Luminal CCK-releasing factor stimulates CCK release from human intestinal endocrine and STC-1 cells.
CCK is secreted into the blood from intestinal endocrine cells following ingestion of a meal. Recently, it has been demonstrated that the ability of certain foods to stimulate CCK release is mediated by endogenously produced CCK-releasing factors. A newly discovered luminal CCK-releasing factor (LCRF) is secreted into the intestine, where it stimulates CCK secretion. However, the mechanism whereby LCRF affects intestinal epithelial cells is unknown. The current study was designed to determine whether LCRF has a direct effect on CCK cells to stimulate hormone secretion. In dispersed human intestinal mucosal cells, LCRF (5-200 nM) significantly stimulated CCK release in a concentration-dependent manner. This stimulatory effect was absent in calcium-free media and was inhibited by the L-type calcium-channel blockers diltiazem and nifedipine. To examine direct cellular effects of LCRF on CCK cells, further studies were conducted in the CCK-containing enteroendocrine cell line STC-1. As in native cells, LCRF significantly stimulated CCK release from STC-1 cells in a calcium-dependent manner. In cells loaded with a calcium-sensitive dye, LCRF stimulation produced a rapid increase in intracellular calcium. To examine the electrophysiological basis for this stimulation, whole cell recordings were made from STC-1 cells. Whole cell calcium currents were identified under basal conditions; moreover, calcium-channel activity was increased by LCRF. These studies demonstrate that 1) LCRF has a direct effect on human intestinal cells to stimulate CCK secretion, 2) stimulated hormone release is calcium dependent, and 3) LCRF activates calcium currents in CCK cells, which leads to CCK secretion.


Tuning Electroluminescence from a Plasmonic Cavity-Coupled Silicon Light Source.
The combination of Moore's law and Dennard's scaling rules have constituted the fundamental guidelines for the silicon-based semiconductor industry for decades. Furthermore, the enormous growth of global data volume has pushed the demand for complex and densely packed devices. In recent years, it has become clear that wired interconnects impose increasingly severe speed and power limitations onto integrated circuits as scaling slows toward a halt. To overcome these limitations, there is a clear need for optical data processing. Despite significant progress in the development of silicon photonics, light sources remain challenging owing to the indirect bandgap of group IV materials. It is therefore highly desirable to develop new concepts for a silicon light source that meets efficiency and footprint requirements similar to their electronic counterparts. Here, we demonstrate an electrically driven and tunable silicon light source by matching the resonant modes of a silver nanocavity with the hot luminescence spectrum of an avalanching p-n junction. The cavity significantly enhances phonon-assisted recombination of hot carriers by tailoring the local density of states at the size-tunable resonance. Such tunable nanoscale emitter may be of great interest for short-reach communications, microdisplays or lab-on-chip applications.


Relationships Between Different Internal and External Training Load Variables and Elite International Women's Basketball Performance.
To investigate the relationships between internal and external training load (TL) metrics with elite international women's basketball performance. Sessional ratings of perceived exertion, PlayerLoad™/minute, and training duration were collected from 13 elite international-level female basketball athletes (age 29.0 [3.7] y, stature 186.0 [9.8] cm, body mass 77.9 [11.6] kg) during the 18 weeks prior to the International Basketball Federation Olympic qualifying event for the 2016 Rio Olympic Games. Training stress balance, differential load, and the training efficiency index were calculated with 3 different smoothing methods. These TL metrics and their change in the last 21 days prior to competition were examined for their relationship to competition performance as coach ratings of performance. For a number of TL variables, there were consistent significant small to moderate correlations with performance and significant small to large differences between successful and unsuccessful performances. However, these differences were only evident for external TL when using exponentially weighted moving averages to calculate TL. The variable that seemed most sensitive to performance was the change in training efficiency index in the last 21 days prior to competition (performance r = .47-.56, P < .001 and difference between successful and unsuccessful performance P < .001, f2 = 0.305-0.431). Internal and external TL variables were correlated with performance and distinguished between successful and unsuccessful performances among the same players during international women's basketball games. Manipulating TL in the last 3 weeks prior to competition may be worthwhile for basketball players' performance, especially in internal TL.


Metabolic profiling of Medicago truncatula cell cultures reveals the effects of biotic and abiotic elicitors on metabolism.
GC-MS-based metabolite profiling was used to analyse the response of Medicago truncatula cell cultures to elicitation with methyl jasmonate (MeJa), yeast elicitor (YE), or ultraviolet light (UV). Marked changes in the levels of primary metabolites, including several amino acids, organic acids, and carbohydrates, were observed following elicitation with MeJa. A similar, but attenuated response was observed following YE elicitation, whereas little response was observed following UV elicitation. MeJa induced the accumulation of the triterpene beta-amyrin, a precursor to the triterpene saponins, and LC-MS analysis confirmed the accumulation of triterpene saponins in MeJa-elicited samples. In addition, YE induced a slight, but significant accumulation of shikimic acid, an early precursor to the phenylpropanoid pathway, which was also demonstrated to be YE-inducible by LC-MS analyses. Correlation analyses of metabolite relationships revealed perturbation of the glycine, serine, and threonine biosynthetic pathway, and suggested the induction of threonine aldolase activity, an enzyme as yet uncharacterized from plants. Members of the branched chain amino acid pathway accumulated in a concerted fashion, with the strongest correlation being that between leucine and isoleucine (r2=0.941). While UV exposure itself had little effect on primary metabolites, the experimental procedure, as revealed by control treatments, induced changes in several metabolites which were similar to those following MeJa elicitation. Sucrose levels were lower in MJ- and YE-elicited samples compared with control samples, suggesting that a portion of the effects observed on the primary metabolic pool are a consequence of fundamental metabolic repartitioning of carbon resources rather than elicitor-specific induction. In addition, beta-alanine levels were elevated in all elicited samples, which, when viewed in the context of other elicitation responses, suggests the altered metabolism of coenzyme A and its esters, which are essential in secondary metabolism.


Non-association of IL-12 +1188 and IFN-γ +874 polymorphisms with cytokines serum level in occult HBV infected patients.
Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI. In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA. Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of HBsAg-/anti-HBc+ samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines. According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.


Clinical and immunochemical study of the serum IgG fraction not precipitated in a zinc-sodium salicylate reagent.
A reagent made of zinc sulphate (0-08 M) in a 0-4 M sodium salicylate solution at pH 7-3 precipitated most of the IgG when a small volume of human serum was added. Sera with normal IgG levels or polyclonal hyperglobulinaemia showed a close correlation between total IgG and zinc-precipitated IgG (r = + 0-95). In clinical material, not including IgG myeloma, zinc-soluble IgG varied between 0 and 6 mg/ml and was independent of the IgG serum concentration. In 31 normal subjects the average IgG concentration, as determined by the Technicon immunonephelometric method, was 10-2 +/- 1-7 mg/ml for total IgG and 2-2 +/- 1-0 mg/ml for the soluble fraction. Among 173 sera, including 24 from cord blood, 16 from pregnant women, and 133 from patients with miscellaneous diseases, no pathological conditions except three cases of IgG myeloma were found with a zinc-soluble IgG definitely above the normal values; zinc-soluble IgG levels were often low in patients with hyperglobulinaemia, and the difference was highly significant in liver disease. kappa and gamma light chains as well as the four IgG-Hp chain subclasses were found in both zinc-soluble fractions of normal IgG. A study of myeloma monoclonal IgG showed that globulins of classes 1, 3, and 4 could be either soluble or insoluble in the zinc reagent. One, G2, was mainly insoluble. Hexose and antistreptolysin contents per milligram normal IgG were not significantly different in either fraction. It is suggested that zinc-soluble IgG consists of the recently synthesized molecules, the zinc-solubility of which has not yet been decreased by protein association, lipid interaction, antigen binding, or enzymatic denaturation. Within this hypothesis, a low level of soluble IgG would mean either an increased precatabolic protein or a decreased synthesis.


Literacy, cultural diversity, and client education.
Client education offers many challenges to health care professionals. There is a mismatch between the reading level of most clients and the reading level of printed materials used in health education. Social and cultural factors also influence how our clients are able to learn about their health. These problems can lead to noncompliance with treatments, missed appointments, wrong dosages of medication, and undue fear among our clients. There are things that health care professionals can do to make written materials more user-friendly and culturally more acceptable.


Highly Efficient Encapsulation and Phase Separation of Apolar Molecules by Magnetic Shell-by-Shell-Coated Nanocarriers in Water.
We report on the development of a supramolecular nanocarrier concept that allows for the encapsulation and separation of small apolar molecules from water. The nanocarriers consist of shell-by-shell-coated nanoparticles such as TiO2 and ferromagnetic Fe3 O4 . The first ligand shell is provided by covalently bound hexadecyl phosphonic acid (PAC16 ) and the second shell by noncovalently assembled amphiphiles rendering the hybrid architecture soluble in water. Agitation of these constructs with water containing the hydrocarbons G1-G4, the fluorescent marker G5, the polychlorinated biphenyl PCB 77, or crude oil leads to a very efficient uptake (up to 411 %) of the apolar contaminant. In case of the hybrids containing a Fe3 O4 core, straightforward phase separation by the action of an external magnet is provided. The load can easily be released by a final treatment with an organic solvent.


