[Application of disposable oval circumcision anastomat in pediatric urology].
Objective: To summarize the application experience of Ai Tong (Chinese Shang Ring) disposable oval circumcision anastomat in pediatric urology. Methods: A retrospective study of 1 481 cases of pediatric urology using a disposable oval circumcision anastomat at Xuzhou Children's Hospital from October 2014 to December 2017 was performed. The average age at the time of surgery was 5.2 (2-14 years) years. Among them, there were 1 226 cases of phimosis, 32 cases of scar phimosis in chronic infection, 23 cases of phimosis or redundant prepuce with urethral duplication, 29 cases of foreskin trauma, 35 cases of phimosis or redundant prepuce with urethral cyst, 3 cases of phimosis or redundant prepuce with urethral stricture, 108 cases of phimosis or redundant prepuce with webbed penis, 6 cases of phimosis with penile downward bending, 4 cases of phimosis with short frenulum preputii, and 15 cases of relatively normal foreskin development, I° and II° hypospadias with unapparent penile downward bending, and megalourethra with complete foreskin hypospadias. Results: All operations were completed successfully. The postoperative circumcision time was less than 5 days on 2 cases(0.1%), and was longer than 25 days on 9 cases(0.6%). The average postoperative circumcision time was 13.2 days. During a follow-up period of 3 months, except for 2 cases (0.1%) of frenulum preputii edema, all other cases had a satisfactory foreskin appearance. They had no obvious foreskin scar hyperplasia, the foreskin cutting edge was neat, the foreskin ligament was intact, the foreskin was left and right symmetrical, and the foreskin was preserved in the absence of erection to cover the coronary sulcus to 1/3 of the glans. All children with hypospadias had no urethral stricture and urethral fistula, and the penis was satisfactory. Conclusions: Ai Tong (Chinese Shang Ring) disposable oval circumcision anastomat is satisfactory in the treatment of various diseases of pediatric urology. With a low incidence of postoperative complications, it may be easy to carry out this procedure at grass-roots hospital.


Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145.
To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.


Induction of innate immune response through TLR2 and dectin 1 prevents type 1 diabetes.
Studies have suggested a correlation between the decline in infectious diseases and increase in the incidence of type 1 diabetes (T1D) in developed countries. Pathogens influence the disease outcome through innate immune receptors such as TLRs. Here we report the effect of ligation of TLR2 and dectin 1 on APCs and the influence of innate immune response induced through these receptors on T1D. Exposure of APCs of NOD mice to zymosan, a fungal cell wall component that interacts with TLR2 and dectin 1, resulted in the release of significant amounts of IL-10, TGF-beta1, IL-2, and TNF-alpha. Treatment of pre- and early hyperglycemic mice with zymosan resulted in suppression of insulitis, leading to a significant delay in hyperglycemia. T cells from zymosan-treated mice showed reduced ability to induce diabetes in NOD-Scid mice compared with control T cells. Zymosan treatment induced suppression of T1D was associated with an increase in the L-selectin(high) T cell frequencies and enhanced suppressor function of CD4(+)CD25(+) T regulatory cells. Further, activation by anti-CD3-Ab induced larger amounts of TGF-beta1 and/or IL-10 production by CD4(+)CD25(+) and CD4(+)CD25(-) T cells from zymosan-treated mice. These results show that innate immune response through TLR2 and dectin 1 results in suppressor cytokine production by APCs and promotes the regulatory function of T cells. Our study demonstrates the possible involvement of signaling through innate immune receptors such as TLR2 and dectin 1 in reduced T1D incidence under the conditions of low hygiene, and the potential of targeting them for treating T1D.


CORRELATED RESPONSES IN LIFE-HISTORY TRAITS TO ARTIFICIAL SELECTION FOR BODY WEIGHT IN DROSOPHILA MELANOGASTER.
Drosophila melanogaster that had been successfully selected on rich and poor larval medium for increased and decreased fresh weight at eclosion were tested on an intermediate medium for correlated responses in longevity, fertility, and hatchability. Larger flies laid more eggs early in life and lived shorter lives than smaller flies, which not only lived longer but also laid more eggs later in life. This supports the notion of a mortality cost of reproduction in Drosophila. The total number of eggs laid per lifetime did not differ between the two groups. The percentage of offspring hatched started at normal levels (about 50% of eggs laid), then declined rapidly in large flies. In small flies, hatchability started at a lower level early in life (40-65%), but declined less rapidly, and later in life was higher than the hatchability of eggs laid by larger flies.


Acute Rhinosinusitis as an Infrequent Cause of Symptomatic Cluster Headache: Report of Seven Cases.
Cluster headache (CH) is a primary headache disorder characterized by unilateral headache attacks lasting 15 to 180 minutes, occurring between two and eight times a day, and accompanied by autonomic symptoms ipsilateral to the pain. However, cases of symptomatic CH that occur secondary to an underlying structural pathology have also been reported in the literature. In this report, seven patients are presented who were admitted with signs of CH and diagnosed with acute rhinosinusitis depending on extensive clinical and radiologic examinations. Symptomatic CH, though rarely reported in the literature compared to CH, should be kept in mind in patients presenting with the first attack of CH. Moreover, in such patients, whether the pain becomes worse when bending forward and becomes sensitive on palpation should be questioned, and a radiologic work-up should be performed to rule out secondary causes such as rhinosinusitis. In the present cases, the resolution of CH attacks with acute sinusitis therapy confirmed the diagnosis.


Application of machine learning to predict the inhibitory activity of organic chemicals on thyroid stimulating hormone receptor.
With the promotion of carbon neutrality, it is also important to synchronously promote the assessment and sustainable management of chemicals so as to protect public health. Humans and animals are possibly exposed to endocrine disruptors that have inhibitory effects on thyroid stimulating hormone receptor (TSHR). As such, it is important to identify chemicals that inhibit TSHR and to develop models to predict their inhibitory activity. In this study, 5952 compounds derived from a cyclic adenosine monophosphate (cAMP) analysis, a key signaling pathway in thyrocytes, were used to establish a binary classification model comparing methods that included random forest (RF), extreme gradient boosting (XGB), and logistic regression (LR). The prediction model based on RF showed the highest identification accuracy for revealing chemicals that may inhibit TSHR. For the RF model, recall was calculated at 0.89, balance accuracy was 0.85, and its receiver operating characteristic (ROC) curve-area under (AUC) was 0.92, indicating that the model had very high predictive capacity. The lowest CDocker energy (CE) and CDocker interaction energy (CIE) for chemicals and TSHR were determined and were subsequently introduced into the predictive model as descriptors. A regression model, extreme gradient boosting-Regression (XGBR), was successfully established yielding an R2 = 0.65 to predict inhibitory activity for active compounds. Parameters that included dissociation characteristics, molecular structure, and binding energy were all key factors in the predictive model. We demonstrate that QSAR models are useful approaches, not only for identifying chemicals that inhibit TSHR, but for predicting inhibitory activity of active compounds.


Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection.
The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19™). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. Covax-19 vaccine induced high spike protein binding antibody levels that neutralised the original lineage B.1.319 virus from which the vaccine spike protein was derived, as well as the variant B.1.1.7 lineage virus. Covax-19 vaccine also induced a high frequency of spike-specific CD4 + and CD8 + memory T-cells with a dominant Th1 phenotype associated with the ability to kill spike-labelled target cells in vivo. Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus given two weeks after the last immunisation. Notably, ferrets that received the two higher doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting that in addition to lung protection, Covax-19 vaccine may have the potential to reduce virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.


[The definition of the term "mold"].
The term "moulds" refers to an ecological category, not to a taxonomic or morphological one. Moulds can be characterized by 1. ruderal life strategy, 2. filamentous growth form, 3. fast growth, 4. high sporulation capacity, 5. predominantly vegetative reproduction, 6. parasexual cycle, 7. sensitivity to soil fungistasis, 8. ubiquitous occurrence, 9. cosmopolitan distribution, 10. production of a rich spectrum of metabolites (including diversified secondary metabolites, in contrast to yeasts) released into substrates resp. media. These properties qualify the moulds and antagonists of man, but also as particularly useful tools of general and industrial microbiology.


Hydration kinetics, ion-release and antimicrobial properties of white Portland cement blended with zirconium oxide nanoparticles.
This study examines the impact of 20 wt% zirconium oxide nanoparticles on the early hydration kinetics of white Portland cement by isothermal conduction calorimetry and transmission electron microscopy. The findings confirm that the nano-ZrO2 particles do not directly participate in the chemical reactions during cement hydration; although, they do divert the normal hydration processes and accelerate the initial setting reactions. The rate of heat evolution and the extent of the exotherm associated with these reactions are reduced in the presence of nano-ZrO2. The incorporation of nano-ZrO2 into the cement also decreases the solubility of the silicate phases but does not compromise its capacity to release hydroxide ions. There was no observed difference in the antimicrobial activity of the nano-ZrO2-blended and unblended cement pastes against S. aureus and E. coli; however, a modest reduction in this property was noted against P. aeruginosa for the blended cement.


Molecular cloning and characterization of a Streptococcus sanguis DNase necessary for repair of DNA damage induced by UV light and methyl methanesulfonate.
We developed a method for cloning cellular nucleases from streptococci. Recombinant lambda gt11 bacteriophage containing streptococcal nuclease determinants were identified by the production of pink plaques on toluidine blue O DNase plates. We used this technique to clone a 3.2-kilobase-pair EcoRI fragment with DNase activity from the chromosome of Streptococcus sanguis. The locus was designated don (DNase one) and could be subcloned and stably maintained on plasmid vectors in Escherichia coli. Minicell analyses of various subclones of the don locus allowed us to determine the coding region and size of the Don nuclease in E. coli. The don gene product had an apparent molecular mass of 34 kilodaltons and degraded native DNA most efficiently, with lesser activity against denatured DNA and no detectable activity against RNA. S. sanguis don deletion mutants were constructed by transformation of competent cells with in vitro-prepared plasmid constructs. S. sanguis don deletion mutants retained normal transformation frequencies for exogenously added donor DNA. However, when compared with Don+ wild-type cells, these mutants were hypersensitive to DNA damage induced by UV light and methyl methanesulfonate. An S. sanguis don-specific DNA probe detected homology to chromosomal DNA isolated from Streptococcus pneumoniae and Streptococcus mutans Bratthall serogroups d and g. Our results suggested that the don locus was the S. sanguis allele of the previously described S. pneumoniae major exonuclease and was involved in repair of DNA damage. Furthermore, hybridization studies suggested that the don locus was conserved among species of oral streptococci.


