Detection and characterization by immunoblot analysis of potentially diagnostic Leishmania infantum polypeptides in human visceral leishmaniasis.
Humoral immune responses were studied in 53 sera from 18 patients with visceral leishmaniasis by immunoblot analysis. Sera from visceral leishmaniasis patients recognized antigens with molecular weights ranging from < 14 kDa to more than 100 kDa. Bands ranging between 49 and < 14 kDa were the most specific. The 40, 33 and 17 kDa antigens were recognized by 90%, 79% and 79% of the patients sera, respectively. Sera from one patient with Chagas' disease identified 8 of 11 antigens of the specific region. Treatment with periodate eliminated the cross-reaction in three of these antigens (40, 29, 26 kDa). The study of serial sera collected from the different patients showed a decrease in intensity or dissappearance in some of the diagnostic bands, particularly the 17 kDa band. The band of 17 kDa seems to be useful to study the clinical evolution, for post-treatment control and also for epidemiologic purposes. (It has been identified in 7% of control sera from endemic areas.) Immunoblot could be a valuable tool in the diagnosis of visceral leishmaniasis, being more sensitive and specific than other serologic tests.


Valorization of agricultural waste for biogas based circular economy in India: A research outlook.
Environmental deterioration and the need for energy security are intrinsic problems linked with the linear economy based on fossil fuels. Recently, a transformation to a sustainable circular bio-economy is being experienced where biomass waste is being valorized for energy production as well as minimization of waste and greenhouse gas emissions. The agricultural waste, generated in vast quantities in India is a prospective feedstock for biogas production. Agri-waste to biogas based circular economy requires an integration of agri-waste management, biogas production and utilization and policy support. This paper comprehensively discusses the potential of biogas production from agricultural waste, its upgradation and utilization along with the government initiatives, policy regulations. In addition, barriers that impede the development of an efficient agri-waste to biogas based circular economy, and the future research opportunities to meet the growing needs for agri-waste management, energy production and climate change mitigation are discussed.


Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients.
Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased. The percentage of CD8+ T cells is decreased in acute KD, notably effector memory CD8+ T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.


Does Rbmy have a role in sperm development in mice?
The Y(d1) deletion in mice removes most of the multi-copy Rbmy gene cluster that is located adjacent to the centromere on the Y short arm (Yp). XY(d1) mice develop as females because Sry is inactivated, probably because it is now juxtaposed to centromeric heterochromatin. We have previously produced XY(d1)Sry transgenic males and found that they have a substantially increased frequency of abnormal sperm. Staining of testis sections with a polyclonal anti-RBMY antibody appeared to show a marked decrease of RBMY protein in the spermatids of XY(d1)Sry males compared to control males, which led us to suggest that this may be responsible for the increase in sperm anomalies. In the current study we sought to determine whether augmenting Rbmy expression specifically in the spermatids of XY(d1)Sry males would ameliorate the sperm defects. An expressing Rbmy transgene driven by the spermatid-specific mouse protamine 1 promotor (mP1Rbmy) was therefore introduced into XY(d1)Sry males. This failed to reduce the frequency of abnormal sperm. In the course of this study, a new RBMY antibody was generated that, in contrast to the original antibody, failed to detect RBMY in spermatid stages by immunostaining. The lack of RBMY was confirmed by western blotting of lysates from purified round spermatids and elongating spermatids. The implications of these results for the proposed role for RBMY in sperm development are discussed.


Barriers and facilitators to exclusive breastfeeding in rural Pakistan: a qualitative exploratory study.
Exclusive breastfeeding (EBF) of children until six months of age is considered one of the most critical interventions in tackling childhood undernutrition. EBF rates are suboptimal in Pakistan, particularly in rural areas where child undernutrition is most prevalent. This study aimed to explore barriers to EBF in a rural context of Pakistan. The study was conducted in the rural district Matiari of Sindh, Pakistan, during Jan-March 2020. We used a qualitative exploratory study design and conducted 36 focus group discussions (FGDs). Participants were purposively selected mothers who had not practiced EBF during their previous childbirth, their spouses and mothers-in-law, and lady health workers (LHWs) serving in the study catchment. FGDs were audio-recorded, transcribed, and translated into English from the local language and analysed using thematic content analysis. Barriers to EBF included low awareness and cultural practices of prelacteal feeds, insufficient breast milk production, undernutrition of mothers, mothers' occupation as fieldworkers, less birth spacing, low awareness about the correct technique of breastfeeding, maternal and child ailments, abnormal breasts, and influence of in-laws to start top-up feeds. Several facilitators were identified: family support, appropriate maternal diet, maternal awareness, and support in the neighborhood. Barriers to EBF are multifaceted in rural areas, and interventions aiming to improve adherence to EBFshould be multipronged. Awareness-raising alone might not be sufficient, and other interventions should be designed to address the barriers of maternal malnutrition, insufficient milk production, and socio-cultural practices. In addition, safe alternatives to breast milk may be necessary if breastfeeding is truly not feasible. Lack of breast milk substitutes is particularly challenging for poor rural women who cannot afford infant formula milk.


Conscious visual abilities in a patient with early bilateral occipital damage.
A 21-year-old male presented with occipital lobes that were extensively damaged by bilateral infarcts present at birth. The absence of the striate cortex was confirmed with anatomic and functional MRI and high-resolution EEG. His cortical visual impairment was severe, but he retained a remarkable ability to see fast-moving stimuli. Horizontal optokinetic nystagmus could be elicited from either eye. Resolution acuity was close to normal providing the patient was allowed to move his head and eyes. The direction of motion in random-dot patterns could be discriminated with perfect accuracy at speeds above 2 deg/s, and the patient reported that he could 'see' the motion at fast but not at slow speeds. This conscious residual vision for motion is known as Riddoch's phenomenon, but it has never been reported in the complete absence of the striate cortex. Functional neuroimaging revealed activation that was outside the motion-responsive regions of the extrastriate cortex. This case demonstrates remarkable plasticity in the human visual system and may have implications for understanding the functional organization of the motion pathways.


Applicability of effective pair potentials for active Brownian particles.
We have performed a case study investigating a recently proposed scheme to obtain an effective pair potential for active Brownian particles (Farage et al., Phys. Rev. E 91, 042310 (2015)). Applying this scheme to the Lennard-Jones potential, numerical simulations of active Brownian particles are compared to simulations of passive Brownian particles interacting by the effective pair potential. Analyzing the static pair correlations, our results indicate a limited range of activity parameters (speed and orientational correlation time) for which we obtain quantitative, or even qualitative, agreement. Moreover, we find a qualitatively different behavior for the virial pressure even for small propulsion speeds. Combining these findings we conclude that beyond linear response active particles exhibit genuine non-equilibrium properties that cannot be captured by effective pair interaction alone.


New speech tests reveal benefit of wide-dynamic-range, fast-acting compression for consonant discrimination in children with moderate-to-profound hearing loss.
Fast-acting, wide-dynamic-range compression (WDRC) has been shown to give better discrimination of soft speech and shouted speech than linear amplification for moderately hearing-impaired young adults. For severe and profound hearing losses, higher compression ratios are needed. The resultant distortion of the temporal envelope and reduced modulation depth may offset improvements in audibility offered by WDRC. This study compares the effectiveness of WDRC and linear amplification for children with different degrees of hearing loss. Pre-recorded tests of closed-set consonant confusions and open-set word recognition were developed to assess performance. Three groups of subjects (aged 4-14 years) with moderate (51-70 dB), severe (71-90 dB) and profound (91-115 dB) hearing loss were fitted with hearing aids programmed with WDRC or linear amplification. The frequency response was adjusted to match each child's own hearing aid prescription. For each group, stimuli were presented both in quiet and in noise at levels chosen to avoid floor and ceiling effects. Consonant confusion scores for the profound and severe groups combined and for the moderate group were significantly better with WDRC than with linear amplification. Open-set test results showed greater variability. Although mean scores were higher for WDRC than for linear processing, the effects were of marginal statistical significance.


Pubertal growth as a determinant of adult height in boys with constitutional delay of growth and puberty.
In boys with constitutional delay of growth and puberty, adult height may be inconsistent with parental (target) height. We aimed at studying which period of growth was important to account for adult height being above or below target height. In this retrospective study, adult height measured after 20 years in 39 patients was compared with target height and height data obtained at about 6 and 12 years of age and at diagnosis of delayed puberty (mean 14.6 years). Twenty-eight patients were untreated while 11 received testosterone enanthate (50 or 100 mg/month for 6 months). The growth data from both groups were pooled since they were not different. On average, the adult height standard deviation score (-0. 6 +/- 0.8, mean +/- SD) was similar to target height (-0.5 +/- 0.6). There were, however, marked individual differences since adult height varied between 1.7 SD (11 cm) below target height and 1.4 SD (9.5 cm) above target height. Multiple regression analysis showed that the most significant determinant of the difference between adult height and target height was height catch up during puberty (p < 0.002). We conclude that the magnitude of height catch up during puberty is a significant determinant of adult height in boys with constitutional delay of growth and puberty. Thus, optimizing pubertal growth may be a relevant therapeutic aim for adult height in boys with short stature and delayed puberty. Copyrightz1999S. KargerAG,Basel


Growth hormone secretory rates in children as estimated by deconvolution analysis of 24-h plasma concentration profiles.
The kinetics of growth-hormone (GH) distribution and elimination was estimated in five GH-deficient children who received 11 intravenous single injections of GH. The plasma disappearance data were analyzed in terms of a two-compartment model. The kinetic parameters obtained were then used in calculating the GH-secretory rate by a numerical deconvolution technique. A simple formula was derived for calculation of the cumulated secretion from the area under the concentration curve of 145 healthy children of various ages, heights, and stages of puberty. The estimated 24-h GH secretion increased with age, corresponding to a two- to fourfold increase during the adolescence period. The highest secretions were found in pubertal stages 3-4. In prepubertal children the heights correlated markedly with the secretion of GH (r = 0.83). Thus an indication of the range of the GH secretion in normal growing children is found, which is important to estimate substitution doses for treatment of GH-deficient children.


