 in different subregions of the mesocorticolimbic system distinctly contributes to cue- and drug-induced reinstatement of cocaine-seeking behavior. TAAR1 has been indicated as a modulator of the dopaminergic system. Previous research showed that systemic administration of TAAR1 agonists could attenuate cocaine-related behaviors, suggesting that TAAR1 may be a promising drug target for the treatment of cocaine addiction. However, the specific role of TAAR1 in subregions of the mesocorticolimbic system in drug addiction is unknown. Here, we first showed that TAAR1 mRNA is expressed throughout the subregions of the mesocorticolimbic system. Then, by using a local pharmacological activation method, we demonstrated that TAAR1 in different subregions of the mesocorticolimbic system distinctly contributes to cue- and drug-induced reinstatement of cocaine-seeking behavior.


A maize (E)-beta-caryophyllene synthase implicated in indirect defense responses against herbivores is not expressed in most American maize varieties.
The sesquiterpene (E)-beta-caryophyllene is emitted by maize (Zea mays) leaves in response to attack by lepidopteran larvae like Spodoptera littoralis and released from roots after damage by larvae of the coleopteran Diabrotica virgifera virgifera. We identified a maize terpene synthase, Terpene Synthase 23 (TPS23), that produces (E)-beta-caryophyllene from farnesyl diphosphate. The expression of TPS23 is controlled at the transcript level and induced independently by D. v. virgifera damage in roots and S. littoralis damage in leaves. We demonstrate that (E)-beta-caryophyllene can attract natural enemies of both herbivores: entomopathogenic nematodes below ground and parasitic wasps, after an initial learning experience, above ground. The biochemical properties of TPS23 are similar to those of (E)-beta-caryophyllene synthases from dicotyledons but are the result of repeated evolution. The sequence of TPS23 is maintained by positive selection in maize and its closest wild relatives, teosinte (Zea sp) species. The gene encoding TPS23 is active in teosinte species and European maize lines, but decreased transcription in most North American lines resulted in the loss of (E)-beta-caryophyllene production. We argue that the (E)-beta-caryophyllene defense signal was lost during breeding of the North American lines and that its restoration might help to increase the resistance of these lines against agronomically important pests.


Psychodiagnostics: Classification of the Yips Phenomenon based on Musician's Dystonia.
Similar to musician's focal dystonia, a task-specific phenomenon known as yips, has also been reported in professional athletes. Yips is usually described as focal dystonia, or choking under pressure, or as lying on a continuum between both. Based on the common occupational conditions across musicians and athletes, the present exploratory study aimed to investigate whether musicians diagnosed with focal dystonia and golfers affected with yips, can be similarly subclassified based on their psychological profiles. Twenty healthy musicians, 20 musicians with focal dystonia, 20 healthy golfers, and 20 yips-affected golfers went through a test battery including three psycho-diagnostic standardized questionnaires (the Competitive Trait Anxiety Inventory, the Frost's Multidimensional Perfectionism Scale, and the Stress Coping Questionnaire), measuring trait cognitive and somatic anxiety, perfectionistic tendencies and different stress coping strategies. Findings based on a clustering procedure suggest that similar to musician's dystonia, yips-affected golfers can be classified into those with and those without specific elevated perfectionistic, stress and anxiety traits. The roles of these different psychological profiles as possible triggering factors of the yips are discussed and compared with those of musician's dystonia. The current study suggests that the yips phenomenon might cover a broader range of different subtypes of movement disturbances than those already suggested in the literature. Finally, a theoretical model, which explains the role of the different triggering factors in the discrimination of the different subtypes, is suggested. A better classification and understanding of the different subtypes of yips could lead to a more accurate diagnosis and to the design of more individualized treatment intervention.