Experience with the use of polyglycolic acid suture material (Dexon) in 500 surgical patients.
A highly concise review is presented of the experimental and clinical literature concerning polyglycolic acid suture material, marketed for clinical use for the first time in 1970. It is a synthetic, completely absorbable, non-toxic product, which not only offers a number of advantages over catgut, but may also be used where non-absorbable materials were formerly applied exclusively. Our favorable experiences in 500 patients, who were subjected to many different kinds of general surgical operations, are in agreement with those published in the literature. We have gained the impression that suture fistulization, which may lead to protracted morbidity after use of non-absorbable material, has decreased in incidence and severity after the use of PGA suture material. This is a definite advantage.


Voter model dynamics in complex networks: Role of dimensionality, disorder, and degree distribution.
We analyze the ordering dynamics of the voter model in different classes of complex networks. We observe that whether the voter dynamics orders the system depends on the effective dimensionality of the interaction networks. We also find that when there is no ordering in the system, the average survival time of metastable states in finite networks decreases with network disorder and degree heterogeneity. The existence of hubs, i.e., highly connected nodes, in the network modifies the linear system size scaling law of the survival time. The size of an ordered domain is sensitive to the network disorder and the average degree, decreasing with both; however, it seems not to depend on network size and on the heterogeneity of the degree distribution.


Insulin receptor expression and activity in the brains of nondiabetic sporadic Alzheimer's disease cases.
We investigated the contents of the insulin receptor-beta subunit (IRβ) and [Tyr1162/1163]-phosphorylated IRβ as surrogate indices of total IR content and IR activation in postmortem hippocampal formation brain specimens from nondiabetic sporadic Alzheimer's disease (AD) cases. We found no significant changes in the brain contents of total IRβ or [Tyr1162/1163]-phosphorylated IRβ, suggesting normal IR content and activation in the brains of nondiabetic sporadic AD cases. Moreover, total IRβ and [Tyr1162/1163]-phosphorylated IRβ levels in the hippocampal formation are not correlated with the severity of amyloid or tau-neuropathology. Exploring the regulation of glycogen synthase kinase 3 (GSK3) α/β, key IR-signaling components, we observed significantly lower levels of total GSK3 α/β in brain specimens from nondiabetic AD cases, suggesting that impaired IR signaling mechanisms might contribute to the onset and/or progression of AD dementia. Outcomes from our study support the development of insulin-sensitizing therapeutic strategies to stimulate downstream IR signaling in nondiabetic AD cases.


A microprocessor controlled multi-channel evoked potential data acquisition system.
A stored program control system is described for the acquisition of evoked potential (EP) data. It is a small, portable and flexible system with a variety of input and output possibilities. The system presents a low cost solution to the problem of acquisition of evoked potential data. A novel method of converting and reducing sixteen channels of EEG analogue data to their digital equivalent is shown. It is adaptable for the inter active control of experiments and is sophisticated enough to deal with the complexities of experimental control as well as data manipulation. One of the major advantages of the system is that both the sequencing of the functions and their detailed make-up can be readily altered by programming to meet the individual requirements of any given situation.


A qualitative study on the experiences of young adults with eating disorders transferring from pediatric to adult care.
The study's objective was to identify systemic facilitators and barriers of transferring young adults (ages 17-21) with eating disorders from pediatric to adult health and mental health services. Qualitative interviews were conducted and three themes emerged: (a) difficulties navigating care during the transfer period; (b) challenges achieving and maintaining recovery due to systemic barriers after the transfer of care;and (c) recommendations for facilitating the transfer between systems of care. From the perspective of young adults with eating disorders our study shows that the transition to adult care services may be improved with increased coordination, communication, and collaborative partnerships between pediatric and adult providers.


Heart to Heart.
A person who has had a myocardial infarction often gets excellent emergency treatment at a hospital, and is able to go home or even return to work in a matter of days. Despite this quick recovery, all is not perfect, because the infarction stops blood and oxygen flow, which can quickly kill heart tissue. Unlike many other types of human tissue, heart tissue doesn't regenerate, so heart function is compromised.


Effect of cyclooxygenase and NO synthase inhibitors on antinociceptive action of acetaminophen.
The influence of cyclooxygenase (COX) and NO synthase inhibitors on antinociceptive action of acetaminophen (ACETA) was studied in rats. ACETA increased the nociceptive threshold for both mechanical (Randall-Selitto test) and chemical stimuli (writhing test). In both models the existence of ceiling dose of ACETA was observed. Indomethacin (IND), an inhibitor preferentially acting on COX-1, as well as nimesulide (NIM) and celecoxib (CECOX), i.e. respectively preferential and selective inhibitors of COX-2, markedly decreased the antinociceptive activity of ACETA in Randall-Selitto test. In contrast, IND increased, whereas both NIM and CECOX did not have any effect on ACETA action in writhing test. Pretreatment with LG-nitro-L-arginine (L-NO-ARG), an unspecific inhibitor of NO synthase, 7-nitroindazole (7-NI), relatively specific inhibitor of neuronal NO synthase, and L-N6(1-iminoethyl)lysine (L-NIL), relatively selective inhibitor of inducible NO synthase, significantly increased the action of the lower doses of ACETA (50 and 100 mg/kg) in writhing test, whereas it did not modify the effects of the higher doses. Similar effect of L-NO-ARG and 7-NI was observed in Randall-Selitto test, whereas L-NIL did not influence the action of ACETA. The possible involvement of COX and NO synthase systems in antinociceptive activity of ACETA is discussed.


[Giant esophageal lipoma].
Esophageal lipomas are uncommon benign tumors. The main symptom of this type of tumor is dysphagia due to esophageal obstruction. The diagnostic studies of choice are endoscopy, radiological investigation with contrast administration, computed tomography, and echoendoscopy. We present an unusual case of giant pediculated esophageal lipoma which manifested clinically with dysphagia. Management was surgical.


Spread of ticks and tick-borne diseases in Germany due to global warming.
Tick-transmitted diseases like tick-borne encephalitis and Lyme Borreliosis have been well known in Germany for decades. Global climate changes may influence the emergence and reemergence of diseases. Ongoing research now gives an additional focus on other tick-borne pathogens such as Coxiella burnetii, Rickettsia conorii, Anaplasma phagocytophilum and Babesia spp., the causative agents of Q-fever, Mediterranean spotted fever, Anaplasmosis and Babesiosis, respectively. The epidemiology of these pathogens was investigated on ticks as well as on rodents, the main hosts. Therefore adults of Dermacentor spp. (n = 862) and rodents (n = 119) were collected and examined for the existence of C. burnetii and Rickettsia spp. by polymerase chain reaction (PCR). In none of the ticks and rodents C. burnetii could be detected, in contrast to Rickettsia spp. where the infection rate in ticks was about 20%. Over and above that, nymphs and adults of Ixodes ricinus were also collected and investigated by PCR for A. phagocytophilum (n = 5,424), Rickettsia helvetica (n = 1,187) and Babesia spp. (n = 3,113). Thereby infection rates of 1%, 8.9% and 1%, respectively, could be determined. The prevalence in rodents was 5.3% for A. phagocytophilum and 0.8% for Babesia microti. None of the rodents was R. helvetica positive.


Regulation of endometrial cell proliferation by estrogen-induced BDNF signaling pathway.
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factors family. Recent studies indicated that the level of BDNF in follicular fluid is a marker for oocyte quality and infertility. Here, we intend to further investigate the function of BDNF and its signaling pathway in the regulation of endometrial cells proliferation. We found that BDNF is a critical growth factor in endometrial cells. Activation of signal transducer and activator of transcription 3 signaling pathway is required for BNDF-regulated endometrial cell proliferation. Furthermore, BDNF is an effector of estrogen in endometrial cells. Finally, we investigated the different role of Val66Met, a single-nucleotide polymorphism of the BDNF gene, in regulating endometrial cells proliferation. The results showed that BDNFV66M polymorphism is a loss-of-function polymorphism in the regulation of endometrial cells growth. Given the correlation between endometriosis and infertility, it is important to understand the role of BDNF in regulating endometrial cells proliferation and to develop new therapeutic strategies for the treatment of endometriosis-related infertility.


IGFBP3, a transcriptional target of homeobox D10, is correlated with the prognosis of gastric cancer.
Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element "TTAT". Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.


Attenuation of reinforcing and psychomotor stimulant effects of amphetamine by aripiprazole.
Partial dopamine agonists are potential medications for the treatment of amphetamine addiction. They have been hypothesized to stabilize the dopamine system by acting as antagonists during high dopaminergic tone resulting from amphetamine use and as agonists during withdrawal. Aripiprazole is an atypical antipsychotic that acts as a partial D2 dopamine and a serotonin 5-HT₁(A) agonist and a serotonin 5-HT₂(A) antagonist. The aim of the present study was to examine the effects of aripiprazole on behaviors induced and maintained by d-amphetamine. To this end, intravenous d-amphetamine self-administration [fixed ratio 3 (FR3) schedule, 0.02 mg/infusion] and d-amphetamine-induced (0, 1.5 mg/kg intraperitoneally) locomotor activity, as well as spontaneous locomotor activity and sucrose pellet selfadministration (FR3 schedule) were studied in male Wistar rats after aripiprazole (0, 0.3, 1, 3 mg/kg i.p.) administration. Aripiprazole pre-treatment resulted in bidirectional effects on amphetamine self-administration. The 1 mg/kg dose increased, and the highest dose decreased the number of amphetamine infusions. In the locomotor activity experiments, aripiprazole attenuated amphetamine-induced activity dose-dependently and tended to suppress spontaneous activity. The highest aripiprazole doses decreased also sucrose pellet self-administration. The increase in amphetamine self-administration with the intermediate aripiprazole dose, as well as the decrease in amphetamine-induced locomotor activity, suggests that aripiprazole acted as a dopamine antagonist. Suppression of amphetamine and sucrose self-administration by the highest aripiprazole dose was probably caused by non-specific effects. Together, these results indicate that under conditions of dopaminergic stimulation, aripiprazole attenuates the reinforcing and psychomotor stimulant effects of d-amphetamine, but the dose range for this effect is rather limited.