A proteomic view to characterize the effect of chitosan nanoparticle to hepatic cells: is chitosan nanoparticle an enhancer of PI3K/AKT1/mTOR pathway?
Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system widely. Our current investigation studies were the bioeffects of the chitosan nanoparticle uptake by liver cells. In this experiment, the characterizations of chitosan nanoparticles were measured by transmission electron microscopy and particle size analyzer. The average size of the chitosan nanoparticle was 224.6 ± 11.2 nm, and the average zeta potential was +14.08 ± 0.7 mV. Moreover, using proteomic approaches to analyze the differential protein expression patterns resulted from the chitosan nanoparticle uptaken by HepG2 and CCL-13 cells identified several proteins involved in the PI3K/AKT1/mTOR pathway. Our experimental results have demonstrated that the chitosan nanoparticle may involve in the liver cancer cell metastasis and proliferation.


Functional Differentiation of Cholecystokinin-Containing Interneurons Destined for the Cerebral Cortex.
Although extensively studied postnatally, the functional differentiation of cholecystokinin (CCK)-containing interneurons en route towards the cerebral cortex during fetal development is incompletely understood. Here, we used CCKBAC/DsRed mice encoding a CCK promoter-driven red fluorescent protein to analyze the temporal dynamics of DsRed expression, neuronal identity, and positioning through high-resolution developmental neuroanatomy. Additionally, we developed a dual reporter mouse line (CCKBAC/DsRed::GAD67gfp/+) to differentiate CCK-containing interneurons from DsRed+ principal cells during prenatal development. We show that DsRed is upregulated in interneurons once they exit their proliferative niche in the ganglionic eminence and remains stably expressed throughout their long-distance migration towards the cerebrum, particularly in the hippocampus. DsRed+ interneurons, including a cohort coexpressing calretinin, accumulated at the palliosubpallial boundary by embryonic day 12.5. Pioneer DsRed+ interneurons already reached deep hippocampal layers by embryonic day 14.5 and were morphologically differentiated by birth. Furthermore, we probed migrating interneurons entering and traversing the cortical plate, as well as stationary cells in the hippocampus by patch-clamp electrophysiology to show the first signs of Na+ and K+ channel activity by embryonic day 12.5 and reliable adult-like excitability by embryonic day 18.5. Cumulatively, this study defines key positional, molecular, and biophysical properties of CCK+ interneurons in the prenatal brain.


Altered distribution of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4) and the N-methyl-D-aspartate receptor subunit NMDAR1 in the hippocampus of patients with temporal lobe epilepsy.
In patients with therapy-refractory temporal lobe epilepsy (TLE), alterations of glutamate receptors have been proposed as a mechanism for enhanced excitability. Using commercially available monoclonal antibodies specific for the N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 and for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit GluR2(4), we have examined the distribution of these polypeptides in human hippocampal tissue that was surgically removed from patients with intractable TLE. Surgical specimens were classified according to the presence of Ammon's horn sclerosis (AHS) or a focal lesion in the temporal lobe. Cell counts and a densitometric analysis of the immunoreactivity patterns were carried out for all hippocampal subfields. NMDAR1 and GluR2(4) levels were markedly reduced in patients with AHS, primarily in those subfields with substantial neuronal cell loss (in particular CA1, CA4 and CA3), compared to those seen in patients with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of the dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 showed no significant up-regulation in this sublayer. When the receptor staining intensity was normalized for alterations in neuronal density, no significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patients with chronic intractable TLE.


The challenges of searching for and retrieving qualitative studies.
The authors' purpose in this article is to report the results of their search and retrieval efforts to date in an ongoing study to develop the procedural, analytic, and interpretive techniques to conduct qualitative meta-synthesis projects, using studies on women with HIV infection as the method case. For researchers conducting qualitative meta-synthesis projects, the ideal goal is to retrieve all of the relevant studies in a field--not simply a sample of them. Bates's model of berrypicking is used as the framework to describe the techniques used to conduct these searches. The authors discuss, in particular, the challenges of working with bibliographic databases, including choosing which databases to search, learning about the idiosyncrasies of working with each database, developing a list of search terms, and refining inclusion criteria regarding which studies to include in the meta-synthesis. Recommendations are given for searchers and writers of qualitative research.


The transcriptional basis of chromosome pairing.
Pairing between homologous chromosomes is essential for successful meiosis; generally only paired homologs recombine and segregate correctly into haploid germ cells. Homologs also pair in some somatic cells (e.g. in diploid and polytene cells of Drosophila). How homologs find their partners is a mystery. First, I review some explanations of how they might do so; most involve base-pairing (i.e. DNA-DNA) interactions. Then I discuss the remarkable fact that chromosomes only pair when they are transcriptionally active. Finally, I present a general model for pairing based upon the DNA-protein interactions involved in transcription. Each chromosome in the haploid set has a unique array of transcription units strung along its length. Therefore, each chromatin fibre will be folded into a unique array of loops associated with clusters of polymerases and transcription factors; only homologs share similar arrays. As these loops and clusters, or transcription factories, move continually, they make and break contact with others. Correct pairing would be nucleated when a promoter in a loop tethered to one factory binds to a homologous polymerizing site in another factory, before transcription stabilizes the association. This increases the chances that adjacent promoters will bind to their homologs, so that chromosomes eventually become zipped together with their partners. Pairing is then the inevitable consequence of transcription of partially-condensed chromosomes.


Slow reductive elimination from arylpalladium parent amido complexes.
We report reductive eliminations of primary arylamines from a series of bisphosphine-ligated arylpalladium(II) parent amido complexes that counter several established trends. In contrast to arylamido and alkylamido complexes of the aromatic bisphosphines DPPF and BINAP, parent amido complexes of these ligands do not form or undergo reductive elimination of monoarylamines. However, arylpalladium parent amido complexes ligated by the alkylbisphosphine CyPF-t-Bu do form in good yield and undergo reductive elimination. Despite the basicity of the parent amido ligand and the typically faster reductive elimination from complexes containing more basic amido ligands, the CyPF-t-Bu-ligated arylpalladium parent amido complexes undergo reductive elimination much more slowly than the analogous complexes containing arylamido or alkylamido ligands. Moreover, the parent amido complexes form more rapidly and are more stable thermodynamically in a series of exchange processes than the arylamido complexes. Computational studies support the overriding influence of steric effects on the stability and reactivity of the parent amido complex. The slow rate of reductive elimination causes the arylpalladium amido complex to be the resting state of the coupling of aryl halides with ammonia catalyzed by CyPF-t-Bu-ligated palladium, and this resting state contrasts the Pd(0) or arylpalladium(II) resting states of reactions of aryl halides with amines catalyzed by most palladium complexes.


Hyperinsulinemia and in vivo very-low-density lipoprotein-triglyceride kinetics.
The effect of hyperinsulinemia (2 wk of twice daily NPH insulin) on the kinetics of very-low-density lipoprotein (VLDL)-triglyceride (TG) was studied in rats. To avoid profound hypoglycemia the rats were allowed sucrose ad libitum. Two control groups were needed: chow only and ad libitum sucrose-supplemented (high-CHO). The insulin-treated rats had 15 times higher IRI and 50% lower plasma glucose levels than either control group. Their TG production exceeded and their TG concentrations were less than those of either control group. This indicated that their TG removal was increased even more than their TG production. This increase in TG production occurred despite lower plasma free fatty acid (FFA) levels, suggesting that a greater proportion of TG fatty acids came from a source other than FFA. Compared with chow controls, high-CHO controls had the same peripheral IRI, a slight increase in TG production, and an increase in TG concentration. The differences between the effects of CHO supplementation alone or together with injected insulin may relate to the IRI and/or the route of access of insulin (peripheral vs. portal). The present studies indicate that hyperinsulinemia, either directly or indirectly, accelerates triglyceride turnover.


NAD+, ADP-ribosylation and transcription in permeabilized mammalian cells.
When permeabilized hamster fibroblasts were incubated with 4 mM-NAD+, the substrate for poly(ADP-ribose) polymerase, RNA polymerase I activity was inhibited by about 85%. This inhibition was not relieved by prior incubation of cells with 3-aminobenzamide, a potent inhibitor of the poly(ADP-ribose) polymerase. Digestion of cells with pancreatic deoxyribonuclease I resulted in the inhibition of RNA polymerase I by 80% and the activation of poly(ADP-ribose) polymerase by up to 300%; prior incubation with 3-aminobenzamide did not prevent the inhibition of the RNA polymerase activity. No radioactivity was found associated with RNA polymerase I during later stages of purification of this enzyme from permeabilized cells previously incubated with [14C]NAD+. The inhibitory effect of NAD+ on RNA polymerase I was not specific for NAD+, as other small, negatively charged molecules with a nuclear location also inhibited the enzyme. The results do not support the concept of a role for ADP-ribosylation in transcription catalysed by RNA polymerase I.


Managed care and ERISA: synopsis and case law review.
Managed care organizations (MCOs) have become the predominant health care model in the United States. Through cost containment arrangements with providers, incentives for patients to pursue less costly care and reductions in the provision of unnecessary care, MCOs are more intimately involved in the delivery of health care than their former fee-for-service insurance company counterparts. However, this new role has not implied increased liability, largely because of The Employee Retirement Income Security Act of 1974 (ERISA). This article provides an overview of ERISA and a review of the important legal cases in this area, including the three most recent Supreme Court cases. Courts have struggled with interpreting ERISA, and decisions have been difficult to reconcile. Frustration with this statute and the failure of the U.S. Congress to amend it, has led to more liberal interpretations of ERISA in recent years.


