Stereochemical preference toward oncotarget: Design, synthesis and in vitro anticancer evaluation of diastereomeric β-lactams.
In the battle against cancer discovery of new and novel chemotherapeutic agent demands extreme obligation. Development of anticancer compounds with higher potency and reduced side-effects is timely and challenging. A small series of fourteen diastereomeric β-lactams (seven pairs) were synthesized through multi-step process exploring [2+2] ketene-imine cycloaddition as the key step. Comparative stereochemical preferences were studied through computational docking and validated by in vitro evaluation. β-tubulin was considered as possible molecular target and in vitro anticancer evaluation was conducted against SiHa, B16F10, K562 and Chang cell lines. Caspase-3 activation assay and hematoxylin/eosin staining of the cells were also accomplished. Better docking scores of the cis- over the trans-β-lactams indicated favorable β-lactam-β-tubulin interactions in cis-geometry. In vitro (IC50) evaluation confirmed better anticancer activity of the cis-diastereoisomers. Apoptosis-induced cell death was supported by caspase-3 activation study. A cis-β-lactam [(±)-Cis-3-amino-1-phenyl-4-(p-tolyl) azetidin-2-one, 6C] was found to be more active (in vitro) than the marketed natural drug colchicine against SiHa and B16F10 (six times higher potency) cell lines. Reduced toxicity (compared to colchicine) in Chang cells confirmed better site-selectivity (accordingly less side-effects) of 6C than colchicine. Aside from 6C, most of the reported molecules demonstrated good to strong in vitro anticancer activity against SiHa and B16F10 cancer cell lines. Stereochemical preferences of the cis-β-lactams over their trans-counterparts, toward the molecular target β-tubulin, was confirmed by docking studies and in vitro anticancer evaluation. Apoptosis was identified as the cause of cell death. The lead 6C exhibited higher potency and selectivity than the marketed drug colchicine both in silico as well as in vitro.


Profile of the oral microbiota from preconception to the third trimester of pregnancy and its association with oral hygiene practices.
The oral microbiota plays vital roles in both oral and systemic health, but limited studies have explored the transition of the female oral microbiota from preconception to pregnancy along with pronounced hormonal fluctuations. To characterize the oral microbiota among women in preconception and pregnancy through a prospective study and to explore the associations between the oral microbiota and oral hygiene practices. A total of 202 unstimulated saliva samples were collected from 101 women in both preconception and late pregnancy. The oral microbiota was analyzed using 16S rRNA gene sequencing. The Ace and phylogenetic diversity (PD) index were significantly lower in the third trimester than preconception. The pathogenic taxa Prevotella and Atopobium parvulum were significantly higher during late pregnancy than preconception. Women with overall better oral hygiene practice showed lower richness and diversity in preconception compared to women with poorer oral hygiene practice. The abundance of pathogens such as Dialister during both preconception and pregnancy decreased among women with better oral hygiene practice. The composition of the oral microbiota changed slightly from preconception to late pregnancy, with more pathogens in saliva samples during pregnancy. Improving oral hygiene practices has the potential to maintain oral micro-ecological balance.


Reliability of Bayesian posterior probabilities and bootstrap frequencies in phylogenetics.
Many empirical studies have revealed considerable differences between nonparametric bootstrapping and Bayesian posterior probabilities in terms of the support values for branches, despite claimed predictions about their approximate equivalence. We investigated this problem by simulating data, which were then analyzed by maximum likelihood bootstrapping and Bayesian phylogenetic analysis using identical models and reoptimization of parameter values. We show that Bayesian posterior probabilities are significantly higher than corresponding nonparametric bootstrap frequencies for true clades, but also that erroneous conclusions will be made more often. These errors are strongly accentuated when the models used for analyses are underparameterized. When data are analyzed under the correct model, nonparametric bootstrapping is conservative. Bayesian posterior probabilities are also conservative in this respect, but less so.


A catalytic borylation/dehalogenation route to o-fluoro arylboronates.
A two-step Ir-catalyzed borylation/Pd-catalyzed dehalogenation sequence allows for the net synthesis of fluoroarenes where the boronic ester is ortho to fluorine. Key elements of this approach include the use of a halogen para to the fluorine to block meta Ir-catalyzed borylation and the chemoselective Pd-catalyzed dehalogenation by KF activated polymethylhydrosiloxane (PMHS).


A rule-based expert system for laboratory diagnosis of hemoglobin disorders.
To illustrate the utility of a rule-based expert system in diagnosing hemoglobin disorders. A rule-based expert system was developed for diagnosing hemoglobin disorders. This expert system runs on IBM-compatible personal computers and uses a backward-chaining search strategy to draw conclusions. Laboratory data (ie, results of hemoglobin electrophoresis, quantitative measurements of hemoglobin F and hemoglobin A2 levels, and result of a sickle cell screen) are processed by the system using defined rules to obtain a set of differential diagnoses. Additional data, such as hematologic parameters, ethnicity of the patient, and the presence or absence of certain clinical signs and symptoms, aid in making a final diagnosis. The rules in the current version of this expert system include diagnostic criteria for 71 hemoglobin disorders. Regional academic medical center. We tested the system by using 58 survey sample cases offered by the College of American Pathologists during the period of January 1989 through December 1994. The established diagnosis for a given case must be included in the list of differential diagnoses suggested by the expert system. The expert system included the actual diagnosis as one of the top four differential diagnoses in 90% of the cases, whereas all the laboratories participating in the survey included it in 84% (mean) of the cases. We propose that this user-friendly expert system is a potential tool for computer-assisted diagnosis of hemoglobin disorders.


Psychosocial work characteristics predicting daytime sleepiness in day and shift workers.
Characteristics of work organization other than working time arrangements may contribute importantly to daytime sleepiness. The present study was designed to identify the psychosocial factors at work that predict daytime sleepiness in a sample of day and shift workers. Participants working at a pulp and chemical factory completed an annual questionnaire regarding psychosocial factors at work using the U.S. National Institute for Occupational Safety and Health Generic Job Stress Questionnaire (i.e., quantitative workload, variance in workload, job control, support from supervisor, coworkers, or family/friends, job satisfaction, and depressive symptoms), as well as daytime sleepiness (through the Epworth Sleepiness Scale [ESS]) and sleep disturbances for three years starting in 2002 (response rates, 94.6-99.0%). The present analysis included 55 day workers (11 women) and 57 shift workers (all men) who participated in all three years of the study, worked under the same work schedule throughout the study period, and had no missing data on any of the daytime sleep items. A repeated-measures analysis of covariance (ANCOVA) was used to test the effects of work schedule (day vs. shift work) and psychosocial factors at work in 2002 on the ESS scores in subsequent years, with sleep duration, insomnia symptoms, chronic diseases, and sleepiness levels at baseline as covariates. Given significant and near-significant interactions of work schedules with psychosocial factor or study year, the ANCOVA, with the factors of psychosocial work characteristics and study year, was performed by type of work schedule. The results indicated a significant main effect of psychosocial work characteristics (p = 0.010, partial eng2 = 0.14) and an almost significant main effect of study year (p = 0.067, partial eng2 = 0.06) and interaction between psychosocial work characteristics and study year (p = 0.085, partial eng2 = 0.06) for variance in workload among the day work group. The day workers reporting high variance in workload in 2002 exhibited significantly higher ESS scores in 2003 and 2004 than did those reporting low variance in workload. The ANCOVA for the shift work group showed a main effect of psychosocial work characteristics for job satisfaction (p = 0.026, partial eng2 = 0.10) and depressive symptoms (p = 0.094, partial eng2 = 0.06) with the interaction between psychosocial work characteristics and study year for job satisfaction (p = 0.172, partial eng2 = 0.04) and depressive symptoms (p = 0.035, partial eng2 = 0.07). The shift workers with low job satisfaction and high symptoms of depression in 2002 showed significantly greater ESS scores in 2003 and/or 2004 than did those with opposite characteristics. These results may suggest a potential predictive value of variance in workload for day workers as well as job satisfaction and depressive symptoms for shift workers with respect to daytime sleepiness. The present findings may imply that redesigning these aspects of work environment would be of help in managing daytime sleepiness.


Identification of a major carbohydrate capping group of the L-selectin ligand on high endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis X.
We investigated the molecular species of sulfated sialyl Lewis X determinants, the putative L-selectin ligand, expressed on high endothelial venules (HEV) in human lymph nodes. Comparison of the reactivity pattern of HEV with the reactivity of the pure 6-sulfo, 6'-sulfo, or 6,6'-bissulfo sialyl Lewis X determinant with hitherto known anti-sialyl Lewis X antibodies strongly suggested 6-sulfo sialyl Lewis X to be the best candidate for the major sulfated sialyl Lewis X determinant on HEV, followed by 6,6'-bissulfo sialyl Lewis X, whereas 6'-sulfo sialyl Lewis X was unlikely. We newly generated monoclonal antibodies (mAbs) G152 and G72 directed against 6-sulfo sialyl Lewis X, which intensely labeled HEV in immunohistochemical examination and inhibited binding of recombinant L-selectin-IgG to HEV, suggesting that the determinant serves as a ligand for L-selectin. To test the concomitant expression of 6, 6'-bissulfo sialyl Lewis X, specific mAbs (G2706, G27011, G27037, and G27039) were generated, but all antibodies failed to react to HEV. Next, we established mAbs (AG97 and AG273) directed against 6-sulfo Lewis X, the asialo form of 6-sulfo sialyl Lewis X. The antibodies were not reactive to untreated HEV, but strongly reacted to sialidase-treated HEV. This indicated the predominance of the sialylated form of 6-sulfo sialyl Lewis X and minimal expression of its asialo form, corroborating that it was synthesized by fucosyltransferase VII, the isoenzyme that preferentially produces the sialylated form of the determinant.


Photon number distributions from a diode laser.
We use balanced homodyne detection to characterize light from a diode laser as it crosses the threshold. We measure the single-time second-order correlation function g(2), and also extract the photon number distribution. Just above the laser threshold, we find that the measured g(2) exceeds the prediction of the semiclassical single-mode laser model. From the reconstructed photon number distributions, we conclude that this excess is due to emission from nonlasing modes. For higher pumping current, the light noise increases due to a different mechanism, possibly mode competition or mode partition noise.


