Respiratory tract clearance of 14C-labeled diesel exhaust compounds associated with diesel particles or as a particle-free extract.
Radiolabeled diesel exhaust particles or dichloromethane extracts of these particles were intratracheally instilled (10 mg) into Fischer-344 rats and the clearance of 14C radioactivity was measured. Approximately 88% of the 14C radioactivity associated with the particles was soluble in dichloromethane. The clearance of 14C radioactivity from lungs occurred in two phases. The initial, more rapid phase of lung clearance of both particle-associated 14C radioactivity (Particle 14C) and extract-associated 14C radioactivity (Extract 14C) was very similar (t 1/2 approximately equal to 3 hr). However, the second phase of lung clearance of the remaining Particle 14C was much slower (t 1/2 approximately equal to 25 days) than the second phase of lung clearance of the Extract 14C (t 1/2 approximately equal to 2.9 days). Tracheal clearance rates of 14C radioactivity from both instillation studies were both rapid and similar (t 1/2 approximately equal to 10-12 hr). These results indicate that diesel engine exhaust particles reduce the lung clearance rate of the organic compounds associated with these particles. These studies also point to the possibility that the rate limiting step in the lung clearance of organic compounds associated with inhaled diesel exhaust particles may be the rate at which they dissociate from these particles in vivo. This is because the long-term clearance rate of the particle-associated organic compounds was shown here to be much slower than that of the same organic compounds in a particle-free form but not as slow as the lung clearance rate reported for diesel exhaust core particles (T.L. Chan, P.S. Lee, W.E. Hering, J. Appl. Toxicol. 1, 77-82 (1981].(ABSTRACT TRUNCATED AT 250 WORDS)


Utilisation of health management information and its determinant factors among health professionals working at public health facilities in North Wollo Zone, Northeast Ethiopia: a cross-sectional study.
The study aimed to assess health management information utilisation and associated factors among health professionals working at public health facilities in North Wollo Zone, Northeast Ethiopia. The study was conducted at public health facilities in the North Wollo Zone, Northeast Ethiopia. A total of 664 (56.3% male and 43.7% female) health professionals participated in the study. All health professionals permanently working in North Wollo Zone were included in this study. However, health professionals who were not present during the data collection period by any means and who had less than 6 months of experience were not included in this study. The main outcome measure was health management information utilisation. About 58.4% (n=388) (95% CI: 54.4% to 62.0%) of the study participants use health management information. The multivariable logistic regression model indicated that participants who had managerial positions are more likely to use health management information with an adjusted OR (AOR) of 3.11 and 95% CI 1.84 to 5.24. Similarly, having a good motivation level (AOR=4.42 (95% CI: 2.82 to 6.93)), perceived good culture of health information (AOR=6.17 (95% CI: 3.35 to 11.36)), a standard set of indicators (AOR=4.11 (95% CI: 2.65 to 6.38)), having good governance of health information system (AOR=1.75 (95% CI:1.13 to 2.72)) and health management information system (HMIS) training (AOR=3.10 (95% CI: 1.89 to 5.07)) were the predictors positively associated with higher utilisation of health management information. This study revealed that utilisation of health management information was still inadequate. Enhancing motivation, building a culture of information use, having standardised indicators, strengthening the governance of health information systems and comprehensive HMIS training were measures to be taken to improve utilisation of health management information in this study setting.


Sequential soil washing techniques using hydrochloric acid and sodium hydroxide for remediating arsenic-contaminated soils in abandoned iron-ore mines.
Sequential washing techniques using single or dual agents [sodium hydroxide (NaOH) and hydrochloric acid (HCl) solutions] were applied to arsenic-contaminated soils in an abandoned iron-ore mine area. We investigated the best remediation strategies to maximize arsenic removal efficiency for both soils and arsenic-containing washing solution through conducting a series of batch experiments. Based on the results of a sequential extraction procedure, most arsenic prevails in Fe-As precipitates or coprecipitates, and iron exists mostly in the crystalline forms of iron oxide. Soil washing by use of a single agent was not effective in remediating arsenic-contaminated soils because arsenic extractions determined by the Korean standard test (KST) methods for washed soils were not lower than 6mg kg(-1) in all experimental conditions. The results of X-ray diffraction (XRD) indicated that iron-ore fines produced mobile colloids through coagulation and flocculation in water contacting the soils, containing dissolved arsenic and fine particles of ferric arsenate-coprecipitated silicate. The first washing step using 0.2M HCl was mostly effective in increasing the cationic hydrolysis of amorphous ferrihydrite, inducing high removal of arsenic. Thus, the removal step of arsenic-containing flocs can lower arsenic extractions (KST methods) of washed soils. Among several washing trials, alternative sequential washing using 0.2M HCl followed by 1M HCl (second step) and 1M NaOH solution (third step) showed reliable and lower values of arsenic extractions (KST methods) of washed soils. This washing method can satisfy the arsenic regulation of washed soil for reuse or safe disposal application. The kinetic data of washing tests revealed that dissolved arsenic was easily readsorbed into remaining soils at a low pH. This result might have occurred due to dominant species of positively charged crystalline iron oxides characterized through the sequential extraction procedure. However, alkaline extraction using NaOH was effective in removing arsenic readsorbed onto the surface of crystalline minerals. This is because of the ligand displacement reaction of hydroxyl ions with arsenic species and high pH conditions that can prevent readsorption of arsenic.


Integrating functional MRI information into radiotherapy planning of CNS tumors-early experiences.
The purpose of our study was to examine the integration of functional MRI (fMRI) information into 3D based planning process of the central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2008 four patients with astrocytoma were enrolled to this study. Before the planning process conventional planning CT, postoperative MR and individual functional MRI examinations were delivered. For the functional MRI examination the following four types of stimulus were applied: acoustic, visual, somatosensory and numeral. Three different theoretical planning situations were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information and IMRT plan with fMRI information. For plan comparison DVH analysis, and NTCP model were used. fMRI based OR definition resulted in 4 additional OR's in the contouring process. As these cases demonstrate, an average of 50% dose reduction was achieved in OR, OR2 and OR3 with IMRT and fMRI based 3D planning, especially in case of midline localization and big tumor extent. IMRT provides additional sparing effect in the optic tract and brainstem, especially for localizations close to the midline. Our results demonstrated that using fMRI information in conventional 3D based treatment planning potentially benefits significant dose reduction in critical organs, with no compromise in PTV coverage. fMRI can be widely used even in low grade cases (long life expectancies, lower acute and late toxicity in radiotherapy) and in cases with high grade astrocytomas or metastases (higher dose to PTV with better risk organ sparing in radiotherapy).


