Seasonal Hydration Status of Common Bryophyte Species in Azorean Native Vegetation.
Bryophytes play a crucial role in the ecosystem's water compartment due to their unique ability to retain water. However, their role within temperate native ecosystems is mostly unknown. To address this knowledge gap, a study was conducted on Terceira Island (Azores), focusing on 14 bryophyte species found at different altitudes (40 m, 683 m, and 1012 m); five samples were collected monthly, per species and location, and their fresh, saturated, and dry weights were examined in the laboratory; four species were collected from more than one site. Generalized linear models (GLM) were used to assert the influence of climate factors (temperature, precipitation, and relative humidity) and environmental variables on two water indicators: field water content (FWC) and relative water content (RWC). None of the examined factors, per se, were able to explain all cases. Species appear to respond to climate according to a limiting factor effect: at lower elevations, precipitation was determinant, while at medium elevations, FWC was influenced by a combination of precipitation and relative humidity. At higher elevations, temperature was retained for seven of the nine studied species. The RWC values indicated that the 14 bryophyte species remained hydrated throughout the year but rarely reached their maximum water-holding capacity, even at the highest altitude. Understanding the mechanisms by which native bryophytes acquire, store, and release water is crucial for comprehending the resilience of native vegetation in the face of climate change. This knowledge can also enable the development of strategies to mitigate the effects of climate change and protect vital water resources.


Multimodal chemo-magnetic control of self-propelling microbots.
We report a controlled migration of an iron nanoparticle (FeNP) coated polymer micromotor. The otherwise diffusive motion of the motor was meticulously directed through an in situ pH-gradient and an external magnetic field. The self-propulsion owing to the asymmetric catalytic decomposition of peroxide fuel was directed through a pH gradient imposed across the motor-surface, while the magnetic field induced an external control on the movement and the speed of the motor. Interestingly, the sole influence of the pH gradient could move the motor as high as ∼25 body lengths per second, which was further magnified by the external assistance from the magnetic field. Applying a magnetic field against the pH directed motion helped in the quantitative experimental estimation of the force-field required to arrest the chemotactic migration. The influence of the coupled internal and external fields could halt, steer or reverse the direction the motor inside a microchannel, rotate the motor around a target, and deliver the motor to a cluster of cells. This study showcases a multimodal chemical-magnetic field regulated migration of micro-machines for sensing, transport, and delivery inside a fluidic environment.


Inhibition of adenylate cyclase attenuates adenosine receptor-mediated relaxation in coronary artery.
This study was designed to evaluate whether the adenylate cyclase inhibitor 2',5'-dideoxyadenosine (DDA) would attenuate the relaxation produced by adenosine analogs in order to provide functional evidence in support of the working hypothesis that adenosine receptor-mediated relaxation of coronary artery involves adenylate cyclase. Rings from porcine left anterior descending coronary artery were mounted in organ chambers for measurement of isometric force. Rings contracted with KCl (30 mM) relaxed in a concentration-dependent manner to 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), isoproterenol, sodium nitroprusside (SNP) and forskolin. Treatment of coronary rings with DDA (50 microM) significantly attenuated the relaxation produced by CAD, NECA, forskolin and isoproterenol, but had no effect on the relaxation response to SNP. The nucleoside transport inhibitor dilazep (10 microM) completely reversed the inhibitory effect of DDA on the relaxation produced by forskolin and CAD, whereas dilazep only partially reversed the DDA inhibition of NECA-induced relaxation. In a membrane preparation from porcine coronary artery CAD, but not NECA, increased cyclic AMP production in a GTP-dependent manner. DDA significantly decreased basal cyclic AMP production and also decreased CAD-, forskolin-, GTP- and NaF-stimulated cyclic AMP production. These results provide functional and biochemical evidence in support of the working hypothesis that adenosine receptor-mediated coronary relaxation involves adenylate cyclase. Furthermore, the results from this study suggest that the signaling mechanisms responsible for adenosine receptor-mediated coronary relaxation are more complicated than a single receptor coupled with adenylate cyclase because 1) dilazep completely reversed the inhibitory effect of DDA on the CAD relaxation but not the NECA relaxation, and 2) NECA did not increase cyclic AMP production.


Vitamin B12 may be more effective than nortriptyline in improving painful diabetic neuropathy.
Despite many therapeutic options, painful diabetic neuropathy is still a common and challenging complication of diabetes mellitus and is often resistant to treatment with current modalities. In this randomized, single-blind clinical trial we compared the efficacy of parenteral vitamin B(12) and nortriptyline, for symptomatic improvement of pain, paresthesia, burning, freezing, stabbing and electrical sensation. Changes in nerve conduction parameters of amplitude, duration and latency were also compared. One hundred patients (50 in each group) completed the study. After treatment, the pain score based on a visual analogue scale decreased 3.66 units in the vitamin B(12) group and 0.84 units in the nortriptyline group (P <0.001). Similarly, the paresthesia score decreased 2.98 units versus 1.06 units (P <0.001). The decrements of tingling sensation were 3.48 units versus 1.02 units (P <0.001). Changes in vibration, position, pinprick and nerve conduction parameters were not significant in two groups. In conclusion, vitamin B(12) is more effective than nortriptyline for the treatment of symptomatic painful diabetic neuropathy.


Antibody responses to Campylobacter infections determined by an enzyme-linked immunosorbent assay: 2-year follow-up study of 210 patients.
An enzyme-linked immunosorbent assay (ELISA) was adapted to measure immunoglobulin G (IgG), IgM, and IgA classes of human serum antibody to Campylobacter jejuni and Campylobacter coli. Heat-stable antigen, a combination of C. jejuni serotype O:1,44 and O:53 in the ratio 1:1, was used as a coating antigen in the ELISA test. A total of 631 sera from 210 patients with verified Campylobacter enteritis were examined at various intervals after infection, and a control group of 164 sera were tested to determine the cut-off for negative results. With a 90th percentile of specificity, IgG, IgM, and IgA showed a sensitivity of 71, 60, and 80%, respectively. By combining all three antibody classes, the sensitivity was 92% within 35 days after infection, whereas within 90 days after infection, a combined sensitivity of 90% was found (IgG 68%, IgM 52%, and IgA 76%). At follow-up of the patients, IgG antibodies were elevated 4.5 months after infection but exhibited a large degree of variation in antibody decay profiles. IgA and IgM antibodies were elevated during the acute phase of infection (up to 2 months from onset of infection). The antibody response did not depend on Campylobacter species or C. jejuni serotype, with the important exception of response to C. jejuni O:19, the serotype most frequently associated with Guillain-Barré syndrome. All of the patients infected with this serotype had higher levels of both IgM (P = 0.006) and IgA (P = 0.06) compared with other C. jejuni and C. coli serotypes.


Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window.
The testicular dysgenesis syndrome (TDS) hypothesis, which proposes that common reproductive disorders of newborn and adult human males may have a common fetal origin, is largely untested. We tested this hypothesis using a rat model involving gestational exposure to dibutyl phthalate (DBP), which suppresses testosterone production by the fetal testis. We evaluated if induction of TDS via testosterone suppression is restricted to the "masculinization programming window" (MPW), as indicated by reduction in anogenital distance (AGD). We show that DBP suppresses fetal testosterone equally during and after the MPW, but only DBP exposure in the MPW causes reduced AGD, focal testicular dysgenesis, and TDS disorders (cryptorchidism, hypospadias, reduced adult testis size, and compensated adult Leydig cell failure). Focal testicular dysgenesis, reduced size of adult male reproductive organs, and TDS disorders and their severity were all strongly associated with reduced AGD. We related our findings to human TDS cases by demonstrating similar focal dysgenetic changes in testes of men with preinvasive germ cell neoplasia (GCNIS) and in testes of DBP-MPW animals. If our results are translatable to humans, they suggest that identification of potential causes of human TDS disorders should focus on exposures during a human MPW equivalent, especially if negatively associated with offspring AGD.


Hand hygiene among general practice dentists: a survey of knowledge, attitudes and practices.
Hand hygiene (HH) is a primary practice used to reduce the risk and spread of infection. The authors conducted a study to examine the self-reported knowledge, attitudes and practices of general practice dentists (GPDs) regarding HH and factors associated with HH and skin condition. The authors mailed a four-page closed-ended questionnaire to a random sample of active GPDs drawn from a list supplied by the New York State Dental Association. The authors classified eight GPDs as ineligible, leaving a net sample of 352. They received 234 responses, for a response rate of 66 percent. At the start of the practice day, 71 percent of GPDs often/almost always/always washed with soap but never/almost never disinfected with an alcohol-based hand sanitizer. Twenty-two percent often/almost always/always washed with soap and disinfected with alcohol-based hand sanitizers. GPDs with good/excellent knowledge of the Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene in Health-Care Settings were more likely to report acceptable HH behavior. Approximately one-third of GPDs had limited/ moderate knowledge of the CDC HH guideline. Most GPDs use soap and water for HH frequently, and a smaller number of GPDs use alcohol-based hand sanitizers for HH frequently. Results show that 25 percent of GPDs or fewer maintain inadequate HH. Knowledge of the CDC HH guideline needs to be heightened. Practice Implications. Further education of the dental community is warranted to improve HH compliance, efficacy of HH practices and skin health.


