Iagnosis and treatment of myelitis after lumbar reoperation: A case report.
At present, acute myelitis (AM) is a great challenge to diagnosis and treatment because of its complicated etiology, critical condition, and poor prognosis, and it is easy to leave different degrees of limb motor dysfunction. The report of this case is helpful to improve the understanding of AM after lumbar surgery, reduce misdiagnosis and provide reference for clinical treatment. This study reported a case of AM after lumbar reoperation. Before the patient was diagnosed as AM, we gave high-dose hormone anti-inflammatory and detumescence symptomatic treatment according to empirical treatment, and the effect was ideal and rehabilitation treatment was actively carried out at the right time. After 10 months of follow-up, the patient recovered well. Because lumbar surgery is a contraindication of lumbar puncture, the patient's diagnosis was confirmed by thoracic magnetic resonance imaging. Magnetic resonance imaging of thoracic vertebra on the 17th day after lumbar operation showed that small round T1W1 signal, slightly higher T2W1 signal and T2-fat suppression imaging equal signal were seen in the horizontal spinal cord of thoracic vertebra 10. According to the empirical treatment, patients have been given high-dose hormone therapy after operation, and comprehensive treatment such as comprehensive training of paraplegic limbs, joint loosening training, electric massage and other rehabilitation training will be carried out when the general condition of patients improves. After 10 months of follow-up, there were no major sequelae such as limb paralysis. Due to the rarity of AM in clinical work, it is easy for doctors to ignore the disease and miss the best treatment stage, which will lead to serious sequelae.


Using Principles of Motor Control to Analyze Performance of Human Machine Interfaces.
There have been significant advances in biosignal extraction techniques to drive external biomechatronic devices or to use as inputs to sophisticated human machine interfaces. The control signals are typically derived from biological signals such as myoelectric measurements made either from the surface of the skin or subcutaneously. Other biosignal sensing modalities are emerging. With improvements in sensing modalities and control algorithms, it is becoming possible to robustly control the target position of a end effector. It remains largely unknown to what extent these improvements can lead to naturalistic human-like movement. In this paper, we sought to answer this question. We utilized a sensing paradigm called sonomyography based on continuous ultrasound imaging of forearm muscles. Unlike myoelectric control strategies which measure electrical activation and use the extracted signals to determine the velocity of an end-effector; sonomyography measures muscle deformation directly with ultrasound and uses the extracted signals to proportionally control the position of an end-effector. Previously, we showed that users were able to accurately and precisely perform a virtual target acquisition task using sonomyography. In this work, we investigate the time course of the control trajectories derived from sonomyography. We show that the time course of the sonomyography-derived trajectories that users take to reach virtual targets reflect the trajectories shown to be typical for kinematic characteristics observed in biological limbs. Specifically, during a target acquisition task, the velocity profiles followed a minimum jerk trajectory shown for point-to-point arm reaching movements, with similar time to target. In addition, the trajectories based on ultrasound imaging result in a systematic delay and scaling of peak movement velocity as the movement distance increased. We believe this is the first evaluation of similarities in control policies in coordinated movements in jointed limbs, and those based on position control signals extracted at the individual muscle level. These results have strong implications for the future development of control paradigms for assistive technologies.


Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors.
In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity. The mechanisms underlying the positive effects of ACE inhibition and beta-adrenergic blockade are largely unknown, but hemodynamic factors (vasodilation) may contribute by improving the access of glucose and insulin to skeletal muscle. The drugs, which were favorable or neutral with respect to insulin sensitivity, caused no changes in lipids or glucose homeostasis. In contrast, beta-blockers, except pindolol, had negative effects on triglycerides and high-density lipoprotein cholesterol, and thiazide diuretics caused adverse effects on total serum cholesterol, low-density lipoprotein cholesterol, and total and very-low-density lipoprotein triglyceride. The metabolic action of antihypertensive drugs is an important factor to consider in the choice of a proper treatment strategy in both diabetic and nondiabetic patients with hypertension.


Triptorelin embonate (6-month formulation).
A 6-month formulation of the gonadotropin-releasing hormone agonist triptorelin embonate (designed to deliver 22.5 mg of triptorelin over a 6-month period) has been developed for use in the treatment of advanced prostate cancer. Following intramuscular administration of the 6-month formulation of triptorelin embonate 22.5 mg to men with advanced prostate cancer (subset of 15 patients from the pivotal clinical trial), serum testosterone levels initially increased, followed by a rapid, sustained decrease. Castrate serum testosterone levels (i.e. < or =1.735 nmol/L) were achieved in a geometric mean time of 18.8 days. The 6-month formulation of triptorelin embonate achieved and maintained castrate serum testosterone levels in patients with advanced prostate cancer (n = 120), according to the results of the pivotal, noncomparative, multicentre trial (patients received intramuscular triptorelin embonate 22.5 mg on day 1 and at month 6 [week 24]). By day 29, 97.5% of patients had castrate serum testosterone levels. Castrate serum testosterone levels were maintained from months 2 to 12 in 93.0% of patients. Prior to the second injection at month 6, 98.3% of patients had castrate serum testosterone levels, and 98.3% of patients had castrate serum testosterone levels at study completion. The 6-month formulation of triptorelin embonate 22.5 mg was generally well tolerated in patients with advanced prostate cancer; adverse events were of mild severity in the majority of patients. Drug-related adverse events (e.g. hot flushes) were consistent with the pharmacological action of triptorelin. Injection-site reactions occurred in 6.7% of triptorelin embonate recipients.


Jerk-locked back averaging and dipole source localization of magnetoencephalographic transients in a patient with epilepsia partialis continua.
In order to localize the generator site of epileptiform discharges, we applied the techniques of jerk-locked back averaging (JBA) of magnetoencephalographic (MEG) activities and dipole source localization in a patient with epilepsia partialis continua (EPC), who showed continuous, focal myoclonic jerks in the right arm. The myoclonic discharges in the right thenar muscle were used as a trigger pulse. JBA revealed consistent EEG and MEG transients that coincided consistently and constantly preceded the myoclonic jerks. The estimated dipoles of MEG were localized in a restricted area in the left precentral area, which closely correlated with the area of epileptic discharges recorded in electrocorticography. Therefore, JBA of MEG is considered to be a useful non-invasive method for localizing the epileptogenic area in EPC.


Deoxyribonucleic acid methyltransferase 3B promotes epigenetic silencing through histone 3 chromatin modifications in pituitary cells.
Epigenetic dysregulation is implicated in pituitary neoplasia as the cause of silencing of several tumor suppressor genes. However, the upstream mediators of such events remain unknown. We examined the three members of the DNA methyltransferase (DNMT) enzyme family in normal and neoplastic human and mouse pituitary cells. This study was performed at a university-affiliated cancer research institute. Gene expression, promoter DNA methylation, histone modifications, and cell proliferation were determined. In contrast to DNMT1 and DNMT3a, DNMT3b was expressed at relatively higher levels in neoplastic pituitary cells. However, examination of the human DNMT3b 5' region showed uniformly low DNA methylation levels with little difference between normal and tumor samples. Through pharmacological methylation inhibition or histone deacetylation inhibition, we identified that DNMT3b gene expression is subject to histone modifications. Down-regulation of DNMT3b resulted in induction of retinoblastoma, p21, and p27, and reduction in cell proliferation. These targeted effects were associated with enhanced histone 3 acetylation and diminished histone methylation. Our findings identify DNMT3b as a putative mediator of epigenetic control through histone modifications of gene expression in pituitary cells.


Regulation of cell proliferation and patterning in Drosophila oogenesis by Hedgehog signaling.
The localized expression of Hedgehog (Hh) at the extreme anterior of Drosophila ovarioles suggests that it might provide an asymmetric cue that patterns developing egg chambers along the anteroposterior axis. Ectopic or excessive Hh signaling disrupts egg chamber patterning dramatically through primary effects at two developmental stages. First, excess Hh signaling in somatic stem cells stimulates somatic cell over-proliferation. This likely disrupts the earliest interactions between somatic and germline cells and may account for the frequent mis-positioning of oocytes within egg chambers. Second, the initiation of the developmental programs of follicle cell lineages appears to be delayed by ectopic Hh signaling. This may account for the formation of ectopic polar cells, the extended proliferation of follicle cells and the defective differentiation of posterior follicle cells, which, in turn, disrupts polarity within the oocyte. Somatic cells in the ovary cannot proliferate normally in the absence of Hh or Smoothened activity. Loss of protein kinase A activity restores the proliferation of somatic cells in the absence of Hh activity and allows the formation of normally patterned ovarioles. Hence, localized Hh is not essential to direct egg chamber patterning.


Diosgenin, a plant-derived sapogenin, exhibits antiviral activity in vitro against hepatitis C virus.
Diosgenin (3β-hydroxy-5-spirostene, 1), a plant-derived sapogenin, is used as a dietary supplement. However, the biological effects of 1 related to viral replication remain unexplored. In this study, the effects of 1 on hepatitis C virus (HCV) replication were evaluated. Based on a reporter-based HCV subgenomic replicon system, 1 was found to inhibit HCV replication at low micromolar concentrations. The EC(50) (concentration at which 50% of HCV replication is inhibited) of 1 was 3.8 μM. No cellular toxicity was observed at this concentration. Diosgenin (1) also significantly reduced the levels of viral RNA and viral proteins as evaluated by quantitative real-time reverse transcriptase PCR and Western blot analysis, respectively. In addition, in an alternative HCV antiviral system more closely aligned to all steps involved in the HCV infection and life cycle, 1 totally abolished HCV replication at 20 μM. Moreover, 1 reduced the phosphorylation of signal transducer and activator of transcription 3. A combination of 1 and interferon-α exerted an additive effect on the resultant anti-HCV activity.