[Nurse style of central vein! Our experience in the peripherally inserted central venous catheter].
What is PICC line insertion? The PICC is a soft, flexible catheter which is made of polyurethane or silicone, and is inserted via an upper or lower extremity peripheral vein into superior or inferior vena cava. The origin of PICC line dates back to the early 1950s. Since the introduction of the PICC catheter, this method of venous catheterization has gone through many changes as regards the technique of insertion or the type of catheter used. Despite the routine use of PICC line worldwide, little progress has been made in its use in Hungary. In this short review we will briefly summarise the use of PICC line, its indications, advantages, disadvantages, and on complementary devices which are necessary during the procedure. We discuss our experience in insertion of PICC line at Pécs University, where the procedure is solely done by a certified registered nurse. We hope that with continuous progression of nurse competency, this procedure will be implemented at a higher scale in Hungary. Orv Hetil. 2017; 158(22): 856-863.


Role of testosterone levels and of hypophysis in the HCG-induced modifications of the 7 alpha-hydroxylation and 5 alpha-reduction processes in incubated rat testes.
The role of a direct or a hypophysis-mediated influence of increased testosterone levels in the effects of a long-term high-dose HCG administration (10 IU/day) upon the 7 alpha-hydroxylation and 5 alpha-reduction activities of incubated testes of mature rats was investigated. Administration of high doses of HCG to hypophysectomized rats resulted in the same metabolic changes as in normal rats, namely, a large decrease in the 7 alpha-hydroxylation and an increase in the 5 alpha-reduction processes. Administration of testosterone-propionate (0.2 mg and 20 mg/day) for several days to hypophysectomized rats and to normal rats receiving and substitutive dose of 1 IU HCG/day, did not modify the testicular metabolization pattern. These findings indicate that the decrease in testicular 7 alpha-hydroxylation activity induced by long-term administration of high doses of HCG is probably not mediated by the hypophysis nor by the extracellular testosterone levels.


[Current situation and countermeasures of two-way referral between wound healing department and community health system].
This study analyzed the current situation and problems of two-way referral between wound healing department of general hospitals and community health service centers through stipulated interview with physicians in general hospitals and community health service centers, and patients visiting these organizations from March 2011 to April. It was found that the current two-way referral process for wound repair were facing a series of problems, including hospitals-transfer difficulty, incomplete two-way referral policy and undefined practice protocol, information-sharing obstacle between general hospitals and community health service centers. The critical countermeasures for overcoming these obstacles in two-way referral of wound ailments shall include construction of further linkage mechanism among all levels of hospitals, establishment of the drug-obtaining mechanism, establishment of an explicit two-way referral process of wound repair, and establishment of a database of diagnosis and treatment information of patients that can be accessed by doctors of different levels of hospitals, etc.


Can uterine artery pulsatility index predict fetal chromosomal abnormality in early pregnancy loss? A retrospective cohort study.
Early pregnancy loss (EPL) or spontaneous loss of an intrauterine pregnancy within the first trimester occurs commonly worldwide. It is useful to predict the possibility of fetal chromosomal abnormalities using other cheap and easily available markers. This study aimed to evaluate whether the uterine artery pulsatility index (UtA-PI) can predict fetal chromosomal abnormality in early pregnancy loss (EPL). This was a retrospective cohort study including 148 women who underwent dilation and curettage for missed abortion. The UtA-PI was measured and evaluated by transvaginal ultrasound. Abnormal UtA-PI was identified through the mean of left and right UA-PI ≥ 90th percentiles of the relevant values for the corresponding gestational age. Copy number variation sequencing (CNV-seq) was performed on EPL cases without maternal cell contamination. 107 (72.3%) cases were classified with normal UtA-PI, while 41 (27.7%) cases were classified with abnormal UtA-PI. The fetal chromosomal abnormality rate was significantly higher in cases with normal UtA-PI than in those with abnormal UtA-PI (67.3% vs 22.0%, P = 7.1 × 10-7). Compared to cases with abnormal UtA-PI, the risk of fetal chromosomal abnormalities in cases with normal UtA-PI increased with an odds ratio of 7.3 (95% confidence interval [CI]: 3.2‒17.0, P = 4 × 10-7). The predictive value of normal UtA-PI alone for fetal chromosomal abnormalities was shown to have an area under the curve of 0.67‒0.71 in our population. The UtA-PI seems to be lower and less likely to be elevated in EPL with fetal chromosomal abnormalities compared to those without aneuploidies. We suggest that UtA-PI should be examined in all EPL patients.


Attitudes to depression and psychiatric medication amid the enduring financial crisis in Attica: Comparison between 2009 and 2014.
Only a handful of studies have explored the effect of the financial crisis on public attitudes to mental illness. This study examines changes in lay attitudes to depression and psychiatric medication between 2009 and 2014 in Attica region. Furthermore, it explored a potential interaction with employment status. Data were drawn from two surveys conducted in 2009 and 2014 using the same sampling procedure, interview mode, and survey instrument. Specifically, a random and representative sample of 586 people was recruited in 2009 and of 604 in 2014. Attitudes to depression were measured by the Personal Stigma subscale of the Depression Stigma Scale and attitudes to psychiatric medication by a self-constructed scale with good psychometric properties. Data collection occurred via telephone. There has been no overall change in lay attitudes to depression. Nonetheless, a positive change was recorded with regard to the belief that depression is a sign of personal weakness and a negative change with respect to people with depression being dangerous. Attitudes to psychiatric medication have worsened during the study period. Employment status was not found to interact with the survey year. Anti-stigma efforts should be tailored on counteracting the dangerousness stereotype, while they should prioritize targeting attitudes to psychiatric medication.


Long noncoding RNA UCA1 induced by SP1 promotes cell proliferation via recruiting EZH2 and activating AKT pathway in gastric cancer.
Long noncoding RNA UCA1 has emerged as a novel regulator in cancer initiation and progression of various cancers. However, function and underlying mechanism of UCA1 in the progression of gastric cancer (GC) remain unclear. In the present study, we report that UCA1 expressed highly in GC tissues and GC cells, which was partly induced by SP1. UCA1 promoted GC cell proliferation and G1/S transition in vitro and in vivo. Moreover, UCA1 exerted its function through interacting with EZH2, promoting direct interaction with cyclin D1 promoter to activate the translation of cyclin D1. Furthermore, AKT/GSK-3B/cyclin D1 axis was activated to upregulate cyclin D1 due to overexpression of UCA1. In addition, EZH2 and phosphorylated AKT induced by UCA1 could impact each other to form a positive feedback to promote cyclin D1 expression. This study demonstrated that UCA1 as a critical regulator involved in GC proliferation and cell cycle progression by promoting cyclin D1 expression, which indicates that it may be clinically a potential therapeutic target in GC.


Specificity and sensitivity of skin test reactions to extracts of Toxocara canis and Ascaris suum. I. Skin tests done on infected guinea pigs.
The specificity and sensitivity of adult and larval somatic antigens, and perienteric fluid of Toxocara canis and Ascaris suum were investigated by using intradermal skin tests in guinea pigs. These animals were infected with low doses (0.01, 0.1 or 1.0 egg/g) of these helminths. Toxocara larval antigen (TL) induced larger reactions in Toxocara-infected animals than did the other antigens, suggesting a superior sensitivity for this antigen. In addition, Ascaris perienteric fluid (AP) provoked skin responses in these animals of a magnitude similar to those induced by TL. The reciprocal relationship, i.e., comparable reactivity of AP and TL in Ascaris-infected animals, was not apparent. In general, Ascaris larval antigen and AP elicited larger intradermal reactions than other antigens in Ascaris-infected animals. The results of this study indicated no superiority of adult antigens in differentiating Ascaris and Toxocara infections.


The human ribosomal DNA array is composed of highly homogenized tandem clusters.
The structure of the human ribosomal DNA (rDNA) cluster has traditionally been hard to analyze owing to its highly repetitive nature. However, the recent development of long-read sequencing technology, such as Oxford Nanopore sequencing, has enabled us to study the large-scale structure of the genome. Using this technology, we found that human cells have a quite regular rDNA structure. Although each human rDNA copy has some variations in its noncoding region, contiguous copies of rDNA are similar, suggesting that homogenization through gene conversion frequently occurs between copies. Analysis of rDNA methylation by Nanopore sequencing further showed that all the noncoding regions are heavily methylated, whereas about half of the coding regions are clearly unmethylated. The ratio of unmethylated copies, which are speculated to be transcriptionally active, was lower in individuals with a higher rDNA copy number, suggesting that there is a mechanism that keeps the active copy number stable. In addition, the rDNA in progeroid syndrome patient cells with reduced DNA repair activity had more unstable copies compared with control normal cells, although the rate was much lower than previously reported using a fiber-FISH method. Collectively, our results clarify the view of rDNA stability and transcription regulation in human cells, indicating the presence of mechanisms for both homogenizations to ensure sequence quality and maintenance of active copies for cellular functions.


Catheter-directed urokinase thrombolysis: an adjunct to PTA/surgery for management of lower extremity thromboembolic disease.
Catheter-directed thrombolysis was used either alone or as an adjunct to percutaneous transluminal angioplasty (PTA) or surgery for peripheral vascular occlusion on 112 occasions in 102 patients. Symptom duration ranged from < one to > twenty-eight days. Thrombolytic therapy using urokinase plasminogen activator thrombolysis (uPAT), including intrathrombic injection when possible, was successful (> 50% lysis) in 99 procedures (88%). Technical failure (< 50% lysis) occurred in 13 procedures (12%). In 9 of the 13 failures, intrathrombic injection of urokinase was not possible, but the duration of occlusion was > twenty-eight days in all but 1. Two other failures were from embolic sources and 2 more occurred in patients with a hypercoagulable state. The uPAT was adjunctive to PTA/surgery in 56 cases (50%). PTA following uPAT was required and successfully performed in 24 of 27 cases (88.9%). Surgery followed lytic therapy in another 32 (including the 3 failed PTAs). In the remaining 56 cases (50%), no additional intervention was required. There were 20 complications (18%), minor in 16 of 20 (80%). Minor complications included small puncture site hematomas and distal embolization resolved by continued lytic therapy. Four major complications occurred. One was retroperitoneal hemorrhage directly contributing to the only death in the series. The other 3 were hematuria (2) and femoral neuropathy (1). The authors conclude that catheter-directed lytic therapy alone or as an adjunct to PTA/surgery is a valuable approach to peripheral vascular thromboembolic disease. It is less likely to succeed in chronic occlusion. The incidence of complications is moderate but acceptable.


