Projecting the impact of hypothetical early life interventions on adiposity in children living in low-income households.
It is difficult to evaluate the effectiveness of interventions aimed at reducing early childhood obesity using randomized trials. Objective To illustrate how observational data can be analysed using causal inference methods to estimate the potential impact of behavioural 'interventions' on early childhood adiposity. Methods We used longitudinal data from 1054 children 1-5 years old enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children and followed (WIC) from 2008 to 2010 for a mean duration of 23 months. The data came from a random sample of WIC families living in Los Angeles County in 2008. We used the parametric g-formula to estimate the impact of various hypothetical behavioural interventions. Results Adjusted mean weight-for-height Z score at the end of follow-up was 0.73 (95% CI 0.65, 0.81) under no intervention and 0.63 (95% CI 0.38, 0.87) for all interventions given jointly. Exclusive breastfeeding for 6 months or longer was the most effective intervention [population mean difference = -0.11 (95% CI -0.22, 0.01)]. Other interventions had little or no effect. Conclusions Compared with interventions promoting healthy eating and physical activity behaviours, breastfeeding was more effective in reducing obesity risk in children aged 1-5 years. When carefully applied, causal inference methods may offer viable alternatives to randomized trials in etiologic and evaluation research.


Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand.
To measure the comparative effectiveness of metformin versus insulin for initial pharmacological management of gestational diabetes mellitus (GDM). We conducted a population-based retrospective cohort study using administrative claims, maternity care, and laboratory result data from New Zealand. We followed pregnant women aged 15 to 45 from GDM diagnosis through delivery and assessed outcomes using maternity care and hospitalization data. We adjusted for covariates using inverse probability of treatment weights and multiple imputation for missing covariate information. We estimated unadjusted and adjusted risk ratios (RRs), risk differences (RDs) per 100, and 95% confidence intervals (CIs). Linear regression was used to estimate the association of treatment with birthweight. We stratified analyses by ethnicity and infant sex in prespecified sensitivity analyses. We compared 3818 metformin-treated pregnancies with 3450 insulin-treated pregnancies. We observed differences in treatment initiation by ethnicity, socioeconomic status, region, and calendar year. Treatment groups were similar in age, body mass index (BMI), and timing of diagnosis/treatment initiation. After adjustment, metformin was associated with reduced absolute risk of planned elective c-section (RD = -2.3, 95% CI, -4.3 to -0.3), large for gestational age (RD = -3.7, 95% CI, -5.5 to -1.8), and neonatal hypoglycemia (RD = -5.0, 95% CI, -6.9 to -3.2) compared with insulin. There were no clinically meaningful differences in average birthweight between metformin- and insulin-treated pregnancies. We observed variation in estimates by ethnicity and infant sex for some neonatal outcomes. Metformin appears to be an effective treatment for women with GDM and may reduce risk of some adverse neonatal outcomes when compared with insulin.


Experimental and theoretical study of a truly functional biomimetic molybdenum oxotransferase analogue system.
Density functional theory (DFT) computations at the B3LYP/Lanl2DZ level were used to elucidate the oxygen atom transfer (OAT) and coupled electron proton transfer (CEPT) reaction steps involved in the biomimetic catalytic cycle performed by polymer-supported Mo VIO2(NN')(2) complexes [NN'=phenyl-(pyrrolato-2-ylmethylene)-amine] with water as oxygen source, trimethyl-phosphane as oxygen acceptor and one-electron oxidising agents. The DFT method employed has been validated against experimental data [X-ray crystal structures of a NN' ligand and a Mo VIO2(NN')2 complex as well as kinetic data]. The rate-limiting step in the forward-OAT from [Mo VIO2] to PMe3 is the attack of PMe3 at an oxo ligand with DeltaG not equal (298 K)=64.6 kJ mol(-1). Dissociation of the product OPMe3 is facile with DeltaG( not equal) (298 K)=26.3 kJ mol(-1) giving a mono-oxo [Mo IVO] complex which fills its coordination sphere with a further PMe3 substrate with DeltaG not equal (298 K)=39.2 kJ mol(-1). One-electron oxidation to a Mo(V) phosphane complex precedes the coordination of water/hydroxide. Additionally, the comproportionation of [Mo VIO(2)] and [Mo IVO] to dinuclear oxo-bridged [O=MoV-O-MoV=O] species has been calculated as the thermodynamic sink in this system and the back-OAT from dmso to mono-oxo [Mo IVO] to give [Mo VIO2] has been shown to involve an equilibrium between stereoisomeric [Mo VIO2] complexes with an activation barrier of DeltaG not equal (298 K)=113.1 kJ mol(-1).


Brain stem auditory evoked potentials as a tool in the clinical assessment of children with posterior fossa tumors.
The use of brain stem auditory evoked potentials (BAEP) as a diagnostic modality in children with posterior fossa neoplasms is described. Thirty-one patients were examined; their diagnoses were medulloblastoma (12), brain stem glioma (9), cerebellar astrocytoma (6), and ependymoma (4). Distinct differences in the type and severity of waveform abnormalities were observed among the different tumor types, possibly related to location and invasiveness. Medulloblastomas frequently demonstrate normal waveforms, while brain stem gliomas demonstrate severe disruption of BAEP patterns. Ependymomas may result in a variety of abnormal studies, while cerebellar astrocytomas induce mild abnormalities or result in a normal exam. The use of brain stem auditory evoked potentials in the diagnosis of pediatric brain tumors, as well as the underlying mechanisms of the abnormalities, is discussed.


Tartrazine exposure results in histological damage, oxidative stress, immune disorders and gut microbiota dysbiosis in juvenile crucian carp (Carassius carassius).
Tartrazine (TZ) is an azo dye widely used in foods, cosmetics, beverages, textile, and leather. In recent years, there are reports on detecting azo dyes in the aquatic environment, so the impact of these compounds on aquatic organisms could not be ignored. In this study, we aimed to evaluate the adverse effects of TZ exposure on teleosts' embryo development and juvenile's health by using crucian carp (Carassius carassius) as the experimental fish. The results showed that embryos exposed to TZ (0.19, 0.76 and 1.5 mM) exhibited a deformity, delayed egg resorption and decreased fertilization and hatching rate. When the juvenile fish were exposed to TZ at a level higher than those present in water for 30 days caused severe histopathological damages of the gill, intestine, kidney and liver. Antioxidant enzymes (CAT, SOD and GSH-Px) activities in the gill, intestine and liver, exhibited a decreasing trend after TZ exposure, while MDA contents elevated. TZ exposure also resulted in the upregulation of pro-inflammatory cytokines (il1 and il6), lysozymes (lyz), complement component 3 (c3), and β-defensin 3 (defb3). In addition, TZ exposure also affected the intestinal microbiota structure. In summary, the data in the present study indicated that TZ exposure reduce the embryo fertilization and hatching rate; cause histopathological damage of tissues, trigger oxidative stress, innate immune disorders and dysbiosis of gut microbiota in juvenile crucian carp. Therefore, it is necessary to be informed about the hazards of TZ exposure and the discharge of the dye into waters should be strictly administrated to prevent environmental pollution.


Occurrence and significance of arrhythmias associated with atrial-triggered ventricular pacing.
A review of electrocardiograms from 85 patients with atrial-triggered ventricular pacing (VAT, VDD, DDD) showed that various disturbances of rhythm were relatively common, and that the effects of an arrhythmia could be aggravated by this type of pacing. In certain circumstances even potentially dangerous ventricular extrasystoles were induced by the pacemaker. Abnormal triggering, sometimes with regular sinus rhythm, could also induce tachycardia. Our observations provided indications for a pacemaker design that would avoid such disturbing effects. The best available pacer for atrial-triggered ventricular pacing is the programmable DDD type.


High glucose and interleukin 1β-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4.
Hyperglycaemia and inflammatory can induce apoptosis in vascular endothelial cells, which contributes to the development of vascular complications in diabetes. Endothelial cells depend on glycolysis for their energy metabolism, and monocarboxylate transporters (MCTs) regulate intracellular pH by mediating the influx and efflux of lactate. Here, we evaluate the role of MCT4 in high glucose (HG) and interleukin 1β (IL-1β)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). We demonstrate that aortic endothelium damage is severe in db/db mice by using scanning ion conductance microscopy (SICM). HG and IL-1β decrease MCT4 and its location on plasma membrane, as well as increase lactic acid accumulation and apoptosis in HUVECs. Knockdown of MCT4 blocks lactate efflux to result in lactic acid accumulation and pH dropping, which is involved in triggering apoptosis in HUVECs.


Primary repair of complete atrioventricular canal in patients less than 2 years old.
Twenty-seven consecutive patients less than 2 years of age underwent primary intracardiac repair of complete atrioventricular (A-V) canal. Three (19 percent) of the 16 operated on after January 1, 1975 died in the hospital, a smaller proportion than the 8 of 11 patients who died in the hospital after operation between 1972 and 1975 (P = 0.005). The date of operation as a continuous variable is also related to the probability of hospital death (P = 0.016). Age at operation was not related to hospital mortality among the total group of 27 infants, nor were the anatomic characteristics of the anterior and posterior bridging leaflets, the location and size of the interventricular communications or the duration or technique of profound hypothermia (total circulatory arrest versus low perfusion flow rate). The improved results in the 16 patients operated on since January 1, 1975 are believed to be primarily the result of an improved ability to construct "mitral" and "tricuspid" valves from the common A-V valve. Fourteen of the 16 hospital survivors are alive and well 5 to 60 months after operation. These results and the natural history of patients with this malformation indicate that there should be no change in the policy of performing elective intracardiac repair before age 2 years and primary repair rather than pulmonary arterial banding when operation is required in the early months of life.


