Syncope as a health risk for soldiers - influence of medical history and clinical findings on the sensitivity of head-up tilt table testing.
Syncope is a relevant health problem in military environments. Reliable diagnosis is challenging. Tilt table testing is an important tool for syncope diagnosis. The aim of this study was to determine whether signs such as prodromal symptoms, co-morbidity, frequency of syncopal events, body length, body mass index, and electrocardiography abnormalities can be used to predict the success of tilt table testing at diagnosing syncope. Data from 100 patients with histories of syncope or pre-syncope, who were diagnosed using head-up tilt table testing, were retrospectively analyzed in a cross-sectional analysis. The diagnostic procedure was based upon a modified version of the Westminster protocol without any pharmacological provocation. Patients showing pathological reaction patterns during tilt table testing suffered from prodromal symptoms, such as dizziness and sweating, significantly more often. The patients reported more injuries resulting from syncopal events and more previous syncopal events, and the prevalence of co-morbidity was greater among patients presenting negative findings during tilt testing. An asthenic-leptosomal physique was not confirmed as a risk factor for syncopal events as is the case for idiopathic arterial hypotension. However, patients with pathological reaction patterns during tilt table testing were significantly taller. This finding was detected for both females and males. No significant predictors were found in the electrocardiogram (ECG) patterns of patients showing syncope during tilt table testing. Frequency of prior syncope and prodromal symptoms, and increased body length with an otherwise good state of health influence the predictive value of tilt table testing for syncope diagnosis. In particular, if these factors are present, tilt table testing should be considered part of the diagnostic algorithm for soldiers with recurrent syncope.


Individual choice of opioids and formulations: strategies to achieve the optimum for the patient.
The role of opioid therapy in chronic musculoskeletal disease continues to be controversial. However, recent years have seen a gradual shift towards the use of opioid therapy in chronic non-malignant pain (CNMP) following recognition that at least a subpopulation of such patients appears to benefit from long-term opioid treatment. Misconceptions about opioids and the associated risk of dependence stemmed from older research that was fundamentally flawed. More recent, rigorous research has yielded clearer statistics on opioid dependence and has highlighted the need for screening to identify individuals who may require closer monitoring during long-term opioid therapy. Controlled-release formulations (oral and transdermal) for the management of steady pain, in conjunction with fast-acting, immediate-release formulations for the management of breakthrough pain, may be available for a wide range of opioid analgesics, providing comprehensive therapy systems for use in CNMP. However, there are no universal criteria that can be confidently used to select CNMP patients who might profit from or be responsive to opioid therapy. Opioid treatment must therefore be individualised for each patient, based on a clear understanding of drug absorption, metabolism, toxicity and binding characteristics, using opioid switching strategies where appropriate. Practical guidelines for opioid therapy in CNMP include regular and systematic checks of treatment results to adjust therapy for each individual patient and to ensure optimum benefit.


Does previous caesarean section at full dilatation increase the likelihood of subsequent spontaneous preterm birth?
There is emerging evidence that caesarean section at full dilatation is associated with an increased risk of subsequent spontaneous preterm birth. To investigate the association between caesarean section at full dilatation and spontaneous preterm birth in subsequent pregnancies. This was a retrospective cohort study of women who had two consecutive births at Royal Prince Alfred Hospital, 1989-2015. Our main comparison group was women who had emergency caesarean sections during the first stage of labour. Secondary comparison groups were women who had elective caesarean sections, instrumental deliveries and unassisted vaginal deliveries. The primary outcome was spontaneous preterm birth (<37 weeks gestation) in a subsequent pregnancy. There were 2672 women who had an emergency caesarean section, with 2142 (80%) performed during the first stage of labour and 533 (20%) at full dilatation. The rates of spontaneous preterm birth in a subsequent pregnancy were 1.7% and 3.8%, respectively (odds ratio 2.2 (95%CI 1.3-3.8), P = 0.003). The hazard ratio for spontaneous onset of labour at any given gestation from 20 weeks until full term was 1.4 (95%CI 1.2-1.6) and did not change after adjusting for maternal age and body mass index. There is a significantly higher rate of subsequent spontaneous preterm birth in women who had a caesarean section at full dilatation compared with women who had a caesarean section during the first stage of labour. Awareness of this as a risk factor may warrant referral to a high-risk obstetric or preterm birth clinic.


Fractionation of the Gulf toadfish intestinal precipitate organic matrix reveals potential functions of individual proteins.
The regulatory mechanisms behind the production of CaCO3 in the marine teleost intestine are poorly studied despite being essential for osmoregulation and responsible for a conservatively estimated 3-15% of annual oceanic CaCO3 production. It has recently been reported that the intestinally derived precipitates produced by fish as a byproduct of their osmoregulatory strategy form in conjunction with a proteinaceous matrix containing nearly 150 unique proteins. The individual functions of these proteins have not been the subject of investigation until now. Here, organic matrix was extracted from precipitates produced by Gulf toadfish (Opsanus beta) and the matrix proteins were fractionated by their charge using strong anion exchange chromatography. The precipitation regulatory abilities of the individual fractions were then analyzed using a recently developed in vitro calcification assay, and the protein constituents of each fraction were determined by mass spectrometry. The different fractions were found to have differing effects on both the rate of carbonate mineral production, as well as the morphology of the crystals that form. Using data collected from the calcification assay as well as the mass spectrometry experiments, individual calcification promotional indices were calculated for each protein, giving the first insight into the functions each of these matrix proteins may play in regulating precipitation.


COVID-19 Disruptions of Food Systems and Nutrition Services in Ethiopia: Evidence of the Impacts and Policy Responses.
Since its first case of COVID-19 on March 13, 2020, Ethiopia has exerted efforts to curb the spread of SARS-CoV-2 (COVID-19) without imposing a nationwide lockdown. Globally, COVID-19 related disruptions and mitigation measures have impacted livelihoods and food systems, nutrition, as well as access and use of health services. To develop a comprehensive understanding of the impacts of the COVID-19 pandemic on food systems, health services, and maternal and child nutrition and to synthesize lessons from policy responses to the COVID-19 pandemic in Ethiopia. We conducted a review of literature and 8 key informant interviews across government agencies, donors, and non-governmental organizations (NGOs), to map the impacts of the COVID-19 pandemic on the food and health systems in Ethiopia. We summarized policy responses and identified recommendations for future actions related to the COVID-19 pandemic and other future emergencies. The impacts of the COVID-19 pandemic were felt across the food system and include limited agriculture inputs due to travel restrictions and closed borders restricting trade, reduced in-person support by agriculture extension workers, income losses, increases in food prices, and the reduction in food security and dietary diversity. Maternal and child health services were disrupted due to fear of contacting COVID-19, diversion of resources, and lack of personal protective equipment. Disruptions eased over time due to the expansion of social protection through the Productive Safety Net Program, and the increased outreach and home service provision by the health extension workers. Ethiopia experienced disruptions to food systems and maternal and child nutrition services due to the COVID-19 pandemic. However, by expanding existing social protection programs and public health infrastructure and leveraging partnerships with non-state actors, the extent of the impact of the pandemic was largely minimized. Nevertheless, vulnerabilities and gaps remain and there is a need for a long-term strategy that considers the potential for future pandemics and other shocks.


Engineering Camelina sativa (L.) Crantz for enhanced oil and seed yields by combining diacylglycerol acyltransferase1 and glycerol-3-phosphate dehydrogenase expression.
Plant seed oil-based liquid transportation fuels (i.e., biodiesel and green diesel) have tremendous potential as environmentally, economically and technologically feasible alternatives to petroleum-derived fuels. Due to their nutritional and industrial importance, one of the major objectives is to increase the seed yield and oil production of oilseed crops via biotechnological approaches. Camelina sativa, an emerging oilseed crop, has been proposed as an ideal crop for biodiesel and bioproduct applications. Further increase in seed oil yield by increasing the flux of carbon from increased photosynthesis into triacylglycerol (TAG) synthesis will make this crop more profitable. To increase the oil yield, we engineered Camelina by co-expressing the Arabidopsis thaliana (L.) Heynh. diacylglycerol acyltransferase1 (DGAT1) and a yeast cytosolic glycerol-3-phosphate dehydrogenase (GPD1) genes under the control of seed-specific promoters. Plants co-expressing DGAT1 and GPD1 exhibited up to 13% higher seed oil content and up to 52% increase in seed mass compared to wild-type plants. Further, DGAT1- and GDP1-co-expressing lines showed significantly higher seed and oil yields on a dry weight basis than the wild-type controls or plants expressing DGAT1 and GPD1 alone. The oil harvest index (g oil per g total dry matter) for DGTA1- and GPD1-co-expressing lines was almost twofold higher as compared to wild type and the lines expressing DGAT1 and GPD1 alone. Therefore, combining the overexpression of TAG biosynthetic genes, DGAT1 and GPD1, appears to be a positive strategy to achieve a synergistic effect on the flux through the TAG synthesis pathway, and thereby further increase the oil yield.


Epigenetic analysis in rheumatoid arthritis synoviocytes.
Rheumatoid arthritis (RA) is a complex chronic systematic disease with progressive destruction of the joints by invasive synoviocytes. To characterize the key regulators involved in the development of RA, we obtained multilayer epigenomics data including DNA methylation by whole-genome bisulfite sequencing, miRNA profiles, genetic variations by whole-exome sequencing, and mRNA profiles from synoviocytes of RA and osteoarthritis (OA) patients. The overall DNA methylation patterns were not much different between RA and OA, but 523 low-methylated regions (LMRs) were specific to RA. The LMRs were preferentially localized at the 5' introns and overlapped with transcription factor binding motifs for GLI1, RUNX2, and TFAP2A/C. Single base-scale differentially methylated CpGs were linked with several networks related to wound response, tissue development, collagen fibril organization, and the TGF-β receptor signaling pathway. Further, the DNA methylation of 201 CpGs was significantly correlated with 27 expressed miRNA genes. Our interpretation of epigenomic data of the synoviocytes from RA and OA patients is an informative resource to further investigate regulatory elements and biomarkers responsible for the pathophysiology of RA and OA.