Evaluation of hearing handicap. The American Academy of Otolaryngology and American Council of Otolaryngology (AA0-ACO)
The American Academy of Otolaryngology and American Council of Otolaryngology (AAO-ACO) define hearing handicap as a disability to understand sentences under everyday vocal and listening conditions, and describe procedures for its estimation from pure-tone threshold hearing levels. Research now reveals that the AAO-ACO procedures underestimate measured hearing handicap by the equivalent of averaged pure-tone threshold losses of 17 dB at high-percentage handicaps to 35 dB at low-percentage handicaps. It is proposed that AAO-ACO procedures be modified as follows: (a) adjust hearing levels for presbycusis when estimating handicap due to noise or other factors than presbycusis; (b) change averaged hearing level "fences" from present 25 dB to 15 dB for 0 percent and from present 92 dB to 75 dB for 100 percent handicap; and (c) change weight for "worse" ear contribution from present 1/6 to 1/4 for binaural listening.


Seroepidemiologic studies of hantavirus infection among wild rodents in California.
A total of 4,626 mammals were serologically tested for antibodies to Sin Nombre virus. All nonrodent species were antibody negative. Among wild rodents, antibody prevalence was 8.5% in murids, 1.4% in heteromyids, and < 0.1% in sciurids. Of 1,921 Peromyscus maniculatus (deer mice), 226 (11.8%) were antibody positive, including one collected in 1975. The highest antibody prevalence (71.4% of 35) was found among P. maniculatus on Santa Cruz Island, off the southern California coast. Prevalence of antibodies among deer mice trapped near sites of human cases (26.8% of 164) was significantly higher than that of mice from other sites (odds ratio = 4.5; 95% confidence interval = 1.7, 11.6). Antibody prevalence increased with rising elevation (> 1,200 meters) and correlated with a spatial cluster of hantavirus pulmonary syndrome cases in the Sierra Nevada.


Erratum.
In the article "String as a theory of everything" by M. Mitchell Waldrop (Research News, 20 Sept., p. 1251), the last line of the first column was inadvertantly omitted. The affected sentence should have read, "Not only were the strong interactions far more complex than predicted by field theory, but the particles that participated in the strong interactions-the hadrons, a group that includes protons, neutrons, pi mesons, and many others-seemed to be relatively large, extended objects as much as 1 Fermi across (10(-13) centimeter)." In the next-to-the-last line of the second full paragraph in column 2 on page 1252, 10(-19) should have been 10(+19). Finally, the words "quandary" (page 1251, column 1, paragraph 6, line 2) and "quark" (page 1252, column 3, last paragraph, line 18) were misspelled.


MR Defecography in Assessing Functional Defecation Disorder: Diagnostic Value of the Defecation Phase in Detection of Dyssynergic Defecation and Pelvic Floor Prolapse in Females.
Dyssynergic defecation (DD) and pelvic floor prolapse often coexist in female functional defecation disorder. A retrospective study was performed to evaluate the ability of dynamic MR sequences with the straining and defecation phase to detect paradoxical puborectalis contraction and occult multiple-compartments disorders. Fifty-three females clinically diagnosed with DD underwent magnetic resonance defecography. The dynamic sequences consist of rest, squeeze, straining, and defecation. The straining phase (pre rectal filling) and defecation phase (post rectal filling) were acquired to assess for pelvic floor relaxation and pelvic organ descent. MR images were analyzed by 2 radiologists with regard to paradoxical puborectalis contraction (changes in the anorectal angle [ARA]) and the presence of pelvic organ prolapse in straining phase and defecation phase independently. Statistical analysis was performed using Wilcoxon's matched-pairs signed-ranks test and Crosstabs test for matched pairs. Among the 53 patients with DD, 24 individuals (45.3%) were diagnosed DD with multifocal disorders. Comparison between the straining and the defecation phase revealed that there was no significant difference in the change of the ARA (p > 0.05), while significant differences were found in cystocele, vaginal or cervical prolapse, rectocele and descending perineum syndrome between the straining and the defecation phase (p < 0.05). The defecation phase with impaired evacuation distinguished additional anterior/middle compartments findings in female DD patients. The straining phase and the defecation phase have the same ability in assessing paradoxical puborectalis contraction of the DD. Compared with the straining phase, the defecation phase provides the maximum stress to the pelvic floor resulting in complete levator ani relaxation. In addition to diagnosing the abnormal anorectal function, the defecation phase with the discharge of the rectal filling demonstrates maximum anterior/middle pelvic organ descent in DD patients.


Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters.
A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. ClinicalTrials.gov Identifier: NCT02708901 . Retrospectively registered: March 4, 2016.


The Role of Brain Cholesterol and its Oxidized Products in Alzheimer's Disease.
The human brain is the most cholesterol-rich organ harboring 25% of the total cholesterol pool of the whole body. Cholesterol present in the central nervous system (CNS) comes, almost entirely, from the endogenous synthesis, being circulating cholesterol unable to cross the blood-brain barrier (BBB). Astrocytes seem to be more active than neurons in this process. Neurons mostly depend on cholesterol delivery from nearby cells for axonal regeneration, neurite extension and synaptogenesis. Within the brain, cholesterol is transported by HDL-like lipoproteins associated to apoE which represents the main apolipoprotein in the CNS. Although CNS cholesterol content is largely independent of dietary intake or hepatic synthesis, a relationship between plasma cholesterol level and neurodegenerative disorders, such as Alzheimer's disease (AD), has often been reported. To this regard, alterations of cholesterol metabolism were suggested to be implicated in the etiology of AD and amyloid production in the brain. Therefore a special attention was dedicated to the study of the main factors controlling cholesterol metabolism in the brain. Brain cholesterol levels are tightly controlled: its excessive amount can be reduced through the conversion into the oxidized form of 24-S-hydroxycholesetrol (24-OH-C), which can reach the blood stream. In fact, the BBB is permeable to 24-OH-C as well as to 27-OH-C, another oxidized form of cholesterol mainly synthesized by non- neural cells. In this review, we summarize the main mechanisms regulating cholesterol homeostasis and review the recent advances on the role played by cholesterol and cholesterol oxidized products in AD. Moreover, we delineate possible pharmacological strategies to control AD progression by affecting cholesterol homeostasis.


Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial.
Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care. This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6-10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535. Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6-10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4-14·4]), equivalent to 13 h (95% CI 5-21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection. Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes. National Institute for Health Research Efficacy and Mechanisms Evaluation Programme.


Osteopontin and its integrin receptor alpha(v)beta3 are upregulated during formation of the glial scar after focal stroke.
Microglia and astrocytes in the peri-infarct region are activated in response to focal stroke. A critical function of activated glia is formation of a protective barrier that ultimately forms a new glial-limiting membrane. Osteopontin, a provisional matrix protein expressed during wound healing, is induced after focal stroke. The present study was performed to determine the spatial and temporal expression of osteopontin and its integrin receptor alpha(v)beta3 during formation of the peri-infarct gliotic barrier and subsequent formation of a new glial-limiting membrane. Spontaneously hypertensive rats (n = 19) were subjected to permanent occlusion of the middle cerebral artery and killed 3, 6, and 24 hours and 2, 5, and 15 days after occlusion. The spatial and temporal expression of osteopontin mRNA was determined by in situ hybridization, and that of osteopontin ligand and its integrin receptor alpha(v)beta3 was determined by immunohistochemistry. Osteopontin mRNA was expressed de novo in the peri-infarct region from 3 to 48 hours; by 5 days osteopontin mRNA expression was restricted to the infarct. Osteopontin protein was expressed by peri-infarct microglia beginning at 24 hours and by microglia/macrophages at 48 hours in the infarct. Integrin receptor alpha(v)beta3 was expressed in peri-infarct astrocytes at 5 and 15 days. Early microglial/macrophage expression of osteopontin mRNA defines the borders and final infarct area at 24 hours. At 5 days osteopontin ligand is at a distance from the peri-infarct astrocytes expressing integrin receptor alpha(v)beta3. By 15 days astrocytes expressing integrin receptor alpha(v)beta3 are localized in an osteopontin-rich region concomitant with formation of the new glial-limiting membrane. The de novo expression and interaction of osteopontin ligand with its receptor integrin alpha(v)beta3 suggest a role in wound healing after focal stroke.


Causes and Consequences of Interdialytic weight gain.
Higher interdialytic weight gain (IDWG) is associated with higher predialysis blood pressure and increased mortality. IDWG is also increasingly being recognized as an indicator of nutritional status. We studied in detail the associations of various patient factors and nutritional parameters with IDWG. We collected data during one week for IDWG and hemodynamic parameters in 138 prevalent adult haemodialysis patients on a thrice-weekly haemodialysis schedule. A multivariate linear regression analysis was employed to identify factors that are associated with IDWG. The mean (±SD) age was 62.5 (±18.2) years, 36% were female, 36% had diuresis, and 23% had diabetes. Patients in the highest IDWG tertile were significantly younger, more frequently male, and had a significantly higher subjective global assessment score (SGA). A higher IDWG as a percentage of body weight (%IDWG) was associated with a younger age, greater height and weight, absence of diuresis, and lower postdialysis plasma sodium levels. The model with these five parameters explained 37% of the variance of %IDWG. Predialysis, intradialysis, and postdialysis diastolic blood pressure was significantly higher in the highest tertile of IDWG. The most important associations of %IDWG are age, height, weight, diuresis, and postdialysis sodium. Patients with the highest IDWG have significantly higher diastolic blood pressures.


Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir.
The crystal structure of 3C proteinase (3C(pro)) from Enterovirus 71 (EV71) was determined in space group C2221 to 2.2 Å resolution. The fold was similar to that of 3C(pro) from other picornaviruses, but the difference in the β-ribbon reported in a previous structure was not observed. This β-ribbon was folded over the substrate-binding cleft and constituted part of the essential binding sites for interaction with the substrate. The structure of its complex with rupintrivir (AG7088), a peptidomimetic inhibitor, was also characterized in space group P212121 to 1.96 Å resolution. The inhibitor was accommodated without any spatial hindrance despite the more constricted binding site; this was confirmed by functional assays, in which the inhibitor showed comparable potency towards EV71 3C(pro) and human rhinovirus 3C(pro), which is the target that rupintrivir was designed against.


Prostate tumor volume measurement with combined T2-weighted imaging and diffusion-weighted MR: correlation with pathologic tumor volume.
To retrospectively determine the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying cancer in the prostate peripheral zone (PZ) and to assess the accuracy of tumor volume measurements made with T2-weighted imaging and combined T2-weighted and DW MR imaging by using surgical pathologic examination as the reference standard. The institutional review board issued a waiver of informed consent for this HIPAA-compliant study. Forty-two patients underwent endorectal MR at 1.5 T before undergoing radical prostatectomy for prostate cancer and had at least one PZ tumor larger than 0.1 cm(3) at surgical pathologic examination. On T2-weighted images, an experienced radiologist outlined suspected PZ tumors. Two apparent diffusion coefficient (ADC) cutoff values were identified by using the Youden index and published literature. Image cluster analysis was performed on voxels within the suspected tumor regions. Associations between volume measurements from imaging and from pathologic examination were assessed by using concordance correlation coefficients (CCCs). The sensitivity and specificity of ADCs for identifying malignant PZ voxels were calculated. In identifying malignant voxels, respective ADC cutoff values of 0.0014 and 0.0016 mm(2)/sec yielded sensitivity of 82% and 95% and specificity of 85% and 65%, respectively. Sixty PZ cancer lesions larger than 0.1 cm(3) were found at pathologic examination; 43 were detected by the radiologist. CCCs between imaging and pathologic tumor volume measurements were 0.36 for T2-weighted imaging, and 0.46 and 0.60 for combined T2-weighted and DW MR imaging with ADC cutoffs of 0.0014 and 0.0016 mm(2)/sec, respectively; the CCC of combined T2-weighted and DW MR imaging (ADC cutoff, 0.0016 mm(2)/sec) was significantly higher (P = .006) than that of T2-weighted imaging alone. Adding DW MR to T2-weighted imaging can significantly improve the accuracy of prostate PZ tumor volume measurement. http://radiology.rsnajnls.org/cgi/content/full/252/2/449/DC1.


Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.
Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by recurrent episodes of unexplained fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. Human TRKA encodes a high-affinity tyrosine kinase receptor for nerve growth factor (NGF), a member of the neurotrophin family that induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. We have recently demonstrated that TRKA is responsible for CIPA by identifying three mutations in a region encoding the intracellular tyrosine kinase domain of TRKA in one Ecuadorian and three Japanese families. We have developed a comprehensive strategy to screen for TRKA mutations, on the basis of the gene's structure and organization. Here we report 11 novel mutations, in seven affected families. These are six missense mutations, two frameshift mutations, one nonsense mutation, and two splice-site mutations. Mendelian inheritance of the mutations is confirmed in six families for which parent samples are available. Two mutations are linked, on the same chromosome, to Arg85Ser and to His598Tyr;Gly607Val, hence, they probably represent double and triple mutations. The mutations are distributed in an extracellular domain, involved in NGF binding, as well as the intracellular signal-transduction domain. These data suggest that TRKA defects cause CIPA in various ethnic groups.


A Nondestructive Method to Distinguish the Internal Constituent Architecture of the Intervertebral Discs Using 9.4 Tesla Magnetic Resonance Imaging.
An in vitro study of the intervertebral disc (IVD) structure using 9.4T magnetic resonance imaging (MRI). Investigate the potential of ultrahigh-field strength MRI for higher quality 3-dimensional (3D) volumetric MRI datasets of the IVD to better distinguish structural details. MRI has the advantages of being nondestructive and 3D in comparison to most techniques used to obtain the structural details of biological tissues, however, its poor image quality at higher resolution is a limiting factor. Ultrahigh-field MRI could improve the imaging of biological tissues but the current understanding of its application for spinal tissue is limited. 2 ovine spinal segments (C7-T1, T2-T3) containing the IVD were separately imaged using 2 sequences; 3D spin echo (multislice-multiecho) pulse sequence for the C7-T1 sample and 3D gradient echo (fast-low-angle-shot) pulse sequence for the T2-T3 sample. The C7-T1 sample was subsequently decalcified and imaged again using the same scanning parameters. Histological sections obtained from the decalcified sample were stained followed by digital scanning. Observations from corresponding MRI slices and histological sections were compared as a method of confirmation of morphology captured under MRI. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and relative-contrast values were calculated for quantitative evaluation of image quality. Measurements from histology sections and corresponding MRI slices matched well. Both sequences revealed finer details of the IVD structure. Under the spin echo sequence, the annulus lamellae architecture was distinguishable and the SNR and CNR values were higher. The relative contrast was considerably higher between high (nucleus) and low (bone) signal constituents, but between the nucleus and the annulus the relative contrast was low. Under the gradient echo sequence, although the relative contrasts between constituents were poor, the fiber orientation was clearly manifested. The obtained positive results demonstrate the potential of ultrahigh-field strength MRI to nondestructively capture the IVD structure. N/A.


Management trend and safety of vaginal delivery for term breech fetuses in a tertiary care hospital of Karachi, Pakistan.
To investigate the safety of vaginal delivery for term breech fetuses in a tertiary-care hospital of Pakistan. We reviewed the medical records of all live singleton breech deliveries at or beyond 37 weeks of gestation, at the Aga Khan University Hospital, Karachi, from January 1988 to December 1995. Rate of cesarean section increased from 48% (1988) to 74% (1995). Out of 287 subjects, 158 underwent elective cesarean section while 129 received a trial of labor, 77% of which delivered vaginally. There was no neonatal or maternal death. Compared to babies delivered by emergency or elective cesarean section, those delivered vaginally had significantly more neonatal intensive-care unit admissions (none and 5% versus 13%) and higher rates of birth trauma (none and 0.6% versus 7%). However, there was no significant difference in the Apgar score at 5 minutes and the risk of maternal complications by delivery mode. Allowing trial of labor to carefully selected mothers can result in vaginal delivery in 77% of the cases. However, the risk of trauma and neonatal intensive-care unit admissions, among vaginal births may favor the decision of elective cesarean section, unless rigorous pre-delivery assessment and conduct of delivery by adequately trained obstetricians is performed.


Geometric modulation of induced plasmonic circular dichroism in nanoparticle assemblies based on backaction and field enhancement.
Chiral cysteine-directed assemblies of Au@Ag core-shell nanocrystals (CSNCs) and Au/Ag nanorods with end-to-end (ETE) and side-by-side (SBS) configurations are fabricated and used to explore the definitive factors affecting the chiral response. The interaction between cysteine and metallic nanoparticles leads to intense and widely tunable plasmonic circular dichroism (PCD) ranging from a near-infrared (NIR) to ultraviolet (UV) regime. More importantly, it was observed that, in Ag nanorod and CSNC samples with varied aspect ratios, the ETE assembled patterns exhibit much larger PCD enhancement than SBS assemblies in an l/d-cysteine solvent environment. Very surprisingly, such a giant PCD response in these assemblies is completely different from that of the Au nanorod assembly case as reported earlier. Experimental and theoretical studies reveal that the interplay between the local field enhancement and backaction, triggered by the geometric configuration differentia of covered achiral CTAB molecules on Ag and Au surfaces, plays a crucial role in chiral response variances and leads to geometry-dependent optical activities. This work not only sheds light on understanding the relationship between the configuration of plasmonic nanostructure assemblies and geometry-manipulated circular dichroism, but also paves the way for predictive design of plasmonic biosensors or other nanodevices with controllable optical activities from the UV to the NIR light range.


Emergency surgeons' perceptions and attitudes towards antibiotic prescribing and resistance: a worldwide cross-sectional survey.
Antibiotic resistance (AMR) is a growing public health problem worldwide, in part related to inadequate antibiotic use. A better knowledge of physicians' motivations, attitudes and practice about AMR and prescribing should enable the design and implementation of effective antibiotic stewardship programs (ASPs). The objective of the study was to assess attitudes and perceptions concerning AMR and use of antibiotics among surgeons who regularly perform emergency or trauma surgery. A cross-sectional web-based survey was conducted contacting 4904 individuals belonging to a mailing list provided by the World Society of Emergency Surgery. Participation was voluntary and anonymous. The survey was open for 5 weeks (from May 3, 2017, to June 6, 2017), within which two reminders were sent. The self-administered questionnaire was developed by a multidisciplinary team; reliability and validity were assessed. The overall response rate was 12.5%. Almost all participants considered AMR an important worldwide problem, but 45.6% of them underrated the problem in their own hospitals. Surgeons provided with periodic reports on local AMR demonstrated a lower underrating in their hospital. Only 66.3% of the surgeons stated to receive periodic reports on local AMR data, and among them, 56.2% had consulted them to select an antibiotic in the previous month. Availability of systematic reports about AMR, availability of guidelines for therapy of infections, and advice from an infectious diseases specialist were considered very helpful measures to improve antibiotic prescribing by 68.0, 65.7, and 64.9%, respectively. Persuasive and restrictive ASPs were both considered helpful measures by 64.5%. Moreover, 86.3% considered locally developed guidelines more useful than national ones. Only 21.9% received formal training in antibiotic prescribing in the previous year; among them, 86.6% declared to be interested in receiving more training. Availability of periodic reports on local AMR data was considered an important tool to guide surgeons in choosing the correct antibiotic and to increase awareness of the problem of AMR. Local guidelines for therapy of infections should be implemented in every emergency surgery setting, and developed by a multidisciplinary team directly involving surgeons, infectious diseases specialists, and microbiologists, and formally established in an ASP.