[Effects of peri-immunosupressive therapy period infection on hematologic response and survival of severe aplastic anemia].
To explore the effects of peri-immunosuppressive treatment(IST)infection on outcomes of severe and very severe aplastic anemia(SAA/VSAA)patients. Medical record and follow-up data of 105 SAA/VSAA who underwent first-line IST were retrospectively analyzed to find out the characters of infections(1 month before to 3 months after IST), and its effects on hematologic response and survival. Of 105 patients, a total of 270 febrile episodes were recorded in 97 patients(92.4%)during their peri- IST periods, with the median infections of 2(1-7)episodes in each patient with the median febrile duration of 7(1-47)days. Respiratory system(35.1%)was the primary anatomic site of infection. Bacteria(88.2%)were common causes of total 169 pathogenic bacteria in 96 clear pathogenic bacteria episodes. And patients who got infection 1 month before IST had much lower 6- month hematologic response rate than their counterpart ones(50.8% vs 80.0%, P=0.004). Multiple febrile episodes ( ≥3 times) and the total febrile duration ≥4 days showed the best sensitivity and specificity according to the ROC curve analysis. The 5-year overall survival of the 105 patients was 76%. The 5- year OS of patients with multiple febrile episodes ( ≥3 times) were much lower than their counterpart ones[(59.6±7.2)% vs(89.5±4.0)%](P<0.01). The 5-year OS of the total febrile duration ≥4 days was much lower than their counterpart ones[(63.4±5.8)% vs 100.0%](P<0.01). Infections 1 month before IST were associated with hematologic response. Multiple febrile episodes(≥3 times) and infections with the febrile duration ≥4 days presented inferior hematologic response and survival.


Hebeloma species associated with Cistus.
The genus Hebeloma has a number of species highly specific to Cistus and others that occur with several host genera. This paper discusses the species of Hebeloma that appear to be ectomycorrhizal with Cistus, judging from their occurrence when Cistus is the only available host. The previously unknown species H. plesiocistum spec. nov. is described. We also provide a key to the known Hebeloma associates of Cistus. Molecular analyses based on ITS sequence data further illustrate the distinctness of the newly described species and difficulties in the species delimitation with view to H. erumpens. Specific associations with Cistus may have evolved more than once within the genus Hebeloma.


Hepatitis C virus recurrence in living donor liver transplant recipients.
Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) is a universal phenomenon. Recent reports have suggested an earlier and more aggressive recurrence in the living donor liver transplant (LDLT) population. The aim of this study was to compare the histological recurrence of HCV after LDLT versus deceased donor transplantation (DDT). Twenty-nine patients underwent LT for HCV-related end-stage liver disease at our institution between April 2001 and March 2003 (42 months). Twenty patients underwent DDT, and nine patients LDLT. Laboratory data were collected on a weekly to biweekly basis and HCV PCR was performed before LT and 3-4 months and yearly post-LT. Liver biopsies were performed as needed and per institutional protocol at 7 days, at 4 months, and yearly thereafter. All biopsies were evaluated by a single pathologist and scored for rejection (Banff score) and chronic hepatitis (Ishak score system). The predominant genotype in the DDT and LDLT groups was genotype 1 (DDT = 70%, LDLT = 79%). HCV RNA titers pre-LT and 3-4 months after LT did not differ. The incidence of rejection was higher in the DDT group (P < 0.05). There was a trend toward improved Ishak stage and grade in the LDLT group at 4 and 12 months post-LT, however, this trend did not reach statistical significance. No histological difference in the recurrence or severity rate was observed at 4 or 12 months post-LT in the DDT group vs. the LDLT group.


Vaso-occlusive crises and costs of sickle cell disease in patients with commercial, Medicaid, and Medicare insurance - the perspective of private and public payers.
To characterize vaso-occlusive crises (VOCs) and describe healthcare costs among commercially-insured, Medicaid-insured, and Medicare-insured patients with sickle cell disease (SCD). The IBM Truven Health MarketScan Commercial (2000-2018), Medicaid Analytic eXtract (2008-2014), and Medicare Research Identifiable Files (2012-2016) databases were used to identify patients with ≥2 SCD diagnoses. Study measures were evaluated during a 12-month follow-up period, stratified by annual number of VOCs (i.e. 0, 1, and ≥2). Among 16,092 commercially-insured patients (mean age = 36.7 years), 35.3% had 1+ VOCs. Mean annual total all-cause healthcare costs were $15,747, $27,194, and $64,555 for patients with 0, 1, and 2+ VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 31.0%, 1 VOC = 53.1%, 2+ VOCs = 65.4%) and SCD-related costs (0 VOC = 56.4%, 1 VOC = 78.4%, 2+ VOCs = 93.9%). Among 18,287 Medicaid-insured patients (mean age = 28.5 years, fee-for-service = 50.2%), 63.9% had 1+ VOCs. Mean annual total all-cause healthcare costs were $16,750, $29,880, and $64,566 for patients with 0, 1, and 2+ VOCs, respectively. Inpatient costs (0 VOC = 37.2%, 1 VOC = 64.3%, 2+ VOCs = 72.9%) and SCD-related costs (0 VOC = 60.9%, 1 VOC = 73.8%, 2+ VOCs = 92.2%) accounted for a significant proportion of total all-cause healthcare costs. Among 15,431 Medicare-insured patients (mean age = 48.2 years), 55.1% had 1+ VOCs. Mean annual total all-cause healthcare costs were $21,877, $29,250, and $58,308 for patients with 0, 1, and ≥2 VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 47.9%, 1 VOC = 54.9%, 2+ VOCs = 67.5%) and SCD-related costs (0 VOC = 74.9%, 1 VOC = 84.4%, 2+ VOCs = 95.3%). VOCs managed at home were not captured. Analyses were descriptive in an observational setting; thus, no causal relationships can be inferred. A high proportion of patients experienced VOCs across payers. Furthermore, inpatient and SCD-related costs accounted for a significant proportion of total all-cause healthcare costs, which increased with VOC frequency.


Octamers and nanoparticles as hemoglobin based blood substitutes.
Progress in developing a blood substitute is aided by new biotechnologies and a better understanding of the circulatory system. For Hb based solutions, there is still a debate over the best set of fundamental parameters concerning the oxygen affinity which is correlated with the oxidation rate, the cooperativity, the transporter size, and of course the final source of material. Genetic engineering methods have helped discover novel globins, but not yet the quantity necessary for the high demand of blood transfusions. The expanding database of globin properties has indicated that certain individual parameters are coupled, such as the oxygen affinity and the oxidation rate, indicating that one must accept a compromise of the best parameters. After a general introduction of these basic criteria, we will focus on two strategies concerning the size of the oxygen transporter: Hb octamers, and Hb integrated within a nanoparticle.


PACES: a primary care tool to detect mental health disorders in Indigenous Colombians.
The aim of this research was to present the process of intercultural creation and validation, in addition to the analysis of the psychometric properties of the Parenting, Behavior, Emotions and Suicide risk scale. A cross-sectional study, cultural adaptation and validation with an ethnic approach were carried out by expert judges in mental health; subsequently, the instrument was applied, and a factorial analysis was carried out, and it was established that there was agreement between the instrument results and two expert perspectives regarding spiritual disharmony. The sample consisted of 168 families of children and young people (54.8% women, 45.2% men), with a mean age of 11.2 years, in Colombia. Regarding the geographical location, 44% were from Guajira, 44.6% were from Nariño and 11.3% were from Vaupés, from the Wayuu, Awá and Emberá communities, respectively. The scale showed high reliability (Chronbach's α=0.911), and in the factorial analysis the following parenting domains were formed from the parents: involvement, monitoring and bond, from boys, girls and young people; suicidal risk perceived by caregivers and perceived by children and young people; in addition to a total mental health risk. The questions that inquired about hallucinations and seizures did not show grouping in any factor, and two questions were eliminated. Similarly, a high inter-rater concordance was shown, with a higher Cohen's κ coefficient for all domains. There are few intercultural and early detection studies of parenting and mental health problems in children and youth that have an ethnic approach. It is observed that the instrument serves as a means of monitoring mental health issues in children and adolescents, as well as the parenting practices employed in their socialization, from both the perspective of caregivers and the young individuals themselve. This study indicates that the scale is an adequate tool, quick and easy to administer in first-level care settings.


Evaluation of influenza-specific humoral response by microbead array analysis.
Quantitation and determination of antigen specificity of systemic and mucosal immune responses to influenza vaccination is beneficial for future vaccine development. Previous methods to acquire this information were costly, time consuming and sample exhaustive. The benefits of suspension microbead array (MBA) analysis are numerous. The multiplex capabilities of the system conserve time, money and sample, while generating statistically powerful data. To demonstrate the use of the assay by comparing the humoral influenza-specific responses of two cohorts from two countries that differed in circulating influenza strains and rates of influenza vaccination. Influenza hemagglutinin (HA) from different strains were coated on microbeads and incubated with serum samples to capture immunoglobulin (Ig) A(1) and IgG(1) host antibodies. Statistically significant differences in IgA(1) and IgG(1) exist between the serum samples from Winnipeg (Manitoba) donors and those from Kenyan (Africa) donors. Data were compared using Mann-Whitney nonparametric tests. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti-HA IgA(1) to A/Wyoming/3/2003 (P=0.044), A/Vietnam/1203/2004 (P=0.0179), A/New Caledonia/20/99 (P<0.0001) and B/Tokyo/53/99 (P=0.0002). No differences were seen between the groups in their response to B/Jilin/20/2003. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti-HA IgG(1) to A/Wyoming/3/2003 (P=0.0135), B/Tokyo/53/99 (P=0.006) and B/Jilin20/2003 (P=0.026). Influenza-specific IgA(1) and IgG(1) antibodies were successfully detected using MBA technology. A significant difference in antibody response was observed between Winnipeg and Kenyan donor serums. MBA analysis is a relatively quick and cost-effective method for serum antibody analysis. The potential to simultaneously assay small sample volumes for a multitude of antigens makes this method invaluable for future vaccine response monitoring.