Excitation energy transfer (EET) between molecules in condensed matter: a novel application of the polarizable continuum model (PCM).
We present a quantum-mechanical theory to study excitation energy transfers between molecular systems in solution. The model is developed within the time-dependent (TD) density-functional theory and the solvent effects are introduced in terms of the polarizable continuum model (PCM). Unique characteristic of this model is that both "reaction field" and screening effects are included in a coherent and self-consistent way. This is obtained by introducing proper solvent-specific operators in the Kohn-Sham equations and in the corresponding TD scheme. The solvation model exploits the integral equation formalism (IEF) version of PCM and it defines the solvent operators on a molecular cavity modeled on the real three-dimensional (3D) structure of the solute systems. Applications to EET in dimers of ethylene and naphtalene are presented and discussed.


Evaluation of different antibiotics in inhibiting colonization of Vibrio cholerae O1 and O139 in the rabbit intestine.
The effects of furazolidone, erythromycin and azithromycin in inhibiting colonisation of Vibrio cholerae O1 and O139 in the rabbit intestine were tested. Both V. cholerae O1 and O139 highly colonised the gut in control rabbits. The colonisation of furazolidone-resistant strains in the rabbit intestine was prevented effectively by both erythromycin and azithromycin. In furazolidone-sensitive strains, the efficacies of erythromycin and azithromycin were very much comparable to furazolidone. These results suggested that azithromycin may be subjected to clinical trial in comparison to furazolidone and erythromycin for the treatment of cholera due to O1 and O139 infection in children.


Novel and divergent bipartite mycoviruses associated with the ectomycorrhizal fungus Sarcosphaera coronaria.
Members of the family Partitiviridae are reported from a variety of fungal and plant taxa. After dsRNA-preparation, deep sequencing, and bioinformatics, we here reveal the existence of various divergent partitiviruses co-infecting the ectomycorrhizal fungus Sarcosphaera coronaria, symbiotically associated with the pine species Pinus brutia in Turkey. A total of 75 complete or nearly complete sequences related to the members of Alphapartitivirus and Betapartitivirus, were detected from the ascocarp sample of the fungal isolate. Two of the identified partitivirus genome segments encoding for partitiviral capsid protein represent evolutionarily distinct members of Alphapartitivirus, indicating that they may have diverged in the presence of long spatial isolation. In an attempt to match the two genome segments of the identified partitiviruses and distinguish individual species co-inhabiting a single host, nine possible genome segment pairs were identified.


Two-Dimensional Living Supramolecular Polymerization: Improvement in Edge Roughness of Supramolecular Nanosheets by Using a Dummy Monomer.
Supramolecular polymers are formed through nucleation (i. e., initiation) and polymerization processes, and kinetic control over the nucleation process has recently led to the realization of living supramolecular polymerization. Changing the viewpoint, herein we focus on controlling the polymerization process, which we expect to pave the way to further developments in controlled supramolecular polymerization. In our previous study, two-dimensional living supramolecular polymerization was used to produce supramolecular nanosheets with a controlled area; however, these had rough edges. In this study, the growth of the nanosheets was controlled by using a 'dummy' monomer to produce supramolecular nanosheets with smoothed edges.


Solitary fibrous tumor of the meninges.
The clinical, radiologic, and pathologic features of a case of solitary fibrous tumor of the meninges at the base of the brain are reported. The tumor caused clinical symptoms in a 42-year-old Caucasian male which were indicative of compression of hypothalamus, basal ganglia, and third ventricle. Radiologically it was a large extra-axial mass isointense to brain parenchyma on precontrast T1-weighted images that filled the suprasellar cistern and deformed the left cerebral peduncle. At surgery, the tumor was firm to hard and attached to dura. Histologically the tumor was composed of spindle-cell proliferation in a collagen-rich background but exhibited regional variations. CD34 immunoreactivity was a prominent histologic finding. Ultrastructural features of meningioma, such as complex interdigitation of cell processes and intercellular specialized junctions were absent. The cells showed the typical appearances of fibroblasts with proximity of banded collagen and precollagen and cytoplasmic rough-surfaced endoplasmic reticulum. DNA ploidy analysis showed diploid DNA content. Awareness of this neoplasm may lead to increasingly frequent recognition and the current WHO classification of brain neoplasms should be modified to include this new entity.


Barriers and facilitators to medicine collection through the CCMDD programme at a Durban Hospital.
South Africa has rekindled health reform efforts through the implementation of the Centralised Chronic Medicine Dispensing and Distribution (CCMDD) programme, as a precursor towards achieving envisioned National Health Insurance (NHI). The CCMDD programme enables stable patients to collect chronic medicines dispensed centrally from designated pick-up-points (PuPs). Barriers and facilitators of chronic medicine collection exist at different levels. To identify barriers and facilitators associated with patients' characteristics and noncollection of CCMDD patient medicine parcels (PMPs). The study was conducted at a regional public sector hospital which provides support for 19 primary facilities. An observational cross-sectional comparative study was conducted. There was no statistically significant difference in collection status in terms of most of the variables compared. Patients who had been on treatment longer or who were receiving multiple items were more likely to collect medication, as were patients with arthritis, HIV and AIDS, but the association was no longer significant after adjusting for other confounders. Patients using internal PuPs were significantly more likely to collect their PMPs than patients using external PuPs, and this may have implications for achieving CCMDD objectives. This study has revealed that recently diagnosed patients are enrolled onto the CCMDD programme whilst the chronic condition stability is not yet attained. Patients were also enrolled onto the programme at the referral facility instead of being down-referred. This study makes a case for evaluation research to further assess the CCMDD programme implementation, in order to improve uptake and cost-effectiveness.


Criteria for the detection of sleep-associated bruxism in humans.
Surface electromyography of the masseter and electrocardiogram recordings of heart activity during sleep were performed on nine subjects who suffer from an oral motor dysfunction (bruxism during sleep. Signals were monitored in the subject's home sleeping environment over 4 consecutive nights. A total of 36 nights of data were analyzed to perform the following: (1) describe the nature and magnitude of total masseter muscle electromyographic activity above a minimum threshold of 3% of each subject's individually established maximum voluntary contraction level; and (2) describe electrocardiograph rate changes (using the R-R interval) that occurred in relation to these electromyographic elevations. From these data, criteria for detection of bruxism events were established and combined into a fully automated event detection algorithm. The mean number and duration of the detected bruxism events are reported. The underlying logic for the criteria selected, and what effect other possible criteria would have on the separation of abnormal from normal motor events, is also presented and discussed.


Teratogenic and reproductive studies of policosanol in the rat and rabbit.
The present studies evaluated the teratogenic potential and reproductive toxicity of Policosanol, a new hypocholesterolemic drug. Policosanol was administered by oral gavage to Sprague-Dawley rats and New Zealand White rabbits during the period of organogenesis at dosages up to 500 and 1,000 mg/kg/day, respectively. There was no evidence of teratogenicity or any other embryonal toxicity. In a fertility and reproductive study female rats were treated with Policosanol by oral gavage at dosages up to 500 mg/kg/day, 2 weeks prior to mating and throughout mating and pregnancy to day 21 of lactation. Males were given treatment 60 days before and during mating. Reproductive parameters of mothers were normal. There was no evidence that treatment affected the survival, postnatal growth, or behavior of the offspring. No maternal treatment-related adverse side effects occurred in these studies. It is concluded that Policosanol was not teratogenic in either rats or rabbits, nor did it induce reproductive toxicity in rats.


Role of Pyroptosis in Respiratory Diseases and its Therapeutic Potential.
Pyroptosis is an inflammatory type of regulated cell death that is dependent on inflammasome activation and downstream proteases such as caspase-1 or caspase 4/5/11. The main executors are gasdermins, which have an inherent pore-forming function on the membrane and release inflammatory cytokines, such as interleukin (IL)-1β, IL-18 and high mobility group box 1. Emerging evidence demonstrates that pyroptosis is involved in the pathogenesis of various pulmonary diseases. In this review, we mainly discuss the biological mechanisms of pyroptosis, explore the relationship between pyroptosis and respiratory diseases, and discuss emerging therapeutic strategies for respiratory diseases.


Chronic constipation: advances in management.
Only a relatively small percentage of clinically constipated patients seek medical attention and most can be managed satisfactorily with conservative measures. This review mainly addresses those patients who have refractory or difficult-to-manage functional constipation who are referred to gastrointestinal specialists. Areas of review include insights into pathophysiology, the utility of diagnostic testing and the author's opinions concerning available pharmacologic agents, the role of behavioural therapies and the indications for surgical interventions in this heterogeneous group of patients.