Impaired brain glymphatic flow in experimental hepatic encephalopathy.
Neuronal function is exquisitely sensitive to alterations in the extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain is thought to result from liver disease and may contribute to neuronal dysfunction and cognitive impairment. This study was designed to test the hypothesis that the accumulation of these substances, such as bile acids, may result from reduced clearance from the brain. In a rat model of chronic liver disease with minimal HE (the bile duct ligation [BDL] model), we used emerging dynamic contrast-enhanced MRI and mass-spectroscopy techniques to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from the brain. Immunofluorescence of aquaporin-4 (AQP4) and behavioural experiments were also performed. We identified discrete brain regions (olfactory bulb, prefrontal cortex and hippocampus) of altered glymphatic clearance in BDL rats, which aligned with cognitive/behavioural deficits. Reduced AQP4 expression was observed in the olfactory bulb and prefrontal cortex in HE, which could contribute to the pathophysiological mechanisms underlying the impairment in glymphatic function in BDL rats. This study provides the first experimental evidence of impaired glymphatic flow in HE, potentially mediated by decreased AQP4 expression in the affected regions. The 'glymphatic system' is a newly discovered brain-wide pathway that facilitates clearance of various substances that accumulate in the brain due to its activity. This study evaluated whether the function of this system is altered in a model of brain dysfunction that occurs in cirrhosis. For the first time, we identified that the clearance of substances from the brain in cirrhosis is reduced because this clearance system is defective. This study proposes a new mechanism of brain dysfunction in patients with cirrhosis and provides new targets for therapy.


Dysfunctional cognitions, attributional style, and depression in bulimia.
A group of 44 bulimic women (DSM-III) as well as 38 women with no indication of an eating disorder, comparable with respect to age, weight and height, were studied by means of the Beck Depression Inventory (BDI), the Dysfunctional Attitude Scale (DAS), the Attributional Style Questionnaire (ASQ), and an Eating Disorder Questionnaire (EDQ). Bulimics showed significantly higher BDI, DAS and ASQ (bad events) scores, respectively. In both groups BDI scores were significantly correlated with DAS and ASQ (bad events) results. BDI was highly predictive of severity of bulimia while no significant prediction was obtained from either DAS or ASQ (bad events) scores. The findings provide first evidence that dysfunctional attitudes and depressive attributional style are predominant in bulimic women but at the same time are not necessarily predictive of the severity of the disorder.


Spinal and cranial motor nerve roots in amyotrophic lateral sclerosis and X-linked recessive bulbospinal muscular atrophy: morphometric and teased-fiber study.
Amyotrophic lateral sclerosis (ALS) and adult onset X-linked recessive bulbospinal muscular atrophy (SPMA), constituting the category of adult onset form of motor neuron disease, were analyzed on motor nerve roots. The results of morphometric analysis on ventral spinal roots (VSR) of all spinal segments from ALS and SPMA revealed the following three findings: (1) the large-myelinated alpha-motoneuron fibers were markedly decreased in number throughout all segments; (2) thin-myelinated autonomic preganglionic fibers were almost completely preserved; (3) small-intermediate-myelinated fibers which are considered to correspond to gamma-motoneuron fibers were generally well preserved in ALS, but decreased by one-half to one-third in SPMA. However, all the components of the nerve roots of the oculomotor, trochlear, and abducent nerves were completely preserved in both ALS and SPMA. Moreover, the teased-fiber study showed that the regenerating-sprouting process rarely occurred in the VSR of ALS and SPMA. The present study suggested that the site of the primary lesion seems to be in the alpha-motoneuron fibers in motor neuron diseases, such as ALS or SPMA. However, the marked discrepancy in the pathologic change in the alpha-motoneuron fibers in the VSR and the nerve roots innervating the external ocular muscles was noteworthy.


The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age.
What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. This study was a prospective study including 193 healthy women of reproductive age. Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.


A double-orifice tricuspid valve associated with a divided right atrium.
Right atrioventricular valve duplication is a rare congenital anomaly with only isolated cases of a double-orifice tricuspid valve having been described. This article presents a case of the surgical repair of a double-orifice tricuspid valve associated with a divided right atrium, a ventricular septal defect, and Wolff-Parkinson-White syndrome.


Atrophy of the pedunculopontine nucleus region in patients with sleep-predominant seizures: A voxel-based morphometry study.
Non-rapid eye movement (NREM) sleep increases interictal epileptiform discharges and frequency of seizures, whereas REM sleep suppresses them. The pedunculopontine nucleus (PPN), one of the REM sleep-modulating structures, is postulated to have a potent antiepileptogenic role. We asked if patients with sleep-predominant seizures (SPS) show volume changes in the region of the PPN compared to those with seizures occurring during awake state only (nSPS). The volume of the PPN region was assessed in patients with SPS, those with nSPS, and healthy volunteers, through voxel-based morphometry and automated, nonbiased region of interest (ROI) analysis of T1 magnetic resonance (MR) images. The volume of PPN region was statistically smaller in patients with SPS (n = 33) than in those with nSPS (n = 40) and healthy controls (n = 30) after controlling for covariates. These results suggest that a structural change in the PPN may be associated with sleep-predominant timing of seizure occurrence. Our findings might help understand the intervening pathomechanism that lies between the human sleep-wake cycle and epilepsy.


Selecting the optimal nutrients recovery application for a biogas slurry based on its characteristics and the local environmental conditions: A critical review.
Digestate (effluent of biogas plants) became the main bottleneck for biogas industry expansion because it often exceeds the capacity of surrounding croplands as fertilizer. Nutrients recovery from digestate is a promising solution for closing nutrients cycles and generating high value-added byproducts. In fact, numerous nutrients recovery technologies were reported and utilized for that purpose. However, each technology has optimum working conditions, while digestates have different characteristics due to the different substrates, digestion conditions, and handling methods. On the other hand, no protocol has been reported yet for selecting the optimal nutrients recovery technology or sequenced technologies for different digestates regarding their characteristics and the surrounding environmental conditions. In this study, an interactive flowchart was suggested and discussed for selecting the most appropriate technology or sequential techniques among the different alternatives. The whole digestate utilization technologies, solid-liquid separation technologies, liquid and solid processing technologies were included.