AXL Inhibitor TP-0903 Reduces Metastasis and Therapy Resistance in Pancreatic Cancer.
Pancreatic cancer is the third leading cause of cancer-related deaths in the United States with a 5-year survival less than 5%. Resistance to standard therapy and limited response to immune checkpoint blockade due to the immunosuppressive and stroma-rich microenvironment remain major challenges in the treatment of pancreatic cancer. A key cellular program involved in therapy resistance is epithelial plasticity, which is also associated with invasion, metastasis, and evasion of immune surveillance. The receptor tyrosine kinase AXL is a key driver of tumor cell epithelial plasticity. High expression and activity of AXL is associated with poor prognosis, metastasis, and therapy resistance in multiple types of cancer including pancreatic. Here, we show that an AXL inhibitor (TP-0903), has antitumor and therapy sensitizing effects in preclinical models of pancreatic ductal adenocarcinoma (PDA). We demonstrate that TP-0903 as a single agent or in combination with gemcitabine and/or anti-programmed cell death protein 1 (PD1) antibody has anti-metastatic and anti-tumor effects in PDA tumor bearing mice, leading to increased survival. In addition, gene expression analysis of tumors demonstrated upregulation of pro-inflammatory and immune activation genes in tumors from TP-0903-treated animals compared with the vehicle, indicating pharmacologic inhibition of AXL activation leads to an immunostimulatory microenvironment. This effect was augmented when TP-0903 was combined with gemcitabine and anti-PD1 antibody. These results provide clear rationale for evaluating TP-0903 in the treatment of pancreatic cancer.


Psychoneuroimmunology: An area of interest for the psychopharmacologist?
Anecdotal evidence suggesting a causal relationship between psychiatric illness, environmental stress and a malfunctioning immune system goes back to antiquity. Recently, clinical and experimental studies have established the interrelationship between neuro- endocrine regulation, the immune system and abnormalities in central neurotransmission which may be deranged as a consequence of stressful events. This short review is an attempt to assess the evidence implicating altered immune responsiveness in depression and to consider the impact of different types of environmental stress in triggering the immune malfunction. While these findings are of considerable biological importance, it is presently unclear whether the immunological changes are primary or secondary to the disease states.


Anti-thymic stromal lymphopoietin antibody suppresses airway remodeling in asthma through reduction of MMP and CTGF.
Thymic stromal lymphopoietin (TSLP) mediates immune reaction in patients with asthma. Matrix metalloproteinase (MMP), connective tissue growth factor (CTGF), and transforming growth factor-β (TGF-β) are inflammatory mediators whose responses to the anti-TSLP antibody are unknown. This study examined the effect of an anti-TSLP antibody on MMP, CTGF, TGF-β, and airway structural changes in airway remodeling in asthma. Mice were randomly divided into phosphate-buffered-saline-challenged (PBS), ovalbumin-challenged (OVA), and ovalbumin-challenged with anti-TSLP antibody (OVA + anti-TSLP) groups. Airway responsiveness and serum ovalbumin-specific immunoglobulin E were measured. Differential cell counts and MMP-2 and MMP-9 were evaluated in bronchoalveolar lavage fluid (BALF). Airway structural changes were quantified using morphometric analysis and presentation by immunohistochemistry staining. Lung CTGF, TGF-β, and TSLP were analyzed using western blot. Airway responsiveness was significantly lower in OVA + anti-TSLP and PBS groups than in OVA group. Airway structural changes exhibited less smooth muscle thickness in OVA + anti-TSLP and PBS groups than in OVA group. MMP-2 and MMP-9 in BALF and CTGF, TGF-β, and TSLP in lungs significantly decreased in OVA + anti-TSLP and PBS groups compared with OVA group. Anti-TSLP antibody exerts the preventive effect of decreasing airway structural changes through reduction of MMP, TGF-β, and CTGF in airway remodeling of asthma.


Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA-34a axis.
Delphinidin, one of the main anthocyanidins, has potent anti-cancer properties. In this study, we investigated the effect of delphinidin on 1-methyl-1-nitrosourea (MNU)-induced breast carcinogenesis on rats and the mechanism of delphinidin via negative regulation of the HOTAIR/microRNA-34a axis. We found administration of delphinidin could effectively suppress MNU-induced mammal breast carcinogenesis. Delphinidin downregulated the level of HOTAIR and upregulated miR-34a in breast carcinogenesis. Western blot analysis confirmed that delphinidin treatment can significantly decrease the expression of β-catenin, glycogen synthase kinase-3β (Gsk3β), c-Myc, cyclin-D1, and matrix metalloproteinase-7(MMP-7) expression in breast cancer cells, and inhibition of miR-34a significantly reduced the effect of delphinidin on c-Myc, cyclin-D1, and MMP-7. HOTAIR overexpression also blocked the effect of delphinidin on miR-34a and the Wnt/β-catenin signaling pathway in MDA-MB-231 cells. RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay results showed that delphinidin upregulated miR-34a by inhibiting HOTAIR, coupled with enhancement of the zeste homolog 2 (EZH2) and histone H3 Lys27 trimethylation (H3K27me3). This study indicated that delphinidin may potentially suppress breast carcinogenesis and exert its anti-cancer effect through the HOTAIR/miR-34a axis. These findings provided new evidence for the use of delphinidin in preventing breast carcinogenesis.


Cherax (Astaconephrops) gherardii, a new crayfish (Decapoda: Parastacidae) from West Papua, Indonesia.
Cherax (Astaconephrops) gherardii n. sp. is a moderate burrowing crayfish endemic to the Ajamaru Lakes of West Papua, Indonesia. This species is one of the crayfish species from this region that are exploited for ornamental purposes. Its commonly used commercial name in the pet trade is "Rainbow Crayfish" or "Blue Moon Crayfish", and its native name is "udang kuku biru". The new species is genetically and morphologically similar to Cherax boesemani, however, both species may be easily distinguished morphologically or by using sequence divergence, which is substantial for considering C. gherardii n. sp. to be a valid species.


Ca2+-Dependent Regulation of NFATc1 via KCa3.1 in Inflammatory Osteoclastogenesis.
In inflammatory arthritis, the dysregulation of osteoclast activity by proinflammatory cytokines, including TNF, interferes with bone remodeling during inflammation through Ca2+-dependent mechanisms causing pathological bone loss. Ca2+-dependent CREB/c-fos activation via Ca2+-calmodulin kinase IV (CaMKIV) induces transcriptional regulation of osteoclast-specific genes via NFATc1, which facilitate bone resorption. In leukocytes, Ca2+ regulation of NFAT-dependent gene expression oftentimes involves the activity of the Ca2+-activated K+ channel KCa3.1. In this study, we evaluate KCa3.1 as a modulator of Ca2+-induced NFAT-dependent osteoclast differentiation in inflammatory bone loss. Microarray analysis of receptor activator of NF-κB ligand (RANKL)-activated murine bone marrow macrophage (BMM) cultures revealed unique upregulation of KCa3.1 during osteoclastogenesis. The expression of KCa3.1 in vivo was confirmed by immunofluorescence staining on multinucleated cells at the bone surface of inflamed mouse joints. Experiments on in vitro BMM cultures revealed that KCa3.1-/- and TRAM-34 treatment significantly reduced the expression of osteoclast-specific genes (p < 0.05) alongside decreased osteoclast formation (p < 0.0001) in inflammatory (RANKL+TNF) and noninflammatory (RANKL) conditions. In particular, live cell Ca2+ imaging and Western blot analysis showed that TRAM-34 pretreatment decreased transient RANKL-induced Ca2+ amplitudes in BMMs by ∼50% (p < 0.0001) and prevented phosphorylation of CaMKIV. KCa3.1-/- reduced RANKL+/-TNF-stimulated phosphorylation of CREB and expression of c-fos in BMMs (p < 0.01), culminating in decreased NFATc1 protein expression and transcriptional activity (p < 0.01). These data indicate that KCa3.1 regulates Ca2+-dependent NFATc1 expression via CaMKIV/CREB during inflammatory osteoclastogenesis in the presence of TNF, corroborating its role as a target candidate for the treatment of bone erosion in inflammatory arthritis.