"Pulmonary valve replacement diminishes the presence of restrictive physiology and reduces atrial volumes": a prospective study in Tetralogy of Fallot patients.
Pulmonary valve replacement (PVR) reduces right ventricular (RV) volumes in the setting of long-term pulmonary regurgitation after Tetralogy of Fallot (ToF) repair; however, little is known of its effect on RV diastolic function. Right atrial volumes may reflect the burden of RV diastolic dysfunction. The objective of this paper is to evaluate the clinical, echocardiographic, biochemical and cardiac magnetic resonance (CMR) variables, focusing particularly on right atrial response and right ventricular diastolic function prior to and after elective PVR in adult patients with ToF. This prospective study was conducted from January 2009 to April 2013 in consecutive patients > 18 years of age who had undergone ToF repair in childhood and were accepted for elective PVR. Twenty patients (mean age: 35 years; 70% men) agreed to enter the study. PVR was performed with a bioporcine prosthesis. Concomitant RV reduction was performed in all cases when technically possible. Pulmonary end-diastolic forward flow (EDFF) decreased significantly from 5.4 ml/m(2) to 0.3 ml/m(2) (p < 0.00001), and right atrial four-chamber echocardiographic measurements and volumes by 25% (p = 0.0024): mean indexed diastolic/systolic atrial volumes prior to surgery were 43 ml/m(2) (SD+/-4.6)/63 ml/m(2) (SD+/-5.5), and dropped to 33 ml/m(2) (SD+/-3)/46 ml/m(2) (SD+/-2.55) post-surgery. All patients presented right ventricular diastolic and systolic volume reductions, with a mean volume reduction of 35% (p < 0.00001). Right ventricular diastolic dysfunction was common in a population of severely dilated RV patients long term after ToF repair. Right ventricular diastolic parameters improved as did right atrial volumes in keeping with the known reduction in RV volumes, after PVR.


Dental fluorosis decline after changes to supplement and toothpaste regimens.
In 1989/90, in 659 12-year-olds in Perth (F 0.8 mg/L) and the Bunbury region of Western Australia (WA) (F approximately 0.25 mg/L), dental fluorosis prevalences were 40.2% and 33.0%. Fluoride supplements (OR 4.63) and extended residence in a fluoridated area (OR 4.06) were significant risk factors; toothpaste ingestion variables had ORs greater than unity; in 1990, DMFT for this age group was 0.84. School Dental Service took steps to discourage supplement and toothpaste ingestion and to promote low fluoride toothpaste for children < 6 years of age. To evaluate the effect of this campaign on fluorosis and caries. Between May-July 2000, 582 10-year-olds were examined for dental fluorosis (TF index) and dental caries (DMFT) in school dental clinics. Fluorosis prevalence was 22.2% in Perth and 10.8% in the Bunbury region. Overall prevalence was 18.0% and of this, 80.2% was TF 1, 17.9% was TF 2 and just 1.9% was TF 3. In 1989/90, 79 children had used supplements before the age of 4 year; in 2000 only 40 had done so (P < 0.001). Mean DMFT values in Perth and Bunbury were 0.32 and 0.28 (P > 0.05). Low F toothpaste, unavailable in 1989/90, had been used by 24.5%. The only significant risk factor was residence, OR 2.0. Fluorosis prevalence seems to have fallen in parallel with a reduction in discretionary intake from supplements and toothpaste. No increase in dental caries experience was recorded. Because the teeth examined in this study were at risk of fluorosis in 1992-95, very soon after policies changed, and because people are slow to change health habits, it seems reasonable to expect a further improvement when teeth mineralised in the late 1990s become visible.


Altered temporal organization of plasma insulin oscillations in chronic renal failure.
Chronic renal failure (CRF) is associated with mechanistically unexplained impaired insulin sensitivity. Erratic insulin secretory patterns typify other states of insulin resistance. We sought to investigate possible alterations of plasma insulin oscillations in CRF. We assessed high- and low-frequency insulin and glucose oscillations in 7 male CRF patients and 11 controls by multiparametric deconvolution analysis and cluster analysis, approximate entropy (ApEn) statistic, and cross-ApEn statistics. Insulin sensitivity was appraised by euglycemic hyperinsulinemic clamps. Despite impaired glucose disappearance rates in CRF, fasting and 24-h mean insulin and glucose concentrations did not differ between patients and controls. However, patients showed a 2.5-fold increase of insulin elimination half-life, reduced frequency of both rapid (6.1 +/- 0.4 vs. 7.1 +/- 0.2 h(-1), P < 0.001) and slow oscillations of insulin release (0.54 +/- 0.11 vs. 0.71 +/- 0.1 h(-1), P < 0.001), lack of acceleration and paradoxically more orderly slow insulin and glucose pulses after meals, and increased temporal coupling between insulin and glucose patterns (cross-ApEn: 0.58 +/- 0.13 vs. 1.37 +/- 0.23, P < 0.001). Postprandial glucose intolerance was inferable by prolonged and amplified blood glucose excursions despite exaggerated insulin bursts of almost 3-fold higher area. In summary, CRF is associated with a complex disruption of the temporal organization of insulin release, which differs from abnormalities observed to date in other states of insulin resistance.


Experimental coronary air embolism. Assessment of time course of myocardial ischemia and the protective effect of cardiopulmonary bypass.
In 74 mongrel dogs 0.02 ml air/kg of body weight was injected into the left anterior descending coronary artery (LAD). Forty-three dogs were studied without (group I) and 31 with (group II) extracorporeal circulation (ECC). Time course and extent of myocardial ischemia were assessed by continous thermographic measurements as well as by fluorescence techniques. Coronary air embolism resulted in an immediate decrease of myocardial temperature associated with transmural ischemia. In 31 surviving dogs (72%) of group I this phenomenon was fully reversible within 8.7 minutes as compared with 5.4 minutes in 100% of the surviving dogs from group II. No postembolic death occurred in the group II animals. In group II the postembolic temperature decrease was significantly less than that in group I, and, in addition, the myocardial area involved was significantly smaller. The results indicate that the extent of myocardial ischemia following coronary air embolism and its time course can be well-documented by means of thermocardiography; using extracorporeal circulation survival can be improved and myocardial damage minimized.


Association of glyphosate exposure with multiple adverse outcomes and potential mediators.
Glyphosate (GLY) is a widely used herbicide with potential adverse effects on public health. However, the current epidemiological evidence is limited. This study aimed to investigate the potential associations between exposure to GLY and multiple health outcomes. The data on urine GLY concentration and nine health outcomes, including type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), obesity, chronic kidney disease (CKD), hepatic steatosis, cancers, chronic obstructive pulmonary disease (COPD), and neurodegenerative diseases (NGDs), were extracted from NHANES (2013-2016). The associations between GLY exposure and each health outcome were estimated using reverse-scale Cox regression and logistic regression. Furthermore, mediation analysis was conducted to identify potential mediators in the significant associations. The dose-response relationships between GLY exposure with health outcomes and potential mediators were analyzed using restricted cubic spline (RCS) regression. The findings of the study revealed that individuals with higher urinary concentrations of GLY had a higher likelihood of having T2DM, hypertension, CVD and obesity (p < 0.001, p = 0.005, p < 0.001 and p = 0.005, respectively). In the reverse-scale Cox regression, a notable association was solely discerned between exposure to GLY and the risk of T2DM (adjusted HR = 1.22, 95% CI: 1.10, 1.36). Consistent outcomes were also obtained via logistic regression analysis, wherein the adjusted OR and 95% CI for T2DM were determined to be 1.30 (1.12, 1.52). Moreover, the present investigation identified serum high-density lipoprotein cholesterol (HDL) as a mediator in this association, with a mediating effect of 7.14% (p = 0.040). This mediating effect was further substantiated by RCS regression, wherein significant dose-response associations were observed between GLY exposure and an increased risk of T2DM (p = 0.002) and reduced levels of HDL (p = 0.001). Collectively, these findings imply an association between GLY exposure and an increased risk of T2DM in the general adult population.


The Cell Wall of the Human Fungal Pathogen Aspergillus fumigatus: Biosynthesis, Organization, Immune Response, and Virulence.
More than 90% of the cell wall of the filamentous fungus Aspergillus fumigatus comprises polysaccharides. Biosynthesis of the cell wall polysaccharides is under the control of three types of enzymes: transmembrane synthases, which are anchored to the plasma membrane and use nucleotide sugars as substrates, and cell wall-associated transglycosidases and glycosyl hydrolases, which are responsible for remodeling the de novo synthesized polysaccharides and establishing the three-dimensional structure of the cell wall. For years, the cell wall was considered an inert exoskeleton of the fungal cell. The cell wall is now recognized as a living organelle, since the composition and cellular localization of the different constitutive cell wall components (especially of the outer layers) vary when the fungus senses changes in the external environment. The cell wall plays a major role during infection. The recognition of the fungal cell wall by the host is essential in the initiation of the immune response. The interactions between the different pattern-recognition receptors (PRRs) and cell wall pathogen-associated molecular patterns (PAMPs) orientate the host response toward either fungal death or growth, which would then lead to disease development. Understanding the molecular determinants of the interplay between the cell wall and host immunity is fundamental to combatting Aspergillus diseases.


Hemodynamic response to resistance exercise with and without blood flow restriction in healthy subjects.
To compare the hemodynamic response during resistance exercise at high intensity (HI), low intensity (LI) and low intensity with blood flow restriction (LI-BFR) in healthy subjects. Twelve men performed three sets of unilateral knee extension exercises at LI-BFR and LI (15 repetitions; 20% of 1RM) and HI (8 repetitions; 80% of 1RM). The blood flow restriction was accomplished using a sphygmomanometer positioned on the thigh and inflated to the point of blood flow interruption (167·9 ± 16·6 mmHg). The hemodynamic variables were obtained by continuous beat-to-beat photoplethysmography. Rating of perceived exertion (RPE) and blood lactate were also measured. The HI session showed higher values (P<0·05) in all sets than the LI and LI-BFR for diastolic blood pressure, heart rate and rate-pressure product. The LI-BFR showed higher values than the LI only in the 3rd set for systolic blood pressure, heart rate and rate-pressure product. Blood lactate was higher in the HI (4·2 ± 0·2 mmol) and LI-BFR (4·1 ± 0·3 mmol) than the LI (3·5 ± 0·3 mmol). Rating of perceived exertion was higher in the LI-BFR (7·9 ± 0·3) than the HI (6·4 ± 0·4) and LI (3·2 ± 0·4). The LI-BFR session exhibited similar blood lactate to the HI, a higher rating of perceived response than the HI and LI, and equal or lower hemodynamic responses than the HI.