Short-Term Effects of Thin-Layer Sand Placement on Salt Marsh Grasses: A Marsh Organ Field Experiment.
Salt marshes can build in elevation with sea-level rise through accumulation of inorganic sediment and organic matter, but marshes worldwide are under threat of drowning due to rapid rates of sea-level rise that outpace natural marsh building rates. The application of a thin layer of sediment to the marsh surface (thin-layer placement [TLP]) is a tool to build elevation and decrease flooding stress, but its effects on marsh plants are understudied, especially in New England. In a novel application of a marsh organ experiment (i.e. rows of pots at different elevations), the addition of 10 cm of sand to pots planted with Spartina alterniflora and Spartina patens resulted in fewer stems than controls for S. patens but not S. alterniflora after 2 months. However, total biomass and root mass were not significantly impacted for either species, suggesting plants will fully recover from TLP over longer timescales. Effects of TLP on biomass and stem density did not vary significantly by elevation. Although long-term research is still needed, short-term equivalency in biomass between TLP treatments and controls suggests TLP of 10 cm is a promising strategy to enhance the ability of marshes to build vertically as sea level rises in New England.


The quality of post and cores made using a reduce-time casting technique.
This study investigated the castability or casting completeness, surface roughness and dimensional accuracy of castings produced using a technique that requires as little as 24 minutes from the time of investment. A total of 225 gold castings (45 per group) were fabricated using two standard and three accelerated casting protocols. For each casting protocol, 15 castings were made from a rectangular, diamond-shaped mesh Duralay pattern to be used for castability evaluation; 15 castings were made from a flat, square pattern for measurement of surface roughness, and 15 castings were made from a tapered Duralay dowel to evaluate dimensional accuracy. Castings made with Fast Fire 15 and Ceramigold investment with shortened burnout times were compared to those made using Beauty Cast and Fast Fire 15 investment following the manufacturer's recommendations. Castability was evaluated by counting the number of diamonds cast in a rectangular mesh. A profilometer was used to measure surface roughness. To check dimensional accuracy, the casting was replaced in the original mold and a traveling microscope was used to measure the size difference at 32x magnification. There were no statistically significant differences in castability and dimensional accuracy throughout all groups (p > .05). There was a statistically significant difference in the surface roughness of casts formed by Ceramigold compared to the other groups (p < .001). The short casting time using Fast Fire 15 can produce post and core castings that are of a quality acceptable for clinical use.


Association of alpha-adducin Gly460Trp polymorphism with coronary artery disease in a Korean population.
Coronary artery disease is caused by multiple genetic and environmental factors. The disease is also closely associated with cardiovascular conditions such as hypertension. In order to investigate any possible role of hypertension candidate genes in the disease development and progression, we examined the association of the polymorphisms of 31 hypertension candidate genes with coronary artery disease. Genetic polymorphisms of 31 hypertension candidate genes were initially screened by resequencing DNA samples from 24 unrelated individuals in a Korean population. Association analysis was performed using 1284 unrelated Korean men, including 749 coronary artery disease subjects and 535 normal healthy controls. We identified a total of 409 single nucleotide polymorphisms including 40 nonsynonymous single nucleotide polymorphisms, 32 insertions/deletions and four microsatellites. Among 40 nonsynonymous single nucleotide polymorphisms, 29 were examined for an association with coronary artery disease. A significant association with coronary artery disease was observed in a polymorphism of the ADD1 gene (Gly460Trp; +29017G/T) (odds ratio 0.71-0.81; P = 0.01-0.04). The same polymorphism was also associated with the number of arteries with significant coronary artery stenosis in the coronary artery disease patients (P = 0.01) as well as the increase in systolic blood pressure (P = 0.02). The ADD1 Gly460Trp polymorphism is significantly associated with an increased risk of coronary artery disease as well as blood pressure, indicating that ADD1 plays a role in the pathogenesis of coronary artery disease as well as hypertension.


Is bone mineral composition disrupted by organochlorines in east Greenland polar bears (Ursus maritimus)?
We analyzed bone mineral density (BMD) in skulls of polar bears (Ursus maritimus) (n = 139) from East Greenland sampled during 1892-2002. Our primary goal was to detect possible changes in bone mineral content (osteopenia) due to elevated exposure to organochlorine [polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane (DDT) and its metabolites, chlordanes (CHLs), dieldrin, hexacyclohexanes, hexachlorobenzene] and polybrominated diphenyl ether (PBDE) compounds. To ensure that the BMD value in skull represented the mineral status of the skeletal system in general, we compared BMD values in femur and three lumbar vertebrae with skull in a subsample. We detected highly significant correlations between BMD in skull and femur (r = 0.99; p < 0.001; n = 13) and skull and vertebrae (r = 0.97; p < 0.001; n = 8). BMD in skulls sampled in the supposed pre-organochlorine/PBDE period (1892-1932) was significantly higher than that in skulls sampled in the supposed pollution period (1966-2002) for subadult females, subadult males, and adult males (all, p < 0.05) but not adult females (p = 0.94). We found a negative correlation between organochlorines and skull BMD for the sum of PCBs (SigmaPCB; p < 0.04) and SigmaCHL (p < 0.03) in subadults and for dieldrin (p < 0.002) and SigmaDDT (p < 0.02) in adult males; indications for SigmaPBDE in subadults were also found (p = 0.06). In conclusion, the strong correlative relationships suggest that disruption of the bone mineral composition in East Greenland polar bears may have been caused by organochlorine exposure.


Diagnosis of vertebral fractures. A comparison of conventional radiography, conventional tomography, and computed axial tomography.
Thirty patients with acute thoracic, lumbar, or thoracolumbar fractures, dislocations, or fracture-dislocations were evaluated with standard radiographs, conventional polytomography, and computerized axial tomography. The resulting ninety studies were coded, randomized, and independently interpreted by three radiologists. The diagnostic accuracy of the interpretations based on the computerized tomography scans combined with standard radiographs equaled that of the interpretations based on just the tomograms in the evaluation of fractures of posterior elements. In addition, computerized tomography was superior to the other methods in demonstrating impingement on the neural canal as well as injuries to other organ systems. Also, when compared with conventional polytomography, computerized tomography could be completed with less risk to the patient (no changes in position and ten times less radiation). We concluded that computerized tomography should replace conventional polytomography as the initial study to augment standard radiographs in the assessment of thoracic and lumbar fractures. Conventional polytomography should be reserved for patients in whom precise evaluation of the pars interarticularis is deemed necessary.


Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin.
In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin.


The bromotyrosine derivative ianthelline isolated from the arctic marine sponge Stryphnus fortis inhibits marine micro- and macrobiofouling.
The inhibition of marine biofouling by the bromotyrosine derivative ianthelline, isolated from the Arctic marine sponge Stryphnus fortis, is described. All major stages of the fouling process are investigated. The effect of ianthelline on adhesion and growth of marine bacteria and microalgae is tested to investigate its influence on the initial microfouling process comparing with the known marine antifoulant barettin as a reference. Macrofouling is studied via barnacle (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis) phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro- and macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory concentration (MIC) values 0.1-10 μg/mL) and barnacle larval settlement (IC50 = 3.0 μg/mL). Moderate effects are recorded on M. edulis (IC50 = 45.2 μg/mL) and microalgae, where growth is more affected than surface adhesion. The effect of ianthelline is also investigated against human pathogenic bacteria. Ianthelline displayed low micromolar MIC values against several bacterial strains, both Gram positive and Gram negative, down to 2.5 μg/mL. In summary, the effect of ianthelline on 20 different representative marine antifouling organisms and seven human pathogenic bacterial strains is presented.


An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.
The amphetamine isomer β-methylphenylethylamine (BMPEA) was first synthesized in the early 1930s, but its efficacy and safety in humans has not been studied. Recently, the United States Food and Drug Administration (FDA) detected BMPEA in dietary supplements labelled as containing Acacia rigidula. Over a year after the FDA reported its findings, we analyzed Acacia rigidula dietary supplements to determine if BMPEA had been removed. Supplements were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry. Diluted methanolic extract from each supplement was run three times and each data set obtained was analyzed using Agilent MassHunter Qualitative Analysis. The presence of BMPEA was confirmed by accurate mass, retention time and mass spectra match against a reference standard. Quantification of BMPEA was determined using an eight-point calibration curve of spiked standard to a matrix blank. Twenty-one brands of Acacia rigidula supplements were analyzed. More than half (11/21; 52.4%) of the Acacia rigidula supplement brands contained BMPEA. The stimulant was present at quantities such that consumers following recommended maximum daily servings would consume a maximum of 93.7 mg of BMPEA per day. Consumers of Acacia rigidula supplements may be exposed to pharmacological dosages of an amphetamine isomer that lacks evidence of safety in humans. The FDA should immediately warn consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA in dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd.


Information technology to support patient engagement: where do we stand and where can we go?
Given the strong push to empower patients and make them partners in their health care, we evaluated the current capability of hospitals to offer health information technology that facilitates patient engagement (PE). Using an ontology mapping approach, items from the American Hospital Association Information Technology Supplement were mapped to defined levels and categories within the PE Framework. Points were assigned for each health information technology function based upon the level of engagement it encompassed to create a PE-information technology (PE-IT) score. Scores were divided into tertiles, and hospital characteristics were compared across tertiles. An ordered logit model was used to estimate the effect of characteristics on the adjusted odds of being in the highest tertile of PE-IT scores. Thirty-six functions were mapped to specific levels and categories of the PE Framework, and adoption of each item ranged from 23.5 to 96.7%. Hospital characteristics associated with being in the highest tertile of PE-IT scores included medium and large bed size (relative to small), nonprofit (relative to government nonfederal), teaching hospital, system member, Midwest and South regions, and urban location. Hospital adoption of PE-oriented technology remains varied, suggesting that hospitals are considering how technology can create partnerships with patients. However, PE functionalities that facilitate higher levels of engagement are lacking, suggesting room for improvement. While hospitals have reached modest levels of adoption of PE technologies, consistent monitoring of this capacity can identify opportunities to use technology to facilitate engagement.


