Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder.
About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.


A review of twinning in horses and the possible therapeutic value of supplemental progesterone to prevent abortion of equine twin fetuses the latter half of the gestation period.
Equine twinning, related abortion and progestogen plasma concentrations during the gestation period were reviewed. The supplemental administration of exogenous progesterone apparently prevented impending twin abortions in three mares after midgestation. A single viable twin and a mummified fetus were delivered at term by the mares.


Automated segmentation of MR imaging to determine normative central nervous system cerebrospinal fluid volumes in healthy volunteers.
An accurate non-invasive method to determine total body cerebrospinal fluid volume has a number of potential diagnostic and therapeutic applications. Herein we describe a technique for automated segmentation of total body MRI data to determine cranial and spinal CSF volume in 15 healthy adults. These in vivo estimates of CSF volume exceed the standard reported volume of 150mL in human adults and provide normative data for diagnosis of disease states such as hydrocephalus and therapy including pharmacologic dosimetry. No correlation was observed between patient height or weight and total body CSF volume.


Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation.
Brain metastases can contribute to a decreased quality of life for patients with cancer, often leading to malaise, neurologic dysfunction, or death. Intracerebral hemorrhage (ICH) is an especially feared complication in patients with brain metastases given the potential for significant morbidity and mortality. We aim to characterize patients with cancer and brain metastases admitted to hospitals nationwide and identify factors associated with ICH. The 2016 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) was queried for all patients with cancer hospitalized with a diagnosis of brain metastases. Admissions with a primary or secondary diagnosis of ICH were further identified. Baseline differences in demographic, clinical, socioeconomic, and hospital-related characteristics between patients with and without ICH were assessed by chi-square, Mann-Whitney U, and ANOVA testing. Multivariable logistic regression was used to identify factors associated with ICH. Weighted frequencies were used to create national estimates for all data analysis. In 2016, a total 145,225 hospitalizations were associated with brain metastases, of which 4,145 (2.85%) had a concurrent diagnosis of ICH. Patients with ICH were more likely to have a longer length of stay (median 5 days vs 4 days, p < 0.001) and a higher cost of stay (median $14,241.14 vs $10,472.54, p < 0.001). ICH was found to be positively associated with having a diagnosis of melanoma (odds ratio [OR] 5.01; 95% Confidence Interval [CI] 3.50-7.61) and kidney cancer (OR 2.50; 95% CI 1.69-3.72). Patients on long-term anticoagulation had a higher risk of ICH (OR 1.49; CI 1.15-1.91). Approximately 3% of patients hospitalized with brain metastases also had a diagnosis of ICH, which was significantly associated with longer length of stay and cost. Patients with melanoma, kidney cancer, and on long-term anticoagulation had a higher risk of ICH. Physicians should consider the risks of anticoagulation carefully for patients with brain metastases, especially those with melanoma and kidney cancer.


The ST segment depression pattern in asymptomatic peri-menopausal female athletes.
ST segment has not been well investigated in asymptomatic peri-menopausal female athletes, when the CV risk is higher. The aims of the study is to investigate the prevalence of ST segment depression in peri-menopausal female athletes, divided in four age groups. in a cohort of 6010 female athletes aged 45-65 years old, 161 subjects were selected for the presence of ST segment depression, revealed by maximal ergometric test. All athletes were also evaluated by physical examination and echocardiography. Inclusion criteria for ST segment depression were ST depression >0.5 mm respect to baseline and its depth was divided in 0.5 mm, 0.5-1 mm, 1-2 mm categories. Its behavior was classified in ascending, horizontal and descending and it was studied in relation to the age range (<51; 51-55; 56-60; >60). ST segment depression was mainly evident in inferolateral leads in all groups (63%, 70,3%, 71%, 63,6%, for <51; 51-55, 56-60 and 61-65 respectively) with horizontal pattern (52,2%, 59,5%, 57,8%, 63,6%) and 1-2 mm depth (43,5%, 46,7%, 60,6%), with the exception of the range 51-55, mainly showing a depth of 0,5-1 mm (45,9%). The older group showed increased SBP (137.5 mmHg, p = 0.007) and BMI (24.3, p = 0.093) values. Mitral prolapse was shown in 11,8% while 36,6% showed systolic flattening of mitral leaflets. ST depression in asymptomatic menopausal female athletes is frequent and it is characterized by a specific presentation pattern. This is particularly important in the menopausal age when CV risk factors are more prevalent.


Involvement of alternative oxidase in the regulation of sensitivity of Sclerotinia sclerotiorum to the fungicides azoxystrobin and procymidone.
Sclerotinia sclerotiorum is a filamentous fungal pathogen that can infect many economically important crops and vegetables. Alternative oxidase is the terminal oxidase of the alternative respiratory pathway in fungal mitochondria. The function of alternative oxidase was investigated in the regulation of sensitivity of S. sclerotiorum to two commercial fungicides, azoxystrobin and procymidone which have different fungitoxic mechanisms. Two isolates of S. sclerotiorum were sensitive to both fungicides. Application of salicylhydroxamic acid, a specific inhibitor of alternative oxidase, significantly increased the values of effective concentration causing 50% mycelial growth inhibition (EC50) of azoxystrobin to both S. sclerotiorum isolates, whereas notably decreased the EC50 values of procymidone. In mycelial respiration assay azoxystrobin displayed immediate inhibitory effect on cytochrome pathway capacity, but had no immediate effect on alternative pathway capacity. In contrast, procymidone showed no immediate impact on capacities of both cytochrome and alternative pathways in the mycelia. However, alternative oxidase encoding gene (aox) transcript and protein levels, alternative respiration pathway capacity of the mycelia were obviously increased by pre-treatment for 24 h with both azoxystrobin and procymidone. These results indicate that alternative oxidase was involved in the regulation of sensitivity of S. sclerotiorum to the fungicides azoxystrobin and procymidone, and that both fungicides could affect aox gene expression and the alternative respiration pathway capacity development in mycelia of this fungal pathogen.


Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing.
Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.


Type 2 diabetes and impaired glucose tolerance in North-China-based rural community adults.
To estimate the prevalence of type 2 diabetes and impaired glucose tolerance (IGT), and to identify potential risk factors among adults in rural areas in North China. Multistage random cluster sampling in a cross-sectional study. Data were collected in 2005 from 1058 adults aged >20 years. Body mass index (BMI), waist and hip circumferences, 2-hour postprandial glucose (2-hPG) and other data were collected. The prevalence of diabetes and IGT was higher for both men and women in the study group compared with the national averages (diabetes: 7.17% and 7.01%, respectively; IGT: 7.55% and 7.95%, respectively). Men aged ≥60 years and women aged 50-59 years had the highest prevalence of diabetes compared with other age groups (9.62% and 9.21% respectively). Both men and women aged ≥60 years had the highest prevalence of IGT. A sudden increase in 2-hPG level was seen in women aged ≥40 years. Those with BMI ≥28 kg/m(2) were at two-fold higher risk than normal. The risk for glucose tolerance abnormalities was almost 1.55-fold higher in subjects with waist/height ratio (WHtR) ≥0.50. The odds ratio for diabetes was 0.32 (95% confidence interval 0.10-0.98) in subjects with an annual family income ≥30,000 yuan compared with those with lower incomes. These results indicate that rural populations in North China have a higher prevalence of type 2 diabetes and IGT compared with national averages. Women aged ≥40 years warrant more attention to avoid glucose tolerance abnormalities. BMI and WHtR are predictive of the prevalence of glucose tolerance abnormalities. High annual family income appears to be a protective factor for type 2 diabetes.


Models of interaction between nucleic acids and proteins. Hydrogen bonding of arginine with nucleic acid bases, phosphate groups and carboxylic acids.
Complex formation between the side chain of arginine and nucleic acid bases has been investigated by proton magnetic resonance in dimethylsulfoxide. Simultaneous formation of two hydrogen bonds leads to a selectivity of arginine interaction towards cytosine and guanine. A comparison is made of the interaction of arginine side chain with nucleic acid bases, phosphate and carboxylate anions. It is shown that interaction between carboxylate and arginine is stronger than between phosphate and arginine. These results are discussed with respect to the selective recognition of nucleic acid bases by arginine side chains and by the arginyl-glutamyl ion pair which could form in proteins interacting with nucleic acids.


Localization of lactate dehydrogenase isozymes in human muscle tissues by the mixed aggregation immunocytochemical technique.
Lactate dehydrogenase (LDH) isozyme composition and localization was determined in sections of skeletal, heart and smooth muscle by the mixed aggregation immunocytochemical method using first antibody directed against purified human LDH-A4 (M4) or LDH-B4 (H4) followed by the enzymes LDH-A4 and LDH-B4, respectively. An even distribution of the two monomers in all fibres was seen with heart muscle and smooth muscle. Heart muscle had a low concentration of A-monomers and a high concentration of B-monomers, whereas the smooth muscle had equal concentrations of the two monomers. In contrast, skeletal muscle from m. quadriceps femoris was found to be composed of two muscle fibre types, one containing mainly A-, the other mainly B-monomers. On the basis of succinate dehydrogenase activity it was shown that the red (type 1) fibres contain mainly B-monomers and the white (type 2) fibres mainly A-monomers of LDH.


Follow-up of patients with proved occluded internal carotid artery. Clinical and angiographic correlation.
Patients with angiographically proven occluded ICA were subjected to a clinical follow-up. In about 25%, further ischemic attacks ipsilateral to the occluded ICA occurred. The pathogenesis of ischemia and the management of these patients is discussed.