Screening new cancer patients for psychological distress using the hospital anxiety and depression scale.
The diagnosis of a life-threatening illness creates immediate psychosocial distress for the patient and his or her family. The threat is real and the rational response is to be afraid. We need to be reaching out to patients and their families and not waiting for crises. The responsibility remains with the healthcare system and psychosocial healthcare professionals to identify those who are in most need. Psychological distress is something that can be relatively easily measured and responded to when psychosocial oncology healthcare professionals are immediately available to address those needs. This paper describes the process used to gather this information, how that information has been used by the psychosocial clinicians in the Supportive Care programme, and what we have learned, in terms of a retrospective data analysis, about our patient population. At the Cancer Centre in Thunder Bay, Ontario, Canada new cancer patients complete the HADS on the day of their first appointment. Since October 2000 we have collected baseline psychological distress data for 3,035 new cancer patients who fully completed all 14 items on the HADS. Of those, 781 patients, or 25.7%, scored above cut-off points and were given a telephone call. We were able to contact 607 (or 77.7%) of these patients. Five hundred and eight (or 83.7%) of those contacted made, and subsequently attended, one or more appointments with a psychosocial counsellor.


Post-endoscopic procedure satisfaction scores: Can we improve?
To organize post-procedure satisfaction data into a useful reference and analyze patient-centered parameters to find trends that influence patient satisfaction. A robust database of two cohorts of outpatients that underwent an endoscopic procedure at Georgetown University Hospital at two separate three-month intervals ranging from November 2012 to January 2013 and November 2015 to January 2016 was compiled. Time of year was identical to control for weather/seasonal issues that may have contributed to the patient experience. The variables recorded included age, sex, body mass index (BMI), type of procedure, indication for procedure, time of the procedure, length of the procedure, type of prep used, endoscopist, satisfactory score, and comments/reasons for score. For continuous variables, differences in averages were tested by two sample t-test, Wilcoxon rank sum test, and ANOVA as appropriate. For categorical variables, differences in proportions between two groups were tested by χ2 test. Correlation test and linear regression analyses were conducted to examine relationships between length of procedure and continuous predictors. A P value < 0.05 used to indicate statistically significant relationship. The primary outcome of this study was to assess if telephone outreach after an endoscopic intervention was a satisfactory method of obtaining post-procedure satisfaction scores from patients at a tertiary care center. With the addition of post-procedure calls, instilled in January 2014, the response rate was 40.5% (508/1256 patients) from a prior completion rate of 3.4% (31/918) with the mail out survey initially. There was a statistically significant improved response rate pre and post intervention with P < 0001. The secondary outcome of this study was to assess if we could use predictive analytics to identify independent predictors of procedure length, such as gender, age, type of procedure, time of procedure, or BMI. The combined pre and post intervention data was used in order to optimize the power to identify independent predictors of procedure length. The total number of patient's data analyzed was 2174. There was no statistically significant difference in procedure length between males and females with P value 0.5282. However, there was a small (1 min), but statistically significant difference (P = 0.0185) in procedure length based on the time of day the procedure took place, with afternoon procedures having a longer duration than morning procedures. The type of procedure was an independent predictor of procedure length as demonstrated with P value < 0.0001. There is a statistically significant correlation between age and procedure length, although it is only a weak relationship with a correlation coefficient < 0.3. Contrary to patient age, BMI did not have a statistically significant correlation with procedure length (P = 0.9993), which was also confirmed by linear regression analysis. Our study proves calling patients after endoscopy improves post-procedure satisfaction response rates and changing procedural time allotment based on patient characteristics would not change endoscopic workflow.


Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas.
The aim of the study was the evaluation of morphology and immunophenotype of canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours, located in skin, oral cavity and spleen were surgically excised, fixed and processed for histopathology and immunohistochemistry (CD79α, CD18, proliferating cell nuclear antigen, metallothionein). Histologically, tumours were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin, or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression of CD79α antigen. The expression of CD18 was observed in canine cutaneous and splenic tumours. In canine tumours expression of metallothionein was low to moderate, while in feline plasmacytomas - absent or low. In canine tumours, the mitotic index and proliferating cell nuclear antigen index were positively correlated with the expression of metallothionein. In feline tumours no correlation between mitotic index, proliferating cell nuclear antigen and metallothionein was found. This is the first study describing expression of metallothionein in canine and feline extramedullary plasmacytoma.


A novel immunoliposome mediated by CD123 antibody targeting to acute myeloid leukemia cells.
The application of the tumor targeting antibody-mediated immunoliposomes (ILP) provides us a potential effective strategy for treating malignancies, such as acute myeloid leukemia (AML). CD123, which is specifically overexpressed on AML cells, plays an important role in cell cycling and enhances the cell resistance to the apoptotic stimuli. Given such a unique role of CD123 in AML cells, we aim to develop a novel drug targeting delivery system using CD123 monoclonal antibody (mAb) in this study. On the basis of the daunorubicin (DNR) loaded PEGylated liposomes (DNR-LP), a post-insertion method was applied to covalently attach the anti-CD123 mAb onto the surface of the liposomes to obtain the anti-CD123 mAb modified immunoliposomes (CD123-ILP). Immunoliposomes with different anti-CD123 mAb density (mAb/liposomal S100PC, molar ratio, 0.06%, L-CD123-ILP and 0.14%, H-CD123-ILP) were prepared, respectively. The expressions of CD123 in KG-1a, Kasumi-1, HL-60, NB4 and THP-1 cells were determined by flow cytometry. The cell binding and uptake assays revealed that CD123-ILP was internalized into the CD123+ AML cells, while the MTT assay indicated that CD123-ILP had stronger inhibitory effect on the growth of THP-1 and KG-1a cells, in which CD123 were highly expressed. Furthermore, in vitro drug release studies of DNR-LP and CD123-ILP showed a sustained release profile for both systems, which were further confirmed by in vivo pharmacokinetics study of liposomal DNR in rats. In this study, we reported the development of CD123-ILP for the first time by our best knowledge, which offered a promising drug targeting delivery system against CD123+ AML cells.


Improving care practices for patients with multidrug-resistant organisms: one facility's evolution.
The care of patients with multidrug-resistant organisms (MDROs) varies in rehabilitation settings. Implementation of strict contact isolation in some facilities may limit patients from reaching their rehabilitation goals. This article describes our rehabilitation and long-term acute care facility's efforts to develop a policy that would enable patients with MDROs to meet their rehabilitation goals within a safe environment. A multidisciplinary team developed a two-track care process allowing staff to quickly identify appropriate activities for these patients. The team also developed educational materials for staff and families, addressed cleaning practices, and standardized the criteria for follow-up cultures and discontinuation of isolation. The MDRO policy was instituted throughout the hospital in August 1999. The incidence of nosocomially acquired MDROs has decreased slightly from the baseline rate of .076 per 100 patient days to .039 per 100 patient days during the 4-month period following the implementation of the policy.


Breitenlohner-Freedman Bound on Hyperbolic Tilings.
We establish how the Breitenlohner-Freedman (BF) bound is realized on tilings of two-dimensional Euclidean Anti-de Sitter space. For the continuum, the BF bound states that on Anti-de Sitter spaces, fluctuation modes remain stable for small negative mass squared m^{2}. This follows from a real and positive total energy of the gravitational system. For finite cutoff ϵ, we solve the Klein-Gordon equation numerically on regular hyperbolic tilings. When ϵ→0, we find that the continuum BF bound is approached in a manner independent of the tiling. We confirm these results via simulations of a hyperbolic electric circuit. Moreover, we propose a novel circuit including active elements that allows us to further scan values of m^{2} above the BF bound.


Status of lipids as a risk factor for stroke.
There is mounting epidemiologic evidence to support the relationship of lipids as a risk factor for ischemic stroke. We review epidemiologic and pathophysiologic evidence for such a link. Treatment of hyperlipidemia is addressed within the context of overall cardiovascular disease risk but also for stroke prevention.


Linear tricationic room-temperature ionic liquids: synthesis, physiochemical properties, and electrowetting properties.
Efficient and facile synthesis of novel linear tricationic room-temperature ionic liquids was performed, and their physiochemical properties were determined. Different physiochemical properties were observed according to the structural variations such as the cationic moiety and the counteranion of the ionic liquid. The electrowetting properties of these ionic liquids were also investigated, and linear tricationic ionic liquids were shown to be advantageous as effective electrowetting materials due to their high structural flexibility.


Synergistic induction of NY-ESO-1 antigen expression by a novel histone deacetylase inhibitor, valproic acid, with 5-aza-2'-deoxycytidine in glioma cells.
NY-ESO-1, one of the most immunogenic cancer/testis antigens, provides attractive targets for cancer immunotherapy. NY-ESO-1 has been demonstrated to be expressed in a range of solid tumors via DNA demethylation and/or histone modification; however, it has been rarely expressed in glioma. The reversibility of these epigenetic aberrations is potentially attractive for glioma treatment with DNA-methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), leading to reactivation of silenced genes. We previously demonstrated de novo induction of NY-ESO-1 in glioma cells by DNMTi. In this study, we show that an anticonvulsant, i.e., valproic acid (VPA), also acting as an HDACi, enhances induction of NY-ESO-1 in synergy with DNMTi. Chromatin assays demonstrated that combination of DNMTi and VPA elicited significant DNA demethylation, histone H3 Lys9 demethylation, and acetylation. These findings not only shed light on an epigenetic immunotherapy, but also suggest that the silencing of NY-ESO-1 is mediated by histone modification.