Accelerated ribosome formation and growth in neonatal pig hearts.
Rapid growth (5 mg dry heart/h) of the left ventricular free wall (LVFW) in the newborn pig heart accompanied by lack of growth of the right ventricular free wall (RVFW) represents a unique natural model of cardiac enlargement that is free of pathophysiological influences. By 3 days of life, LVFW was 71% larger than at 4 h of age. Rates of protein synthesis were measured during perfusion of isolated pig hearts with bicarbonate buffer containing glucose, lactate, insulin, and plasma concentrations of amino acids of an aortic pressure of 60 mmHg. In hearts from pigs that were 18 h of age, rates of protein synthesis were the same in RVFW and LVFW, but in 2-day-old pigs the rate was 52% greater in LVFW than RVFW. During the first 3 days of life, RNA content (mg/g) increased 3.4-fold faster in LVFW than RVFW. When RNA content was expressed per total heart portion, the increase was 7.9-fold greater. Because approximately 85% of total RNA is rRNA, these values indicated much more rapid formation of ribosomes in the LVFW than RVFW. When ribosome formation was measured in vitro in hearts from 48-h-old pigs, rates of formation were 39% greater in LVFW than RVFW, and at 18 h of age, ribosome formation was 40% faster in LVFW than RVFW. These findings indicated that formation of new ribosome preceded accelerated synthesis of total heart proteins. These findings indicated that rapid growth of LVFW compared with no growth of RVFW was associated with a 67% faster rate of ribosome formation and a 32% greater rate of protein synthesis.


Negative control of hemoglobin production in somatic cell hybrids due to heme deficiency.
In somatic cell hybrids formed by the fusion of mouse erythroleukemic cells with mouse primary bone marrow cells, retention of the X chromosome contributed by the bone marrow parent is correlated with inhibition of hemoglobin accumulation in response to dimethyl sulfoxide. The inhibition of hemoglobin accumulation is not due to the absence of globin mRNA. Dimethyl sulfoxide-treated hybrid cells accumulate polyribosomal globin mRNA to levels comparable to those of the parental erythroleukemic cells under the same conditions. Heme, or its precursor delta-aminolevulinc acid, can overcome the effects of the bone marrow X chromosome and induce hemoglobin accumulation in the dimethyl sulfoxide-treated hybrid cells. The data suggest that the X chromosome contributed by the bone marrow cells inhibits hemoglobin production by inhibiting inducible heme biosynthesis, most probably at the step catalyzed by delta-aminolevulinic acid synthetase (EC 18.104.22.168).


Synthesis, antiviral activity, and biological properties of vinylacetylene analogs of enviroxime.
A series of vinylacetylene analogs of Enviroxime (1) was synthesized. The new compounds are potent inhibitors of poliovirus in tissue culture. Cross-sensitivity with Enviroxime-derived mutants shows that the new compounds have the same mechanism of action as Enviroxime, which involves the viral 3A protein. In studies with Rhesus monkeys, the p-fluoro derivative 12 was found to be unique in providing oral bioavailability. Metabolism studies using hepatic microsomes suggest that this procedure would be a useful in vitro method for selecting the appropriate animal model for testing oral absorption. Compound 12 was found to be efficacious by oral administration in treating a Coxsackie A21 infection in CD-1 mice.


Ultrasensitive Detection of Dual Cancer Biomarkers with Integrated CMOS-Compatible Nanowire Arrays.
A direct, rapid, highly sensitive and specific biosensor for detection of cancer biomarkers is desirable in early diagnosis and prognosis of cancer. However, the existing methods of detecting cancer biomarkers suffer from poor sensitivity as well as the requirement of enzymatic labeling or nanoparticle conjugations. Here, we proposed a two-channel PDMS microfluidic integrated CMOS-compatible silicon nanowire (SiNW) field-effect transistor arrays with potentially single use for label-free and ultrasensitive electrical detection of cancer biomarkers. The integrated nanowire arrays showed not only ultrahigh sensitivity of cytokeratin 19 fragment (CYFRA21-1) and prostate specific antigen (PSA) with detection to at least 1 fg/mL in buffer solution but also highly selectivity of discrimination from other similar cancer biomarkers. In addition, this method was used to detect both CYFRA21-1 and PSA real samples as low as 10 fg/mL in undiluted human serums. With its excellent properties and miniaturization, the integrated SiNW-FET device opens up great opportunities for a point-of-care test (POCT) for quick screening and early diagnosis of cancer and other complex diseases.


Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.
Neuronal apoptosis is a very important event in the development of the central nervous system (CNS), but the underlying mechanisms remain to be elucidated. We have previously shown that safrole oxide, a small molecule, induces integrin beta4 expression and promotes apoptosis in vascular endothelial cells. In this study, the effects of safrole oxide on cell growth and apoptosis have been examined in primary cultures of mouse neurons. Safrole oxide was found to significantly inhibit neuronal cell growth and to induce apoptosis. The inhibitory and apoptotic activities of safrole oxide followed a dose- and time-dependent manner. Interestingly, the expression of integrin beta4 was significantly inhibited with safrole oxide treatment. Furthermore, safrole oxide dramatically increases the level of intracellular reactive oxygen species (ROS) and the activity of NADPH oxidase. Moreover, manganese-dependent superoxide dismutase (MnSOD) activity was decreased significantly with safrole oxide treatment. Our study thus demonstrates that safrole oxide induces neuronal apoptosis through integrin beta4, ROS, NADPH, and MnSOD.


Synthesis of novel fatty-acyl gratisin derivatives.
To find candidates with high antimicrobial and low hemolytic activities, many gratisin (GR) analogues have been designed and synthesized. In the present account, we synthesized novel derivatives of GR having both the polycationic and fatty acyl groups, cyclo{-Val(1)-Orn(2)-Leu(3)-D-Phe(4)-Pro(5)-D-Lys(6)(X)-Val(7)-Orn(8)-Leu(9)-D-Phe(10)-Pro(11)-D-Lys(12)-} {X=-CO(CH(2))(6)CH(3) (1), -Lys-CO(CH(2))(6)CH(3) (2), -(Lys)(2)-CO(CH(2))(6)CH(3) (3), and -(Lys)(3)-CO(CH(2))(6)CH(3) (4)}, and examined the biological activities. Among them, we found that 2-4 have differential ionic interaction against the prokaryotic membrane and eukaryotic membrane. In other words, the dissociation with high antimicrobial activity and low hemolytic activity is caused by the addition of D-Lys(6)-{(Lys)(n)-CO(CH(2))(6)CH(3)} residues at position 6 of [D-Lys(6,12)]-GR. Our findings should be helpful in finding drug candidates with high antimicrobial activity and low hemolytic activity that are capable of combating microbial resistance.


A dual caudal-fin miniature robotic fish with an integrated oscillation and jet propulsive mechanism.
This paper presents the development of a biomimetic robotic fish that uses an integrated oscillation and jet propulsive mechanism to enable good swimming performance for small robotic fish. The designed robotic fish is driven by two caudal fins that flap oppositely, which are equipped in parallel at the fish tail. The propulsive mechanism of dual caudal fins is characterized by using numerical analysis, in which the distance between the two caudal fins is a key factor to the integrated mechanism and plays an important role to swimming performance. This finding has been further verified by experiments performed on a miniature robotic fish prototype with 100 mm length and 30 mm diameter. Experimental results have demonstrated the influence of the distance between the two caudal fins to swimming performance. The designed miniature robotic fish can swim stably and efficiently while exhibiting good motion maneuverability such as turning and braking. The developed robotic fish, with advantages of excellent swimming performance and small size, can be potentially used for monitoring and exploration in the underwater environment.


A new dehydrogenase specific towards aromatic aldehydes from a halophilic bacterium.
A new enzyme showing a dehydrogenase activity towards aromatic aldehydes was isolated, purified and characterized from a halophilic strain isolated from saline environment. The enzyme is a monomer of 54 kDa; it is rather thermostable (optimal temperature: 50 degrees C) showing a broad spectrum of activity in a large pH range with the maximum at pH 9.5. The substrate specificity and the effect of ions were evaluated and compared with analogous described proteins.


Fermented foods and probiotics: An approach to lactose intolerance.
The aim of this review was to present various topics related to lactose intolerance with special attention given to the role of fermented foods and probiotics in alleviating gastrointestinal symptoms. Lactose intolerance is a common digestive problem in which the human body is unable to digest lactose, known as milk sugar. Lactose intolerance can either be hereditary or a consequence of intestinal diseases. Recent work has demonstrated that fermented dairy products and probiotics can modify the metabolic activities of colonic microbiota and may alleviate the symptoms of lactose intolerance. We suggest that, lactose free dairy products could be recommended as alternatives for the alleviation of lactose intolerance and for the promotion of human health and wellness.


Dynamic air-water exchange of polychlorinated biphenyls in the New York-New Jersey Harbor Estuary.
Simultaneous measurements of polychlorinated biphenyls (PCBs) in the air and water over Raritan Bay and New York Harbor were taken in July 1998, allowing the first determinations of air-water exchange fluxes for this heavily impacted system. Average gas-phase concentrations of sigmaPCBs were 1.0 ng m(-3) above Raritan Bay and 3.1 ng m(-3) above New York Harbor. A similar gradient was observed for dissolved water concentrations (1.6 and 3.8 ng L(-1), respectively). Shallow slopes of log K(oc) vs log K(ow) plots indicated a colloidal contribution to the dissolved concentrations, and a three-phase partitioning model was therefore applied. PCBs associated with colloids ranged from 6% to 93% for trichloro- to nonachlorobiphenyls, respectively. Air-water gas exchange fluxes of sigmaPCBs exhibited net volatilization for both Raritan Bay at +400 ng m(-2) day(-1) and New York Harbor at +2100 ng m(-2) day(-1). The correction for the colloidal interactions decreased the volatilization flux of sigmaPCBs by about 15%. Net air-water exchange fluxes of PCBs are expected to remain positive throughout the year due to the large water-air fugacity gradient and relatively constant seasonal water concentrations. The volatilization fluxes are approximately 40 times greater than atmospheric deposition of PCBs via both wet and dry particle deposition, suggesting that the estuary acts as a net source of PCBs to the atmosphere year-round.