Cause-specific long-term mortality in survivors of childhood cancer in Switzerland: A population-based study.
Survivors of childhood cancer have a higher mortality than the general population. We describe cause-specific long-term mortality in a population-based cohort of childhood cancer survivors. We included all children diagnosed with cancer in Switzerland (1976-2007) at age 0-14 years, who survived ≥5 years after diagnosis and followed survivors until December 31, 2012. We obtained causes of death (COD) from the Swiss mortality statistics and used data from the Swiss general population to calculate age-, calendar year-, and sex-standardized mortality ratios (SMR), and absolute excess risks (AER) for different COD, by Poisson regression. We included 3,965 survivors and 49,704 person years at risk. Of these, 246 (6.2%) died, which was 11 times higher than expected (SMR 11.0). Mortality was particularly high for diseases of the respiratory (SMR 14.8) and circulatory system (SMR 12.7), and for second cancers (SMR 11.6). The pattern of cause-specific mortality differed by primary cancer diagnosis, and changed with time since diagnosis. In the first 10 years after 5-year survival, 78.9% of excess deaths were caused by recurrence of the original cancer (AER 46.1). Twenty-five years after diagnosis, only 36.5% (AER 9.1) were caused by recurrence, 21.3% by second cancers (AER 5.3) and 33.3% by circulatory diseases (AER 8.3). Our study confirms an elevated mortality in survivors of childhood cancer for at least 30 years after diagnosis with an increased proportion of deaths caused by late toxicities of the treatment. The results underline the importance of clinical follow-up continuing years after the end of treatment for childhood cancer.


A simplified diphenylamine colorimetric method for growth quantification.
Cell growth needs to be monitored in biological studies and bioprocess optimization. In special circumstances, such as microbial fermentations in media containing insoluble particles, accurate cell growth quantification is a challenge with current methods. Only the Burton method is applicable in such circumstances. The original Burton method was previously simplified by adopting a two-step sample pretreatment in perchloric acid procedure to eliminate the need for DNA extraction. Here, we further simplified the Burton method by replacing the previous two-step perchloric acid pretreatment with a new and one-step diphenylamine reagent pretreatment. The reliability and accuracy of this simplified method were assessed by measuring the biomass of four model microorganisms: Escherichia coli, Streptomyces clavuligerus, Saccharomyces cerevisiae, and Trichoderma reesei grown in normal media or those containing solid particles. The results demonstrate that this new simplified method performs comparably to the conventional methods, such as OD600 or the previously modified Burton method, and is much more sensitive than the dry weight method. Overall, the new method is simple, reliable, easy to perform, and generally applicable in most circumstances, and it reduces the operation time from more than 12 h (for the previously simplified Burton method) to about 2 h.


Effects of morphine and morphine withdrawal on brainstem neurons innervating hypothalamic nuclei that control the pituitary-adrenocortical axis in rats.
Different data support a role for brainstem noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) in the control of hypothalamus - pituitary - adrenocortical (HPA) axis. However, little is known regarding the functional adaptive changes of noradrenergic afferent innervating the PVN and supraoptic nucleus (SON) during chronic opioid exposure and upon morphine withdrawal. Here we have studied the expression of Fos after administration of morphine and during morphine withdrawal in the rat hypothalamic PVN and SON. Fos production was also studied in brainstem regions that innervate hypothalamic nuclei: the nucleus of solitary tract (NTS - A2) and the ventrolateral medulla (VLM - A1) and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurons during morphine withdrawal. Male rats were implanted with s.c. placebo or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received an injection of saline i.p., morphine i.p., saline s.c. or naloxone s.c. Acute morphine administration produced an increase in Fos expression at hypothalamic nuclei and in the brainstem regions, and tolerance developed towards this effect. Precipitated morphine withdrawal induced marked Fos immunoreactivity within the PVN and SON. Concomitantly, numerous neurons in the brainstem were stimulated by morphine withdrawal. Moreover, catecholaminergic-positive neurons in the brainstem showed a significant increase in Fos expression in response to morphine withdrawal. These findings demonstrate that chronic activation of opioid receptors results in altered patterns of immediate-early genes (IEG) expression in the PVN and SON, which occurs concurrently with an increased activity of their inputs from the brainstem.


Serial analysis of gene expression to assess the endothelial cell response to an atherogenic stimulus.
Activation of human, arterial endothelial cells (ECs) is an early event in the pathogenesis of atherosclerosis. To identify the repertoire of genes that are differentially expressed after activation, we used serial analysis of gene expression (SAGE) to compare the mRNA spectrum of quiescent ECs with that of ECs activated for 6h with a strong atherogenic stimulus. SAGE methodology generates concatenated 'tags' of 10bp that are derived from a specific mRNA. About 5% of over 12000 tags analyzed is derived from genes that are differentially expressed (at least 5-fold up- or downregulated). These transcript tags are derived from only 56 genes, close to 1% of the total number of analyzed genes. Among these 56 differentially expressed genes are 42 known genes, including the hallmark endothelial cell activation markers interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), plasminogen activator inhibitor 1 (PAI-1), Gro-alpha, Gro-beta and E-selectin. Differential transcription of a selection of the upregulated genes was confirmed by Northern blot analysis. A novel observation is the upregulation of activin betaA mRNA, a member of the transforming growth factor beta family. Apparent discrepancies between this novel technology and conventional methods are discussed. In conclusion, we demonstrate that for the application of SAGE, a moderate number of analyzed transcript tags suffices to reveal the significant alterations of EC transcription that results from a strong atherogenic stimulus.


Prevalence of dengue antibodies in healthy children and adults in different Colombian endemic areas.
Colombia is a dengue hyperendemic country; however, the prevalence of antibodies against dengue in the general population including the inhabitants of rural areas is unknown. This study aimed to determine the prevalence of dengue IgM and IgG antibodies in healthy children and adults in urban and rural areas of seven different endemic regions in Colombia between 2013 and 2015. Blood samples from healthy volunteers (1,318) were processed by serology (by indirect IgG and capture IgM and IgG ELISA) and molecular tests to detect viral RNA and circulating serotypes. The seroprevalence of IgG for dengue were 85% in children and over 90% for adults. In addition to the high IgM positive rate (14.9%) and secondary recent infection marker rate (capture IgG, 16%), 8.4% of the healthy volunteers were positive for dengue virus (DENV) RNA. This study confirmed the broad and permanent circulation of DENV in Colombia and the high rates of infection and reinfection suffered by its inhabitants. This information can be used by the health authorities to strengthen vector control and vaccine policies and review the algorithms of diagnosis and disease management in children and adults.


Angiotensin-(3-4) normalizes blood pressure, decreases Na+ and energy intake, but preserves urinary Na+ excretion in overweight hypertensive rats.
Hypertension, one of the most common and severe comorbidities of obesity and overweight, is a worldwide epidemic affecting over 30% of the population. We induced overweight in young male rats (aged 58 days) by exposure to a hypercaloric high lipid (HL) diet in which 70% of the calories originated from fat. The HL diet also contained 33 or 57% higher Na+ than the control (CTR) diet. Over the following weeks the HL rats gradually became overweight (490 ± 12 g vs 427 ± 7 g in the CTR group after 15 weeks) with high visceral fat. They developed elevated systolic blood pressure (SBP) (141 ± 1.9 mmHg), which was fully restored to CTR values (128 ± 1.1 mmHg) by oral administration of Ang-(3-4) (Val-Tyr), the shortest renin-angiotensin-derived peptide. The overweight rats had lower plasma Na+ concentration that augmented to CTR values by Ang-(3-4) treatment. Na+ ingestion was depressed by 40% as result of the Ang-(3-4) treatment, whereas the urinary excretion of Na+ (UNaV) remained unmodified. The preservation of UNaV after Ang-(3-4) treatment - despite the sharp decrease in the dietary Na+ intake - can be ascribed to the normalization of renal type 1 angiotensin II receptors and Na+-transporting ATPases, both up-regulated in overweight rats. These renal effects complete a counterregulatory action on elevated renin-angiotensin activity that allows the high SBP to be normalized and body Na+ homeostasis to be restored concomitantly in overweight rats.


Stimulatory effects of human pancreatic polypeptide on rat pancreatic acini.
The effect of human pancreatic polypeptide (HPP) on rat pancreatic acini has been studied. It was found that HPP stimulated amylase and lipase release from the acini. The secretory response of acini to HPP was dose-dependent in a sigmoidal fashion. Between 10(-9) M and 10(-8) M concentration of HPP there was a slow increase of enzyme release to about 40-60% over basal release. At concentrations of HPP above 10(-8) M there was a rapid increase of enzyme release, amounting to 4-6 times over basal release at 10(-6) M concentration of HPP. The potency of HPP compared to other secretagogues at 10(-7) M concentration was 45% of CCK, 60% of carbachol and 75% of secretin. HPP did not inhibit the effect of CCK, secretin and carbachol on amylase release. The amylase release stimulated by HPP was accompanied by an increase in 45Ca2+ efflux. Atropine or dibutyryl cyclic GMP did not influence the effect of HPP. It is concluded that HPP stimulates the release of enzymes from rat pancreatic acini and that Ca2+ may be a mediator for this secretion.


Synergistic Manganese(I) C-H Activation Catalysis in Continuous Flow: Chemoselective Hydroarylation.
Chemoselective hydroarylations were accomplished by a novel synergistic Brønsted acid/manganese(I)-catalyzed C-H activation manifold. Thus, alkynes bearing O-leaving groups could, for the first time, be employed for C-H alkenylations without concurrent β-O elimination, thereby setting the stage for versatile late-stage diversifications. Also described is the first manganese-catalyzed C-H activation in continuous flow, thus enabling efficient hydroarylations within only 20 minutes.