Ecological context and metapopulation dynamics affect sex-ratio variation among dioecious plant populations.
Populations of dioecious flowering plants commonly exhibit heterogeneity in sex ratios and deviations from the equilibrium expectation of equal numbers of females and males. Yet the role of ecological and demographic factors in contributing towards biased sex ratios is currently not well understood. Species-level studies from the literature were analysed to investigate ecological correlates of among-population sex-ratio variation and metapopulation models and empirical data were used to explore the influence of demography and non-equilibrium conditions on flowering sex ratios. The survey revealed significant among-population heterogeneity in sex ratios and this was related to the degree of sampling effort. For some species, sex-ratio bias was associated with the proportion of non-reproductive individuals, with greater male bias in populations with a lower proportion of individuals that were flowering. Male-biased ratios were also found at higher altitudes and latitudes, and in more xeric sites. Simulations and empirical data indicated that clonal species exhibited greater heterogeneity in sex ratios than non-clonal species as a result of their slower approach to equilibrium. The simulations also indicated the importance of interactions between reproductive mode and founder effects, with greater departures from equilibrium in clonal populations with fewer founding individuals. The results indicate that sex-based differences in costs of reproduction and non-equilibrium conditions can each play important roles in affecting flowering sex ratios in populations of dioecious plants.


Tyrosine phosphorylation modulates the activity of TRPV4 in response to defined stimuli.
Src family tyrosine kinases (SFKs) regulate the function of several transient receptor potential (TRP) family members, yet their role in the regulation of the vanilloid subfamily member 4 protein (TRPV4) remains controversial. TRPV4 is a calcium-permeable channel activated by numerous physical and chemical stimuli. Here we show that SFKs mediate tyrosine phosphorylation of TRPV4 in different cell lines. Using mass spectrometric analysis, we identified two novel phosphorylation sites in the cytosolic N- and C-terminal tails of TRPV4. Substitution of either tyrosine with phenylalanine led to a substantial reduction in the overall tyrosine phosphorylation level of TRPV4, suggesting that these two tyrosines constitute major phosphorylation sites. Both mutants efficiently localized to the plasma membrane, indicating that neither tyrosine is required for trafficking of TRPV4 in the secretory pathway. Analysis of the channel function demonstrated a crucial role of the N-terminal tyrosine residue in the activation of TRPV4 by heat, mechanical (shear) stress, hypotonic cell swelling, and phorbol 12-myristate 13-acetate, but not in the activation by synthetic ligand 4alpha-phorbol 12,13-didecanoate. Furthermore, the response of TRPV4 to phorbol 12-myristate 13-acetate was SFK-dependent. Because the SFK-mediated phosphorylation of the N-terminal tyrosine occurred before TRPV4 activation, tyrosine phosphorylation appears to sensitize rather than activate this channel. Reactive oxygen species, known to mediate inflammatory pain, strongly up-regulated TRPV4 phosphorylation in the presence of SFKs. Our findings indicate that tyrosine phosphorylation of TRPV4 represents an important modulatory mechanism, which may underlie the recently described function of TRPV4 in inflammatory hyperalgesia.


[Observation over three seasons of respiratory syncytial virus infection in a geriatric health service facility].
To characterize the impact of respiratory syncytial virus (RSV) infection on respiratory illness in a geriatric health service facility. All facility residents were observed for respiratory symptoms from January 2010 to March 2012. The presence of an RSV antigen was examined in selected patients using rapid antigen test. I observed one outbreak of RSV and four outbreaks of respiratory infection without RSV. I also observed two cases of sporadic RSV infection, one of which had pneumonia. An RSV outbreak in the facility was observed only when RSV cases from pediatricians were four times more frequently reported than the usual seasonal average. More patients with severe respiratory illness were observed during an RSV outbreak than during other outbreaks. RSV can cause severe respiratory illness in elderly patients. Repeated invasion from surrounding infectious environments may be essential for an RSV outbreak to occur. Moreover, although the sensitivity of rapid RSV antigen tests may have influenced the results of the current study, such sensitivity in elderly patients is reportedly diverse in the literature, and the reasons for such variation have not yet been elucidated. We postulate that a reason for such variation is a viral co-infection, in particular of the bocavirus, which has a reported high incidence of co-infection and which affects viral shedding. Furthermore, human metapneumovirus has been reported to influence the severity of RSV infection. Most of these knowledges concerning the influence of co-infection were obtained from pediatric studies, therefore we need further investigations targetting elderly patients.


SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE UNITED STATES.
The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration. Consecutive patients (n = 200) with neovascular age-related macular degeneration were studied. A Control Cohort included patients with good (20/20-20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to 20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort 4: 20/800 to no light perception. An interviewer-administered, standardized, written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely to neovascular age-related macular degeneration. The mean annual societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged $39,910 (P < 0.001). Study Subcohort 1 costs averaged $20,339, while Subcohort 4 costs averaged $82,984. Direct ophthalmic medical costs comprised 17.9% of Study Cohort societal ophthalmic costs, versus 74.1% of Control Cohort societal ophthalmic costs (P < 0.001) and 10.4% of 20/800 to no light perception subcohort costs. Direct nonmedical costs, primarily caregiver, comprised 67.1% of Study Cohort societal ophthalmic costs, versus 21.3% ($1,302/$6,116) of Control Cohort costs (P < 0.001) and 74.1% of 20/800 to no light perception subcohort costs. Total societal ophthalmic costs associated with neovascular age-related macular degeneration dramatically increase as vision in the better-seeing eye decreases.


A novel assay to determine acetylcholinesterase activity: The application potential for screening of drugs against Alzheimer's disease.
Acetycholinesterase (AChE) that regulates hydrolysis of acetylcholine (ACh) in the brain, is an important target for treatment of Alzheimer's disease (AD), a feature of which is ACh deficiency. However, the methods to precisely determine AChE activity are still under development. We developed a new method to exploit acetylcholine-d4 as a surrogate substrate of ACh and measure product choline-d4 via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay detected activity of AChE present in the normal mouse brain, which is consistent with the standard Ellman assay that determines products spectrophotometrically. In AD mouse models, the result of LC-MS/MS assay showed significant higher AChE activity than that seen in control normal mice, while treatment of AD mice with an AChE inhibitor, huperzine A, led to partial decreases in AChE activity. Our results suggest that this surrogate-based LC-MS/MS method is a new, sensitive and convenient assay for the determination of AChE activity, providing a useful means for screening active compounds that target AChE.


Highly sensitive and selective nonenzymatic detection of glucose using three-dimensional porous nickel nanostructures.
Highly sensitive and selective nonenzymatic detection of glucose has been achieved using a novel disposable electrochemical sensor based on three-dimensional (3D) porous nickel nanostructures. The enzyme-free sensor was fabricated through in situ growing porous nickel networks on a homemade screen-printed carbon electrode substrate via electrochemically reducing the Ni(2+) precursor, along with continuously liberating hydrogen bubbles. The resulting nickel-modified electrode was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectrometry (EDX), powder X-ray diffractometry (XRD), and electrochemical techniques. Cyclic voltammetric, alternating-current impedance, and amperometric methods were used to investigate the catalytic properties of the assembled sensor for glucose electro-oxidation in alkaline media. Under optimized conditions, the enzymeless sensor exhibited excellent performance for glucose analysis selectively, offering a much wider linear range (from 0.5 μM to 4 mM), an extremely low detection limit (0.07 μM, signal-to-noise ratio (S/N) of 3), and an ultrahigh sensitivity of 2.9 mA/(cm(2) mM). Importantly, favorable reproducibility and long-term performance stability were obtained thanks to the robust frameworks. Application of the proposed sensor in monitoring blood glucose was also demonstrated.


Moderate intensity aerobic exercise may enhance neuroplasticity of the contralesional hemisphere after stroke: a randomised controlled study.
Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to determine whether a single bout of moderate intensity aerobic exercise can enhance neuroplasticity in people with stroke. Participants were randomly assigned (1:1) to a 20-min moderate intensity exercise intervention or remained sedentary (control). Transcranial magnetic stimulation measured corticospinal excitability of the contralesional hemisphere by recording motor evoked potentials (MEPs). Intermittent Theta Burst Stimulation (iTBS) was used to repetitively activate synapses in the contralesional primary motor cortex, initiating the early stages of neuroplasticity and increasing excitability. It was surmised that if exercise increased neuroplasticity, there would be a greater facilitation of MEPs following iTBS. Thirty-three people with stroke participated in this study (aged 63.87 ± 10.30 years, 20 male, 6.13 ± 4.33 years since stroke). There was an interaction between Time*Group on MEP amplitudes (P = 0.009). Participants allocated to aerobic exercise had a stronger increase in MEP amplitude following iTBS. A non-significant trend indicated time since stroke might moderate this interaction (P = 0.055). Exploratory analysis suggested participants who were 2-7.5 years post stroke had a strong MEP facilitation following iTBS (P < 0.001). There was no effect of age, sex, resting motor threshold, self-reported physical activity levels, lesion volume or weighted lesion load (all P > 0.208). Moderate intensity cycling may enhance neuroplasticity in people with stroke. This therapy adjuvant could provide opportunities to maximize stroke recovery.


Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1.
Meiotic recombination differs from mitotic recombination in that DSBs are repaired using homologous chromosomes, rather than sister chromatids. This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-specific proteins, Hop1 and Red1. HOP1 contains two functional domains, called the N and C domains. Analysis of a point mutation that specifically inactivates the C domain (hop1-K593A) reveals that the N domain is sufficient for Hop1 localization to chromosomes and for Red1 and Hop1 interactions. The C domain is needed for spore viability, for chromosome synapsis, and for preventing DMC1-independent DSB repair, indicating it plays a role in the BSCR. All of the hop1-K593A phenotypes can be bypassed by fusion of ectopic dimerization domains to Mek1, suggesting that the function of the C domain is to promote Mek1 dimerization. Hop1 is a DSB-dependent phosphoprotein, whose phosphorylation requires the presence of the C domain, but is independent of MEK1. These results suggest a model in which Hop1 phosphorylation in response to DSBs triggers dimerization of Mek1 via the Hop1 C domain, thereby enabling Mek1 to phosphorylate target proteins that prevent repair of DSBs by sister chromatids.