Intimate partner violence and child loss: an evaluation of 7 sub-Saharan African countries.
Intimate partner violence (IPV) and child loss disproportionately affect women in sub-Saharan Africa (SSA). Little research has examined the relationship between IPV and child loss in SSA. We used data from Demographic Health Surveys in 7 countries in SSA (Côte d'Ivoire, Democratic Republic of the Congo, Namibia, Sierra Leone, Togo, Zambia, and Rwanda). Women's Health Module questions assessed lifetime physical, sexual, and emotional IPV. Child loss was calculated as the difference between the number of child births and the number of living children. Logistic regression was conducted adjusting for age, marital status, educational attainment, location of residence, wealth, sexually transmitted infections, and country of origin. Data were weighted and analysed using STATA Software (14.0). Among women who gave birth, approximately one third (31.7%) reported that they lost 1 or more children. Nearly half (44.3%) reported that they experienced physical IPV during their lifetime. Women who had experienced physical, emotional, or sexual IPV were significantly more likely to report a loss of 1 or more children (OR=1.20, 95% confidence interval (CI)= [1.08, 1.33]; OR=1.30, 95% CI= [1.16, 1.45]; OR=1.42, 95% CI= [1.23, 1.65], respectively) in comparison with women who had not experienced IPV controlling for potentially influential covariates. Women who were older, married, had lower educational attainment, and had lower income were more likely to have lost 1 or more children. These results suggest that women who experienced all types of and cumulative exposure to IPV may be more likely to lose a child in SSA.


Congenital Aneuploidy in Klinefelter Syndrome with B-Cell Acute Lymphoblastic Leukemia Might Be Associated with Chromosomal Instability and Reduced Telomere Length.
Rare congenital aneuploid conditions such as trisomy 13, trisomy 18, trisomy 21 and Klinefelter syndrome (KS, 47,XXY) are associated with higher susceptibility to developing cancer compared with euploid genomes. Aneuploidy frequently co-exists with chromosomal instability, which can be viewed as a "vicious cycle" where aneuploidy potentiates chromosomal instability, leading to further karyotype diversity, and in turn, paving the adaptive evolution of cancer. However, the relationship between congenital aneuploidy per se and tumor initiation and/or progression is not well understood. We used G-banding analysis, array comparative genomic hybridization analysis and quantitative fluorescence in situ hybridization for telomere length analysis to characterize the leukemic blasts of a three-year-old boy with KS and B-cell acute lymphoblastic leukemia (B-ALL), to gain insight into genomic evolution mechanisms in congenital aneuploidy and leukemic development. We found chromosomal instability and a significant reduction in telomere length in leukemic blasts when compared with the non-leukemic aneuploid cells. Reviewing published cases with KS and B-ALL revealed 20 additional cases with B-ALL diagnostic cytogenetics. Including our present case, 67.7% (14/21) had acquired two or more additional chromosomal aberrations at B-ALL diagnosis. The presented data indicate that congenital aneuploidy in B-ALL might be associated with chromosomal instability, which may be fueled by enhanced telomere attrition.


The Peptidolipide J (CH(3)-(CH(2))(n)-CO-D Phe-L Ile-L Ile-L Phe-L Ala-O-CH(3)) is obtained also in acidic form by a chromatographic artefact. In chloroformic solutions the ester and the acid behave in a very different way: the acid has a stable conformation, as shown by the infra-red spectra and the optical rotary dispersion; this conformation is stabilized by hydrogen bonding between two peptide chains associated as a carboxylic dimer.


Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis.
Intercellular adhesion molecule (ICAM)-5 (telencephalin) is an adhesion molecule in telencephalic neurons of the mammalian brain that binds to the leukocyte integrin CD11a/CD18. The authors observed that human cerebral neurons also expressed ICAM-5 and that ICAM-5--mediated neuron--leukocyte binding in cultured hippocampal neurons. This led the authors to examine ICAM-5 expression during clinical CNS inflammation. The authors found, by immunoblotting, a 115-kDa soluble form of ICAM-5 (sICAM-5) cleaved from the membrane-bound (130 kDa) ICAM-5, and established an ELISA assay to measure it. CSF samples of patients with acute encephalitis and MS were studied. sICAM-5 was increased in encephalitis (320 plus minus 107 ng/mL; n = 25), as compared with patients with MS (128 plus minus 10 ng/mL; n = 16) and control subjects without CNS disease (137 plus minus 6 ng/mL; n = 42) (p < 0.001). The concentration of sICAM-5 correlated with the performance in the immediate recall task (p = 0.013) and with the leukocyte count in the CSF (p = 0.02), especially in cases caused by herpes simplex virus (HSV) (r = 0.94; p = 0.002). sICAM-5 is cleaved from CNS into CSF during acute encephalitis, and it may mediate leukocyte--neuron interactions. sICAM-5 release from cerebral neurons may actively regulate immune responses and leukocyte adhesion during microbial neuroinvasion in humans during encephalitis.


Identification of Underlying Inflammation in Vogt-Koyanagi-Harada Disease with Sunset Glow Fundus by Multiple Analyses.
To evaluate underlying subclinical ocular inflammation in Vogt-Koyanagi-Harada (VKH) disease with sunset glow fundus (SGF) by multiple analyses. Retrospective observational study. Clinical records of 34 eyes of 17 VKH patients with SGF in whom laser flare photometry (LFP), enhanced depth imaging optical coherence tomography (EDI-OCT), and indocyanine green angiography (ICGA) were performed on the same day were reviewed. The mean age was 57.3 ± 16.3 years, and the mean duration from the initial onset of uveitis was 47.1 ± 22.1 months. Flare counts, ICGA scores, and subfoveal choroidal thickness (SFCT) were compared between eyes. Although clinical ocular inflammation was observed only in 4 eyes (11.8%), inflammatory signs were observed in 23 out of 34 eyes by LFP (67.6%), in 27 eyes by ICGA (79.4%), and in 10 eyes by SFCT (29.4%). Active inflammatory signs detected by ICGA were observed in 77.8% by LFP and in 25.9% by SFCT. The strength of agreement (Cohen's kappa coefficient) between positive ICGA score and positive flare score was 0.406 (95% CI: 0.076-0.7359, P < 0.01), but there was no association between positive ICGA score and increased SFCT. In addition, positive flare count was the significant prognostic factor of positive ICGA score with odds ratio 11.7. Subclinical ocular inflammation signs were detected in most VKH patients with SGF by ICGA and a substantial proportion of which were also detected by LFP, whereas SFCT was less sensitive to detect subclinical inflammation.


Development and Application of a Novel SPE-Method for Bioassay-Guided Fractionation of Marine Extracts.
The biological diversity of marine habitats is a unique source of chemical compounds with potential use as pharmaceuticals, cosmetics and dietary supplements. However, biological screening and chemical analysis of marine extracts pose specific technical constraints and require adequate sample preparation. Here we report an improved method on Solid Phase Extraction (SPE) to fractionate organic extracts containing high concentration of salt that hampers the recovery of secondary metabolites. The procedure uses a water suspension to load the extracts on a poly(styrene-divynylbenzene)-based support and a stepwise organic solvent elution to effectively desalt and fractionate the organic components. The novel protocol has been tested on MeOH-soluble material from three model organisms (Reniera sarai, Dendrilla membranosa and Amphidinium carterae) and was validated on a small panel of 47 marine samples, including sponges and protists, within discovery programs for identification of immuno-stimulatory and anti-infective natural products.


Calcified Amorphous Tumor Causing Shower Embolism to the Brain: A Case Report with Serial Echocardiographic and Neuroradiologic Images and a Review of the Literature.
An 89-year-old woman with chronic atrial fibrillation, hypertension, chronic heart failure, and dementia was admitted to our hospital due to multiple small cerebral and cerebellar infarctions. Transthoracic echocardiogram revealed a floating calcified mass lesion arising from the endocardium of the posterior portion of the mitral annulus with mitral annular calcification. Furthermore, the mass had a heterogeneity of the echogenicity. The mass was diagnosed as a calcified amorphous tumor based on specific echocardiographic features. Serial echocardiograms showed shrinkage and disappearance of the mass, and magnetic resonance image revealed new infarction in the left occipital lobe. Embolization of the mass appeared to cause systemic embolism.


Fungal rhinosinusitis and imaging modalities.
This report provides an overview of fungal rhinosinusitis with a particular focus on acute fulminant invasive fungal sinusitis (AFIFS). Imaging modalities and findings that aid in diagnosis and surgical planning are reviewed with a pathophysiologic focus. In addition, the differential diagnosis based on imaging suggestive of AFIFS is considered.


Metal-Triazolate-Framework-Derived FeN4 Cl1 Single-Atom Catalysts with Hierarchical Porosity for the Oxygen Reduction Reaction.
The construction of single-atom catalysts (SACs) with high single atom densities, favorable electronic structures and fast mass transfer is highly desired. We have utilized metal-triazolate (MET) frameworks, a subclass of metal-organic frameworks (MOFs) with high N content, as precursors since they can enhance the density and regulate the electronic structure of single-atom sites, as well as generate abundant mesopores simultaneously. Fe single atoms dispersed in a hierarchically porous N-doped carbon matrix with high metal content (2.78 wt %) and a FeN4 Cl1 configuration (FeN4 Cl1 /NC), as well as mesopores with a pore:volume ratio of 0.92, were obtained via the pyrolysis of a Zn/Fe-bimetallic MET modified with 4,5-dichloroimidazole. FeN4 Cl1 /NC exhibits excellent oxygen reduction reaction (ORR) activity in both alkaline and acidic electrolytes. Density functional theory calculations confirm that Cl can optimize the adsorption free energy of Fe sites to *OH, thereby promoting the ORR process. The catalyst demonstrates great potential in zinc-air batteries. This strategy selects, designs, and adjusts MOFs as precursors for high-performance SACs.


Stone removal by percutaneous papillary balloon dilatation for cystic duct and bile duct stones after cholecystectomy and distal gastrectomy with Roux-en-Y gastrojejunostomy.
A 71-year-old woman was referred to our department for abdominal pain. She was diagnosed with acute obstructive cholangitis due to cystic duct and bile duct stones after cholecystectomy and Roux-en-Y gastrojejunostomy. Two years ago, the patient underwent endoscopic and laparoscopic treatment for cystic duct and bile duct stones, however, the stones remained. This time, she was treated with stone removal using percutaneous papillary balloon dilatation (PPBD). Large stones in the common hepatic and bile ducts were crushed by electrohydraulic lithotripsy and then pushed out into the duodenum through the dilated papilla of Vater using a balloon catheter covered with the sheath and cholangioscopy. Stone in the cystic duct was pulled to the common bile duct and pushed to the duodenum. Stone removal using PPBD is an excellent alternative for patients with cystic duct and bile duct stones unable to be treated with endoscopic or laparoscopic stone removal.