Molecular ionic junction for enhanced electronic charge transfer.
We present the first evidence of charge injection improvement in an organic electroluminescent device provided by a single ionic molecular layer. A hole-dominated, hybrid organic-inorganic light-emitting device is used as a probe to verify the effectiveness of the ionic compound monolayer on modifying the metal oxide cathode. The rearrangement of ions under an applied bias induces a strong field at the electrode-organic interface resulting in an enhancement of the electron injection into the organic semiconductor. A strong decrease in turn-on voltage for electroluminescence is observed for the device containing the ionic molecular monolayer.


Aetiology and management of chronic granulomatous osteomyelitis: look before you leap.
We report a rare difficult-to-manage case of chronic granulomatous osteomyelitis due to Burkholderia pseudomallei, the category two organism with atypical sensitivity pattern. The patient was a 29-year-old who presented with a history of dull aching pain in the left thigh region for one year. Local examination revealed a diffuse swelling and tenderness. Any similar presentation should therefore always be supported by microbiological opinion to prevent prolonged morbidity, especially in immunocompromised patients.


Neutrophil-lymphocyte Ratio and C-reactive Protein Level in Patients with Major Depressive Disorder Before and After Pharmacotherapy.
Neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) level are useful biomarkers of inflammation. This study aimed to assess NLR and CRP level in patients with major depressive disorder before and after pharmacotherapy to determine whether NLR or CRP could be used as biomarkers of severity of major depression and whether there was any sex difference. Patients with major depression who received no pharmacotherapy 1 month prior to the study were included. Their haemoglobin, total white blood cell count, neutrophil and lymphocyte counts, NLR, and CRP levels were evaluated at baseline and 12 weeks post pharmacotherapy, as were the Montgomery Asberg Rating Scale for Depression, the Scale for Impact of Suicidality Management and Assessment and Planning of Care (SIS-MAP), and the Clinical Global Impression Scale - Severity. 24 male and 26 female patients were included. At 12 weeks after pharmacotherapy, males had a higher haemoglobin level (p = 0.025), higher total white blood cell count (p = 0.018), and lower percentage of neutrophils (p = 0.019) than females. There was no sex difference in NLR or CRP. From baseline to 12 weeks, males had no significant change in any blood parameter, but females had a significantly greater increase in the percentage of neutrophils (p = 0.0001) and decrease in the percentage of lymphocytes (p = 0.012), resulting in a significantly increased NLR (p = 0.001). Both males and females had significant improvement on all 3 scales (p < 0.001). At 12 weeks, in males, the increase in NLR positively correlated with CRP as well as the Montgomery-Asberg Depression Rating Scale and the SIS-MAP, but not the Clinical Global Impression-Severity Scale. In females, the increase in NLR did not correlate with CRP or any of the scales. In female patients, the NLR increased in response to antidepressant therapy while CRP remained unchanged. This indicated that inflammation has a role in the pathogenesis of major depression.


Genetic interactions of Drosophila melanogaster arrest reveal roles for translational repressor Bruno in accumulation of Gurken and activity of Delta.
arrest mutants have pleiotropic phenotypes, ranging from an early arrest of oogenesis to irregular embryonic segmentation defects. One function of arrest is in translational repression of oskar mRNA; this biochemical activity is presumed to be involved in other functions of arrest. To identify genes that could provide insight into how arrest contributes to translational repression or that may be targets for arrest-dependent translational control, we screened deficiency mutants for dominant modification of the arrest phenotype. Only four of the many deficiencies tested, which cover approximately 30% of the genome, modified the starting phenotype. One enhancer, identified fortuitously, is the Star gene. Star interaction with arrest results in excess Gurken protein, supporting the model that gurken is a target of repression. Two modifiers were mapped to individual genes. One is Lk6, which encodes a protein kinase predicted to regulate the rate-limiting initiation factor eIF4E. The second is Delta. The interaction between arrest and Delta mimics the phenotype of homozygous Delta mutants, suggesting that arrest could positively control Delta activity. Indeed, arrest mutants have significantly reduced levels of Delta protein at the interface of germline and follicle cells.