[Methods and equipment for processing x-ray films by x-ray television].
A review of television methods used for processing the X-ray films shows that in the future the technique that combines television and roentgen will allow more precise diagnose in accordance to X-ray patterns on the basis of such processes as harmonization, subtraction, artificial colour painting to emphasize the details of the organs under study, and with application of automatic measurement of geometric parameters of the organ image.


All-Inorganic Polyoxometalates Act as Superchaotropic Membrane Carriers.
Polyoxometalates (POMs) are known antitumoral, antibacterial, antiviral, and anticancer agents and considered as next-generation metallodrugs. Herein, a new biological functionality in neutral physiological media, where selected mixed-metal POMs are sufficiently stable and able to affect membrane transport of impermeable, hydrophilic, and cationic peptides (heptaarginine, heptalysine, protamine, and polyarginine) is reported. The uptake is observed in both, model membranes as well as cells, and attributed to the superchaotropic properties of the polyoxoanions. In view of the structural diversity of POMs these findings pave the way toward their biomedical application in drug delivery or for cell-biological uptake studies with biological effector molecules or staining agents.


Task-Driven Orbit Design and Implementation on a Robotic C-Arm System for Cone-Beam CT.
This work applies task-driven optimization to the design of non-circular orbits that maximize imaging performance for a particular imaging task. First implementation of task-driven imaging on a clinical robotic C-arm system is demonstrated, and a framework for orbit calculation is described and evaluated. We implemented a task-driven imaging framework to optimize orbit parameters that maximize detectability index d'. This framework utilizes a specified Fourier domain task function and an analytical model for system spatial resolution and noise. Two experiments were conducted to test the framework. First, a simple task was considered consisting of frequencies lying entirely on the fz-axis (e.g., discrimination of structures oriented parallel to the central axial plane), and a "circle + arc" orbit was incorporated into the framework as a means to improve sampling of these frequencies, and thereby increase task-based detectability. The orbit was implemented on a robotic C-arm (Artis Zeego, Siemens Healthcare). A second task considered visualization of a cochlear implant simulated within a head phantom, with spatial frequency response emphasizing high-frequency content in the (fy , fz ) plane of the cochlea. An optimal orbit was computed using the task-driven framework, and the resulting image was compared to that for a circular orbit. For the fz -axis task, the circle + arc orbit was shown to increase d' by a factor of 1.20, with an improvement of 0.71 mm in a 3D edge-spread measurement for edges located far from the central plane and a decrease in streak artifacts compared to a circular orbit. For the cochlear implant task, the resulting orbit favored complementary views of high tilt angles in a 360° orbit, and d' was increased by a factor of 1.83. This work shows that a prospective definition of imaging task can be used to optimize source-detector orbit and improve imaging performance. The method was implemented for execution of non-circular, task-driven orbits on a clinical robotic C-arm system. The framework is sufficiently general to include both acquisition parameters (e.g., orbit, kV, and mA selection) and reconstruction parameters (e.g., a spatially varying regularizer).


First web space soft tissue release in bunion surgery: functional outcomes of a new technique.
The current approach to soft tissue release in bunion surgery is through an incision in the dorsum of the first web space between the first and second metatarsals. However, the soft tissue release through this approach can be excessive or inadequate for the correction required. In addition, it leaves a visible scar. A new technique described here provides a stepwise protocol to limit the extent of soft tissue release to only what is required for the correction. The purpose of this study was to evaluate functional outcomes of the new technique. The authors conducted a retrospective chart review of 76 patients (88 procedures) and functional outcome analysis of 38 patients (44 procedures) who underwent first web space release utilizing the new technique. The mean followup was 3.8 years. The mean age was 50.8 (range, 24 to 74) years; 98% were female patients and 2% were male. The majority of the patients (89%) had good or excellent results. The surgical scar was hidden between the first and second toes in the web fold. The average Olerud-Molander score was 86.4 out of 100. None of the patients reviewed had nerve injury, recurrence of deformity, hallux varus, or revision surgery. The new technique for the first web space soft tissue release was a reliable technique that can be used as an adjunctive surgical procedure in correction of hallux valgus. Since the incision is in the web fold, the resulting scar is hidden.


Good training allows excellent results for laparoscopic Nissen fundoplication even early in the surgeon's experience.
Laparoscopic antireflux surgery is the gold standard for surgical treatment of gastroesophageal reflux disease (GERD), and a well-defined learning curve for the procedure has been described. This study aimed to assess whether the surgeon's experience has an effect on 1-year symptom scores and patient satisfaction. All the patients who underwent antireflux surgery were entered into a prospectively maintained database including 1-year postoperative symptom scores. The database was queried in June 2008 to identify patients who had been followed up for 1 year. To decrease variability, the patients with a large hiatal hernia (>5 cm), paraesophageal hernia, treatment with partial fundoplication, a required Collis gastroplasty, or treatment with a transthoracic procedure were excluded from the study. From September 2003 to March 2007, 215 consecutive patients underwent primary antireflux surgery. Of these 215 patients, 158 (93 women with a mean age of 50.9 ± 13.6 years; range, 18-87 years) met the inclusion criteria and were divided into three groups: early group (9/2003-10/2004), mid group (10/2004-12/2005), and late group (12/2005-3/2007). Experience significantly decreased the mean operative time (P < 0.05) and the hospital stay (P < 0.05). Additionally, the number of patients who required reoperative intervention also decreased with experience. There was no difference in the patient-reported symptom scores at 1 year for heartburn (mean, 0.3 ± 0.7), regurgitation (mean, 0.1 ± 0.4), or dysphagia (mean, 0.3 ± 0.6) (P > 0.05 for each). However, chest pain (mean, 0.2 ± 0.4) was significantly improved with experience (P < 0.05). The overall patient-reported mean satisfaction was 9.0 ± 1.9 (P > 0.05, scale, 1-10), and 14.5% (19/131) of the patients reported use of acid suppression medications. A high degree of 1-year symptom resolution and satisfaction can be achieved even early in a surgeon's experience provided there is adequate training and maintenance of strict adherence to technique.


Identification of a Candidate Mutation in the COL1A2 Gene of a Chow Chow With Osteogenesis Imperfecta.
Osteogenesis imperfecta (OI) is a genetic disease that occurs in humans and animals. Individuals with OI exhibit signs of extreme bone fragility and osteopenia with frequent fractures and perinatal lethality in severe cases. In this study, we report the clinical diagnosis of OI in a dog and the use of targeted next-generation sequencing to identify a candidate autosomal dominant mutation in the COL1A2 gene. A 5-month-old male Chow Chow was examined with a fractured left humerus and resolving, bilateral femoral fractures. Radiographs revealed generalized osteopenia and bilateral humeral, radial, and femoral fractures. Targeted next-generation sequencing of genes associated with OI in humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936 + 1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates. Altogether, these findings reveal a candidate autosomal splice donor site mutation causing OI in an individual Chow Chow.


Twist1 Activation in Muscle Progenitor Cells Causes Muscle Loss Akin to Cancer Cachexia.
Cancer cachexia is characterized by extreme skeletal muscle loss that results in high morbidity and mortality. The incidence of cachexia varies among tumor types, being lowest in sarcomas, whereas 90% of pancreatic ductal adenocarcinoma (PDAC) patients experience severe weight loss. How these tumors trigger muscle depletion is still unfolding. Serendipitously, we found that overexpression of Twist1 in mouse muscle progenitor cells, either constitutively during development or inducibly in adult animals, caused severe muscle atrophy with features reminiscent of cachexia. Using several genetic mouse models of PDAC, we detected a marked increase in Twist1 expression in muscle undergoing cachexia. In cancer patients, elevated levels of Twist1 are associated with greater degrees of muscle wasting. Finally, both genetic and pharmacological inactivation of Twist1 in muscle progenitor cells afforded substantial protection against cancer-mediated cachexia, which translated into meaningful survival benefits, implicating Twist1 as a possible target for attenuating muscle cachexia in cancer patients.


Histamine production by transplantable argyrophilic gastric carcinoid of Praomys (Mastomys) natalensis.
A transplantable argyrophilic gastric carcinoid of Praomys (Mastomys) natalensis contained appreciable amounts of histamine. Dialyzed, microsome-free supernatant of tumor tissue produced definite amounts of histamine in the presence of L-histidine and pyridoxal phosphate. These findings may relate to hypersecretion of gastric acid and formation of multiple ulcers in the stomach and duodenum of Mastomys bearing carcinoids.


Fat-soluble bioactive components in colored rice varieties.
Bioactive components in rice vary depending on the variety and growing condition. Fat-soluble components such as γ-oryzanol, tocopherols, tocotrienols, carotenoids, and fatty acids were analyzed in brown, sugary brown, red, and black rice varieties using established high-performance liquid chromatography (HPLC) and GC methodologies. In addition, these colored rice varieties were further analyzed using a high-resolution liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) (LTQ-Orbitrap XL) to identify the [M-H](-) ions of γ-oryzanol, ranging from m/z 573.3949 to 617.4211. The highest content of tocopherols (α-, 1.5; γ-, 0.5 mg/100 g) and carotenoids (lutein 244; trans-β carotene 25 μg/100 g) were observed in black rice; tocotrienols (α-, 0.07; γ-, 0.14 mg/100 g) in red rice, and γ-oryzanol (115 mg/100 g) in sugary brown rice. In all colored rice varieties, the major fatty acids were palmitic (16:0), oleic (18:1n-9), and linoleic (18:2n-6) acids. When the γ-oryzanol components were further analyzed by LC-MS/MS, 3, 10, 8, and 8 triterpene alcohols or sterol ferulates were identified in brown, sugary brown, red, and black rice varieties, respectively. Such structural identification can lead to the elucidation of biological function of each component at the molecular level. Consumption of colored rice rich in beneficial bioactive compounds may be a useful dietary strategy for achieving optimal health.