The Diagnostic Importance of Recombinant Allergen IgE Testing in Patients with Hymenoptera Venom Allergy: Comparison of Two Methods.
Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting. In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP. We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods. The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HV allergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms. IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts.


Comparison of the diagnostic performance of microscopic examination with nested polymerase chain reaction for optimum malaria diagnosis in Upper Myanmar.
Accurate diagnosis of Plasmodium infection is crucial for prompt malaria treatment and surveillance. Microscopic examination has been widely applied as the gold standard for malaria diagnosis in most part of malaria endemic areas, but its diagnostic value has been questioned, particularly in submicroscopic malaria. In this study, the diagnostic performance of microscopic examination and nested polymerase chain reaction (PCR) was evaluated to establish optimal malaria diagnosis method in Myanmar. A total of 1125 blood samples collected from residents in the villages and towns located in Naung Cho, Pyin Oo Lwin, Tha Beik Kyin townships and Mandalay of Upper Myanmar were screened by microscopic examination and species-specific nested PCR method. Among the 1125 blood samples, 261 samples were confirmed to be infected with malaria by microscopic examination. Evaluation of the 1125 samples by species-specific nested PCR analysis revealed that the agreement between microscopic examination and nested PCR was 87.3% (261/299). Nested PCR successfully detected 38 Plasmodium falciparum or Plasmodium vivax infections, which were missed in microscopic examination. Microscopic examinations also either misdiagnosed the infected Plasmodium species, or did not detect mixed infections with different Plasmodium species in 31 cases. The nested PCR method is more reliable than conventional microscopic examination for the diagnosis of malaria infections, and this is particularly true in cases of mixed infections and submicroscopic infections. Given the observed higher sensitivity and specificity of nested PCR, the molecular method holds enormous promise in malaria diagnosis and species differentiation, and can be applied as an effective monitoring tool for malaria surveillance, control and elimination in Myanmar.


Molecular cloning and characterization of a dehydration-inducible cDNA encoding a putative 9-cis-epoxycarotenoid dioxygenase in Arachis hygogaea L.
A rate-limiting step in abscisic acid (ABA) biosynthesis in plants is catalyzed by 9-cis-epoxycarotenoid dioxygenase (NCED). Here we present the cloning, characterization of a cDNA from dehydrated peanut (Arachis hygogaea L.) leaves that encodes a putative NCED. The 2486-bp full-length cDNA (designated as AhNCED1), obtained by rapid amplification of cDNA ends (RACE), has an open reading frame of 601 amino acid residues and encodes a protein with a calculated molecular weight of 66.86 kDa and an isoelectric point of 8.39. Sequence analysis shows that the deduced amino acid sequence of AhNCED1 shares high identity with the reported NCED protein sequences. There is a 30-amino-acid chloroplast-targeting peptide at the N-terminus of the AhNCED1 protein predicted by iPSORT algorithm. Semi-quantification by duplex RT-PCR reveals that the expression of AhNCED1 is up-regulated by dehydration and that rehydration represses its expression. The organ specific expression pattern of AhNCED1 has been examined, which indicates its dominant expression in leaves and stems. Molecular analysis of the drought-inducible gene of peanut may be useful to investigate the response of agricultural crops to drought stress.


Ureaplasma serotypes associated with the bovine urogenital tract.
One hundred and thirty-one ureaplasma isolates were tested using the immunoperoxidase system. Thirty-four were from semen, 34 from preputial washes of normal bulls and 63 were from vaginal swabs from herds experiencing infertility problems and/or vulvovaginitis. The serotypes from semen were T44 (12.1%), Bu2 (11.2%), D48 (2.8%), T315 (0.9%) and T288 (0.9%). Those from preputial washes were T44 (9.3%), Bu2 (8.4%), T288 (7.5%), D48 (0.9%) and T95 (0.9%). From vaginal swabs the serotypes were D48 (22.4%), Bu2 (10.3%), T45 (4.7%), T288 (3.8%) and T315 (1.9%).


Validation of an equation for calculation of glucose appearance during nonsteady state in sheep.
The purpose of this study was to validate the calculation of the rate of glucose appearance (RA) during nonsteady state for sheep. The RA given by the modified single-compartment model was compared with the actual rate derived from the sum of the infusion of exogenous glucose and endogenous production as determined from hepatic production of glucose. Using a pool fraction of 0.65, the error associated with calculation of RA was about 10%.


Endoplasmic Reticulum Stress Response of Trabecular Meshwork Stem Cells and Trabecular Meshwork Cells and Protective Effects of Activated PERK Pathway.
This study aimed to investigate the differential responses of trabecular meshwork stem cells (TMSCs) and trabecular meshwork (TM) cells to endoplasmic reticulum (ER) stress inducers. Human TM cells and TMSCs were exposed to tunicamycin, brefeldin A, or thapsigargin. Cell apoptosis was evaluated by flow cytometry. ER stress markers were detected by quantitative PCR, Western blotting, and immunostaining. Morphologic changes were evaluated by transmission electron microscopy. Cells were treated with the PERK inhibitor GSK2606414 or the elF2α dephosphorylation inhibitor Salubrinal together with tunicamycin to evaluate their effects on ER stress. Both TMSCs and TM cells underwent apoptosis after 48- and 72-hour treatment with ER stress inducers. ER stress triggered the unfolded protein response (UPR) with increased expression of GRP78, sXBP1, and CHOP, which was significantly lower in TMSCs than TM cells. Swollen ER and mitochondria were detected in both TMSCs and TM cells. Neither GSK2606414 nor salubrinal alone activated UPR. GSK2606414 significantly reduced cell survival rates after tunicamycin treatment, and salubrinal increased cell survival rates. The increased expression of GRP78, sXBP1, CHOP, and GADD34 peaked at 6 or 12 hours and lasted longer in TM cells than TMSCs. Salubrinal treatment dramatically increased OCT4 and CHI3L1 expression in TMSCs. In response to ER stress inducers, TMSCs activated a lower level of UPR and lasted shorter than TM cells. Inhibition of elF2α dephosphorylation had a protective mechanism against cell death. Stem cells combined with salubrinal may be a more effective way for TM regeneration in glaucoma.


Acute dental infections managed in an outpatient parenteral antibiotic program setting: prospective analysis and public health implications.
The number of Acute Dental Infections (ADI) presenting for emergency department (ED) care are steadily increasing. Outpatient Parenteral Antibiotic Therapy (OPAT) programs are increasingly utilized as an alternative cost-effective approach to the management of serious infectious diseases but their role in the management of severe ADI is not established. This study aims to address this knowledge gap through evaluation of ADI referrals to a regional OPAT program in a large Canadian center. All adult ED and OPAT program ADI referrals from four acute care adult hospitals in Calgary, Alberta, were quantified using ICD diagnosis codes in a regional reporting system. Citywide OPAT program referrals were prospectively enrolled over a five-month period from February to June 2014. Participants completed a questionnaire and OPAT medical records were reviewed upon completion of care. Of 704 adults presenting to acute care facilities with dental infections during the study period 343 (49%) were referred to OPAT for ADI treatment and 110 were included in the study. Participant mean age was 44 years, 55% were women, and a majority of participants had dental insurance (65%), had seen a dentist in the past six months (65%) and reported prior dental infections (77%), 36% reporting the current ADI as a recurrence. Median length of parenteral antibiotic therapy was 3 days, average total course of antibiotics was 15-days, with a cumulative 1326 antibiotic days over the study period. There was no difference in total duration of antibiotics between broad and narrow spectrum regimes. Conservative cost estimate of OPAT care was $120,096, a cost savings of $597,434 (83%) compared with hospitalization. ADI represent a common preventable cause of recurrent morbidity. Although OPAT programs may offer short-term cost savings compared with hospitalization, risks associated with extended antibiotic exposures and delayed definitive dental management must also be gauged.


Preoperative determination of appropriate cutting line for proximal gastrectomy to avoid postoperative jejunal ulcer.
Although proximal gastrectomy has become a procedure of choice for patients' early cancer in the upper third of stomach, no clinical guide for optimal gastric resection in order to avoid postoperative jejunal ulcer is available. The aim of this study was to investigate whether determining the distribution of parietal and chief cells of the stomach using Congo red test is clinically relevant. The F-line was defined as a boundary line between fundic and intermediate area of the stomach according to the pathological findings in 29 patients who underwent total gastrectomy for early gastric cancer, whereas the f-line was regarded as a boundary line between intermediate and pyloric area. In the additional 6 patients undergoing vagus-preserving proximal gastrectomy with jejunal pouch interposition, endoscopic Congo red test was preoperatively performed to determine the F-f-line. The distances from the pyloric ring to f-line on the lesser and greater curvatures were variable. Long-term outcomes of proximal gastrectomy guided by preoperative endoscopic Congo red test were favorable. It is suggested that preoperative endoscopic Congo red test is useful to determine the appropriate cutting line in order to avoid postoperative jejunal ulcer after proximal gastrectomy.


The role of O-GlcNAc transferase in regulating the gene transcription of developing and failing hearts.
Heart failure treatment currently centers on symptom management, primarily through reductions in systemic blood pressure and fluid retention. The O-linked attachment of β-N-acetylglucosamine to cardiac proteins is increased in cardiovascular disease and heart failure, and O-GlcNAc transferase (OGT) is the enzyme that catalyzes this addition. Deletion of OGT is embryonically lethal, and cardiomyocyte-specific OGT knockdown causes the exacerbation of heart failure. Stem cell therapy is currently a major focus of heart failure research, and it was recently discovered that OGT is intricately involved with stem cell differentiation. This article focuses on the relationship of OGT with epigenetics and pluripotency, and integrates OGT with several emerging areas of heart failure research, including calcium signaling.