Effects of animal type (wild vs. domestic) and diet alfalfa level on intake and digestibility of European adult rabbits (Oryctolagus cuniculus).
The aim of this study was to evaluate the effect of the level of alfalfa in the diet on feed intake and digestibility of two types of rabbits, wild (Oryctolagus cuniculus algirus) vs. domestic (O. cuniculus cuniculus). Ten wild (W; mean LW = 927 g) and 10 domestic (D; mean LW = 4,645 g) adult rabbit does were fed ad libitum two pelleted diets: a control diet (C) with 15% of dehydrated alfalfa hay (as feed basis) and a test diet (A) with 36% of dehydrated alfalfa hay (as feed basis), according to a change-over design. Wild does dry matter (DM) intake per kg live weight (BW) was 55% higher (p < .001) than the intake of the D ones (58 g vs. 37 g DM per kg BW respectively). However, no difference (p > .05) was found when intake was expressed per kg0.75 BW (ca. 56 g DM) and tended to be higher (p = .07) in D does when expressed per kg0.67 BW (62 g vs. 55 g DM). Domestic does showed a higher (p < .05) DM, organic matter, crude energy and neutral detergent fibre digestibility (3; 2; 3; 3 percentage points respectively) than W does. The amount of nutrients and energy digested by D does was lower per kg BW (p < .001), similar per kg0.75 BW (p > .05) and tended to be higher per kg0.67 BW (p < .1) than in W does. The diet content of alfalfa did not affect (p > .05) the feed intake nor the diet digestibility. This study suggests that W rabbits exhibit a higher intake per kg BW and a lower digestibility than their D counterparts, which results in similar digestible nutrient and energy intake per kg BW powered to 0.75. The nutritive value of dehydrated alfalfa for rabbits, evaluated through intake and digestibility, seems to be equivalent to their base diets (forage plus concentrate).


Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment.
There is little evidence that dehydroepiandrosterone (DHEA) has beneficial effects on physical and psychological functions in older women. We investigated the effect of DHEA supplementation on cognitive function and ADL in older women with cognitive impairment. A total of 27 women aged 65-90 years (mean ± standard deviation, 83 ± 6) with mild to moderate cognitive impairment (Mini-Mental State Examination, MMSE; 10-28/30 points), receiving long-term care at a facility in Japan were enrolled. Twelve women were assigned to receive DHEA 25 mg/day p.o. for 6 months. The control group (n = 15) matched for age and cognitive function was followed without hormone replacement. Cognitive function was assessed by MMSE and Hasegawa Dementia Scale-Revised (HDS-R), and basic activities of daily living (ADL) by Barthel Index at baseline, 3 and 6 months. Plasma hormone levels including testosterone, DHEA, DHEA-sulfate and estradiol were also followed up. After 6 months, DHEA treatment significantly increased plasma testosterone, DHEA and DHEA-sulfate levels by 2-3-fold but not estradiol level compared to baseline. DHEA administration increased cognitive scores and maintained basic ADL score, while cognition and basic ADL deteriorated in the control group (6-month change in DHEA group vs control group; MMSE, +0.6 ± 3.2 vs -2.1 ± 2.2, P < 0.05; HDS-R, +2.8 ± 2.8 vs -0.3 ± 4.1, P < 0.05; Barthel Index, +3.7 ± 7.1 vs -2.7 ± 4.6, P = 0.05). Among the cognitive domains, DHEA treatment improved verbal fluency (P < 0.05). DHEA supplementation in older women with cognitive impairment may have beneficial effects on cognitive function and ADL.