Expression and purification of Streptococcus pneumoniae hyaluronate lyase from Escherichia coli.
Pneumococcal hyaluronate lyase enzyme breaks down hyaluronan of the extracellular matrix of tissues and possibly contributes to the invasion of host tissue and to the penetration of host defenses by this bacterial pathogen. In light of the emergence of increasing numbers of antibiotic-resistant strains, the understanding of the mechanism of action of hyaluronate lyase enzyme may lead to a better understanding of interactions between a host and bacterial pathogens and may contribute to more efficient treatment of bacterial infections. The native Streptococcus pneumoniae hyaluronate lyase enzyme has a molecular mass of 107 kDa but undergoes conversion to smaller enzymatically active forms. The truncated 83-kDa functional form of the enzyme has been cloned into the pET-21d vector, expressed in Escherichia coli, and purified to homogeneity using a nickel affinity column with chelating Sepharose fast flow media. The recombinant enzyme is active and stable and the availability of large quantities of the enzyme will help in its biochemical and biophysical characterization. As a number of other Gram-positive surface proteins, it appears that the enzyme is anchored via its carboxy-terminal part to the pneumococcal cell wall by a covalent linkage with peptidoglycan structures.


Effect of coinfection with influenza virus and bacteria on host damage.
Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.


Prognostic factors for survival and radiation necrosis after stereotactic radiosurgery alone or in combination with whole brain radiation therapy for 1-3 cerebral metastases.
In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. 340 patients with 1-3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS ≤ 70: 122 days; KPS > 70: 342 days), for RPA (recursive partitioning analysis) class (RPA class I: 1800 days; RPA class II: 281 days; RPA class III: 130 days), irradiated volume (≤2.5 ml: 354 days; > 2.5 ml: 234 days), prescribed dose (≤18 Gy: 235 days; > 18 Gy: 351 days), gender (male: 235 days; female: 327 days) and whole brain radiotherapy (+WBRT: 341 days/-WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA class and gender. MRI and clinical symptoms suggested radiation necrosis in 21 patients after SRS +/- whole brain radiotherapy (WBRT). In five patients clinically relevant radiation necrosis was confirmed by PET imaging. SRS alone or in combination with WBRT represents a feasible option as initial treatment for patients with brain metastases; however a significant subset of patients may develop neurological complications. Performance status, RPA class and gender were identified to predict improved survival in cerebral metastasized patients.


Testing for the erythropoiesis-stimulating agent Sotatercept/ACE-011 (ActRIIA-Fc) in serum by means of Western blotting and LC-HRMS.
Sotatercept (formerly ACE-011) is a glycosylated, dimeric fusion protein composed of the extracellular domain of the human activin receptor type IIA (ActRIIA) and the Fc region of human IgG1. The protein-based drug candidate acts as a ligand trap which competitively binds to activin A and other members of the transforming growth factor beta superfamily, thus blocking signalling through ActRIIA. Since the inhibition of activin A was found to significantly increase bone formation and quality, Sotatercept was originally developed for the treatment of diseases involving bone loss. But as the protein therapeutic also stimulates erythropoiesis by a mechanism independent of the EPO receptor, it has been evaluated for the treatment of anaemia in rare blood diseases such as beta thalassemia. Due to its positive effects on erythropoiesis and bone formation, Sotatercept may also be misused as performance-enhancing agent in sports. Within this study, two complementary detection assays for Sotatercept and related ActRIIA-Fc fusion proteins in serum samples were developed. While the first assay combines affinity purification and Western blotting to generically detect ActRIIA-Fc fusion proteins irrespective of their amino acid sequence, the liquid chromatography-high resolution mass spectrometry (LC-HRMS) method is highly specific for proteolytic peptides originating from the receptor and Fc domain of Sotatercept. Both approaches can readily be modified to include other pharmaceutical proteins such as therapeutic antibodies, and serve as proof-of-concept for the capability of the approach to detect TGF-β inhibitors and Fc fusion proteins in doping control serum samples. Copyright © 2016 John Wiley & Sons, Ltd.


Creation of a quantitative recipient risk index for mortality prediction after cardiac transplantation (IMPACT).
No recipient risk index exists predicting short-term mortality after orthotopic heart transplantation (OHT). We utilized United Network for Organ Sharing (UNOS) data to develop a novel quantitative recipient risk score for use in OHT. A prospectively collected open cohort of 21,378 primary OHT patients (1997 to 2008) was randomly divided into subgroups. The training cohort (n=17,079) was used for score derivation and the test cohort (n=4,299) was used for independent validation. Recipient specific variables associated with 1-year mortality (exploratory p value<0.2) were incorporated stepwise into a multivariable logistic regression model. The final model contained variables which maximized explanatory power (assessed by pseudo R2, area under the curve, and likelihood-ratio test). A risk index was created by apportioning points approximating the relative impact of variables on 1-year mortality. The Kaplan-Meier method was used to assess impact of risk score on short-term survival. The 50-point scoring system incorporated 12 recipient specific variables. Derivation and validation cohort scores ranged from 0 to 33 and 0 to 27, respectively (mean 6.1±3.7 and 6.1±3.7). Each point increased the odds of 1-year death by 14% in the derivation cohort (odds ratio 1.14 [1.13 to 1.15], p<0.001) and 15% in the validation cohort (odds ratio 1.15 [1.12 to 1.17], p<0001). One-year survivals in the validation cohort (by increments of 3 points) were the following: 0 to 2 (92.5%); 3 to 5 (89.9%); 7 to 9 (86.3%); and 10 or greater (74.9%); p<0.001. Patients transplanted with risk scores of 20 or higher had 1-year mortality rates greater than 50%. We present a novel internally validated OHT recipient risk score, which is highly predictive of 1-year mortality. This risk index may prove valuable for patient prognosis, organ allocation, and research stratification in OHT.


Implementation of patient safety strategies in European hospitals.
This study is part of the Methods of Assessing Response to Quality Improvement Strategies (MARQuIS) research project on cross-border care, investigating quality improvement strategies in healthcare systems across the European Union (EU). To explore to what extent a sample of acute care European hospitals have implemented patient safety strategies and mechanisms and whether the implementation is related to the type of hospital. Data were collected on patient safety structures and mechanisms in 389 acute care hospitals in eight EU countries using a web-based questionnaire. Subsequently, an on-site audit was carried out by independent surveyors in 89 of these hospitals to assess patient safety outputs. This paper presents univariate and bivariate statistics on the implementation and explores the associations between implementation of patient safety strategies and hospital type using the chi(2) test and Fisher exact test. Structures and plans for safety (including responsibilities regarding patient safety management) are well developed in most of the hospitals that participated in this study. The study found greater variation regarding the implementation of mechanisms or activities to promote patient safety, such as electronic drug prescription systems, guidelines for prevention of wrong patient, wrong site and wrong surgical procedure, and adverse events reporting systems. In the sample of hospitals that underwent audit, a considerable proportion do not comply with basic patient safety strategies--for example, using bracelets for adult patient identification and correct labelling of medication.


Gamma knife radiosurgery for treatment of trigeminal neuralgia in multiple sclerosis patients.
Trigeminal neuralgia is a paroxysmal pain syndrome commonly associated with multiple sclerosis. While gamma knife radiosurgery has been shown to be an effective treatment for most cases of trigeminal neuralgia, it is considered to be less efficacious in patients with multiple sclerosis and less viable as a treatment option. Seven patients with multiple-sclerosis-associated trigeminal neuralgia were identified from 50 consecutive patients treated for trigeminal neuralgia at the Memorial-Hermann Gamma Knife Radiosurgery Center. A Leksell gamma knife was used to deliver 80 or 90 Gy to a single 4-mm isocenter targeting the fifth nerve root entry zone into the pons. The patients were followed for a median period of 28 months and graded on a scale of 1 to 5, adopted from the Barrow Neurological Institute. All 7 patients showed excellent responses to radiosurgery with complete resolution of their pain and cessation of pain medications. The time to maximal response varied from 1 day to 8 months after treatment. The only complication was persistent facial numbness over the distribution of V2 and V3 which occurred in 4 patients. One patient experienced a recurrence of pain (grade 3) 24 months after radiation treatment, and she is currently being treated with carbamazepine. Gamma knife radiosurgery is an effective treatment option for trigeminal neuralgia patients with multiple sclerosis. These patients should be informed that there appears to be a higher incidence of facial numbness and that a longer period of several months should be allowed before the full effects of treatment may be observed as compared to the general population.


Rotenone Treatment Reveals a Role for Electron Transport Complex I in the Subcellular Localization of Key Transcriptional Regulators During T Helper Cell Differentiation.
Recent advances in our understanding of tumor cell mitochondrial metabolism suggest it may be an attractive therapeutic target. Mitochondria are central hubs of metabolism that provide energy during the differentiation and maintenance of immune cell phenotypes. Mitochondrial membranes harbor several enzyme complexes that are involved in the process of oxidative phosphorylation, which takes place during energy production. Data suggest that, among these enzyme complexes, deficiencies in electron transport complex I may differentially affect immune responses and may contribute to the pathophysiology of several immunological conditions. Once activated by T cell receptor signaling, along with co-stimulation through CD28, CD4 T cells utilize mitochondrial energy to differentiate into distinct T helper (Th) subsets. T cell signaling activates Notch1, which is cleaved from the plasma membrane to generate its intracellular form (N1ICD). In the presence of specific cytokines, Notch1 regulates gene transcription related to cell fate to modulate CD4 Th type 1, Th2, Th17, and induced regulatory T cell (iTreg) differentiation. The process of differentiating into any of these subsets requires metabolic energy, provided by the mitochondria. We hypothesized that the requirement for mitochondrial metabolism varies between different Th subsets and may intersect with Notch1 signaling. We used the organic pesticide rotenone, a well-described complex I inhibitor, to assess how compromised mitochondrial integrity impacts CD4 T cell differentiation into Th1, Th2, Th17, and iTreg cells. We also investigated how Notch1 localization and downstream transcriptional capabilities regulation may be altered in each subset following rotenone treatment. Our data suggest that mitochondrial integrity impacts each of these Th subsets differently, through its influence on Notch1 subcellular localization. Our work further supports the notion that altered immune responses can result from complex I inhibition. Therefore, understanding how mitochondrial inhibitors affect immune responses may help to inform therapeutic approaches to cancer treatment.