Ecological Specialization and Evolutionary Reticulation in Extant Hyaenidae.
During the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four species: the bone-cracking spotted, striped, and brown hyenas, and the specialized insectivorous aardwolf. Previous studies investigated the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and insectivory, defining traits of the extant species, remain elusive. Here, we generated an aardwolf genome and analyzed it together with the remaining three species to reveal their evolutionary relationships, genomic underpinnings of their scavenging and insectivorous lifestyles, and their respective genetic diversities and demographic histories. High levels of phylogenetic discordance suggest gene flow between the aardwolf lineage and the ancestral brown/striped hyena lineage. Genes related to immunity and digestion in the bone-cracking hyenas and craniofacial development in the aardwolf showed the strongest signals of selection, suggesting putative key adaptations to carrion and termite feeding, respectively. A family-wide expansion in olfactory receptor genes suggests that an acute sense of smell was a key early adaptation. Finally, we report very low levels of genetic diversity within the brown and striped hyenas despite no signs of inbreeding, putatively linked to their similarly slow decline in effective population size over the last ∼2 million years. High levels of genetic diversity and more stable population sizes through time are seen in the spotted hyena and aardwolf. Taken together, our findings highlight how ecological specialization can impact the evolutionary history, demographics, and adaptive genetic changes of an evolutionary lineage.


The effects of trans-cranial direct current stimulation intervention on fear: A systematic review of literature.
Intensifying fear and fear of pain may lead to some diseases such as panic disorder, phobias, post-traumatic stress disorder (PTSD), anxiety disorders, depression, etc. A number of studies indicated positive effect of transcranial direct current stimulation (tDCS) on controlling fear and some studies did not observe any effect or even negative effect on decreasing fear. Due to lack of consensus in the findings of research, we aimed to systematically review studies, which investigated the effect of tDCS on fear. A literature search was conducted using the databases of PubMed, Science Direct, OVID, CINAHL, PEDro, Cochrane, Scopus and MEDLINE. Fear, fear memory, fear of pain, anxiety, post-traumatic stress disorder, electrical brain stimulation were applied as keywords. The valid assessment scale was used to evaluate the methodological quality of the included studies. The results of this systematic review revealed that the cathodal tDCS (c-tDCS) on the left dorsolateral prefrontal cortex (DLPFC) as compared to anodal tDCS (a-tDCS) could significantly reduce fear and modulate the fear memory. In addition, the findings of this study showed that the c-tDCS has positive effect on behavioural parameters of fear, while it cannot change biochemical parameters of fear during limited sessions of intervention. Application of c-tDCS on the left DLPFC could significantly reduce fear and modulate the fear memory.


Quantitative analysis of prostatic intraepithelial neoplasia on tissue sections.
The changes in nuclear morphology (karyometry) and DNA content in prostatic intraepithelial neoplasia (PIN) were analyzed on tissue sections. The cases of PIN were subdivided into PIN 1 and PIN 2 based on the degree of proliferation and the anaplasia of the secretory cells lining the ducts and acini. Cases of nodular hyperplasia (NH) and adenocarcinoma were also studied for comparative purposes. Karyometric analysis showed a progression of most values from NH to PIN to carcinoma. The DNA analysis showed a decrease in the frequency of nuclei in the diploid range and an increase in the percentage of nuclei in the other ploidy regions (especially between 2c and 4c and in the tetraploid range) from NH to PIN to carcinoma. Forward stepwise discriminant analysis showed similarities between NH and PIN 1 and between PIN 2 and carcinoma. These findings suggest that the evolution towards adenocarcinoma is characterized by progressive morphologic derangements of the nuclei and by the transformation of the diploid DNA content into a nondiploid one, with the changes taking place at the level of PIN 2.


Smokeless tobacco use in Nepal.
Tobacco use is widely prevalent in different forms in Nepal. These habits are deeply rooted among different age groups and gender. There is no information available on all aspects of smokeless tobacco (SLT) use and its implications in Nepal. To review the types of SLT products available in Nepal, prevalence of SLT use, correlates of SLT use, SLT-related harm, and existing gaps in information and policy implications. This review is mainly based on information from literature, and some WHO and other documents. The prevalence of smokeless tobacco use is high, particularly among males and disadvantaged groups. SLT users have multiple habits of tobacco chewing, smoking and drinking. Despite SLT products being manufactured in the unorganized sector, they are also largely imported from India. People have easy access to various SLT products. There is a general lack of information on the health hazards of SLT use to the population. This calls for research on the issue. In order to succeed in reducing SLT use in Nepal, addressing the challenges of enforcing the Tobacco Control Act through a multisectoral approach and developing capacity of sectors other than health is of vital importance.


Correlation of Functional Independence Measure for Children (WeeFIM) with developmental language tests in children with developmental delay.
The Functional Independence Measure for Children (WeeFIM) is a simple tool for assessing the functional independence of three domains: mobility, self-care, and cognition. Children are usually apprehensive about performing standardized structured language or developmental tests, and only licensed professionals can administer standardized tests. We attempted to apply the Functional Independence Measure for Children for assessing children with developmental delay and to assess for any correlation of these scores with standardized language tests. We recruited 49 children with developmental delay, and the Functional Independence Measure for Children was administered. Two standardized language tests (Symbolic Play Test and Reynell Language Developmental Scale) were administered to assess language age. There was a significant correlation between Functional Independence Measure for Children scores with both verbal comprehension age and verbal expression age. There was no correlation of Functional Independence Measure for Children scores with gender, age, or having domestic helpers. Having trained staff administer the Functional Independence Measure for Children can reliably correlate the current language ability of a child with developmental delay; thus, the test can be used as a quick screening tool for targeted training.


Vasopressin Continuous Infusion Improves Intracranial Pressure and Patient Outcomes after Surgical Clipping or Endovascular Coiling of Cerebral Aneurysm.
Hypertensive therapy prevents vasospasm-related delayed ischemic neurologic deficit and infarcts. New alternatives would include vasopressin which has vasoconstrictive effects and positive influence on cerebral perfusion pressure (CPP) and intracranial pressure (ICP). The aim of this study is to demonstrate the value of vasopressin intravenous infusion (IVI) in decreasing ICP and preventing vasospasm following surgical clipping or endovascular coiling. A triple-blind prospective randomized controlled study. Thirty patients, 25-60 years, both genders, had undergone surgical clipping or endovascular coiling for a cerebral aneurysm, World Federation of Neurosurgical Societies (WFNS) grade 1-3 (15 patients in each); Group I (Vasopressin): 0.1-0.4 unit/min and Group II (Norepinephrine): 5-20 ug/min with target systolic blood pressure 160-180 mmHg. SPSS version 25 software was used for analysis. Invasive mean arterial pressure (MAP) showed the insignificant difference between the two groups, but ICP showed a significant decrease in Group V from hour 24 to 168 hence calculated CPP showed a significant increase in Group V at most times from hour 36 to 168. Glasgow Coma Scale showed a significant decrease in Group N from hour 138 due to the occurrence of vasospasm. The incidence of vasospasm, mechanical ventilation, and 28-day mortality were significantly lower in Group V with 81% risk reduction of vasospasm and better survival. Vasopressin IVI improved ICP, MAP, CPP and patient outcomes safely by reducing the incidence of cerebral vasospasm, and 28-day mortality after clipping or coiling of the cerebral aneurysm.


A Simple Gas-Solid Treatment for Surface Modification of Li-Rich Oxides Cathodes.
Li-rich layered oxides with high capacity are expected to be the next generation of cathode materials. However, the irreversible and sluggish anionic redox reaction leads to the O2 loss in the surface as well as the capacity and voltage fading. In the present study, a simple gas-solid treatment with ferrous oxalate has been proposed to uniformly coat a thin spinel phase layer with oxygen vacancy and simultaneously realize Fe-ion substitution in the surface. The integration of oxygen vacancy and spinel phase suppresses irreversible O2 release, prevents electrolyte corrosion, and promotes Li-ion diffusion. In addition, the surface doping of Fe-ion can further stabilize the structure. Accordingly, the treated Feox-2 % cathode exhibits superior capacity retention of 86.4 % and 85.5 % at 1 C and 2 C to that (75.3 % and 75.0 %) of the pristine sample after 300 cycles, respectively. Then, the voltage fading is significantly suppressed to 0.0011 V per cycle at 2 C especially. The encouraging results may play a significant role in paving the practical application of Li-rich layered oxides cathode.


Er:YAG laser for brackets bonding: a SEM study after debonding.
The introduction of Er:YAG laser in dentistry for ablation of hard tissues advocated an alternative method of enamel etching for orthodontics purpose. 55 extracted human third molars were inserted in acrylic resin blocks and divided into five groups of 11 teeth. Group 1 was treated with 37% orthophosphoric acid for 30 seconds. Group 2 was treated with laser irradiation (Er:YAG Fidelius III, Fotona, Slovenia) at 80 mJ and 4 Hz. Group 3 underwent laser treatment (80 mJ, 4 Hz), followed by 37% orthophosphoric acid for 30 seconds. The teeth in Group 4 were treated with laser at 40 mJ and 10 Hz. The teeth in Group 5 were treated with laser (40 mJ, 10 Hz), followed by 37% orthophosphoric acid for 30 seconds. The adhesive remnant index was determined after debonding. Kruskas-Wallis test showed that location parameters (median and mean) are significantly different between Groups 2 and 4 when compared with control group; on the contrary no significant difference was detected between Groups 3 and 5 with the controls. The use of Er:YAG laser alone, as in Groups 2 and 4, showed no significant advantages over phosphoric acid in the bonding procedure for orthodontics brackets.


Diffuse fluorescence fiber probe for in vivo detection of circulating cells.
There has been significant recent interest in the development of technologies for enumeration of rare circulating cells directly in the bloodstream in many areas of research, for example, in small animal models of circulating tumor cell dissemination during cancer metastasis. We describe a fiber-based optical probe that allows fluorescence detection of labeled circulating cells in vivo in a diffuse reflectance configuration. We validated this probe in a tissue-mimicking flow phantom model in vitro and in nude mice injected with fluorescently labeled multiple myeloma cells in vivo. Compared to our previous work, this design yields an improvement in detection signal-to-noise ratio of 10 dB, virtually eliminates problematic motion artifacts due to mouse breathing, and potentially allows operation in larger animals and limbs.