Tuberculosis among migrant workers in Taiwan.
Although the worldwide incidence of tuberculosis (TB) has been slowly decreasing, the migrant workers remains an important gap for regional TB control. In Taiwan, the numbers of the migrant workers from countries with high TB incidence increase significantly in past decades and the impact on public health remains unknown. This study aimed to explore the difference of TB incidence between Taiwanese and the migrant workers. The migrant workers are obligated to receive pre-arrival, post-arrival and regular chest X-ray screening during their stay in Taiwan. We retrospectively collected these data extracted from the Alien Workers Health Database in Centers for Disease Control, Taiwan from Jan. 1, 2004 to Dec. 31, 2013. Poisson regression models were used to compare the hazard ratios of TB between Taiwanese and the migrant workers after adjusting gender and age groups. The total migrant workers in Taiwan reached 314,034 persons in 2004 and 489,134 persons in 2013, accounting for 2% of Taiwan population. The TB incidence of migrant workers was similar to Taiwanese (53-73.7 per 105 vs 45.5-76.8 per 105). Comparing with Taiwanese, the TB risk was significantly lower in male migrant workers (HR: 0.76; 95% CI: 0.70-0.83, P < 0.001), but higher in female migrant workers (HR: 1.40; 95% CI: 1.35-1.46, P < 0.001). Besides, we found that the TB risk in migrant workers was 5.30-fold (95% CI: 4.83-5.83, P < 0.001) in youngest group (≤24 year-old) comparing with Taiwanese. Migrant workers in Taiwan have higher TB incidence than Taiwanese in young groups, especially in females. The mainstay young laborers with latent tuberculosis infection risk is an important vulnerability for public health. Further investigation and health screening are warranted.


Sensorineural hearing loss caused by metastatic prostatic carcinoma: a case report.
Metastases to the temporal bone are a recognized, if rare, cause of otological symptoms including sudden sensorineural hearing loss. Carcinoma of the prostate is a common cancer which frequently metastasizes to bone but is only rarely reported in the temporal bone. We report a case of sudden sensorineural hearing loss due to metastatic prostatic carcinoma in the temporal bone.


[Radical prostatectomy in locally advanced prostate cancer].
Due to an inverse stage migration, the proportion of patients with more aggressive and locally advanced prostate cancer (PCa) has increased over the last few years. The natural history in these patients shows a higher risk of local complications and worse oncologic outcome. To analyze the impact of radical prostatectomy (RP) in patients with locally advanced PCa. A review of the literature was performed using PubMed and MEDLINE databases focusing on articles addressing locally advanced PCa. Current guidelines recommend local therapy in patients with locally advanced PCa among other treatment options. Thereby no strong evidence favoring radiotherapy or RP is present. Compared to patients without local treatment, RP may improve oncologic outcome and decrease the risk of local complications. Due to more difficult surgery and an increased need of multimodal therapy, higher perioperative morbidity and worse functional outcomes compared to patients with localized PCa are reported. No reliable prospective data indicating a widespread use of neoadjuvant treatment exists. Indication for further adjuvant or salvage therapies depends on pathologic results and postoperative course. RP is one of the treatment options with good long-term results which can be offered to patients with locally advanced PCa. Nevertheless, patients need to be counselled especially about the worse postoperative functional outcome compared to patients with localized PCa.


Aluminum-induced conformational changes in calmodulin alter the dynamics of interaction with melittin.
Studies were undertaken to examine the impact of aluminum-induced structural changes in bovine brain calmodulin on the protein's interface region with melittin, a model for calmodulin's target enzymes. Both steady-state and time-dependent fluorescence characteristics of the single tryptophanyl residue of melittin were employed to derive information on aluminum-related changes in the fluorophore's microenvironment. In the presence of stoichiometric amounts of aluminum ions, calmodulin's target region with melittin appears to be more polar than that with aluminum absent. As a result, upon association of melittin with aluminum-calmodulin, the enhancement of helical arrays is less pronounced. The fluorophore's average microenvironment also is modified such that its apparent lifetime is shortened when aluminum is present. In the presence of aluminum ions, the solvation structure of calmodulin is possibly changed, which may be unfavorable for a proper fit between calmodulin and target proteins.


Inhibition of HIV infection by flavanoids.
Of a variety of flavanoids, the flavans were generally more effective than flavones and flavanones in selective inhibition of HIV-1, HIV-2 or SIV infection. Studies of their effects on the binding of sCD4 and antibody to gp120 indicated that the effective compounds interact irreversibly with gp120 to inactive virus infectivity and block infection.


Studies on the mechanism of inhibition of redox enzymes by substituted hydroxamic acids.
Substituted primary hydroxamic acids were found to inhibit the catalytic activity of a number of redox enzymes. The inhibition was not related to the nature of the metal-active site of the enzyme nor to the nature of the oxygen-containing substrate. Two easily available enzymes, mushroom tyrosinase (monophenol,dihydroyphenylalanine:oxygen oxidoreductase, EC 18.104.22.168) and horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 188.8.131.52), which were potently inhibited by hydroxamic acids, were chosen for more detailed study. A kinetic analysis of the inhibitory effects on the partially purified tyrosinase of mushroom (Agaricus bispora) revealed that inhibition was reversible and competiitive with respect to reducing substrate concentration, but was not competitive with respect to molecular oxygen concentration. A spectrophotometric and EPR study of the binding of salicylhydroxamic acid to horseradish peroxidase revealed that his hydroxamic acid was bound to the enzyme in the same manner as a typical substrate, hydroquinone. Spectroscopic and thermodynamic measurements of the binding reactions suggested that this binding site is close, to but, not directly onto, the heme group of the enzyme. From these results it is concluded that the mode of inhibition of hydroxamic acid need not be, as generally supposed, by metal chelation, and mechanisms involving either hydrogen bonding at the reducing substrate binding site or the formation of a charge transfer complex between hydroxamic acid and an electron-accepting group in the enzyme are considered to be more feasible. The relevance of these findings to deductions on the nature of other hydroxamic acid-inhibitable systems is discussed.


Impact of intra- and extrauterine growth on bone mineral density and content in the neonatal period of very-low-birth-weight infants.
Very-low-birthweight infants (VLBWIs) are at high risk for suboptimal bone mineral density (BMD) and bone mineral content (BMC). Small-for-gestational-age (SGA) status also causes reduced bone mineralization in full-term infants. However, the impact of intrauterine and postnatal extrauterine growth on BMD and BMC in VLBWIs is inconclusive. We retrospectively investigated n=68 VLBWIs, comprising 45 appropriate-for-gestational-age (AGA) and 23 SGA infants who underwent lumbar spine dual-energy X-ray absorptiometry at term-equivalent age. BMD and BMC did not differ between AGA and SGA VLBWIs. Subgroup analyses of infants with birthweight<1000 g vs 1000-1500 g, and GA<27 weeks vs ≥ 27 weeks also showed no differences in BMD and BMC between AGA and SGA infants. In contrast, infants with extrauterine growth restriction (EUGR) showed significantly lower values than those without (BMD: 0.124 ± 0.023 vs 0.141 ± 0.032 g/cm(2), P=0.02; BMC: 0.80 ± 0.26 vs 0.94 ± 0.23 g, P=0.04). There were no differences between AGA and SGA infants with EUGR. However, in the AGA cohort, infants with EUGR showed significantly lower values than those without (BMD: 0.121 ± 0.022; 0.141 ± 0.03 g/cm(2), P=0.02; BMC: 0.73 ± 0.23 vs 0.94 ± 0.23 g, P=0.005). Multiple regression analyses showed GA, weight and head circumference at birth, and weight percentile at term correlated with term BMD. Conversely, only weight percentile at term significantly correlated with term BMC. EUGR, rather than IUGR, is a risk factor for reduced BMD and BMC in the neonatal period in VLBWIs.


Reflux esophagitis.
Reflux esophagitis and its complications are not only common clinical problems but also problems that can be accurately defined by careful history taking and a knowledge of the pathophysiology of the various manifestations. An element of objective assessment, however, is required to define and substantiate fully an individual patient's problem. Only when disabling subjective and intractable objective complications persist after good medical treatment should surgical intervention be considered. Various antireflux procedures are currently available and all can be effective. Surgeons should review their own experiences and make alterations that they perceive will correct the types of problems encountered. In our current technique for the surgical management of gastroesophageal reflux in the common clinical setting, normal esophageal peristalsis is present, the fundus is adequate for plication, and sufficient esophageal mobilization can be effected to permit reduction of the entire stomach and fundoplication below the diaphragm. In addition, the procedure should be restricted to patients who do not have stenosis or have stenosis that can be readily dilated to 50 French.


Temperature-dependent development and reproductive traits of Tetranychus macfarlanei (Acari: Tetranychidae).
Development and reproductive traits of Tetranychus macfarlanei Baker & Pritchard (Acari: Tetranychidae) were investigated on kidney bean, Phaseolus vulgaris L., at eleven constant temperatures. Tetranychus macfarlanei was able to develop and complete its life cycle at temperatures ranging from 17.5 to 37.5°C. At 15 and 40°C, a few eggs (2-4%) hatched but further development was arrested. Development from egg to adult was slowest at 17.5°C and fastest at 35°C for both females and males. Using Ikemoto and Takai's linear model, the estimated lower developmental thresholds for egg-to-female adult, egg-to-male adult and egg-to-egg development were 12.9-13.0°C. The thermal constants for the respective stages were 110.85, 115.99 and 125.32 degree-days (DD). The intrinsic optimum temperatures (T (Φ)) calculated by non-linear SSI model were determined as 24.4, 24.4 and 24.2°C for egg-to-female adult, egg-to-male adult and egg-to-egg development, respectively. The net reproductive rate (R (0)) was highest at 25°C (167.4 females per female) and lowest at 17.5°C (42.6 females per female). The intrinsic rate of natural increase, r (m), increased linearly with the rising of temperature from 0.102 at 17.5°C to 0.441 day(-1) at 35°C. These values suggested that T. macfarlanei could be growing quickly in response to increasing temperatures from 17.5 to 35°C and provide a basis for predicting its potential geographical range.


Active chemotherapy for metastatic stromal cell tumor of the testis.
Metastatic stromal cell tumors of the testis are largely refractory to chemotherapy. We report a case of a young man with widely metastatic testicular stromal cell tumor who achieved complete clinical remission following chemotherapy with etoposide, ifosfamide, cisplatin, and bleomycin.