Stretch-Induced Reductions in Throwing Performance Are Attenuated by Warm-up Before Exercise.
Recent investigations have suggested that static stretching (SS) performed before exercise reduces muscular performance. However, it is yet unknown whether dynamic warm-up exercises performed together with SS may actually minimize the detrimental acute effects of stretching on muscular performance. This study aimed to assess the effects of static shoulder stretching exercises, dynamic warm-up exercises, or both together, on muscular performance evaluated by ball throwing. Twenty-one female handball players (age: 16.2 ± 1.0 years [range: 14-18 years], height: 167.0 ± 10.0 cm [range: 158-179 cm], and body mass: 63.3 ± 7.6 kg [range: 50.4-77.4 kg]) performed SS, dynamic warm-up exercises or both, targeting the muscles of the upper limbs. Thereafter, medicine ball throwing distance and handball ball throwing speed tests were performed. Static stretching performed before the medicine ball throwing test reduced performance when compared with the warm-up exercises (95% confidence interval [CI] = 0.02-0.17, p ≤ 0.05, effect size [ES] = 0.34). When a warm-up exercise routine was added to SS, the detrimental effects of SS were abolished (95% CI = -0.01 to 0.18, p > 0.05, ES = 0.31). The throwing speed was the same over the 3 conditions. In conclusion, warm-up exercises performed together with SS abolished the impairment in medicine ball throwing distance. We recommend that athletes perform warm-up exercises together with SS before activity to avoid detrimental effects on muscle strength.


[Reversal of multidrug resistance of tumor cells by anti-mdr1 ribozyme].
To stably reverse the multidrug resistance (MDR) of breast carcinoma cells in vitro. Two anti-mdr-1 ribozyme plasmids, RZ196 and RZ179, were constructed with EGFP as reporter gene and transfected into drug-resistant breast carcinoma cells in vitro. The expression of EGFP was observed by laser confocal microscopy. Flow cytometry, RT-PCR and Rhodamine123 efflux assay were used to detect P-glyco protein (p-gp) and mdr-1 mRNA. After transfection with RZ196 and RZ179, the mdr-1 indices were reduced from 2.20 to 0.76 and 1.40, the expression rates of p-gp were reduced from 55.0% to 4.6% and 18.2%, the fluorescence intensity increased from 22.0% to 46.2% and 70.1%, TCL reduced from 75% to 28% and 43% respectively. In addition, the expression of ribozyme plasmid in tumor cells was stable under G418 selection. After two months, the mdr-1 indices remained at 0.81 and 1.47 in the cells transfected RZ196 and RZ179 respectively. The expression rates of p-gp were 5.2% and 19.5% and the Rh123 fluorescence intensity was 51.4% and 71.6% respectively. Both anti-mdr-1 ribozyme RZ196 and RZ179 can stably reverse MDR phenotype of breast carcinoma cells in vitro. RZ196 construct appears to be more effective.


Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) Immunotherapy: A Promising Breakthrough in Cancer Therapeutics.
The advent of immune checkpoint inhibitors has revolutionized cancer therapy by leveraging the body's immune system to combat malignancies effectively. Among these groundbreaking agents, programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have emerged as pivotal therapeutic approaches. PD-L1, a key protein expressed on the surface of various cells, including cancer cells, plays a central role in immune regulation by interacting with the programmed cell death protein 1 (PD-1) receptor on T-cells leading to immune suppression. The substantial increase in PD-L1 expression on cancer cell surfaces has driven the exploration of PD-1/PD-L1 inhibitors as potential immunotherapeutic agents. These inhibitors are monoclonal antibodies designed to impede the PD-L1 and PD-1 interaction and disrupt the immunosuppressive signal, thereby reinvigorating the anti-tumor immune response mediated by activated T-cells. Clinical trials investigating PD-1/PD-L1 inhibitors have demonstrated remarkable efficacy in the treatment of diverse advanced or metastatic cancers, including leukemia, non-small cell lung (NSCLC), hepatocellular, melanoma, gastric, colorectal, and breast cancers, among others. Regulatory approvals have been granted for both monotherapy and combination therapy with other cancer treatments, encompassing chemotherapy and additional immune checkpoint inhibitors. While PD-1/PD-L1 inhibitors have exhibited significant success, they are not devoid of challenges. The emergence of intrinsic or acquired resistance, as well as immune-related adverse events, warrants thorough investigation and management. Consequently, researchers have embarked on combination trials to augment the therapeutic potential of PD-1/PD-L1 inhibitors and surmount resistance mechanisms.


Predicting the likelihood of lower respiratory tract Ureaplasma infection in preterms.
To develop predictive models of Ureaplasma spp lower airway tract infection in preterm infants. A dataset was assembled from five cohorts of infants born <33 weeks gestational age (GA) enrolled over 17 years (1999-2016) with culture and/or PCR-confirmed tracheal aspirate Ureaplasma status in the first week of life (n=415). Seventeen demographic, obstetric and neonatal factors were analysed including admission white blood cell (WBC) counts. Best subset regression was used to develop three risk scores for lower airway Ureaplasma infection: (1) including admission laboratory values, (2) excluding admission laboratory values and (3) using only data known prenatally. GA and rupture of membranes >72 hours were significant predictors in all 3 models. When all variables including admission laboratory values were included in the regression, WBC count was also predictive in the resulting model. When laboratory values were excluded, delivery route was found to be an additional predictive factor. The area under the curve for the receiver operating characteristic indicated high predictive ability of each model to identify infants with lower airway Ureaplasma infection (range 0.73-0.77). We developed predictive models based on clinical and limited laboratory information available in the perinatal period that can distinguish between low risk (<10%) and high risk (>40%) of lower airway Ureaplasma infection. These may be useful in the design of phase III trials of therapeutic interventions to prevent Ureaplasma-mediated lung disease in preterm infants and in clinical management of at-risk infants.


Structural characteristics of small-molecule inhibitors targeting FTO demethylase.
Studies have shown that the FTO gene is closely related to obesity and weight gain in humans. FTO is an N6-methyladenosine demethylase and is linked to an increased risk of obesity and a variety of diseases, such as acute myeloid leukemia, type 2 diabetes, breast cancer, glioblastoma and cervical squamous cell carcinoma. In light of the significant role of FTO, the development of small-molecule inhibitors targeting the FTO protein provides not only a powerful tool for grasping the active site of FTO but also a theoretical basis for the design and synthesis of drugs targeting the FTO protein. This review focuses on the structural characteristics of FTO inhibitors and discusses the occurrence of obesity and cancer caused by FTO gene overexpression.


Cause-specific mortality of psychiatric inpatients and outpatients in a general hospital in Korea.
This study aimed to examine the cause-specific excess mortality of psychiatric patients in a general hospital in Korea. Between January 1995 and December 2006, 29 986 patients presented to the outpatient clinic of a general hospital in Seoul, Korea, or were admitted to that hospital for psychiatric disorders. Their cause-specific mortality risk was compared with that of age-matched patients from the general Korean population. The mortality risk of psychiatric patients was 1.6 times higher than that of the general population. Inpatients, younger adults, and patients with alcohol use disorders or schizophrenia had the highest standardized mortality rates (SMRs). Alcohol use disorder was associated with extremely high SMRs of more than 20 for hematological disease and digestive system disease. Effective preventive measures are required to reduce the excess mortality of psychiatric patients, particularly alcohol-dependent patients and younger patients who have been admitted for general psychiatric care.


Multiparametric Kelvin Probe Force Microscopy for the Simultaneous Mapping of Surface Potential and Nanomechanical Properties.
We report high-resolution multiparametric kelvin probe force microscopy (MP-KPFM) measurements for the simultaneous quantitative mapping of the contact potential difference (CPD) and nanomechanical properties of the sample in single-pass mode. This method combines functionalities of the force-distance-based atomic force microscopy and amplitude-modulation (AM) KPFM to perform measurements in single-pass mode. During the tip-sample approach-and-retract cycle, nanomechanical measurements are performed for the retract part of nanoindentation, and the CPD is measured by the lifted probe with a constant tip-sample distance. We compare the performance of the proposed method with the conventional KPFMs by mapping the CPD of multilayer graphene deposited on n-doped silicon, and the results demonstrate that MP-KPFM has comparable performance to AM-KPFM. In addition, the experimental results of a custom-fabricated polymer grating with heterogeneous surfaces validate the multiparametric imaging capability of the MP-KPFM. This method can have potential applications in finding the inherent link between nanomechanical properties and the surface potential of the materials, such as the quantification of the electromechanical response of the deformed piezoelectric materials.


Emerging threat of candida resistance among neonates at a teaching institute of Jharkhand.
In the past few decades, candidemia has escalated to worrisome levels, leading to substantial morbidity and mortality in neonates. The rise in anti-fungal drug resistance demands prompt diagnosis and treatment. This study aimed to determine the speciation and susceptibility pattern of Candida species recovered from special care new-born units and identify risk factors for developing candidemia in neonates. A total of 580 blood samples from clinically suspected septicemic neonates were collected and subjected to culture. Cultures positive for yeasts were sub-cultured on Sabouraud dextrose agar. Identification of a suspected purified colony of Candida was confirmed to the species level by both conventional and automated techniques matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. Anti-fungal susceptibility of isolates was performed by an automated method (VITEK 2 system) using VITEK 2 cards. Multi-variate logistic regression analysis was used to identify risk factors associated with candidemia. A total of 56 (9.66%) isolates of Candida species were recovered from 580 blood cultures. Non-albicans Candida species predominated with 82.14% of cases, whereas 17.86% of cases were caused by Candida albicans. Candida tropicalis (46.42%) was the most common isolate recovered, followed by Candida albicans (17.8%). Risk factor analyses identified a very low birth weight [odds ratio (OR) =4.05, 95% confidence interval (CI) =2.03-8.08] and prolonged antibiotic therapy (OR = 3.79, 95% CI = 1.7-8.7) among others as significant predictors of candidemia. All the Candida isolates showed 100% sensitivity to voriconazole and micafungin, whereas the overall sensitivities for fluconazole, amphotericin B, caspofungin, and flucytosine were 85.71%, 96.43%, 96.43%, and 91.07%, respectively. Candidemia is a life-threatening condition in neonates. Identification of Candida species and routine anti-fungal susceptibility is a must to select a suitable and effective anti-fungal therapy to revoke emerging resistance to anti-fungals.