[Early and late (during 3 years) results of coronary bypass operation in patients with ischemic heart disease with moderate dyslipoproteinemia].
The study of efficacy of rehabilitation and clinical-instrumental characteristics of coronary failure in patients with ischemic heart disease (IHD) of high functional classes and moderate dyslipoproteinemia early (1.6 months) and late (1 and 3 years) after coronary by-pass operation. The examination covered 119 males with IHD (mean age 51.8 +/- 6.9 years) 1.6 months and 3 years after coronary by-pass operation. Lipid spectrum of blood plasma, frequency of anginal attacks, 24-h nitroglycerin requirement, results of bicycle exercise and loading myocardial scintigraphy were assessed. The patients were divided into two groups. In 82 patients of group 1 total cholesterol ranged within 3 years after the surgery from 5.2 to 6.5 mmol/l, 37 patients of group 2 had no lipid disorders. Within 12 months after direct myocardial revascularization, the groups had similar clinical-instrumental characteristics. 3 years after the operation, patients of group 1 exhibited a rise in anginal attacks frequency, nitroglycerin requirement, size of unstable perfusion defects by 84.6, 88.8 and 26.4%, respectively. Exercise tolerance diminished by 18.7%. Moderate defects in lipid metabolism influence progression of coronary failure. This becomes especially pronounced within 3 years after coronary by-pass operation.


Effect of general anesthetics on IOP in rats with experimental aqueous outflow obstruction.
To determine the effect of several common general anesthetics on intraocular pressure (IOP) after experimental aqueous outflow obstruction in the rat. A single episcleral vein injection of hypertonic saline was used to sclerose aqueous humor outflow pathways and produce elevated IOP in Brown Norway rats. Animals were housed in either standard lighting or a constant low-level light environment. Awake IOPs were determined using a TonoPen (Mentor, Norwell, MA) immediately before induction of anesthesia by either isoflurane, ketamine, or a mixture of injectable anesthetics (xylazine, ketamine, and acepromazine). For each anesthetic, IOPs were measured immediately after adequate sedation (time 0) and at 5-minute intervals, up to 20 minutes. RESULTS; Awake IOPs ranged from 18 to 52 mm Hg. All anesthetics resulted in a statistically significant (P: < 0.01) reduction in measured IOP at every duration of anesthesia when compared with the corresponding awake IOP. With increasing duration of anesthesia, measured IOP decreased approximately linearly for both the anesthetic mixture and isoflurane. However, with ketamine, IOP declined to 48% +/- 11% (standard lighting) and 60% +/- 7% (constant light) of awake levels at 5 minutes of anesthesia, where it remained stable. In fellow eyes, the SD of the mean IOP in animals under anesthesia was always greater than the corresponding SD of the awake mean. Anesthesia's effects in normal eyes and eyes with elevated IOP were indistinguishable. All anesthetics resulted in rapid and substantial decreases in IOP in all eyes and increased the interanimal variability in IOPs. Measurement of IOP in awake animals provides the most accurate documentation of pressure histories for rat glaucoma model studies.


Catabolite repression of beta-galactosidase synthesis in Escherichia coli.
1. Repression by glucose of beta-galactosidase synthesis is spontaneously reversible in all strains of Escherichia coli examined long before the glucose has all been consumed. The extent of recovery and the time necessary for reversal differ among various strains. Other inducible enzymes show similar effects. 2. This transient effect of glucose repression is observed in constitutive (i(-)) and permease-less (y(-)) cells as well as in the corresponding i(+) and y(+) strains. 3. Repression is exerted by several rapidly metabolizable substrates (galactose, ribose and ribonucleosides) but not by non-metabolized or poorly metabolized compounds (2-deoxyglucose, 2-deoxyribose, phenyl thio-beta-galactoside and 2-deoxyribonucleosides). 4. The transient repression with glucose is observed in inducible cells supplied with a powerful inducer of beta-galactosidase synthesis (e.g. isopropyl thio-beta-galactoside) but not with a weak inducer (lactose); in the latter instance glucose repression is permanent. Diauxic growth on glucose plus lactose can be abolished by including isopropyl thio-beta-galactoside in the medium. 5. In some strains phosphate starvation increases catabolite repression; in others it relieves it. Adenine starvation in an adenine-requiring mutant also relieves catabolite repression by glycerol but not that by glucose. Restoration of phosphate or adenine to cells starved of these nutrients causes a pronounced temporary repression. Alkaline-phosphatase synthesis is not affected by the availability of adenine. 6. During periods of transient repression of induced enzyme synthesis the differential rate of RNA synthesis, measured by labelled uracil incorporation in 2min. pulses, shows a temporary rise. 7. The differential rate of uracil incorporation into RNA falls during exponential growth of batch cultures of E. coli. This is equally true for uracil-requiring and non-requiring strains. The fall in the rate of incorporation has been shown to be due to a real fall in the rate of RNA synthesis. The significance of the changes in the rate of RNA synthesis is discussed. 8. A partial model of catabolite repression is presented with suggestions for determining the chemical identification of the catabolite co-repressor itself.


There's alcohol in my soap: portrayal and effects of alcohol use in a popular television series.
Two studies are reported addressing the media influences on adolescents' alcohol-related attitudes and behaviours. A content analysis was conducted to investigate the prevalence of alcohol portrayal in a Dutch soap series. The coding scheme covered the alcohol consumption per soap character, drinking situations and drinking times. Inter-coder reliability was satisfactory. The results showed that alcohol portrayal was prominent and that many instances of alcohol use reflected undesirable behaviours. To assess the influence of such alcohol cues on adolescents, a 2x2 experiment was conducted focusing on the separate and combined effects of alcohol portrayal in the soap series and surrounding alcohol commercials. Whereas the alcohol commercials had the expected effects on adolescents' attitudes, the alcohol-related soap content only appeared to have unexpected effects. Adolescents who were exposed to the alcohol portrayal in the soap series had a less positive attitude towards alcohol and lower drinking intentions. Implications of these findings for health policy and future research are discussed.


Pathogenic or not? Assessing the clinical relevance of copy number variants.
The availability of commercially produced genomic microarrays has resulted in the wide spread implementation of genomic microarrays, often as a first-tier diagnostic test for copy number variant (CNV) screening of patients who are suspected for chromosomal aberrations. Patients with intellectual disability (ID) and/or multiple congenital anomalies (MCA) were traditionally the main focus for this microarray-based CNV screening, but the application of microarrays to other (neurodevelopmental) disorders and tumor diagnostics has also been explored and implemented. The diagnostic workflow for patients with ID is now well established, relying on the identification of rare CNVs and determining their inheritance patterns. However, experience gained through screening large numbers of samples has revealed many subtleties and complexities of CNV interpretation. This has resulted in a better understanding of the contribution of CNVs to genomic disorders not only via de novo occurrence, but also via X-linked and recessive inheritance models as well as through models taking into account mosaicisms, imprinting, and digenic inheritance. In this review, we discuss CNV interpretation within the context of these different genetic disease models and common pitfalls that can occur when searching for supportive evidence that a CNV is clinically relevant.


AEROSOLS AS A SOURCE OF WIDESPREAD MYCOPLASMA CONTAMINATION OF TISSUE CULTURES.
Mycoplasma isolates were cultured from 15 antibiotic-free cell cultures obtained from a single laboratory. Complement-fixation tests showed that these isolates were antigenically related to each other but were unrelated to M. hominis type 1, M. hominis type 2, M. arthritidis, M. laidlawii type B, Mycoplasma sp. H.Ep. #2 (Barile), or M. salivarium. Examination of serum used to feed the infected cell lines revealed no Mycoplasma. Infection resulting from cross-contamination by a single Mycoplasma strain from one cell culture to another was investigated. Although the organisms were not found in the air over the work area, aerosols containing these contaminants were produced in tissue culture bottles during the trypsinization of cell monolayers. The minimal infectious dose of Mycoplasma for tissue cultures was measured, and it was determined that one organism was capable of initiating an infection in a tissue culture. The pattern of contamination and the small dose required for infection indicated that Mycoplasma contamination was spread from one tissue culture to another via aerosols. It was demonstrated that Mycoplasma can be transferred from one cell culture to another through the use of a common burette for dispensing medium.