Saponins from Harpullia cupanioides.
Five new saponins have been isolated from the stem bark of Harpullia cupanioides and identified as 3-O-beta-D-glucopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 22-O-angeloyl-A1-barrigenol, 3-O-beta-D-glucopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 28-O-angeloyl-A1-barrigenol, 3-O-beta-D-galactopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 28-O-angeloyl-A1-barrigenol. 3-O-beta-D-galactopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 16-O-beta, beta-dimethylacryloyl-camelliagenin A and 3-O-beta-D-glucopyranosyl(1-->2)[alpha-L-rhamnopyranosyl(1-->3)] beta-D-glucuronopyranosyl 28-O-angeloyl-camelliagenin A. The structures were elucidated by analysis of 2D-NMR spectra and mass spectra.


The effects of an abrupt increase in taxes on candy and soda in Norway: an observational study of retail sales.
Fiscal policies are used to promote a healthier diet; however, there is still a call for real-world evaluations of taxes on unhealthy foods and beverages. We aimed to evaluate the effect of an abrupt increase, of respectively 80 and 40%, in the excising Norwegian taxes on candy and beverages on volume sales of candy and soda. We expected sales to fall. We analyzed electronic point of sale data covering approximately 98% of volume sales of grocery stores in Norway. In two pre-registered models with weekly (log-)sales of taxed candy and soda from 3884 individual stores, we modeled the difference between the jump (discontinuity) in the trend around the time of the increase in taxes and the corresponding jump in the trend in a control season from the previous years (Model 1). In addition, we modeled the difference between the intervention and the control season in their changes in average sales (Model 2). Model 1 showed a 6.1% (one-sided 95% CI: not applicable (NA), 23.4, p-value = 0.26) increase and a - 3.9% (95% CI: NA, 4.9, p-value = 0.23) reduction in the differences in the jump in the trends, for candy and soda, respectively. The second model showed a relative decrease of - 4.9% (95% CI: NA, 1.0, p-value = 0.08) in the average sales of candy and an increase of 1.5% (95% CI: NA, 5.0, p-value = 0.24) in sales of soda. Supplementary analyses suggested that the results were sensitive to clustering on the time dimension. When using two different quasi-experimental designs to model changes in volume sales of taxed candy and soda, we were not able to detect reductions in sales that coincided with an increase in the taxes. Variation across time makes it difficult to detect potentially small changes in sales even when using an entire country's worth of sales data on the level of individual stores. We speculate that the tax increases were too modest to affect the prices to alter sales sufficiently.


Adsorption and removal of phthalic acid and diethyl phthalate from water with zeolitic imidazolate and metal-organic frameworks.
ZIF-8 (zinc-methylimidazolate framework-8), one of the zeolitic imidazolate frameworks (ZIFs), has been used for the removal of phthalic acid (H2-PA) and diethyl phthalate (DEP) from aqueous solutions via adsorption. The adsorption capacity of the ZIF-8 for H2-PA was much higher than that of a commercial activated carbon or other typical metal-organic frameworks (MOFs). Because the surface area and pore volume of the adsorbents showed no favorable effect on the adsorption of H2-PA, the remarkable adsorption with ZIF-8 suggests a specific favorable interaction (electrostatic interaction) between the positively charged surface of ZIF-8 and the negatively charged PA anions. In addition, acid-base interactions also have a favorable contribution in the adsorption of H2-PA, based on the adsorptive performances of pristine and amino-functionalized MOFs and adsorption over ZIF-8 at acidic condition (pH=3.5). The reusability of ZIF-8 was also demonstrated after simple washing with methanol. On the other hand, ZIF-8 was not effective in adsorbing DEP probably because of little charge of DEP in a water solution.


2-(4-Methyl-phen-yl)-3-oxo-4-phenyl-2,3,3a,4,9,9a-hexa-hydro-1H-benzo[f]iso-indole-6-carbo-nitrile.
In the title compound, C26H22N2O, one phenyl ring, one five-membered N-heterocyclic ring and one six-membered carbocyclic ring make up the hexa-hydro-benzo[f]iso-indole core. Another phenyl group is attached to the heterocyclic N atom as a substituent. The non-aromatic five- and six-membered rings both exhibit boat conformations. In the crystal, weak C-H⋯O and C-H⋯N inter-actions establish the observed three-dimensional structure. The crystal studied was refined as an inversion twin.


Outpatient Combined Group and Individual Cognitive-Behavioral Treatment for Patients With Migraine and Tension-Type Headache in a Routine Clinical Setting.
To test the long-term clinical effectiveness (follow-up at 3, 6 and 12 months) of an outpatient combined group and individual cognitive-behavioral treatment (CBT) for headache patients following standard medical care. A decrease in headache intensity, frequency, headache-specific impairment, depression, and change of pain-related cognitions was expected. The efficacy of CBT for primary headaches has been confirmed in research, yet the translation into clinical practice has remained untested thus far. In this single-group outcome study, 87 headache patients diagnosed with migraine and/or tension-type headache received (1) headache-specific medication for 10 weeks and (2) a subsequent CBT treatment made up of 13 individual and 12 group sessions consisting of psychoeducation, progressive muscle relaxation, coping strategies for pain and stress, and goal setting skills. Booster group sessions after 3 and 6 months were implemented to stimulate individual goal attainment, and follow-up measures were recorded up to 12 months. A significant decrease was found for all primary and secondary outcome criteria, ie, average headache intensity (prae M: 6.0, standard deviation [SD]: 1.5 vs follow-up [FU] 1 year M: 5.1, SD: 1.9), headache frequency (prae M: 16.0, SD: 9.5 vs FU 1 year M: 13.4, SD: 9.9), and catastrophizing (prae M: 3.4, SD: 1.0 vs FU 1 year M: 2.6, SD: 1.1). Coping strategies were increased (prae M: 3.4, SD: .9 vs FU 1 year M: 4.0, SD: 1.0). CBT treatment is a useful component within a routine clinical setting and can improve standard medical care thereby helping patients in managing their headache pain.


Activation of mTOR signaling by novel fluoromethylene phosphonate analogues of phosphatidic acid.
Phosphonate analogues of phosphatidic acid (PA) were synthesized in which the bridging oxygen was replaced by an alpha-monofluoromethylene (-CHF-) or alpha-difluoromethylene (-CF(2)-) moiety using hydrolytic kinetic resolution (HKR) of a racemic epoxide as the key step. Since PA activates signaling in the mTOR (mammalian target of rapamycin) pathway, these metabolically stabilized PA analogues were evaluated in quiescent HEK 293 cells. Most of these analogues surpassed PA in activating S6 kinase, a downstream target of mTOR signaling. The unnatural (2R) analogues were more slightly active than the natural (2S) enantiomers for both the mono- and difluoromethylene phosphonates.


Cloning and tissue expression of ATP-binding cassette transporters in cynomolgus macaques.
Cynomolgus macaques are used in preclinical studies in part because of their evolutionary closeness to humans. However, drug transporters, including ATP-binding cassette (ABC) transporters, which are essential for the absorption and excretion of drugs, have not been fully investigated at the molecular level in cynomolgus macaques. In this study, ABCB4, ABCC3, ABCC4, and ABCG2 cDNAs were newly identified and characterized, along with ABCB1, ABCB11, and ABCC2 cDNAs previously identified, in cynomolgus macaques. All seven cynomolgus ABC transporters had high sequence identities (96-98%) with their human orthologs in terms of amino acid sequences and were also most closely clustered with their human orthologs by phylogenetic analysis. Furthermore, the gene structures and genomic organization were similar in cynomolgus macaques and humans. The mRNAs of these cynomolgus ABC transporters, as analyzed using the quantitative polymerase chain reaction, showed distinct tissue expression patterns. Among the ten tissues, ABCB1, ABCC2, ABCC3, and ABCG2 mRNAs were most abundantly expressed in jejunum; ABCB4 and ABCB11 in liver; and ABCC4 in kidney, which are similar to the expression patterns of human ABC transporters. These results suggest molecular similarities of the ABC transporters in cynomolgus macaques and humans.


[Clear-cell hidradenoma of an unusual location].
A case of clear cell hidradenoma, which develops from the eccrine glands of the skin, is reported. Specially the histological characteristics, the histogenesis and the unusual localisation of this tumor are described.


The effect of photodynamic therapy on tumor cell expression of major histocompatibility complex (MHC) class I and MHC class I-related molecules.
Photodynamic therapy (PDT) is FDA-approved anti-cancer modality for elimination of early disease and palliation in advanced disease. PDT efficacy depends in part on elicitation of a tumor-specific immune response that is dependent on cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. The cytolytic potential of CTLs and NK cells is mediated by the ability of these cells to recognize major histocompatibility complex (MHC) class I and MHC class I-related molecules. The MHC class I-related molecules MICA and MICB are induced by oxidative stress and have been reported to activate NK cells and co-stimulate CD8(+) T cells. The purpose of this study was to examine the effect of PDT on tumor cell expression of MHC classes I and II-related molecules in vivo and in vitro. Human colon carcinoma Colo205 cells and murine CT26 tumors were treated with 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH)-PDT at various doses. MHC classes I and I-related molecule expression following treatment of Colo205 cells was temporally examined by flow cytometry using antibodies specific for components of MHC class I molecules and by quantitative PCR using specific primers. Expression of MHC class I-related molecules following HPPH-based PDT (HPPH-PDT) of murine tumors was monitored using a chimeric NKG2D receptor. In vitro HPPH-PDT significantly induces MICA in Colo205 cells, but had no effect on MHC class I molecule expression. PDT also induced expression of NKG2D ligands (NKG2DL) following in vivo HPPH-PDT of a murine tumor. Induction of MICA corresponded to increased NK killing of PDT-treated tumor cells. PDT induction of MICA on human tumor cells and increased expression of NKG2DL by murine tumors following PDT may play a role in PDT induction of anti-tumor immunity. This conclusion is supported by our results demonstrating that tumor cells have increased sensitivity to NK cell lysis following PDT.


Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide.
Highly metastatic breast cancers, such as triple-negative subtypes (TNBC), require the most effective treatments. Since interleukin-13 receptor (IL-13R)α2 is reportedly over-expressed in some cancers, we investigated here its expression and the feasibility of therapeutically targeting this receptor in breast cancer using a novel hybrid cytolytic peptide (Pep-1-Phor21) consisting of IL-13Rα2-binding (Pep-1) and cytolytic (Phor21) domains. This study demonstrates that particularly TNBC tissues and cells display the prominent expression of IL-13Rα2. Furthermore, Pep-1-Phor21 induced the rapid necrosis of tumor cells expressing cell-surface IL-13Rα2. Notably, IL-13Rα2 expression was found to be epigenetically regulated in breast cancer cells in that the inhibition of histone deacetylase (HDAC) or DNA methyltransferase (DNMT) upregulated IL-13Rα2 expression, thereby sensitizing them to Pep-1-Phor21. IL-13Rα2-negative non-malignant cells were refractory to these epigenetic effects. Consistent with its cytolytic activity, Pep-1-Phor21 readily destroyed IL-13Rα2-expressing breast cancer spheroids with HDAC or DNMT inhibition, further enhancing cytolytic activity. Therefore, the Pep-1-Phor21-mediated targeting of IL-13Rα2 is a potentially novel therapeutic strategy for TNBC. Given that tumor cells can be selectively sensitized to Pep-1-Phor21 via the epigenetic up-regulation of IL-13Rα2, a combined adjuvant approach involving Pep-1-Phor21 and epigenetic inhibitors may be an effective strategy.


Anticonvulsant and toxicity evaluation of some 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-ones.
To further investigate anticonvulsant activity of quinoline derivatives, a series of 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one derivatives was synthesized starting from 7-hydroxyl-3,4-dihydro-2(1H)-quinoline. In initial (phase I) screening and quantitative (phase II) evaluation, compound 7-benzyloxyl-4,5-dihydro-[1,2,4]thiazolo[4,3-a]quinoline-1(2H)-one (3f) was among the most active but also has the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED(50)) of 12.3 mg/kg, median toxicity dose (TD(50)) of 547.5 mg/kg, and the protective index (PI) of 44.5, which is much greater than PI of the prototype drugs phenytoin, phenobarbital, carbamazepin, and valproate. Compound 3f was chosen for further evaluation. In phase III pharmacological test, the compound had median hypnotic dose (HD(50)) and median lethal dose (LD(50)) of 1204 mg/kg and >3000 mg/kg, respectively, thus demonstrating much greater margin of safety compared to prototype drugs. The compound 3f also showed significant oral activity against MES-induced seizures and low oral neurotoxicity in mice in phase IV pharmacological test. Possible structure-activity relationship was discussed.


Association of genetic variation of the RIL gene, encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women.
Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved. One candidate gene, the reversion-induced LIM gene ( RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1). In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD) and a genetic variation (-3333T-->C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation -3333T-->C and radial BMD ( r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis.


Flow dynamics in internal thoracic artery grafts 10 years after coronary artery bypass grafting.
Flow dynamics in internal thoracic artery grafts 10 years after surgery are not known. Doppler examination was performed in native internal thoracic arteries as a control (n = 8) and in internal thoracic artery grafts to the left anterior descending coronary artery 6 months postoperatively (group A, n = 25), at 5 years (group B, n = 14), and at 10 years (group C, n = 11). Each graft group showed a diastolic to systolic peak velocity ratio of less than 1.0 at the proximal end, and more than 1.0 at the distal end, but the control group showed a ratio of less than 1.0 throughout the length of the artery. The diastolic peak velocity of the graft groups was significantly faster than that of the control group at the distal end (versus group A, p < 0.01; versus group B, p < 0.005; and versus group C, p < 0.05). The systolic peak velocity of the graft groups was significantly lower than that of the control at the proximal end (versus group A, p < 0.0001; versus group B, p < 0.005; and versus group C, p < 0.0005). There were no significant differences of flow velocities among the graft groups and graft diameter among the four groups. Although the internal thoracic artery is systolic predominant, when native artery is used as graft, it changes its hemodynamics to diastolic predominance, especially at the distal end. Even after 10 years, graft flow dynamics are unchanged. This hemodynamic character may be one of the factors related to the superior long-term patency.


Botox induced muscle paralysis rapidly degrades bone.
The means by which muscle function modulates bone homeostasis is poorly understood. To begin to address this issue, we have developed a novel murine model of unilateral transient hindlimb muscle paralysis using botulinum toxin A (Botox). Female C57BL/6 mice (16 weeks) received IM injections of either saline or Botox (n = 10 each) in both the quadriceps and calf muscles of the right hindleg. Gait dysfunction was assessed by multi-observer inventory, muscle alterations were determined by wet mass, and bone alterations were assessed by micro-CT imaging at the distal femur, proximal tibia, and tibia mid-diaphysis. Profound degradation of both muscle and bone was observed within 21 days despite significant restoration of weight bearing function by 14 days. The muscle mass of the injected quadriceps and calf muscles was diminished -47.3% and -59.7%, respectively, vs. saline mice (both P < 0.001). The ratio of bone volume to tissue volume (BV/TV) within the distal femoral epiphysis and proximal tibial metaphysis of Botox injected limbs was reduced -43.2% and -54.3%, respectively, while tibia cortical bone volume was reduced -14.6% (all P < 0.001). Comparison of the contralateral non-injected limbs indicated the presence of moderate systemic effects in the model that were most probably associated with diminished activity following muscle paralysis. Taken as a whole, the micro-CT data implied that trabecular and cortical bone loss was primarily achieved by bone resorption. These data confirm the decisive role of neuromuscular function in mediating bone homeostasis and establish a model with unique potential to explore the mechanisms underlying this relation. Given the rapidly expanding use of neuromuscular inhibitors for indications such as pain reduction, these data also raise the critical need to monitor bone loss in these patients.


Effect of sublethal concentrations of waterborne copper on lipid peroxidation and enzymatic antioxidant response in Gambusia holbrooki.
The aim of the current research was to assess the possible influence of copper sulphate contamination on the antioxidant enzymatic defenses and lipid peroxidation (LPO) in the mosquitofish (Gambusia holbrooki). Quadruplicated lots of this fish were exposed to three increasing sub-lethal concentrations of Cu (0.10; 0.17 and 0.25mgCu/L) and a control without Cu for 20 days. Previous to laboratory acclimation, 8 fish were taken to define the initial population. At the end of the trials, 12 fish/sex/treatment were sampled for the determination of levels of copper in gills, metallothioneins (MTs) content, total lipids, fatty acids profiles and antioxidant enzymatic activity, as well as lipid peroxidation. Most of the antioxidant enzymatic defenses assayed were not activated and lipid peroxidation decreased significantly in fish exposed to any concentration of copper applied. This leads us to presume the existence of a protective mechanism against peroxidation other than the enzymatic antioxidant defense, which could be related to the observed increase of copper content in the gills.


Determination of the two-component systems regulatory network reveals core and accessory regulations across Pseudomonas aeruginosa lineages.
Pseudomonas aeruginosa possesses one of the most complex bacterial regulatory networks, which largely contributes to its success as a pathogen. However, most of its transcription factors (TFs) are still uncharacterized and the potential intra-species variability in regulatory networks has been mostly ignored so far. Here, we used DAP-seq to map the genome-wide binding sites of all 55 DNA-binding two-component systems (TCSs) response regulators (RRs) across the three major P. aeruginosa lineages. The resulting networks encompass about 40% of all genes in each strain and contain numerous new regulatory interactions across most major physiological processes. Strikingly, about half of the detected targets are specific to only one or two strains, revealing a previously unknown large functional diversity of TFs within a single species. Three main mechanisms were found to drive this diversity, including differences in accessory genome content, as exemplified by the strain-specific plasmid in IHMA87 outlier strain which harbors numerous binding sites of conserved chromosomally-encoded RRs. Additionally, most RRs display potential auto-regulation or RR-RR cross-regulation, bringing to light the vast complexity of this network. Overall, we provide the first complete delineation of the TCSs regulatory network in P. aeruginosa that will represent an important resource for future studies on this pathogen.


Progressive retinal structure abnormalities in multiple system atrophy.
Objective measures of disease progression that can be used as endpoints in clinical trials of MSA are necessary. We studied retinal thickness in patients with MSA and assessed changes over time to determine its usefulness as an imaging biomarker of disease progression. This was a cross-sectional study including 24 patients with MSA, 20 with PD, and 35 controls, followed by a longitudinal study of 13 MSA patients. Patients were evaluated with high-definition optical coherence tomography and the Unified Multiple System Atrophy Rating Scale. Evaluations were performed at baseline and at consecutive follow-up visits for up to 26 months. MSA subjects had normal visual acuity and color discrimination. Compared to controls, retinal nerve fiber layer (P = 0.008 and P = 0.001) and ganglion cell complex (P = 0.013 and P = 0.001) thicknesses were reduced in MSA and PD. No significant differences between MSA and PD were found. Over time, in patients with MSA, there was a significant reduction of the retinal nerve fiber layer and ganglion cell complex thicknesses, with estimated annual average losses of 3.7 and 1.8 μm, respectively. Visually asymptomatic MSA patients exhibit progressive reductions in the thickness of the retinal nerve fiber layer and, to a lesser extent, in the macular ganglion cell complex, which can be quantified by high-definition optical coherence tomography. Specific patterns of retinal nerve fiber damage could be a useful imaging biomarker of disease progression in future clinical trials.


Differentiation-dependent changes in levels of C/EBPβ repressors and activators regulate human papillomavirus type 31 late gene expression.
The liver-enriched transcriptional activator protein (LAP) isoform of CCAAT/enhancer binding protein β (C/EBPβ) is shown to be a major activator of differentiation-dependent human papillomavirus (HPV) late gene expression, while the liver-enriched inhibitory protein (LIP) isoform negatively regulates late expression. In undifferentiated cells, LIPs act as dominant-negative repressors of late expression, and upon differentiation, LIP levels are significantly reduced, allowing LAP-mediated activation of the late promoter. Importantly, knockdown of C/EBPβ isoforms blocks activation of late gene expression from complete viral genomes upon differentiation.


Glasgow prognostic score is a better predictor of the long-term survival in patients with gastric cancer, compared to the modified Glasgow prognostic score or high-sensitivity modified Glasgow prognostic score.
Inflammation influences cancer progression by increasing catabolism and impairing nutrient absorption. We compared the prognostic ability of three inflammation-based prognostic scoring systems-the Glasgow prognostic score (GPS), modified GPS (mGPS), and high-sensitivity mGPS (HS-mGPS)-in gastric cancer patients. We retrospectively examined 434 curatively resected gastric cancer patients to evaluate the prognostic ability of scoring systems for overall survival (OS) and cancer-specific survival (CSS). OS analysis identified the following independent prognostic factors: GPS model: pathological stage (pStage, p < 0.001), carcinoembryonic antigen (CEA, p = 0.004), and GPS 1 (hazard ratio [HR], 1.929; 95% confidence interval [CI], 1.152-3.228; p = 0.013); mGPS model: body mass index (BMI, p = 0.027), pStage (p < 0.001), and CEA (p < 0.001); HS-mGPS model: BMI (p = 0.029), pStage (p < 0.001), and CEA (p = 0.003). mGPS and HS-mGPS were not independent prognostic factors for OS. CSS analysis of the GPS model identified pStage (p < 0.001), CEA (p = 0.015), and GPS 1 (HR; 2.095, 95% CI; 1.025-4.283; p = 0.043) and 2 (HR, 2.812; 95% CI, 1.111-7.116; p = 0.029) as independent prognostic factors; however, mGPS and HS-mGPS were not independent prognostic factors for CSS. Log-rank tests demonstrated significant differences in OS among patients with GPS 0 vs. 1 (p < 0.001) and 0 vs. 2 (p < 0.001) and in CSS among the three GPS (0 vs. 1; p = 0.005, 0 vs. 2; p < 0.001, 1 vs. 2; p = 0.009). GPS most reliably predicts long-term survival of gastric cancer patients.