GluR2-R4 AMPA subunit study in rat vestibular nuclei after unilateral labyrinthectomy: an in situ and immunohistochemical study.
In the present investigation, we address the question of whether the expression of GluR2-R4 subunits mRNAs and GluR2 and GluR4 subunits protein of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors are modulated in the vestibular nuclei following unilateral labyrinthectomy. Specific GluR2-R4 radioactive oligonucleotides were used to probe sections of rat vestibular nuclei according to in situ hybridization methods. The signal was detected by means of film or emulsion photography. GluR2 and GluR4 subunit expression were also measured in control and operated rats by use of specific monoclonal GluR2 and GluR4 antibodies. Animals were killed at different stages following the lesion: 1, 3 or 8 days for the in situ hybridization study and 4 and 8 days for the immunohistochemical study. In normal animals, several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei expressed all the GluR2, GluR3 and GluR4 subunit mRNAs. Moreover, numerous vestibular nuclei neurons are endowed with AMPA receptors containing the GluR2 and the GluR4 subunits. In unilaterally labyrinthectomized rats, no asymmetry could be detected on autoradiographs between the two medial vestibular nuclei probed with the GluR2 and the GluR4 oligonucleotide probes regardless of the delay following the lesion. However, compared to control, a bilateral decrease (-22%) in GluR3 gene expression was observed in the medial vestibular nuclei 3 days after the lesion followed by a return to normal at day 8 post-lesion. No significant asymmetrical changes in the density of GluR2- and GluR4-immunopositive cells could be detected between the intact and deafferented sides in any part of the vestibular nuclear complex and at any times (day 4 or day 8) following the lesion. Our data show that the removal of glutamatergic vestibular input induced an absence of modulation of GluR2 and GluR4 gene and subunits expression. This demonstrates that GluR2 and GluR4 expression do not play a role in the recovery of the resting discharge of the deafferented medial vestibular nuclei neurons and consequently in the functional restoration of the static postural and oculomotor deficits. The functional role of the slight and bilateral GluR3 mRNA decrease in the vestibular nuclei remains to be elucidated.


Isolation of rabies virus from bats in Bolivia.
Rabies virus was isolated from apparently normal blood-sucking (Desmodus rotundus) and insectivorous (Artibeus planirostris) bats caught in Bolivia. The virus was identified by immunofluorescence, biological and sero-neutralisation tests.


Differential Effects of Early Adversity and Posttraumatic Stress Disorder on Amygdala Reactivity: The Role of Developmental Timing.
Posttraumatic stress disorder (PTSD) is associated with altered processing of threat-related stimuli. Neurobiological models implicate right amygdala hyperreactivity in these alterations, but this potential biomarker also has been observed in individuals exposed to adverse childhood experiences (ACEs) (i.e., abuse and neglect) without psychopathology. Separation of the differential contributions of PTSD and ACEs to amygdala reactivity might benefit from incorporating the developmental timing of the events. We conducted comprehensive retrospective interviews assessing ACEs for each life year between the ages of 1 and 17 years in a sample of 60 women exposed to trauma (including 34 participants with PTSD and 26 healthy participants). Functional magnetic resonance imaging was used to extract amygdala reactivity to threatening versus neutral scenes. Amygdala reactivity was predicted from PTSD diagnosis, total ACE severity, and ACE severity by life year using random forest regression. PTSD and ACEs significantly predicted reactivity in the right amygdala (R2 = 7%) but did not explain variance in the left amygdala. ACEs during both a prepubertal (ages 3 and 4) and a postpubertal (ages 16 and 17) period emerged as particularly predictive, while total ACE severity did not contribute to prediction. Follow-up analyses revealed a positive relationship between amygdala activity and PTSD and a negative relationship between amygdala activity and ACEs during predictive life years. The opposing effects of PTSD and ACEs caution against simplistic etiological and diagnostic interpretations of amygdala function. The identification of potentially sensitive periods for the effects of ACEs on amygdala reactivity to threat may help to uncover interactions between traumatization and development of PTSD.


A Systems Factorial Technology dataset using visual and tactile cues to guide balance.
This data contains response times for 19 participants from a Systems Factorial Technology paradigm using visual and vibratory cues, as described in "The Balance Between Vision and Touch [1]". These cues could indicate one of four directions, and participants responded by shifting their weight in that direction. This was detected using a Wii Balance Board. Each participant has 720 trials: 1/3 with only a haptic cue, 1/3 with only vision, and 1/3 with both. Cues were equally divided into high and low salience versions.


Gene Gun DiOlistic Labelling of Retinal Ganglion Cells.
Gene gun DiOlistic labelling enables the detailed visualization of retinal ganglion cells (RGCs) dendritic structure. Since the level of labelling is independent of cellular health, it is useful for the characterization of neuronal structure in degenerating neurons where expressed reporters may be inadequate. The method uses compressed helium gas to fire tungsten or gold microparticles coated in carbocyanine dyes (DiD, DiI, DiO) into flat mounted retinas. Here we describe the methods to optimize labelling and ensure a high yield of adequately labelled cells, with a focus on retinal ganglion cells.


Cue-framing effects in source remembering: a memory misattribution model.
During source remembering, selectively emphasizing one source in the retrieval query "Is this item from Source A?" can yield different accuracy than emphasizing the alternate source in "Is this item from Source B?" even if those are the only two possible origins. One account of this cue-framing effect holds that it reflects different active monitoring strategies encouraged by the two cue frames. An item memory misattribution (IMM) model instead assumes that this effect reflects the uncontrolled use of item recognition during confirmatory source judgments, and an IMM model simulation predicted a quantitative relationship between recognition levels and the cue-framing effect. Experiments 1 and 3 confirmed these predictions by using study repetitions to manipulate recognition levels, and Experiments 2 and 3 also demonstrated the effect with new source tasks not previously considered. The data suggest that, in addition to qualitative monitoring strategies, subjects also use the availability of item memory in a heuristic fashion during confirmatory source attributions.


Effect of highly branched α-glucans synthesized by dual glycosyltransferases on the glucose release rate.
Increasing α-1,6 linkages in starch molecules generates a large amount of α-limit dextrins (α-LDx) during α-amylolysis, which decelerate the release of glucose at the intestinal α-glucosidase level. This study synthesized highly branched α-glucans from sucrose using Neisseria polysaccharea amylosucrase and Rhodothermus obamensis glycogen branching enzyme to enhance those of slowly digestible property. The synthesized α-glucans (Mw: 1.7-4.9 × 107 g mol-1) were mainly composed of α-1,4 linkages and large proportions of α-1,6 linkages (7.5%-9.9%). After treating the enzymatically synthesized α-glucans with the human α-amylase, the quantity of branched α-LDx (36.2%-46.7%) observed was higher than that for amylopectin (26.8%) and oyster glycogen (29.1%). When the synthetic α-glucans were hydrolyzed by mammalin α-glucosidases, the glucose generation rate decreased because the amount of embedded branched α-LDx increased. Therefore, the macro-sized branched α-glucans with high α-LDx has the potential to be used as slowly digestible material to attenuate postprandial glycemic response.


The effect of isobutylmethylxanthine on the photoresponse and phosphorylation of phosphatidylinositol in octopus retina.
The effect of isobutylmethylxanthine on the photoresponse and the phosphorylation of phosphatidylinositol was studied. The recovery of photoresponse after a bright flash was greatly altered by the addition of isobutylmethylxanthine. Phosphatidylinositol phosphorylation, assessed by the incorporation of label from [gamma-32P]ATP, was influenced by isobutylmethylxanthine. Incorporation of 32P was decreased into diphosphoinositide and triphosphoinositide, and increased into phosphatidic acid. These changes were interpreted by introducing a parameter, phi, calcium charge of the plasma membrane.


Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.
Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.