Dehydration of pollock skin prior to gelatin production.
Alaska pollock (Theragra chalcogramma) is the U.S.A.'s largest commercial fishery, with an annual catch of over 1 million tons. During pollock processing, the skins are discarded or made into fish meal, despite their value for gelatin production. The absence of gelatin-processing facilities in Alaska necessitates drying of the skins before transport to decrease the moisture content, but conventional hot-air drying is expensive. This study evaluated a less energy-intensive technology, the use of desiccants for reducing water weight in pollock skins prior to shipment. To ensure that the functional properties of gelatin obtained from dried pollock skins were not affected during desiccation, gelatins were prepared from each skin-drying treatment and compared with gelatin extracted from air-dried pollock skins. None of the desiccation treatments decreased the gel strength of pollock skin gelatin, nor were there major differences in gelling temperature or viscosity among the gelatin solutions. This suggests that pollock skins can be economically stabilized for transport to a gelatin-processing facility through the use of regenerable desiccants that are already common in the food industry. Pollock skins destined for gelatin production can be stabilized using chemical desiccants prior to shipment. The dehydration process does not harm the functional properties of gelatin, such as gel strength, gelling temperature, and viscosity. This research suggests that fish skins can be economically stabilized for transport to a gelatin-processing facility through the use of regenerable desiccants that are already common in the food industry.


Influence of Dynamic Surface Tension on the Spreading of Surfactant Solution Droplets Impacting onto a Low-Surface-Energy Solid Substrate
We have investigated the impact of single droplets of various surfactant solutions on a low-surface-energy solid substrate using a high-frequency visualization technique (one picture every 100 μs). Whatever the surfactant, the drop spreads and retracts in about 1 s under the action of inertia and capillarity, respectively. During retraction, the capillary waves can be amplified and, in some cases, even yield droplet bouncing. Then, the droplet may slowly spread again due to gravity and the unbalanced capillary forces at the contact line between the droplet and the substrate. During the fast spreading process (2-3 ms), the droplet surface increases by almost one order of magnitude since its shape changes from a sphere to a flat pancake; this causes a strong deviation from thermodynamic equilibrium. The relevant surface property is therefore the dynamic surface tension which we have evaluated using a maximum bubble pressure apparatus. We have shown that droplet retraction is drastically influenced by the adsorption kinetics of the surfactant which limits the return to equilibrium surface tension.


Boosting Photovoltaic Output of Ferroelectric Ceramics by Optoelectric Control of Domains.
Photo-ferroelectric single crystals and highly oriented thin-films have been extensively researched recently, with increasing photovoltaic energy conversion efficiency (from 0.5% up to 8.1%) achieved. Rare attention has been paid to polycrystalline ceramics, potentially due to their negligible efficiency. However, ceramics offer simple and cost-effective fabrication routes and stable performance compared to single crystals and thin-films. Therefore, a significantly increased efficiency of photo-ferroelectric ceramics contributes toward widened application areas for photo-ferroelectrics, e.g., multisource energy harvesting. Here, all-optical domain control under illumination, visible-range light-tunable photodiode/transistor phenomena and optoelectrically tunable photovoltaic properties are demonstrated, using a recently discovered photo-ferroelectric ceramic (K0.49Na0.49Ba0.02)(Nb0.99Ni0.01)O2.995. For this monolithic material, tuning of the electric conductivity independent of the ferroelectricity is achieved, which previously could only be achieved in organic phase-separate blends. Guided by these discoveries, a boost of five orders of magnitude in the photovoltaic output power and energy conversion efficiency is achieved via optical and electrical control of ferroelectric domains in an energy-harvesting circuit. These results provide a potentially supplementary approach and knowledge for other photo-ferroelectrics to further boost their efficiency for energy-efficient circuitry designs and enable the development of a wide range of optoelectronic devices.


Tetra-arsenic tetra-sulfide (As4S 4) promotes apoptosis in retinoid acid -resistant human acute promyelocytic leukemic NB4-R1 cells through downregulation of SET protein.
Tetra-arsenic tetra-sulfide (As4S4) is an arsenic compound with antitumor activity, especially in acute promyelocytic leukemia (APL) that are resistant to retinoic acid (RA). Although recent studies have revealed that the therapeutic action of As4S4 is closely associated with the induction of cellular apoptosis, the exact molecular mechanism underlying this action in RA-resistant APL remains to be clarified. In this study, we found that As4S4-induced apoptosis was accompanied by reduced mRNA and protein expression of SET gene in RA-resistant NB4-R1 cells. Moreover, RNAi knockdown of SET gene further promoted As4S4-induced apoptosis, while SET overexpression recovered the cell viability, suggesting that As4S4 induces apoptosis through the reduction of SET protein in NB4-R1 cells. We also observed that the knockdown of SET gene resulted in the upregulation of protein phosphatase 2 (PP2A) expression and the downregulation of promyelocytic leukemia and retinoic acid receptor α fusion gene (PML-RARα) expression, which were enhanced by As4S4 treatments. By contrast, overexpression of SET gene resulted in PP2A downregulation and PML-RARα upregulation, which were abolished by As4S4 pretreatment. Since PP2A is a proapoptotic factor and PML-RARα is an antiapoptotic factor, our results suggest that As4S4-induced apoptosis in RA-resistant NB4-R1 cells is through the downregulation of SET protein expression, which, in turn, increases PP2A and reduces PML-RARα expressions to lead to cell apoptosis.


Transformation of pristine and citrate-functionalized CeO2 nanoparticles in a laboratory-scale activated sludge reactor.
Engineered nanomaterials (ENMs) are used to enhance the properties of many manufactured products and technologies. Increased use of ENMs will inevitably lead to their release into the environment. An important route of exposure is through the waste stream, where ENMs will enter wastewater treatment plants (WWTPs), undergo transformations, and be discharged with treated effluent or biosolids. To better understand the fate of a common ENM in WWTPs, experiments with laboratory-scale activated sludge reactors and pristine and citrate-functionalized CeO2 nanoparticles (NPs) were conducted. Greater than 90% of the CeO2 introduced was observed to associate with biosolids. This association was accompanied by reduction of the Ce(IV) NPs to Ce(III). After 5 weeks in the reactor, 44 ± 4% reduction was observed for the pristine NPs and 31 ± 3% for the citrate-functionalized NPs, illustrating surface functionality dependence. Thermodynamic arguments suggest that the likely Ce(III) phase generated would be Ce2S3. This study indicates that the majority of CeO2 NPs (>90% by mass) entering WWTPs will be associated with the solid phase, and a significant portion will be present as Ce(III). At maximum, 10% of the CeO2 will remain in the effluent and be discharged as a Ce(IV) phase, governed by cerianite (CeO2).


The first 50Myr of dinosaur evolution: macroevolutionary pattern and morphological disparity.
The evolutionary radiation of dinosaurs in the Late Triassic and Early Jurassic was a pivotal event in the Earth's history but is poorly understood, as previous studies have focused on vague driving mechanisms and have not untangled different macroevolutionary components (origination, diversity, abundance and disparity). We calculate the morphological disparity (morphospace occupation) of dinosaurs throughout the Late Triassic and Early Jurassic and present new measures of taxonomic diversity. Crurotarsan archosaurs, the primary dinosaur 'competitors', were significantly more disparate than dinosaurs throughout the Triassic, but underwent a devastating extinction at the Triassic-Jurassic boundary. However, dinosaur disparity showed only a slight non-significant increase after this event, arguing against the hypothesis of ecological release-driven morphospace expansion in the Early Jurassic. Instead, the main jump in dinosaur disparity occurred between the Carnian and Norian stages of the Triassic. Conversely, dinosaur diversity shows a steady increase over this time, and measures of diversification and faunal abundance indicate that the Early Jurassic was a key episode in dinosaur evolution. Thus, different aspects of the dinosaur radiation (diversity, disparity and abundance) were decoupled, and the overall macroevolutionary pattern of the first 50Myr of dinosaur evolution is more complex than often considered.


Pseudomonas chlororaphis Produces Two Distinct R-Tailocins That Contribute to Bacterial Competition in Biofilms and on Roots.
R-type tailocins are high-molecular-weight bacteriocins that resemble bacteriophage tails and are encoded within the genomes of many Pseudomonas species. In this study, analysis of the P. chlororaphis 30-84 R-tailocin gene cluster revealed that it contains the structural components to produce two R-tailocins of different ancestral origins. Two distinct R-tailocin populations differing in length were observed in UV-induced lysates of P. chlororaphis 30-84 via transmission electron microscopy. Mutants defective in the production of one or both R-tailocins demonstrated that the killing spectrum of each tailocin is limited to Pseudomonas species. The spectra of pseudomonads killed by the two R-tailocins differed, although a few Pseudomonas species were either killed by or insusceptible to both tailocins. Tailocin release was disrupted by deletion of the holin gene within the tailocin gene cluster, demonstrating that the lysis cassette is required for the release of both R-tailocins. The loss of functional tailocin production reduced the ability of P. chlororaphis 30-84 to compete with an R-tailocin-sensitive strain within biofilms and rhizosphere communities. Our study demonstrates that Pseudomonas species can produce more than one functional R-tailocin particle sharing the same lysis cassette but differing in their killing spectra. This study provides evidence for the role of R-tailocins as determinants of bacterial competition among plant-associated Pseudomonas in biofilms and the rhizosphere.IMPORTANCE Recent studies have identified R-tailocin gene clusters potentially encoding more than one R-tailocin within the genomes of plant-associated Pseudomonas but have not demonstrated that more than one particle is produced or the ecological significance of the production of multiple R-tailocins. This study demonstrates for the first time that Pseudomonas strains can produce two distinct R-tailocins with different killing spectra, both of which contribute to bacterial competition between rhizosphere-associated bacteria. These results provide new insight into the previously uncharacterized role of R-tailocin production by plant-associated Pseudomonas species in bacterial population dynamics within surface-attached biofilms and on roots.


Variations in microbicide gel acceptability among young women in the USA and Puerto Rico.
In a multi-site study of vaginal microbicide acceptability conducted with sexually active young women, quantitative assessments revealed significant differences in acceptability by site. Participants in Puerto Rico rated the gel more favourably than mainland US participants in terms of liking the gel and likelihood of future use. To explain these differences, we examined responses to qualitative behavioural assessments. Young women in mainland USA associated gel leakage with uncomfortable sensations experienced during menstruation, while young women in Puerto Rico had positive associations of gel use with douching. These negative or positive associations affected assessments of the gel's physical qualities. In addition, young women's perceptions of primary partners' support for microbicide use influenced sexual satisfaction with the gel and, ultimately, product acceptability. Finally, geographic HIV-risk context contributed to heightened HIV-risk perception, which influenced likelihood of future microbicide use, even for women in stated monogamous relationships. Future microbicide acceptability studies should take into account potential differences in acceptability by site such as HIV-risk perception based on local HIV prevalence, popularity of vaginal hygiene products in a specific area and male attitudes in different cultures concerning women's use of HIV protection strategies.