Potassium supplementation in hypertensive patients with diuretic-induced hypokalemia.
Changes in potassium balance have been found to have variable effects on the blood pressure of animals, and the administration of potassium supplements has been reported to lower the blood pressure of normokalemic hypertensive patients. To assess the effect of potassium repletion in hypokalemic hypertension, we administered either potassium chloride, 60 mmol per day, or placebo tablets, each for six weeks, in a randomized, double-blind, crossover trial to 16 hypertensive patients who had diuretic-induced hypokalemia and who continued to take a constant amount of diuretic. We selected patients whose control serum potassium levels were below 3.5 mmol per liter. In association with an average rise in the serum potassium concentration of 0.56 mmol per liter, the mean blood pressure fell by an average of 5.5 mm Hg (P = 0.004), with at least a 4 mm Hg fall observed in 9 of the 16 patients. The fall in blood pressure correlated with a fall in plasma renin activity (r = 0.568, P = 0.043) but not with changes in plasma aldosterone levels or other variables. We conclude that short-term potassium supplementation that ameliorates diuretic-induced hypokalemia may induce a significant fall in blood pressure.


Cross-Sectional Blood Metabolite Markers of Hypertension: A Multicohort Analysis of 44,306 Individuals from the COnsortium of METabolomics Studies.
Hypertension is the main modifiable risk factor for cardiovascular morbidity and mortality but discovering molecular mechanisms for targeted treatment has been challenging. Here we investigate associations of blood metabolite markers with hypertension by integrating data from nine intercontinental cohorts from the COnsortium of METabolomics Studies. We included 44,306 individuals with circulating metabolites (up to 813). Metabolites were aligned and inverse normalised to allow intra-platform comparison. Logistic models adjusting for covariates were performed in each cohort and results were combined using random-effect inverse-variance meta-analyses adjusting for multiple testing. We further conducted canonical pathway analysis to investigate the pathways underlying the hypertension-associated metabolites. In 12,479 hypertensive cases and 31,827 controls without renal impairment, we identified 38 metabolites, associated with hypertension after adjusting for age, sex, body mass index, ethnicity, and multiple testing. Of these, 32 metabolite associations, predominantly lipid (steroids and fatty acyls) and organic acids (amino-, hydroxy-, and keto-acids) remained after further adjusting for comorbidities and dietary intake. Among the identified metabolites, 5 were novel, including 2 bile acids, 2 glycerophospholipids, and ketoleucine. Pathway analysis further implicates the role of the amino-acids, serine/glycine, and bile acids in hypertension regulation. In the largest cross-sectional hypertension-metabolomics study to date, we identify 32 circulating metabolites (of which 5 novel and 27 confirmed) that are potentially actionable targets for intervention. Further in-vivo studies are needed to identify their specific role in the aetiology or progression of hypertension.


Fungicidal Activity of Recombinant Javanicin against Cryptococcus neoformans Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes.
The occurrence of Cryptococcus neoformans, the human fungal pathogen that primarily infects immunocompromised individuals, has been progressing at an alarming rate. The increased incidence of infection of C. neoformans with antifungal drugs resistance has become a global concern. Potential antifungal agents with extremely low toxicity are urgently needed. Herein, the biological activities of recombinant javanicin (r-javanicin) against C. neoformans were evaluated. A time-killing assay was performed and both concentration- and time-dependent antifungal activity of r-javanicin were indicated. The inhibitory effect of the peptide was initially observed at 4 h post-treatment and ultimately eradicated within 36 to 48 h. Fungal outer surface alteration was characterized by the scanning electron microscope (SEM) whereas a negligible change with slight shrinkage of external morphology was observed in r-javanicin treated cells. Confocal laser scanning microscopic analysis implied that the target(s) of r-javanicin is conceivably resided in the cell thereby allowing the peptide to penetrate across the membrane and accumulate throughout the fungal body. Finally, cryptococcal cells coped with r-javanicin were preliminarily investigated using label-free mass spectrometry-based proteomics. Combined with microscopic and proteomics analysis, it was clearly elucidated the peptide localized in the intracellular compartment where carbohydrate metabolism and energy production associated with glycolysis pathway and mitochondrial respiration, respectively, were principally interfered. Overall, r-javanicin would be an alternative candidate for further development of antifungal agents.


Risk behaviour in Swedish adolescents: is shared physical custody after divorce a risk or a protective factor?
The increase in shared physical custody in Sweden has been dramatic; 20 years ago only a small percentage of adolescents lived in shared physical custody, but currently ∼30% of the adolescents whose parents have separated or divorced divide their residence between parents. We hypothesized that living in shared physical custody or in a single-parent family is associated with a higher prevalence of adolescent risk behaviour than living in a two-parent family. Data on 15-year-old adolescents from the 2005/2006 to 2009/2010 Swedish Health Behaviour in School-aged Children (HBSC) survey were analysed using logistic regression. Adolescents living in shared physical custody had slightly higher rates of risk behaviour compared with adolescents from two-parent families, but significantly lower rates than their counterparts from single-parent families. Their odds of being a smoker or having been drunk were 60 and 50% higher, respectively, than those of their counterparts in two-parent families. Shared physical custody after marriage break-up seems to constitute a health protective factor for adolescents' health and problem behaviour. In order to deepen our understanding of the positive and negative aspects of shared physical custody, our study should be followed by qualitative analyses and longitudinal studies of adolescents' experiences.


Update on Juvenile Spondyloarthritis.
Spondyloarthritis (SpA) is a blanket term encompassing entities such as enthesitis-related arthritis, nonradiographic axial SpA, and ankylosing spondylitis. These diseases share many clinical features, including a predilection for inflammation of the entheses and the sacroiliac joints. The nomenclature is based on the evolution of the classification of the disease and the age of the patient. SpA has a prevalence of approximately 1% of the population of the United States, with 10% to 20% of patients experiencing the onset during childhood. Children with onset of arthritis before age 16 years are classified as having juvenile idiopathic arthritis. Children with enthesitis and/or sacroiliitis are further classified as belonging to the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. The initial manifestations can be subtle and will usually include a peripheral pattern of arthritis and enthesitis. It may take several years for axial disease to develop in children. Except for an association with the human leukocyte antigen (HLA-B27) serotype, there are no laboratory markers for the disease, and the radiographic findings are often negative. A careful clinical evaluation for evidence of inflammation in the entheses and the joints and a search for comorbidities are required. Magnetic resonance imaging facilitates the early detection of sacroiliitis, an important feature that may be clinically silent. Because recent studies indicate that earlier introduction of therapy can help achieve better outcomes, rapid identification and treatment of children with SpA is essential.


Communicative strategies in a neonatal intensive care unit.
Counseling is a professional intervention based on skills to communicate and to build relationships. The project 'Not alone', related to counseling at our Neonatal Intensive Care Unit, is aimed to let counseling become a 'shared culture' for all the care givers. The first essential aspect is to form the ability of counseling through periodic courses for all professionals of the department (physicians, nurses, and physiotherapists). In our department, a professional counselor is present assisting the medical staff in direct counseling. The counselor's intervention allows a better parent orientation in the situation. A more effective sharing of these rules also facilitates the communication among parents and medical staff. Periodic meetings are established among the medical staff, in which the professional counselor discusses difficult situations to share possible communicative strategies. We wanted to have not only a common communicative style, but also common subjects, independent from the characteristics of each of us. Individuals are often faced with diverse situations. For every setting that we more frequently face in communication (for example the first interview with a parent of a very preterm infant) we have built an 'algorithm' that follows a pattern: (1) information always given; (2) frequent questions from parents; and (3) frequent difficulties in the communication. We also need to record important moments, for instance the 'case history of the communication': in fact it would be desirable to have the case history, a sheet dedicated to important communications that are absolutely to be shared with other professionals.


Linking environmental and demographic data to predict future population viability of a perennial herb.
Recent advances in stochastic demography provide tools to examine the importance of random and periodic variation in vital rates for population dynamics. In this study, we explore with simulations the effect of disturbance regime on population dynamics and viability. We collected 7 years of demographic data in three populations of the perennial herb Primula farinosa, and used these data to examine how variation in vital rates affected population viability parameters (stochastic growth rate, lambda(S)), and how vital rates were related to weather conditions. Elasticity analysis indicated that the stochastic growth rate was very sensitive to changes in regeneration, quantified as the production, survival, and germination of seeds. In one of the study years, all seedlings and mature plants in the demography plots died. This extinction coincided with the driest summer during the study period. Simulations suggested that a future increase in the frequency of high-mortality years due to climate change would result in reduced population growth rate, and an increased importance of survival in the seed bank for population viability. The results illustrate how the limited demographic data typically available for many natural systems can be used in simulation models to assess how environmental change will affect population viability.


Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group.
To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia. A prospective cohort study; median duration of follow-up was 2.4 years. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival times according to neurocognitive classification. University-based research unit. A volunteer sample of 414 individuals seropositive for HIV-1. Subjects were classified at their baseline evaluation as neuropsychologically (NP) normal or abnormal (impaired in > or = 2 NP test domains). A subgroup of NP abnormal subjects met operational criteria for HIV-associated minor cognitive motor disorder; the remaining subjects were designated NP impaired. Subjects with frank dementia were excluded. Mortality. At the baseline evaluation, 256 (62%) of 414 subjects were designated normal; 109 (26%). NP impaired; and 49 (12%), minor cognitive motor disorder. One hundred six participants (26%) died during follow-up. Compared with the NP normal group, the unadjusted relative risk (RR) of death for all NP abnormal subjects (minor cognitive motor disorder and NP impaired) was significantly increased (RR, 1.7; 95% confidence interval [CI], 1.2-2.6; P < .005). After adjusting for concurrently measured predictors of survival (CD4 lymphocyte counts, Centers for Disease Control and Prevention HIV disease classification, hemoglobin concentration, and serum beta 2-microglobulin) in proportional hazards models, mortality for all NP abnormal subjects remained elevated (RR, 1.8; 95% CI, 1.2-2.8; P < .01). The elevation in mortality risk for subjects with minor cognitive motor disorder was statistically significant (RR, 2.2; 95% CI, 1.2-3.8; P < .01); for NP impaired subjects it was marginally significant (RR, 1.6; 95% CI, 1.0-2.8; P = .06). The HIV-infected individuals with NP impairment had a higher risk of dying than those without impairment. This was particularly true for those meeting syndromic diagnostic criteria.