New satellite-based estimates show significant trends in spring phenology and complex sensitivities to temperature and precipitation at northern European latitudes.
Recent climate warming has altered plant phenology at northern European latitudes, but conclusions regarding the spatial patterns of phenological change and relationships with climate are still challenging as quantitative estimates are strongly diverging. To generate consistent estimates of broad-scale spatially continuous spring plant phenology at northern European latitudes (> 50° N) from 2000 to 2016, we used a novel vegetation index, the plant phenology index (PPI), derived from MODerate-resolution Imaging Spectroradiometer (MODIS) data. To obtain realistic and strong estimates, the phenology trends and their relationships with temperature and precipitation over the past 17 years were analyzed using a panel data method. We found that in the studied region the start of the growing season (SOS) has on average advanced by 0.30 day year-1. The SOS showed an overall advancement rate of 2.47 day °C-1 to spring warming, and 0.18 day cm-1 to decreasing precipitation in spring. The previous winter and summer temperature had important effects on the SOS but were spatially heterogeneous. Overall, the onset of SOS was delayed 0.66 day °C-1 by winter warming and 0.56 day °C-1 by preceding summer warming. The precipitation in winter and summer influenced the SOS in a relatively weak and complex manner. The findings indicate rapid recent phenological changes driven by combined seasonal climates in northern Europe. Previously unknown spatial patterns of phenological change and relationships with climate drivers are presented that improve our capacity to understand and foresee future climate effects on vegetation.


Influence of sludge age on the performance of MFC treating winery wastewater.
The objective of this paper was to determine the influence of sludge age on microbial fuel cell (MFC) performance for generating electricity and removing organic matter from winery wastewater. Six Solid Retention Times (SRT) were used: 1.2, 1.4, 1.8, 2.3, 3.5 and 7.0 d. Results demonstrate that the electricity generation increases by decreasing the SRT, selecting electrogenic microorganisms, once the specific organic loading rate (SOLR) increased and the competition for substrate was reduced. Decreasing the SRT, coulombic efficiency can be increased from 3.4% to almost 42.2% and maximum power density from 58 to 890 mW m(-2). However the SRT did not influence on organic matter removal in biological treatment, because only a small part of COD was removed oscillating around 600 mg L(-1) d(-1)and it was very similar at all SRT studied.


Evaluation of uveal and capsule biocompatibility of a single-piece hydrophobic acrylic intraocular lens with ultraviolet-ozone treatment on the posterior surface.
To evaluate a single-piece hydrophobic acrylic intraocular lens (IOL) with ultraviolet-ozone (UV-O3) treatment on the posterior surface and compare it with an identical untreated IOL in a rabbit model. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Experimental study. Study IOLs were implanted in the right eyes and control IOLs in the left eyes of 10 New Zealand rabbits. Slitlamp examinations were performed 1 to 6 weeks postoperatively. Neodymium:YAG (Nd:YAG) posterior capsulotomy was performed in both eyes of 5 rabbits after the 4-week slitlamp examination. At 6 weeks, the rabbits were killed humanely and their globes were enucleated. Capsular bag opacification was scored from the posterior aspect (Miyake-Apple view), and the eyes were processed for histopathology. At 4 weeks, the mean posterior capsule opacification (PCO) scores were 0.88 ± 0.33 (SD) in the study eyes and 2.55 ± 1.13 in the control eyes (P=.003, 2-tailed paired t test). Performance of Nd:YAG posterior capsulotomy was similar in both groups. Gross postmortem examination also showed statistically less peripheral PCO in eyes with the study IOLs than in control eyes. There was no difference in histopathologic findings between study eyes and control eyes and no signs of untoward inflammation or toxicity in any eye evaluated. Treatment of the posterior surface of a single-piece hydrophobic acrylic IOL with UV-O3 appears to prevent PCO, likely by increasing adhesion between the posterior capsule and the IOL while retaining uveal biocompatibility. Performance of Nd:YAG posterior capsulotomy was similar between treated IOLs and untreated IOLs.


Quality management in neuropathology.
Quality management will have an increasing impact on the field of clinical neurosciences. The neuropathological examination of surgical or autopsy samples obtained from the central nervous system (CNS) and related structures, cerebrospinal fluid, peripheral nerve or skeletal muscle serves three major purposes: to identify a structural correlate of the disease, provide a reliable basis for treatment strategies and to investigate underlying pathogenic mechanisms. In order to achieve histopathological diagnosis at a consistent quality, quality management and control have to be implemented at different levels. At the local site, these concern neuropathological services, such as acquisition of tissue specimens, handling and staining procedures as well as diagnostic examination. Training programs offered in slide seminars and diagnostic workshops are important tools to highlight new developments and maintain high standards. National reference centers for brain tumors, neurodegenerative disorders, prion or muscle and nerve diseases assist with a second opinion in difficult cases and support epidemiological as well as clinical therapy trials. An international panel of neuropathologists has established guidelines for the classification of brain tumors, recently updated during a WHO 2000 consensus conference. Finally, the standardized histopathological and cytological diagnosis of CNS disorders plays also an important role in providing quality control for associated fields of the clinical neurosciences, such as neuroradiology, neurology, psychiatry and neurosurgery.


Chitin: Formation of Helically Structured Chitin/CaCO3 Hybrids through an Approach Inspired by the Biomineralization Processes of Crustacean Cuticles (Small 38/2015).
Biomineral-inspired hybrids forming helically ordered structures are developed by T. Kato and co-workers on page 5127. These helical hybrids consist of liquid-crystalline chitin and CaCO3 . They resemble the structures of crustacean cuticles such as the exoskeleton of a lobster or crayfish. These hybrids are formed through CaCO3 crystallization on the liquidcrystalline chitin templates. Polymer-stabilized amorphous CaCO3 is incorporated into the liquid-crystalline chitin templates. This approach is useful for the development of new hierarchical hybrid materials from abundant natural resources.


Brain-stem, middle latency and late cortical evoked potentials in children with speech and language disorders.
The topography of the brain-stem (ABR), middle latency (MLR) and cortical (ACR) evoked responses was investigated in children with normal speech and language development and those with either a language or motor speech disorder. The aim was to determine whether it is possible to discriminate between the groups of children in terms of the evoked potential characteristics. There were significant inter-group differences, particularly relating to the amplitude of the different responses. The ABR in both the language and motor speech groups exhibited smaller amplitudes for waves I, III and V than the control group, with no change in latency. Two explanations were suggested; firstly abnormal functioning of the peripheral hearing mechanism even though the hearing thresholds were normal which could be a secondary effect due to deprivation of normal speech and language development; and secondly far-field recording effects due to differences in the electrical conductivity of tissue and the distance separating the generator site and recording electrodes. The MLR in the motor speech group was significantly larger at the mastoid and temporal electrode sites than either the control or language groups. This was considered to be an enhanced myogenic response like the other exaggerated brain-stem reflexes seen in congenital suprabulbar paresis. Significantly larger amplitudes of the ACR were also recorded from the motor speech group at the Cz electrode site. This was thought to be due to underactivity of some normal cortical inhibitory system and not a direct result of increased MLR amplitude. The ACR in the language disordered children exhibited an abnormal left temporal hemispheric dominance and a more inverted or 'dissimilar' wave form at the T3 electrode site on the correlation analysis. These findings suggest impaired functioning of the left temporal cortex in our children who have failed to develop language normally. We feel that this has more significance for the language abnormality than the low amplitude ABRs which were observed in both the language and motor speech disordered children.


Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial.
The aim of this study was to investigate the role of pre-treatment aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) + bevacizumab (B) or CT alone. Patients randomly received CT+B or CT alone as first-line therapy. CT consisted of either FOLFOX4 or FOLFIRI at the clinician's discretion. Out of the 284 patients enrolled, increased ALRI levels were associated with shorter PFS and OS (p<0.0001). At baseline, median PFS was 10.3 months (95% CI 9.4-12.0) and 8.0 months (95 % CI 6.8-8.9), and median OS was 25.2 months (95 % CI 21.3-30.2) and 18.8 months (95 % CI 16.6-21.7) for patients with low (<14) and high (≥14) ALRI levels, respectively (HR 1.43, 95% CI 1.12-1.82, p=0.004; HR=1.51, 95% CI 1.17-1.96, p<0.001). Interaction tests on ALRI levels and treatment efficacy in the CT+B and the CT groups were statistically significant for PFS (p=0.0003), but not for OS (p=0.228). Our results indicate that ALRI is a good prognostic and predictive marker for mCRC patients candidate for CT+B.


Crawford modification of Denis Browne hypospadias procedure.
At Alder Hey Children's Hospital 96 hypospadias repairs were performed from 1969 to 1975, using the Crawford modification of the Denis Browne procedure. The technique is decribed in detail. A 7.29 per cent fistula rate occurred in 69 distal penile, 18 penile, 8 penoscrotal and 1 perineal repairs. The advantageous difference between the Crawford modification and the original description of Denis Browne is that the meatus is placed well onto the glans penis.


Ferroelectric mesocrystals of bismuth sodium titanate: formation mechanism, nanostructure, and application to piezoelectric materials.
Ferroelectric mesocrystals of Bi0.5Na0.5TiO3 (BNT) with [100]-crystal-axis orientation were successfully prepared using a topotactic structural transformation process from a layered titanate H1.07Ti1.73O4·nH2O (HTO). The formation reactions of BNT mesocrystals in HTO-Bi2O3-Na2CO3 and HTO-TiO2-Bi2O3-Na2CO3 reaction systems and their nanostructures were studied by XRD, FE-SEM, TEM, SAED, and EDS, and the reaction mechanisms were given. The BNT mesocrystals are formed by a topotactic structural transformation mechanism in the HTO-Bi2O3-Na2CO3 reaction system and by a combination mechanism of the topotactic structural transformation and epitaxial crystal growth in the HTO-TiO2-Bi2O3-Na2CO3 reaction system, respectively. The BNT mesocrystals prepared by these methods are constructed from [100]-oriented BNT nanocrystals. Furthermore, these reaction systems were successfully applied to the fabrication of [100]-oriented BNT ferroelectric ceramic materials. A BNT ceramic material with a high degree of orientation, high relative density, and small grain size was achieved.