[Comparative study of inactivated cultured vaccines against tick-borne encephalitis manufactured in Russia and in Austria by the "Immuno" firm].
Inactivated culture vaccine against tick-borne encephalitis (TBE) FSME-Immun-Inject produced in Austria ("Immuno") was compared to vaccine produced in the Institute of Poliomyelitis and viral encephalitis by immunological activity, safety, reactogenicity. In mice, no significant differences in protective activity of the vaccines were found when test-strains were diverse strains of TBE virus. Seroconversion in the sera from the vaccinated two times was not significantly different by the level of antibodies determined for both eastern and western serotypes of TBE virus.


Vapor-phase Raman spectra, theoretical calculations, and the vibrational and structural properties of cis- and trans-stilbene.
The vapor-phase Raman spectra of cis- and trans-stilbene have been collected at high temperatures and assigned. The low-frequency skeletal modes were of special interest. The molecular structures and vibrational frequencies of both molecules have also been obtained using MP2/cc-pVTZ and B3LYP/cc-pVTZ calculations, respectively. The two-dimensional potential map for the internal rotations around the two Cphenyl-C(═C) bonds of cis-stilbene was generated by using a series of B3LYP/cc-pVTZ calculations. It was confirmed that the molecule has only one conformer with C2 symmetry. The energy level calculation with a two-dimensional Hamiltonian was carried out, and the probability distribution for each level was obtained. The calculation revealed that the "gearing" internal rotation in which the two phenyl rings rotate with opposite directions has a vibrational frequency of 26 cm(-1), whereas that of the "antigearing" internal rotation in which the phenyl rings rotate with the same direction is about 52 cm(-1). In the low vibrational energy region the probability distribution for the gearing internal rotation is similar to that of a one-dimensional harmonic oscillator, and in the higher region the motion behaves like that of a free rotor.


Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures.
Young patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide short-term pain relief but are only palliative in nature. Joint replacement, a successful procedure in the older population, is controversial in younger patients, who are less satisfied and experience higher failure rates. Therefore, while traditionally not indicated for the treatment of OA, cartilage repair has become a focus of increased interest due to its potential to provide pain relief and alter the progression of degenerative disease, with the hope of delaying or obviating the need for joint replacement. The field of cartilage repair is seeing the rapid development of new technologies that promise greater ease of application, less demanding rehabilitation and better outcomes. Concurrent procedures such as meniscal transplantation and osteotomy, however, remain of crucial importance to provide a normalized biomechanical environment for these new technologies. Systematic review, Level II.


Assessment of heavy metal accumulation and health risk in three essential edible weeds grown on wastewater irrigated soil.
The main problem facing Egypt recently is the shortage of available water resources. Therefore, farmers resort to use wastewater for irrigation. So, the present work aims to assess the impacts of wastewater irrigation on the productivity of three edible weeds (Cichorium endivia, Sonchus oleraceous and Beta vulgaris) and its effect on the nutritional value of plants and its risk on human health. This study will focus on Shibin Al Kanater region, and the physicochemical characteristics of drainage water, canal water, drainage water-irrigated soils and canal-irrigated soils were estimated. The vegetative and traits of edible weeds were determined including their photosynthetic pigments, organic and inorganic nutrients content, and heavy metals content. The health risk index (HRI) associated with consumption of polluted plants was created using the estimated exposure factor of a crop to the oral reference dosage of the toxic metal. The main results showed that biomass productivity of S. oleraceous, B. vulgaris and C. endivia increased due to drainage water irrigation with increasing percentage as 27.9, 19.6, and 19.1%, respectively. Irrigation with drainage water significantly increased the photosynthetic pigments of edible weeds. Irrigation with drainage water increased carbohydrate content, crude protein, total soluble sugar, and gross energy in all studied weeds. C. endivia, S. oleraceus and B. vulgaris plants irrigated with canal and drainage water could accumulate Fe, Zn, Cu, and Co in their roots. C. endivia, S. oleraceus and B. vulgaris plants irrigated with canal water indicated HRI more than the unit for Mn, Cu, Pb, and Cd. This research advises that regulation be put in place to prohibit irrigation using untreated drainage and to restrict the discharge of industrial, domestic, and agricultural wastewater into irrigation canals.


Socioeconomic Status and Childhood Cancer Incidence: A Population-Based Multilevel Analysis.
The etiology of childhood cancers remains largely unknown, especially regarding environmental and behavioral risk factors. Unpacking the association between socioeconomic status (SES) and incidence may offer insight into such etiology. We tested associations between SES and childhood cancer incidence in a population-based case-cohort study (source cohort: Minnesota birth registry, 1989-2014). Cases, ages 0-14 years, were linked from the Minnesota Cancer Surveillance System to birth records through probabilistic record linkage. Controls were 4:1 frequency matched on birth year (2,947 cases and 11,907 controls). We tested associations of individual-level (maternal education) and neighborhood-level (census tract composite index) SES using logistic mixed models. In crude models, maternal education was positively associated with incidence of acute lymphoblastic leukemia (odds ratio (OR) = 1.10, 95% confidence interval (CI): 1.02, 1.19), central nervous system tumors (OR = 1.12, 95% CI: 1.04, 1.21), and neuroblastoma (OR = 1.15, 95% CI: 1.02, 1.30). Adjustment for established risk factors-including race/ethnicity, maternal age, and birth weight-substantially attenuated these positive associations. Similar patterns were observed for neighborhood-level SES. Conversely, higher maternal education was inversely associated with hepatoblastoma incidence (adjusted OR = 0.70, 95% CI: 0.51, 0.98). Overall, beyond the social patterning of established demographic and pregnancy-related exposures, SES is not strongly associated with childhood cancer incidence.


Type 2 diabetic patient-centered care.
The prevalence of diabetes mellitus has increased worldwide including Thailand. Management of diabetes should be considered biological and psychosocial. Patient-centered care was applied in the present study. Patient-centered care is a process interaction between the clinician and the patient. It refers to the clinician's behavioral skill in the consultation. Patient-centered care customizes seeking and accepting the patient's ideas, seeking and giving recognition and encouragement, treatment recognition and decision making in response to the individual patient's perspective. To evaluate the efficacy of patient-centered care on type 2 diabetes mellitus. Their fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), eating and exercise behavior, compliance, symptoms of diabetes as well as satisfaction were compared before and after the intervention. The quasi-experimental design (controlled before and after intervention) was conducted among 78 patients with type 2 diabetes mellitus who regularly attended the outpatient clinic, Family Medicine Department, whose FPG was more than 150 mg/dL, non pregnant, could communicate well in Thai and had no other complications. The patients were required to follow on Wednesday morning every 6-10 weeks for one year. A group of 6-10 patients was appointed in each visit. The six interconnecting components of patient-centered care were applied. (1) The patients and the researchers were introduced to each other to enhance the relationship between the patients, doctors and researchers. (2) In each visit, by using a group process and individual approach, the authors explored, assessed and analyzed both the disease, the illness (patient's ideas, feelings, expectations and functions), drug compliance, eating and exercise behavior. (3) The patient's life, family history, psychological and social behaviors were emphasized. (4) Setting the goals of FPG level that is achievable and agreeable to both the physician and patients. (5) Each patient was required to attend both nutrition and exercise education workshops. (6) Self care and self records on food items as well as nutrition and exercise practice were emphasized in order to incorporate them into their lifestyle. There were 53 females (67.9%) and 25 males (32.1%). Average age was 57.2 years. Diabetes duration was 6.75 +/- 5.45 years. Mean FPG of overall subjects decreased 43.07 +/- 76.32 mg/dL. About 16.44% had FPG below 126 mg/dL. 55.13% retained the same hypoglycemic medications, 10.5% had decreased dosage. Amongst 33 subjects (42.3%) who completed the program, FPG decreased 73.58 +/- 70.99 mg/dL (p < 0. 000). HbA1c decreased 0. 92 +/- 1.41% (p = 0. 001). Eating behavior (p < 0.000) and exercise behavior (p < 0.05) were better. Symptoms of diabetes were improved. Patient's satisfaction indicated that they had a better understanding of the disease and illness. They were eager to share their experiences with others and able to develop a relationship with the health care team. Amongst 45 patients (57.7%) who partially followed the program, FPG decreased 39.55 +/- 68.54 mg/dL (p = 0. 001). Glycemic control of type 2 diabetes subjects was improved by patient-centered care. Eating and exercise behaviors, compliance, symptoms of diabetes were better. This pilot study showed that the health status was improved not only by the biological indicators but also by behavior. The present study provided a beneficial impact on improving the health status of type 2 diabetes.


Inability to move one's face dampens facial expression perception.
Humans rely heavily on facial expressions for social communication to convey their thoughts and emotions and to understand them in others. One prominent but controversial view is that humans learn to recognize the significance of facial expressions by mimicking the expressions of others. This view predicts that an inability to make facial expressions (e.g., facial paralysis) would result in reduced perceptual sensitivity to others' facial expressions. To test this hypothesis, we developed a diverse battery of sensitive emotion recognition tasks to characterize expression perception in individuals with Moebius Syndrome (MBS), a congenital neurological disorder that causes facial palsy. Using computer-based detection tasks we systematically assessed expression perception thresholds for static and dynamic face and body expressions. We found that while MBS individuals were able to perform challenging perceptual control tasks and body expression tasks, they were less efficient at extracting emotion from facial expressions, compared to matched controls. Exploratory analyses of fMRI data from a small group of MBS participants suggested potentially reduced engagement of the amygdala in MBS participants during expression processing relative to matched controls. Collectively, these results suggest a role for facial mimicry and consequent facial feedback and motor experience in the perception of others' facial expressions.