Unclassified cardiomyopathy in a geriatric cat.
A 15-year-old, neutered male, domestic shorthair presented with dyspnea. Unclassified cardiomyopathy was diagnosed. Treatment resulted in a profound bradycardia, which was attributed to the administration of a beta-adrenergic blocker. The pathogenesis of unclassified cardiomyopathy is discussed and the side effects of beta-adrenergic blockers and angiotensin converting enzyme inhibitors are reviewed.


Characterization of the equilibrium intermediates in acid denaturation of human stefin B.
Acid-induced denaturation of recombinant human stefin B was followed using circular dichroism (CD) and fluorimetry. By comparing different spectroscopic probes, a number of equilibrium intermediates were detected. In pH denaturation at very low salt concentration (0.03 M NaCl) four states can be distinguished: N - I(N) - I1 - U, where N is the native state, I(N) is a native-like intermediate, I1 is an acid intermediate state with properties of a molten globule and U is the unfolded state. State 1, exhibits no near-ultraviolet CD but has some residual far-ultraviolet CD. It differs from U in its ability to increase fluorescence of 1-anilino-naphthalene 8-sulfonate (ANS). In 0.42 M salt, the pH denaturation is three-state between the dimeric native state N2 and intermediates I(N2) and I2, which are also dimeric according to size-exclusion chromatography. The acid intermediate I2 is more structured than I1: it binds ANS to a lower extent an I1, its Tyr residues are protected from the solvent, it shows some near-ultraviolet CD and its far-ultraviolet CD is even more intense than that for the native state. 1H-NMR spectra confirmed the overall structural features of the acid intermediates. To obtain the enthalpies of unfolding, microcalorimetric measurements were performed under conditions where the acid intermediates are maximally populated (18 degrees C): state I(N) from pH 5.0 to 4.6, 0.03 M salt: state I1 below pH 3.8, 0.42 M salt; and state I1 in equilibrium with I(N) at pH 4.05, 0.03 M salt. Enthalpies of unfolding for states I(N) and I1 were comparable to those of the native state. The enthalpy of unfolding for state I1 could not be determined.


[Cytotoxicity study of heparin coated polyvinyl chloride material].
In this study, heparin ionically coated polyvinyl chloride (PVC) material was prepared by heparin-benzalkonium chloride complex (Group A), heparin-benzalkonium bromide complex (Group B) and heparin-polyethyleneimine compound (Group C). Cytotoxicity evaluation was conducted by direct cell contact evaluation and MTT colorimetry method. The results showed Group A and Group B caused L-929 cells to die out while Group C showed good compatibility with cells. The OD levels of Group A and B were lower than that of the Group C in MTT test. Method A and method B of heparin coating had remarkable cytotoxicity, while method C had little cytotoxicity and could be further studied for clinical use.


MOF-Derived Double-Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging-Guided Sonodynamic Therapy.
The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.


Winners and losers of land use change: A systematic review of interactions between the world's crane species (Gruidae) and the agricultural sector.
While agricultural intensification and expansion are major factors driving loss and degradation of natural habitat and species decline, some wildlife species also benefit from agriculturally managed habitats. This may lead to high population densities with impacts on both human livelihoods and wildlife conservation. Cranes are a group of 15 species worldwide, affected both negatively and positively by agricultural practices. While eleven species face critical population declines, numbers of common cranes (Grus grus) and sandhill cranes (Grus canadensis) have increased drastically in the last 40 years. Their increase is associated with higher incidences of crane foraging on agricultural crops, causing financial losses to farmers. Our aim was to synthesize scientific knowledge on the bilateral effects of land use change and crane populations. We conducted a systematic literature review of peer-reviewed publications on agriculture-crane interactions (n = 135) and on the importance of agricultural crops in the diet of cranes (n = 81). Agricultural crops constitute a considerable part of the diet of all crane species (average of 37%, most frequently maize (Zea mays L.) and wheat (Triticum aestivum L.)). Crop damage was identified in only 10% of all agriculture-crane interactions, although one-third of interactions included cranes foraging on cropland. Using a conceptual framework analysis, we identified two major pathways in agriculture-crane interactions: (1) habitat loss with negative effects on crane species dependent on specific habitats, and (2) expanding agricultural habitats with superabundant food availability beneficial for opportunistic crane species. The degree to which crane species can adapt to agricultural land use changes may be an important factor explaining their population response. We conclude that multi-objective management needs to combine land sparing and land sharing strategies at landscape scale. To support viable crane populations while guaranteeing sustainable agricultural production, it is necessary to include the perspectives of diverse stakeholders and streamline conservation initiatives and agricultural policy accordingly.


[Site-specific monoPEGylated interferon alpha2a mediated by microbial transglutaminase].
PEGylation is considered one of the most successful techniques to improve the characteristics of protein drugs including to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. One known PEG modification method is to attach PEG to the free amino group, typically at lysine residues or at the N-terminal amino acid with no selectivity, resulting in a heterogeneous product mixture. This lack of selectivity can present problems when a therapeutic PEGylated protein is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic PEGylation of proteins is one route to overcome this limitation. Transglutaminases (TGase) are enzyme candidates for site-specific PEGylation. We use human interferon alpha 2a (IFN α2a) as a test case, and predict that the potential modification residues are Gln101 by computational approach as it contains 12 potential PEGylation sites. IFN α2a was PEGylated by Y shaped PEG40k-NH2 mediated by microbial transglutaminase. Our results show that the microbial transglutaminase mediated PEGylation of IFN α2a was site-specific only at the site of Gln101 in IFN α2a, yielding the single mono-conjugate PEG-Gln101-IFN α2a with a mass of 59 374.66 Da. Circular dichroism studies showed that PEG-Gln101-IFN α2a preserved the same secondary structures as native IFN α2a. As expected, the bioactivity and pharmacokinetic profile in rats of PEG-Gln101-IFN α2a revealed a significant improvement to unmodified IFN α2a, and better than PEGASYS.


Targeting Platelets for the Treatment of Cancer.
The majority of cancer-associated mortality results from the ability of tumour cells to metastasise leading to multifunctional organ failure and death. Disseminated tumour cells in the blood circulation are faced with major challenges such as rheological shear stresses and cell-mediated cytotoxicity mediated by natural killer cells. Nevertheless, circulating tumour cells with metastatic ability appear equipped to exploit host cells to aid their survival. Despite the long interest in targeting tumour-associated host cells such as platelets for cancer treatment, the clinical benefit of this strategy is still under question. In this review, we provide a summary of the latest mechanistic and clinical evidence to evaluate the validity of targeting platelets in cancer.


A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain.
This study describes a method for the identification of the substrates of specific serine kinases. An antibody specific for the phosphomotif generated by the kinase is used to isolate phosphorylated substrates by immunoprecipitation, and the isolated proteins are identified by tandem mass spectrometry of peptides. This method was applied to the identification of substrates for the protein kinase Akt, which specifically phosphorylates the RXRXXS/T motif. 3T3-L1 adipocytes were treated with insulin to activate Akt, and the putative Akt substrate proteins were isolated by immunoprecipitation with an antibody against the phospho form of this motif. This led to the identification of a novel 160-kDa substrate for Akt. The 160-kDa substrate for Akt, which was designated AS160, has a Rab GAP domain. Recombinant AS160 was shown to be a substrate for Akt, and two sites of phosphorylation, both in RXRXXS/T motifs, were identified by mass spectrometry and mutation. Insulin treatment of adipocytes caused AS160 to redistribute from the low density microsomes to the cytosol.


Effect of hyperthermia alone and in combination with anticancer drugs on the viability of P388 leukemic cells.
Effect of local tumor hyperthermia (42 degrees C) at various intervals ranging from 1 to 5 h and in combination with antineoplastic drugs was investigated on P388 murine lymphocytic leukemic cells by using an in vitro-in vivo bioassay method. It was observed that a 1-h exposure resulted in a one log cell kill. In combination studies with hyperthermia and anticancer drugs, 1-h exposure to hyperthermia along with 10 micrograms/ml in vitro concentration of adriamycin (NSC 23127), vincristine (NSC 67574), or 5-fluorouracil (NSC 19893) resulted in the synergistic cell killing action against P388 leukemic cells. However, cyclophosphamide (NSC 26271) and cytosine arabinoside (NSC 63878) did not show any enhanced therapeutic effect.


Quality of life following bone marrow transplantation.
Quality of life (QOL) studies in bone marrow transplantation (BMT) recipients are increasingly regarded as one of the ways to evaluate the outcome of BMT. Recent reports continue to detail acute and late psychosocial problems in BMT recipients. More and more longitudinal studies of QOL and comparisons of QOL outcomes after BMT or alternative nontransplant treatments are appearing in the literature. Several interventions that may promote positive effects on psychosocial adjustment are suggested: attention to patients' coping styles by the healthcare team, encouragement of aerobic exercise, attempts to lessen patients' levels of anxiety, and the presence of at least one staff member identified by the patient as an important source of support over time--all may have positive influences on QOL.


[Questions raised by the clinical and biological polymorphism of atopic dermatitis].
AD is not clearly located amongst the diseases of allergy, but it has some common features with respiratory tract allergy. 1. The disregulation of IgE and also T cell abnormalities. 2. Long-lasting inflammatory flare-up of AD resembles more delayed-type mechanisms of hypersensitivity than the precocious immediate type of respiratory allergy. Furthermore, the accumulation of inflammatory cells (PMN and monocytes-macrophages) in the sites involved in AD have not yet been thoroughly investigated. 3. Another feature of AD is its frequent association with respiratory tract allergy, though the immediate type reactions observed with respiratory symptoms are not necessarily linked by common mechanisms to AD cutaneous lesions. 4. Cutaneous lesions that suggest AD are often seen in disorders where there are genetic abnormalities, though in spite of a common eczematous aspect, the etiology and prognosis are entirely different from AD.