Identification, synthesis and pharmacological activity of moxonidine metabolites.
The metabolism of moxonidine, 4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methyl-5-pyrimidinamine, LY326869, in rats, mice, dogs, and humans has been examined. At least 17 metabolites were identified or tentatively identified in the different species by HPLC, LC/MS and LC/MS/MS. The identities of seven of the major metabolites have been verified by independent synthesis. The metabolites are generally derived from oxidation and conjugation pathways. Oxidation occurred at the imidazolidine ring as well as the methyl at the 2 position of the pyrimidine ring. All seven metabolites were examined in the spontaneously hypertensive rats (3 mg kg(-1), i.v.) for pressure and heart rate. Only one, 2-hydroxymethyl-4-chloro-5-(imidazolidin-2-ylidenimino)-6-methoxypyrimidine, exerted a short-lasting decrease in blood pressure, albeit attenuated in magnitude compared to moxonidine.


Methylation-assisted bisulfite sequencing to simultaneously map 5fC and 5caC on a genome-wide scale for DNA demethylation analysis.
Active DNA demethylation is mediated by ten-eleven translocation (TET) proteins that progressively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). We have developed a methylation-assisted bisulfite sequencing (MAB-seq) method that enables direct genome-scale mapping and quantification of 5fC and 5caC marks together at single-base resolution. In bisulfite sequencing (BS), unmethylated cytosine residues (Cs), 5fCs and 5caCs, are converted to uracil and cannot be discriminated from each other. The pretreatment of the DNA with the CpG methylation enzyme M.SssI, which converts only the Cs to 5mCs, protects Cs but not 5fCs and 5caCs, which enables direct detection of 5fCs and 5caCs as uracils. Here we also describe an adapted version of the protocol to perform reduced-representation MAB-seq (RRMAB-seq) that provides increased coverage on CpG-rich regions, thus reducing the execution costs and increasing the feasibility of the technique. The main advantage of MAB-seq is to reduce the number of chemical/enzymatic DNA treatments required before bisulfite treatment and to avoid the need for prohibitive sequencing coverage, thus making it more reliable and affordable than subtractive approaches. The method presented here is the ideal tool for studying DNA demethylation dynamics in any biological system. Overall timing is ∼3 d for library preparation.


Incidental capture of rarely diagnosed pediatric tumor: an infant boy with clear cell sarcoma of the kidney.
Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm that accounts for less than 5% of all pediatric renal tumors. Compared with Wilms' tumor, CCSK has a higher rate of relapse, greater propensity for bone metastasis, and poorer overall survival. We present the case of a 19-month-old boy with a large renal mass diagnosed incidentally by ultrasonography during surveillance for vesicoureteral reflux. This report describes the rare occurrence of an incidental radiologic capture of CCSK and provides a brief review of disease pathology.


The precise origin of the tectospinal pathway in three common laboratory animals: a study using the horseradish peroxidase method.
The horseradish peroxidase tracing method has been used to study the cells of origin of the tectospinal projections in the opossum, the tree shrew, and the cat. The present data show that only those collicular neurons which occupy the deep (ventral to the stratum opticum) tectal laminae send axons to the cervical spinal cord. In particular, layer IV contains the greatest number of spinal projecting neurons. Our results also reveal that while only the large sized collicular neurons project upon the cervical spinal cord in the opossum and the tree shrew, neurons comprising several different size categories do so in the cat. We thus suggest that several different descending channels exist over which the superior colliculus can influence the neck musculature in the cat.


CMS moving steadlly toward P4P; quality pros express reservations.
CMS official predicts system will become reality in two to four years. Some observers say pay for performance already is embedded in Medicare structure. Updating information systems, care in data analysis enable more complete compliance.


Influence of sulfamethazine (SMT) on the adsorption of antimony by the black soil: Implication for the complexation between SMT and antimony.
This paper reported when sulfamethazine (SMT) and antimony (Sb(V)) coexisted in aqueous solution at pH of 3.0, 5.0 and 7.0, the complexation between SMT and Sb(V) occurred. Such a complexation impeded the adsorption of Sb(V) on the black soil. The higher the solution pH value was, the more the amount of Sb(V) was prevented from adsorbing on the black soil. The maximum adsorption capacity (qm) of Sb(V) at the presence of SMT under pH of 3.0, 5.0 and 7.0 was 5.28, 3.45 and 1.95 mg/g, respectively. -NH2, NH, SO and CN of pyrimidine ring carried by SMT acted as the complexation sites with Sb(V). The complexation constant K were - 3.15, -3.26 and - 3.48 at pH of 7.0, 5.0 and 3.0, respectively, indicating that the complexation strength between SMT and Sb(V) followed the order of pH 7.0 > pH 5.0 > pH 3.0. The binding energy between Sb(V) and the CN group of pyrimidine ring was the highest (1.42 eV), and then followed by the groups of -NH (1.37 eV), SO (0.66 eV) and -NH2 (0.39 eV). Besides SO and CN, Sb(V) tends to complex with NH via coordination bond at pH of 7.0 while -NH2 via cation-π interaction at pH 3.0 and 5.0. Compared to pH of 5.0, the strength of cation-π interaction at pH of 3.0 weakened according to the molecular electrostatic potential map. These results demonstrated that different from the situation where Sb(V) exists in aqueous solution alone, the coexistence of SMT with Sb(V) affected the adsorption behavior of Sb(V) in soil and solution pH was also an influence factor. These findings in this paper would be helpful for further understanding the mobility, bioavailability and other environmental behavior of Sb(V) in soil when Sb(V) coexists with antibiotics even other organic compounds.


Pyrolysis self-activation: An environmentally friendly method to transform biowaste into activated carbon for arsenic removal.
A green method for production of activated carbon and combustible gas was introduced. Without any external reagents and gases, the H2O and CO2 produced by the pyrolysis of bamboo shoot shells were used as activators. The prepared activated carbon had good arsenic adsorption properties with the maximum adsorption capacities of 10.9 mg/g for As(III) and 16.0 mg/g for As(V). The gaseous products were mostly CO and H2, with higher heating value of 11.7 MJ/Nm3. Thermogravimetric experiments were performed in N2, H2O and CO2 atmospheres to simulate the self-activation process and investigate the self-activation mechanism. This work will help to improve the competitiveness of self-activation technology and reduce the production cost of activated carbon.


Performance monitoring following conflict: internal adjustments in cognitive control?
The purpose of this study was to investigate the effects of strategic conflict-related adjustments in cognitive control processes on indices of performance monitoring. Previous research has examined the ability of parametric task-related manipulations to bias attention to errors; however, the present study sought to elucidate the effects of internal adjustments in control mediated by the anterior cingulate cortex on error-related conflict processing. High-density event-related potentials (ERPs) were obtained from 124 healthy individuals (68 female, 66 male) during a modified Eriksen flanker task. Behavioral measures (i.e., error rates, response times [RTs]) and N2 amplitudes showed significant conflict adaptation (i.e., previous-trial congruencies influenced current-trial measures). For error trials, the error-related negativity (ERN) was more negative for errors on high-conflict (i.e., incongruent) trials following high-conflict trials relative to errors on high-conflict trials following low-conflict (i.e., congruent) trials. These findings indicate that error-related conflict-monitoring processes adjust according to the post-conflict recruitment of strategic cognitive control and suggest an ongoing interplay between conflict and internal adjustments in control resources. Interpretations from the perspective of the conflict monitoring theory of cognitive control, the reinforcement learning theory, and the response-outcome theory of the ERN are discussed.


A yoga & exercise randomized controlled trial for vasomotor symptoms: Effects on heart rate variability.
Heart rate variability (HRV) reflects the integration of the parasympathetic nervous system with the rest of the body. Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV. We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a randomized clinical trial of treatments for vasomotor symptoms in peri/post-menopausal women. Randomized clinical trial of behavioral interventions in women with vasomotor symptoms (n=335), 40-62 years old from three clinical study sites. 12-weeks of a yoga program, designed specifically for mid-life women, or a supervised aerobic exercise-training program with specific intensity and energy expenditure goals, compared to a usual activity group. Time and frequency domain HRV measured at baseline and at 12 weeks for 15min using Holter monitors. Women had a median of 7.6 vasomotor symptoms per 24h. Time and frequency domain HRV measures did not change significantly in either of the intervention groups compared to the change in the usual activity group. HRV results did not differ when the analyses were restricted to post-menopausal women. Although yoga and exercise have been shown to increase parasympathetic-mediated HRV in other populations, neither intervention increased HRV in middle-aged women with vasomotor symptoms. Mixed results in previous research may be due to sample differences. Yoga and exercise likely improve short-term health in middle-aged women through mechanisms other than HRV.


Families' experience of oncogenetic counselling: accounts from a heterogeneous hereditary cancer risk population.
This paper reports the results of semi-structured family interviews conducted with a purposive sample of nine families (comprising 50 individuals) involved in cancer genetic counselling at a Portuguese public hospital. Qualitative analysis resulted in thematic categories illustrating: (1) how families go through cancer genetic counselling (eliciting risk awareness, the motivators, risk management, the psychosocial context of familial engagement in genetic counselling, and the familial pathways of cancer risk tracking); and (2) how families incorporate genetic risk into family life (strategies for family resilience, and the meanings and values that permeate the experience). Families have recognised the value of genetic counselling in enabling participants to take measures to confront disease risk; however, the experience was dominated by distressing feelings. A set of ethical-relational principles guided the experience. Familial experiences on genetic counselling and tracking of cancer susceptibility encompass a sense of trajectory that takes the form of an historical and intergenerational narrative process, linking past, present and possible futures. Such process implies an ongoing set of individual and interactional experiences taking place over time. Specific changes associated with the illness timeline and with individual and family developmental lifespan transitions are thus acknowledged. These results may help genetics healthcare practitioners understand how families perceive, respond to and accommodate cancer risk counselling, and thus illuminate family-oriented tenets for planning and practice.