Effects of gamma radiation on the electrical properties of InAs/InGaAs quantum dot-based laser structures grown on GaAs and Si substrates by molecular beam epitaxy.
This study investigates the impact of gamma radiation on the electrical properties of InAs/InGaAs quantum dot-based laser structures grown on both GaAs (Sample A) and Si (Sample B) substrates using molecular beam epitaxy. The research explores the electrical characteristics of the lasers before and after being exposed to gamma radiation employing current-voltage (I-V), capacitance-voltage (C-V), deep level transient spectroscopy (DLTS) and Laplace DLTS techniques. The results show that the electrical properties of the lasers change due to gamma radiation exposure, and the extent of the change depends on the substrate used for growth. The I-V results revealed that the ideality factor (n) and built-in voltage were increased in Sample A and Sample B after radiation. Nonetheless, the series resistance (Rs) at room temperature decreased in both samples after radiation. Overall, this study provides valuable insights into the effects of gamma radiation on the electrical properties of InAs/InGaAs quantum dot lasers and highlights the importance of considering substrate materials in the design of radiation-hardened electronic devices.


Outcome evaluation of a thoracoscopic pericardial window procedure or subtotal pericardectomy via thoracotomy for the treatment of pericardial effusion in dogs.
To evaluate the disease-free interval (DFI) and median survival time (MST) in dogs with idiopathic and neoplastic pericardial effusion surgically treated by a thoracoscopic pericardial window procedure or subtotal pericardectomy via thoracotomy and to compare DFI and MST in dogs with and without a mass on preoperative echocardiography that underwent either surgical technique. Retrospective cohort study. 58 dogs with pericardial effusion. Medical records between 1985 and 2010 were evaluated. Dogs were included in the study if they had confirmed pericardial effusion and underwent a thoracoscopic pericardial window procedure or subtotal pericardectomy via thoracotomy. Clinical signs of dogs at initial evaluation were similar, with the exception of lethargy, between dogs treated by subtotal pericardectomy via thoracotomy or the pericardial window procedure. Dogs with idiopathic pericardial effusion that underwent the thoracoscopic pericardial window procedure had significantly shorter DFI and MST than did those treated by subtotal pericardectomy via thoracotomy. For neoplastic pericardial effusion, DFI and MST were not significantly different between dogs treated with either surgical technique. Dogs with idiopathic pericardial effusion treated with a subtotal pericardectomy via thoracotomy had a significantly longer DFI and MST, compared with dogs treated by the thoracoscopic pericardial window procedure. This difference in outcome may be related to inaccuracy of the initial diagnosis or ineffectiveness of the pericardial window to palliate the signs of idiopathic pericardial effusion long term.


Reliability of human cortical organoid generation.
The differentiation of pluripotent stem cells in three-dimensional cultures can recapitulate key aspects of brain development, but protocols are prone to variable results. Here we differentiated multiple human pluripotent stem cell lines for over 100 d using our previously developed approach to generate brain-region-specific organoids called cortical spheroids and, using several assays, found that spheroid generation was highly reliable and consistent. We anticipate the use of this approach for large-scale differentiation experiments and disease modeling.


[The role of trace elements concerning to disorders of lipid metabolism].
Modified LDL, caused by many factors, is associated with increased atherogenisity. In many modified LDLs, it is recognized that LDL oxidation occurs in vivo, and oxidized LDL demonstrates enhanced cellular uptake by macrophage scavenger receptor, foam cell formation. In vitro, iron and zinc are necessary for oxidized LDL and lipid peroxisides, and considering these elements to participate in vivo, particularly hyperlipidemia. In fact, hyperlipidemia with high serum levels iron or zinc concentration is a risk factor of coronary heart disease. Further, the possibility of selenium insufficiency accelerated lipid peroxisides in vivo, because glutathione peroxidase (GSHPx), the antioxidant effect, includes selenium, and GSHPx hyperproduction are recognized in atherosclerotic lesion. It is known that oxidized LDL are more excessive in hyperlipidemia, so hyperlipidemia may suffer more from trace element status in vivo. Enzymes and hormones, influencing lipid metabolism, are necessary for many trace elements their activation. Trace elements may therefore, be important in several stage of lipid metabolism.


[Enzymatic production of superoxide by human polymorphonuclear leukocytes in burns].
Production of superoxide anion by polymorphonuclear leukocytes (PMNL) was studied in donors and patients with burns. N-formyl-L-Met-L-Leu-L-Phe (FMLP) was used as an activator of PMNL. Evaluation in production of superoxide anion, caused by the activating effect of FMLP, proved to be useful as a diagnostic and prognostic criterion. 56 preparations of blood were studied in 21 patients with burns within the periods of acute burns toxemia, burns septicotoxemia and convalescence. Superoxide anion generating activity correlated with the disease severity: content of superoxide anion was distinctly decreased within the period of sepsis development. At the same time, complex treatment of the patients, involving step-by-step autodermoplastics, antibacterial preparations and immunotherapy, enabled to restore the superoxide anion production up to normal values. Evaluation of the superoxide anion generating activity by PMNL in the patients with severe forms of burns enabled to estimate the state of cell immunity in the patients depending on severity of burns trauma, period of burn disease and adequacy of the treatment applied.


Salt, blood pressure and the renin-angiotensin system.
Much evidence from epidemiological, migration, intervention, animal and genetic studies suggests that salt intake plays an important role in regulating blood pressure (BP). At the same time, many clinical trials have shown that reducing salt intake lowers BP. However, the magnitude of the fall in BP for a given reduction in salt intake varies with age, ethnic group and BP levels. This difference has been suggested to be related to the responsiveness of the renin-angiotensin system (RAS). However, the sympathetic nervous system, the kallikrein-kinin system, the nitric oxide system, and many eicosanoids may also play a role. In this article, we address the important role of the RAS in determining the fall in BP with salt reduction.


Phylogenetic analysis of the 16S rDNA of the cytoplasmic bacterium Wolbachia from the novel host Folsomia candida (Hexapoda, Collembola) and its implications for wolbachial taxonomy.
Wolbachia pipientis are intracellular, transovarially inherited alpha-Proteobacteria in invertebrates. Four major Wolbachia groups exist: A, B (contained in divergent arthropods), C and D (harbored by Nematoda). By means of transmission electron microscopy, we observed Wolbachia-like bacteria in a primitive insect, Folsomia candida (Hexapoda, Collembola, Isotomidae). 16S rDNA analysis proved them to constitute a novel lineage, henceforth named group E, in the wolbachial phylogenetic tree. It shares 97.8% 16S rDNA homology with its nearest neighbors, groups A and B, which diverged from it more recently. We propose (i) a new taxon E for the Wolbachia strain in F. candida, (ii) that the single-described Wolbachia pipientis fall apart into at least three species: C, D and the large E-A-B complex. F. candida's group E Wolbachia rekindle the question about invasive capacities of free-living ancestral wolbachiae and horizontal transfer.


Sustained impact of short-term international medical mission trips: resident perspectives.
To assess perspectives of residents: (1) who participated in short-term international medical mission trips (STIMMTs) as medical students regarding impact of the experiences on their professional development; and (2) who did not participate in STIMMTs regarding barriers to participation. Three hundred seventy-nine residents from 16 programs at two Florida institutions completed surveys requesting Participant and Trip Details and Impact of Participation (including items rating learning, cultural competency, and social responsibility). One hundred thirty-one residents participated in at least one STIMMT. They identified improved adaptability to new healthcare settings, communication with patients and professionals from different backgrounds, and appreciation for the impact of culture on health as positive outcomes. Leading barriers to STIMMT participation included cost, timing, and lack of availability. Years after participation in STIMMTs, residents perceived sustained benefits in cultural competency, communication skills, adaptability, and desire for service. Institutions may consider facilitating STIMMTs as one way to address standards specified by accrediting authorities to provide training in cultural competency, social responsibility, altruism, and understanding the importance of caring for underserved populations. Barriers to STIMMT participation may be reduced through availability of institution-sponsored scholarships, identification of external grant and scholarship opportunities, and coordination of fund-raising activities.


Development and psychometric evaluation of an instrument to assess venous leg ulcer lifestyle knowledge among nurses.
Development and psychometric testing of an instrument to assess venous leg ulcer lifestyle knowledge. Nurses often lack knowledge to provide adequate leg ulcer advice. No valid and reliable instruments are available to assess knowledge on venous leg ulcer advice among nurses. The instrument was developed based on a literature review and patient cases. Content validity was evaluated in a Delphi procedure by nine leg ulcer experts. Item-analysis, construct validity and stability were assessed. A sample of 350 nurses and student nurses participated. Data collection took place between February and April 2009. The instrument included four topics: (1) Compression therapy, (2) Physical activity/leg exercises, (3) Leg elevation and (4) Pain management. Multiple-choice questions were developed to assess factual knowledge. Patient cases were developed to assess more complex cognitive skills. Content validity was established. The quality of the response alternatives varied between 0.01 and 0.68. The difficulty index for questions evaluating factual knowledge ranged from 0.12 to 0.78. Patient cases' questions had a difficulty index between 0.07 and 0.60. The score of participants with (theoretically expected) more expertise was significantly higher than the score of participants with (theoretically expected) less expertise. The intraclass correlation coefficients ranged between 0.71 and 0.77. Eleven questions had moderate kappa-values (0.41-0.60), and in eight questions, there was fair agreement (0.30-0.40). An instrument with an acceptable content validity and construct validity was developed. The instrument can be applied in nursing education, nursing practice and nursing research to evaluate venous leg ulcer advice knowledge.