"Moderate" adjuvant chemotherapy-induced leukopenia is beneficial for survival of patients with early breast cancer: a retrospective study.
The association between chemotherapy-induced leukopenia (CIL) and survival for patients with early breast cancer (EBC) is not known. We investigated the relationship between different grades of CIL and survival in patients with EBC receiving adjuvant chemotherapy. A total of 442 patients with EBC receiving a regimen containing an anthracycline (A) and taxane (T) were included into our analysis. Survival analyses were undertaken using Kaplan-Meier curves. The P-value was calculated using the log rank test. Subgroup analysis was conducted to investigate the correlation of CIL grade and survival based on the clinicopathological characteristics of patients. Afterwards, univariate and multivariate analyses screened out independent prognostic factors to construct a prognostic model, the robustness of which was verified. Patients with EBC who experienced grade 2-4 ("moderate" and "severe") CIL were associated with longer overall survival (OS) than those with grade 0-1 (mild) CIL (P = 0.021). Compared with patients with mild CIL, OS was longer in patients with severe CIL (P = 0.029). Patients who suffered from moderate CIL tended to have longer OS than those with mild CIL (P = 0.082). Nevertheless, there was no distinguishable difference in OS between moderate- or severe-CIL groups. Subgroup analysis revealed that patients with moderate CIL had longer OS than those with mild CIL among patients who were premenstrual, or with human epidermal growth factor receptor 2-positive (HER2+), > 3 lymph nodes with metastases, a tumor diameter > 5 cm. A prognostic model based on menstrual status, N stage, and CIL grade showed satisfactory robustness. The grade of CIL was strongly associated with the prognosis among patients with EBC who received a regimen containing both anthracyclines and taxanes. Patients with a "moderate" CIL grade tended to have better survival outcomes.


Plakoglobin (gamma-catenin) has TCF/LEF family-dependent transcriptional activity in beta-catenin-deficient cell line.
Beta-catenin is an essential element for the transcriptional activation of target genes in the Wnt signaling cascade and is also a cell adhesion molecule that couples with cadherins. Although plakoglobin (gamma-catenin), a closely related homologue of beta-catenin, is also known to be a cell adhesion molecule, its function as a transcriptional factor has not been revealed in detail. Using a human malignant mesothelioma cell line, NCI-H28, in which we have identified a homozygous deletion of the beta-catenin gene, we studied whether plakoglobin has a T-cell factor/lymphocyte enhancer factor (TCF/LEF) family-dependent transcriptional activity. Transfection with the wild-type plakoglobin expression vector induced accumulation of plakoglobin in the nucleus. Immunoprecipitation assay with cotransfection of plakoglobin and either TCF-4 or LEF-1 detected binding of plakoglobin to TCF-4 or LEF-1. Luciferase reporter assay demonstrated transcriptional activity of the wild-type plakoglobin when transfected with TCF/LEF, although plakoglobin showed less activity than beta-catenin. Exogenous plakoglobin was also shown to promote entrance of exogenous beta-catenin into the nuclei. Furthermore, small interfering RNA directed against plakoglobin suppressed expression of endogenous plakoglobin and its transcriptional activity, suggesting that endogenous plakoglobin has a weak transcriptional activity. These results suggest that plakoglobin can activate the Wnt signaling cascade directly without interaction of beta-catenin, and that plakoglobin has multiple functions as a transcriptional activator and a cell adhesion molecule like beta-catenin.


Tick-borne pathogens of zoonotic and veterinary importance in cattle ticks in Ghana.
Ticks are important vectors involved in the transmission of pathogens of zoonotic and veterinary importance. In this study, ticks were collected from cattle in Navrongo, Kintampo, and Kumasi and screened for pathogen DNA using PCR and Sanger sequencing. A total of 454 ticks were collected, morphologically identified and confirmed using primers that target the 660-bp segment of the mitochondrial COI gene. The predominant tick species was Amblyomma variegatum (70.26%). DNA was extracted from 85 tick pools and screened for the presence of Rickettsia DNA based on the 639 bp of the outer membrane protein A (ompA) gene, Ehrlichia/Anaplasma DNA based on the 345 bp fragment of the 16SrRNA gene and Babesia/ Theileria DNA based on the 560 bp fragment of the ssrRNA gene. From the 85 tick pools, the DNA of pathogens detected were Rickettsia africae (36.47%), Rickettsia aeschlimannii (16.47%), Ehrlichia canis (2.35%), Babesia occultans (1.18%), Theileria velifera (1.18%) and a symbiont Candidatus Midichloria mitochondrii (8.24%). This study reports the first molecular detection of Candidatus Cryptoplasma californiense (1.18%) in Ghana. Coinfections were recorded in 8.24% of the tick pools. The findings of this study highlight the importance of tick species in Ghana and the need to adopt effective control measures to prevent pathogen spread.


Dual-task-related gait changes in the elderly: does the type of cognitive task matter?
Dual-task-related gait changes among older adults while they perform spoken verbal tasks have been reported frequently. The authors examined whether the type of walking-associated spoken verbal task matters for dual-task-related gait changes in 16 older adults classified as transitionally frail. Mean stride time increased significantly when they walked and performed an arithmetic or a verbal fluency task compared with when they only walked (p < .001), whereas the coefficients of variation increased significantly only when they walked and performed the arithmetic task (p = .005) but not the verbal fluency task (p = .134). Those findings suggest that stride time variability under a dual-task condition depends on the type of walking-associated spoken verbal task.


[Effect of urbanization on the future of agricultural development in Costa Rica].
The future agricultural development of Central America must be based of studies of land capacity in order to assure a sustained yield of the environment. The industrial development of the region, as well as the construction of the highways and rural roads must be carefully planned as a means of environmental conservation. New towns, housing developments, recreational facilities and highways should be planned to the effect that they occupy non-productive lands and thus minimize the modern trend of covering the best agricultural soils with concrete jungles. In recent years the price of agricultural lands has shown a tremendous rise, due mainly to the demand of land for urbanization. This situation has induced many farmers to abandon their lands, therefore, a selective land taxation system is suggested to encourage the cultivation of these suburban areas.


Dual-process theories and consciousness: the case for 'Type Zero' cognition.
A step towards a theory of consciousness would be to characterize the effect of consciousness on information processing. One set of results suggests that the effect of consciousness is to interfere with computations that are optimally performed non-consciously. Another set of results suggests that conscious, system 2 processing is the home of norm-compliant computation. This is contrasted with system 1 processing, thought to be typically unconscious, which operates with useful but error-prone heuristics. These results can be reconciled by separating out two different distinctions: between conscious and non-conscious representations, on the one hand, and between automatic and deliberate processes, on the other. This pair of distinctions is used to illuminate some existing experimental results and to resolve the puzzle about whether consciousness helps or hinders accurate information processing. This way of resolving the puzzle shows the importance of another category, which we label 'type 0 cognition', characterized by automatic computational processes operating on non-conscious representations.


Necessary and sufficient quantum information characterization of Einstein-Podolsky-Rosen steering.
Steering is the entanglement-based quantum effect that embodies the "spooky action at a distance" disliked by Einstein and scrutinized by Einstein, Podolsky, and Rosen. Here we provide a necessary and sufficient characterization of steering, based on a quantum information processing task: the discrimination of branches in a quantum evolution, which we dub subchannel discrimination. We prove that, for any bipartite steerable state, there are instances of the quantum subchannel discrimination problem for which this state allows a correct discrimination with strictly higher probability than in the absence of entanglement, even when measurements are restricted to local measurements aided by one-way communication. On the other hand, unsteerable states are useless in such conditions, even when entangled. We also prove that the above steering advantage can be exactly quantified in terms of the steering robustness, which is a natural measure of the steerability exhibited by the state.


[Obturation ileus in cancer of the large intestine].
The analysis of treatment and diagnosis is presented for 168 colon cancer patients with occlusive ileus. Late diagnosis is responsible for high percentage of palliative operations (61.9%) with a 26% mortality. Radical surgery involves, as a rule, delayed primary one-stage resection and establishment of a single- or doubled-barreled anus. The mortality in this case reaches 19%. Advances in colon cancer treatment results and ways to reduce mortality in this conditions lie in early diagnosis and better knowledge by general practitioners of occlusive ileus pathogenesis and clinical appearance.


Temporomandibular joint disc: a proposed histopathological degeneration grading score system.
The purpose of this study was to draw up a TMJ disc histopathological score that is a semi-quantitative transcription of the entire spectrum of TMJ disc degenerative diseases related to changes in disc tissue, and then validate the proposed grading, in order to contribute to a standardized histopathological diagnosis. Sections from sixty two temporomandibular joint disc specimens affected by tissue degenerative changes and stained with Hematoxylin & Eosin (H&E) were collected from among those found in the archives of the Department of Dentistry at Catania University. Specimens, included anterior, intermediate and posterior disc bands. Based on a literature search regarding the most frequent histopathological changes detected in TMJ disc tissue a grading score was designed. This score takes into account pathological disc tissue transformation i.e. collagen bundles, non-specific degenerative changes and the presence of blood vessels. This grading system results in a score ranging from 0 up to 8 for heavily degenerated disc tissue. Two observers performed the assessment of the TMJ disc H&E stained sections. Each specimen was scored twice by each observer after a minimum interval of 1 week. The average TMJ disc degeneration score of the TMJ disc sample was 3.89+/-1.37. There was an almost perfect agreement, between the two observers, and degeneration scores from the two observers were highly correlated. The introduction of this validated degeneration score system may be of major importance for future research and collaboration between different centers in order to improve knowledge in TMJ disc histopathology.