Assessing the Usefulness of Different Silicone Tubes in External Dacryocystorhinostomy.
External dacryocystorhinostomy is a surgical procedure for the treatment of lacrimal drainage system disorders. To assess the usefulness of different silicone tubes in external dacryocystorhinostomy. This study sampled 97 patients with lacrimal drainage system disorders who underwent the external dacryocystorhinostomy using two different silicone tubes. Forty one patients (Group A) underwent external dacryocystorhinostomy with silicone intubation using Nunchaku-style tubes, while in 56 patients (Group B) dacryocystorhinostomy was performed with O'Donoghue silicone tubes. The data was analyzed using T-test, Chi-squared test and Fisher's test. The success rate was evaluated by achieved patency to irrigation and relief of epiphora. Patency in the group with Nunchaku-style tubes was 95.1% compared to 94.6% in the group with O'Donoghue silicone tubes (p>0.05). Both tubes in external dacryocystorhinostomy were useful in the management of lacrimal drainage system disorders. Although it is easier and quicker to intubate and extubate Nunchaku-style tubes compared to O'Donoghue silicone tubes, there was no statistically significant difference in success rate between the compared groups.


Gradient of deficit in cone responses in the incomplete form of congenital stationary night blindness revealed by multifocal electroretinography.
Multifocal electroretinograms were recorded in one case of incomplete form of congenital stationary night blindness. First order kernel revealed reduced cone macular P1 responses with normal implicit time (22.7 nV, 33.3 ms; normal 43.3 +/- 8.2 nV, 32.7 +/- 0.6 ms) whereas more peripheral responses exhibited low responses of extremely delayed implicit time (5.1 nV, 47.5 ms; normal 7.4 +/- 2.1 nV, 32.3 +/- 0.8 ms). Responses from the first slice of the second kernel were present in the macular area but absent from the more peripheral areas. In comparison, mfERGs in the complete form of CSNB showed normal amplitude but slightly delayed responses at all eccentricities and normal second kernel responses. Results are discussed in terms of the dichotomy in synaptic transmission between macular and peripheral cones.


Service users' views regarding user involvement in mental health services: A qualitative study.
Service user involvement is emphasised in many strategies, plans and declarations globally. However, in practice, service user involvement is not always achieved and remains at a tokenistic level. To explore the views of service users on user involvement in mental health service. Explorative descriptive study design. The study was conducted in one psychiatric hospital and in two mental health organisations in western Finland. The data was generated through three focus group interviews and analysed with qualitative content analysis. User involvement means that people using mental health services are respected, listened to and can act in co-operation with professionals so than they feel that they can influence their own care and treatment. The participants articulated concrete factors that promote or inhibit user involvement. Service user involvement can be enhanced by strengthening service users´ position, by developing the mental health care system and by specific training for professionals. The views of service users in this study concerning the realisation of user involvement and the factors promoting and preventing it were realistic. They are basic elements of patient-centred care and of all human interaction. Our participants described service user involvement in their own care and treatment. They emphasised the need to have more information, and wanted to be more involved in decision-making about their own care and treatment. They called for better care planning and co-ordination as one way to increase service user involvement. These also have implications for mental health services at the system level.


CT retrograde pancreatography using an indwelling balloon catheter.
We report a new technique for computed tomography (CT) of the pancreas during retrograde injection of contrast material into the pancreatic duct via an in situ balloon catheter placed by duodenoscopy (CT-RP). The method resulted in more stable ductgrams at CT than were obtained with other methods. Our data suggest that CT-RP provides useful information in evaluating pancreatic lesions that produce subtle or insignificant abnormalities of the outline of the pancreas and the ductal system on conventional CT and ERP.


Mammalian chiasma frequencies as a test of two theories of recombination.
A broad survey of asexuality in the animal kingdom is sufficient to reject all theories of sex and recombination except two: the Red Queen and the Tangled Bank. The Red Queen theory states that an organism's biotic environment tends to be 'contrary', consistently evolving to the detriment of the organism; sex and recombination result in progeny genetically distinct from their parents and grandparents and thus less susceptible to the antagonistic advances made during the previous generations, particularly by their parasites. The alternative theory, the Tangled Bank, states that sex and recombination function to diversify the progeny from each other, thus reducing competition between them. An extensive survey of mammalian recombination shows that the total number of chiasmata in excess of one per bivalent is strongly correlated with generation time but uncorrelated with fecundity. We conclude that crossing-over may function to combat antagonists with short generation times but does not function to reduce sib competition. Chromosome number is selectively neutral with respect to these factors.


Phage adsorption to bacteria in the light of the electrostatics: a case study using E. coli, T2 and flow cytometry.
The addition of sodium chloride to freshwater or diluted minimal salt medium increases the adsorption of T2 phages on Escherichia coli. For the first time the adsorption in diluted minimal salt medium was measured by counting unadsorbed phages (i.e. free particles) using flow cytometry, allowing a gentle separation between adsorbed and unadsorbed phages. Flow cytometry was able to detect weakly adsorbed phage that remained undetected using classical centrifugation-based methods and this allowed us to show that increasing ionic strength enhances the phage adsorption to its bacterial host with an extremely low detection limit. A key result was that the adsorption in high ionic strength (i.e. 100 mM) reached 4.5±0.1×10⁻⁵ mL/min which is 1400 fold higher than previously reported values. In order to understand the mechanism underpinning such a weak phage adsorption, the zeta potentials and the diffusion coefficient of the particles were measured by dynamic light scattering. The bacterial cells and the phages had zeta potentials between -60 mV and -10 mV and -30 mV and -10 mV, respectively. The diffusion coefficient of the phage was 2.8±0.4×10⁻¹² m² s⁻¹ corresponding to a hydrodynamic radius of 104±15 nm. However significant adsorption occurs in conditions where the DLVO theory predicts that minimal encounter, suggesting that forces other that electrostatic repulsion and Van der Waals interaction (e.g. potential impurities, particle shape and other biological characteristics) are likely to interplay.


Interactions between Inhibitory Interneurons and Excitatory Associational Circuitry in Determining Spatio-Temporal Dynamics of Hippocampal Dentate Granule Cells: A Large-Scale Computational Study.
This paper reports on findings from a million-cell granule cell model of the rat dentate gyrus that was used to explore the contributions of local interneuronal and associational circuits to network-level activity. The model contains experimentally derived morphological parameters for granule cells, which each contain approximately 200 compartments, and biophysical parameters for granule cells, basket cells, and mossy cells that were based both on electrophysiological data and previously published models. Synaptic input to cells in the model consisted of glutamatergic AMPA-like EPSPs and GABAergic-like IPSPs from excitatory and inhibitory neurons, respectively. The main source of input to the model was from layer II entorhinal cortical neurons. Network connectivity was constrained by the topography of the system, and was derived from axonal transport studies, which provided details about the spatial spread of axonal terminal fields, as well as how subregions of the medial and lateral entorhinal cortices project to subregions of the dentate gyrus. Results of this study show that strong feedback inhibition from the basket cell population can cause high-frequency rhythmicity in granule cells, while the strength of feedforward inhibition serves to scale the total amount of granule cell activity. Results furthermore show that the topography of local interneuronal circuits can have just as strong an impact on the development of spatio-temporal clusters in the granule cell population as the perforant path topography does, both sharpening existing clusters and introducing new ones with a greater spatial extent. Finally, results show that the interactions between the inhibitory and associational loops can cause high frequency oscillations that are modulated by a low-frequency oscillatory signal. These results serve to further illustrate the importance of topographical constraints on a global signal processing feature of a neural network, while also illustrating how rich spatio-temporal and oscillatory dynamics can evolve from a relatively small number of interacting local circuits.


[Not Available].
The fumonisin contents of extrudates and corn flakes were analysed by different analytical methods (AOAC method, ELISA, alcaline hydrolysis of extracts or samples). All methods revealed decrease of fumonisin contents after thermal processing.


Pharmacological comparison of the potential antidepressant UP 614-04 with viloxazine and imipramine; behavioral studies.
1. Several behavioral tests were used to compare the pharmacological activity of the potential antidepressant UP 614-04 with those of viloxazine and imipramine. 2. Orally-administered UP 614-04, like viloxazine, reduced locomotor activity in mice, and, like viloxazine and imipramine, it antagonized the hypothermia or ptosis induced by reserpine or tetrabenazine and the hypothermia induced by a high dose of apomorphine. 3. UP 614-04 antagonized oxotremorine-induced hypothermia, and to a lesser extent, oxotremorine-induced tremors, indicating that it possesses some CNS anticholinergic activity. 4. Both imipramine and viloxazine were more potent than UP 614-04 in potentiating yohimbine toxicity in mice. 5. Orally-administered UP 614-04 potentiated d-amphetamine-induced stereotypy to a greater extent than viloxazine, but to a lesser extent than imipramine. 6. Intraperitoneally-injected UP 614-04 was much more potent than viloxazine in increasing tryptamine convulsive potential in rats, indicating that it might exert an inhibitory action on monoamine oxidase. 7. These results indicate that UP 614-04 has a behavioral profile that is consistent with an antidepressant action, but that it differs from imipramine and viloxazine.


The contribution of the carotenoid to the visible circular dichroism of the light-harvesting antenna of Rhodospirillum rubrum.
The visible c.d. spectrum of wild-type Rhodospirillum rubrum shows positive bands [Dratz, Schultz & Sauer (1966) Brookhaven Symp. Biol. 19, 303-318] that are largely due to the B880 antenna pigments, bacteriochlorophyll a and carotenoids. The bacteriochlorophyll c.d. band was absent from the spectrum of R. rubrum G9, a mutant unable to synthesize coloured carotenoids, and could be partly restored by adding extracted carotenoids to freeze-dried membrane vesicles isolated from that mutant. Therefore it seems to arise from either bacteriochlorophyll-carotenoid interactions or bacteriochlorophyll-protein interactions that are induced by the carotenoid. The more complex carotenoid c.d. band had different shapes in native and reconstituted carotenoid-containing membranes. Such differences suggest that the optical activity of the carotenoid in the B880 antenna arises from both non-degenerate and degenerate interactions.