Functional expression and characterization of a plant K+ channel gene in a plant cell model.
To express and characterize the function of a plant ion channel gene in plant cells, it is necessary to establish a model system that lacks the endogenous channel activity and can be genetically transformed. Patch-clamp techniques were used to survey voltage-dependent K+ channel activities in different cell types of tobacco plants. Interestingly, mesophyll cells lacked the inward K+ current found in guard cells. A transgene containing the inward K+ channel gene KAT1 from Arabidopsis was constructed and expressed in the mesophyll cells of transgenic tobacco plants. Expression of the KAT1 gene produced a large voltage-dependent inward current across the plasma membrane of mesophyll protoplasts. The KAT1 current was carried by K+ and activated at voltage more negative than -100 mV. This K+ current had a single-channel conductance of 6-10 pS and was highly sensitive to TEA, Cs+ and Ba2+. This study represents the first example in which a plant ion channel gene is functionally expressed and studied in plant cells. Tobacco mesophyll cells will provide a useful model for functional characterization of inward K+ channel genes from higher plants.


Sliding window discretization: a new method for multiple band matching of bacterial genotyping fingerprints.
Microbiologists have traditionally applied hierarchical clustering algorithms as their mathematical tool of choice to unravel the taxonomic relationships between micro-organisms. However, the interpretation of such hierarchical classifications suffers from being subjective, in that a variety of ad hoc choices must be made during their construction. On the other hand, the application of more profound and objective mathematical methods--such as the minimization of stochastic complexity--for the classification of bacterial genotyping fingerprints data is hampered by the prerequisite that such methods only act upon vectorized data. In this paper we introduce a new method, coined sliding window discretization, for the transformation of genotypic fingerprint patterns into binary vector format. In the context of an extensive amplified fragment length polymorphism (AFLP) data set of 507 strains from the Vibrionaceae family that has previously been analysed, we demonstrate by comparison with a number of other discretization methods that this new discretization method results in minimal loss of the original information content captured in the banding patterns. Finally, we investigate the implications of the different discretization methods on the classification of bacterial genotyping fingerprints by minimization of stochastic complexity, as it is implemented in the BinClass software package for probabilistic clustering of binary vectors. The new taxonomic insights learned from the resulting classification of the AFLP patterns will prove the value of combining sliding window discretization with minimization of stochastic complexity, as an alternative classification algorithm for bacterial genotyping fingerprints.


Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh.
Previous studies have shown that selected strains of lactobacilli that are administered orally result in a modest reduction of diarrhea duration. However, duration alone is not considered optimal for therapeutic evaluation of any agent in diarrhea. To examine the effect of a new probiotic, Lactobacillus paracasei strain ST11 (ST11), in acute childhood diarrhea by using evaluation criteria recommended by the World Health Organization. In a randomized, double-blind, placebo-controlled clinical trial, 230 male infants and young children, 4 to 24 months of age, presenting with diarrhea of <2 days' duration were admitted to the metabolic research ward of the International Centre for Diarrheal Disease Research, Bangladesh, and fed 10(10) colony-forming units of lyophilized ST11 or placebo daily for 5 days. Stool output and frequency, oral rehydration solution intake, and excretion of rotavirus were monitored daily. No effect of ST11 treatment on severe rotavirus diarrhea was observed. However, the probiotic treatment did significantly reduce cumulative stool output (225 +/- 218 vs 381 +/- 240 mL/kg), stool frequency (27.9 +/- 17 vs 42.5 +/- 26), and oral rehydration solution intake (180 +/- 207 vs 331 +/- 236 mL/kg) in children with less-severe nonrotavirus diarrhea compared with those receiving placebo treatment. A significantly higher proportion of nonrotavirus children receiving ST11 had their diarrhea resolve within 6 days of therapy (ST11 versus placebo: 76% vs 49%). ST11 has a clinically significant benefit in the management of children with nonrotavirus-induced diarrhea, but it is ineffective in those with rotavirus diarrhea.


Oncologic surveillance in bladder cancer following radical cystectomy: A systematic review and meta-analysis.
The existing guidance on bladder cancer surveillance following radical cystectomy is limited and variable. Additionally, the effect of surveillance on mortality is debatable. Herein, we perform a systematic review to evaluate the characteristics of alternative oncologic surveillance protocols and determine the association of detection of asymptomatic vs. symptomatic recurrences on mortality. An electronic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases was performed from 1970 to 2015. In all, 3 reviewers independently assessed the 1,729 candidate studies for eligibility and abstracted data based on an a priori established protocol. Outcomes were pooled using random effects meta-analysis. We identified 7 studies for inclusion that were uncontrolled and thereby represented a body of evidence at high risk of bias; 5 studies developed surveillance protocols using a methodology similar to that of established guidelines. The majority proposed a pathologic stage-stratified approach, but ended surveillance for all patients at 5 years. Detection of asymptomatic recurrences was associated with a nonsignificant reduction in mortality (relative risk = 0.78; 95% CI: 0.58-1.04). This effect became statistically significant when upper and lower urinary tract recurrences were included in the analyses (relative risk = 0.69; 95% CI: 0.59-0.79). Only sparse evidence supports alternative oncologic surveillance protocols for bladder cancer following radical cystectomy. The majority of existing protocols proposed similar strategies to those recommended by published guidelines. Detecting asymptomatic recurrences may lead to a reduction in overall mortality, which could provide a rationale for surveillance.


On the possibility of time-lapse ultrahigh-resolution optical coherence tomography for bladder cancer grading.
It has been recently demonstrated that the cellular details of bladder epithelium embedded in speckle noise can be uncovered with time-lapse ultrahigh-resolution optical coherence tomography (TL-uOCT) by proper time-lapse frame averaging that takes advantage of cellular micromotion in fresh biological tissue ex vivo. Here, spectral-domain 3-D TL-uOCT is reported to further improve the image fidelity, and new experimental evidence is presented to differentiate normal and cancerous nuclei of rodent bladder epithelia. Results of animal cancer study reveal that despite a slight overestimation (e.g., <10%) of nuclear size (D(N)) to histological evaluation, TL-uOCT is capable of distinguishing normal (D(N) approximately 7 microm) and cancerous (e.g., high-grade D(N(") ) approximately 13 microm) urothelia, which may potentially be very useful for enhancing the diagnosis of nonpapillary bladder cancer. More animal study is being conducted to examine the utility to differentiate hyperplasia, dysplasia, and carcinoma in situ.


Effects of alpha-adrenergic agonists on intracellular and intramitochondrial pH in rat proximal nephrons.
Rat proximal tubular segments were used to examine alpha-adrenoceptor alterations in Na+-H+ exchange by monitoring intracellular pH (pHi) and mitochondrial matrix pH (pHm). To obtain pHi, tubules were incubated with the cell-permeant fluorescent probe, 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein acetoxymethyl ester in a HCO3--free Na+ buffer. The intracellular distribution of the weak acid [2-14C] 5,5-dimethyloxazolidine-2,4-dione was used to calculate pHm, using values of medium pH, pHi, cell volume, and matrix content. Several selective alpha 1- and alpha 2-adrenoceptor agonists and the endogenous mixed agonist, norepinephrine, all produced dose-related increases in pHi. With each of the agonists tested, a maximum increase in pHi was observed at 1 microM final concentrations, with peak effects occurring in less than 1 min. Pretreatment with ethylisopropyl amiloride (EIPA, 10 microM), a specific inhibitor of proximal Na+-H+ exchange, blocked receptor-stimulated increases in pHi, as well as stimulation of Na+-H+ exchange by phorbol ester (PMA, 0.1 microM). Similarly, selective alpha 1- (prazosin, 0.1 microM) and alpha 2-(idazoxan, 0.1 microM) adrenoceptor antagonists inhibited alterations in agonist-induced pHi changes, whereas PMA-stimulated increases in pHi remained unaffected. Neither alpha 1- nor alpha 2-adrenoceptor agonists produced differences in pHm. Adrenoceptor agonist-induced pHi changes were also assessed at various concentrations of external Na+ (0-135 mM). It was observed that 0 and 10 mM external Na+ concentrations significantly reduced alpha 1- and alpha 2-adrenoceptor-stimulated pHi changes; Km values for the alpha 1-agonist phenylephrine and the alpha 2-agonist B-HT 933 were 18.0 +/- 2.1 and 22.7 +/- 2.6, respectively. In summary, stimulation by alpha-adrenergic agonists may be blocked at the receptor level with specific alpha-antagonists or at the exchanger with EIPA. The increase in cellular pH induced by these agonists is sensitive to external Na+ and reflects alpha-adrenoceptor activation of the Na+-H+ exchanger.