Correlation of anterior chamber-associated immune deviation with suppression of corneal epithelial rejection in mice.
The authors investigated the effect of anterior chamber corneal (AC) inoculation of genetically graft-identical antigen on T-cell immunity and the suppression of alloepithelial rejection in mice. Antigen-specific suppression of delayed-type hypersensitivity (DTH) and suppression transferability were tested in BALB/c mice injected with irradiated allogeneic B10.D2 splenocytes into AC. Other groups of BALB/c mice received irradiated B10.D2, BALB/c, or C3H/He splenocytes in the AC of the right eye. Seven days later, B10.D2 or C3H/He corneal lenticules were grafted at the limbus of the left eye (keratoepithelioplasty). Alloepithelial rejection of each grafted eye was evaluated according to clinical findings. The DTH response of the keratoepithelioplasty recipients against B10.D2 minor antigen was tested at the end of clinical observation (4 months after grafting). Also examined was spleen component transfer from BALB/c mice with AC inoculation of B10.D2 splenocytes to syngeneic acceptors and its effect on suppression of epithelial rejection against B10.D2 antigen. Inoculation of B10.D2 splenocytes into BALB/c AC induced antigen-specific DTH suppression, which suppression was transferable. During the 4-month observation period, AC inoculation of B10.D2 minor antigen significantly enhanced the survival of B10.D2-derived epithelium, but not of C3H/He-derived epithelium, in BALB/c mice. However, AC inoculation of BALB/c or C3H/ He splenocytes did not enhance B10.D2 epithelial survival in BALB/c mice. Incapability of antigen-specific DTH response generation was observed in the BALB/c mice with B10.D2 splenocytes in the right AC and B10.D2-derived epithelium in the left eye. Single transfer of spleen components from BALB/c mice with AC inoculation of B10.D2 splenocytes to syngeneic acceptors only delayed B10.D2 minor antigen-stimulated epithelial rejection, whereas supplementary transfers of the identical spleen components at different time intervals showed more significant effect in rejection delay. The results showed that AC inoculation of B10.D2 splenocytes in BALB/c mice induced antigen-specific suppression of DTH response, in a phenomenon termed anterior chamber-associated immune deviation (ACAID). It also was shown definitely that ACAID can suppress alloepithelial rejection in a murine keratoepithelioplasty model. Adoptive transfer of splenocytes from ACAID-induced mice merely affords short-term suppression of epithelial rejection, suggesting that an additional mechanism may be involved in ACAID maintenance.


Cell volume regulation in chondrocytes.
Chondrocytes are the cells within cartilage which produce and maintain the extracellular matrix. Volume regulation in these cells is vital to their function and occurs in several different physiological and pathological contexts. Firstly, chondrocytes exist within an environment of changing osmolarity and compressive loads. Secondly, in osteoarthritic joint failure, cartilage water content changes and there is a notable increase in chondrocyte apoptosis. Thirdly, endochondral ossification requires chondrocyte swelling in association with hypertrophy. Regulatory volume decrease (RVD) and regulatory volume increase (RVI) have both been observed in articular chondrocytes and this review focuses on the mechanisms identified to account for these. There has been evidence so far to suggest TRPV4 is central to RVD; however other elements of the pathway have not yet been identified. Unlike RVD, RVI appears less robust in articular chondrocytes and there have been fewer mechanistic studies; the primary focus being on the Na(+)-K(+)-2Cl(-) co-transporter. The clinical significance of chondrocyte volume regulation remains unproven. Importantly however, transcript abundances of several ion channels implicated in volume control are changed in chondrocytes from osteoarthritic cartilage. A critical question is whether disturbances of volume regulation mechanisms lead to, result from or are simply coincidental to cartilage damage.


PAPPA2 is increased in severe early onset pre-eclampsia and upregulated with hypoxia.
Severe early onset pre-eclampsia is a serious pregnancy complication, believed to arise as a result of persistent placental hypoxia due to impaired placentation. Pregnancy-associated plasma protein A2 (PAPPA2) is very highly expressed in the placenta relative to all other tissues. There is some evidence that PAPPA2 mRNA and protein are increased in association with pre-eclampsia. The aim of the present study was to characterise the mRNA and protein expression, as well as localisation, of PAPPA2 in an independent cohort of severe early onset pre-eclamptic placentas. We also examined whether exposing placental explants to hypoxia (1% oxygen) changed the expression of PAPPA2. Expression of PAPPA2 mRNA and protein was upregulated in severe early onset pre-eclamptic placentas compared with preterm controls and localised to the syncytiotrophoblast. Interestingly, protein localisation was markedly reduced in term placenta. Syncytialisation of BeWo cells did not change PAPPA2 expression. However, hypoxia upregulated PAPPA2 mRNA and protein expression in primary placental explants. Together, our data suggest that PAPPA2 may be upregulated in severe pre-eclampsia and, functionally, this may be mediated via increased placental hypoxia known to occur with this pregnancy disorder.


The Chinese social benefit system in transition: reforms and impacts on income inequality.
Economic reforms since the late 1970s have made China one of the world's fastest growing economies but have also led to greater unmet social welfare needs and growing income inequality. This article describes social policy trends in urban and rural China and reviews recent empirical evidence on the transitions and impacts of its social benefit system. The evidence reveals that although urban social benefits experienced significant cutbacks, they are still much more generous than the minimal social benefits for rural residents and migrants. This extremely inequitable situation calls for a larger, progressive social benefit system in China.


Conformational Dynamics of Specific Aβ Oligomers Govern Their Ability To Replicate and Induce Neuronal Apoptosis.
Oligomers of amyloid-β (Aβ) have emerged as the primary toxic agents responsible for early synaptic dysfunction and neuronal death in Alzheimer's disease (AD). Characterization of oligomers is an important step in the progress toward delineating the complex molecular mechanisms involved in AD pathogenesis. In our previous reports, we established that a distinct 12-24mer neurotoxic oligomer of Aβ42, called Large Fatty Acid derived Oligomers (LFAOs), exhibits a unique property of replication in which LFAOs directly duplicate to quantitatively larger amounts upon interacting with monomers. This self-propagative process of replication is somewhat reminiscent of prion propagation. In this report, we sought to investigate the concentration-dependent conformational dynamics LFAOs undergo and how such transitions manifest in their ability to replicate and induce neuronal apoptosis. The results indicate that LFAOs undergo a concentration-dependent transition between 12mers and disperse 12-24mers with a dissociation constant (Kd) of 0.1 μM. The two species differ in their respective tertiary/quaternary structures but not their secondary structures. This conformational dynamics of LFAOs correlates with their ability to replicate and to induce apoptosis in SH-SY5Y human neuroblastoma cells, with 12mers being more neurotoxic and prone to replication than 12-24mers. The latter result implicates the replication process dominates at low physiological concentrations. The observations made in this report may have profound significance in deciphering the elusive roles of Aβ oligomer phenotypes and in determining their prion-type behavior in AD pathology.


Direct imaging of charge transport in progressively reduced graphene oxide using electrostatic force microscopy.
Graphene oxide (GO) has emerged as a multifunctional material that can be synthesized in bulk quantities and can be solution processed to form large-area atomic layered photoactive, flexible thin films for optoelectronic devices. This is largely due to the potential ability to tune electrical and optical properties of GO using functional groups. For the successful application of GO, it is key to understand the evolution of its optoelectronic properties as the GO undergoes a phase transition from its insulating and optically active state to the electrically conducting state with progressive reduction. In this paper, we use a combination of electrostatic force microscopy (EFM) and optical spectroscopy to monitor the emergence of the optoelectronic properties of GO with progressive reduction. EFM measurements enable, for the first time, direct visualization of charge propagation along the conducting pathways that emerge on progressively reduced graphene oxide (rGO) and demonstrate that with the increasing degree of reduction, injected charges can rapidly migrate over a distance of several micrometers, irrespective of their polarities. Direct imaging reveals the presence of an insurmountable potential barrier between reduced GO (rGO) and GO, which plays the decisive role in the charge transport. We complement charge imaging with theoretical modeling using quantum chemistry calculations that further demonstrate that the role of barrier in regulating the charge transport. Furthermore, by correlating the EFM measurements with photoluminescence imaging and electrical conductivity studies, we identify a bifunctional state in GO, where the optical properties are preserved along with good electrical conductivity, providing design principles for the development of GO-based, low-cost, thin-film optoelectronic applications.


Connexin 43 remodeling induced by LMNA gene mutation Glu82Lys in familial dilated cardiomyopathy with atrial ventricular block.
Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases. We studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C)) using confocal imaging and Western blotting analysis. Cx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all. Our findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.


Ocular dominance columns in New World monkeys.
Squirrel monkeys normally lack ocular dominance columns in V1. This study shows that squirrel monkeys can exhibit clear ocular dominance columns if they are made strabismic within a few weeks of birth. Columns were seen only in layer 4C beta and were coarser than the overlying blob pattern in the same animal. In physiological recordings from layer 4C of a normal squirrel monkey, single units were mostly monocular, but units driven by the two eyes were intermixed. These results suggest that in squirrel monkeys activity-dependent mechanisms do normally segregate geniculate inputs from the two eyes, but on a much finer scale than in Old World primates. Strabismic owl monkeys also showed ocular dominance columns; normal owl monkeys showed variable expression. Because ocular dominance columns, when present in New World monkeys, tend to occur in later-maturing parts of layer 4C, I hypothesize that a difference in the relative timing of the maturation of geniculocortical inputs and intracortical lateral connectivity explains the variability of ocular dominance column expression in New World monkeys.


Antibacterial Activity of Aluminum in Clay from the Colombian Amazon.
The problems of antibiotic overuse compel us to seek alternative antibacterial agents. Some clays have been shown to kill antibiotic-resistant human pathogens and may provide an alternative to known antibiotics. Here we show that Al toxicity plays a central role in the antibacterial action of a kaolin-rich clay from the Colombian Amazon (AMZ). Antibacterial susceptibility testing shows minimum inhibitory concentrations of 80 mg/mL against a model Escherichia coli (ATCC 25922). The clay buffered the media pH to ∼4.6 and Eh values to +360 mV. Chemical analysis of AMZ and bacteria showed that Al, P, and transition metals (Fe, Cu, Mn, and Zn) were exchanged during incubation at 37 °C. Only Al derived from the clay exceeded the minimum inhibitory concentrations for E. coli under acidic conditions. Ion imaging showed elevated Al levels in the bacterial membrane, and high intracellular Fe levels, relative to those of untreated controls. Phosphorus depletion in E. coli after reaction with AMZ, together with evidence of membrane permeabilization, suggests that Al reacts with membrane phospholipids, enhancing intracellular transport of metals. These results highlight the importance of dissolved Al for amplifying the toxicity of transition metals to human pathogens.