Intramedullary bone tissue reaction of ion-releasing resin-modified glass-ionomer restoration versus two calcium silicate-based cements: an animal study.
This comparative study was conducted to assess the intramedullary bone tissue reaction of an ion-releasing resin modified glass-ionomer cement with claimed bioactivity (ACTIVA bioactive resin) restorative material versus Mineral Trioxide Aggregate High Plasticity (MTA HP) and bioceramic putty iRoot BP Plus. Fifty-six adult male Wistar rats were assigned into 4 equal groups (14 rats each). A surgical intramedullary bi-lateral tibial bone defects were performed in rats of the control group I (GI) and left without any treatment to be considered as controls (n = 28). The rats of groups II, III and IV were handled as group I except that the tibial bone defects were filled with ACTIVA, MTA HP and iRoot BP, respectively. In all groups, rats were euthanized after one month and specimens were processed to histological investigation, SEM examination and EDX elemental analysis. In addition, semi-quantitative histomorphometric scoring system was conducted for the following parameters; new bone formation, inflammatory response, angiogenesis, granulation tissue, osteoblasts and osteoclasts. The clinical follow-up outcome of this study revealed the recovery of rats after 4 days post-surgical procedure. It was observed that the animal subjects returned to their routine activities, e.g., walking, grooming and eating. The rats showed normal chewing efficiency without any weight loss or postoperative complications. Histologically, the control group sections showed scanty, very thin, new bone trabeculae of immature woven type located mostly at the peripheral part of the tibial bone defects. These defects exhibited greater amount of thick bands of typically organized granulation tissue with central and peripheral orientation. Meanwhile, bone defects of ACTIVA group showed an empty space surrounded by thick, newly formed, immature woven bone trabeculae. Moreover, bone defects of MTA HP group were partially filled with thick newly formed woven bone trabeculae with wide marrow spaces presented centrally and at the periphery with little amount of mature granulation tissue at the central part. The iRoot BP Plus group section exhibited an observable woven bone formation of normal trabecular structures with narrow marrow spaces presented centrally and at the periphery showed lesser amount of well-organized/mature granulation tissue formation. Kruskal Wallis test revealed total significant differences between the control, ACTIVA, MTAHP and iRoot BP Plus groups (p < 0.05). Meanwhile, Mann-Whitney U test showed significant difference between control and ACTIVA groups, Control and MTA HP groups, control and iRoot BP Plus groups. ACTIVA and MTA HP groups, ACTIVA and iRoot BP Plus (p ˂ 0.05) with no significant difference between MTA HP and iRoot BP Plus (p > 0.05). The elemental analysis outcome showed that the lesions of the control group specimens were filled with recently created trabecular bone with limited marrow spaces. EDX tests (Ca and P analysis) indicated a lower degree of mineralization. Lower amounts of Ca and P was expressed in the mapping analysis compared with other test groups. Calcium silicate-based cements induce more bone formation when compared to an ion-releasing resin modified glass-ionomer restoration with claimed bioactivity. Moreover, the bio-inductive properties of the three tested materials are likely the same. Clinical significance: bioactive resin composite can be used as a retrograde filling.


Effect of estrous cycle phase on clinical pathology values in beagle dogs.
In dogs, the diestrus phase is considerably longer than in most domestic animals, and is characterized by high circulating progesterone concentrations that may influence clinical pathology values. The objective of this retrospective study was to investigate differences in clinical pathology data in dogs in diestrus compared with data from dogs in all other phases of the estrous cycle. Phase of the estrous cycle was determined by histologic evaluation of reproductive tissues from 86 control female Beagles that had participated in 23 toxicity studies. Serum biochemical, hematologic, and urinalysis values from dogs in diestrus were compared with data from dogs in all other estrous cycle phases using a 2-tailed t-test. In Beagles in diestrus (n = 38), serum cholesterol concentrations and eosinophil counts were 35% (P < .0001) and 45.8% (P = .0035) higher, respectively, than for Beagles in all other phases of the estrous cycle (n = 48). Furthermore, Beagles in diestrus had 14% lower AST activity (P = .0011), 1% lower chloride concentration (P = .0224), 7.8% lower hemoglobin concentration (P < .0001), 7.8% lower RBC count (P < .0001), and 7.6% lower hematocrit (P < .0001) compared with female dogs in all other phases of the estrous cycle. Urine values did not differ significantly between groups. Differences in clinical pathology values between dogs in different phases of the estrous cycle could potentially confound interpretation of data in toxicity studies, which often have small group sizes. Interpretation of clinical pathology data in female dogs should be performed with due consideration given to the phase of the estrous cycle.


Gastrointestinal perforation in infants.
We found that the mortality rate was no greater in patients with necrotizing enterocolitis complicated by perforation compared with the rate in those with other causes of perforation in similar weight classes. Iatrogenic injuries had a 50 percent mortality rate in all gestational age and birth weight categories and, therefore, great caution and surveillance are of utmost importance when using invasive monitoring and therapeutic modalities to prevent this cause of perforation. Term infants had a preponderance of mechanical causes of perforation which mainly occurred in the foregut and proximal midgut, whereas premature infants have a preponderance of asphyxial or ischemic events underlying perforations which mainly occurred in the ileocolic region and were often associated with necrotizing enterocolitis. Although neonatal intestinal perforation is a catastrophic event, the very premature infant weighing less than 1,000 g at birth is at significantly greatest risk. The discouraging 20 percent survival rate in the less than 1,000 g premature infants presents a challenge to the surgeon, since the overall survival rate was 59 percent and the term infants had a 78 percent survival rate. A substantial share of the mortality in the infants weighing less than 1,000 g at birth relates to the occurrence of intracerebral hemorrhage and bronchopulmonary dysplasia. Vigorous medical and surgical approaches can be used to salvage premature infants in all weight classes with gastrointestinal perforation.


Structure-antitumour activity relationships for new platinum complexes.
Fourteen platinum (Pt) coordination complexes with different ligands, which include both Pt(II) and Pt(IV) complexes, were prepared, characterized and tested for their in vitro cytotoxic effects on KB cells and for their antitumour activity against some tumour systems (L1210 and P388 leukaemia, ADJ/PC6A plasma cell tumour and Yoshida sarcoma). The majority of the ligands were derivatives of aniline or pyridine, but complexes with tranylcypromine, guanethidine and octodrine were also synthetized. Depending on cytotoxicity the Pt-compounds could be divided into 3 groups. The compounds with a high cytotoxicity (ED50 = 0.1-1 microgram/ml) were also active against L1210 and P-388 leukaemia; a correlation between cytotoxicity and antitumour activity was not always observed. In these complexes the oxidation state of the Pt appears to be critical for their activity.