Sputum bacteriology and antibiotic sensitivity patterns of community-acquired pneumonia in hospitalized adult patients in Nigeria: a 5-year multicentre retrospective study.
A clear knowledge of the pathogens responsible for community-acquired pneumonia (CAP) in a given region and their antibiotic sensitivity patterns is necessary for optimal treatment. We determined the common bacterial pathogens causing CAP in Nigeria and further reviewed their antibiotic senstivity patterns with a view to providing recommendations to improve antibiotic management of CAP. Case notes of all adult patients who were 18 years or more admitted to four major tertiary hospitals in South East Nigeria with a diagnosis of CAP between 2008 and 2012 were retrospectively studied. To be eligible, patients were required to have sputum culture and sensitivity results available. Socio-demographic, clinical, pre-admission and in-hospital treatment data were also obtained. Of 400 patients with a radiologically confirmed diagnosis of CAP, 232 fulfilled the study criteria; 122 (52.6%) were women and the mean age was 50.6 ± 18.8 years. Aetiological agents were identified from sputum in 189 (81.5%) patients. Streptococcus pneumoniae (n = 90, 47.6%) was the most frequent isolate followed by Klebsiella pneumoniae (n = 62, 32.8%), Staphylococcus aureus (n = 24, 12.7%) and Streptococcus pyogenes (n = 13, 6.9%). The pathogens were most sensitive to levofloxacin (77%), ceftazidime (75.5%) and ofloxacin (55.8%). The susceptibility of the isolates to antibiotics most frequently presecribed for empirical therapy was low (co-amoxiclav, 47.6%; ciprofloxacin, 45.9% and ceftriaxone, 47.6%) and this was associated with higher mortality and/or longer duration of hospital stay in survivors. Strep. pneumoniae and K. pneumoniae were the most common causes of CAP. The pathogens were most sensitive to levofloxacin and ceftazidime. We suggest that these antibiotics should increasingly be considered as superior options for empirical treatment of CAP in Nigeria.


Ultrathin amorphous coatings on lunar dust grains.
UItrathin amorphous coatings have been observed by high-voltage electron microscopy on micrometer-sized dust grains from the Apollo 11, Apollo 12, Apollo 14, and Luna 16 missions. Calibration experiments show that these coatings result from an "ancient" implantation of solar wind ions in the grains. This phenomenon has interdisciplinary applications concerning the past activity of the sun, the lunar albedo, the ancient lunar atmosphere and magnetic field, the carbon content of lunar soils, and lunar dynamic processes.


Ethidium bromide stimulation of DNA polymerase activity by stabilization of the primer-template duplex.
Plant DNA polymerases and E. coli DNA polymerase I, but not animal DNA polymerases or avian reverse transcriptase, are strongly stimulated by ethidium bromide (EtdBr) when TMP incorporation is followed using a short oligo dT primer at 37 degrees C. The effect is observed with a poly A template in the presence of Mg2+ or Mn2+ and of poly dA template only in the presence of magnesium ions. When a longer primer like poly dT is used, EdtBr inhibited wheat DNA polymerase C activity. This result prompted us to study the effect of the incubation temperature on the drug mediated stimulation. With oligo dT primer the stimulation by EdtBr is not observed at a temperature of incubation lower than 35 degrees C. It is shown that the Tm of poly A-dT12 is around 35 degrees C and that EdtBr will clearly increase this value. The stimulation is lost when the enzyme is preincubated with the primer alone whereas it is not affected when the enzyme is preincubated with the template.


Multilayer Nanofilms via Inkjet Printing for Stabilizing Growth Factor and Designing Desired Cell Developments.
Biologically versatile basic fibroblast growth factor (bFGF), well known for roles of signaling molecules between cells and regulating various cellular processes, has been proven to utilize specific functionalities. However, the remarkable functions are inclinable to dwindle with decrease of bFGFs' activity. In nanoscale, developing thin films with intrinsic characteristics of building molecules can facilitate handling various materials for desired purposes. Fabricating nanofilm and handling sensitive materials without detriment to activity via highly productive manufacturing are significant for practical uses in the field of biomedical applications. Herein, a multilayered nanofilm fabricating system is developed by inkjet printing to incorporate bFGF successfully. It is demonstrated that water mixed with glycerol as biological ink maintains stability of bFGFs through simulation and experimental study. With highly stable bFGFs, the proliferation of human dermal fibroblast is enhanced and the undifferentiated state of induced pluripotent stem cell is maintained by the controlled release of bFGF.