Nondermatophytic filamentous fungi infection in South America--reality or misdiagnosis?
For the last 10 years, a steady increment in the diagnosis of nondermatophyte filamentous fungal infections has been observed. This trend also applies to the valuation of the medical mycology. It can be attributed, in part, to the increased concern of the population with the aesthetic aspect, the easiest access to health information, and the increased demand for specialized jobs. Moreover, increase in the diagnosis of new emerging fungi is also caused by the improvement of the diagnostic techniques available as well as the qualification and constant update of the professionals in medical mycology. Another relevant aspect is the valorization of medical mycology in the medical curriculum. Misdiagnosis can lead to treatment failures, because not all nail diseases are caused by fungi. Therefore, the importance of clinical diagnosis is strictly associated with laboratory results.


Tacrolimus metabolite cross-reactivity in different tacrolimus assays.
Tacrolimus (FK506) is an immunosuppressive drug with great clinical promise. There is a controversy regarding the role of tacrolimus metabolites in immunosuppression and toxicity, and immunoassays and immunophilin binding assays have not been adequately tested for metabolite cross-reactivity. Methods are limited to HPLC and HPLC-MS for quantifying the parent drug. Mixed lymphocyte culture assay (MLC) is the preferred functional bioassay for the measurement of parent drug and active metabolites but it is not practical for routine laboratory use. Due to differences in assay methods and reagent specificity, the concentration of tacrolimus in a given specimen may vary among different assay kit manufacturers. The objective of this study was to evaluate the degree of cross-reactivity or interference of the three first-generation tacrolimus metabolites [13-O-demethyl (M-I), 31-O-demethyl (M-II) and 15-O-demethyl (M-III)] among two different tacrolimus immunoassays (Immunoassay: PRO-Trac II FK506, Abbott IMx tacrolimus-II); and the radioreceptor assays (RRA) using minor immunophilins (14, 37, and 52 kDa immunophilins) and tacrolimus binding protein (FKBP12). First-generation tacrolimus metabolites (M-I, M-II, and M-III) spiked in drug-free whole blood were assayed with RRA using three minor immunophilins (14, 37, and 52 kDa) and two commercial immunoassay procedures (Incstar PRO-Trac II tacrolimus, Abbott IMx tacrolimus II). The results were compared to previously published FKBP-12 RRA data and their immunosuppressive potency. The first generation tacrolimus metabolites (M-I, M-II, and M-III) were tested using concentrations of 10 and 20 ng/mL. The significance of the metabolite interference (% of the total interference) was calculated based on the relative concentration of each metabolite present at steady-state trough concentrations in renal transplant recipients (22). Metabolite I, which has no functional immunosuppressive activity showed minimal interference compared to M-II and M-III in all assays except the 14 kDa RRA. The Incstar PRO-Trac II tacrolimus assay showed the least M-I interference. Metabolite-II, which has a pharmacologic potency similar to the parent drug, showed a significant interference in the immunoassays and significant interference in radioreceptor assays. Metabolite III, which is pharmacologically inactive, produces 3-10% interference in the different assays if its presence in the blood is 6% of the parent drug. The total interference from these three metabolites was greater in the immunoassays than in the receptor assays. Receptor assays for tacrolimus provide results closer to the target value than do immunoassays.


Exploration of an imide capture/N,N-acyl shift sequence for asparagine native peptide bond formation.
Imide capture of a C-terminal peptidylazide with a side-chain thioacid derivative of an N-terminally protected aspartyl peptide leads to the formation of an imide bond bringing the two peptide ends into close proximity. Unmasking of the N(α) protecting group and intramolecular acyl migration results in the formation of a native peptide bond to asparagine.


Production of late IFN-α induced by plasma γ-globulin fraction proteins and their metal complexes.
Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes they form with human serum γ-globulin induce the production of IFN-α by human blood cells throughout the periods of up to 72 h. Zinc cation-modified protein by 1.6 times (p<0.05) more actively induces late IFN-α than the control γ-globulin; γ-globulin-copper metal complex is 2-fold (p<0.002) more effective than the control protein. The results indicate that functional relationships between the components inducing the production of late IFN-α differ from the effects realized during the early period of induction.


Differential distribution and non-collateralization of central amygdaloid neurons projecting to different medullary regions.
The distributions of central amygdaloid nucleus (Ce) neurons projecting to different medullary regions were investigated using the retrograde transport of iontophoretically applied Fast Blue or bisbenzimide. Neurons projecting to the nucleus of the solitary tract were located throughout the medial, lateral and ventral subdivisions of the Ce whereas cells projecting to the parvicellular reticular formation and ventrolateral medulla were confined to the medial subdivision of the Ce. Combined injections of fluorescent dyes into these medullary areas resulted in only occasional double-labelled cells. The results suggest that Ce projections to a variety of medullary sites arise from separate populations of neurons with partially overlapping distributions in the medial Ce.


Inhibitory mechanisms in epileptiform activity induced by low magnesium.
In rat hippocampal slices epileptiform activity was induced by superfusion with Mg(2+)-free artificial cerebrospinal fluid (ACSF). Paroxysmal depolarization shifts (PDS) were evoked by electrical stimulation of Schaffer collaterals. To investigate the afterpotentials that follow PDS, intracellular recordings were made from CA1 pyramidal cells. The experiments revealed that several components are engaged in the generation of PDS afterpotentials in Mg(2+)-free ACSF. A long lasting component which determined the overall duration of the PDS afterhyperpolarization was blocked by intracellular application of ethylenebis(oxonitrilo)-tetraacetate (EGTA); concomitantly, the afterhyperpolarizations following depolarizing current injections were blocked. This indicated that the long lasting component was due to a slow Ca(2+)-activated K+ current. The block of Ca(2+)-activated K+ current uncovered a depolarizing PDS afterpotential with an N-shaped voltage dependence, suggesting that this depolarizing afterpotential component may be due to an N-methyl D-aspartate (NMDA) conductance. Intracellular injection of Cl- revealed that the PDS were followed by Cl- currents lasting about 500 ms. This component could be blocked by application of bicuculline suggesting that it is due to a synaptically GABA-mediated (i.e. gamma-aminobutyric acid) Cl- current. A comparison of PDS afterpotentials in Mg(2+)-free ACSF and those in other models of epileptiform activity suggests that similar sequences of inhibitory components are activated in spite of different pharmacological alterations of membrane conductances which induce the epileptiform discharges.


Mobilization of stored calcium for phasic contraction induced by norepinephrine in rabbit aorta.
In Ca-free solution norepinephrine (NE) produced only a phasic contraction in the media-intima layer of rabbit aorta. The second application of NE was almost ineffective. Incubation of the muscle with Ca for a short period (Ca loading) restored the ability to produce a phasic contraction in Ca-free solution. Various ions and compounds were applied to the muscle prior to the Ca loading or prior to NE application and it was found that these treatments variously affected the NE-induced phasic contraction. The data suggest that the NE-induced phasic contraction in Ca-free solution results from Ca release from cellular sites and that a hyperbolic relationship exists between the amount of Ca at these sites and the magnitude of the contraction. These sites take up extracellular Ca by a process sensitive to La3+ but not to D600; the Ca influx stimulated by high K solution, which is sensitive to D600 and also contributes to refilling of these sites; NE releases this stored Ca by a process sensitive to procaine, caffeine and theophylline and, in this manner, elicits a phasic contraction.


Spinal cord tumor leading to urinary retention resulting from Schistosoma mansoni infection in a child.
Schistosomose mansoni is an endemic disease in Brazil. It rarely affects the central nervous system, particularly in children. We report the case of a child that presented with an acute spinal cord compression condition, resulting from a mass that proved to be a granuloma caused by a Schistosoma mansoni infection. Proper treatment had no effect on the regression of urological symptoms and the child had to undergo a Mitrofanoff principle.


Distal radial arterial hypertrophy after transradial intervention: A serial intravascular ultrasound study.
Transradial intervention (TRI) may cause damage to the radial artery (RA). We have demonstrated intima-media thickening and luminal narrowing of the distal RA after TRI using intravascular ultrasound (IVUS). This study aimed to determine the predictors of intima-media thickening of RA after TRI in the same patients using serial IVUS. We enrolled 110 consecutive patients who underwent TRI. IVUS of RA was immediately performed after TRI and repeated 6 months later. Volumetric analyses were performed for the distal RA. The intima-media volume (IMV) increased from 53.56±10.85mm3 to 58.70±13.04mm3 (p=0.0022), whereas the lumen volume (LV) decreased from 146.87±40.53mm3 to 129.64±45.78mm3 (p=0.0018) and vessel volume (VV) decreased from 201.23±44.55mm3 to 188.34±52.25mm3 (p=0.0306). Multiple regression analysis revealed diabetes as the most powerful independent predictor of the percentage change in IMV of the distal RA after TRI. The percentage change in IMV significantly increased in the DM group compared with non-DM group (p<0.001). The percentage change in IMV was significantly positively correlated with HbA1c. Serial IVUS of the distal RA revealed a significant increase in IMV and decreases in LV and VV. Diabetes was the most powerful independent predictor of the percentage change in IMV of the distal RA after TRI. The percentage change in IMV was significantly positively correlated with HbA1c.


Five to 15 year follow-up of resolved idiopathic central serous chorioretinopathy.
To recognize the long-term sequelae of resolved idiopathic central serous chorioretinopathy (ICSC) in relation to visual acuity, contrast sensitivity, and lesion size between time elapsed since disease onset. Patients were recruited from fluorescein angiogram records between January 1985 and December 1995 with confirmed ICSC. Visual acuity, contrast sensitivity, and digital fundus photographs were recorded on follow-up. Comparison with the initial red-free photographs were made. There was no statistically significant deterioration of visual acuity over time compared to eyes with ICSC after initial resolution and the normal eyes. The change of lesion size over time was also statistically insignificant. Contrast sensitivity compared to visual acuity showed positive correlation in both ICSC and normal eyes, but the results were statistically insignificant. Lesion size correlates negatively with visual acuity and contrast sensitivity although this was statistically insignificant. This study shows little, if any, correlation between time and progression of retinal pigment epitheliopathy following resolution of ICSC. Visual acuity did not seem to worsen over time. Our data were not statistically significant, but it does give insight into the natural history of what is still a relatively poorly understood disease.