The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson's Disease.
The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota-gut-brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to identifying various neuronal cytotypes belonging to ENS in baseline conditions. The second part of the study provides evidence on how these very same neurons are altered during Parkinson's disease. In fact, although being defined as a movement disorder, Parkinson's disease features a number of degenerative alterations, which often anticipate motor symptoms. Among these, the GI tract is often involved, and for this reason, it is important to assess its normal and pathological structure. A deeper knowledge of the ENS is expected to improve the understanding of diagnosis and treatment of Parkinson's disease.


Efficacy of Anti-mesothelin Immunotoxin RG7787 plus Nab-Paclitaxel against Mesothelioma Patient-Derived Xenografts and Mesothelin as a Biomarker of Tumor Response.
Purpose: The purpose of this study was to evaluate the antitumor efficacy of the reduced immunogenicity anti-mesothelin immunotoxin RG7787 plus nab-paclitaxel against primary mesothelioma cell lines and tumor xenografts and the utility of mesothelin as a biomarker of tumor response.Experimental Design: Early-passage human malignant mesothelioma cell lines NCI-Meso16, NCI-Meso19, NCI-Meso21, and NCI-Meso29 were evaluated for sensitivity to RG7787 or nab-paclitaxel alone or in combination. In addition, the antitumor activity of RG7787 plus nab-paclitaxel was evaluated using NCI-Meso16, NCI-Meso21, and NCI-Meso29 tumor xenografts in immunodeficient mice. Serum mesothelin was measured at different time points to determine whether its levels correlated with tumor response.Results: All four primary mesothelioma cell lines highly expressed mesothelin with 41 × 103 to 346 × 103 mesothelin sites per cell and were sensitive to RG7787, with IC50 ranging from 0.3 to 10 ng/mL. Except for NCI-Meso19, these cells were also sensitive to nab-paclitaxel, with IC50 of 10 to 25 ng/mL. In vitro, RG7787 plus nab-paclitaxel led to decreased cell viability compared with either agent alone. In NCI-Meso16 tumor xenografts, treatment with RG7787 plus nab-paclitaxel led to sustained complete tumor regressions. Similar antitumor efficacy was observed against NCI-Meso21 and NCI-Meso29 tumor xenografts. In all three tumor xenograft models, changes in human serum mesothelin correlated with response to therapy and were undetectable in mice with complete tumor regression with RG7787 and nab-paclitaxel.Conclusions: RG7787 plus nab-paclitaxel is very active against primary human mesothelioma cells in vitro as well as in vivo, with serum mesothelin levels correlating with tumor response. These results indicate that this combination could be useful for treating patients with mesothelioma. Clin Cancer Res; 23(6); 1564-74. ©2016 AACR.


Pulmonary vein isolation by radiosurgery: implications for non-invasive treatment of atrial fibrillation.
Electrical isolation of the pulmonary veins (PVs) has been established in clinical routine as a curative treatment for atrial fibrillation (AF). While catheter ablation carries procedural risks, radiosurgery might be able to non-invasively induce lesions at the PV ostia to block veno-atrial electrical conduction. This porcine feasibility and dose escalation study determined the effect of radiosurgery on electrophysiologic properties of the left atrial-PV junction. Eight adult Goettingen mini-pigs underwent electrophysiological voltage mapping in the left atrium and the upper right PV. Radiation was delivered with a conventional linear accelerator. A single homogeneous dose ranging from 22.5 to 40 Gy was applied circumferentially to the target vein antrum. Six months after radiosurgery, electrophysiological mapping was repeated and a histological examination performed. Voltage mapping consistently showed electrical potentials in the upper right PV at baseline. Pacing the target vein prompted atrial excitation, thus proving veno-atrial electrical conduction. After 6 months, radiation had reduced PV electrogram amplitudes. This was dose dependent with a mean interaction effect of -5.8%/Gy. Complete block of atrio-venous electrical conduction occurred after 40 Gy dose application. Histology revealed transmural scarring of the targeted PV musculature with doses >30 Gy. After 40 Gy, it spanned the entire circumference in accordance with pulmonary vein isolation. Pulmonary vein isolation to treat AF can be achieved by radiosurgery with a conventional linear accelerator. Yet, it requires a high radiation dose which might limit clinical applicability.


Efficacy and safety of zaleplon at peak plasma levels.
Zaleplon is a non-benzodiazepine sleep medication that shows efficacy as a sleep inducer comparable to that of other hypnotics but with significantly fewer residual effects. In addition, evaluations of psychomotor or memory function at zaleplon peak plasma levels show much less impairment than noted with other hypnotics, suggesting an improved benefit-to-risk profile for zaleplon compared with older available agents. Thus, zaleplon can be used to treat symptoms of insomnia when they occur without the concern of next-day psychomotor or memory impairment, whether administered at bedtime or later during the night. Such an approach permits physicians to reformulate their strategies for safe and effective management of sleeplessness.


Alzheimer's disease: diagnosis and treatment.
This review describes and evaluates developments in the early diagnosis and the treatment of Alzheimer's disease. It is hoped that early diagnosis of the disorder will enable treatment that will reduce or arrest the associated cognitive loss so that affected individuals can retain significant function and institutionalization can be delayed or averted. Diagnostic techniques, including use of neuropsychological measures, functional imaging measures, and biological markers, are reviewed; such techniques are useful for confirming diagnosis but do not replace a comprehensive clinical evaluation. Potential treatment modalities, such as techniques to enhance neurotransmission, replace estrogen effects, reduce the effects of free radicals, and combat inflammation, are explored. Cholinesterase inhibitors are the only modality thus far shown in large-scale studies to be effective, but their effect is small.


Chitosan and α-cellulose-based mupirocin topical film-forming spray: Optimization, in vitro characterization, antimicrobial studies and wound healing activity.
The study aimed to develop a biopolymer-based mupirocin film-forming spray (MUP-FFS) for wound healing using chitosan and α-cellulose. MUP-FFS formulation was optimized by box-Behnken design, wherein the amount of chitosan, glycerol, and microfluidizer cycles showed a significant effect on the drying time and sprayability, but drug release remained unaffected. The optimized MUP-FFS formulation prepared by 13 microfluidizer cycles containing chitosan (0.125 %), glycerol (2.76 %) was quickly sprayable with 235 s drying time. The viscosity, spray uniformity and occlusive potential were found optimum for MUP-FFS. MUP-FFS released 98.066 % of MUP, 2-fold and 4-fold greater than the marketed ointment and MUP-API. The transmission electron microscopy displayed a homogeneous fibrous network, and scanning electron microphotographs showed uniform drug distribution on the MUP-film surface. The antimicrobial study revealed the efficacy of MUP-FFS against S.aureus and E.coli, wherein the former was more susceptible to formulation than the later. MUP-FFS indicated better wound contraction and healing than other groups on 7th and 14th day in rats. On Day-21, MUP-FFS could regress TGF-β1 to a normal level similar to the marketed formulation, which was also reflected in histopathological observations. Therefore, MUP-FFS can be a treatment option for chronic wounds, applied without touch and with minimal mechanical pressure.


Endogenous assays of DNA methyltransferases: Evidence for differential activities of DNMT1, DNMT2, and DNMT3 in mammalian cells in vivo.
While CpG methylation can be readily analyzed at the DNA sequence level in wild-type and mutant cells, the actual DNA (cytosine-5) methyltransferases (DNMTs) responsible for in vivo methylation on genomic DNA are less tractable. We used an antibody-based method to identify specific endogenous DNMTs (DNMT1, DNMT1b, DNMT2, DNMT3a, and DNMT3b) that stably and selectively bind to genomic DNA containing 5-aza-2'-deoxycytidine (aza-dC) in vivo. Selective binding to aza-dC-containing DNA suggests that the engaged DNMT is catalytically active in the cell. DNMT1b is a splice variant of the predominant maintenance activity DNMT1, while DNMT2 is a well-conserved protein with homologs in plants, yeast, Drosophila, humans, and mice. Despite the presence of motifs essential for transmethylation activity, catalytic activity of DNMT2 has never been reported. The data here suggest that DNMT2 is active in vivo when the endogenous genome is the target, both in human and mouse cell lines. We quantified relative global genomic activity of DNMT1, -2, -3a, and -3b in a mouse teratocarcinoma cell line. DNMT1 and -3b displayed the greatest in vivo binding avidity for aza-dC-containing genomic DNA in these cells. This study demonstrates that individual DNMTs can be tracked and that their binding to genomic DNA can be quantified in mammalian cells in vivo. The different DNMTs display a wide spectrum of genomic DNA-directed activity. The use of an antibody-based tracking method will allow specific DNMTs and their DNA targets to be recovered and analyzed in a physiological setting in chromatin.


Medullary carcinoma of the breast: Role of contrast-enhanced MRI in the diagnosis of multiple breast lesions.
Medullary carcinoma is a rare breast carcinoma with a syncytial growth pattern and high-grade cytology. It can be difficult to diagnose and may be missed on conventional imaging as the findings may overlap with benign lesions i.e. fibroadenomas. The authors report a case of a 25-year-old female who presented with multifocal breast lumps diagnosed with medullary carcinoma and fibroadenomas. Imaging and pathological correlation with contrast-enhanced MRI are presented in the diagnosis of these lesions.


At what cost? The social impact of American Indian gaming.
American Indian gaming has been called the "new buffalo." It has the potential to greatly influence cultural traditions on American Indian reservations. This study looks at the social impact that American Indian gaming is having on one reservation in northern Minnesota. Tribal members share strong feelings, both positive and negative, about the issue. Concerns about gaming include an increase in gambling abuse and addiction; a lack of appropriate child care; and concern that gaming is replacing traditional social activities. Some express concern that American Indian values are being replaced by materialism. Supporters of gaming point out that gaming provides tribal members with an opportunity to learn job skills and have gainful employment. Implications for social policy are given.