Druggability assessment of mammalian Per-Arnt-Sim [PAS] domains using computational approaches.
Per-Arnt-Sim (PAS) domains are key regions that occur in different regulatory proteins from all kingdoms of life. PAS domains show a remarkably conserved structural scaffold, despite a highly variable primary sequence. In this study we have attempted to address some of the gaps in knowledge regarding the druggability of PAS-A domains, differences in structure and dynamics within the PAS domain family and how this affects the druggability potential, as well as give insight into the druggability of steroid receptor coactivators and putative binding modes of the NCOA1. Investigations were performed through a range of computational methods including molecular docking studies, atomistic molecular dynamics simulations, and hotspot mapping. Atomistic molecular dynamics simulations show that the function of the AhR PAS-B domain is regulated by the dynamics of the highly conserved tyrosine Y322 residue, which acts as a "gatekeeper" controlling the access to the binding cavity and finely tuning the binding affinity. Furthermore, the transition between the partially unfolded and helical conformation of the loop1 segment within PAS-B domains was shown to be essential for the generation of "druggable" sites, especially for the NCOA1 PAS-B domain. Finally, our simulations indicated the undruggability of PAS-A domains, caused by the inherent characteristics of their putative binding sites. In conclusion, this work emphasises the role of intrinsic dynamics in tuning the druggability of PAS-B domains and shows that PAS-B domains of steroid receptor coactivators, such as NCOA1, can be targeted by small molecule ligands, which highlights the potential of developing new therapeutics designed to target these coactivators using structure-based approaches.


Insights into female germ cell biology: from in vivo development to in vitro derivations.
Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.


Minimal aortic injury of the thoracic aorta: imaging appearances and outcome.
The aim of this study is to describe the frequency, computed tomographic angiography (CTA) imaging appearance, management, and outcome of patients who present with minimal thoracic aortic injury. This retrospective study was Institutional Review Board-approved. Eighty-one patients with blunt traumatic aortic injuries (BTAI) were identified between 2004 and 2008, comprising 23 patients with minimal aortic injury (MAI) (mean age, 43.2 years ±18.2 years; 12 males and 11 females) and 58 patients with non-minimal aortic injury (mean age, 42.6 years ±22.7 years). CTA imaging was reviewed for each patient to differentiate those with MAI from those with non-MAI BTAI. Inclusion criteria for MAI on CTA were: post-traumatic abnormality of the internal contour of the aorta wall projecting into the lumen, intimal flap, intraluminal filling defect, intramural hematoma, and no evidence of an abnormality to the external contour of the aorta. Relevant follow-up imaging for MAI patients was also reviewed for resolution, stability, or progression of the vascular injury. The electronic medical record of each patient was reviewed and mechanism of injury, injury severity score, associated injuries, type and date of management, outcome, and days from injury to last medical consultation. Minimal aortic injury represented 28.4 % of all BTAI over the study period. Mean injury severity score (37.1), age (43.2 years), and gender did not differ significantly between MAI and non-MAI types of BTAI. Most MAI occurred in the descending thoracic aorta (16/23, 69 %). Without operative or endovascular repair, there was no death or complication due to MAI. One death occurred secondary to MAI (4.4 %) in a patient who underwent endovascular repair and surgical bypass, compared with an overall mortality rate of 8.6 % in the non-MAI BTAI group (p = 0.508). The most common CT appearance of MAI was a rounded or triangular intra-luminal aortic filling detect (18/23 patients, 78 %). In a mean of 466 days of clinical follow-up, no complications were observed in survivors treated without endovascular repair or operation. Minimal aortic injury is identified by multi-detector row CT in more than a quarter of cases of BTAI and has a low mortality. Conservative management is associated with an excellent outcome.


Transcriptional landscape of pathogen-responsive lncRNAs in tomato unveils the role of hydrolase encoding genes in response to Botrytis cinerea invasion.
LncRNAs have gained increasing attention owing to their important regulatory roles on growth and stress responses of plants. However, the mechanisms underlying the functions of lncRNAs in fruit-pathogen interaction are still largely unknown. In this study, a total of 273 lncRNAs responding to Botrytis cinerea infection were identified in tomato fruit, among which a higher percentage of antisense lncRNAs were targeted to the genes enriched in hydrolase activity. To ascertain the roles of these lncRNAs, seven hydrolase-related transcripts were transiently knocked-down by virus-induced gene silencing. Silencing of lncRNACXE20 reduced the expression level of a carboxylesterase gene, further enhancing the resistance of tomato to B. cinerea. In contrast, silencing of lncRNACHI, lncRNAMMP, lncRNASBT1.9 and lncRNAPME1.9 impaired the resistance to B. cinerea, respectively. Further RT-qPCR assay and enzymatic activity detection displayed that the attenuated resistance of lncRNAMMP and lncRNASBT1.9-silenced plants was associated with the inhibition on the expression of JA-related genes, while the decreased resistance of lncRNACHI-silenced plants resulted in reduced chitinase activity. Collectively, these results may provide references for deciphering the mechanisms underlying specific lncRNAs to interfere with B. cinerea infection by regulating the expression of defence-related genes or affecting hydrolase activity.


Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle hydrogel for enhanced dermal delivery.
Coenzyme Q10 (Q10) loaded solid lipid nanoparticles (SLN) were prepared by the high speed homogenization method and incorporated into Carbopol 974P hydrogels. Compritol 888 ATO (C888) was employed as the lipid base; Poloxamer 188 (P188) and Tween 80 (Tw80) were used as surfactant and co-surfactant. Optimum particle size with narrow distribution was obtained as 152.2 nm for blank and 142.4 nm for Q10 loaded SLNs. The overall charge of loaded SLNs was -13.7 ± 1.3 mV. Q10 entrapment efficiency was 89 % and the production yield was 94 %. Transmission electron microscopy analysis provided evidence of colloidal size, spherical shape while differential scanning calorimetry analysis confirmed recrystallization of the lipid after the preparation of SLNs. Trolox equivalent antioxidant capacity (TEAC) analysis has shown that antioxidant potential of Q10 can be protected in SLNs. Rheological characteristics demonstrated that the SLN incorporating gels were shear thinning and the mechanical strength of the gels was suitable for topical application. Diffusion studies from rat abdominal skin revealed that the delivery of Q10 was doubled in SLN incorporating gels, approximately 40 μg cm-2, in comparison with gels prepared with only Q10 (not incorporated in SLNs). As a result, it can be stated that Q10-SLN loaded gels can be successful delivery systems for carrying Q10 efficiently into the skin without losing its antioxidant properties.


Oral atenolol compared to oral propranolol for infantile hemangioma.
Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its β-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic β-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).


Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity.
The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with wortmannin and docetaxel as model drugs, we determined the relationship between the release kinetics and therapeutic efficacy and toxicity of the drugs. We have determined that drug release kinetics can affect the therapeutic efficacy of NP docetaxel and NP wortmannin in vitro and in vivo. Our study also demonstrates that a decrease in drug release kinetics can result in a decrease in the hepatotoxicity of CLS NP wortmannin. Using two model drugs, the current findings provide the first direct evidence that NP drug release profile is a critical factor in determining the NP therapeutics' efficacy and toxicity in vivo.


Block copolymer self-assembly for nanophotonics.
The ability to control and modulate the interaction of light with matter is crucial to achieve desired optical properties including reflection, transmission, and selective polarization. Photonic materials rely upon precise control over the composition and morphology to establish periodic interactions with light on the wavelength and sub-wavelength length scales. Supramolecular assembly provides a natural solution allowing the encoding of a desired 3D architecture into the chemical building blocks and assembly conditions. The compatibility with solution processing and low-overhead manufacturing is a significant advantage over more complex approaches such as lithography or colloidal assembly. Here we review recent advances on photonic architectures derived from block copolymers and highlight the influence and complexity of processing pathways. Notable examples that have emerged from this unique synthesis platform include Bragg reflectors, antireflective coatings, and chiral metamaterials. We further predict expanded photonic capabilities and limits of these approaches in light of future developments of the field.


Fabry Disease Screening in Patients With Kidney Transplant: A Single-Center Study in Turkey.
Fabry disease is a rare X-linked multisystemic lysosomal storage disorder of the glycosphingolipid metabolic pathway. Nephropathy is one of the most important complications of Fabry disease, and patients with classical phenotype are at risk of developing endstage kidney disease. In this study, we investigated the use of screening for Fabry disease in kidney transplant recipients at our center. We screened 301 kidney transplant recipients with functioning grafts. Analyses for α-galactosidase A gene mutation were performed in all female and male kidney transplant recipients. We also measured leukocyte α-galactosidase A enzyme activity in patients with identified GLA mutation. In 301 kidney transplant recipients, mean age was 42.9 ± 12.5 years, and the number of male patients was 180 (60%). Mean time after transplant was 79 ± 56 months, and estimated glomerular filtration rate was 66.8 ± 21 mL/min/1.73 m². One male patient who was diagnosed with Fabry disease before kidney transplant was also evaluated (mutation in the α-galactosidase A gene, c.1093_1101dup [p.Tyr365_lle367dup]). In 2 female patients, p.A143T (c.427G>A) mutation of unknown significance and p.D313Y (c.937G>T) heterozygous mutation were identified; however, leukocyte ?-galactosidase A enzyme activity was normal in these patients (63.7 and 67.3 nmol/h/mg protein). In the patient diagnosed with Fabry disease, family screening revealed 4 additional affected family members. Although prevalence was shown to be low in our center (1/301 patients; 0.33%), screening studies in kidney transplant recipients may help to detect new patients before they develop life-threatening complications such as renal involvement.