Involvement of batrachotoxin binding sites in ginsenoside-mediated voltage-gated Na+ channel regulation.
Recently, we showed that the 20(S)-ginsenoside Rg3 (Rg3), an active ingredient of Panax ginseng, inhibits rat brain NaV1.2 channel peak currents (INa). Batrachotoxin (BTX) is a steroidal alkaloid neurotoxin and activates NaV channels through interacting with transmembrane domain-I-segment 6 (IS6) of channels. Recent report shows that ginsenoside inhibits BTX binding in rat brain membrane fractions. However, it needs to be confirmed whether biochemical mechanism is relevant physiologically and which residues of the BTX binding sites are important for ginsenoside regulations. Here, we demonstrate that mutations of BTX binding sites such as N418K and L421K of rat brain NaV1.2 and L437K of mouse skeletal muscle NaV1.4 channel reduce or abolish Rg3 inhibition of I(Na) and attenuate Rg3-mediated depolarizing shift of the activation voltage and use-dependent inhibition. These results indicate that BTX binding sites play an important role in modifying Rg3-mediated Na+ channel properties.


Effect of unit and operatory lights on the consistency of light-activated composites.
The extent to which the flow of composite resin is reduced when exposed to dental lights was studied. Samples were exposed to operating lights of various intensities for varying periods of time. After exposure each sample was placed under a fixed load and the resulting average diameter was calculated. Data from the testing of samples exposed to dental lights were analyzed by a two-way analysis of variance with subsequent Tukey multiple comparison test. Diameter comparisons were significant (p less than 0.05) between the controls and samples exposed to the 960 fc light at 6 minutes, the 1920 fc light at 4 minutes, the 2880 fc light at 2 minutes, and the 5120 and 7680 fc lights at 1 minute. The smaller diameters observed with respect to increased intensity and time of exposure show that either variable or the combination of both variables will alter the consistency of composite resin.


Treatment Outcomes of Arytenoid Dislocation by Closed Reduction: A Multidimensional Evaluation.
This study aimed to investigate the treatment outcomes of arytenoid dislocation by a multidimensional evaluation. From April 2010 to May 2018, the records of 57 patients with a history of arytenoid dislocation were reviewed. All the patients were treated with closed reduction under local anesthesia. Arytenoid motion, grade, roughness, breathiness, asthenia, strain, maximum phonation time, self-assessed Voice Handicap Index, and acoustic voice analysis were used to evaluate the clinical outcomes. Following closed reduction, 57 patients were divided into "recovered" (n = 24), "improved" (n = 15), and "ineffective" (n = 18) groups. There were no major complications resulting from surgical intervention. Closed reduction under local anesthesia continues to be an effective and well-tolerated method for treating arytenoid dislocation. The trichotomy of the treatment results of arytenoid dislocation by a multidimensional evaluation may be more accurate to evaluate the results of arytenoid dislocation.


Infectivity of bovine leukaemia virus infected cattle: an ELISA for detecting antigens expressed in in vitro cultured lymphocytes.
A simple ELISA is described for quantifying expression of bovine leukaemia virus (BLV) antigens in short-term cultures of peripheral blood lymphocytes (PBL) isolated from infected cattle. The PBL-ELISA demonstrated that antigen expression levels in infected cattle could vary by more than 50-fold. Inoculation of sheep with dilutions of lymphocytes from two BLV-infected cattle, differentiated in the PBL-ELISA by 50 to 100-fold, suggested that antigen expression levels were correlated with infectivity. Haematological data indicated that increased antigen expression in PBL cultures was associated with an increased number of circulating B-lymphocytes, irrespective of whether or not an animal had lymphocytosis. This supported the hypothesis that BLV-infected cattle that are PBL-ELISA positive are more infectious and may present a greater risk of transmitting the disease. The applicability of the PBL-ELISA to a field situation was assessed with 98 BLV-infected cattle from three commercial dairy herds with infection prevalences of 11%, 23% and 47%. Similar percentages (49%, 50% and 52%) of PBL-ELISA positive cattle were identified among those infected cattle available for testing in the three herds. An additional 22 infected cattle from an experimental herd were tested to assess the stability of antigen expression levels over an 8 month period. Fewer (27%) of these cattle were identified as PBL-ELISA positive and antigen expression levels were generally lower than those observed in the commercial herds. Antigen expression levels in the experimental herd remained stable over the period of the study. The potential of the PBL-ELISA to assist in BLV eradication programs by identifying those seropositive cattle with the greatest potential to transmit infection is discussed.


Role of spectral detail in sound-source localization.
Sounds heard over headphones are typically perceived inside the head (internalized), unlike real sound sources which are perceived outside the head (externalized). If the acoustical waveforms from a real sound source are reproduced precisely using headphones, auditory images are appropriately externalized and localized. The filtering (relative boosting, attenuation and delaying of component frequencies) of a sound by the head and outer ear provides information about the location of a sound source by means of the differences in the frequency spectra between the ears as well as the overall spectral shape. This location-dependent filtering is explicitly described by the head-related transfer function (HRTF) from sound source to ear canal. Here we present sounds to subjects through open-canal tube-phones and investigate how accurately the HRTFs must be reproduced to achieve true three-dimensional perception of auditory signals in anechoic space. Listeners attempted to discriminate between 'real' sounds presented from a loudspeaker and 'virtual' sounds presented over tube-phones. Our results show that the HRTFs can be smoothed significantly in frequency without affecting the perceived location of a sound. Listeners cannot distinguish real from virtual sources until the HRTF has lost most of its detailed variation in frequency, at which time the perceived elevation of the image is the reported cue.


An Infant with a Prolonged Sympathomimetic Toxidrome after Lisdexamfetamine Dimesylate Ingestion.
Stimulant medications are approved to treat attention deficit hyperactivity disorder (ADHD) in children over the age of 6 years. Fatal ingestion of stimulants by children has been reported, although most ingestions do not result in severe toxicity. Lisdexamfetamine dimesylate, a once daily long-acting stimulant, is a prodrug requiring conversion to its active form, dextroamphetamine, in the bloodstream. Based on its unique pharmacokinetics, peak levels of d-amphetamine are delayed. We describe a case of accidental ingestion of lisdexamfetamine dimesylate in an infant. A previously healthy 10-month-old infant was admitted to the hospital with a 5-h history of tachycardia, hypertension, dyskinesia, and altered mental status of unknown etiology. Confirmatory urine testing, from a specimen collected approximately 16 h after the onset of symptoms, revealed an urine amphetamine concentration of 22,312 ng/mL (positive cutoff 200 ng/mL). The serum amphetamine concentration, from a specimen collected approximately 37 h after the onset of symptoms, was 68 ng/mL (positive cutoff 20 ng/mL). Urine and serum were both negative for methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA, Ecstasy), and methylenedioxyethamphetamine (MDEA). During the hospitalization, it was discovered that the infant had access to lisdexamfetamine dimesylate prior to the onset of symptoms. Amphetamine ingestions in young children are uncommon but do occur. Clinicians should be aware of signs and symptoms of amphetamine toxicity and consider ingestion when a pediatric patient presents with symptoms of a sympathetic toxidrome even when ingestion is denied.


Thromboxane synthetase inhibition with CGS 13080 improves coronary blood flow after streptokinase-induced thrombolysis.
The focus of this investigation was to examine the potential beneficial effects of the selective thromboxane synthetase inhibitor CGS 13080 (imidazo [1,5-a] pyridine-5-hexanoic acid) on coronary blood flow after streptokinase-induced thrombolysis. Thrombotic occlusion of the circumflex coronary artery was produced by electrolytic (100 microA anodal current) injury to the intimal surface of the circumflex coronary artery at the site of a noncircumferential stenosis in dogs anesthetized with pentobarbital to have open-chest surgery. Intracoronary streptokinase, 6000 IU/kg in 3 ml saline solution, was infused at 0.05 ml/min for 1 hour, beginning 30 minutes after the formation of an occlusive thrombus. The animals were assigned randomly to two groups. In group I (n = 10) the intravenous infusion of vehicle was begun simultaneously with the intracoronary administration of streptokinase and continued for 2 hours after thrombolysis had been achieved. The animals in group II (n = 10) received intravenous CGS 13080 (1 mg/kg/hr) along with intracoronary streptokinase. Infarct size was assessed by a dual perfusion technique with Evans blue and triphenyltetrazolium stains to demarcate the normally perfused myocardium from the area at risk and the infarct zone within the risk region. The two groups did not differ with respect to baseline coronary blood flow, time to the development of coronary artery thrombotic occlusion, or time to achieve thrombolysis. Oscillations in coronary blood flow were more frequent in group I than in group II (group I, 9 +/- 2.2; group II, 4.4 +/- 0.8 oscillation/min X 100, p less than 0.05 [mean +/- SEM)].(ABSTRACT TRUNCATED AT 250 WORDS)


Percutaneous Nephrolithotomy in Patients With BMI >50: Single Surgeon Outcomes and Feasibility.
To evaluate the use of percutaneous nephrolithotomy (PNL) and technical approach in the super obese population (body mass index [BMI] ≥ 50). We performed a retrospective review of 31 consecutive PNL cases with a BMI > 50 from a single surgeon (SYN) from 1995 to 2013. Procedures were performed in the prone position, and upper pole access was used. Operative time, length of hospital stay, stone burden, complication rates, and stone-free rates were measured. Of the 31 patients who underwent PNL (age 51.2 ± 12; 71% female), the mean BMI was 59.1 ± 6 kg/m(2) (range 50.4-71.7 kg/m(2)). Mean stone burden was 3.8 cm ± 2. The majority of patients (90.3%) had an upper pole puncture site for access with an operative time of 122.1 ± 75 minutes. The technique was similar to non-obese patients; however, there was a need for extra-long instrumentation. The overall stone-free rate was 71%, with utilization of a second-look PNL in 11 cases. The complication rate, Clavien grade 3 or higher, was 9.7% (3 of 31). PNL is technically feasible, safe, and effective in patients with a BMI ≥ 50. The complication rate, length of hospital stay, and stone-free rate with use of second-look PNL in super obese patients are comparable to severely obese patients. Intervention should not be automatically ruled out or delayed based on the patient's BMI alone.