Photonic-chip-based tunable slow and fast light via stimulated Brillouin scattering.
We report the first (to our knowledge) demonstration of photonic chip based tunable slow and fast light via stimulated Brillouin scattering. Slow, fast, and negative group velocities were observed in a 7 cm long chalcogenide (As(2)S(3)) rib waveguide with a group index change ranging from ~-44 to +130, which results in a maximum delay of ~23 ns at a relatively low gain of ~23 dB. Demonstration of large tunable delays in a chip scale device opens up applications such as frequency sensing and true-time delay for a phased array antenna, where integration and delays ~10 ns are highly desirable.


[Prevention, early detection and monitoring of cutaneous melanoma].
In parallel to the development of new treatments, considerable work remains to be done with regard on the one hand to early detection, and on the other, to the prevention of the main extrinsic risk factor, namely ultraviolet rays. Caregivers have an important educational role to play with patients and their families concerning these different aspects.


Screw stripping and its prevention in the hexagonal socket of 3.5-mm titanium locking screws.
There have been several reports about the difficulties in removing 3.5-mm titanium locking screws from plates due to the stripping or rounding of the hexagonal screw socket. We investigated whether stripping the locking screw sockets can be prevented by using different screwdrivers or interposing materials into the socket during removal. We overtightened 120 3.5-mm titanium locking screws (Depuy Synthes, Paoli, PA) equally into locking plates on sawbone tibia models, applying a uniform torque of 4.5 Nm, exceeding the recommended torque of 1.5 Nm. Twenty screws each were removed using a straight-handle 2.5-mm screwdriver, T-handle screwdriver, hex key wrench, and straight-handle screwdriver with a non-dominant hand. In addition, 20 screws were removed using foil from a suture packet inserted into the screw socket or using parts of a latex glove inserted into the screw socket. The incidence rates of screw stripping using the straight-handle screwdriver, T-handle screwdriver, hex key wrench, non-dominant hand, foil interposition, and latex glove interposition were 75%, 40%, 35%, 90%, 60%, and 70%, respectively. When a T-handle screwdriver or hex key wrench was used, the probability of screw stripping was 4.50 times (odds ratio = 4.50, 95% confidence interval = 1.17 to 17.37, p = 0.03) and 5.57 times (odds ratio = 5.57, 95% confidence interval = 1.42 to 21.56, p = 0.01) lower than that with the straight-handle screwdriver, respectively. Foil or latex glove interpositions did not prevent screw stripping. Thus, in the current experimental study, T-handle screwdriver or hex key wrench usage decreased the incidence rate of screw stripping during removal compared to straight-handle screwdriver use.


Engineering pH-Sensitive Single-Domain Antibodies.
There is increasing interest in expanding an antibody beyond high affinity and specificity. One such feature is custom regulation of the binding event, such as pH-dependent control. Here, we provide a methodology for generating single-domain antibodies (sdAbs) that bind their antigen in a pH-dependent fashion. As each sdAb is unique, we start by providing the conceptual framework for designing a combinatorial histidine scanning library within a sdAb-antigen-binding interface. Methods are provided to create a phage display library, containing up to 1 × 1010 unique members where each permutation of histidine substitution is sampled within the confines of the specified interface region(s). Finally, we describe phage display protocols for the selection and analysis of unique pH-dependent sdAb clones.


Television system for verification and documentation of treatment fields during intraoperative radiation therapy.
Intraoperative radiation therapy (IORT) involves direct treatment of tumors or tumor beds with large single doses of radiation. The verification of the area to be treated before irradiation and the documentation of the treated area are critical for IORT, just as for other types of radiation therapy. A television system which allows the target area to be directly imaged immediately before irradiation has been developed. Verification and documentation of treatment fields has made the IORT television system indispensable.


Comparisons of directionally selective with other ganglion cells of the turtle retina: intracellular recording and staining.
Directionally selective (DS) and other ganglion cells of the turtle retina were studied in in vitro eyecup preparations by using intracellular recording and staining techniques. DS ganglion cells responded to moving gratings with periodic, depolarizing synaptic potentials in both preferred and null directions. Although depolarizations were usually larger in the preferred than in the null directions, in a few cells spike discharges were directional but depolarizations were not. Directionality could disappear if inappropriate field sizes or grating spatial frequencies were used. Unlike non-DS cells, one-half of the DS cells penetrated showed two sizes of action potentials upon photostimulation. It is proposed that the smaller spikes originated at axonal initial segments and failed to invade the somas actively. DS cells also exhibited postspike depolarizations (PSDs). Three types of DS ganglion cells (ON-OFF, OFF center, and ON center) were identified morphologically with Lucifer yellow injection. Other ganglion cells, which were also recorded from and stained intracellularly, are compared to the DS cells.


Acridine orange stain in the early detection of bacteria in blood cultures.
A total of 1,592 blood cultures without macroscopic signs of bacterial growth in the first 12-24 h of incubation were processed for both acridine orange stain and blind subculture. One hundred and twenty-one (7.6%) blood cultures were positive by either method; of these, 105 (8.68%) were positive by both methods, 11 (9.1%) positive by acridine orange and negative by subculture, and 5 (4.1%) negative by acridine orange and positive by subculture. The difference between the 116 blood cultures positive by acridine orange and the 110 blood cultures positive by subculture was not statistically significant (p greater than 0.1). Gram stain performed on all acridine orange positive cultures failed to reveal bacteria in 14 cases. Acridine orange staining is a sensitive, rapid and reliable method for detecting bacteria in blood cultures early during incubation. The method is inexpensive and easy to perform and can be substituted for blind subcultures.


Apparent diffusion coefficient in thoracolumbar intervertebral discs of healthy young volunteers.
Apparent diffusion coefficient values (ADC) of healthy intervertebral discs of young volunteers in the thoracolumbar spine were determined using a single-shot EPI sequence. ADC(z) was in the lumbar spine slightly higher than ADC(x) or ADC(y). In vivo diffusion measurements of intervertebral discs may offer a novel diagnostic tool to evaluate disc diseases in early phases.


Identification & characterization of Shiga toxin-producing Escherichia coli isolates from patients with diarrhoea in Iran.
Verotoxigenic Escherichia coli are important serotypes of enterohaemorrhagic E. coli (EHEC) subgroup that cause attaching and effacing lesions in enterocytes by producing verotoxins or shiga-like toxins resulting in haemorrhagic colitis (HC) and haemolytic uremic syndrome (HUS). The aim of this study was to detect these serotypes specially E. coli O157:H7 in stool samples of patients with diarrhoea and identification of virulence genes (STX1, STX2, Hly and EAE) in Shahrekord-Iran area using PCR technique. Two hundred diarrhoeal stool samples of patients were collected through 2007-2008. Microbiological and biochemical examinations were done to detect the E. coli. Serological tests carried out to identify the O157 or O157:H7 serotypes. Of the 58 E. coli isolates, 16 (27.6%) were detected as STX1 carrying E. coli, four (6.9%) carrying STX2, eight (13.8%) carrying both STX1 and STX2, and 12 (20.7%) were Hly carrying E. coli, but none of the isolates contained EAE gene. None of the isolates were E. coli O157 or O157:H7 serotypes. Our results revealed that verotoxigenic E. coli isolates other than O157 serotype were involved in causing diarrhoea in Shahrekord-Iran.


Phg, a novel member of the autotransporter family present in Bordetella species.
Several proteins encoded in the genomes of Bordetella species show significant sequence similarity to the autotransporter domains of surface exposed or secreted virulence factors of bordetellae such as pertactin, tracheal colonization factor or Vag8. One of these putative autotransporters, provisionally termed Phg, is encoded by the pertactin homologous gene (phg), which is highly conserved in Bordetella pertussis, B. bronchiseptica and B. parapertussis, but absent in B. avium and B. petrii. In contrast to homologues with documented functions in host interaction and virulence, several key amino acids probably involved in proteolytic processing of the autotransporter domain are not conserved in Phg. The transcription start site of phg was identified by primer extension analysis, but differential transcription of phg could not be detected in B. bronchiseptica strains under conditions that lead to enhanced expression of other known Bordetella autotransporter proteins. A mutant of B. pertussis was constructed in which major parts of phg are substituted by a kanamycin resistance cassette. Virulence testing of this mutant in a mouse respiratory infection model showed the same colonization properties as the wild-type strain.


Getting the message. Pioneering organizations are using tools like text messaging to enable patients to take better control of their health.
As text messaging becomes more established in everyday routines by millions of users, healthcare organizations are embracing the technology as a powerful tool to allow patients to better manage their health. Two health provider networks, Kaiser Permanente and Riverview Health System, have launched successful pilots and plan to build on those initiatives.


Deciphering the effects of gene deletion on yeast longevity using network and machine learning approaches.
Longevity is one of the most basic and one of the most essential properties of all living organisms. Identification of genes that regulate longevity would increase understanding of the mechanisms of aging, so as to help facilitate anti-aging intervention and extend the life span. In this study, based on the network features and the biochemical/physicochemical features of the deletion network and deletion genes, as well as their functional features, a two-layer model was developed for predicting the deletion effects on yeast longevity. The first stage of our prediction approach was to identify whether the deletion of one gene would change the life span of yeast; if it did, the second stage of our procedure would automatically proceed to predict whether the deletion of one gene would increase or decrease the life span. It was observed by analyzing the predicted results that the functional features (such as mitochondrial function and chromatin silencing), the network features (such as the edge density and edge weight density of the deletion network), and the local centrality of deletion gene, would have important impact for predicting the deletion effects on longevity. It is anticipated that our model may become a useful tool for studying longevity from the angle of genes and networks. Moreover, it has not escaped our notice that, after some modification, the current model can also be used to study many other phenotype prediction problems from the angle of systems biology.


[Meningioma of the anterior visual pathways. Epidemiology and clinical symptoms].
Meningiomas are found incidentally or because of characteristic but non-specific symptoms. In Germany approximately 1,000 new diseases in the area of the anterior visual pathways are expected per year. Around one quarter of all incidentally diagnosed meningiomas eventually need treatment. The typical patient is a female around the age of 50 years as more than 80 % of the patients are women. The typical presenting symptom is visual acuity loss followed by diplopia, visual field defects and proptosis are experienced in about 10 %. In primary optic nerve meningiomas the optic disc is swollen or atrophic, rarely normal and in meningiomas invading the optic nerve from another origin the optic disc is either normal or atrophic and rarely swollen.