Bio-SCAN: A CRISPR/dCas9-Based Lateral Flow Assay for Rapid, Specific, and Sensitive Detection of SARS-CoV-2.
Simple, rapid, specific, and sensitive point-of-care detection methods are needed to contain the spread of SARS-CoV-2. CRISPR/Cas9-based lateral flow assays are emerging as a powerful alternative for COVID-19 diagnostics. Here, we developed Bio-SCAN (biotin-coupled specific CRISPR-based assay for nucleic acid detection) as an accurate pathogen detection platform that requires no sophisticated equipment or technical expertise. Bio-SCAN detects the SARS-CoV-2 genome in less than 1 h from sample collection to result. In the first step, the target nucleic acid sequence is isothermally amplified in 15 min via recombinase polymerase amplification before being precisely detected by biotin-labeled nuclease-dead SpCas9 (dCas9) on commercially available lateral flow strips. The resulting readout is visible to the naked eye. Compared to other CRISPR-Cas-based pathogen detection assays, Bio-SCAN requires no additional reporters, probes, enhancers, reagents, or sophisticated devices to interpret the results. Bio-SCAN is highly sensitive and successfully detected a clinically relevant level (4 copies/μL) of synthetic SARS-CoV-2 RNA genome. Similarly, Bio-SCAN showed 100% negative and 96% positive predictive agreement with RT-qPCR results when using clinical samples (86 nasopharyngeal swab samples). Furthermore, incorporating variant-specific sgRNAs in the detection reaction allowed Bio-SCAN to efficiently distinguish between the α, β, and δ SARS-CoV-2 variants. Also, our results confirmed that the Bio-SCAN reagents have a long shelf life and can be assembled locally in nonlaboratory and limited-resource settings. Furthermore, the Bio-SCAN platform is compatible with the nucleic acid quick extraction protocol. Our results highlight the potential of Bio-SCAN as a promising point-of-care diagnostic platform that can facilitate low-cost mass screening for SARS-CoV-2.


bollito: a flexible pipeline for comprehensive single-cell RNA-seq analyses.
bollito is an automated, flexible and parallelizable computational pipeline for the comprehensive analysis of single-cell RNA-seq data. Starting from FASTQ files or preprocessed expression matrices, bollito performs both basic and advanced tasks in single-cell analysis integrating >30 state-of-the-art tools. This includes quality control, read alignment, dimensionality reduction, clustering, cell-marker detection, differential expression, functional analysis, trajectory inference and RNA velocity. bollito is built using the Snakemake workflow management system, which easily connects each execution step and facilitates the reproducibility of results. bollito's modular design makes it easy to incorporate other packages into the pipeline enabling its expansion with new functionalities. Source code is freely available at https://gitlab.com/bu_cnio/bollito under the MIT license. Supplementary data are available at Bioinformatics online.


Estimated incidence of erythema migrans in five regions of France and ecological correlations with environmental characteristics.
While several studies conducted on Lyme borreliosis (LB) risk in the United States showed an association with environmental characteristics, most of European studies considered solely the effect of climate characteristics. The aims of this study were to estimate incidence of erythema migrans (EM) in five regions of France and to analyze associations with several environmental characteristics of the place of residence. LB surveillance networks of general practitioners (GPs) were set up for a period of 2 years in five regions of France. Participating GPs reported all patients with EM during the study period. Data were pooled according to a standardized EM case definition. For each area with a participating GP, age-standardized incidence rates and ratios were estimated. Associations with altitude, indicators of landscape composition, and indicators of landscape configuration were tested with multivariate Poisson regression. Standardized estimated incidence rates of EM per 10(5) person-years were 8.8 [95% confidence interval (CI)=7.9-9.7] in Aquitaine, 40.0 (95% CI 36.4-43.6) in Limousin, 76.0 (95% CI 72.9-79.1) in the three participating départements of Rhône-Alpes, 46.1 (95% CI 43.0-49.2) in Franche-Comté, and 87.7 (95% CI 84.6-90.8) in Alsace. In multivariate analysis, age-adjusted incidence rates increased with the altitude (p<0.0001) and decreased with forest patch density (p<0.0001). The marked variations in EM risk among the five regions were partly related to differences in landscape and environmental characteristics. The latter may point out potential risk areas and provide information for targeting preventive actions.


Heterochromatin protein 1a is required for an open chromatin structure.
The Drosophila melanogaster fourth chromosome contains interspersed domains of active and repressive chromatin. We investigated a stock harboring a silenced transgene inserted into Dyrk3 and near Caps-two expressed genes on chromosome four. In an HP1a-deficient background, transgene expression was activated while, paradoxically, expression of Dyrk3 and Caps was reduced. We found that the promoters of Dyrk3 and Caps contained DNase I hypersensitive sites but also possessed methylated histone H3 and HP1a, marks of repressive chromatin. In HP1a-deficient flies, the Dyrk3 and Caps promoters displayed diminished accessibility to nuclease digestion, revealing a surprising role for HP1a in opening chromatin.


Viral gene transfer of dominant-negative Kv4 construct suppresses an O2-sensitive K+ current in chemoreceptor cells.
Hypoxia initiates the neurosecretory response of the carotid body (CB) by inhibiting one or more potassium channels in the chemoreceptor cells. Oxygen-sensitive K(+) channels were first described in rabbit CB chemoreceptor cells, in which a transient outward K(+) current was reported to be reversibly inhibited by hypoxia. Although progress has been made to characterize this current with electrophysiological and pharmacological tools, no attempts have been made to identify which Kv channel proteins are expressed in rabbit CB chemoreceptor cells and to determine their contribution to the native O(2)-sensitive K(+) current. To probe the molecular identity of this current, we have used dominant-negative constructs to block the expression of functional Kv channels of the Shaker (Kv1.xDN) or the Shal (Kv4.xDN) subfamilies, because members of these two subfamilies contribute to the transient outward K(+) currents in other preparations. Delivery of the constructs into chemoreceptor cells has been achieved with adenoviruses that enabled ecdysone-inducible expression of the dominant-negative constructs and reporter genes in polycistronic vectors. In voltage-clamp experiments, we found that, whereas adenoviral infections of chemoreceptor cells with Kv1.xDN did not modify the O(2)-sensitive K(+) current, infections with Kv4.xDN suppressed the transient outward current in a time-dependent manner, significantly depolarized the cells, and abolished the depolarization induced by hypoxia. Our work demonstrate that genes of the Shal K(+) channels underlie the transient outward, O(2)-sensitive, K(+) current of rabbit CB chemoreceptor cells and that this current contributes to the cell depolarization in response to low pO(2).


Trends in the maternal investment of harbour porpoises are uncoupled from the dynamics of their primary prey.
Harbour porpoises in the Bay of Fundy and Gulf of Maine feed primarily on Atlantic herring. Herring stocks have undergone dramatic fluctuations in abundance over the past three decades due to changes in fishing intensity. In order to understand the effects of these changes in prey abundance on the patterns of maternal investment, I examined interdecadal variation in the size of porpoise calves measured in August prior to weaning. Female harbour porpoises exhibited significant variation in maternal investment between 1970 and 1999. During the 1980s, females consumed more herring and produced larger calves. Surprisingly, however, this increased maternal investment occurred during the period of lowest prey abundance, perhaps because the herring stock assessment does not reflect the availability or quality of prey to female porpoises.


The ubiquitin ligase c-CBL is expressed in undifferentiated marmoset monkey pluripotent stem cells but is not a general stem cell marker.
The protein c-CBL is a ubiquitin ligase. It catalyzes the last step of the transfer of ubiquitin to target proteins. Upon completion of polyubiquitination, the target proteins are degraded. Clinically, it is important that c-CBL is mutated in a subset of patients who develop myeloid malignancies, which are diseases of the hematopoietic stem or progenitor cells. c-CBL has also been shown to be expressed by human spermatogonia. The whole spermatogonial cell population possesses a subset that comprises also the spermatogonial stem cells. Based on these findings we hypothesized that c-CBL might be a general stem cell marker. To test this, we first validated the antibody using marmoset bone marrow and adult testis. In both tissues, the expected staining pattern was observed. Western blot analysis revealed only one band of the expected size. Then, we examined the expression of c-CBL in marmoset monkey embryonic stem (ES) cells, induced pluripotent stem (iPS) cells and adult stem cells. We found that c-CBL is strongly expressed in undifferentiated marmoset iPS cells and ES cells. However, adult stem cells in the gut and the stomach did not express c-CBL, indicating that c-CBL is not a general stem cell marker. In summary, c-CBL is strongly expressed in pluripotent stem cells of the marmoset monkey as well as in selected adult stem cell types. Future studies will define the function of c-CBL in pluripotent stem cells.


Prior treatment with captopril attenuates carbon tetrachloride-induced liver injury in mice.
The present investigation focused on the possible hepatoprotective potential of captopril on carbon tetrachloride (CCl4)-induced acute liver injury in mice. Twenty-four hours after a single intraperitoneal injection of CCl4 (20 microl/Kg), hepatotoxicity was evidenced in the serum by elevated levels of aspartate transaminase (AST; EC: 220.127.116.11), alanine transaminase (ALT; EC: 126.96.36.199) and lactate dehydrogenase (LDH; EC: 18.104.22.168) and in the liver by depleted level of reduced glutathione (GSH), enhanced activity of glutathione peroxidase (GSH-Px; EC: 1I.11.1.9) and elevated level of lipid peroxides (LP). Captopril was given orally at three dose levels viz., 10, 25 and 50 mg/Kg/day for three consecutive days before subjecting the animals to the hepatotoxin. With the exception of the lowest dose namely, 10 mg/Kg/day, captopril afforded protection against CCl4-induced hepatotoxicity to different extents. Thus, the elevated activities of the enzymes AST, ALT, LDH and GSH-Px as well as the enhanced lipid peroxidation were markedly reduced below those elicited by the hepatotoxin, reaching values closer to the control, though still statistically higher. Captopril, however, did not ameliorate the depletion of GSH produced by CCl4. The data reported herein reveal a protective potential of captopril against the acute hepatotoxicity induced by CCl4 in mice. This hepatoprotection could be attributed, at least in part, to the free radical scavenging properties of the drug.


Relation of Pretransplant Peak Oxygen Consumption to Outcomes After Heart Transplantation.
Peak exercise oxygen consumption (pVO2) is an important predictor of prognosis in patients with heart failure (HF). The association between pretransplant pVO2 and post-transplantation outcomes in HF patients has not been previously studied. We identified adult OHT recipients with available pVO2 in the United Network for Organ Sharing registry (2000 to 2015). Patients were divided into 3 categories using Weber classification: class B (pVO2 16 to 20 ml/kg/min), class C (pVO2 10 to 16 ml/kg/min), and class D (pVO2 <10 ml/kg/min). Postoperative outcomes (mortality, renal failure, rejection) were compared between the groups. A total of 9,623 patients were included in this analysis; the mean age was 54 ± 11 years, 74% were male, 75% were white and 59% had nonischemic etiology of HF. The mean pVO2 was 11.7 ± 3.6 ml/kg/min: 1,202 (12.5%) in class B, 6,055 (62.9%) in class C, and 2,366 (24.6%) were in class D. At a median follow-up of 6.1 years, 2,730 (28.4%) died. Post-transplantation survival decreased with decreasing pVO2; 1 and 5-year survival: B (92%, 80%), C (90%, 79%), and D (87%, 75%), p <0.001 by log-rank. After multiple adjustments, patients in class D had significantly higher post-transplantation mortality compared with class C (Hazard Ratio (HR) 1.21 [1.03 to 1.43], p = 0.02). When analyzed as a continuous variable, each 1 ml/kg/min increase in pVO2 was associated with 2% decrease in mortality during follow-up (adjusted HR 0.98 [0.96 to 0.99], p <0.001). Patients in class D had significantly prolonged (>14 days) hospitalization (adjusted Odds Ratio (OR) 1.42 [1.20 to 1.68], p <0.001) and a trend toward increased need for dialysis (adjusted OR 1.36 [1.00 to 1.84], p = 0.05) compared with patients in class B. In this large cohort, lower pretransplant pVO2 was associated with greater mortality and morbidity after OHT. These results suggest that earlier transplantation might improve post-transplantation outcomes in advanced HF patients.