[Interparental conflict and mental health in children and adolescents: the mediating effect of self-concept].
To examine the mediating effect of self-concept between interparental conflict and mental health in children and adolescents. A total of 689 students (10-18 years) were surveyed using the convenient sampling method, and their mental health, self-concept, and interparental conflict were examined by the general status questionnaire, Strengths and Difficulties Questionnaire, Self-Description Questionnaire, and Children's Perception of Interparental Conflict Scale. Structural equation modeling (SEM) and simultaneous analysis of several groups were used to construct the mediator model and analyze the data, respectively. The Bootstrap method was used to assess the significance of the mediating effects. Interparental conflict was positively correlated with mental health of children and adolescents (P<0.05), but was negatively correlated with self-concept (P<0.01). Self-concept was negatively correlated with mental health (P<0.01). Self-concept had a partial (60%) mediating effect between interparental conflict and mental health. Academic stage, but not gender, had a regulatory role on interparental conflict, mental health, and self-concept. Self-concept plays an important role between interparental conflict and mental health. It is necessary to improve self-concept level in children and adolescents exposed to interparental conflict.


Molecular mechanism of different flower color formation of Cymbidium ensifolium.
Cymbidium ensifolium is one of the national orchids in China, which has high ornamental value with changeable flower colors. To understand the formation mechanism of different flower colors of C. ensifolium, this research conducted transcriptome and metabolome analyses on four different colored sepals of C. ensifolium. Metabolome analysis detected 204 flavonoid metabolites, including 17 polyphenols, 27 anthocyanins, 75 flavones, 34 flavonols, 25 flavonoids, 18 flavanones, and 8 isoflavones. Among them, purple-red and red sepals contain a lot of anthocyanins, including cyanidin, pelargonin, and paeoniflorin, while yellow-green and white sepals have less anthocyanins detected, and their metabolites are mainly flavonols, flavanones and flavonoids. Transcriptome sequencing analysis showed that the expression levels of the anthocyanin biosynthetic enzyme genes in red and purple-red sepals were significantly higher than those in white and yellow-green sepals of C. ensifolium. The experimental results showed that CeF3'H2, CeDFR, CeANS, CeF3H and CeUFGT1 may be the key genes involved in anthocyanin production in C. ensifolium sepals, and CeMYB104 has been proved to play an important role in the flower color formation of C. ensifolium. The results of transformation showed that the CeMYB104 is involved in the synthesis of anthocyanins and can form a purple-red color in the white perianth of Phalaenopsis. These findings provide a theoretical reference to understand the formation mechanism of flower color in C. ensifolium.


Refractive null correctors for aspheric surfaces.
The usefulness of a refractive null corrector is limited by how closely its aberrated wavefront can match the aspheric surface that requires testing. Guidance in both the design of the asphere to insure its nullability and the design of the null corrector is presented. A functional and constructional compendium of null corrector designs is proffered.


α-Amino-iso-Butyric Acid Foldamers Terminated with Rhodium(I) N-Heterocyclic Carbene Catalysts.
To investigate how remotely induced changes in ligand folding might affect catalysis by organometallic complexes, dynamic α-amino-iso-butyric acid (Aib) peptide foldamers bearing rhodium(I) N-heterocyclic carbene (NHC) complexes have been synthesized and studied. X-ray crystallography of a foldamer with an N-terminal azide and a C-terminal Rh(NHC)(Cl)(diene) complex showed a racemate with a chiral axis in the Rh(NHC) complex and a distorted 310 helical body. Replacing the azide with either one or two chiral L-α-methylvaline (L-αMeVal) residues gave diastereoisomeric foldamers that each possessed point, helical and axial chirality. NMR spectroscopy revealed an unequal ratio of diastereoisomers for some foldamers, indicating that the chiral conformational preference of the N-terminal residue(s) was relayed down the 1 nm helical body to the axially chiral Rh(NHC) complex. Although the remote chiral residue(s) did not affect the stereoselectivity of hydrosilylation reactions catalysed by these foldamers, these studies suggest a potential pathway towards remote conformational control of organometallic catalysts.