Testing for sensory threshold in drinking water with added calcium: a first step towards developing a calcium fortified water.
Background: Food fortification is an effective strategy that has been recommended for improving population calcium inadequate intakes. Increasing calcium concentration of water has been proposed as a possible strategy to improve calcium intake. The objective of this study was to determine the sensory threshold of different calcium salts added to drinking water using survival analysis. Methods: We performed the triangle test methodology for samples of water with added calcium using three different calcium salts: calcium chloride, calcium gluconate and calcium lactate. For each salt, a panel of 54 consumers tested seven batches of three water samples. Data were adjusted for chance and sensory threshold was estimated using the survival methodology and a discrimination of 50%. Results: The threshold value estimation for calcium gluconate was 587 ± 131 mg/L of water, corresponding to 25% discrimination, for calcium lactate was 676 ± 186 mg/L, corresponding to 50% discrimination, and for calcium chloride was 291 ± 73 mg/L, corresponding to 50% discrimination. Conclusions: These results show that water with calcium added in different salts and up to a concentration of 500 mg of calcium/L of water is feasible. The calcium salt allowing the highest calcium concentration with the lowest perceived changes in taste was calcium gluconate. Future studies need to explore stability and acceptability over longer periods of time.


Short-term prospective memory deficits in chronic back pain patients.
Chronic pain, particularly low back pain, is widespread. Although a great deal is known about the impact that this has on quality of life and physical activity, relatively little has been established regarding the more cognitive effects of pain. This study aims to find out whether individuals with chronic pain experience memory deficits in prospective memory (PM), the process of remembering to do things at some future point in time. Examples of PM include remembering to keep an appointment, such as a visit to a clinic, or to perform a particular task, such as paying a bill on time. The PM of 50 participants with chronic pain was compared with 50 pain-free participants. Each participant completed the Prospective Memory Questionnaire, which assesses three aspects of prospective memory (short-term habitual, long-term episodic, and internally cued), and records the use of strategies to aid remembering. In comparison to those not in pain, participants with chronic pain had significantly impaired short-term prospective memory, an effect which was evident even after co-varying use of analgesics and other drugs. These findings provide new insights into prospective memory dysfunction in people with chronic pain. Possible mechanisms for this dysfunction are discussed and suggestions for future research given.


State-of-the-Art lecture. Antiproliferative actions of angiotensin-(1-7) in vascular smooth muscle.
Hemodynamic factors, circulating hormones, paracrine factors, and intracrine factors influence vascular smooth muscle growth and plasticity. The well-characterized role of angiotensin II in the modulation of vascular tone and cell function may be critically involved in the mechanisms by which vascular smooth muscle responds to signals associated with vascular endothelial dysfunction and increases in oxidative stress. Studies from this laboratory suggest that the trophic actions of angiotensin II may be intrinsically regulated by angiotensin-(1-7), a separate product of the angiotensin system derived from the common substrate, angiotensin I. Exposure of cultured vascular smooth muscle cells to angiotensin-(1-7) inhibited the trophic actions of angiotensin II and reduced the expression of the mitogenic effects of both normal serum and platelet-derived growth factor. The growth-inhibitory actions of angiotensin-(1-7) were blocked by the selective D-alanine(7)-angiotensin-(1-7) antagonist and the nonselective angiotensin receptor blocker sarcosine(1)-threonine(8)-angiotensin II. In contrast, subtype-selective antagonists for the AT(1) and AT(2) receptors had no effect on the inhibitory actions of angiotensin-(1-7), a finding that is consistent with the pharmacological characterization of a high-affinity (125)I-labeled angiotensin-(1-7) binding site in the vasculature by use of selective and nonselective angiotensin II receptor antagonists. The relevance of these findings to the proliferative response of vascular smooth muscle cells after endothelial injury was confirmed by assessment of the effect of a 12-day infusion of angiotensin-(1-7) on neointimal formation. In these experiments, the proliferative response produced by injuring the carotid artery was inhibited by angiotensin-(1-7) through a mechanism that could not be explained by changes in arterial pressure. Because plasma angiotensin-(1-7) increased to levels comparable to those found in animals and human subjects given therapeutic doses of angiotensin-converting enzyme inhibitors, angiotensin-(1-7) may be one factor participating in the reversal of vascular proliferation during inhibition of angiotensin II formation or activity.


Characterisation of hexokinase in Toxoplasma gondii tachyzoites.
We have cloned the hexokinase [E.C. 220.127.116.11] gene of Toxoplasma gondii tachyzoite and obtained an active recombinant enzyme with a calculated molecular mass of 51,465Da and an isoelectric point of 5.82. Southern blot analysis indicated that the hexokinase gene existed as a single copy in the tachyzoites of T. gondii. The sequence of T. gondii hexokinase exhibited the highest identity (44%) to that of Plasmodium falciparum hexokinase and lower identity of less than 35% to those of hexokinases from other organisms. The specific activity of the homogeneously purified recombinant enzyme was 4.04 micromol/mg protein/min at 37 degrees C under optimal conditions. The enzyme could use glucose, fructose, and mannose as substrates, though it preferred glucose. Adenosine triphosphate was exclusively the most effective phosphorus donor, and pyrophosphate did not serve as a substrate. K(m) values for glucose and adenosine triphosphate were 8.0+/-0.8 microM and 1.05+/-0.25mM, respectively. No allosteric effect of substrates was observed, and the products, glucose 6-phosphate and adenosine diphosphate, had no inhibitory effect on T. gondii hexokinase activity. Other phosphorylated hexoses, fructose 6-phosphate, trehalose 6-phosphate which is an inhibitor of yeast hexokinase, and pyrophosphate, also did not affect T. gondii hexokinase activity. Native hexokinase activity was recovered in both the cytosol and membrane fractions of the whole lysate of T. gondii tachyzoites. This result suggests that T. gondii hexokinase weakly associates with the membrane or particulate fraction of the tachyzoite cell.


Randomised controlled factorial trial of dietary advice for patients with a single high blood pressure reading in primary care.
To assess the effect of brief interventions during the "watchful waiting" period for hypertension. Factorial trial. General practice. 296 patients with blood pressure > 160/90 mm Hg were randomised to eight groups defined by three factors: an information booklet; low sodium, high potassium salt; prompt sheets for high fruit, vegetable, fibre; and low fat. Blood pressure (primary outcome); secondary outcomes of diet, weight, and dietary biomarkers (urinary sodium:potassium (Na:K) ratio; carotenoid concentrations). Blood pressure was not affected by the booklet (mean difference (diastolic blood pressure) at one month 0.2, 95% confidence interval 1.6 to 2.0), salt (0.13; 1.7 to 2.0), or prompts (0.52; 1.3 to 2.4). The salt decreased Na:K ratio (difference 0.32; 0.08 to 0.56, P = 0.01), and the prompts helped control weight (difference 0.39 (0.85 to 0.05) kg at one month, P = 0.085; 1.2 (0.1 to 2.25) kg at six months, P = 0.03). Among those with lower fruit and vegetable consumption (< 300 g per day), prompts increased fruit and vegetable consumption and also carotenoid concentrations (difference 143 (16 to 269) mmol/l, P < 0.03) but did not decrease blood pressure. During watchful waiting, over and above the effect of brief advice and monitoring, an information booklet, lifestyle prompts, and low sodium salt do not reduce blood pressure. Secondary analysis suggests that brief interventions-particularly lifestyle prompts-can make useful changes in diet and help control weight, which previous research indicates are likely to reduce the long term risk of stroke.


Groundwater Isolation Governs Chemistry and Microbial Community Structure along Hydrologic Flowpaths.
This study deals with the effects of hydrodynamic functioning of hard-rock aquifers on microbial communities. In hard-rock aquifers, the heterogeneous hydrologic circulation strongly constrains groundwater residence time, hydrochemistry, and nutrient supply. Here, residence time and a wide range of environmental factors were used to test the influence of groundwater circulation on active microbial community composition, assessed by high throughput sequencing of 16S rRNA. Groundwater of different ages was sampled along hydrogeologic paths or loops, in three contrasting hard-rock aquifers in Brittany (France). Microbial community composition was driven by groundwater residence time and hydrogeologic loop position. In recent groundwater, in the upper section of the aquifers or in their recharge zone, surface water inputs caused high nitrate concentration and the predominance of putative denitrifiers. Although denitrification does not seem to fully decrease nitrate concentrations due to low dissolved organic carbon concentrations, nitrate input has a major effect on microbial communities. The occurrence of taxa possibly associated with the application of organic fertilizers was also noticed. In ancient isolated groundwater, an ecosystem based on Fe(II)/Fe(III) and S/SO4 redox cycling was observed down to several 100 of meters below the surface. In this depth section, microbial communities were dominated by iron oxidizing bacteria belonging to Gallionellaceae. The latter were associated to old groundwater with high Fe concentrations mixed to a small but not null percentage of recent groundwater inducing oxygen concentrations below 2.5 mg/L. These two types of microbial community were observed in the three sites, independently of site geology and aquifer geometry, indicating hydrogeologic circulation exercises a major control on microbial communities.