Exploring perceived occupational balance in women with fibromyalgia. A descriptive study.
People with chronic pain conditions such as fibromyalgia may experience occupational limitations and imbalances in their basic and instrumental occupations of daily living, leisure, work, and social participation. To describe occupational balance in persons with fibromyalgia and to analyze whether it is associated with self-reported disability and self-efficacy to manage symptoms. A cross-sectional study was carried out. Individuals with fibromyalgia were invited to participate. Occupational balance was assessed with the Occupational Balance Questionnaire; self-reported disability was assessed with the World Health Organization Disability Assessment Schedule, WHODAS 2.0-12; and self-efficacy was evaluated with the 8-item version of the Arthritis Self-Efficacy Scale. Data were analyzed using multiple linear regression with a forward stepwise procedure. One hundred women with fibromyalgia were included. Occupational balance was 26.96 ± 12.09; however, scores differed between the mild disability group and the moderate disability group (33.11 ± 9.99 vs. 20.29 ± 10.61, p < 0.001). Multiple linear regression analyses revealed that self-reported disability and self-reported pain management explained 58.1% of the variance in occupational balance. Women with fibromyalgia showed low occupational balance. Self-reported disability and self-reported pain management were associated with occupational balance. Occupational therapy practitioners can design intervention programs focussing on occupational balance and self-efficacy to manage symptoms.


Harnessing the Quantum Behavior of Spins on Surfaces.
The desire to control and measure individual quantum systems such as atoms and ions in a vacuum has led to significant scientific and engineering developments in the past decades that form the basis of today's quantum information science. Single atoms and molecules on surfaces, on the other hand, are heavily investigated by physicists, chemists, and material scientists in search of novel electronic and magnetic functionalities. These two paths crossed in 2015 when it was first clearly demonstrated that individual spins on a surface can be coherently controlled and read out in an all-electrical fashion. The enabling technique is a combination of scanning tunneling microscopy (STM) and electron spin resonance, which offers unprecedented coherent controllability at the Angstrom length scale. This review aims to illustrate the essential ingredients that allow the quantum operations of single spins on surfaces. Three domains of applications of surface spins, namely quantum sensing, quantum control, and quantum simulation, are discussed with physical principles explained and examples presented. Enabled by the atomically-precise fabrication capability of STM, single spins on surfaces might one day lead to the realization of quantum nanodevices and artificial quantum materials at the atomic scale.


Invited commentary: multiple human papillomavirus infections and type replacement-anticipating the future after human papillomavirus vaccination.
Prophylactic human papillomavirus (HPV) vaccination with 3 doses of either of 2 commercially available vaccines is highly efficacious in preventing infections with the most carcinogenic types of HPV (HPV 16 and HPV 18) at the cervix and other anatomical sites at which HPV-related cancers develop. Concern has been raised that eradicating the most virulent HPV types, 16 and 18, could result in 1 or more of the types that are not targeted by the vaccine occupying the ecological niche created by the elimination of these types, referred to as type replacement. In this issue of the Journal, Yang et al. (Am J Epidemiol. 2014;180(11):1066-1075) report on concurrent infections with multiple HPV types in unvaccinated women who underwent cervical screening in New Mexico (December 2007-April 2009) to identify possible interactions between HPV types, which if present could suggest the possibility of type replacement. Consistent with previous reports, they show minimal type-specific interactions among women with normal cytology, which they consider an indication that type replacement of HPV 16/18 is unlikely to be an issue in the general population postvaccination. Type replacement may be of less concern with the introduction of multivalent vaccines that include most of the carcinogenic HPV types; continued surveillance postvaccination should improve our understanding of the impact of HPV vaccination on type distribution and screening performance.


PPARalpha and PPARbeta are differentially affected by ethanol and the ethanol metabolite acetaldehyde in the MCF-7 breast cancer cell line.
The activity and/or the level of the peroxisome proliferator-activated receptors (PPARs) in liver and oligodendrocytes are regulated by ethanol. Despite the association between ethanol consumption and breast cancer risk, and the increasing evidence for an involvement of PPARs in some cancers, there have been no studies on the effect of ethanol or its metabolite acetaldehyde on PPARs in breast cancer. Using the MCF-7 breast cancer cell line, we examined the relationship between ethanol and its metabolite acetaldehyde on PPARalpha and PPARbeta transactivation. Ethanol (20 mM) reduced the potency of the PPARbeta ligand GW0742, evident by a rightward shift in the GW0742 dose-response curve, whereas for PPARalpha activation by GW7647, ethanol mediated its effects primarily through reducing efficacy as evidenced by a reduction in maximal response. Using the enzyme inhibitors 4-methylpyrazole and cyanamide and the metabolite acetaldehyde, we showed that PPARalpha and PPARbeta are differentially modulated by ethanol and acetaldehyde. While acetaldehyde is responsible for the inhibition of PPARalpha ligand inhibition with a concentration that inhibits 50% of activity (IC50) of 111 nM, acetaldehyde has no effect on PPARbeta or its ligand activation. Instead, inhibition of PPARbeta transactivation is mediated directly by ethanol. The differential effect of ethanol and acetaldehyde on PPARalpha and PPARbeta further underscores the differences between these receptors and may indicate the relevance of PPARs in the effects of ethanol in the human breast.


Association between PD-L1 and HPV status and the prognostic value for HPV treatment in premalignant cervical lesion patients.
The difference of PD-L1 expression between only HPV-positive patients and premalignant cervical lesion patients did not be reported in present studies. And to test the PD-L1 expression in some cervical cell lesion studies using cervical exfoliated cells sample also was ignored. Meanwhile, the PD-L1 expression as a predictive biomarker still existed controversy. So in the study, first to compare the expression of PD-L1 between only HPV-positive patients and premalignant cervical lesion patients, then to research the association between PD-L1 and HPV status, lastly to explore the possible prognostic value for HPV treatment in premalignant cervical lesion patients.Cervical exfoliated cells samples of 54 premalignant cervical lesion patients with HPV16 infection were collected; meanwhile the cervical exfoliated cells samples from 20 healthy women without HPV infection and 20 patients with only HPV16 infection but cervical cytology normal were collected as 2 control groups. Flow-through hybridization and gene chip (FHGC) was used to detect the HPV type, the PD-L1 expression was tested by Flow cytometry analysis, the methylation-sensitive high-resolution melting (MS-HRM) was used to test the HPV16 L1 gene methylation. The 54 premalignant cervical lesion patients were followed up in 18 months to assess the prognostic value of PD-L1 for HPV treatment.The PD-L1 positive cell rate and mean fluorescence intensity of PD-L1 positive cell in premalignant cervical lesion patients with HPV16 infection were higher than 2 control groups. Mean fluorescence intensity of PD-L1 positive cell were increased in 54 cases when existing multiple HPV status and high HPV16-L1 gene methylation (L1 gene methylation more than 50%). High PD-L1 expression (PD-L1 positive cell rate more than 10%), high HPV16-L1 gene methylation, and multiple HPV infection status could prolong the time to clean HPV infection by Kaplan-Meier analysis. Multivariate Cox proportional hazards analysis also showed that all of high PD-L1 expression, high HPV-L1 methylation, and multiple HPV infection status should increase the risk of HPV unclearance in premalignant cervical lesion patients; the hazard ratio (HR) was 2.043 (CI: 1.050-3.973), 2.797 (CI: 1.277-6.122), and 3.050 (CI: 1.406-6.615).PD-L1 expression only was correction with HPV infection when the infection induced the cervical cells to create the lesion. PD-L1 was the risk factor of HPV unclearance in premalignant cervical lesion patients, so anti-PD-L1 therapy could be a potential effectiveness way of HPV infection in premalignant cervical lesion patients.


Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC).
Prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival, based on prognostic factors, such as serum calcitonin doubling time (Ct DT). Pretargeted radioimmunotherapy (pRAIT) is a novel targeted radionuclide therapy, using a bispecific monoclonal antibody (BsMAb) and a radiolabeled bivalent hapten, designed to improve the therapeutic index and to deliver increased tumor-absorbed doses to relatively radioresistant solid tumors. Pretargeting has demonstrated a more favorable therapeutic index and clinical efficacy than directly labeled anti-carcinoembryonic antigen (CEA) MAb in preclinical MTC models. Moreover, two phase I/II clinical trials assessing anti-CEA × anti-DTPA-indium BsMAb (murine F6x734 and chimeric hMN14x734) with (131)I-di-DTPA-indium showed encouraging therapeutic results in progressive, metastatic, MTC patients, with an improved survival in intermediate- and high-risk (pre-pRAIT Ct DT, <2 years) patients, as compared to contemporaneous untreated patients (median overall survival, 110 months vs 61 months; P < 0.030). pRAIT efficacy has been recently confirmed in a prospective multicenter phase II study assessing hMN14x734 and (131)I-di-DTPA-indium in rapidly progressive MTC patients. New pRAIT compounds are now available with fully humanized, recombinant, trivalent BsMAb (anti-CEA TF2) and histamine-succinyl-glutamine (HSG) peptides. The HSG peptide allows easy and stable labeling with different radiometals, such as (177)Lu or (90)Y beta-emitters having favorable physical features for pRAIT or (68)Ga and (18)F positron-emitters, allowing the development of a highly sensitive and specific immuno-positron emission tomography method in MTC or other CEA-positive tumors.