Physicochemical characterization of human S-protein and its function in the blood coagulation system.
S-protein, the main inhibitor of the assembly of the membrane attack complex of complement, was isolated from human plasma by a simple purification procedure, which includes barium citrate adsorption, ammonium sulphate precipitation, chromatography on DEAE-Sephacel and Blue Sepharose and gel filtration on Sephacryl S-200. The homogeneous protein (sedimentation coefficient 4.6 S) was obtained in approx. 5% yield relative to its concentration in plasma, which was found to be 0.3-0.5 mg/ml. The final product did not cross-react with antisera against complement proteins or other proteinase inhibitors of human plasma. On polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, S-protein migrated as a single-chain band with an apparent Mr of 74000 under non-reducing conditions and as a doublet of Mr 78000 and 65000 upon reduction. In plasma or serum S-protein also existed in two forms of corresponding Mr values, as was evidenced by an immunoblot enzyme-linked immunosorbent assay technique. S-protein was found to be an acidic glycoprotein with 10% (W/W) carbohydrate content and several isoelectric points in the range pH 4.75-5.25, and it contained one free thiol group per molecule of protein. The functional properties of S-protein in the complement system were demonstrated by its ability to inhibit complement-dependent cell lysis in a concentration-dependent manner (Ki 0.6 microM) and by its incorporation into the nascent SC5b-7 complex. A new function for S-protein could be revealed in the blood coagulation system. The slow progressive inhibition of thrombin by antithrombin III was not affected by S-protein, whereas the purified protein interfered with the fast inactivation of thrombin clotting as well as amidolytic activity by antithrombin III-heparin complex. The acceleration of this inhibition reaction by heparin was counteracted by S-protein, indicating the ability of S-protein to neutralize heparin activity.


Multidrug residues and antimicrobial resistance patterns in waste milk from dairy farms in Central California.
Waste milk (WM) is a common source of feed for preweaned calves in US dairy farms. However, limited information is available about characteristics of this product, including concentration of drug residues and potential hazards from antibiotic-resistant bacteria present in the milk. The aims of this cross-sectional study were to (1) identify and measure the concentration of antimicrobial residues in raw WM samples on dairy farms in the Central Valley of California, (2) survey farm management practices for factors associated with the occurrence of specific antimicrobial residues in raw WM, (3) characterize the antimicrobial resistance patterns of E. coli cultured from raw WM samples, and (4) evaluate the potential association between WM quality parameter and risk of identifying drug residues in milk. A single raw bulk tank WM sample was collected from dairy farms located in California's Central Valley (n = 25). A questionnaire was used to collect information about farm management practices. Waste milk samples were analyzed for a multidrug residue panel using liquid chromatography-tandem mass spectrometry. Bacteria were cultured and antimicrobial resistance was tested using standard techniques; milk quality parameters (fat, protein, lactose, solids-not-fat, somatic cell count, coliform count, and standard plate count) were also measured. Of the 25 samples collected, 15 (60%) contained detectable concentrations of at least 1 antimicrobial. Of the drug residue-positive samples, 44% (11/25) and 16% (4/25) had detectable concentrations of β-lactams and tetracycline, respectively. The most prevalent drug residues were ceftiofur (n = 7, 28%), oxytetracycline (n = 4, 16%), and cephapirin (n = 3, 12%). No significant associations were identified between farm characteristics or management practices and presence of drug residues in WM. In this study, 20% of farms did not pasteurize WM before feeding to calves. Two of the 10 Escherichia coli isolated from WM samples were multidrug resistant. Streptococcus spp. (n = 21, 84%) was the most common genus cultured from WM samples, followed by Staphylococcus spp. (n = 20, 80%) and E.coli (n = 10, 40%). Mycoplasma spp. was cultured from 2 WM samples (n = 2, 8%). The presence of drug residues in WM at concentrations that increase selection of resistant bacteria indicates the need for additional studies targeting on-farm milk treatments to degrade drug residues before feeding to calves. The presence of multidrug-resistant E. coli in WM urges the need for on-farm practices that reduce calf exposure to resistant bacteria, such as pasteurization.


Evidence-based behavioral medicine: what is it and how do we achieve it?
The goal of evidence-based medicine is ultimately to improve patient outcomes and quality of care. Systematic reviews of the available published evidence are required to identify interventions that lead to improvements in behavior, health, and well-being. Authoritative literature reviews depend on the quality of published research and research reports. The Consolidated Standards for Reporting Trials (CONSORT) Statement (www.consort-statement.org) was developed to improve the design and reporting of interventions involving randomized clinical trials (RCTs) in medical journals. We describe the 22 CONSORT guidelines and explain their application to behavioral medicine research and to evidence-based practice. Additional behavioral medicine-specific guidelines (e.g., treatment adherence) are also presented. Use of these guidelines by clinicians, educators, policymakers, and researchers who design, report, and evaluate or review RCTs will strengthen the research itself and accelerate efforts to apply behavioral medicine research to improve the processes and outcomes of behavioral medicine practice.


Localized intestinal radiation and liquid diet enhance survival and permit evaluation of long-term intestinal responses to high dose radiation in mice.
In vivo studies of high dose radiation-induced crypt and intestinal stem cell (ISC) loss and subsequent regeneration are typically restricted to 5-8 days after radiation due to high mortality and immune failure. This study aimed to develop murine radiation models of complete crypt loss that permit longer-term studies of ISC and crypt regeneration, repair and normalization of the intestinal epithelium. In C57Bl/6J mice, a predetermined small intestinal segment was exteriorized and exposed to 14 Gy-radiation, while a lead shield protected the rest of the body from radiation. Sham controls had segment exteriorization but no radiation. Results were compared to C57Bl/6J mice given 14 Gy-abdominal radiation. Effects of elemental liquid diet feeding from the day prior to radiation until day 7 post-radiation were assessed in both models. Body weight and a custom-developed health score was assessed every day until day 21 post-radiation. Intestine was assessed histologically. At day 3 after segment radiation, complete loss of crypts occurred in the targeted segment, while adjacent and remaining intestine in segment-radiated mice, and entire intestine of sham controls, showed no detectable epithelial damage. Liquid diet feeding was required for survival of mice after segment radiation. Liquid diet significantly improved survival, body weight recovery and normalization of intestinal epithelium after abdominal radiation. Mice given segment radiation combined with liquid diet feeding showed minimal body weight loss, increased food intake and enhanced health score. The segment radiation method provides a useful model to study ISC/crypt loss and long-term crypt regeneration and epithelial repair, and may be valuable for future application to ISC transplantation or to genetic mutants that would not otherwise survive radiation doses that lead to complete crypt loss. Liquid diet is a simple intervention that improves survival and facilitates long-term studies of intestine in mice after high dose abdominal or segment radiation.


Selective uptake of cholesteryl esters from apolipoprotein-E-free high-density lipoproteins by rat parenchymal cells in vivo is efficiently coupled to bile acid synthesis.
[3H]Cholesteryl ester-labelled human high-density lipoprotein (HDL) was injected into rats and its decay, intrahepatic cellular distribution and the kinetics of biliary secretion were determined. At 10 min after injection the hepatic uptake of cholesteryl esters from HDL was 3-fold higher as compared with the apolipoprotein. Selective uptake was exerted only by parenchymal cells (5.6-fold more cholesteryl esters than apolipoprotein) and not by liver endothelial or Kupffer cells. The kinetics of biliary secretion of processed cholesteryl esters initially associated with HDL or low-density lipoprotein (LDL) were compared in unrestrained rats, equipped with permanent catheters in bile duct, duodenum and heart. At 72 h after injection of [3H]cholesteryl oleate-labelled HDL, 51.0 +/- 2.5% of the injected dose was recovered as bile acids, which is about twice as high as the secretion of biliary radioactivity after injection of [3H]cholesteryl oleate-labelled LDL. Oestradiol treatment stimulated only liver uptake of LDL cholesteryl esters, and resulted in a 2-fold higher liver uptake than with HDL. However, the rate of radioactive bile acid formation from [3H]cholesteryl oleate-labelled HDL was still more rapid than for LDL. It is concluded that the selective uptake pathway for cholesteryl esters from HDL in parenchymal cells is more efficiently coupled to the formation of bile acids than is the cholesteryl ester uptake from LDL. This efficient coupling may facilitate the role of HDL in reverse cholesterol transport.


Genotoxicity of p-nitrocinnamaldehyde and related alpha, beta-unsaturated carbonyl compounds in two bacterial assays.
Seventeen cinnamaldehydes, cinnamic acids, 2-furylacroleins and related compounds were tested in the Salmonella preincubation reversion assay and in the SOS chromotest. Of eight compounds containing nitrogroups, seven were clearly mutagenic in the presence of S9 mix and six in its absence; whereas none of the parent compounds not containing a nitrogroup and none of the congeners containing chlorine, methoxy or amino groups were mutagenic. Metabolic epoxidation was excluded in additional experiments using SKF525, an inhibitor of mono-oxygenases, and trichloropropene oxide, an inhibitor of epoxide hydrolases. Less or no mutagenicity was found in the nitroreductase deficient strains Salmonella typhimurium TA100NR or TA98NR and in the O-acetyltransferase deficient strains TA100/1,8-DNP6 or TA98/1,8-DNP6 except with 5-nitro-2-furylacrolein which exhibited decreased mutagenicity in TA100NR when compared with TA100 but the highest mutagenicity in TA100/1,8-DNP6. Less or no genotoxic activity was found in the SOS chromotest when using the nitroreductase deficient Escherichia coli strain PQ253 whereas all seven compounds tested were positive in strain PQ37. The results demonstrate the importance of the nitro group and that the compounds are activated either by bacterial nitroreductase or by the nitroreductase in the S9 mix. A chemical activation of the acrolein moiety by the negative inductive effect of the nitro group is unlikely. The genotoxicity of the cinnamyl compounds is dependent on the position of the nitro group in the phenyl ring. The genotoxicities of the p-nitro compounds were about two orders of magnitude higher than those of the ortho and meta congeners. The comparison between the Ames test and the SOS chromotest showed good agreement.