Immunogenic Potential and Therapeutic Efficacy of Multi-Epitope Encapsulated Silk Fibroin Nanoparticles against Pseudomonas aeruginosa-Mediated Urinary Tract Infections.
Pseudomonas aeruginosa (P. aeruginosa) causing urinary tract infections (UTIs) are a major concern among hospital-acquired infections. The need for an effective vaccine that reduces the infections is imperative. This study aims to evaluate the efficacy of a multi-epitope vaccine encapsulated in silk fibroin nanoparticles (SFNPs) against P. aeruginosa-mediated UTIs. A multi-epitope is constructed from nine proteins of P. aeruginosa using immunoinformatic analysis, expressed, and purified in BL21 (DE3) cells. The encapsulation efficiency of the multi-epitope in SFNPs is 85% with a mean particle size of 130 nm and 24% of the encapsulated antigen is released after 35 days. The vaccine formulations adjuvanted with SFNPs or alum significantly improve systemic and mucosal humoral responses and the cytokine profile (IFN-γ, IL-4, and IL-17) in mice. Additionally, the longevity of the IgG response is maintained for at least 110 days in a steady state. In a bladder challenge, mice treated with the multi-epitope admixed with alum or encapsulated in SFNPs demonstrate significant protection of the bladder and kidneys against P. aeruginosa. This study highlights the promising therapeutic potential of a multi-epitope vaccine encapsulated in SFNPs or adjuvanted with alum against P. aeruginosa infections.


The incidence of cardiovascular events is largely reduced in patients with maximally tolerated drug therapy and lipoprotein apheresis. A single-center experience.
Lipoprotein apheresis (LA) is the elective therapy for homozygous and other forms of familial hypercholesterolemia (FH) and familial combined hypercholesterolemia (FCH), resistant/intolerant to lipid lowering drugs, and hyperlipoproteinemia(a) for which drugs are not available. To assess the effect of LA on the incidence of adverse cardiac or vascular events (ACVE) at the time period of pre-initiation of apheresis and during the LA treatment. We collected data of 30 patients (mean age 62 ± 8 years, males 73%), with FH, or FCH and cardiovascular disease on maximally tolerated lipid lowering therapy and LA treatment (median 5 years, interquartile range 3-8 years). Associated hyperlipoproteinemia(a) was present in 16/30 subjects. The LA treatment was performed biweekly as clinically indicated by dextran-sulfate or heparin-induced LDL precipitation apheresis. The ACVE incidence, before and after treatment, was evaluated by statistical analyses. The ACVE incidence occurred before and after the LA treatment inception, were 86 and 15 events respectively. Notably, 6/15 of ACVE were secondary to stent restenosis and 7/15 follow-up events occurred during the first 5 years. The AVCE rates/year were 0.58 and 0.13 respectively (p < 0.001). Our data confirm long-term efficacy and positive impact of LA on morbidity in patients with FH and FCH and atherosclerotic disease at maximally tolerated lipid lowering therapy.


Signal amplification for electrochemical immunosensing by in situ assembly of host-guest linked gold nanorod superstructure on immunocomplex.
An amplification strategy for signal tracing was developed by introducing a host-guest binding reaction into the assembly process of gold nanorods (AuNRs) superstructure. The amplification pathway firstly used a thio-β-cyclodextrin (SH-β-CD) functionalized gold nanoparticles to label signal antibody, and then in situ assembled multi-layer SH-β-CD end-functionalized AuNRs to sandwich immunocomplex on immunosensor surface by using 4,4,4,4-(21H, 23H-porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) as a bridge to achieve simple and convenient host-guest reaction. The built end-to-end AuNRs superstructure showed excellent performance for the signal amplification in connection with the electrochemical biosensing by preoxidation and then voltammetric analysis of gold element. Using α-fetoprotein as an analyte, the immunosensor was constructed by covalently binding capture antibody to chitosan-carbon nanotubes-poly(diallyldimethylammonium chloride) modified electrode. The superstructure rich in AuNRs brought an enhanced detection sensitivity of protein, which could detect α-fetoprotein in a linear range from 0.5 pg mL(-1) to 0.5 ng mL(-1) with a detection limit down to 0.032 pg mL(-1). The immunoassay exhibited good stability and acceptable reproducibility and accuracy. The in situ superstructure assembly could be extended to other labeled recognition systems, providing a promising novel avenue for signal amplification and potential applications in bioanalysis and clinical diagnostics.


Analysis of anticancer drugs: a review.
In the last decades, the number of patients receiving chemotherapy has considerably increased. Given the toxicity of cytotoxic agents to humans (not only for patients but also for healthcare professionals), the development of reliable analytical methods to analyse these compounds became necessary. From the discovery of new substances to patient administration, all pharmaceutical fields are concerned with the analysis of cytotoxic drugs. In this review, the use of methods to analyse cytotoxic agents in various matrices, such as pharmaceutical formulations and biological and environmental samples, is discussed. Thus, an overview of reported analytical methods for the determination of the most commonly used anticancer drugs is given.


Heart Rate Reduction Improves Right Ventricular Function and Fibrosis in Pulmonary Hypertension.
The potential benefit of heart rate reduction (HRR), independent of β-blockade, on right ventricular (RV) function in pulmonary hypertension (PH) remains undecided. We studied HRR effects on RV fibrosis and function in PH and RV pressure-loading models. Adult rats were randomized to 1) sham controls, 2) monocrotaline (MCT)-induced PH, 3) SU5416 + hypoxia (SUHX)-induced PH, or 4) pulmonary artery banding (PAB). Ivabradine (IVA) (10 mg/kg/d) was administered from 2 weeks after PH induction or PAB. Exercise tolerance, echocardiography, and pressure-volume hemodynamics were obtained at a terminal experiment 3 weeks later. RV myocardial samples were analyzed for putative mechanisms of HRR effects through fibrosis, profibrotic molecular signaling, and Ca++ handling. The effects of IVA versus carvedilol on human induced pluripotent stem cell-derived cardiomyocytes beat rate and relaxation properties were evaluated in vitro. Despite unabated severely elevated RV systolic pressures, IVA improved RV systolic and diastolic function, profibrotic signaling, and RV fibrosis in PH/PAB rats. RV systolic-elastance (control, 121 ± 116; MCT, 49 ± 36 vs. MCT+IVA, 120 ± 54; PAB, 70 ± 20 vs. PAB+IVA, 168 ± 76; SUHX, 86 ± 56 vs. SUHX +IVA, 218 ± 111; all P < 0.05), the time constant of RV relaxation, echo indices of RV function, and fibrosis (fibrosis: control, 4.6 ± 1%; MCT, 13.4 ± 6.5 vs. MCT+IVA, 6.7 ± 2.6%; PAB, 11.4 ± 4.5 vs. PAB+IVA, 6.4 ± 5.1%; SUHX, 10 ± 4.6 vs. SUHX+IVA, 3.9 ± 2.2%; all P < 0.001) were improved by IVA versus controls. IVA had a dose-response effect on induced pluripotent stem cell-derived cardiomyocytes beat rate by delaying Ca++ loss from the cytoplasm. In experimental PH or RV pressure loading, HRR improves RV fibrosis, function, and exercise endurance independent of β-blockade. The balance between adverse tachycardia and bradycardia requires further study, but judicious HRR may provide a promising strategy to improve RV function in clinical PH.