Successful resuscitation of an extremely low birth weight premature infant in delma island community hospital, United arab emirates.
Because of their physical size and physiological immaturity, resuscitation of extremely very low birth weight premature infants is a big dilemma for neonatologists in any hospital. The resuscitation may present an additional challenge to the caregiver if it is undertaken in a remote community hospital with limited technical facilities and health personnel. We present the case of successful resuscitation of a 23-week-old premature infant, with a birth weight of 650 g, at Delma Island Community Hospital, United Arab Emirates. Despite the comparatively limited facilities for such a resuscitation, the rapid ethical decisions made when considering the resuscitation of such a borderline viable fetus, were key in avoiding long term neurological and pulmonary problems and contributed to the outcome of a healthy infant.


Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAPWorkshop on Periodontitis and Systemic Diseases.
This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue. This report examined biological plausibility, epidemiology and early results from intervention trials. Plausibility: Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation. In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective. There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C-reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles - supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention. It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.


The design of zinc-substituted cobalt (pyro)phosphates as efficient bifunctional electrocatalysts for zinc-air batteries.
In an effort to rationally design economic electrocatalysts, zinc-substituted cobalt phosphate and pyrophosphate were prepared using facile template-free combustion synthesis. They act as efficient stable bifunctional electrocatalysts due to the tuning of oxygen affinity by zinc substitution and catalytically active cobalt sites. Exploiting their bifunctional activity, these cobalt (pyro)phosphates were incorporated into a zinc-air battery in an alkaline electrolyte.


Ribonucleotide reductase from Fusarium oxysporum does not Respond to DNA replication stress.
Ribonucleotide reductase (RNR) catalyzes the rate limiting step in dNTP biosynthesis and is tightly regulated at the transcription and activity levels. One of the best characterized responses of yeast to DNA damage is up-regulation of RNR transcription and activity and consequently, elevation of the dNTP pools. Hydroxyurea is a universal inhibitor of RNR that causes S phase arrest. It is used in the clinic to treat certain types of cancers. Here we studied the response of the fungal plant pathogen Fusarium oxysporum to hydroxyurea in order to generate hypotheses that can be used in the future in development of a new class of pesticides. F. oxysporum causes severe damage to more than 100 agricultural crops and specifically threatens banana cultivation world-wide. Although the recovery of F. oxysporum from transient hydroxyurea exposure was similar to the one of Saccharomyces cerevisiae, colony formation was strongly inhibited in F. oxysporum in comparison with S. cerevisiae. As expected, genomic and phosphoproteomic analyses of F. oxysporum conidia (spores) exposed to hydroxyurea showed hallmarks of DNA replication perturbation and activation of recombination. Unexpectedly and strikingly, RNR was not induced by either hydroxyurea or the DNA-damaging agent methyl methanesulfonate as determined at the RNA and protein levels. Consequently, dNTP concentrations were significantly reduced, even in response to a low dose of hydroxyurea. Methyl methanesulfonate treatment did not induce dNTP pools in F. oxysporum, in contrast to the response of RNR and dNTP pools to DNA damage and hydroxyurea in several tested organisms. Our results are important because the lack of a feedback mechanism to increase RNR expression in F. oxysporum is expected to sensitize the pathogen to a fungal-specific ribonucleotide inhibitor. The potential impact of our observations on F. oxysporum genome stability and genome evolution is discussed.


Coprologic and molecular prevalence of Giardia duodenalis from children in Tabuk City, Saudi Arabia.
Giardia infection in children has been recognized as a significant cause of diarrhea in school children around the world. The objective of the present study was to determine the prevalence and genotypes of Giardia duodenalis in school children in Tabuk City, Saudi Arabia. Fecal samples from 200 children with ages ranging from 9 to 12 years (106 boys and 94 girls) were examined for the presence of Giardia cysts using direct microscopy and ELISA. DNA was extracted from fecal samples and subjected to polymerase chain reaction (PCR) using primers which amplified the partial 18S rRNA locus. Direct microscopy revealed that 9 (4.5%) were positive for Giardia cysts. ELISA and PCR revealed 20 (10%) and 44 (22%) of the samples were positive respectively. Assemblage A was detected through genotyping of Giardia duodenalis isolates prevalent in Tabuk City through sequencing the fragment obtained as a result of amplifying partial 18S rRNA locus.


The neuronal code(s) of the cerebellum.
Understanding how neurons encode information in sequences of action potentials is of fundamental importance to neuroscience. The cerebellum is widely recognized for its involvement in the coordination of movements, which requires muscle activation patterns to be controlled with millisecond precision. Understanding how cerebellar neurons accomplish such high temporal precision is critical to understanding cerebellar function. Inhibitory Purkinje cells, the only output neurons of the cerebellar cortex, and their postsynaptic target neurons in the cerebellar nuclei, fire action potentials at high, sustained frequencies, suggesting spike rate modulation as a possible code. Yet, millisecond precise spatiotemporal spike activity patterns in Purkinje cells and inferior olivary neurons have also been observed. These results and ongoing studies suggest that the neuronal code used by cerebellar neurons may span a wide time scale from millisecond precision to slow rate modulations, likely depending on the behavioral context.


[The retained surgical sponge, an ongoing surgical problem].
The retained surgical sponge seems to be an ongoing problem. Despite the fact that reports of retained surgical sponges are comparatively rare, this problem seems to be more prevalent than is generally appreciated. Even though counting sponges is a tedious task, it should nonetheless be performed with the utmost attention. Although the presence of radiopaque wires in the sponges is helpful in locating these, it does not prevent surgical sponges from being forgotten. These retained sponges can result in serious conditions such as septic complications or pseudo-tumour formation, which in turn might lead to extensive diagnostic and secondary surgical procedures.


Sonoclot's usefulness in prediction of cardiopulmonary arrest prognosis: A proof of concept study.
The aim of the present study was to evaluate the usefulness of measuring whole blood coagulation with Sonoclot to predict return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiopulmonary arrest (OHCA). This was a prospective, observational clinical study on patients with OHCA who were transferred to our emergency department between August 2016 and July 2018. Patients were divided into two groups: patients with return of spontaneous circulation (ROSC[+] group) and those without (ROSC[-] group). We compared the activated clotting time (ACT), clot rate (CR), and platelet function (PF) as measured with Sonoclot, and the fibrinogen degradation products (FDP) level and D-dimer level between the two groups. We analyzed 87 patients: 37 in the ROSC(+) and 50 in the ROSC(-) groups. Regarding ACT, CR, PF, FDP, and D-dimer, we used receiver operating characteristic (ROC) curves to examine how well each factor predicts ROSC. The area under the ROC curve (AUC) of CR was higher than that of the FDP and D-dimer levels. Among patients with cardiogenic cardiac arrest, the AUC of CR was higher than the AUCs of other coagulation factors. In conclusion, viscoelastic blood coagulation measurements using Sonoclot may be useful for predicting ROSC in OHCA patients.


End-of-life care in children: the Brazilian and the international perspectives.
To analyze the medical practices and the end-of-life care provided to children admitted to pediatric intensive care units in different parts of the globe. Articles on end-of-life care published during the last 20 years were selected from the PubMed, MEDLINE and LILACS databases, with emphasis on studies of death in pediatric intensive care units in Brazil, Latin America, Europe and North America, using the following keywords: death, bioethics, pediatric intensive care, cardiopulmonary resuscitation and life support limitation. Publications on life support limitation (LSL) are concentrated in North America and Europe. In North American pediatric intensive care units there is a greater incidence of LSL (approximately 60%) than in Europe or Latin America (30-40%). These differences appear to be related to cultural, religious, legal and economic factors. Over the last decade, LSL in Brazilian pediatric intensive care units has increased from 6 to 40%, with do not resuscitate orders as the most common method. Also of note is the low level of family participation in the decision-making process. A recent resolution adopted by the Federal Medical Council (Conselho Federal de Medicina) regulated LSL in our country, demystifying a certain apprehension of a legal nature. The authors present a proposal for a protocol to be followed in these cases. The adoption of LSL with children in the final phases of irreversible diseases has ethical, moral and legal support. In Brazil, these measures are still being adopted in a timid manner, demanding a change in behavior, especially in the involvement of families in the decision-making process.


Production of conjugated linoleic acid-rich potato chips.
Conjugated linoleic acid (CLA) is found primarily in diary and beef products, but the health benefits of CLA can only be realized if they are consumed at much greater levels than a normal healthy dietary intake. We have recently shown that a CLA-rich soy oil can be produced by simple isomerization of linoleic acid in soy oil by photoirradiation. This oil may allow greatly increased dietary CLA without significantly elevating fat intake. The objective of this study was to prepare CLA-rich potato chips by frying in CLA-rich soy oil. Soy oil was photoisomerized in the presence of iodine catalyst with UV/visible light. The irradiated oil was clay processed to remove the residual iodine and this oil was then used to fry potato chips. Oil was extracted from fried chips and analyzed for its CLA content with gas chromatography. A 1-oz serving of CLA-rich potato chips contained approximately 2.4 g CLA as compared to 0.1 g CLA in 3-oz serving of steak fillet and 0.06 g CLA in 8-oz serving of whole milk. The peroxide value of the oil extracted from potato chips was found to be 1 meq/1000 g sample, which was within the acceptable commercial standards. This study may lead to the commercialization of CLA-rich food products.


Effects of bevacizumab on retinal function in isolated vertebrate retina.
Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application. Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings. During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged. The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.