Basic helix-loop-helix transcription factor heterocomplex of Yas1p and Yas2p regulates cytochrome P450 expression in response to alkanes in the yeast Yarrowia lipolytica.
The expression of the ALK1 gene, which encodes cytochrome P450, catalyzing the first step of alkane oxidation in the alkane-assimilating yeast Yarrowia lipolytica, is highly regulated and can be induced by alkanes. Previously, we identified a cis-acting element (alkane-responsive element 1 [ARE1]) in the ALK1 promoter. We showed that a basic helix-loop-helix (bHLH) protein, Yas1p, binds to ARE1 in vivo and mediates alkane-dependent transcription induction. Yas1p, however, does not bind to ARE1 by itself in vitro, suggesting that Yas1p requires another bHLH protein partner for its DNA binding, as many bHLH transcription factors function by forming heterodimers. To identify such a binding partner of Yas1p, here we screened open reading frames encoding proteins with the bHLH motif from the Y. lipolytica genome database and identified the YAS2 gene. The deletion of the YAS2 gene abolished the alkane-responsive induction of ALK1 transcription and the growth of the yeast on alkanes. We revealed that Yas2p has transactivation activity. Furthermore, Yas1p and Yas2p formed a protein complex that was required for the binding of these proteins to ARE1. These findings allow us to postulate a model in which bHLH transcription factors Yas1p and Yas2p form a heterocomplex and mediate the transcription induction in response to alkanes.


Detecting nuisance species using NGST: Methodology shortcomings and possible application in ballast water monitoring.
Detecting the presence of potential invasive species in ballast water is a priority for preventing their spread into new environments. Next generation sequencing technologies are being increasingly used for exploring and assessing biodiversity from environmental samples. Here we apply high throughput sequencing from DNA extracted from ballast water (BW) samples employing two different platforms, Ion Torrent and 454, and compare the putative species catalogues from the resulting Operational Taxonomic Units (OTU). Water samples were taken from the RV Polastern ballast tank in five different days between the second and the twentieth navigation day. Pronounced decrease of oxygen concentration and increase of temperature occurred in the BW during this time, coincident with a progressively higher proportion of unassigned OTU and short reads indicating DNA degradation. Discrepancy between platforms for species catalogues was consistent with previously published bias in AT-rich sequences for Ion Torrent platform. Some putative species detected from the two platforms increased in frequency during the Polarstern travel, which suggests they were alive and therefore tolerant to adverse conditions. OTU assigned to the highly invasive red alga Polysiphonia have been detected at low but increasing frequency from the two platforms. Although in this moment NGST could not replace current methods of sampling, sorting and individual taxonomic identification of BW biota, it has potential as an exploratory methodology especially for detecting scarce species.


Submucosal fibroids and the relation to heavy menstrual bleeding and anemia.
The objective of the study was to determine the contribution of submucosal fibroids (SMs) to heavy menstrual bleeding (HMB) and anemia among women with HMB. Our retrospective study included premenopausal women who presented to a tertiary care center for HMB between January 2007 and October 2011. All women in this cohort underwent flexible office hysteroscopy (n = 1665) and 259 (15.6%) had SMs. We also reviewed the clinical ultrasounds (n = 914) from these women to determine whether SMs (n = 148) or any fibroids (n = 434) were present in the uterus. Clinical evaluation of bleeding included hemoglobin and pictorial blood loss assessment charts. In our cohort, hysteroscopically diagnosed SMs were associated with significantly lower hemoglobin (adjusted difference -0.35 g/dL; 95% confidence interval [CI], -0.56 g/dL to -0.13g/dL) and higher risk of anemia (odds ratio [OR], 1.46; 95% CI, 1.04-2.03). Women with ultrasound-diagnosed SMs had lower hemoglobin and anemia, but results were not significant once adjusted for confounders (hemoglobin: adjusted difference -0.21 g/dL; 95% CI, -0.47g/dL to 0.06 g/dL; and anemia: OR, 1.28; 95% CI, 0.82-1.97). Ultrasound-diagnosed fibroids anywhere in the uterus were not associated with hemoglobin (P = .7) or anemia (P = .8). Self-reported pictorial blood loss assessment charts scores did not differ between women with and without fibroids diagnosed by either hysteroscopy or ultrasound (P = .4 and P = .9, respectively). SMs were related to lower hemoglobin and higher risk of anemia but not self-reported bleeding scores. Diagnostic modality was important: hysteroscopically diagnosed SMs had lower hemoglobin and more anemia than ultrasound-diagnosed SMs. This may explain the inconsistent results in the literature.


Transient Cell Membrane Disruptions induce Calcium Waves in Corneal Keratocytes.
The purpose of this study was to determine if transient cell membrane disruptions (TPMDs) in single keratocytes can trigger signaling events in neighboring keratocytes. Stromal cells were cultured from human corneas (HCSC) and mouse corneas (MCSC). TPMDs were produced using a multiphoton microscope in Cal-520-AM loaded cells. TPMD-induced calcium increases (Ca++i) were measured in Ca++-containing and Ca++-free solutions containing thapsigargin, ryanodine, BAPTA-AM, 18-α-glycyrrhetinic acid (18α-GA), apyrase, BCTC, AMG 9810, or AMTB. Fluorescence intensity was recorded as the number of cells responding and the area under the fluorescence versus time curve. The maximum distance of responding neighboring cells in ex vivo human corneas was measured. Connexin 43 protein in HCSC and MCSC was examined using immunofluorescence staining, and corneal rubbing was applied to confirm whether TPMDs occur following mechanical manipulation. Our results demonstrate that single cell TPMDs result in Ca++ waves in neighboring keratocytes both in culture and within ex vivo corneas. The source of Ca++ is both intra-and extra-cellular, and the signal can be mediated by ATP and/or gap junctions, and is species dependent. Stromal rubbing confirmed that TPMDs do occur following mechanical manipulation. Keratocyte TPMDs and their associated signaling events are likely common occurrences following minor or major corneal trauma.


A Case of Tuberculous Uveitis Complicated by Myelodysplastic Syndrome.
Background: Recently, the incidence of tuberculosis in compromised hosts has increased.Case: A 52-year-old man suffering from myelodysplastic syndrome (MDS) had pulmonary tuberculosis. On June 22, 1996, we found a disc-sized choroidal lesion with milky appearance on the paramacular in his right eye. After 1 month, a similar choroidal lesion was found near the disc in the same eye. In spite of chemotherapy for MDS and antituberculosis medications, those choroidal lesions gradually enlarged. In November, satellite lesions were found around them. Some retinal exudates and hemorrhage were also detected in both eyes. He died on April 6, 1997. We found Langhan's giant cells in the choroid on the specimen of his eyes. So we judged the choroidal lesions to be tuberculous uveitis.Conclusion: This case showed choroidal tuberculosis and choroidal miliary tuberculosis in the same eye that were resistant to medications. We thought resistance to medication was due to destruction of the immune system by MDS.


Prolonged Exclusive Breastfeeding Through Peer Support: A Cohort Study From a Community Outreach Project in Swaziland.
Swaziland faces great public health challenges, including suboptimal breastfeeding practices and the world's highest prevalence of HIV. The objective of this study was to estimate neonatal and infant mortality rate and rate of exclusive breastfeeding for clients enrolled in a community-based peer support project in peri-urban areas of Swaziland. The intervention builds on the so called "Philani-model" with Mentor Mothers in the community under high level of supervision. Cohort data was collected from journals kept by the Mentor Mothers. Kaplan-Meier and Cox regression were used to analyse data. Neonatal and infant mortality were estimated to 15 respectively 57 per 1000 live births. High level of social vulnerability was associated with risk of neonatal mortality (HR 1.12, CI 95 % 1.01-1.24) while the mother's positive HIV status was associated with infant mortality (HR 2.05, CI 95 % 1.15-3.65). More visits by a Mentor Mother could not be shown to result in lower mortality. The chance to practice exclusive breastfeeding for 6 months was estimated to 50 %. The risk of discontinuing exclusive breastfeeding before 6 months was lower for mothers being unemployed (HR 0.55, CI 95 % 0.44-0.69) or socially vulnerable (HR 0.95, CI 95 % 0.92-0.99) and higher for mothers being HIV positive (HR 1.22, CI 95 % 1.01-1.48). Receiving at least four visits by a Mentor Mother during pregnancy decreased the risk of discontinuing exclusive breastfeeding prematurely (HR 0.82, CI 95 % 0.67-0.99). Peer support with Mentor Mothers thus had a positive impact on exclusive breastfeeding rates in this disadvantaged population.


Phenotypic spectrum of 45,X/46,XY males with a ring Y chromosome and bilaterally descended testes.
To characterize the phenotypic spectrum of males with bilaterally descended testes and a 45,X/46,X,(r)Y karyotype. Retrospective review of patient records; cytogenetic and molecular analysis. Tertiary medical center setting. Five males, two prepubertal and three postpubertal, with a 45,X/46,X(r)Y karyotype and bilaterally descended testes. Linear growth evaluation, testicular endocrine and exocrine studies, cytogenetic and molecular analysis on each patient. Clinical phenotype versus genotype. Both prepubertal males had short stature and low testosterone. All three adults had normal puberty and normal testosterone levels. Two of the adults (one with short stature and one with normal stature) had elevated gonadotropins and azoospermia. The third adult had normal stature, severe oligospermia, normal gonadotropins, and normal serum testosterone. The phenotypic spectrum of males with a 45,X/46,X(r)Y karyotype and bilaterally descended testes varies greatly from males with short stature and spermatogenic failure to males without short stature and less severely affected spermatogenesis. This broad spectrum of phenotypic findings needs to be taken into account when the clinical geneticist encounters a prenatal diagnosis of a 45,X/46,X(r)Y karyotype. This information will also be helpful for pediatric and reproductive endocrinologists in counseling males with bilaterally descended testes and a 45,X/46,X(r)Y karyotype.