Stem Cell-Derived Immature Human Dorsal Root Ganglia Neurons to Identify Peripheral Neurotoxicants.
Safety sciences and the identification of chemical hazards have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically important field of peripheral neurotoxicity is still largely unexplored. A two-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as a functional parameter highly sensitive to disturbances by toxicants was used as an endpoint reflecting specific neurotoxicity. The differentiation of cells toward dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as a first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for the prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants and neurite growth enhancers were correctly identified. Various classes of chemotherapeutic agents causing human peripheral neuropathies were identified, and they were missed when tested on human central neurons. The PeriTox test we established shows the potential of human stem cells for clinically relevant safety testing of drugs in use and of new emerging candidates. The generation of human cells from pluripotent stem cells has aroused great hopes in biomedical research and safety sciences. Neurotoxicity testing is a particularly important application for stem cell-derived somatic cells, as human neurons are hardly available otherwise. Also, peripheral neurotoxicity has become of major concern in drug development for chemotherapy. The first neurotoxicity test method was established based on human pluripotent stem cell-derived peripheral neurons. The strategies exemplified in the present study of reproducible cell generation, cell function-based test system establishment, and assay validation provide the basis for a drug safety assessment on cells not available otherwise.


Application of continuous normal-lognormal bivariate density functions in a sensitivity analysis of municipal solid waste landfill.
The variability of untreated municipal solid waste (MSW) shear strength parameters, namely cohesion and shear friction angle, with respect to waste stability problems, is of primary concern due to the strong heterogeneity of MSW. A large number of municipal solid waste (MSW) shear strength parameters (friction angle and cohesion) were collected from published literature and analyzed. The basic statistical analysis has shown that the central tendency of both shear strength parameters fits reasonably well within the ranges of recommended values proposed by different authors. In addition, it was established that the correlation between shear friction angle and cohesion is not strong but it still remained significant. Through use of a distribution fitting method it was found that the shear friction angle could be adjusted to a normal probability density function while cohesion follows the log-normal density function. The continuous normal-lognormal bivariate density function was therefore selected as an adequate model to ascertain rational boundary values ("confidence interval") for MSW shear strength parameters. It was concluded that a curve with a 70% confidence level generates a "confidence interval" within the reasonable limits. With respect to the decomposition stage of the waste material, three different ranges of appropriate shear strength parameters were indicated. Defined parameters were then used as input parameters for an Alternative Point Estimated Method (APEM) stability analysis on a real case scenario of the Jakusevec landfill. The Jakusevec landfill is the disposal site of the capital of Croatia - Zagreb. The analysis shows that in the case of a dry landfill the most significant factor influencing the safety factor was the shear friction angle of old, decomposed waste material, while in the case of a landfill with significant leachate level the most significant factor influencing the safety factor was the cohesion of old, decomposed waste material. The analysis also showed that a satisfactory level of performance with a small probability of failure was produced for the standard practice design of waste landfills as well as an analysis scenario immediately after the landfill closure.


Efficacy of the fetal-pelvic index for delivery of neonates weighing 4000 grams or greater: a preliminary report.
The fetal-pelvic index was recently introduced as an accurate method of prospectively identifying the presence or absence of fetal-pelvic disproportion. In that report the ability to detect fetal-pelvic disproportion in patients with macrosomic fetuses was not specifically addressed. The objective of this study is to compare the efficacy of three methods used to identify the presence or absence of fetal-pelvic disproportion (the fetal-pelvic index, Colcher-Sussman x-ray pelvimetry, and estimated fetal weight greater than or equal to 4000 gm) in patients delivered of neonates weighing greater than or equal to 4000 gm after an adequate trial of labor (N = 34). Of the 18 patients requiring operative intervention, all but one had a positive fetal-pelvic index value (sensitivity = 94%). Of the 16 patients in whom vaginal deliveries were spontaneous, all but one had a negative value (specificity = 94%). On the basis of these data, the fetal-pelvic index is an accurate method of predicting the presence or absence of fetal-pelvic disproportion in patients delivered of neonates weighing greater than or equal to 4000 gm.


A model of mitochondrial creatine kinase binding to membranes: adsorption constants, essential amino acids and the effect of ionic strength.
The quantitative aspects of mitochondrial creatine kinase (mitCK) binding to mitochondrial membranes were investigated. A simple adsorption and binding model was used for data fitting, taking into account the influence of protein concentration, pH, ionic strength and substrate concentration on the enzyme adsorption. An analysis of our own data as well as of the data from the literature is consistent with the adsorption site of the octameric mitCK being composed of 4 amino acid residues with pK = 8.8 in the free enzyme. The pK value changes to 9.8 upon binding of the protein to the membrane. Lysine is suggested as the main candidate to form the adsorption site of mitCK. Deprotonated octameric mitCK easily dissociated from the membrane (Ka = 0.39 mM at ionic strength I = 7.5 mM and 5 degrees C); after protonation its affinity increased many times (Kah = 39 nM). Determination of mitCK adsorption capacity by another method at pH 7.4, when the enzyme is almost protonated, gave Kah = 15 nM. The effect of ionic strength on mitCK adsorption may be described in terms of Debye-Hückel's theory for activity coefficients assuming the charges of the interacting species to be +4 and -4. The dissociation constant for the mitCK-membrane complex at pH 7.4 and I = 0 was evaluated by different approaches as approx. 1 nM. Extramitochondrial ATP (or ADP) shifted greatly the equilibrium between the adsorbed and the free mitCK towards the solubilized state, since in the adsorbed protein the external ligands had access to four binding sites and in the free protein to eight sites.


Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase.
The drugs troglitazone and metformin are used to reduce the degree of insulin resistance in type 2 diabetes. Both compounds act through different mechanisms which might include opposing effects on the production of adiponectin, an insulin-sensitizer released by adipocytes. This study compared the effects of troglitazone and metformin on adiponectin production by 3T3-L1 adipocytes during 48 h culture. Troglitazone increased adiponectin mRNA and protein expression as well as release, whereas metformin did not affect transcription but reduced protein expression and release. The effect of metformin was also seen with phenformin, and with low-glucose culture, all conditions with a reduced mitochondrial activity and an activated AMP activated protein kinase (AMPK). Addition of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR) also caused a decrease in adiponectin protein expression. These data indicate that metformin and troglitazone exert opposing effects on adiponectin expression and release by differentiated 3T3-L1 adipocytes. The metformin-induced suppression involves an activation of AMP activated protein kinase.


The mitral annulus disjunction as a risk marker in mitral valve prolapse
Disjunction of the mitral valve annulus is a structural abnormality consisting of an atrial displacement of the articulation point of the mitral valve, leading to an altered spatial relationship between the valve and the adjacent posterior ventricular wall. Studies have shown the relationship between mitral annular disjunction, ventricular arrhythmias, and myocardial fibrous degeneration, which increases the risk of sudden death, especially among young women. The case of a 30-year-old woman with no relevant pathological history with frequent palpitations is presented, in whom an increase in ventricular automatism with a progressive increase in the arrhythmic load of up to 20% with a weight of pharmacological management is documented. In a cardiac magnetic resonance, a 15 mm displacement towards the atrium of the mitral leaflets compatible with mitral annular disjunction and late enhancement foci of mesocardial, non-coronary distribution were observed. Given the findings and the persistence of symptoms, an electrophysiological study, 3D mapping, and ablation were performed. Two hyperechoic regions were seen on intracardiac ultrasound, one in the length of the anterior papillary muscle and the other in the mesocardium of the base of the posterior papillary muscle. Both foci related to the morphological sites of interest in which radiofrequency energy was applied. During the procedure presented an episode of ventricular fibrillation. A malignant ventricular extrasystole was considered and therefore a cardio defibrillator was implanted for the secondary prevention of sudden death. The literature was reviewed and the specific pathophysiological relationships between mitral annular disjunction, premature ventricular complexes, and risk of sudden death were analyzed. The role of electrophysiological study and ablation in symptomatic patients refractory to pharmacological treatment is described.


Partial masking in electrocutaneous sensation: a model for sensation matching, with applications to loudness recruitment.
A model for partial masking and other threshold-elevation effects is presented in the context of a sensation-matching paradigm. The model is applied to an electrocutaneous experiment in which the subjects adjusted stimulus intensity on the right-hand fingertip to match sensation levels of standard stimuli presented to the left fingertip. Concurrent mechanical stimulation on the right fingertip masked sensation magnitude in a way consistent with the model. Similarities between this tactile masking effect and analogous auditory phenomena are explored. When applied to loudness matching, the model describes the general shape of loudness contours and it shows that the steep slopes observed in auditory masking and "recruitment" can be a consequence of a threshold shift alone, without a supranormal growth in loudness. The model also shows that a small response bias can distort plots of sensation matching, leading to the suggestion that some varieties of loudness recruitment may not have a sensory basis.