A functional analysis of the repeated methionine initiator tRNA genes (IMT) in yeast.
Standard laboratory yeast strains have from four to five genes encoding the methionine initiator tRNA (IMT). Strain S288C has four IMT genes with identical coding sequences that are colinear with the RNA sequence of tRNA(IMet). Each of the four IMT genes from strain S288C is located on a different chromosome. A fifth IMT gene with the same coding sequence is present in strain A364A but not in S288C. By making combinations of null alleles in strain S288C, we show that each of the four IMT genes is functional and that tRNA(IMet) is not limiting in yeast strains with three or more intact genes. Strains containing a single IMT2, 3 or 4 gene grow only after amplification of the remaining IMT gene. Strains with only the IMT1 gene intact are viable but grow extremely slow; normal growth is restored by the addition of another IMT gene by transformation, providing a direct test for IMT function.


Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation.
FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e., > 40 Gy/s) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤ 0.1 Gy/s have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed an integrated microdosimetric-kinetic (IMK) model for UHDR irradiation enabling the prediction of surviving fraction after UHDR irradiation. The IMK model for UHDR-irradiation considers the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate. The estimate by the developed model could successfully reproduce the in vitro experimental dose-response curve for various cell line types and dose rates. The developed model would be useful for predicting the biological effects under the UHDR irradiation.


Fundamental parenchyma cells are involved in Na+ and Cl- removal ability in rice leaf sheath.
Salt sensitivity in rice plants is associated with the accumulated amount of Na+ and Cl- in shoots and, more significantly, in photosynthetic tissues. Therefore, salt removal ability at the leaf sheath level is an important mechanism of salt tolerance. In the present study we attempted to determine whether rice leaf sheaths excluded Cl- as well as Na+, and to identify the tissues that were involved in the removal ability of both ions. In two rice genotypes, salt-tolerant FL478 and -sensitive IR29, leaf sheaths excluded Na+ and Cl- under NaCl treatment as estimated using their sheath:blade ratios. The sheath:blade ratio of Na+ but not of Cl-, was increased by NaCl treatment. Under NaCl treatment, Na+ concentration was higher in the basal leaf sheath, whereas Cl- concentration was higher in the middle and tip parts. At the tissue level, fundamental parenchyma cells of leaf sheaths retained the highest amounts of Na and Cl when treated with high amount of NaCl. These results imply that the leaf sheath potentially functions to remove excess Na+ and Cl- from xylem vessels in different locations along the axis, with the fundamental parenchyma cells of leaf sheaths being involved in over-accumulation of both Na+ and Cl-.


Retinal flat cells participate in the formation of fibers by retinal neuroblasts in vitro. Time lapse video studies.
Freshly dissociated cells from embryonic chick neural retinas grow in characteristic patterns on flat cells or on chick embryo mesodermal cells. A striking difference between the two patterns is that the cells grown on flat cells are interconnected by a complex network of fibers, whereas those grown on mesodermal cells are aggregated into clusters that remain relatively isolated within the mesodermal monolayer. Analysis by time-lapse video microscopy indicates that two processes produce the fibers. (1) Fibers grow out by the extension of growth cones from cells within aggregates. (2) Neuronal cell aggregates that attach to two flat cells are pulled apart by the movement of the cells beneath them. As the aggregate is pulled apart, portions of the cells remain attached to the two halves, and their cytoplasm is drawn into thin fibers. The lack of fibers on a mesodermal substrate is due to two factors: (1) Aggregates are widely spaced on the substrate surface and do not come into contact often. (2) On those occasions when they do come into contact, the movement of the monolayer is so vigorous that emerging fibers are torn.


Assessment of maternal and child health care services performance in the context of COVID-19 pandemic in Addis Ababa, Ethiopia: evidence from routine service data.
In many settings, health care service provision has been modified to managing COVID-19 cases, and this has been affecting the provision of maternal and child health services. The aim of this study was to assess trends in selected maternal and child health services performance in the context of COVID-19 pandemic. A cross-sectional data review was conducted in Addis Ababa, Ethiopia from April to May 2021. Routine health management information system database was reviewed from Addis Ababa Health Bureau for the period from July 2019 to March 2021 across all quarters. Proportion and mean with standard deviation were computed. T-test was used to assess statistically significant differences in services mean performance. Postnatal care visit, new contraceptives accepters, safe abortion care and number of under-5 years old children treated for pneumonia significantly decreased by 9.3% (p-value 0.04), 20.3% (p-value 0.004), 23.7% (p-value 0.01) and 77.2% (p-value < 0.001), respectively during the first 8 months of the COVID-19 pandemic compared to the previous 8 months' average performance. The trends in Antenatal care first visit, new contraceptive accepters, pentavalent-3 vaccination and under-five children treated for pneumonia began to decline in January to March 2020, a quarter when the COVID-19 pandemic began; with accelerated declines in April to June 2020 following national lockdown. The trends for the stated services began to increase during July-September 2020, the last quarter of national lockdown. Contraceptive accepters and pentavalent-1 vaccination continued to decline and showed no recovery until January-March 2021 when this study was completed. Most of the maternal and child health services performance declined following the onset of COVID-19 pandemic and national lockdown, and most of the services began recovering during July-September 2020, the last quarter of national lockdown. However, new and repeat contraceptive accepters and pentavalent-1 recipients continue to decline and show no recovery during end of the study period. Implementing COVID-19 prevention measures and assuring the community about the safety of service delivery is imperative to ensure continuity of the maternal and child health services. Regular monitoring and evaluation of services performance is required to identify slowly recovering services and respond to potentially volatile changes during the COVID-19 pandemic.


Rate of growth and extent of differentiation reflected by cytoplasmic proteins and antigens of human colon tumor cell lines.
The cytosolic proteins and antigens of 11 human colon tumor cell lines were examined with respect to their rate of growth and state of differentiation. Coomassie blue-stained protein analysis of sodium dodecyl sulfate-containing polyacrylamide gels revealed protein bands at Mr 30,000, 31,000, and 58,000, which were characteristic of slower growing and more differentiated cell lines. More rapidly dividing and disdifferentiated colon cell lines lacked the Mr 30,000 and Mr 58,000 bands; instead, they produced a single protein band that ran between the Mr 30,000 and Mr 31,000 positions on the gel. Western transfer analysis of cytoplasmic antigens further subdivided the 11 cell lines into 3 separate categories. Slowly growing and more differentiated lines produced a Mr 52,000 antigen. Intermediate lines, with respect to growth rate and state of differentiation, produced a Mr 38,000 antigen. The rapidly growing and highly disdifferentiated cell lines contained three cytosolic antigens with molecular weights of 37,000, 39,000, and 48,000. These criteria made it possible to classify these 11 human colon tumor tissue culture cell lines into 3 groups which reflect their state of growth activity and degree of differentiation.


Low incidence of vertebral fractures in early spondyloarthritis: 5-year prospective data of the DESIR cohort.
An increased risk of vertebral fractures (VFs) has been reported in spondyloarthritis (SpA). Our hypothesis is that the prevalence of VFs is lower than reported in previous studies, especially in early SpA. This study aimed at assessing the incidence of radiographical VFs over 5 years in early axial SpA. The DESIR (DEvenir des Spondylarthropathies Indifférenciées Récentes) cohort, which included patients with inflammatory back pain highly suggestive of axial SpA, is the basis of this study. All radiographs of the DESIR cohort had been assessed at a central facility, by one investigator specialised in the field of the diagnosis of VFs according to Genant's method. We assessed the prevalence and incidence of VFs and vertebral deformities at baseline and over 5 years. Five-year X-rays were available for 432 patients (mean age 34.3±8.7 years, 53% women). Diagnosis of VF was doubtful and needed adjudication for 19 patients (4.4%). 13 patients had prevalent VFs (3.0%) which were located at the thoracic spine (12 were grade 1). At 5 years, five patients had an incident VF (1.15%); seven vertebrae were fractured, mostly located at the thoracic spine (n=6/7), and of grade 1 (n=6/7). In the DESIR cohort, a population of early SpA, we found a low prevalence and incidence of VFs (3.0% and 1.15 %), respectively. This confirms our hypothesis that the actual prevalence and incidence of VFvertebral fracture in SpA is lower than that reported in the previous studies.


Update on early childhood caries since the Surgeon General's Report.
The 2000 Surgeon General's Report on Oral Health included a limited discussion of the condition known as early childhood caries. Because of its high prevalence, its impact on young children's quality of life and potential for increasing their risk of caries in the permanent dentition, early childhood caries is arguably one of the most serious and costly health conditions among young children. A necessary first step in preventing dental caries in preschool children is understanding and evaluating the child's caries risk factors. Previous caries experience and white spot lesions should automatically classify a preschool child as high risk for caries. Microbial factors, such as presence of visible plaque and tests that identify a child as having high levels of mutans streptococci, also predict caries in young children. Frequency of sugar consumption, enamel developmental defects, social factors such as socioeconomic status, psychosocial factors, and being an ethnic minority also have shown to be relevant in determining caries risk. On the basis of this knowledge of specific risk factors for an individual, different preventive strategies and different intensities of preventive therapies can be implemented. Caries preventive strategies in preschool children include fluoride therapy, such as supervised tooth brushing with a fluoridated dentifrice, systemic fluoride supplement to children who live in a nonfluoridated area and who are at risk for caries, and professional topical fluoride with fluoride varnish. There is emerging evidence that intensive patient counseling or motivational interviews with parents to change specific behaviors may reduce caries prevalence in their children. Findings regarding antimicrobial interventions, efforts to modify diets, and traditional dental health education are less consistent.