A smartphone-powered photoelectrochemical POCT via Z-scheme Cu2O/Cu3SnS4 for dibutyl phthalate in the environmental and food.
As a major hazardous additive released from microplastics and nanoplastics, identifying dibutyl phthalate (DBP) in complex matrices attracts a growing concern in environmental monitoring and food safety. For the first time, Cu2O/Cu3SnS4 nanoflower is prepared and serves as the photoactive material which can be constructed as a smartphone-based photoelectrochemical (PEC) point-of-care test (POCT). Effectively matching energy levels between Cu2O and Cu3SnS4 accelerated the transfer of photogenerated electron-hole pairs, significantly improving the intelligent PEC POCT performance. The novel Cu2O/Cu3SnS4 has proven to be the Z-scheme heterojunction by density functional theory calculation. A competitive immunoassay has been realized on a Cu2O/Cu3SnS4 modified electrode, dramatically decreasing the photocurrent signal and enhancing POCT sensitivity. The smartphone has been used to record and transfer PEC results. Under optimal conditions, the PEC POCT exhibited a satisfying linear range (0.04-400 ng/mL) and a low detection limit of 7.94 pg/mL in real samples, together with excellent stability, repeatability, reproducibility and selectivity. The PEC POCT system provides good performance and practicability in determining DBP in water and edible oil samples. This proposal provides a practical strategy for the intelligent POCT for environment monitoring and food safety.


Recombinant interferon-gamma applied to the brain ventricular system protects rats against pseudorabies.
We examined the prophylactic efficacy of recombinant rat interferon-gamma (IFN-gamma) administered directly into the brain ventricular system or via the intraperitoneal (i.p.) route against central and peripheral pseudorabies virus (PRV) infection. Intraperitoneally given IFN-gamma completely protected rats against a lethal i.p. PRV infection. The same regimen showed no protective effect against lethal intracerebroventricular (i.c.v.) PRV challenge even if IFN-gamma was given in high concentrations. When given via the i.c.v. route, IFN-gamma protected rats against lethal i.c.v. infection and also evoked partial protection with extended survival times of i.p. infected rats. Our results demonstrate an IFN-gamma-mediated antiviral effect in the central nervous system.


PET imaging evaluation of [(18)F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman primates.
Positron emission tomography (PET) radioligands specific to α7 nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer's disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α7-nAChR-specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[(18)F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([(18)F]DBT-10), in nonhuman primates. [(18)F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [(18)F]DBT-10 PET, with measurement of [(18)F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α7-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [(18)F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (V T/f P). [(18)F]DBT-10 was produced within 90 min at high specific activities of 428 ± 436 GBq/μmol at end of synthesis. Metabolism of [(18)F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15-55%. Uptake of [(18)F]DBT-10 in brain occurred rapidly, reaching peak standardized uptake values (SUVs) of 2.9-3.7 within 30 min. The plasma-free fraction was 18.8 ± 3.4%. No evidence for radiolabeled [(18)F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated V T/f P values were 193-376 ml/cm(3) across regions, with regional rank order of thalamus > frontal cortex > striatum > hippocampus > occipital cortex > cerebellum > pons. Dose-dependent blockade of [(18)F]DBT-10 binding by structural analog ASEM was observed throughout the brain, and occupancy plots yielded a V ND/f P estimate of 20 ± 16 ml/cm(3). These results demonstrate suitable kinetic properties of [(18)F]DBT-10 for in vivo quantification of α7-nAChR binding in nonhuman primates.


Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of tumor necrosis factor-alpha.
Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha are elevated in preeclamptic women and are thought to be an important link between placental ischemia and endothelial dysfunction. The purpose of this study was to determine the role of TNF in mediating hypertension in response to chronic reductions in uterine perfusion (RUPPs) in pregnant rats. Arterial pressure was significantly higher in RUPP rats (138+/-1 mm Hg) than in pregnant rats (107+/-1 mm Hg). Serum TNF-alpha levels in the RUPP rats were 17+/-4 pg/mL compared with 8+/-1 pg/mL in normal pregnant rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma TNF-alpha on renal and systemic hemodynamics in pregnant rats, we infused TNF-alpha for 5 days at a rate of 50 ng/d during days 14 to 19 of gestation in pregnant rats. Serum levels were 7+/-2 pg/mL in the control pregnant rats and 14+/-2 pg/mL in the TNF-alpha-treated pregnant rats. Mean arterial pressure was higher in the TNF-alpha-treated pregnant rats (123+/-3 mm Hg) compared with pregnant controls (96+/-3 mm Hg) at day 19 of gestation. TNF-alpha increased renal vascular resistance in pregnant rats by 182%. Renal plasma flow was 5.4+/-1.2 mL/min in the TNF-alpha-treated group and 9.2+/-1.6 mL/min in the control group. Glomerular filtration rate was 1.7+/-0.4 mL/min in the TNF-alpha-treated group and 2.6+/-0.4 mL/min in the control group. In summary, these data suggest that TNF-alpha may play an important role in mediating the increased arterial pressure in response to chronic RUPPs in pregnant rats.


Anatomical reconstruction of fragments of burned human bones: a necessary means for forensic identification.
The aim of any forensic inquiry concerning accidental or criminal cremations is to identify the victims. This identification depends on an essential approach: a careful collection and ultrasonic cleaning of the fragments and splinters of burned bones, and reconstruction--as far as possible--of bone specimens, which implies that forensic anthropologists are well experienced in the field of burned bones.


Improving acetabular shell deformation testing.
To be FDA approved, acetabular shells must undergo rigorous testing. To prevent implant failure, acetabular shells must be able to tolerate peak loads during impaction with minimal deformation. The implants must therefore be validated in order to ensure that their structural integrity can tolerate peak loads. The current ISO 7206-12 recommends manufacturing an expensive single-purpose testing device to measure the deformation of acetabular shells. In the article, we provide an open access methodology, that can be conducted with minimal expense, for testing acetabular shell deformation. We designed our experimental setup to utilize a servohydraulic materials testing device (Instron) commonly found in biomechanics laboratories and then validated the measurements optically with optical data. Furthermore, we designed an inexpensive acetabular screw fastener which acts as an adaptor that can be used to mount a variety of acetabular shell types just as effectively as current methods and is in compliance with the standards outlined in ISO 7206-12:2016. A Bland-Altman plot comparing the Instron and optical displacement measurements found the standard deviation of bias to be 0.046 mm and an insignificant systemic bias. We have developed and validated a low-cost open-source system that can effectively test acetabular shell deformation that meets ISO standards.


Cost of identifying patients for carotid endarterectomy.
The cost of carotid endarterectomy (CEA) usually considers only the cost of the preoperative investigations and the procedure for the individual patient but ignores the cost incurred in selecting a patient from a referred "pool" of potential candidates or the "total direct program cost." The aim of this study was to estimate the total direct program cost (workup and procedure) of CEA in a large major teaching hospital in Edinburgh, Scotland using a retrospective study design. Participants were patients with transient ischemic attacks and mild strokes referred to the neurovascular clinics for assessment, investigation, and possible CEA. The "workup" was defined as the clinical consultation, carotid duplex, 1 follow-up visit, and a catheter angiogram where indicated. We used data routinely collected from the neurovascular clinics during a 1-year period to estimate the workup cost of patients who might be suitable for CEA. The CEA procedure cost was estimated prospectively in a concurrent study. Estimated costs were applied to the proportions assessed at the different levels of investigation to determine the total direct program cost of CEA. A total of 790 new patients with symptoms suggestive of transient ischemic attacks and mild strokes were identified. Four hundred one (51%) patients were referred for carotid duplex. Duplex identified 78 (10%) with carotid stenosis of > or =70%. Of the total of 790 patients, 26 (3.3%) had catheter angiogram and 18 (2.3%) had CEA. The total direct program cost to investigate this cohort was about 207 000 pounds sterling, with 68% (140 000 pounds sterling) of the cost incurred before any surgery was performed. The cost of identifying suitable patients for carotid surgery is quite high, with more than 30% of the cost attributed to the initial consultation at the neurovascular clinics. The cost of preventing 1 stroke by CEA is in the region of 100 000 pounds sterling at 1997/1998 prices if all the costs incurred in the workup of a cohort for potential CEA are included.


Improved diagnosis of viral encephalitis in adult and pediatric hematological patients using viral metagenomics.
Metagenomic sequencing is a powerful technique that enables detection of the full spectrum of pathogens present in any specimen in a single test. Hence, metagenomics is increasingly being applied for detection of viruses in clinical cases with suspected infections of unknown etiology and a large number of relevant potential causes. This is typically the case in patients presenting with encephalitis, in particular when immunity is impaired by underlying disorders. In this study, viral metagenomics has been applied to a cohort of hematological patients with encephalitis of unknown origin. Because viral loads in cerebrospinal fluid of patients with encephalitis are generally low, the technical performance of a metagenomic sequencing protocol with viral enrichment by capture probes targeting all known vertebrate viral sequences was studied. Subsequently, the optimized viral metagenomics protocol was applied to a cohort of hematological patients with encephalitis of unknown origin. Viral enrichment by capture probes increased the viral sequence read count of metagenomics on cerebrospinal fluid samples 100 - 10.000 fold, compared to unenriched metagenomic sequencing. In five out of 41 (12%) hematological patients with encephalitis, a virus was detected by viral metagenomics which had not been detected by current routine diagnostics. BK polyomavirus, hepatitis E virus, human herpes virus-6 and Epstein Barr virus were identified by this unbiased metagenomic approach. This study demonstrated that hematological patients with encephalitis of unknown origin may benefit from early viral metagenomics testing as a single step approach.