The Ah locus: correlation of intranuclear appearance of inducer-receptor complex with induction of cytochrome P1-450 mRNA.
The Ah locus regulates the induction of cytochrome P1-450 by foreign chemicals such as 3-methyl-cholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. The induction process is controlled by the cytosolic Ah receptor. The cytosolic and nuclear Ah receptors were studied in the liver from inbred C57BL/6N (Ahb/Ahb) mice, inbred DBA/2N (Ahd/Ahd) mice and heterozygotes (Ahb/Ahd) and homozygotes (Ahd/Ahd) derived from the (C57BL/6N X DBA/2N)F1 X DBA/2N backcross. After [3H-1,6]-2,3,7,8-tetrachlorodibenzo-p-dioxin (3H-TCDD) is given in vivo, the receptor in Ahb/Anb and Ahb/Ahd mice is detectable in the cytoplasm and nucleus; in Ahd/Ahd mice the receptor is not measurable in the cytosol, but is found in the nucleus at levels one fourth to one fifth of those in Ahb/Ahb mice. P1-450 (23S) mRNA content was estimated by Northern hybridization and by Rot analysis with a mouse P1-450 cloned cDNA. An excellent dose-response relationship (r = 0.99) was found between the amount of 3H-TCDD-Ah receptor complex appearing in the nucleus and the quantity of P1-450 mRNA induced in mice with all three possible Ah genotypes.


Abdominal wall cellulitis and sepsis secondary to percutaneous cecostomy.
We report 1 case of abdominal wall cellulitis and sepsis which developed following percutaneous placement of a Cope catheter for cecal decompression in a patient with Ogilvie's syndrome. This case highlights that further laboratory investigation and clinical evaluation are needed to determine the safest and most efficacious technique of percutaneous drainage.


An Algorithm for Predicting Neonatal Mortality in Threatened Very Preterm Birth.
To develop a prediction model for neonatal mortality using information readily available in the antenatal period. A multiple logistic regression model of a complete population-based geographically defined cohort of very preterm infants of 23+0 to 30+6 weeks' gestation was used to identify antenatal factors which were predictive of mortality in this population. Infants lt; 23 weeks and those with major anomalies were excluded. Between 1996 and 2012, 1240 live born infants lt; 31 weeks' gestation were born to women residing in Nova Scotia. Decreasing gestational age strongly predicted an increased mortality rate. Other factors significantly contributing to increased mortality included classification as small for gestational age, oligohydramnios, maternal psychiatric disorders, antenatal antibiotic therapy, and monochorionic twins. Reduced neonatal mortality was associated with antenatal use of antihypertensive agents and use of corticosteroids of any duration of therapy given at least 24 hours before delivery. An algorithm was developed to estimate the risk of mortality without the need for a calculator. Prediction of the probability of neonatal mortality is influenced by maternal and fetal factors. An algorithm to estimate the risk of mortality facilitates counselling and informs shared decision making regarding obstetric management.


miR-200a-3p improves neonatal necrotizing enterocolitis by regulating RIPK1.
Necrotizing enterocolitis (NEC) is an acquired disease, which mainly occurs in premature infants or sick newborns. microRNA (miR), as a common non-coding RNA in recent years, is found in many diseases. In this research, miR usefulin NEC is analyzed by GEO. The differentially expressed miRs in NEC were screened by analyzing GSE68054, and miR-200a-3p in IEC-6 cells induced by lipopolysaccharide (LPS) and serum of NEC children were detected by qRT-PCR. The role of miR-200a-3p in LPS-induced IEC-6 cells was tested using CCK-8, PI dyeing, and inflammatory cytokine detection. The direct downstream molecules of miR-200a-3p were identified using TargetScanHuman and verified by luciferase reporter gene assay. The mechanism of action was explored using western blot. miR-200a-3p in IEC-6 treated with NEC and LPS was significantly decreased. In vitro experiments revealed that miR-200a-3p mimetic could inhibit IL-6 and TNF-α in IEC-6 cells induced by LPS and reduce the positive rate of PI. In addition, it was determined that receptor-interacting protein kinase 1 (RIPK1) was a downstream molecule of miR-200a-3p, and overexpression of RIPK1 could aggravate LPS-induced IEC-6 injury, while miR-200a-3p mimics could alleviate the overexpression of RIPK1. miR-200a-3p mimics inhibited the elevation of necrosis-related molecules and the interaction between RIPK1 and RIPK3 in LPS-induced IEC-6 cells. miR-200a-3p can protect intestinal epithelial cells from LPS injury by inhibiting inflammation and necrosis mediated by RIPK1, which provides a possible target for NEC.


Toddlers, Tools, and Tech: The Cognitive Ontogenesis of Innovation.
The development of tool innovation presents a paradox. How do humans have such diverse and complex technology, ranging from smartphones to aircraft, and yet young children find even simple tool innovation challenges, such as fashioning a hook to retrieve a basket from a tube, remarkably difficult? We propose that the solution to this paradox is the cognitive ontogenesis of tool innovation. Using a common measure of children's tool innovation, we describe how multiple cognitive mechanisms work in concert at each step of its process: recognizing the problem, generating appropriate solutions, and the social transmission of innovations. We discuss what the ontogeny of this skill tells us about cognitive and cultural evolution and provide recommendations for future research.


Evidence for an intra-tumoral microbiome in pituitary neuroendocrine tumors with different clinical phenotypes.
Bacteria have been observed in the tumor environment for decades and have been demonstrated to play important roles in the pathogenesis and development of several different tumors. So far there is a clear lack of specific studies relating to the presence of bacteria in pituitary neuroendocrine tumors (PitNETs). In this study, we performed five region-based amplification and bacterial 16 S rRNA sequencing to identify the microbiome of PitNET tissues across four clinical phenotypes. Multiple filter procedures were performed to inhibit the risk of contamination with bacteria and bacterial DNA. Histological analysis was also conducted to validate the localization of bacteria in the intra-tumoral region. We identified common and diverse bacterial types across the four clinical phenotypes of PitNET. We also predicted the potential functions of these bacteria in tumor phenotypes and found that these functions were reported in certain previous mechanistic studies. Our data indicate that the pathogenesis and development of tumors may correlate with the behavior of intra-tumoral bacteria. Histological results, including lipopolysaccharide (LPS) staining and fluorescence in situ hybridization (FISH) for bacterial 16 S rRNA clearly demonstrated the localization of bacteria in the intra-tumoral region. Staining for Iba-1 suggested that the proportion of microglia was more abundant in FISH-positive regions than in FISH-negative regions. Furthermore, in FISH-positive regions, the microglia exhibited a longitudinally branched morphology that was different to the compact morphology observed in FISH-negative regions. In summary, we provide an evidence for the existence of intra-tumoral bacteria in PitNET.


Coexistence of spin liquid state and magnetic correlations in 3d-5dbased triangular-lattice antiferromagnet Sr3CuIr2O9.
Here, we report detailed lattice structure, magnetization (dc and ac) and specific heat measurements on a 3d-5dbased new triple-perovskite material Sr3CuIr2O9. The Sr/Cu forms a layered structure of triangular-lattice while the Ir forms Ir2O9dimers which lie in chain as well as simultaneously makes layered triangular-lattice with neighboring atoms. Due to random site-sharing with Sr2+, the Cu2+(3d9, spin-1/2) forms a diluted magnetic lattice, thus giving a disordered in-plane exchange interaction. Opposed to conventionalJeffmodel, the Ir5+(5d4,Jeff= 0) is believed to be magnetic here which participates both in-chain and in-plane magnetic interactions. This complex lattice structure driven competing exchange interaction leads the ground state to a gapless quantum-spin-liquid state which coexists with (weak) ferromagnetic spin correlations. While underling the importance of spin state (spin-1/2), we believe that the combined effect of lattice structure, geometric frustration, spin-orbit coupling and spin state has given rise this interesting ground state in this material.


[New information concerning pain caused by herniated disk and sciatica. Exposure to disk tissue sensitizes the nerve roots].
Sciatica has long been considered to be solely due to mechanical deformation (compression) of a spinal nerve root by herniating disc tissue. However, recent experimental findings have demonstrated that, even in the absence of mechanical insult, nucleus pulposus-related substances may not only induce significant structural and functional injury to the adjacent nerve root, but also sensitise the nerve root, producing pain in the event of subsequent root compression. Although neither the specific mechanisms nor the active nucleus pulposus-related substances causing pain have yet been identified, the recent findings suggest that the future may well bring new pharmacological treatment alternatives for sciatica and disc herniation.


Implementation of ethics grand rounds in an otolaryngology department.
To create a case-based curriculum designed to teach and discuss the tenets of clinical medical ethics within an otolaryngology department. Survey-based study in a single-institution, academic otolaryngology department. Case-based departmental ethics grand rounds were implemented on a quarterly basis within an academic department of otolaryngology. One-hour sessions were designed to use challenging cases volunteered by clinicians within the department to create a forum for discussion and education about clinical medical ethics. A four-question satisfaction survey was administered to participating clinicians to measure the impact of the program. Five grand rounds were held over 16 months from 2009 to 2011, with four to six cases presented per session. Sessions were well attended and received, with broad coverage of topics and lively discussions. The mean survey score was 18 (median, 19; standard deviation, 2) out of a maximum possible score of 20. When asked if the sessions helped to advance their skills and comfort within the field of medical ethics, 100% of respondents agreed or strongly agreed. A total of 86% of respondents agreed or strongly agreed that the sessions would change how they practiced medicine in a way that would benefit their patients. It is feasible to successfully implement case-based ethics grand rounds within an otolaryngology department. Participants demonstrated a gratifying level of approval, and a stated desire to implement the principles learned within their clinical practice.