VMAT2 Inhibitors in Neuropsychiatric Disorders.
The basal ganglia and dopaminergic pathways play a central role in hyperkinetic movement disorders. Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disorders, but have recently gained more attention following their development for specific indications in the United States. At present, there are three commercially available VMAT2 inhibitors: tetrabenazine, deutetrabenazine, and valbenazine. Pharmacokinetics, metabolism, and dosing vary significantly between the three drugs, and likely underlie the more favorable side effect profile of the newer agents (deutetrabenazine and valbenazine). Tetrabenazine and deutetrabenazine have demonstrated safety and efficacy in the treatment of chorea associated with Huntington's disease, including in randomized controlled trials, although direct comparison studies are limited. Both deutetrabenazine and valbenazine have demonstrated safety and efficacy in the treatment of tardive dyskinesia, with multiple double-blind, placebo-controlled trials, whereas tetrabenazine has been studied less rigorously. There have been no blinded, prospective trials with tetrabenazine in Tourette's syndrome (TS); however, double-blind, placebo-controlled trials in TS are ongoing for both deutetrabenazine and valbenazine. Given the favored side effect profile of newer VMAT2 inhibitors, clinicians should be aware of the distinctions between agents and become familiar with differences in their use, especially as there is potential for their utilization to increase across the range of hyperkinetic movement disorders.


Low cortisol levels and the balance between punishment sensitivity and reward dependency.
The neuro-endocrinological basis of psychopathy, a disorder characterized by lack of fear, is relatively unknown. However, low levels of cortisol may result in fearlessness and have been observed in individuals with psychopathic tendencies. Low fear models state that psychopaths are not motivated to avoid punishment, especially when reward is pending. In agreement, disadvantageous decision making on the IOWA gambling task in psychopaths and psychopathic analogous, indicates low punishment sensitivity and high reward dependency. Here, it was investigated whether low basal cortisol levels predicted the balance between punishment sensitivity and reward dependency in the same manner. As hypothesized, the most disadvantageous pattern of decision making was found in the subjects with the lowest cortisol levels. These findings suggest that low levels of cortisol may set the balance between the sensitivity for punishment and reward dependency towards a pre-disposition for psychopathy.


[A clinical analysis of 123 cases of primary empty sella].
Objective: This study was conducted to analyze the clinical characteristics and pituitary function of patients with primary empty sella (PES). Methods: The clinical data from 123 hospitalized adult patients with PES from January 2010 to May 2016 were retrospectively studied. Results: (1) The average age of the 123 (male 43, female 80) PES patients was (59.2±13.6) years (ranging 24-92 years), among whom 61% patients were in the age group between 50-69 years. (2) The symptoms of the patients included fatigue (56.1%), headache (34.1%), nausea and vomiting (17.9%), gonadal dysfunction (17.1%), visual disturbance (5.7%) and hypopituitarism crisis (3.3%). (3) Hypopituitarism was found in 66 of the 123 patients. Among them, 36.6%, 31.7% and 17.1% were central hypoadrenalism, hypogonadism, and hypothyroidism, respectively.The percentage of hypopituitarism in complete PES was significantly higher than that in partial PES (P<0.05). (4) Sixteen patients were concomitant with other autoimmune diseases including 11 patients with Graves' disease and 2 with Cushing's syndrome due to adrenal adenoma. Conclusions: The incidence of hypopituitarism in PES was 53.7%, in which the pituitary-adrenal axis hypofunction was more common. An overall evaluation of the pituitary function was essential for the patients who had headache and fatigue, or with suspected PES. The patients with hypopituitarism should be given hormone replacement therapy in time and followed up afterword.


[Variants in the definitive organization of the lumbar lymph-conducting pathways in the applied aspect].
Topographic-anatomical investigations gave grounds for the description of 4 stages of the development of the posterior parietal bed of the abdominal cavity. On the basis of the embryo-anatomical systematization three morpho-topographic types of the lumbo-lymphatic pathways were established: right-sided (20%), left-sided (20%) and uniform (60%) types, each of them playing a certain part in metastasizing. Embryo-anatomical grounds are given for operative accesses to the superficial group of the right and left lumbar lymphatic pathways.


[Prospects for application of stem cells from adipose tissue in treating erectile dysfunction].
Although phosphodiesterase type 5 inhibitors are the first-line treatment of ED, some patients remain unresponsive to any pharmacotherapy. To date, the use of stem cells is considered as a new treatment modality for erectile dysfunction. The validity of this assumption has been experimentally proved in preclinical and clinical studies. The main focus is on the stem cells derived from adipose tissue, due to advantages over other sources.


Bacterial translocation and microgap formation at a novel conical indexed implant abutment system for single crowns.
A conometric concept was recently introduced in which conical implant abutments hold the matching crown copings by friction alone, eliminating the need for cement or screws. The aim of this in vitro study was to assess the presence of microgap formation and bacterial leakage at the Acuris conometric restorative interface of three different implant abutment systems. A total of 75 Acuris samples of three implant-abutment systems (Ankylos, Astra Tech EV, Xive) were subjected to microbiological (n = 60) and scanning electron microscopic (SEM) investigation (n = 15). Bacterial migration into and out of the conical coupling system were analyzed in an anaerobic workstation for 48, 96, 144, and 192 h. Bacterial DNA quantification using qrt-PCR was performed at each time point. The precision of the conometric coupling and internal fit of cemented CAD/CAM crowns on corresponding Acuris TiN copings were determined by means of SEM. qrt-PCR results failed to demonstrate microbial leakage from or into the Acuris system. SEM analysis revealed minute punctate microgaps at the apical aspect of the conometric junction (2.04 to 2.64 µm), while mean cement gaps of 12 to 145 µm were observed at the crown-coping interface. The prosthetic morse taper connection of all systems examined does not allow bacterial passage. Marginal integrity and internal luting gap between the ceramic crown and the coping remained within the clinically acceptable limits. Conometrically seated single crowns provide sufficient sealing efficiency, relocating potential misfits from the crown-abutment interface to the crown-coping interface.


Proton Quantum Tunneling: Influence and Relevance to Acidosis-Induced Cardiac Arrhythmias/Cardiac Arrest.
Acidosis and its associated pathologies predispose patients to develop cardiac arrhythmias and even cardiac arrest. These arrhythmias are assumed to be the result of membrane depolarization, however, the exact mechanism of depolarization during acidosis is not well defined. In our study, the model of quantum tunneling of protons is used to explain the membrane depolarization that occurs during acidosis. It is found that protons can tunnel through closed activation and inactivation gates of voltage-gated sodium channels Nav1.5 that are present in the membrane of cardiac cells. The quantum tunneling of protons results in quantum conductance, which is evaluated to assess its effect on membrane potential. The quantum conductance of extracellular protons is higher than that of intracellular protons. This predicts an inward quantum current of protons through the closed sodium channels. Additionally, the values of quantum conductance are influential and can depolarize the membrane potential according to the quantum version of the GHK equation. The quantum mechanism of depolarization is distinct from other mechanisms because the quantum model suggests that protons can directly depolarize the membrane potential, and not only through indirect effects as proposed by other mechanisms in the literature. Understanding the pathophysiology of arrhythmias mediated by depolarization during acidosis is crucial to treat and control them and to improve the overall clinical outcomes of patients.


Enhanced Activity and Stability of Gold/Ceria-Titania for the Low-Temperature Water-Gas Shift Reaction.
Gold supported on ceria-zirconia is one of the most active low temperature water-gas shift catalysts reported to date but rapid deactivation occurs under reaction conditions. In this study, ceria-titania was evaluated as an alternative catalyst support. Materials of different Ce:Ti compositions were synthesized using a sol-gel methodology and gold was supported onto these using a deposition-precipitation method. They were then investigated as catalysts for the low-temperature water-gas shift reaction. Au/Ce0.2Ti0.8O2 exhibited superior activity and stability to a highly active, previously reported gold catalyst supported on ceria-zirconia. High activity and stability was found to be related to the support comprising a high number of oxygen defect sites and a high specific surface area. These properties were conducive to forming a highly active catalyst with well-dispersed Au species.


Measurement of plasma choline in acute coronary syndrome: importance of suitable sampling conditions for this assay.
Blood choline has been proposed as a predictor of acute coronary syndrome (ACS), however different testing procedures might affect the choline concentration because the lysophospholipase D activity of autotaxin (ATX) can convert lysophosphatidylcholine to lysophosphatidic acid (LPA) and choline in human blood. Although the influences of ATX on LPA levels are well known in vivo and in vitro, those on choline have not been elucidated. Therefore, we established suitable sampling conditions and evaluated the usefulness of plasma choline concentrations as a biomarker for ACS. Serum LPA and choline concentrations dramatically increased after incubation depending on the presence of ATX, while their concentrations in plasma under several conditions were differently modulated. Plasma choline levels in genetically modified mice and healthy human subjects, however, were not influenced by the ATX level in vivo, while the plasma LPA concentrations were associated with ATX. With strict sample preparation, the plasma choline levels did not increase, but actually decreased in ACS patients. Our study revealed that ATX increased the choline concentrations after blood sampling but was not correlated with the choline concentrations in vivo; therefore, strict sample preparation will be necessary to investigate the possible use of choline as a biomarker.