[Clinical aspects and differential diagnosis of chronic pancreatitis. Emphasis on the long term course in 258 patients].
Three typical clinical patterns can be distinguished based upon the experience with the long-term course in 258 cases of chronic relapsing pancreatitis. In chronic pancreatitis without local complications there is 1. an early phase, characterized by recurrent episodes of pancreatitis; 2. a late phase, characterized by the triad: absence of pain, severe global pancreatic insufficiency (diabetes/steatorrhea), and pancreatic calcifications (if any). 3. Local complications (e.g. pseudocysts) produce a different pattern characterized by persistent pain and the symptoms of the "pancreatitis tumor", which may cause many different complications such as cholostasis, gastrointestinal bleeding, duodenal obstruction etc. Local complications are observed mainly in the early phase of the disease. Late symptoms such as diabetes, steatorrhea and calcifications indicate that the pancreatitis is virtually "burned out". The occurrence of late symptoms in the course of the disease varies individually.


Interactions in nucleus tractus solitarius between right and left carotid sinus nerves.
Bilateral carotid sinus nerve stimulation was used as a model for studying cardiovascular afferent interactions in the nucleus tractus solitarius (NTS) region of dorso-medial medulla. Extracellular action potential recordings were made from 69 single units, 33 of which were excited independently by both right and left carotid sinus nerves (CSNs). Fifteen of these were located in NTS. Peak latencies to electrical stimulation of NTS neurons were 17.7 +/- 2.1 ms to ipsilateral CSN and 20.9 +/- 1.5 ms to contralateral CSN. Summation of afferent input was routinely demonstrated. In 10 units in NTS, a conditioning stimulus applied to one CSN caused prolonged inhibition of the response to a test stimulus to the same or the other CSN. The duration of inhibition was dependent on the intensity of the conditioning stimulus, not on prior excitation of the unit by the conditioning stimulus. In five additional excitability testing experiments, we found limited evidence to suggest that primary afferent depolarization of the central fibers of one CSN by stimulation of the contralateral CSN might be contributing to this inhibitory interaction. The data suggest that the outcome of integrative interactions between right and left CSN inputs to NTS neurons may depend largely on the temporal sequence of convergent afferent impulses.


Haloxyfop-P-methyl induces developmental defects in zebrafish embryos through oxidative stress and anti-vasculogenesis.
Haloxyfop-P-methyl, an aryloxyphenoxypropionate herbicide, is widely used to eliminate unwanted plants by inhibiting lipid synthesis and inducing oxidative stress. Since haloxyfop-P-methyl targets are limited within plants, few negative side effects on non-target crops have been reported. However, dissolved haloxyfop-P-methyl in rain or groundwater contaminates aquatic environments and affects marine ecosystems. In the present study, treatment with haloxyfop-P-methyl for 48 h induced developmental deficiencies in the eyes and bodies of the zebrafish embryos as a whole and was also linked to increases in the incidence of pericardial edema. Additionally, haloxyfop-P-methyl treatment decreased hatching ratio, embryo viability, and heart rate, while simultaneously increasing the expression levels of apoptotic and inflammatory genes. Moreover, haloxyfop-P-methyl hampered vasculogenesis in the embryos through down-regulation of functional genes, and disruption of vessel formation caused neurodegeneration in the olig2-positive notochord. Collectively, this study newly discovered the oxidative stress-related toxic mechanism of haloxyfop-P-methyl during embryonic development through anti-vasculogenesis, which suppresses neurogenesis of the notochord. This toxicity assessment of haloxyfop-P-methyl on embryogenesis may contribute to establishment of safety profiling of herbicide and to support hazard control in aquatic environment.


High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome.
Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS. A retrospective study. An outpatient clinic for musculoskeletal disorders. Patients diagnosed with FM according to the 1990 American College of Rheumatology criteria or with CFS according to the 1994 Centers for Disease Control criteria were selected. Review of lumbar and sacral magnetic resonance imaging scans including TCs ≥5 mm in size. In total, 197 patients with FM, CFS, or both underwent magnetic resonance imaging. Ninety-one percent were women. The mean age was 48.1 (±11.9) years. TCs were observed in 39% of patients, with a mean size of 11.8 (±5.2) mm. In males, the prevalence was 12%, vs. 42% in females. In patients diagnosed with FM or CFS, the prevalence of TCs was three times higher than that in the general population. This observation supports the hypothesis that STCs, FM, and CFS may share the same pathophysiological mechanism, i.e., moderately increased cerebrospinal fluid pressure, causing irritation of neurons and axons in dorsal root ganglia.


Tackling tobacco: a call to arms for remote area nurses.
Tobacco-related conditions contribute significantly to the health gap between Indigenous and non-Indigenous Australians. Smoking rates in Australia's Indigenous population has failed to decline even though smoking rates in Australia have declined in general. In some Indigenous communities, smoking rates remain very high. This paper outlines a project to investigate appropriate strategies to assist Indigenous smokers to quit and the important role nurses can play.


[An assessment of the relative contribution of the processes of cellular proliferation, polyploidization and hypertrophy to the increase in liver mass at various stages in the postnatal development of rats].
Changes in isolated hepatocyte dry mass, its ploidy and liver mass at different stages of the rat postnatal ontogeny were investigated. The determination of these processes and special calculation made it possible to estimate quantitatively a relative contribution of cell proliferation, polyploidization and hypertrophy, not associated with DNA synthesis to the increase in the liver mass at different stages of the rat development. During the first week after the rat's birth, its liver growth is provided by 61 and 39% with hepatocyte proliferation and hypertrophy, respectively. Between the 14th and the 21st days of development, when considerable functional changes occur in the rat liver, the contributions of proliferative and polyploidization processes, and of cell hypertrophy into the liver mass increasing are roughly identical. Later on, the contribution of cell hypertrophy into the liver growth is noticeably reducing to reach within 1-2 months only 1%. On this developmental stage the liver mass increment by 2/3 is provided due to cell proliferation and by 1/3--to its polyploidization. As a whole, the accelerated growth of the rat liver from the birth to sex puberty is described as follows: the contribution of processes of proliferation and polyploidization, and of cell hypertrophy correspond to 28, 30 and 42%, respectively; afterwards, the liver growth being retarded. Within the period from 2 to 6 months, the liver mass increase is provided mainly (up to 76%) by cell proliferation, the shares of polyploidization and cell hypertrophy being 8 and 16%, respectively.


Continuous Risk Estimation of Acute Kidney Failure with Dense Temporal Data for ICU Patients.
Acute kidney failure is a dangerous complication for ICU patients, and it is difficult to identify at early stage with conventional medical analysis. In recent years, machine learning approaches have been applied to tackle medical diagnosis tasks with great performance. In this work, we deploy machine learning models for early detection of acute kidney failure that can handle static, temporal, sparse and dense data of ICU patients. We investigate different pre-processing methods for patient data to achieve higher prediction performance and how they influence the contribution of different physiological signals in the prediction process.


Electrocardiographic and morphometric features in patients with ventricular tachycardia of right ventricular origin.
To study differences between repetitive monomorphic ventricular tachycardia (RMVT) of right ventricular origin, and ventricular tachycardia in arrhythmogenic right ventricular dysplasia (ARVD). Consecutive groups with RMVT (n = 15) or ARVD (n = 12), comparable for age and function. Analysis of baseline, tachycardia, and signal averaged ECGs, clinical data, and right endomyocardial biopsies. Pathological findings were related to regional depolarisation (QRS width) and repolarisation (QT interval, QT dispersion). There was no difference in age, ejection fraction, QRS width in leads I, V1, and V6, and QT indices. During ventricular tachycardia, more patients with ARVD had a QS wave in V1 (p < 0.05). There were significant differences for unfiltered QRS, filtered QRS, low amplitude signal duration, and the root mean square voltage content. In the absence of bundle branch block, differences became non-significant for unfiltered and filtered QRS duration. Mean (SD) percentage of biopsy surface differed between RMVT and ARVD: normal myocytes (74(3.4)% v 64.5(9.3)%; p < 0.05); fibrosis (3(1.7)% v 8.9(5.2)%; p < 0.05). When all patients were included, there were significant correlations between fibrosis and age (r = 0.6761), and fibrosis and QRS width (r = 0.5524 for lead I; r = 0.5254 for lead V1; and r = 0.6017 for lead V6). The ECG during tachycardia and signal averaging are helpful in discriminating between ARVD and RMVT patients. There are differences in the proportions of normal myocytes and fibrosis. The QRS duration is correlated with the amount of fibrous tissue in patients with ventricular tachycardia of right ventricular origin.


Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases.
The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 µM) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w/v) in an isotonic buffer solution close to the vitreous temperature (31-34 °C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 ± 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 ± 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-α, showing significant results (p ≤ 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime.


Scaling dictates the decoder structure.
Despite fluctuations in embryo size within a species, the spatial gene expression pattern and hence the embryonic structure can nonetheless maintain the correct proportion to the embryo size. This is known as the scaling phenomenon. For morphogen-induced patterning of gene expression, the positional information encoded in the local morphogen concentrations is decoded by the downstream genetic network (the decoder). In this paper, we show that the requirement of scaling sets severe constraints on the geometric structure of such a local decoder, which in turn enables deduction of mutants' behavior and extraction of regulation information without going into any molecular details. We demonstrate that the Drosophila gap gene system achieves scaling in the way consistent with our theory-the decoder geometry required by scaling correctly accounts for the observed gap gene expression pattern in nearly all maternal morphogen mutants. Furthermore, the regulation logic and the coding/decoding strategy of the gap gene system can also be revealed from the decoder geometry. Our work provides a general theoretical framework for a large class of problems where scaling output is achieved by non-scaling inputs and a local decoder, as well as a unified understanding of scaling, mutants' behavior, and gene regulation for the Drosophila gap gene system.