Ultrasound-triggered drug delivery for glioma therapy through gambogic acid-loaded nanobubble-microbubble complexes.
Glioma is one of the most common primary brain tumors. Gambogic acid (GA) is widely used in tumor chemotherapy. However, GA has poor water solubility, low bioavailability, and difficult permeability across the blood-brain barrier (BBB), leading to poor efficacy against brain tumors. In our study, we developed negatively charged GA-loaded PLGA nanobubbles [GA/poly(lactic-co-glycolic acid) (PLGA)] and conjugated them onto the surface of cationic lipid microbubbles (CMBs) through electrostatic interactions. The resulting GA/PLGA-CMB complex was characterized for its particle size, distribution, drug encapsulation efficiency, and ultrasound imaging property, revealing a high drug encapsulation efficiency and excellent contrast imaging capability. Importantly, significantly enhanced GA delivery into the brain could be observed after the intravenous administration of GA/PLGA-CMBs combined with low-intensity focused ultrasound (FUS) due to the cavitation from CMBs, which mediated blood-brain barrier (BBB) opening. Taking advantage of the opened BBB, GA/PLGA nanobubbles could be delivered into the tumor. Then, the second FUS irradiation at higher energy was used to induce the cavitation of GA/PLGA nanobubbles, producing the second cavitation on tumor cells, significantly enhancing the ability of GA to enter tumor cells and inhibit tumor growth inhibition efficacy.


Does living at high altitude increase the risk of bleeding events after total knee arthroplasty? A retrospective cohort study.
Post-operative bleeding after total knee arthroplasty (TKA) is a frequent cause of post-operative complications. This study compared blood loss and indicators of coagulation and fibrinolysis between TKA patients living at low or high altitudes. We retrospectively analyzed 120 patients at our institution who underwent primary TKA from May 2019 to March 2020, and we divided them into those living in areas about 500 m or > 3000 m above sea level. We compared the primary outcome of total blood loss between them. We also compared them in terms of several secondary outcomes: coagulation and fibrinolysis parameters, platelet count, reduction in hemoglobin, hidden blood loss, intra-operative blood loss, transfusion rate, and incidence of thromboembolic events and other complications. Total blood loss was significantly higher in the high-altitude group than in the low-altitude group (mean, 748.2 mL [95% CI, 658.5-837.9] vs 556.6 mL [95% CI, 496.0-617.1]; p = 0.001). The high-altitude group also showed significantly longer activated partial thromboplastin time, prothrombin time, and thrombin time before surgery and on post-operative day one, as well as increased levels of fibrinogen/fibrin degradation product on post-operative days one and three. Ecchymosis was significantly more frequent in the high-altitude group (41.7 vs 21.7%; relative risk (RR) = 1.923 [95% CI, 1.091-3.389]; p = 0.019). The two groups showed similar transfusion rates, and none of the patients experienced venous thromboembolism, pulmonary embolism, or infection. High altitude may alter coagulation and fibrinolysis parameters in a way that increases risk of blood loss after TKA. Such patients may benefit from special management to avoid bleeding events.


Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study.
To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome. Intravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83-91%): SHIFT group, 93% (189/203; 89-96%); LIFT group, 62% (28/45; 47-76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00-1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20-4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03-1.39]; p 0.019), stroke (3.93 [1.94-7.95]; p 0·0001), and brain involvement (5.67 [3.05-10.54]; p < 0.0001) were independently associated with unsuccessful outcomes. Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.


Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens.
Previously, we have reported that the orexigenic peptide ghrelin activates the cholinergic-dopaminergic reward link, involving nicotinic acetylcholine receptors (nAChR). The alpha(3)-alpha(7) and beta(2)-beta(4) subunits of the nAChR can be combined into pentameric nAChRs, with different functional roles. The present experiments show that the locomotor stimulatory effects of ghrelin, either into laterodorsal tegmental area (LDTg) or ventral tegmental area (VTA), are mediated via ventral tegmental nAChR, but neither the alpha(4)beta(2) (using dihydro-beta-erythroidine) nor the alpha(7) (using methyllycaconitine) subtypes appears to be involved. On the other hand, the alpha(3)beta(2), beta(3) and/or alpha(6) (using alpha-conotoxin MII) subtypes in the VTA mediate the stimulatory and DA-enhancing effects of ghrelin, a pattern that ghrelin shares with ethanol (n=5-8). Radioligand-binding experiments shown that ghrelin does not interfere directly with nAChRs (n=26). We therefore suggest that the alpha(3)beta(2), beta(3) and/or alpha(6) subtypes might be pharmacological targets for treatment of addictive behaviours including compulsive overeating and alcoholism.


Mouse embryonic stem cells undergo charontosis, a novel programmed cell death pathway dependent upon cathepsins, p53, and EndoG, in response to etoposide treatment.
Embryonic stem cells (ESCs) are hypersensitive to many DNA damaging agents and can rapidly undergo cell death or cell differentiation following exposure. Treatment of mouse ESCs (mESCs) with etoposide (ETO), a topoisomerase II poison, followed by a recovery period resulted in massive cell death with characteristics of a programmed cell death pathway (PCD). While cell death was both caspase- and necroptosis-independent, it was partially dependent on the activity of lysosomal proteases. A role for autophagy in the cell death process was eliminated, suggesting that ETO induces a novel PCD pathway in mESCs. Inhibition of p53 either as a transcription factor by pifithrin α or in its mitochondrial role by pifithrin μ significantly reduced ESC death levels. Finally, EndoG was newly identified as a protease participating in the DNA fragmentation observed during ETO-induced PCD. We coined the term charontosis after Charon, the ferryman of the dead in Greek mythology, to refer to the PCD signaling events induced by ETO in mESCs.


Trauma in congenital atlanto-axial dislocation.
Congenital atlanto-axial dislocation (AAD) usually presents with chronically progressive compression of the cervico-medullary junction. However, even a minor trauma can cause acute compression with development of quadruplegia and respiratory impairment. At times these may be transient, or trauma may aggravate the compression and lead to progressive quadriplegia. Of 60 children seen with congenital AAD, in 15 it had been associated with trauma. Nine of these 15 AADs were of the mobile variety, and 6 of the fixed variety with odontoid invagination. In 6 children with mobile and 2 with fixed AAD, trauma led to an acute manifestation with quadriplegia. Three of the children also experienced respiratory distress and needed ventilatory support. All 15 were initially treated with skull traction. Once the condition was stabilised, those with the mobile variety underwent fixation in a reduced position and grafting. One of the children with respiratory distress died within 2 days of admission. In 4 of them, sublaminar wiring between C1 and C2 was carried out, and in 3 others wiring between occiput and base of spinous process of C2 was performed. In 1 case a Hartshill loop was used. Among the children with fixed AAD, reduction of the odontoid invagination was obtained in 2, and they underwent fusion. In 4 cases with unsatisfactory reduction, posterior decompression of the foramen magnum and the fused posterior arch of the atlas was performed. The results depended on the degree of neurological deficit in each child.


Bortezomib-induced neuropathy: axonal membrane depolarization precedes development of neuropathy.
Bortezomib is a proteasome inhibitor with high efficacy for multiple myeloma but with severe peripheral neurotoxicity, leading to dose modification and severe neurological disability. This study aimed to investigate the pathophysiology of bortezomib-induced neuropathy. Threshold tracking was used to assess the excitability of sensory and motor axons. Measurements were sequentially performed before and after bortezomib treatment in nine patients with newly diagnosed multiple myeloma. In total, 67% of patients finally developed symptomatic neuropathy. Changes in sensory axonal excitability indices readily occurred after the first course of administration. Patterns of changes in excitability indices suggest membrane depolarization (decreased superexcitability, P<0.001; decreased depolarizing threshold electrotonus 90-100ms, P=0.02). Abnormalities in nerve conduction parameters suggestive of axonal degeneration appeared after the second course of treatment. Bortezomib induces a depolarizing shift in resting membrane potential prior to the development of neuropathy. Membrane depolarization could be associated with impairment of electrogenic Na(+)-K(+)-ATPase-dependent pump caused by toxic effects of bortezomib on mitochondria. Axonal depolarization and hyperexcitability might enhance neurodegeneration in bortezomib-induced neuropathy.


Spatially variant regularization for tissue strain measurement and shear modulus reconstruction.
Regarding the regularization of the displacement vector measurement and shear modulus reconstruction, we propose to properly set the regularization parameters, i.e., to use spatially variant regularization parameters at each point in the region of interest, because the measurement accuracies of the displacements and strains vary spatially. As the measurement accuracies of the strains can be evaluated using the correlation coefficient when using the cross-spectrum phase gradient method, preliminarily the regularization parameters were set proportional to the reciprocal of a power of the correlation coefficient. Such a regularization scheme realizes the spatially uniform stabilities of the strain measurement and shear modulus reconstruction. The effectiveness of this method was verified by showing the regularized results of the axial strain measurement and of one-dimensional (1-D) shear modulus reconstruction obtained in vivo from a human liver carcinoma (that was treated by interstitial microwave coagulation therapy) as well as by a 1-D shear modulus reconstruction obtained using an agar phantom.


Preparation and characterization of reconstructed small intestinal brush border membranes for surface plasmon resonance analysis.
To prepare the surface generated by small intestinal brush border membrane vesicles (BBMVs) for the surface plasmon resonance (SPR) analysis, which allows the real-time measurement of binding events occurring on the intestinal membrane. BBMVs were isolated from Sprague-Dawley rats, suspended in HEPES-buffered saline, and flowed over the surface of a SPR sensor chip composed of dextran derivatives modified with lipophilic residues. The surface coverage was determined from binding of bovine serum albumin to BBMV-immobilized sensor chip. The performance of BBMVs immobilized was evaluated by their interaction with otilonium bromide and bile salts. The stable BBMV surface was achieved when BBMV suspension was flowed over the sensor chip for 8 h at a rate of 2 microl/min. The flow of otilonium bromide resulted in an increased SPR signal because of its binding to calcium channel, which is known to be distributed over the gastrointestinal tact. When bile salts were flowed over ileal and duodenal BBMV surfaces, respectively, a slightly higher SPR signal was observed in the ileal BBMV surface, indicating the specific interaction of bile salts with bile acid transporters. BBMV surfaces may be useful for the estimation of binding events on the intestinal membrane by SPR analysis, especially for the drugs that are orally administrated.