[A case of localized lipomatosis in the pancreatic head presenting a lipoma-like appearance].
A 63-year-old woman with localized lipomatosis in the pancreatic head is reported. She was diagnosed to have a lipoma by clinical data including CT scanning. Histopathological examination of the extirpated mass revealed that the lesion was mostly composed of mature fatty tissue without any lobulation or encapsulation by connective tissue, there was a small amount of scattered pancreatic parenchyma at the peripheral and deeper parts of the mass. No Langerhans' islets were detected. Based on these findings, the lesion was diagnosed as localized lipomatosis in the pancreatic head.


Nonconventional MRI biomarkers for in vivo monitoring of pathogenesis in multiple sclerosis.
To date, biomarkers based on nonconventional MRI have not been standardized for diagnosis and follow-up of patients with multiple sclerosis (MS). The sequential monitoring of pathogenesis in MS by imaging of the normal appearing brain tissue is an important research tool in understanding the early stages of MS. In this review, we focus on the importance of deciphering the physiopathogenesis of the disease cascade in vivo based on imaging biomarkers that allow a correlation with immunohistochemistry and molecular biology findings in order to provide earlier clinical diagnosis and better individualization of treatment and follow-up in patients with MS. Among the nonconventional imaging techniques available, we remark on the importance of proton magnetic resonance spectroscopy imaging because of its ability to assist in the simultaneous evaluation of different events in the pathogenesis of MS that cannot be determined by conventional MRI. Nonconventional MRI and the use of novel contrast agents are expected to elucidate the process of neuroinflammation and excitotoxicity in vivo that characterizes MS, thus leading to more specific neuroprotective and immunomodulatory therapies and reducing progression toward disability.


Polycystic ovary syndrome: anomalies in progesterone production.
The underlying cause of anovulation and miscarriage in polycystic ovary syndrome (PCOS) is unknown. Progesterone may play an important role in oocyte fertilization and embryo implantation. Therefore, in this study we analyse the endocrine function of luteinizing granulosa cells to synthesize progesterone in vivo and in vitro in PCOS and normal patients participating in an in-vitro fertilization programme. Human luteinizing granulosa cells were obtained from 10 patients with normal ovaries (controls) and 10 patients with PCOS by follicular aspiration of individual follicles of each patient and pooled in an attempt to obtain three groups: cells from follicle sizes < or =10,>10< or =15 and > or =16. Serum concentrations of oestradiol and progesterone on the day of human chorionic gonadotrophin (HCG) injection were significantly higher (P < 0.01 and P < 0.05) in PCOS patients than in controls. After HCG stimulation, in-vitro progesterone production was enhanced in granulosa cells of the control group and concentrations increased with follicular size as expected. However, the concentration of progesterone of PCOS patients did not increase with follicular size and there was a significant difference between normal and PCOS groups in follicles >10< or =15 mm (P < 0.05) and > or =16 mm (P < 0.01). Oestradiol production was increased in follicles > or =16 mm in both groups, although this did not reach significance. In summary, it seems that PCOS granulosa cells demonstrate an abnormal capacity to synthesize progesterone in vivo and in vitro. The understanding of granulosa cell function in PCOS may explain the anovulation and miscarriage that occurs in these patients.


Biological insights into the role of TET2 in T cell lymphomas.
Peripheral T cell lymphomas (PTCL) are a heterogenous group of mature T cell lymphomas with an overall poor prognosis. Understanding the molecular heterogeneity in PTCL subtypes may lead to improved understanding of the underlying biological mechanisms driving these diseases. Mutations in the epigenetic regulator TET2 are among the most frequent mutations identified in PTCL, with the highest frequency in angioimmunoblastic T cell lymphomas and other nodal T follicular helper (TFH) lymphomas. This review dissects the role of TET2 in nodal TFH cell lymphomas with a focus on emerging biological insights into the molecular mechanism promoting lymphomagenesis and the potential for epigenetic therapies to improve clinical outcomes.


Establishment of Hy-Line commercial laying hen whole blood gas and biochemistry reference intervals utilizing portable i-STAT1 clinical analyzer.
Blood gas and biochemistry reference intervals were established for 3 genetically distinct commercial varieties (CVs) of Hy-Line laying hens: 2 brown-egg layers (Hy-Line Brown, Hy-Line Silver Brown) and a tint-egg layer (Hy-Line Sonia) utilizing the i-STAT1 analyzer. Each respective variety of laying hen was sampled on a replicate cycle of 2 wk for a total of 6 replicates (35 to 46 wk of age). Blood samples were obtained in the production house from the brachial vein, and subsequently analyzed by the i-STAT1 portable device. i-STAT1 clinical analyzer reports blood gas and biochemistry values for the following parameters: pH, partial pressure of carbon dioxide (pvCO2, mm Hg), partial pressure of oxygen (pvO2, mm Hg), bicarbonate (HCO3, mmol/L), base excess (BE, mmol/L), saturation of oxygen on hemoglobin (sO2%), glucose (Glu, mg/dL), sodium (Na, mmol/L), potassium (K, mmol/L), total concentration of carbon dioxide (TCO2, mmol/L), ionized calcium (iCa, mmol/L), hematocrit (Hct % packed cell volume [PCV]), hemoglobin (Hb, g/dL). A total of 1,800 individual hen i-STAT1 records were utilized in the establishment of reference interval values for the 13 parameters between the 3 CVs. Statistical analysis via ANOVA and Tukey's test revealed significant line differences for all 13 blood gas and chemistry parameters measured, with particularly interesting results in iCa. The blood gas and chemistry parameters collected in this study will serve as reference intervals to set the framework for potential future correlations to genetic markers, physiological abnormalities, and production performance.


Fractal structure of caries.
Between 1991 and 1993, the data of 479 clinical records were compiled about caries in the permanent teeth of subjects of both sexes, whose dental examinations were carried out in a private dental clinic in the city of Salamanca and who were distributed by age into groups of 16-65, 26-55 and 36-45 years. Using the method known as system of expansion-contraction, we showed that caries has a non-linear dynamic, whose evolution in time is difficult to predict and which has a fractal geometry. This study shows the fractal geometry of caries and to achieve this uses a little-known method which will be of great use in future research.


Brachial Artery Aneurysm as a Limb Threatening Condition: a Case Report.
Brachial artery aneurysms are rare but potentially limb threatening condition. The presented case here is a 52-year old male referred to the emergency department complaining a sudden onset and progressive pain with coldness of his right upper extremity during brushing. The right upper extremity was pulseless and three-dimensional computed tomography showed an aneurysm of the proximal right brachial artery associated with arterial occlusion in its distal branch. Embolectomy was done, the aneurysm resected, and the artery successfully re-vascularised by interposing a saphenous vein graft.


Preliminary Study on the Preparation of Conductive Nanosized Calcium Carbonate Utilizing Biogas Slurry by a Synchronous Double Decomposition Coating Method.
Nanosized calcium carbonate (NCC) plays a vital role in the rubber and plastic fields as a filler, but it cannot resolve the electrostatic problem. Humic-acid-based NCC (HA-NCC) was accidentally discovered in the reaction between biogas slurry and calcium chloride (CaCl2), based on nutrient recovery and gradient treatment technology to solve the biogas slurry problem. A preliminary study on the preparation of conductive nanosized calcium carbonate (CNCC) from the HA-NCC was implemented. Meanwhile, a synchronous double decomposition coating method was proposed to properly explain the formation of HA-NCC in the biogas slurry. The CNCC was further obtained through drying and carbonizing the HA-NCC sample. The morphology of CNCC was a square shape with aggregation, and its crystals were calcite. The C content of CNCC was 5% higher than that of the normal CaCO3, implying a synchronous coating effect of soluble HA in biogas slurry on NCC. The weight loss of CNCC was about 2.5% at 630 °C, explaining why the HA-NCC remained black at 550 °C for 4 h. The CNCC was partly ordered and graphitized. The resistivity of the CNCC reached 2.62 × 106 Ω·cm. It could be used as a conductive powder. In view of the favorable characteristics described above, CNCC would be expected to be a filler and antistatic agent for plastics and rubbers to enhance the tensile and bending resistance of polymer materials, while eliminating electrostatic hazards. The results are also of great significance for developing high-end products to realize resource utilization of biogas slurry.


Arterial supply to the rat colon.
Rats are often used as animal models in studies such as on intestinal transplantation and anastomosis healing, which require colectomy. Although detailed information regarding arterial supply is important to establish accurate and reproducible experimental procedures, this has not been studied in the rat colon. Therefore, we analysed the detailed arterial distribution pattern and its individual variations in the colon of 34 rats. The rat colon received colic branches of the ileocolic artery, and the right, middle and left colic arteries. The single left colic artery constantly arose from the caudal mesenteric artery and was distributed to the descending colon, whereas the others showed variations in number and distribution. The ileocolic artery gave rise to one (12%) or two (88%) colic branches supplying the proximal ascending colon, and these branches formed rich, mesh-like anastomoses along the initial portion of the ascending colon. One (74%) or two (26%) right colic arteries originated from the cranial mesenteric artery and supplied the ascending colon and right colic flexure. Moreover, one (38%), two (56%) or three (6%) middle colic arteries emerged from the cranial mesenteric artery and were distributed to the transverse colon, left colic flexure and proximal descending colon. In total, we categorized the individual variations in arterial branching and anastomosis into 11 patterns. Arterial supply to the rat colon showed a specific pattern and frequent individual variations. These findings thus provide essential information for establishing reproducible models of rat colic surgery.


Air Ambulances With Sky-High Charges.
Charges for air ambulance services were 4.1-9.5 times higher than what Medicare paid for the same services in 2016. The median charge ratios (the charge divided by the Medicare rate) for the services increased by 46-61 percent in 2012-16. Air ambulance charges varied substantially across the US, and some of the largest providers had among the highest charges.