[Assignment of a component of protein fluorescence spectra to tryptophan residues by their three-dimensional microoenvironmental properties].
Parameters of fluorescence of three single-tryptophan-containing proteins and of two log-normal components of proteinase K (2 tryptophans) were analyzed in relation to the microenvironment characteristics of indolic atoms in crystal structures of the proteins. For this purpose, it was constructed a system of microenvironment description including accessibility of the atoms to the bulk and bound water; the density, polarity and mobility of environment within radii of 5.5 and 7.5 A from each indolic atom; and the existence of eventual partners in hydrogen bonding with excited fluorophore. The analysis showed that, in the cases of the most shorter-wavelength emission bands (those structured at 308 nm for azurin and at 316 nm for L-asparaginase), as well as of the monomer melittin band at 350 nm, the microenvironment characteristics well agreed to those predicted in the model of discrete states of tryptophan in proteins [1,3,7] and can be used for assignment of protein fluorescence spectral components to individual tryptophan residues. However, differences of the microenvironment parameters included in the system are little discernible for the component bands of proteinase K emission at ca. 330 and 340 nm. In order to reliably assign such components of tryptophan fluorescence, it seems to be sufficient to take into account some additional structural characteristics, which could be revealed in a comprehensive analysis of a great number of proteins possessing such spectral components.


Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial.
After reinsertion on the humerus, the rotator cuff has limited ability to heal. Growth factor augmentation has been proposed to enhance healing in such procedure. This study was conducted to assess the efficacy and safety of growth factor augmentation during rotator cuff repair. Randomized controlled trial; Level of evidence, 1. Eighty-eight patients with a rotator cuff tear were randomly assigned by a computer-generated sequence to receive arthroscopic rotator cuff repair without (n = 45) or with (n = 43) augmentation with autologous platelet-rich fibrin matrix (PRFM). The primary end point was the postoperative difference in the Constant score between the 2 groups. The secondary end point was the integrity of the repaired rotator cuff, as evaluated by magnetic resonance imaging. Analysis was on an intention-to-treat basis. All the patients completed follow-up at 16 months. There was no statistically significant difference in total Constant score when comparing the results of arthroscopic repair of the 2 groups (95% confidence interval, -3.43 to 3.9) (P = .44). There was no statistically significant difference in magnetic resonance imaging tendon score when comparing arthroscopic repair with or without PRFM (P = .07). Our study does not support the use of autologous PRFM for augmentation of a double-row repair of a small or medium rotator cuff tear to improve the healing of the rotator cuff. Our results are applicable to small and medium rotator cuff tears; it is possible that PRFM may be beneficial for large and massive rotator cuff tears. Also, given the heterogeneity of PRFM preparation products available on the market, it is possible that other preparations may be more effective.


Bayesian autoregressive multilevel modeling of burden of diseases, injuries and risk factors in Iran 1990 - 2013.
Statistical modeling and developing new methods for estimating burden of diseases, injuries and risk factors is a fundamental concern in studying the country health situation for better health management and policy making. Bayesian autoregressive multilevel model is a strong method for this kind of study though in complex situations it has its own challenges. Our study aims to describe the way of modeling space and time data through an autoregressive multilevel model and address challenges in complex situation. We will obtain data from different published and unpublished secondary data sources including population-based health surveys (e. g. NHS, DHS, STEP) at national and provincial levels and we also assess epidemiological studies via systematic review for each disease, injuries and risk factor over the period of 1990-2013. These data generally have a multilevel hierarchy and also time correlation. However, statistical analysis of diseases, injuries and risk factors data is primarily facing the problem of information scarcity. Data are generally too scarce to ensure reliable estimates in many practical problems. Also, there may be nonlinear changes over time, different kind of uncertainties in data and incompatible geographical data. We describe Bayesian autoregressive multilevel modeling approach that provides a natural solution to these problems through its ability to sensibly combine information from several sources of data and available prior information. In this hierarchy model levels of each hierarchy borrow information from each other and also lower levels borrow information from higher levels. We will fit the model using Markov Chain Monte Carlo (MCMC) methods because of its capabilities and benefits in complex cases. Our analyses will include different existing sources of data in Iran for 24 years through a rational and reasonable model to estimate burden of diseases, injuries and risk factors for Iran at national, regional and provincial levels while considering several kinds of uncertainties. Comprehensive and realistic estimates are always an issue of request that will be obtained through a suitable statistical modeling considering all dimensions and then can be used for making better decision in real situations.


Inhibition and recovery of DNA synthesis in host tissues and sensitive and resistant B16 melanoma after 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, a predictor of therapeutic efficacy.
Single doses of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea caused transient suppression of [3H]thymidine incorporation into DNA in bone marrow and gastrointestinal mucosa and more prolonged inhibition of such incorporation in B16 melanoma. A single dose of 1-(2-chloroethyl) -3- (trans-4-methylcyclohexyl) -1-nitro-sourea, 16 mg/kg, doubled the mean life-span after treatment of C57BL times DBA/2F1 male mice bearing 12-day-old B16 melanomas. Subsequent doses timed to minimize toxicity and maximize antitumor effect, however, produced no further prolongation of survival, and studies with B16 melanoma previously expsed to 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea demonstrated that the suppression of [3H]thymidine incorporation into DNA was no longer prolonged beyond that seen with normal host tissues. The loss of clinical efficacy was accompanied by a loss of differential suppression of [3H]thymidine incorporation into DNA between the tumor and host tissues.


An Intuitive Endoscope Operating System With an Interface Suitable for Cartesian Coordinate Input.
Endoscopes are useful tools for inspecting and observing places that are inaccessible to humans and ordinary cameras. However, it is difficult to operate an endoscope intuitively because there is an embodiment difference between the endoscope and the human body. In this study, we developed an endoscope operating system that uses a Cartesian coordinate input interface. To investigate the range of movement achieving the required accuracy, we measured the actual movement of the endoscope tip using a magnetic three-dimensional positioning sensor. We compared the actual and estimated positions and postures at the endoscope tip and estimated the errors. The results showed that the error of the thrust output was sufficiently small. Furthermore, we can achieve the required accuracy in the range of movement from -74.9° to 80.0° in the roll direction, and from -37.5° to 50.0° in the yaw direction.Clinical relevance- This paper presents an accurate and intuitive endoscope operating system with a new interface.


Purified Cannabidiol isolate does not inhibit active caspase-1 release in NLRP inflammasome-mediated UVB or ATP-activated keratinocytes or appear to reduce key inflammatory cytokines in UVB-irradiate keratinocytes.
Cannabidiol is a plant-derived cannabinoid that has been suggested to have several human health benefits including potential anti-inflammatory effects. It is now common to find various forms of Cannabidiol, most often referred to as CBD, in nutritional supplements and topical treatments. The mechanisms by which CBD can influence inflammatory pathways in the body, and more particularly in the skin, are presently still unclear. It is known that CBD will bind to cannabinoid receptors, CB1 and CB2, in the body and recent work has shown that in keratinocytes, CBD can regulate inflammation through transcriptional regulation involving the NFƙβ nuclear pathways. The fact that CBD operates through the NFƙβ pathways suggests that, perhaps, the molecule may influence the expression of active caspase-1 through NLRP inflammasome-mediated pathways. Recently, work has published demonstrating that Normal Human Epidermal Keratinocytes (NHEKs) can be activated by UVB and ATP to express active caspase-1 via NLRP inflammasome-mediated pathways. There was a strong interest to see whether highly purified Cannabidiol Isolate (>99% purity) might function to control release of active caspase-1 by testing of NHEKs using the previously described models. In addition, NHEKs expression of non-NLRP inflammasome-induced inflammation markers including IL-6, IL-8 and PGE2 was examined in UVB-activated NHEKs. It was found that purified Cannabidiol Isolate did not influence active caspase-1 release in either UVB or ATP-activated NHEKs suggesting the molecule does not influence the NLRP inflammasome pathways. In addition, it was surprisingly found that the Cannabidiol Isolate did not impact the expression of additional UVB-activated non-NLRP inflammatory markers. Data presented suggest that if Cannabidiol functions as an anti-inflammatory, it does so through pathways not associated with either the NLRP inflammasome-mediated expression of caspase-1 or through the more commonly known expression of interleukin or prostaglandin inflammatory pathways.


Tyrosine phosphorylation-dependent activation of TRPC6 regulated by PLC-γ1 and nephrin: effect of mutations associated with focal segmental glomerulosclerosis.
Transient receptor potential canonicals (TRPCs) play important roles in the regulation of intracellular calcium concentration. Mutations in the TRPC6 gene are found in patients with focal segmental glomerulosclerosis (FSGS), a proteinuric disease characterized by dysregulated function of renal glomerular epithelial cells (podocytes). There is as yet no clear picture for the activation mechanism of TRPC6 at the molecular basis, however, and the association between its channel activity and pathogenesis remains unclear. We demonstrate here that tyrosine phosphorylation of TRPC6 induces a complex formation with phospholipase C (PLC)-γ1, which is prerequisite for TRPC6 surface expression. Furthermore, nephrin, an adhesion protein between the foot processes of podocytes, binds to phosphorylated TRPC6 via its cytoplasmic domain, competitively inhibiting TRPC6-PLC-γ1 complex formation, TRPC6 surface localization, and TRPC6 activation. Importantly, FSGS-associated mutations render the mutated TRPC6s insensitive to nephrin suppression, thereby promoting their surface expression and channel activation. These results delineate the mechanism of TRPC6 activation regulated by tyrosine phosphorylation, and imply the cell type-specific regulation, which correlates the FSGS mutations with deregulated TRPC6 channel activity.