A novel amino cellulose derivative using ATRP method: Preparation, characterization, and investigation of its antibacterial activity.
In this study, we prepared a novel amino cellulose derivative (benzyl cellulose-g-poly [2-(N,N-Dimethylamino)ethyl methacrylate]) via a homogeneous ATRP method. The successful synthesis of the novel amino cellulose was confirmed by FT-IR and 1H NMR. This study addressed the different characteristics of the prepared polymer including the thermal stability, solubility, and X-ray diffraction pattern. The antibacterial activity of the synthesized cellulose derivative was investigated using the diffusion disk method against both gram-negative (Escherichia coli, Salmonella enterica) and gram-positive (Staphylococcus aureus, Bacillus subtilis) bacteria. Based on the inhibition zone, it was confirmed that the prepared benzyl cellulose-g-PDMAEMA possesses acceptable antibacterial activity against Escherichia coli, Salmonella enterica, and Staphylococcus aureus while Bacillus subtilis is resistant to the prepared polymer. Also according to the inhibition zone, it was shown that benzyl cellulose-g-PDMAEMA has more impact on E. coli and Salmonella enterica than Staphylococcus aureus. Molecular dynamics simulation was also used to study the interaction of the synthesized cellulose derivative with a model membrane which presented atomistic details of the polymer-lipid interactions. According to the results obtained from the molecular dynamics simulation, the polymer was able to destabilize the structure of the membrane and clearly express its signs of degradation.


Discrimination learning with light stimuli in restrained American lobster.
Operant discrimination learning has been extensively utilized in the study on the perceptual ability of animals and their higher order brain functions. We tested in this study whether American lobster Homarus americanus, which was previously found to possess ability of operant learning with claw gripping, could be trained to discriminate light stimuli of different intensities. For the current purpose, we newly developed a PC-controlled operant chamber that allowed the animal under a body-fixed condition to perform operant reward learning with claw gripping. Lobsters were first reinforced when they gripped the sensor bar upon presentation of a light cue. Then they were trained to grip the bar only when the light stimulus of a specific intensity was presented to obtain food reward while the stimuli of three different intensities including the reinforced one were presented in a random order. Finally, they were re-trained to grip the bar only when the light stimulus of another intensity that was not rewarded in the preceding training to obtain food while other intensities including the one that was rewarded previously were not rewarded any more. In these training procedures, the operant behavior occurred more frequently in response to the rewarded cue than to the non-rewarded one. The action latency for the reinforced stimuli showed a significant decrease in the course of training. These data demonstrate that lobsters can be trained with the light cues of different intensity as discriminative stimuli under a restrained condition that would allow application of electrophysiological techniques to the behaving subjects.


FOXO1, FOXO3, AND FOXO4 are differently expressed during mouse oocyte maturation and preimplantation embryo development.
Preimplantation embryo development is affected by its environment. FoxO transcription factors are regulated by PI3K/Akt signaling pathway that essentially supports growth and development. FoxO transcription factors are at the interface of crucial cellular processes, orchestrating programs of gene expression that regulate apoptosis, cell-cycle arrest, oxidative stress resistance, DNA repair, glucose metabolism, and differentiation. In the presence of growth factors, FoxO transcription factors are localized in the cytoplasm, whereas under stress conditions they move to the nucleus and trigger transcriptional activities of their target genes. The aim of the present study is to investigate whether FoxO transcription factors are present during in vivo oocyte maturation and preimplantation embryo development. Presence and localizations of FoxO1, FoxO3 and FoxO4 proteins have been determined with immunofluorescence staining. Our results have confirmed that FoxO1, FoxO3 and FoxO4 proteins are differentially expressed in prophase I, metaphase I, metaphase II oocytes, as well as in fertilized oocyte, 2-cell embryo, 4-cell embryo, 8-cell embryo, morula, and blastocyst. FoxOs translocate to nucleus in embryos with developmental delay. Our findings indicate that FoxO transcription factors are present during both oocyte and embryo in vivo maturation and provide fundamental knowledge that FoxOs may regulate in vitro embryo development under stress conditions.


Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I.
Human T-cell lymphotropic virus type I (HTLV-I) is associated with various clinical disorders including adult T cell leukemia, myelopathy, arthropathy. Hypercalcemia resulting from osteoclast activation and a variety of hematopoietic abnormalities have been also observed in HTLV-I infected patients, however, precise mechanism about initial trigger(s) prior to presenting symptoms is still unknown. In this study, to assess effects of HTLV-I on hematopoiesis, we analysed characteristics of early hematopoietic precursors in HTLV-I env-pX transgenic rats. Progenitor cells for osteoclasts were significantly increased even in the marrow of asymptomatic env-pX rats. Progenitors for B cells were also highly enriched, while colony forming cells (CFC) elicited by GM-CSF(CFU-GM) and M-CSF(CFU-M) were comparable to normal littermates. Following arthritis in env-pX transgenic rats, osteoclastogenesis was further augmented and the CFCs were increased. Bone marrow cells carrying adjuvant-induced arthritis retained a constant number of progenitors for osteoclast and B lymphocytes, whereas the number of CFU-GM and CFU-M increased. These results indicate that the env-pX transgene affect early stages of osteoclast and B-cell lineages prior to developing diseases, in contrast, an increase of the CFCs was caused indirectly by arthritis. This study provides a novel standpoint for the mechanisms of pathogenesis by HTLV-I.


Seasonal and daily rhythms of body temperature in the European hamster (Cricetus cricetus) under semi-natural conditions.
Body temperature of five European hamsters exposed to semi-natural environmental conditions at 47 degrees N in Southern Germany was recorded over a 1.5-year period using intraperitoneal temperature-sensitive radio transmitters. The animals showed pronounced seasonal changes in body weight and reproductive status. Euthermic body temperature changed significantly throughout the year reaching its maximum of 37.9 +/- 0.2 degrees C in April and its minimum of 36.1 +/- 0.4 degrees C in December. Between November and March the hamsters showed regular bouts of hibernation and a few bouts of shallow torpor. During hibernation body temperature correlated with ambient temperature. Monthly means of body temperature during hibernation were highest in November (7.9 +/- 0.8 degrees C) and March (8.2 +/- 0.5 degrees C) and lowest in January (4.4 +/- 0.7 degrees C). Using periodogram analysis methods, a clear diurnal rhythm of euthermic body temperature could be detected between March and August, whereas no such rhythm could be found during fall and winter. During hibernation bouts, no circadian rhythmicity was evident for body temperature apart from body temperature following ambient temperature with a time lag of 3-5 h. On average, hibernation bouts lasted 104.2 +/- 23.8 h with body temperature falling to 6.0 +/- 1.7 degrees C. When entering hibernation the animals cooled at a rate of -0.8 +/- 0.2 degrees C.h-1; when arousing from hibernation they warmed at a rate of 9.9 +/- 2.4 degrees C.h-1. Warming rates were significantly lower in November and December than in January and February, and correlated with ambient temperature (r = -0.46, P < 0.01) and hibernating body temperature (r = -0.47, P < 0.01). Entry into hibernation occurred mostly in the middle of the night (mean time of day 0148 hours +/- 3.4 h), while spontaneous arousals were widely scattered across day and night. For all animals regression analysis revealed free-running circadian rhythms for the timing of arousal. These results suggest that entry into hibernation is either induced by environmental effects or by a circadian clock with a period of 24 h, whereas arousal from hibernation is controlled by an endogenous rhythm with a period different from 24 h.


Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice.
Homologous recombination (HR)-based gene therapy using adeno-associated viruses (AAV-HR) without nucleases has several advantages over classic gene therapy, especially the potential for permanent transgene expression. However, the low efficiency of AAV-HR remains a major limitation. Here, we tested a series of small-molecule compounds and found that ribonucleotide reductase (RNR) inhibitors substantially enhance AAV-HR efficiency in mouse and human liver cell lines approximately threefold. Short-term administration of the RNR inhibitor fludarabine increased the in vivo efficiency of both non-nuclease- and CRISPR/Cas9-mediated AAV-HR two- to sevenfold in the murine liver, without causing overt toxicity. Fludarabine administration induced transient DNA damage signaling in both proliferating and quiescent hepatocytes. Notably, the majority of AAV-HR events occurred in non-proliferating hepatocytes in both fludarabine-treated and control mice, suggesting that the induction of transient DNA repair signaling in non-dividing hepatocytes was responsible for enhancing AAV-HR efficiency in mice. These results suggest that use of a clinically approved RNR inhibitor can potentiate AAV-HR-based genome-editing therapeutics.


In situ observation of nanotwins formation through twin terrace growth in pulse electrodeposited Cu films.
Nanotwinned copper (nt-Cu) shows a broad application prospects as interconnection materials in integrated circuit industry, since it combines the excellent mechanical and electrical properties. However, the formation and growth behavior of twin lamellae in pulse electrodeposited copper films are not fully understood. In this work, a series of electroplated copper films are prepared by verifying the electroplating parameters and the microstructures are analyzed using scanning electron microscope (SEM) and transmission electron microscope (TEM). The surface morphology indicates strong evidence of stacked twin terraces and layers, suggesting that nanotwins grow up layer by layer. Combined with in situ characterization by SEM and molecular dynamics (MD) simulation, it is proved that the terraces originate from the triple junction of grain boundaries and grow up by extending along the lateral (111) crystal plane. A twin terrace-growing model for nt-Cu is then deduced, which distinguishes from deformation twins or annealed twins. This growth model would be prospective to help obtain high quality of nt-Cu in industry.


Epigenetic compounds targeting pharmacological target lysine specific demethylase 1 and its impact on immunotherapy, chemotherapy and radiotherapy for treatment of tumor recurrence and resistance.
It has been proven that metastatic recurrence and therapeutic resistance are linked. Due to the variability of individuals and tumors, as well as the tumor's versatility in avoiding therapies, therapy resistance is more difficult to treat. Therapy resistance has significantly restricted the clinical feasibility and efficacy of tumor therapy, despite the discovery of novel compounds and therapy combinations with increasing efficacy. In several tumors, lysine specific demethylase 1 (LSD1) has been associated to metastatic recurrence and therapeutic resistance. For researchers to better comprehend how LSD1-mediated tumor therapy resistance occurs and how to overcome it in various tumors, this study focused on the role of LSD1 in tumor recurrence and therapeutic resistance. The importance of therapeutically targeted LSD1 was also discussed. Most gene pathway signatures are related to LSD1 inhibitor sensitivity. However, some gene pathway signatures, especially in AML, negatively correlate with LSD1 inhibitor sensitivity, but targeting LSD1 makes the therapy-resistant tumor sensitive to physiological doses of conventional therapy. We propose that combining LSD1 inhibitor with traditional tumor therapy can help patients attain a complete response and prevent cancer relapse.