Detection of piRNAs in whitespotted bamboo shark liver.
Piwi-interacting RNAs (piRNAs) are 26 to 31-nt small non-coding RNAs that have been reported mostly in germ-line cells and cancer cells. However, the presence of piRNAs in the whitespotted bamboo shark liver has not yet been reported. In a previous study of microRNAs in shark liver, some piRNAs were detected from small RNAs sequenced by Solexa technology. A total of 4857 piRNAs were predicted and found in shark liver. We further selected 17 piRNAs with high and significantly differential expression between normal and regenerative liver tissues for subsequent verification by Northern blotting. Ten piRNAs were further identified, and six of these were matched to known piRNAs in piRNABank. The actual expression of six known and four novel piRNAs was validated by qRT-PCR. In addition, a total of 401 target genes of the 10 piRNAs were predicted by miRanda. Through GO and pathway function analyses, only five piRNAs could be annotated with eighteen GO annotations. The results indicated that the identified piRNAs are involved in many important biological responses, including immune inflammation, cell-specific differentiation and development, and angiogenesis. This manuscript provides the first identification of piRNAs in the liver of whitespotted bamboo shark using Solexa technology as well as further elucidation of the regulatory role of piRNAs in whitespotted bamboo shark liver. These findings may provide a useful resource and may facilitate the development of therapeutic strategies against liver damage.


Research on the proximity functions of microdosimetry of low energy electrons in liquid water based on different Monte Carlo codes.
The proximity function is an important index in microdosimetry for describing the spatial distribution of energy, which is closely related to the biological effects of organs or tissues in the target area. In this work, the impact of parameters, such as physic models, cut-off energy, and initial energy, on the proximity function are quantitated and compared. According to the track structure (TS) and condensed history (CH) low-energy electromagnetic models, this paper chooses a variety of Monte Carlo (Monte Carlo, MC) codes (Geant4-DNA, PHITS, and Penelope) to simulate the track structure of low-energy electrons in liquid water and evaluates the influence of the electron initial energy, cut-off energy, energy spectrum, and physical model factors on the differential proximity function. The results show that the initial energy of electrons in the low-energy part (especially less than 1 keV) has a greater impact on the differential proximity function, and the choice of cut-off energy has a greater impact on the differential proximity function corresponding to small radius sites (generally less than 10 nm). The difference in the electronic energy spectrum has little effect on the result, and the proximity functions of different physics models show better consistency under large radius sites. This work comprehensively compares the differential proximity functions under different codes by setting a variety of simulation conditions and has basic guiding significance for helping users simulate and analyze the deposition characteristics of microscale electrons according to the selection of an appropriate methodology and cut-off energy.


A magnetic resonance imaging study of the adhesio interthalamica in schizophrenia.
Several recent studies have found a relationship between midline cerebral malformations (cavum septi pellucidum, absence of the adhesio interthalamica) and schizophrenia. In this study, we investigated whether the adhesio interthalamica is more often absent in patients with schizophrenia than healthy cases and whether the absence of the adhesio interthalamica may be related to the volume of the third ventricle. Twenty-six patients (11 male, 15 female) in the schizophrenia group and twenty-nine (11 male, 18 female) cases in the control group were examined by MRI. The adhesio interthalamica was found to be absent more often among patients with schizophrenia compared with control subjects and patients without adhesio interthalamica did not have significantly larger third ventricle volumes. The absence of the adhesio interthalamica may be important in explaining the association between the abnormalities of brain midline structures and schizophrenia.


Carbon monoxide binding in a model of hemoglobin differs between the T and the R conformation.
The ratio between carbon monoxide affinity and oxygen affinity (M) is usually assumed to have a fixed value (Haldane's law), which is about 200. However, this ratio is not a constant but depends on the level of saturation (Roughton, 1970) as well as on pH (Joels and Pugh, 1958). This means that simple procedures cannot be used to calculate the combined effects of simultaneous oxygen and carbon monoxide binding. Application of our mathematical model of hemoglobin (Zock, 1987) shows that this model can account for the above-mentioned phenomena in a straightforward way. Within the context of this mathematical model of human hemoglobin the differences in shape between oxygen equilibrium curve and carbon monoxide equilibrium curve of human hemoglobin could be readily explained by assuming that the ratio between oxygen affinity and carbon monoxide affinity differs between the T and the R conformation.


Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact.
HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment. From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0. Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH. In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.


Genetic examination of hematological parameters in SARS-CoV-2 infection and COVID-19.
People hospitalized with COVID-19 often exhibit altered hematological traits associated with disease prognosis (e.g., lower lymphocyte and platelet counts). We investigated whether inter-individual variability in baseline hematological traits influences risk of acute SARS-CoV-2 infection or progression to severe COVID-19. We report inconsistent associations between blood cell traits with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we also assessed the shared genetic architecture of baseline blood cell traits on COVID-19 related outcomes by Mendelian randomization (MR) analyses. We found significant relationships between COVID-19 severity and mean sphered cell volume after adjusting for multiple testing. However, MR results differed significantly across different freezes of COVID-19 summary statistics and genetic correlation between these traits was modest (0.1), decreasing our confidence in these results. We observed overlapping genetic association signals between other hematological and COVID-19 traits at specific loci such as MAPT and TYK2. In conclusion, we did not find convincing evidence of relationships between the genetic architecture of blood cell traits and either SARS-CoV-2 infection or COVID-19 hospitalization, though we do see evidence of shared signals at specific loci.


Author Correction: Interplay of grounding-line dynamics and sub-shelf melting during retreat of the Bjørnøyrenna Ice Stream.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Iboga interactions with psychomotor stimulants: panacea in the paradox?
Currently, no effective therapy has been approved for the treatment of addiction to stimulant drugs (e.g., cocaine, amphetamine and its methylated derivatives). However, preclinical studies indicate that the naturally-occurring indole alkaloid, ibogaine, and a synthetic iboga alkaloid congener, 18-methoxycoronaridine (18-MC), attenuate stimulant self-administration in laboratory animals. The in vivo pharmacological interactions between iboga agents and stimulant drugs are unclear. Ibogaine enhances the increase in accumbal dopamine produced by the acute administration of stimulant drugs. Consistent with these data, both ibogaine and 18-MC potentiate the expression of stimulant-induced motor behaviors in acute and chronic stimulant-treated animals. To account for the paradox between their effects on self-administration and motor behavior, we proposed that iboga agents interfere with stimulant self-administration by increasing sensitivity to their psychomotor-activating effects. However, this interpretation is contradicted by very recent observations that 18-MC is without effect on the dopamine response to acute cocaine and that both ibogaine and 18-MC block the expression of sensitized levels of dopamine in the nucleus accumbens produced by chronic cocaine administration. Thus, a positive relationship exists between the effects of iboga pretreatment on stimulant-induced dopamine sensitization and stimulant self-administration behavior. These data indicate that iboga agents might attenuate stimulant self-administration by reversing the neuroadaptations theoretically implicated in drug craving and compulsive drug-seeking behavior.


New insights into the regulation of Na+,K+-ATPase by ouabain.
Cardiac glycosides have been widely used in the treatment of congestive heart failure and cardiac arrhythmias. The mechanism of their positive ionotropic effect is well characterized and is based on the inhibition of Na(+),K(+)-ATPase. However, recently it has been discovered that circulating endogenous cardiotonic steroids bind to Na(+),K(+)-ATPase, activate cell signaling pathways, and regulate diverse cellular functions. Thus, they play an important role in both physiological and pathological processes. Circulating endogenous ouabain has been reported to activate several signaling pathways upon binding to Na(+),K(+)-ATPase, and altered plasma levels of this endogenous cardiotonic steroid have been found in several pathologies. This review focuses on ouabain-mediated activation of cell signaling pathways and secondary messengers that conversely may modulate Na(+),K(+)-ATPase function.


Computed tomography diagnosis of partial anomalous pulmonary venous drainage.
A case of the rarely occurring partial anomalous pulmonary venous drainage of the right upper lobe into the azygos arch is presented. Computed tomography (CT) clearly demonstrated the abnormal vessel coursing through the right upper lobe and draining into the azygos arch.


Molecular characterization and identification of Blastocystis and its subtypes from raccoon (Procyon lotor) in north of Iran.
Blastocystis is a zoonotic protozoan parasite frequently identified in the intestinal tract of humans and a vast variety of animals, worldwide. Here, we assessed the prevalence of Blastocystis and its subtypes in stool samples of raccoons. Stool samples from 30 raccoons were collected. Total DNA was extracted, and the barcoding region of the small subunit ribosomal rRNA (SSU rRNA) gene was amplified and sequenced. Specific fragment for Blastocystis was successfully amplified in five samples (16.66%). Sequencing analysis revealed ST1, ST2, and ST3 among 1, 2, and 2 Blastocystis-positive samples. Our results documented the presence of Blastocystis subtypes 1-3 in raccoons. Subtype 1 showed higher similarity to the human isolates of Blastocystis. However, it seems that raccoons may emerge as reservoirs for Blastocystis and may be linked to zoonotic transmission of the protist.