Inverse-micelle-encapsulated water-enabled bond breaking of dialkyl diselenide/disulfide: a critical step for synthesizing high-quality gold nanoparticles.
Inverse-micelle-encapsulated water formed in the two-phase Brust-Schiffrin method (BSM) synthesis of Au nanoparticles (NPs) is identified as essential for dialkyl diselenide/disulfide to react with the Au(III) complex in which the Se-Se/S-S bond is broken, leading to formation of higher-quality Au NPs.


Age effects on the mechanical behavior of human cerebral bridging veins.
It is well established that the probability of occurrence of acute subdural hematomas in traumatic situations increases with age, since the main cause of such hematomas is the mechanical failure of cerebral blood vessels known as bridging veins. This research aims to determine whether there is an effect of age on the mechanical properties of these cerebral vessels, because previous reported studies were conflicting. This study used mechanical tests blue of cerebral bridging veins from post-mortem human subjects. In particular, a series of in vitro tensile tests were performed on a balanced sample of bridging veins from different human subjects. The mechanical parameters measured from the tests were analyzed by means of regression analysis looking for age related effects. The results show that there is a significant effect on both the ultimate strength, maximum stress and strain that the specimens can withstand. The quantitative analysis shows reductions of nearly 50% in ultimate stress, and almost 35% in ultimate strain. Mechanical deterioration of the mechanical strength of cerebral blood vessels seems to be a major factor involved in the increase of frequency of acute subdural hematoma in elderly people in a wide range of life-threatening traumatic situations.


Specificity of hemorrhagic proteinase from Crotalus atrox (western diamondback rattlesnake) venom.
Hemorrhagic proteinase, HTb, isolated from Crotalus atrox (western diamondback rattlesnake) venom was studied for its specificity. HTb showed fibrinogenase activity, hydrolyzing the A alpha chain of fibrinogen first, followed by the cleavage of the B beta chain. HTb is different from thrombin and did not produce a fibrin clot. The degradation products of fibrinogen were found to be different, indicating that the cleavage sites in the A alpha and B beta chains are different from those of thrombin. N-Benzoyl-Phe-Val-Arg-p-nitroanilide was not hydrolyzed by HTb, although this substrate was hydrolyzed by thrombin and reptilase.


[Prospects of Levofloxacin Use in Therapy of Patients with Bronchopulmonary Diseases or Skin and Soft Tissue Pyo-Inflammatory Lesions].
The results of the clinico-microbiological investigation of the levofloxacin efficacy in the treatment of 38 patients with respiratory infections or various pyo-inflammatory lesions are presented. The positive results were stated in 29 (76.3%) patients. No adverse reactions were observed.


Catch-up growth after childhood-onset substitution in primary hypothyroidism: is it a guide towards optimal growth hormone treatment in idiopathic growth hormone deficiency?
Catch-up growth was analyzed in 20 prepubertal children with primary hypothyroidism (PH) starting treatment at an age of 4.4 (1.2-10.1) years and a height (HT) SD score (HT SDS) of -3.1 (+/-0.8). All patients were followed for at least 3 prepubertal years. HT velocity was 12.3 +/- 2.3, 9.0 +/- 1.8 and 7.5 +/- 2.2 cm/year, and change in HT SDS was 1.60 +/- 0.56, 0.57 +/- 0.33 and 0.28 +/- 0.38 during the 1st, 2nd and 3rd year, respectively. The 11 children followed to adult height reached a HT SDS of -0.11 +/- 1.1, all within their target HT range. HT gain (DeltaHT SDS) during the 1st year was correlated with the degree of catch-up growth (r2 = 0.78, p < 0.001). While catch-up growth in childhood-onset PH is complete, this is not the case in GH deficiency (GHD). Based on the auxological characteristics of the patients with PH, HT velocities during the first 2 years were predicted applying prediction models devised for prepubertal children with idiopathic GHD. The modalities of GH treatment observed in the models were used to calculate predicted HT velocities of the PH patients. Observed HT velocities in PH were higher than predicted HT velocities during the 1st (10.67 +/- 1.37 cm/year, p < 0.01) and 2nd (8.35 +/- 0.86 cm/year, p = 0.128) year. The data show that catch-up potential in idiopathic GHD of childhood onset is reduced compared to PH. Since early catch-up as well as total HT recovery in children with GHD are often not reached by present treatment modalities, catch-up growth in PH may serve as a model towards optimizing GH treatment. The data suggest that initial GH doses of 1.0 IU/kg/week, rather than the presently recommended 0. 6 IU/kg/week, need to be given in GHD in order to achieve the degree of early catch-up observed in PH and to consequently improve the final outcome.


Intracortical and intrahippocampal injections of kainic acid in developing rats: an electrographic study.
Electrographic patterns induced by neocortical and hippocampal microinjections of kainic acid (KA) have been studied in curarized 4-30-day-old rats. In younger (4-6-day-old) animals, both hippocampal and neocortical KA application induced, with a long delay, the appearance of sequences of slow spikes, simultaneously occurring in the cortex and hippocampus. The same pattern was observed in about 60% of animals 7-9 days old. In the remaining 40% of the rats of this age, epileptic abnormalities, initially localized in the neocortical or hippocampal injection site were obtained. The latter pattern always appeared in 10-14-day-old rats. In some of these status epilepticus was also reached. In older (15-30 days) animals, the hippocampal injection caused the appearance of hippocampal seizures, always evolving into status epilepticus. In neocortically injected animals, cortical bursts of polyspikes appeared, with or without hippocampal involvement. After 40-60 min, typical hippocampal seizures occurred, later leading to status epilepticus. The simultaneous hippocampal and neocortical response observed in younger rats is attributed to a massive activation of the immature brain structures. The focal response seems to be correlated with a maturational process of glutamate and/or kainate receptors at both hippocampal and neocortical levels. This process is completed during the third week, when a typical selective activation of the limbic structures is obtained.


Dark adaptaion processes in the amphibian rod.
Rod dark adaptation in the amphibian retina appears to be due to three processes: 1. background adaptation, occurring immediately after the extinction of an adapting or bleaching light, 2. intermediate adaptation, that frequently lasts 30 min or more and 3. opsin adaptation, which in the isolated retina where regeneration of rhodopsin is insignificant, is observed a a permanent loss of sensitivity after the completion of intermediate adaptation. Intermediate adaptation is characterized by a linear relation between log threshold and the amount of "retinal" present, a similar relation is obtained between log threshold and the amount of rhodopsin bleached in opsin adaptation. These adaptation processes are discussed in terms of a model of the rod outer segment.


Development of relationship with patient self efficacy scale: Gender, department, and grade level differences.
Self-efficacy has become a cross-disciplinary concept. In the field of healthcare, this concept is considered crucial for nurses; who play an important role in improving the health and well-being of the community. The aim of this study was to develop a "Relationship-with-the-patient self-efficacy scale" (RPSES). A sample of 331 university students (310 females and 21 males; 168 from the midwifery and 162 from the nursing departments) were enrolled in the study. Out of 24 items, 8 behavior items with the highest factor loadings were selected regarding the nurse-patient-relationship self-efficacy according to the results of the preliminary exploratory factor analysis. The final exploratory factor analysis revealed that the selected 8 items of RPSES had a single factor, explaining 83.28% of the total variance. The Cronbach alpha reliability coefficient was c alculated as 0.97. This scale has beendemonstrated to be a valid and reliable instrument.The analyses unfolded that RPSES scores of the students were not different between men and womenand did not differ by the departments the students attended; however, the RPSES scores were different by the grade levels of the students (juniors and seniors). The fourth graders' RPSES scores were higher than those of third graders.


TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma.
The molecular and genetic changes underlying esophageal squamous cell carcinoma (ESCC) tumor formation and rapid progression are poorly understood. Using high-throughput data analysis, we examined molecular changes involved in ESCC pathogenesis and investigated their clinical relevance. Five independent microarray datasets were examined for differentially expressed genes and pathways. For validation, mRNA expression in tumor and matched normal tissues from 16 ESCC cases was examined by cDNA microarray, and protein expression in 97 ESCC specimens was investigated using immunohistochemical stains. The association between clinicopathological parameters and the expression of Aurora kinase A (Aurora-A) and TPX2 was analyzed. The impact of TPX2 expression was also assessed in ESCC cancer cells. AURKA and TPX2, members of the "Role of Ran in mitotic spindle regulation" pathway, were selected for further investigation. Verification by cDNA microarray showed that both genes were overexpressed in tumor tissues, and immunohistochemical staining showed Aurora-A and TPX2 expression in 88.4 and 90.6 % of ESCC specimens, respectively. High TPX2 expression was a significant prognosticator for overall and disease-free survival in univariate analysis and remained an independent prognostic factor in multivariate analysis (HR 1.802, p = 0.037). TPX2 knockdown clones showed inhibited cellular proliferation in growth curve studies and formed fewer colonies in the clonogenic assay. Using bioinformatics resources, which were validated by microarray analysis and immunohistochemistry stains, and manipulation of TPX2 expression in ESCC cell lines, we demonstrated that TPX2 expression is associated with cell proliferation and poor prognosis among patients with resected ESCC.


Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression.
Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis. Here, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions. We found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions. These data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.


Sonographically detectable cysts in polycystic kidney disease in newborn and young infants.
Autosomal dominant (adult type) and autosomal recessive (infantile type) polycystic kidney disease are 2 distinct forms of hereditary cystic renal disease with differing pathologic and clinical features. Glomerulocystic kidney disease is probably a separate entity, whose pathologic features may closely resemble those of autosomal dominant polycystic kidney disease, especially in small infants. An example of each of these conditions in a small infant is presented, all of which had sonographically detectable cysts. Pathologic correlation was available in each case. While there are typical sonographic features of autosomal dominant and autosomal recessive polycystic kidney disease in newborn and young infants, there is no specific appearance of either condition, and glomerulocystic kidney disease can apparently resemble either one. Other investigations, particularly family studies and pathologic verification, are important in order to establish the correct diagnosis.