Rational Design of Silicon Nanodots/Carbon Anodes by Partial Oxidization Strategy with High-Performance Lithium-Ion Storage.
Silicon (Si) is considered a promising anode material for rechargeable lithium-ion batteries (LIBs) due to its high theoretical capacity, low working potential, and safety features. However, the practical use of Si-based anodes is hampered by their huge volume expansion during the process of lithiation/delithiation, and they have relatively low intrinsic electronic conductivity, therefore seriously restricting their application in energy storage. Here, we propose a facile approach to directly transform siliceous biomass (bamboo leaves) into a porous carbon skeleton-wrapped Si nanodot architecture through a partial oxidization strategy and magnesium thermal reaction to obtain a high Si nanodot component composite (denoted as Si/C-O). With the synergistic effect of the porous carbon skeleton structure and uniformly dispersed Si nanodots, the Si/C-O composite anode with a stable structure that can avoid pulverization and accommodate volume expansion during cycling is fabricated. As expected, the biomass-converted Si/C-O anode not only presents a high Si component (59.7 wt %) by TGA but also exhibits an excellent capacity of 1013 mAh g-1 at 0.5 A g-1 and robust cycling stability with a capacity retention of 526 mAh g-1 after 650 cycles. Moreover, the Si/C-O anode demonstrates considerable performance in practical LIBs when assembled with a commercial LiNi0.8Co0.1Mn0.1O2 cathode. This work provides an effective strategy and long-term insights into the utilization of porous Si-based materials converted by biomass to design and synthesize high-performance LIB materials.


Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism.
Vertebrate rhodopsin (Rh) contains 11-cis-retinal as a chromophore to convert light energy into visual signals. On absorption of light, 11-cis-retinal is isomerized to all-trans-retinal, constituting a one-way reaction that activates transducin (Gt) followed by chromophore release. Here we report that bovine Rh, regenerated instead with a six-carbon-ring retinal chromophore featuring a C11=C12 double bond locked in its cis conformation (Rh6mr), employs an atypical isomerization mechanism by converting 11-cis to an 11,13-dicis configuration for prolonged Gt activation. Time-dependent UV-vis spectroscopy, HPLC, and molecular mechanics analyses revealed an atypical thermal reisomerization of the 11,13-dicis to the 11-cis configuration on a slow timescale, which enables Rh6mr to function in a photocyclic manner similar to that of microbial Rhs. With this photocyclic behavior, Rh6mr repeatedly recruits and activates Gt in response to light stimuli, making it an excellent candidate for optogenetic tools based on retinal analog-bound vertebrate Rhs. Overall, these comprehensive structure-function studies unveil a unique photocyclic mechanism of Rh activation by an 11-cis-to-11,13-dicis isomerization.


[Acute lymphoblastic leukemia of adults - a case of prolonged hip pain diagnostics with a surprising conclusion: case report].
Though acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood age, it is a rare diagnosis in adults. This disease often manifests with common and nonspecific symptoms, so it can easily escape an early diagnostics without a proper blood count examination. We present a case of an adult ALL patient suffering only from severe hips and thighs pain, without any significant blood count abnormities leading to the diagnostics. In the second part of the article, we summarize current highlights regarding this disease.Key words: acute lymphoblastic leukemia - adult - biological treatment - bone pain - CAR T-cells - osteolysis - symptoms.


Introducing the Bird Chromosome Database: An Overview of Cytogenetic Studies in Birds.
Bird chromosomes, which have been investigated scientifically for more than a century, present a number of unique features. In general, bird karyotypes have a high diploid number (2n) of typically around 80 chromosomes that are divided into macro- and microchromosomes. In recent decades, FISH studies using whole chromosome painting probes have shown that the macrochromosomes evolved through both inter- and intrachromosomal rearrangements. However, chromosome painting data are available for only a few bird species, which hinders a more systematic approach to the understanding of the evolutionary history of the enigmatic bird karyotype. Thus, we decided to create an innovative database through compilation of the cytogenetic data available for birds, including chromosome numbers and the results of chromosome painting with chicken (Gallus gallus) probes. The data were obtained through an extensive literature review, which focused on cytogenetic studies published up to 2019. In the first version of the "Bird Chromosome Database (BCD)" (https://sites.unipampa.edu.br/birdchromosomedatabase) we have compiled data on the chromosome numbers of 1,067 bird species and chromosome painting data on 96 species. We found considerable variation in the diploid numbers, which ranged from 40 to 142, although most (around 50%) of the species studied up to now have between 78 and 82 chromosomes. Despite its importance for cytogenetic research, chromosome painting has been applied to less than 1% of all bird species. The BCD will enable researchers to identify the main knowledge gaps in bird cytogenetics, including the most under-sampled groups, and make inferences on chromosomal homologies in phylogenetic studies.


Enhanced conversion efficiency in dye-sensitized solar cells based on hydrothermally synthesized TiO2-MWCNT nanocomposites.
A 50% enhancement in the conversion efficiency (4.9-7.37%) is realized in dye-sensitized solar cells using hydrothermally synthesized TiO(2)-multiwalled carbon nanotube (MWCNT) nanocomposites as compared to hydrothermally synthesized TiO(2) without MWCNT and Degussa P25. Several characterizations have been employed to reveal the nature of the modification imparted to the MWCNTs under hydrothermal processing conditions and the resulting TiO(2)-MWCNT conjugation through -COOH groups. Efficient charge transfer in the nanocomposite and efficient electron transport by MWCNT (significantly higher incident-photon-to-current conversion efficiency) are suggested to be the possible reasons for the enhancement.


Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned. This is a review of published studies, which discusses the pros and cons of NGF as a potential urinary biomarker. The evidence is examined and the studies are summarised together in a Table. Questions remain about the reliability, practicality and specificity of NGF as a biomarker for OAB. These questions need to be addressed by further studies that could clarify the points raised. To review the current literature on the use of urinary nerve growth factor (NGF) as a potential biomarker for overactive bladder syndrome (OAB). A comprehensive electronic literature search was conducted using the PubMed database to identify publications relating to urinary NGF. There are a growing number of publications that have measured urinary NGF levels in different types of bladder dysfunction. These range from OAB, bladder pain syndrome, idiopathic and neurogenic detrusor overactivity, bladder oversensitivity and bladder outflow obstruction. Urinary NGF levels do appear to be raised in these pathological states when compared with healthy control samples. In patients with OAB, these raised urinary NGF levels appear to also reduce after successful treatment with antimuscarinics and botulinum toxin A, which indicates a potential use in monitoring responses to treatment. However, raised levels are not limited to OAB, which questions its specificity. Urinary NGF measurements are performed with an enzyme-linked immunosorbent assay using polyclonal antibodies to NGF. The technique requires standardisation, and the different antibodies to NGF require validating. Also a definition of what is the 'normal' range of NGF in urine is still required before it can be used as a diagnostic and prognostic tool. Whilst the evidence for an increased urinary NGF in OAB appears convincing, many questions about its validity remain including: specificity, sensitivity, cost- and time-effectiveness. Many criteria for what constitutes a biomarker still need to be evaluated and met before this molecule can be considered for this role.


Population-based cohort study of the impacts of mild traumatic brain injury in adults four years post-injury.
There is increasing evidence that some people can experience persistent symptoms for up to a year following mild TBI. However, few longitudinal studies of mild TBI exist and the longer-term impact remains unclear. The purpose of this study is to determine if there are long-term effects of mild traumatic brain injury (TBI) four-years later. Adults (aged ≥16 years) identified as part of a TBI incidence study who experienced a mild-TBI four-years ago (N = 232) were compared to age-sex matched controls (N = 232). Sociodemographic variables, prior TBI and symptoms were assessed at the time of injury. Four years post-injury participants completed the Rivermead Post-Concussion Symptom Questionnaire, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index and the Participation Assessment with Recombined Tools. Analysis of covariance was used to compare differences between TBI cases four years post-injury and controls, controlling for prior TBI and depression. A multiple regression model was used to identify the predictors of increased symptoms and reduced participation. The mild-TBI sample experienced significantly increased self-reported cognitive symptoms (F = 19.90, p = <0.01) four years post-injury than controls. There were no differences between the groups for somatic (F = 0.02, p = 0.89) or emotional symptoms (F = 0.31, p = 0.58). Additionally, the mild-TBI group reported significantly poorer community participation across all three domains: productivity (F = 199.07, p = <0.00), social relations (F = 13.93, p = <0.00) and getting out and about (F = 364.69, p = <0.00) compared to controls. A regression model accounting for 41% of the variance in cognitive symptoms in TBI cases revealed a history of TBI, receiving acute medical attention and baseline cognitive symptoms, sleep quality, anxiety and depression were predictive of outcome. The results indicate that whilst somatic and emotional symptoms resolve over time, cognitive symptoms can become persistent and that mild TBI can impact longer-term community participation. Early intervention is needed to reduce the longer-term impact of cognitive symptoms and facilitate participation.


Collagenous colitis, ulcerative colitis, coeliac disease and hyperparathyroidism in one patient: implications for the management of collagenous colitis.
A case of collagenous colitis, ulcerative colitis and coeliac disease all occurring in one individual is reported. In addition to causing confusion over symptoms, this observation coupled with a review of the literature raises the question of whether patients with collagenous colitis should be routinely screened for coeliac disease. Furthermore, the threshold for re-investigating for the possibility of the development of ulcerative colitis may have to be lowered, particularly if symptoms change.


Maternal Postpartum Diet and Postpartum Depression: A Systematic Review.
Compelling evidence from observational studies shows that dietary patterns play a role in the development of depression and depressive symptoms in the general population. However, few studies have specifically sought to explore the association between maternal diet in the postpartum period and PPD. The purpose of this literature review was to synthesise data from existing published studies, examining the association between maternal postpartum diet and PPD symptoms. Relevant studies were identified by systematic search from the Cochrane, MEDLINE, EMBASE, CINAHL, PubMed and PsycInfo databases for articles published between 1835 and April 2020. Of the 931 articles identified, six met eligibility criteria and were included. Four were cross-sectional and two were a cohort design. All but one study showed at least one inverse association, such that greater adherence to a healthy diet in the postpartum period was associated with fewer PPD symptoms. Specifically, if confirmed in further longitudinal and intervention studies, a balanced maternal diet with an emphasis on fruits, vegetables, fish, grains, legumes, and herbs could be a potential option for helping reduce the incidence of PPD. This review provides evidence that the postnatal diet could have an effect on PPD symptoms, although further longitudinal and intervention research is warranted.