Immune modulation following immunization with polyvalent vaccines in dogs.
A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer.


SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: Clinical implications.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections result in the temporary loss of smell and taste in about one third of confirmed cases. We used immunohistochemistry to confirm the presence of ACE2, NRP1 and TMPRSS2 in two cranial nerves (IX and X) that mediate taste where they leave/join the medulla. Samples from three (two paraffin embedded and one frozen) postmortem samples were studied (facial (VII) nerve was not available). We also performed immunohistochemistry using the same antibodies in two human cell lines (oligodendrocytes and fibroblasts), and we isolated RNA from one nerve and performed PCR to confirm the presence of the mRNAs that encode the proteins visualized. All three of the proteins (ACE-2, NRP1 and TMPRSS2) required for SARS-CoV-2 infections appear to be present in all cellular components (Schwann cells, axons, vascular endothelium, and connective tissue) of the human IXth and Xth nerves near the medulla. We also found their mRNAs in the nerve and in human oligodendrocytes and fibroblasts which were stained by antibodies directed at the three proteins examined. Infection of the IXth and Xth nerves by the SARS-CoV-2 virus is likely to cause the loss of taste experienced by many Covid patients. Migration of the virus from the oral cavity through these nerves to brainstem respiratory centers might contribute to the problems that patients experience. This study was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research (NIDCR), NIH (intramural project no. ZDE000755-01), and the Human Brain Tissue Bank, Semmelweis University, Budapest, Hungary from the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002).


A lipid peroxidation-derived aldehyde, 4-hydroxy-2-nonenal and omega 6 fatty acids contents in meats.
4-Hydroxy-trans-2-nonenal (HNE) and omega 6 fatty acids contents were analyzed in pork and beef. The HNE contents in beef (n = 4) and pork (n = 7) were 14.0-150 nmol/g and 1.0-152 nmol/g, respectively. Furthermore, a linear correlation between the content of HNE and the content of total omega 6 fatty acids, linoleic acid, or arachidonic acid was observed in pork.


Gamma knife thalamotomy for Parkinson disease and essential tremor: a prospective multicenter study.
No prospective study of gamma knife thalamotomy for intractable tremor has previously been reported. To clarify the safety and optimally effective conditions for performing unilateral gamma knife (GK) thalamotomy for tremors of Parkinson disease (PD) and essential tremor (ET), a systematic postirradiation 24-month follow-up study was conducted at 6 institutions. We present the results of this multicenter collaborative trial. In total, 72 patients (PD characterized by tremor, n = 59; ET, n = 13) were registered at 6 Japanese institutions. Following our selective thalamotomy procedure, the lateral part of the ventralis intermedius nucleus, 45% of the thalamic length from the anterior tip, was selected as the GK isocenter. A single 130-Gy shot was applied using a 4-mm collimator. Evaluation included neurological examination, magnetic resonance imaging and/or computerized tomography, the unified Parkinson's disease rating scale (UPDRS), electromyography, medication change, and video observations. Final clinical effects were favorable. Of 53 patients who completed 24 months of follow-up, 43 were evaluated as having excellent or good results (81.1%). UPDRS scores showed tremor improvement (parts II and III). Thalamic lesion size fluctuated but converged to either an almost spherical shape (65.6%), a sphere with streaking (23.4%), or an extended high-signal zone (10.9%). No permanent clinical complications were observed. GK thalamotomy is an alternative treatment for intractable tremors of PD as well as for ET. Less invasive intervention may be beneficial to patients.


Antioxidation, anti-inflammation and anti-fibrosis effect of phosphorylated polysaccharides from Pleurotus djamor mycelia on adenine-induced chronic renal failure mice.
The mycelia polysaccharides (MPS) from Pleurotus djamor were prepared and purified by anion exchange column chromatography, and the phosphate content of phosphorylated MPS (PMPS) was 15.22 ± 0.37%. FT-IR spectra, HPLC and 1H and 13C-NMR results showed the PMPS contained α-pyranose structure and the peak area percentage composition of galacturonic acid and glucose were 13.01% and 85.82%, respectively. Animal experiment investigated the antioxidant, anti-inflammation, anti-fibrosis effects of PMPS on kidney in adenine-induced chronic renal failure (CRF) mice. All results including serum biochemical indices, histopathological observation, qRT-PCR, western blotting, immunohistochemical staining manifested the kidney injury could be remitted by PMPS interventions. This experiment suggested that PMPS could remit CRF and other kidney injury related diseases as one kind of dietary supplements and functional foods without toxic side effects.


Cardiovascular magnetic resonance imaging in congenital heart disease as an alternative to diagnostic invasive cardiac catheterization: a single center experience.
The study aims to assess whether the increasing use of cardiovascular magnetic resonance imaging in place of diagnostic cardiac catheterization in the management of pediatric patients with congenital heart disease has had an impact on pediatric cardiac care. Retrospective analysis of data was used. The study was performed at the Evelina Children's Hospital Cardiology Department. PATIENTS. : Elective diagnostic cardiac catheterization or magnetic resonance imaging (MRI) from 2005-2010 are included (n = 896). Indication, length of stay, and incidence of complications were recorded. In cases used to plan surgery, 30-day survival following the procedure was recorded. Surgical outcomes were compared between the two groups. Surgical outcomes planned using MRI were compared with national outcomes from Congenital Cardiac Audit Database. For catheterizations (50 patients, [31 male, median age 3 years, interquartile range 1 to 12]), median hospital stay was 1 day (interquartile range 0 to 3), and complications occurred in 11 (22%). Median hospital stay for MRI (846 patients [517 male, median age 3 years, interquartile range 0 to 9]) was significantly shorter: 0 days (interquartile range 0 to 1, P <.001), with fewer complications (16 [1.9%], P <.0001). Twenty-four catheter and 283 MRI patients underwent surgery within 18 months. One catheter patient (2.0%) and four MRI patients (1.4%) died within 30 days (P =.48). Replacing catheterization with cardiovascular magnetic resonance imaging has resulted in reduced rates of complication and shorter hospital stays without a significant impact on surgical outcome.


Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.
The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.


High airway-to-blood transport of an opioid tetrapeptide in the isolated rat lung after aerosol delivery.
The airway-to-blood absorption of the mu-selective opioid tetrapeptide agonist Tyr-D-Arg-Phe-Phe-NH(2) (MW 631) was investigated in the isolated, perfused, and ventilated rat lung model. The lung metabolism of the peptide was compared after airway and vascular delivery. The concentrations of the parent tetrapeptide and five of its metabolites in the perfusate and in bronchoalveolar lavage fluid were analyzed by LC-MS. The metabolism of the peptide was higher after delivery to the airways compared to vascular delivery. However, the tetrapeptide was highly transported from the air-to-blood side to an extent of 47.8 +/- 10.7% in 2 h. In conclusion, the results prompt investigations of the pulmonary route as a successful alternative to parenteral delivery for this tetrapeptide.