A Neighborhood-Wide Association Study (NWAS): Example of prostate cancer aggressiveness.
Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease. Pennsylvania Cancer Registry data were linked to U.S. Census data. In a successively more stringent multiphase approach, we evaluated the association between neighborhood (n = 14,663 census variables) and prostate cancer aggressiveness(PCA) with n = 6,416 aggressive (Stage≥3/Gleason grade≥7 cases) vs. n = 70,670 non-aggressive (Stage<3/Gleason grade<7) cases in White men. Analyses accounted for age, year of diagnosis, spatial correlation, and multiple-testing. We used generalized estimating equations in Phase 1 and Bayesian mixed effects models in Phase 2 to calculate odds ratios(OR) and confidence/credible intervals(CI). In Phase 3, principal components analysis grouped correlated variables. We identified 17 new neighborhood variables associated with PCA. These variables represented income, housing, employment, immigration, access to care, and social support. The top hits or most significant variables related to transportation (OR = 1.05;CI = 1.001-1.09) and poverty (OR = 1.07;CI = 1.01-1.12). This study introduces the application of high-dimensional, computational methods to large-scale, publically-available geospatial data. Although NWAS requires further testing, it is hypothesis-generating and addresses gaps in geospatial analysis related to empiric assessment. Further, NWAS could have broad implications for many diseases and future precision medicine studies focused on multilevel risk factors of disease.


Daily Meteorological Parameters Influence the Risk of Intracerebral Hemorrhage in a Subtropical Monsoon Basin Climate.
The correlation between meteorological parameters and intracerebral hemorrhage (ICH) occurrence is controversial. Our research explored the effect of daily meteorological parameters on ICH risk in a subtropical monsoon basin climate. We retrospectively analyzed patients with ICH in a teaching hospital. Daily meteorological parameters including temperature (TEM), atmospheric pressure (PRE), relative humidity (RHU), and sunshine duration (SSD) were collected, with the diurnal variation (daily maximum minus minimum) and day-to-day variation (average of the day minus the previous day) calculated to represent their fluctuation. We adopted a time-stratified case-crossover approach and selected conditional logistic regression to explore the effect of meteorological parameters on ICH risk. The influence of monthly mean temperature proceeded via stratified analysis. Air pollutants were gathered as covariates. Our study included 1052 eligible cases with ICH. In a single-factor model, the risk of ICH decreased by 5.9% (P<0.001) for each 1°C higher of the daily mean TEM, and the risk increased by 2.4% (P=0.002) for each 1hPa higher of the daily mean PRE. Prolongation of daily SSD inhibited the risk of ICH, and OR was 0.959 (P=0.007). The risk was raised by 7.5% (P=0.0496) with a 1°C increment of day-to-day variation of TEM. In a two-factor model, the effect of daily mean TEM or daily SSD on ICH risk was still statistically significant after adjusting another factor. The influence of meteorological parameters on ICH risk continued in cold months but disappeared in warm months after stratified analysis. This research indicates daily TEM and SSD had an inverse correlation to ICH risk in a subtropical monsoon basin climate. They were independent when adjusted by another factor. Daily PRE and day-to-day TEM variation were positively related to ICH risk. The correlation of daily meteorological factors on ICH risk was affected by the monthly thermal background.


Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group.
To evaluate the safety and efficacy of an intravenous liposomal dispersion of prostaglandin E1 as TLC C-53 in the treatment of patients with acute respiratory distress syndrome (ARDS). Randomized, prospective, multicenter, double-blind, placebo-controlled, phase III clinical trial. Forty-seven community and university-affiliated hospitals in the United States. A total of 350 patients with ARDS were enrolled in this clinical trial. Patients were prospectively randomized in a 1:1 ratio to receive either liposomal prostaglandin E1 or placebo. The study drug was infused intravenously for 60 mins every 6 hrs for 7 days starting with a dosage of 0.15 microg/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 microg/kg/hr) was attained or intolerance to further increases developed. Patients received standard aggressive medical/surgical care during the infusion period. The primary outcome measure was the time it took to wean the patient from the ventilator. Secondary end points included time to improvement of the PaO2/FIO2 ratio (defined as first PaO2/FIO2 > 300 mm Hg), day 28 mortality, ventilator dependence at day 8, changes in PaO2/FIO2, incidence of and time to development/resolution of organ failure other than ARDS. A total of 348 patients could be evaluated for efficacy. The distribution of variables at baseline describing gender, lung injury scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS or from institution of mechanical ventilation to the first dose of study drug was similar among patients in the liposomal prostaglandin E1 (n = 177) and the placebo (n = 171) treatment arms. There was no significant difference in the number of days to the discontinuation of ventilation in the liposomal prostaglandin E1 group compared with the placebo group (median number of days to off mechanical ventilation, 16.9 in patients receiving liposomal prostaglandin E1 and 19.6 in those administered placebo; p = .94). Similarly, mortality at day 28 was not significantly different in the two groups (day 28 mortality, 57 of 176 (32%) in the liposomal prostaglandin E1 group and 50 of 170 (29%) in patients receiving placebo; p = .55). In contrast, treatment with liposomal prostaglandin E1 was associated with a significantly shorter time to reach a PaO2/FIO2 ratio of >300 mm Hg (median number of days to reaching a PaO2/FIO2 ratio >300 mm Hg: 9.8 days in the liposomal prostaglandin E1 group and 13.7 days in patients receiving the placebo; p = .02). Among the subgroups examined, time to off mechanical ventilation was significantly reduced in patients who received at least 85% of a full dose (i.e., > 45.9 microg/kg) of liposomal prostaglandin E1 (median number of days to discontinuation of ventilation, 10.3 in the liposomal prostaglandin E1 group and 16.3 days in patients receiving placebo; p = .05). The overall incidence of serious adverse events was not significantly different in the liposomal prostaglandin E1 (40%) or placebo-treated (37%) groups. Drug-related adverse events of all kinds were reported in 69% of the patients receiving liposomal prostaglandin E1 compared with 33% of the placebo group, with hypotension and hypoxia (occurring in 52% and 24% of the liposomal prostaglandin E1-treated patients, respectively, and 17% and 5% of the placebo-treated patients, respectively) being noted most frequently. In the intent-to-treat population of patients with ARDS, treatment with liposomal prostaglandin E1 accelerated improvement in indexes of oxygenation but did not decrease the duration of mechanical ventilation and did not improve day 28 survival.


Applications of Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders.
The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to the existence of the blood-brain barrier (BBB), a closely spaced network of blood vessels and endothelial cells that functions to prevent the entry of unwanted substances in the brain. The emergence and advancement of nanotechnology shows favourable prospects to overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties and imaging agents that have dimensions between 1 and 100 nm could potentially be used to ensure enhanced efficacy, cellular uptake, specific transport, and delivery of specific molecules to the brain, owing to their modified physico-chemical features. The conjugates of nanoparticles and medicinal plants, or their components known as nano phytomedicine, have been gaining significance lately in the development of novel neuro-therapeutics owing to their natural abundance, promising targeted delivery to the brain, and lesser potential to show adverse effects. In the present review, the promising application, and recent trends of combined nanotechnology and phytomedicine for the treatment of neurological disorders (ND) as compared to conventional therapies, have been addressed. Nanotechnology-based efforts performed in bioinformatics for early diagnosis as well as futuristic precision medicine in ND have also been discussed in the context of computational approach.


Basic calcium phosphate crystals as a unique therapeutic target in osteoarthritis.
Osteoarthritis (OA) is the most common form of arthritis that occurs in humans. Despite its prevalence, the pathogenesis of OA is not fully understood. Intraarticular basic calcium phosphate (BCP) (an inclusive term for partially carbonate-substituted hydroxyapatite, octacalcium phosphate and tricalcium phosphate) crystals are implicated in OA and are associated with severe degenerative arthritis characterized by marked synovial hyperplasia, aggravated joint degeneration and large joint effusions. Their pathogenicity relates, at least in part, to their ability to stimulate cellular mitogenesis in a number of cell types including macrophages, porcine articular chondrocytes (PAC) and human fibroblasts (HF) and induce prostaglandin, cytokine and matrix metalloproteinase synthesis and secretion in HF and PAC. Identification of BCP crystals in OA joints remains problematic because of the lack of a simple and reliable analytic procedure. There is currently no drug available that prevents the formation or modifies the biological effects of BCP crystals. This review highlights the recent advances in our knowledge of BCP crystal deposition diseases and discusses the potential therapeutic strategies for BCP crystal-associated OA.


GC-MS and GC-IRD studies on the ring isomers of N-methyl-2-methoxyphenyl-3-butanamines (MPBA) related to 3,4-MDMA.
The mass spectra of the controlled substance 3,4-MDMA and its regioisomer 2,3-MDMA are characterized by an imine fragment base peak at m/z 58 and additional fragments at m/z 135/136 for the methylenedioxybenzyl cation and radical cation, respectively. Three positional ring methoxy isomers of N-methyl-2-(methoxyphenyl)-3-butanamine (MPBA) have an isobaric relationship to 2,3- and 3,4-MDMA. All five compounds have the same molecular weight and produce similar EI mass spectra. This lack of mass spectral specificity for the isomers in addition to the possibility of chromatographic co-elution could result in misidentification. The lack of reference materials for the potential imposter molecules constitutes a significant analytical challenge. Perfluoroacylation of the amine group reduced the nitrogen basicity and provided individual fragmentation pathways for discrimination among these compounds based on unique fragment ions and the relative abundance of common ions. Studies using gas chromatography with infrared detection provided additional structure-IR spectra relationships. The underivatized amines and the perfluoroacylated derivatives (PFPA and HFBA) were resolved by capillary gas chromatography on a 100% dimethylpolysiloxane stationary phase. The perfluoroacylated derivatives showed better resolution on a cyclodextrin modified stationary phase.