Primary Care Physician Perceptions of Shared Decision Making in Lung Cancer Screening.
The Centers for Medicare and Medicaid Services (CMS) supports lung cancer screening (LCS) with annual low-dose computed tomography (LDCT) for patients who undergo shared decision-making (SDM) about LCS. Unfortunately, SDM and LCS rates are low in primary care, and, as a result, the potential benefits of LCS are not being realized. The research team interviewed 16 primary care physicians in a large urban medical center (7 in Family and Community Medicine and 9 in Internal Medicine) on their views of SDM and LCS. Interview audio-recordings were transcribed. Coders analyzed the interview transcripts independently using direct content analysis to identify major themes and subthemes. Results of interview analyses show that physicians were aware of LCS but believed that they and their patients would benefit from receiving more information about screening guidelines. Physicians knew about SDM and felt that SDM performance could help to identify issues that are important to patients and may affect their receptivity to LCS. However, many physicians expressed concerns about the time required for SDM and completing SDM about LCS when other issues need to be addressed. They also acknowledged the challenge of engaging patients, especially those with low health literacy, in SDM. In practice, some physicians reported instead of engaging eligible patients in SDM, they simply encourage them to screen. Importantly, most physicians said that they would like to receive training in SDM. Findings from this study indicate that primary care physicians support the dissemination of information about LCS and understand the importance of SDM. Physicians also feel that performing SDM in routine care is challenging but are receptive to additional training in SDM. Health systems should take steps to support SDM and LCS performance in primary care.


Geomicrobiology of manganese(II) oxidation.
Mn(II)-oxidizing microbes have an integral role in the biogeochemical cycling of manganese, iron, nitrogen, carbon, sulfur, and several nutrients and trace metals. There is great interest in mechanistically understanding these cycles and defining the importance of Mn(II)-oxidizing bacteria in modern and ancient geochemical environments. Linking Mn(II) oxidation to cellular function, although still enigmatic, continues to drive efforts to characterize manganese biomineralization. Recently, complexed-Mn(III) has been shown to be a transient intermediate in Mn(II) oxidation to Mn(IV), suggesting that the reaction might involve a unique multicopper oxidase system capable of a two-electron oxidation of the substrate. In biogenic and abiotic synthesis experiments, the application of synchrotron-based X-ray scattering and spectroscopic techniques has significantly increased our understanding of the oxidation state and relatively amorphous structure (i.e. delta-MnO(2)-like) of biogenic oxides, providing a new blueprint for the structural signature of biogenic Mn oxides.


Does substance use disorder treatment completion reduce the risk of treatment readmission in Chile?
Recovery from substance use disorders (SUD) often entails multiple treatment episodes, which clashes with a context of a treatment system with limited resources and long waiting. Treatment retention and completion have been pointed out as key elements for sustainable achievement; however, most of the evidence generated focuses on opioids and injected substances, which is hardly transferable to the Latin American context. This study aims to estimate the effect of SUD treatment completion on the risk of being readmitted to a SUD treatment in Chile. We conducted a retrospective analysis on a database of 107,559 treatment episodes from 85,048 adult patients admitted to SUD treatment during 2010-2019 in Chile. We adjusted two separate Prentice Williams and Petersen Gap Time models, to explore the association between treatment completion (vs. non-completion) and up to the third treatment readmission among residential and ambulatory modalities while controlling for time-varying covariates. To examine whether the effect of treatment completion differs between events, we included an interaction term with the stratification variable. We found that completing the treatment cuts readmission risk for the first event by 17% (Average Hazard Ratio [95% CI] = 0.83 [0.78, 0.88]) and by 14% for the second entry (Average Hazard Ratio [95% CI] = 0.86 [0.78, 0.94]) in ambulatory treatments. We did not find evidence that completing a treatment reduces the readmission risk for residential treatments or third attempts in ambulatory ones. Treatment completion was associated with benefits in cutting readmission risk for the first and second episodes in ambulatory treatments among Chilean adults. It is important to explore different mechanisms than treatment retention for residential treatments.


Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier.
Accumulation of Na(+) channels at the nodes of Ranvier is a prerequisite for saltatory conduction. In peripheral nerves, clustering of these channels along the axolemma is regulated by myelinating Schwann cells through a yet unknown mechanism. We report the identification of gliomedin, a glial ligand for neurofascin and NrCAM, two axonal immunoglobulin cell adhesion molecules that are associated with Na+ channels at the nodes of Ranvier. Gliomedin is expressed by myelinating Schwann cells and accumulates at the edges of each myelin segment during development, where it aligns with the forming nodes. Eliminating the expression of gliomedin by RNAi, or the addition of a soluble extracellular domain of neurofascin to myelinating cultures, which caused the redistribution of gliomedin along the internodes, abolished node formation. Furthermore, a soluble gliomedin induced nodal-like clusters of Na+ channels in the absence of Schwann cells. We propose that gliomedin provides a glial cue for the formation of peripheral nodes of Ranvier.


The effects of planned education given to parents on smoking in the home environment and passive exposure of children aged 0-5: A quasi-experimental pre-post intervention study from Turkey.
This study was carried out to determine the effects of planned education given to parents on smoking status at home and on children's passive smoking exposure. This quasi-experimental study was conducted with the inclusion of 40 parents with at least one child between the ages of 0 and 5 and smoking in their homes, who were registered at a Family Health Center in a city center in the Central Anatolia Region of Turkey, from 1 September 2019 to 30 June 2020. The data of the study were collected using Participant Screening Form, a Personal Information Form, the Fagerstrom Test for Nicotine Dependence, a Smoking Behaviors and Precautions at Home Form, and a Measurement and Follow-up Form. The collected data were analyzed using the SPSS 23.0 package software. In the follow-ups after the planned smoking cessation training given to the parents, the carbon monoxide measurements at their homes decreased significantly throughout the four follow-ups, the number of parents who presented to the smoking cessation outpatient clinic increased, and the number of smoking parents decreased (p < 0.05). It was concluded that the planned education that was given to smoker parents reduced the smoking rates of the parents, lowered the carbon monoxide values measured in their home environments, and thus, it was effective in reducing the passive exposure of their children at the ages of 0 to 5 years to cigarette smoke. Parents who are addicted to cigarettes should be encouraged not to smoke at home, and homes should be included in closed environments where smoking is prohibited.


Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated.
The 5-HT2B receptor agonist, BW 723C86 (10, 30(mg/kg i.p. 30 min pre-test), increased the number of punishments accepted in a rat Vogel drinking conflict paradigm over 3 min, as did the benzodiazepine anxiolytics, chlordiazepoxide (2.5-10 mg/kg p.o. 1 h pre-test) and alprazolam (0.2-5 mg/kg p.o. 1 h pre-test), but not the 5-HT2C/2B receptor agonist, m-chlorophenylpiperazine (mCPP, 0.3-3 mg/kg i.p) or the 5-HT1A receptor agonist, buspirone (5-20 mg/kg p.o. 1 h pre-test). The effect of BW 723C86 was unlikely to be secondary to enhanced thirst, as BW 723C86 did not increase the time that rats with free access to water spent drinking, nor did it reduce sensitivity to shock in the apparatus. The anti-punishment effect of BW 723C86 was opposed by prior treatment with the 5-HT2/2B receptor antagonist, SB-206553 (10 and 20 mg/kg p.o. 1 h pre-test), and the selective 5-HT2B receptor antagonist, SB-215505 (1 and 3 mg/kg p.o. 1 h pre-test), but not by the selective 5-HT2C receptor antagonist, SB-242084 (5 mg/kg p.o.), or the 5-HT1A receptor antagonist, WAY 100635 (0.1 or 0.3 mg/kg s.c. 30 min pre-test). Thus, the anti-punishment action of BW 723C86 is likely to be 5-HT2B receptor mediated. This is consistent with previous reports that BW 723C86 exhibited anxiolytic-like properties in both the social interaction and Geller-Seifter conflict tests.


Optical multiple-analyte immunosensor for water pollution control.
A prototype of a portable optical immunosensor (called river analyser) has been developed. It can be applied for the monitoring of surface water quality. Antibodies carrying a fluorescent label are used for the specific recognition of pollutants, such as frequently applied pesticides. The transduction principle is based on total internal reflection fluorescence (TIRF). The outstanding advantage of the river analyser is, that at least three analytes can be detected simultaneously in one sample. Test cycles and fluid handling are automated and enable unattended measuring.


Response of alkaline phosphatases in the cyanobacterium Anabaena sp. FACHB 709 to inorganic phosphate starvation.
Alkaline phosphatases (APases) play a crucial role in phosphorus (P) metabolism and regulation, but their physiological functions largely remain unclear in cyanobacteria. Here, we identified four putative APase genes, designated as phoA-709, phoD1-709, phoD2-709, and phoS-709, in the cyanobacterium Anabaena sp. FACHB 709, and investigated their response to inorganic phosphate (P(i)) starvation. With the exception of phoD2-709, three other APase genes were expressed at a constant and relative low level in P(i)-replete medium, whereas the expression of all four APase genes was elevated in response to P(i) starvation but phoA-709 significantly. However, disruption of phoA-709 did not affect the total APase activity but caused the expressional up-regulation of phoD1-709 and phoS-709 under P(i)-sufficient and P(i)-limiting conditions. These suggest that, the four APases of Anabaena sp. FACHB 709 are involved in P metabolism and regulation, and PhoA-709 is the main, yet dispensable, APase.


Bone marrow-derived stem cells and "plasticity".
Studies describing plasticity of somatic stem cells have become a focus of interest because clinical applications in the treatment of degenerative diseases would be at hand. In particular, bone marrow-derived cells and their potential to contribute to skeletal and cardiac muscle, liver, neurons and epithelium have recently been studied extensively. Nevertheless, results of these studies have not always been consistent with each other, and yet it remains to be resolved whether plasticity of adult stem cells truly exists. This review will discuss the role of bone marrow-derived stem cells in the field of experimental and clinical plasticity studies. Observations compatible with the concept of stem cell plasticity will be weighed against limitations of the experimental systems employed.