An evaluation of tannery industry wastewater treatment sludge gasification by artificial neural network modeling.
This paper reports on the calorific value of synthetic gas (syngas) produced by gasification of dewatered sludge derived from treatment of tannery wastewater. Proximate and ultimate analyses of samples were performed. Thermochemical conversion alters the chemical structure of the waste. Dried air was used as a gasification agent at varying flow rates, which allowed the feedstock to be quickly converted into gas by means of different heterogeneous reactions. A lab-scale updraft fixed-bed steel reactor was used for thermochemical conversion of sludge samples. Artificial neural network (ANN) modeling techniques were used to observe variations in the syngas related to operational conditions. Modeled outputs showed that temporal changes of model predictions were in close accordance with real values. Correlation coefficients (r) showed that the ANN used in this study gave results with high sensitivity.


HSD17B6 delays type 2 diabetes development via inhibiting SREBP activation.
The SREBP/SCAP/INSIG complex plays an essential role in SREBP activation and de novo lipogenesis. Whether the activation process is affected by hydroxysteroid 17-beta dehydrogenase 6 (HSD17B6) remains unknown. SREBP's transcriptional activities were analyzed using an SRE-luciferase (SRE-luc) reporter in 293T cells, Huh7 hepatoma cells, and primary human hepatocytes following a variety of conditions, including ectopic expression of HSD17B6, HSD17B6 mutants defective in its enzymatic activities, knockdown of HSD17B6, and cholesterol starvation. The interaction between HSD17B6 and SREBP/SCAP/INSIG complex was analyzed in 293T cells, Huh7 cells and mouse liver upon ectopic expression of HSD17B6 and its mutants; the interaction was also analyzed using endogenous proteins. The impacts of HSD17B6 on SREBP target expression, glucose tolerance, diet-induced obesity, and type 2 diabetes (T2D) were examined using Huh7 cells in vitro, and with C57BL/6 and NONcNZO10/LtJ T2D mice in vivo. HSD17B6 binds to the SREBP/SCAP/INSIG complex and inhibits SREBP signaling in cultured hepatocytes and mouse liver. Although HSD17B6 plays a role in maintaining the equilibrium of 5α-dihydrotestosterone (DHT) in the prostate, a mutant defective in androgen metabolism was as effective as HSD17B6 in inhibiting SREBP signaling. Hepatic expression of both HSD17B6 and the defective mutant improved glucose intolerance and reduced hepatic triglyceride content in diet-induced obese C57BL/6 mice, while hepatic knockdown of HSD17B6 exacerbated glucose intolerance. Consistent with these results, liver-specific expression of HSD17B6 in a polygenic NONcNZO10/LtJ T2D mice reduced T2D development. Our study unveils a novel role of HSD17B6 in inhibiting SREBP maturation via binding to the SREBP/SCAP/INSIG complex; this activity is independent of HSD17B6's sterol oxidase activity. Through this action, HSD17B6 improves glucose tolerance and attenuates the development of obesity-induced T2D. These findings position HSD17B6 as a potential therapeutic target for T2D therapy.


First case report of splenomegaly with splenic infarction due to aortic graft infection.
Diagnosis of aortic graft infections (AGI) is challenging. Here, we report a case of AGI with splenomegaly and splenic infarction. A 46-year-old man who underwent total arch replacement for Stanford type A acute aortic dissection one year prior presented to our department with fever, night sweat, and a 20-kg weight loss over several months. Contrast-enhanced computed tomography (CT) revealed splenic infarction with splenomegaly, fluid collection, and thrombus around the stent graft. Positron emission tomography-CT (PET-CT) revealed abnormal 18F-fluorodeoxyglucose uptake in the stent graft and spleen. Transesophageal echocardiography revealed no vegetations. The patient was diagnosed with an AGI and underwent graft replacement. Blood and tissue cultures in the stent graft yielded Enterococcus faecalis. After the surgery, the patient was successfully treated with antibiotics. Splenic infarction and splenomegaly are the clinical findings of endocarditis but are rare in graft infection. These findings could be helpful to diagnose graft infections, which is often challenging.


Efficacy of medical treatment of schistosomal obstructive uropathy as determined by 131I-Hippuran renography.
Ten male patients with obstructive uropathy secondary to Schistosoma haematobium and with associated bacteriuria were evaluated with serial urograms, renograms and renal function tests (endogenous creatinine clearance, maximal urinary concentration and total hydrogen ion excretion) before and after medical treatment. The mean duration of follow-up was 4.2 months. Significant improvement was observed in the renograms and the renal function tests while the degree of obstructive uropathy as determined by urography remained essentially unchanged. Thus the renogram can be a more sensitive test for evaluating the efficacy of treatment in patients with schistosomal obstructive uropathy.


Chlordiazepoxide, an anxiolytic benzodiazepine, impairs place navigation in rats.
There are separate proposals that the hippocampus is involved in 'spatial memory' and in the control of 'anxiety'. Despite a larger number of common effects of anxiolytic drugs and hippocampal lesions, no effect of anxiolytic drugs has yet been reported in those spatial tasks which are particularly sensitive to the effects of hippocampal lesions. The present study addresses this issue. Separate groups of rats were treated, i.p., with 5 mg/kg chlordiazepoxide (an anxiolytic benzodiazepine), 1 mg/kg scopolamine (a muscarinic antagonist which has previously been shown to impair spatial learning) and a saline placebo. They were then trained to find a platform which was hidden in a constant location just under the surface of opaque water in a swimming pool. Separate groups of rats were trained with 4 trials per day and with 1 trial per day. Number of trials per day did not significantly influence the effects of the drugs. Chlordiazepoxide and scopolamine produced similar degrees of impairment in spatial learning to each other--but less impairment than has previously been reported with hippocampal lesions. The effectiveness of the anxiolytic drug chlordiazepoxide in the swimming pool, a specifically spatial task, suggests that the opposing concepts of 'spatial memory' and 'anxiety' which have been used previously to describe hippocampal function may represent different aspects of a unitary concept.


Aldol reactions of the trans-o-hydroxybenzylidenepyruvate hydratase-aldolase (tHBP-HA) from Pseudomonas fluorescens N3.
In this paper, a recombinant trans-o-hydroxybenzylidenepyruvate hydratase-aldolase (tHBP-HA) of Pseudomonas fluorescens N3 was used as a new catalyst for aldol condensation reactions. The reaction of some aldehydes with a different electronic activation catalyzed by tHBP-HA is presented and discussed together with some hints on the product structure. The enzyme is strictly pyruvate-dependent but uses different aldehydes as acceptors. The structure of the products is highly dependent on the electronic characteristics of the aldehyde. The results are interesting for both their synthetic importance and the mechanism of the formation of the products. Not only the products obtained and the recognition power are reported, but also some characteristics of its mechanism are analyzed. The results clearly show that the enzyme is efficiently prepared, purified, and stored, that it recognizes many different substrates, and that the products depend on the substrate electronic nature.