Colorimetric assay of methyldopa bulk drug and tablets as its Fe(III) complex.
A new colorimetric method for the determination of methyldopa is described. The method is based on the reaction of methyldopa with ferric chloride in the pH range of 3.0-3.5 and producing a water soluble (1:2) brown complex with maximum absorbance at 423 nm. The conditional stability constant of the complex at the optimum pH 3.0 and ionic strength 0.4 M, is found to be 10(7.5). Beer's low is obeyed up to 6 mmol/l methyldopa concentration. The RSD of the method is 0.708-1.226%. The proposed method was found to be suitable for the accurate and reproducible analysis of methyldopa bulk drug and tablets which is pointed by high recovery values 99.20-99.79%.


In vivo dynamics of Swi6 in yeast: evidence for a stochastic model of heterochromatin.
The mechanism for transcriptional silencing of pericentric heterochromatin is conserved from fission yeast to mammals. Silenced genome regions are marked by epigenetic methylation of histone H3, which serves as a binding site for structural heterochromatin proteins. In the fission yeast Schizosaccharomyces pombe, the major structural heterochromatin protein is Swi6. To gain insight into Swi6 function in vivo, we have studied its dynamics in the nucleus of living yeast. We demonstrate that, in contrast to mammalian cells, yeast heterochromatin domains undergo rapid, large-scale motions within the nucleus. Similar to the situation in mammalian cells, Swi6 does not permanently associate with these chromatin domains but binds only transiently to euchromatin and heterochromatin. Swi6 binding dynamics are dependent on growth status and on the silencing factors Clr4 and Rik1, but not Clr1, Clr2, or Clr3. By comparing the kinetics of mutant Swi6 proteins in swi6(-) and swi6(+) strains, we demonstrate that homotypic protein-protein interactions via the chromoshadow domain stabilize Swi6 binding to chromatin in vivo. Kinetic modeling allowed quantitative estimation of residence times and indicated the existence of at least two kinetically distinct populations of Swi6 in heterochromatin. The observed dynamics of Swi6 binding are consistent with a stochastic model of heterochromatin and indicate evolutionary conservation of heterochromatin protein binding properties from mammals to yeast.


Star Ratings show hospitals need to improve the discharge process.
For the first time, the Centers for Medicare & Medicaid Services is posting Star Ratings, showing patients' perception of care, on the Hospital Compare website. Ratings are based on the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and include individual scores on 12 composite measures based on the HCAHPS responses as well as state and national averages. A big gap between patients who reported receiving discharge instructions (86%) and those who said they understood what to do at home (52%) indicates that hospitals need to revise their discharge teaching and make sure patients understand their treatment plan. Case managers need to take the time to fully assess all patients--not just those going to post-acute facilities--to find out their living situations, their support systems, and their need for resources after they go home.


The LC7 light chains of Chlamydomonas flagellar dyneins interact with components required for both motor assembly and regulation.
Members of the LC7/Roadblock family of light chains (LCs) have been found in both cytoplasmic and axonemal dyneins. LC7a was originally identified within Chlamydomonas outer arm dynein and associates with this motor's cargo-binding region. We describe here a novel member of this protein family, termed LC7b that is also present in the Chlamydomonas flagellum. Levels of LC7b are reduced approximately 20% in axonemes isolated from strains lacking inner arm I1 and are approximately 80% lower in the absence of the outer arms. When both dyneins are missing, LC7b levels are diminished to <10%. In oda9 axonemal extracts that completely lack outer arms, LC7b copurifies with inner arm I1, whereas in ida1 extracts that are devoid of I1 inner arms it associates with outer arm dynein. We also have observed that some LC7a is present in both isolated axonemes and purified 18S dynein from oda1, suggesting that it is also a component of both the outer arm and inner arm I1. Intriguingly, in axonemal extracts from the LC7a null mutant, oda15, which assembles approximately 30% of its outer arms, LC7b fails to copurify with either dynein, suggesting that it interacts with LC7a. Furthermore, both the outer arm gamma heavy chain and DC2 from the outer arm docking complex completely dissociate after salt extraction from oda15 axonemes. EDC cross-linking of purified dynein revealed that LC7b interacts with LC3, an outer dynein arm thioredoxin; DC2, an outer arm docking complex component; and also with the phosphoprotein IC138 from inner arm I1. These data suggest that LC7a stabilizes both the outer arms and inner arm I1 and that both LC7a and LC7b are involved in multiple intradynein interactions within both dyneins.


Intestinal free trypsin concentrations fall only transiently when rats are fed raw soya flour.
Raw soya flour (RSF) is thought to cause pancreatic hypertrophy in rats because trypsin inhibitor in the flour binds trypsin in the gut lumen and this lowering of free trypsin concentrations leads to the release of cholecystokinin (CCK). Intestinal enzyme concentrations were therefore studied in rats fed RSF for from one hour to 400 days to determine whether free trypsin concentrations were depressed during the period of pancreatic growth (up to six to eight weeks after starting RSF). Intestinal levels of enzymes were raised from one hour after starting the diet up to 400 days, indicating that stimulation of pancreatic secretion continued for as long as this diet was fed. Free trypsin concentrations were, however depressed only for the first 12 hours. It seems unlikely, therefore, that lowered free trypsin concentrations alone stimulate the release of CCK in these animals.


[Choice of fixatives for the immunohistochemical study of antigens using immunoadsorption].
The effect of fixatives on the rat bone marrow antigens was studied by a method combining immunoadsorption and immunodiffusion. This method allows to estimate rapidly and reliably the effect of fixation on immunochemical properties of the antigen under study, using polyvalence antisera. Acetone and ethanol proved to be the best fixatives for the rat bone marrow antigens since they preserved their immunochemical properties. Aldehydes (formaldehyde and glutaraldehyde) "inactivated" the bone marrow antigens.


Expression and enzyme activity determination of human cyclooxygenase-1 and -2 in a baculovirus-insect cell system.
To develop an in vitro intact cell-based assay for screening selective cyclooxygenase inhibitors. Human cyclooxygenase-1 (hCOX-1) and cyclooxygenase-2 (hCOX-2) genes were cloned from human monocyte cell line THP-1 cells and expressed in Spodoptera frugiperda (sf9) insect cell line by Bac-to-Bac baculovirus expression systems. Infected sf9 cells were harvested 24 h post-infection (hpi), and distributed to a 24-well plate, preincubated with various nonsteroidal anti-inflammatory drugs, and challenged with 10 mmol/L arachidonic acid; the cyclooxygenase activity was assessed indirectly by prostaglandin E2-specific radioimmunoassay. Polymerase chain reaction detection demonstrated that hCOX-1 and hCOX-2 were transposed to the bacmid. Western blot analysis showed that infected sf9 cells could express hCOX-1 and hCOX-2 proteins. Radioimmunoassay demonstrated that both recombinant proteins functioned well in sf9 cells. Human cyclooxygenase-1 and cyclooxygenase-2 were successfully expressed in sf9 insect cell line. It can be utilized for the identification of potent and selective inhibitors of hCOX-1 and/or hCOX-2.


Pontibacter ruber sp. nov. and Pontibacter deserti sp. nov., isolated from the desert.
Two strains of bacteria, JC213(T) and JC215(T), were isolated from desert soil. Colonies were red to pink and cells Gram-stain-negative. Both strains were oxidase- and catalase-positive and hydrolysed casein. In both strains, phosphatidylethanolamine was the major polar lipid, iso-C15 : 0 was the major fatty acid and the bacteriohopane derivative, BHD1, was the major hopanoid. The genomic DNA G+C contents of strains JC213(T) and JC215(T) were 52.7 and 46.3 mol%, respectively. 16S rRNA gene sequence comparisons indicated that both strains belong to the genus Pontibacter within the family Cytophagaceae and the phylum Bacteroidetes. Strain JC213(T) showed the highest sequence similarity to Pontibacter populi HLY7-15(T) (96.6 %) and with other species of the genus Pontibacter sequence similarity was less than 96 %. Strain JC215(T) exhibited highest sequence similarity with Pontibacter lucknowensis DM9(T) (95.1 %) and shared 95 % or less sequence similarity with other species of the genus Pontibacter. The sequence similarity between strains JC213(T) and JC215(T) was 95.8 %. Distinct morphological, physiological and genotypic differences from previously described taxa support JC213(T) and JC215(T) being representatives of two novel species of the genus Pontibacter, for which the names Pontibacter ruber sp. nov. and Pontibacter deserti sp. nov. are proposed and the type strains are JC213(T) ( = KCTC 32442(T) = LMG 27669(T)) and JC215(T) ( = KCTC 32443(T) = LMG 27670(T)), respectively.


Hidden in plain sight: discovery of sheath-forming, iron-oxidizing Zetaproteobacteria at Loihi Seamount, Hawaii, USA.
Lithotrophic iron-oxidizing bacteria (FeOB) form microbial mats at focused flow or diffuse flow vents in deep-sea hydrothermal systems where Fe(II) is a dominant electron donor. These mats composed of biogenically formed Fe(III)-oxyhydroxides include twisted stalks and tubular sheaths, with sheaths typically composing a minor component of bulk mats. The micron diameter Fe(III)-oxyhydroxide-containing tubular sheaths bear a strong resemblance to sheaths formed by the freshwater FeOB, Leptothrix ochracea. We discovered that veil-like surface layers present in iron-mats at the Loihi Seamount were dominated by sheaths (40-60% of total morphotypes present) compared with deeper (> 1 cm) mat samples (0-16% sheath). By light microscopy, these sheaths appeared nearly identical to those of L. ochracea. Clone libraries of the SSU rRNA gene from this top layer were dominated by Zetaproteobacteria, and lacked phylotypes related to L. ochracea. In mats with similar morphologies, terminal-restriction fragment length polymorphism (T-RFLP) data along with quantitative PCR (Q-PCR) analyses using a Zetaproteobacteria-specific primer confirmed the presence and abundance of Zetaproteobacteria. A Zetaproteobacteria fluorescence in situ hybridization (FISH) probe hybridized to ensheathed cells (4% of total cells), while a L. ochracea-specific probe and a Betaproteobacteria probe did not. Together, these results constitute the discovery of a novel group of marine sheath-forming FeOB bearing a striking morphological similarity to L. ochracea, but belonging to an entirely different class of Proteobacteria.