Effects of Parent and Child Pre-Intervention Characteristics on Child Skill Acquisition during a School Readiness Intervention.
200 preschool children in Head Start (55% girls; 20% Hispanic, 25% African-American, 55% European American; M age = 4.80 years old) participated in a randomized-controlled trial of a home visiting intervention designed to promote their emergent literacy skills (the Research-based Developmentally Informed parent [REDI-P] program). This study explored concurrent changes in levels of parent support and child literacy skills that occurred over the course of the intervention, and examined the impact of pre-intervention parent support and child literacy skills as potential moderators of parent and child outcomes. Cross-lagged structural equation models and follow-up analyses indicated that intervention had the strongest impact on child literacy skills when parents were high on support at the pre-intervention assessment. Conversely, the REDI-Parent program promoted the greatest gains in parent support when parents entered the program with low levels. These findings suggest that families may benefit from home visit school readiness interventions in different ways: child skill acquisition may be greatest when parents are initially high in support, whereas parenting may improve most when parents are initially low in support.


Role of myofibrillar creatine kinase in the relaxation of rigor tension in skinned cardiac muscle.
In the absence of creatine phosphate, MgATP produced relaxation of rigor tension in chemically-skinned right papillary muscles of the rat, the half maximal effect being obtained at 1.8 mM MgATP. In the presence of 12 mM creatine phosphate and 250 microM ADP, a decrease in MgATP concentration even to 10(-9) M never induced rigor tension. At a very low MgATP concentration (10(-6) M), the half maximal relaxing effect was obtained with 2 mM creatine phosphate, a value close to the Km of isolated MM-creatine kinase for this substrate, or with 14 microM MgADP, a value 5 times lower than the reported Km. An exogenous MgATP regenerating system (phosphoenol pyruvate + pyruvate kinase) was not able to fully relax the fibres. When MM-creatine kinase was inhibited by fluorodinitrobenzene, the dependency of rigor tension on MgATP became the same as it was without creatine phosphate. After washing out the fluorodinitrobenzene the addition of exogenous MM-creatine kinase for half an hour fully relaxed rigor tension; moreover, this effect persisted even after prolonged washout. These results show that endogenous MM-creatine kinase is able to ensure maximal efficiency of myosin ATPase by producing a localized high MgATP/MgADP ratio; they also suggest the existence of rapidly exchangeable binding sites for MM-creatine kinase in cardiac myofibrils.


Water sorption, water solubility, degree of conversion, elastic indentation modulus, edge chipping resistance and flexural strength of 3D-printed denture base resins.
To investigate the water sorption (wsp), water solubility (wsl), degree of conversion (DC), elastic indentation modulus (EIT), edge chipping resistance (ECR) and flexural strength (FS) of 3D-printed, milled and conventionally polymerized denture base resin materials. Specimens (N = 540) were 3D-printed (NextDent Denture 3D+ (DEN), Fotodent Denture (FOT), Freeprint Denture (FRE), V-Print dentbase (VPR)), cut (Ivotion Base (IVO)) and molded (PalaXpress (PAL)) in three geometries. Wsp,wsl,DC, EIT, ECR and FS were tested initially (24 h, 37 °C, H20) and after additional aging (5000 thermal cycles, 5/55 °C). Data were analyzed with Kolmogorov-Smirnov, univariate ANOVA, Kruskal-Wallis, Mann-Whitney U test and Spearman's correlation (p < 0.05) RESULTS: Most 3D-printed denture base resins showed higher wsp (25.31-37.94 μg/mm3) and wsl (0.08-8.27 μg/mm3), but also higher EIT (3.11-4.09 GPa) and FS (60.81-99.57N/mm2) values than the control groups. DEN and VPR showed high DC (89.36-93.53%), EIT (3.77-4.09 GPa) and FS (79.65-99.57N/mm2), while FOT showed low wsp (25.31-27.35 μg/mm3) and wsl (1.01-3.87 μg/mm3) values. In all materials, the examined parameters were affected by aging. Although 3D-printed denture base resins showed promising results with regard to the observed DC and FS, only FOT and FRE surpassed the threshold values defined by the ISO norms.


Indium leucocyte imaging in true pyrexia of unknown origin.
A patient with pyrexia of unknown origin (PUO) was investigated for a focal infection using autologous indium-labelled leucocytes. Only one site of increased activity was observed; this was asymptomatic and subsequently proved to be an infected nasal sinus. This case highlights the necessity, in PUO investigations, of carrying out whole-body imaging rather than just investigating the areas with presenting symptoms.


Encapsulation methods for photo-polymerisable self-healing formulations.
The aim of this work is to encapsulate a self-healing photo-polymerisable material for aerospace applications. To meet the technical requirements of space applications - low and high temperatures: -120 °C (dark side) to +250 °C (solar side); UV radiations: 200-400 nm; low pressure: 10(-4 )Pa - we chose trimethylolpropane triacrylate as healing agent. This monomer polymerises at 190 °C. To avoid its earlier thermal polymerisation, an inhibitor was added to the monomer/photo-initiator formulation. Moreover, among several microencapsulation techniques tested, we chose the sol-gel process to form silica microcapsules containing the self-healing formulation. These microcapsules were characterised by different analysis (scanning electron microscopy (SEM), thermo gravimetric analysis (TGA), Fourier transform infra-red spectroscopy (FTIR), etc.) and satisfied our requirements (size 1-30 μm, thermal stability >250 °C). After the microcapsules breakage, the generation of poly(TMPTA) film by radical photopolymerisation of the released TMPTA monomer was proved by disappearance of the IR peak at 1635 cm(-1) (assigned to TMPTA). The obtained film has a thermal stability above 300 °C.


Validation of the parent version of the World Health Organization Adult ADHD Self-Report Scale for adolescents.
To investigate the validity of a parent version of the World Health Organization Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Self-Report Scale for adolescents (ASRS-AP) and the 6-question screening version (ASRS-AP-S). Adolescent psychiatric outpatients (N = 112, mean age 15 years, 40% boys) and their parents were interviewed with the Kiddie Schedule of Affective Disorders and Schizophrenia (K-SADS), and the parents reported on the ASRS-AP/ASRS-AP-S. Internal consistency (Cronbach's alpha) was 0.93 for ASRS-AP and 0.85 for ASRS-AP-S, 0.91 and 0.87 for the inattention subscale, and 0.91 and 0.72 for the hyperactivity subscale, respectively. The concurrent validity (Spearman's correlation coefficient) between the total K-SADS ADHD symptom severity score and the sum of the score on the ASRS-AP/ASRS-AP-S was 0.75 and 0.66, respectively. Diagnostic accuracy measures for the ASRS-AP and ASRS-AP-S were 78% and 80% sensitivity, 75% and 74% specificity, 73% and 71% positive predictive value (PPV), and 81% and 82% negative predictive value (NPV), respectively. The ASRS-AP and ASRS-AP-S showed high internal consistency and concurrent validity in relation to total K-SADS ADHD symptom severity score. Both scales showed favourable diagnostic accuracy measures.


Automated Prediction of the Response to Neoadjuvant Chemoradiotherapy in Patients Affected by Rectal Cancer.
Rectal cancer is a malignant neoplasm of the large intestine resulting from the uncontrolled proliferation of the rectal tract. Predicting the pathologic response of neoadjuvant chemoradiotherapy at an MRI primary staging scan in patients affected by locally advanced rectal cancer (LARC) could lead to significant improvement in the survival and quality of life of the patients. In this study, the possibility of automatizing this estimation from a primary staging MRI scan, using a fully automated artificial intelligence-based model for the segmentation and consequent characterization of the tumor areas using radiomic features was evaluated. The TRG score was used to evaluate the clinical outcome. Forty-three patients under treatment in the IRCCS Sant'Orsola-Malpighi Polyclinic were retrospectively selected for the study; a U-Net model was trained for the automated segmentation of the tumor areas; the radiomic features were collected and used to predict the tumor regression grade (TRG) score. The segmentation of tumor areas outperformed the state-of-the-art results in terms of the Dice score coefficient or was comparable to them but with the advantage of considering mucinous cases. Analysis of the radiomic features extracted from the lesion areas allowed us to predict the TRG score, with the results agreeing with the state-of-the-art results. The results obtained regarding TRG prediction using the proposed fully automated pipeline prove its possible usage as a viable decision support system for radiologists in clinical practice.


Magnetization reversal, field-induced transitions andH-Tphase diagram of Y1-xCexCrO3.
We report a systematic study of the magnetic phase diagram in theH-Tplane, negative magnetization (NM), exchange interactions and field-induced spin-flop transitions in the distorted perovskite Y1-xCexCrO3. Locked AFM and weak-FM configurations in Γ4(Gz,Fy,Ax) phase of YCrO3(S= 3/2 ground state) unlocks into the Γ2(Fz,Gy,Cx;FzR,CxR) phase of the canted AFM and FM structures with the dilute substitution of Ce (x⩾ 0.05). The asymmetric and symmetric exchange interaction (JAS∼ 0.11 meV andJS∼ 0.85 meV) between the trivalent Ce and Cr enable the positive quartic-anisotropy field (HK4∼ 2.85 × 102Oe) along with the second order anisotropy field (HK2∼ 5.93 × 102Oe). Unlike the pristine YCrO3compound, the Ce incorporated system exhibits a giant fourth-order anisotropy constant (K4= 1.35 × 105erg/c.c.) due to the asymmetric exchange interaction between the trivalent Ce-Cr which further lifts the free energy of the system and causes lag in the onset of AFM ordering showing the significant thermal hysteresis (ΔT∼ 10 K) in the field-cooled (FC)-warming measurement protocol as compared to the FC-cooling mode. The H-T phase diagram, mapped from the isothermal magnetization data and differential magnetic susceptibility data with different measurement protocols clearly distinguishes three prominent regions below theTN(∼150 K), viz (i) long-range canted AFM + weak FM phase (Γ4(Gz,Fy,Ax)), (ii) Γ24mixed phase and (iii) robust Γ2(Fz,Gy,Cx;FzR,CxR) AFM + FM phases. Tunable spin-flopped transition (∼ 30 kOe), significant negative exchange-bias field (HEB∼ 2.5 kOe), huge coercive field (HC∼ 22 kOe) and large NM (ΔM∼ 280 emu/mole) are the unique characteristic features of the current investigated system.