Single-cell transcriptomic profiling of microvascular endothelial cell heterogeneity in congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) is a neonatal anomaly that includes pulmonary hypoplasia and hypertension. We hypothesized that microvascular endothelial cell (EC) heterogeneity is different in CDH lungs and related to lung underdevelopment and remodeling. To test this, we evaluated rat fetuses at E21.5 in a nitrofen model of CDH to compare lung transcriptomes among healthy controls (2HC), nitrofen-exposed controls (NC) and nitrofen-exposed subjects with CDH. Single-cell RNA sequencing with unbiased clustering revealed 3 distinct microvascular EC clusters: a general population (mvEC), a proliferative population and a population high in hemoglobin. Only the CDH mvEC cluster had a distinct inflammatory transcriptomic signature as compared to the 2HC and NC endothelial cells, e.g. greater activation and adhesion of inflammatory cells and production of reactive oxygen species. Furthermore, CDH mvECs had downregulated Ca4, Apln and Ednrb gene expression. Those genes are markers for ECs important to lung development, gas exchange and alveolar repair (mvCa4+). mvCa4+ ECs were reduced in CDH (2HC [22.6%], NC [13.1%] and CDH [5.3%], p < 0.0001). Overall, these findings identify transcriptionally distinct microvascular endothelial cell clusters in CDH, including the distinctly inflammatory mvEC cluster and the depleted group of mvCa4+ ECs, which together may contribute to pathogenesis.


Hypothalamic-Pituitary-Adrenal Axis Responses in Women with Endometriosis-Related Chronic Pelvic Pain.
Some chronic pain conditions and comorbidities suppress the hypothalamic-pituitary-adrenal (HPA) axis and response to dynamic testing. We measured HPA axis responses to corticotropin-releasing hormone (CRH) administration in relation to chronic pelvic pain and endometriosis. In a cross-sectional study of women (n = 54) with endometriosis-associated chronic pelvic pain (n = 22), chronic pelvic pain alone (n = 12), or healthy volunteers (n = 20), adrenocorticotropic-releasing hormone (ACTH) and cortisol levels were measured at 0, 15, 30, and 45 min after intravenous ovine CRH administration. ACTH and cortisol delta (peak-baseline) and area under the curve (AUC) were compared by study group and assessed for association with race and menstrual and non-menstrual pain severity. HPA axis responses did not differ among the racially diverse groups or in those with pain compared with healthy volunteers. However, when stratified by race, ACTH delta (129.9 ± 130.7 vs. 52.5 ± 66.0 pg/mL; p = 0.003), ACTH AUC (4813 ± 4707 vs. 2290 ± 2900 min*pg/mL; p = 0.013), and cortisol delta (26.3 ± 21.5 vs. 13.2 ± 9.7 μg/mL; p = 0.005) were significantly higher in black (n = 10) than predominately white (non-black) subjects (n = 44; 39/44 white). In analyses among primarily white (non-black) women, greater menstrual pain severity was associated with blunted ACTH delta (p = 0.015) and cortisol delta (p = 0.023), and greater non-menstrual pain severity with blunted cortisol delta (p = 0.017). Neuroendocrine abnormalities in women with chronic pelvic pain may differ by pain manifestations and may vary by race. The higher HPA axis response in black women merits investigation in pelvic pain studies stratified by race. In white (non-black) women experiencing pain, a blunted response was related to pain severity suggesting pain affects women independently of endometriosis lesions.


High school cigarette smoking and post-secondary education enrollment: Longitudinal findings from the NEXT Generation Health Study.
The inverse association between smoking and educational attainment has been reported in cross-sectional studies. Temporality between smoking and education remains unclear. Our study examines the prospective association between high school cigarette and smoking post-secondary education enrollment. Data were collected from a nationally representative cohort of 10th graders who participated in the Next Generation Health Study (2010-2013). Ethnicity/race, urbanicity, parental education, depression symptoms, and family affluence were assessed at baseline. Self-reported 30-day smoking was assessed annually from 2010 to 2012. Post-secondary education enrollment was measured in 2013 and categorized as either not enrolled or enrolled in technical school, community college, or 4-year college/university. Multinomial logistic regression was used to evaluate the association between cigarette smoking duration and post-secondary education enrollment (N=1681). Participants who smoked 1, 2, or 3years during high school had lower odds of attending a 4-year college (relative to a no enrollment) than non-smokers (adjusted OR: smoking 1year=0.30, 2years=0.28, 3years=0.14). Similarly, participants who smoked for 2 or 3years were less likely than non-smokers to enroll in community college (adjusted OR: 2years=0.31, 3years=0.40). These associations were independent of demographic and socioeconomic factors. There was a prospective association between high school smoking and the unlikelihood of enrollment in post-secondary education. If this represents a causal association, strategies to prevent/delay smoking onset and promote early cessation in adolescents may provide further health benefits by promoting higher educational attainment.


Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2 cytokine production.
Aging is associated with immune dysfunction and conditions such as inflamm-aging and immunosuppression. Arsenic, an environmental contaminant distributed worldwide, affects the immune system. This study tested the hypothesis that arsenic has distinct effects on T cell proliferation and the production of cytokines by activated T cells. Murine splenocytes from young (2 months) and aged (24-26 months) C57BL/6 mice were exposed to arsenite (As(3+)), the most toxic form of inorganic arsenic, and stimulated with concanavalin A (Con A) or anti-CD3 antibody. T cell proliferation decreased significantly in response to Con A and anti-CD3 at subtoxic doses of arsenite in splenocytes from both young and aged mice. Arsenite, added concurrently with Con A or anti-CD3, significantly inhibited the production of interleukin-2 (IL-2), interferon-γ (IFN-γ), and interleukin-4 (IL-4) by splenocytes from young mice and significantly reduced the production of IL-10 by splenocytes from aged mice. In contrast, the production of IL-2 and IL-4 by splenocytes from aged mice was only slightly affected by arsenite. The results show that arsenic exposure reduces the immune response in splenocytes. Moreover, this effect may be influenced by aging.


Developmental origins of moral masochism: a failure-to-thrive toddler's interactions with mother.
The case of a toddler diagnosed as failure to thrive with an unusual history of "accidents" illustrates the circumstances which may account for the infant's intense attachment to a sadistic love object and lead to moral masochism in adulthood. The observed behaviors of the toddler in interaction with mother show the pathological consequences of the infant's openness to influences of the social environment. He becomes attuned to his mother's wishes and performs behaviors which successfully evoke her attention and reciprocity even if these behaviors are contradictory to his survival. The mother's own experiences with unempathic and hostile parents are reflected in her attitudes and behaviors to the child. Suffering and victimization evoke her interest although she lacks the capacity for an empathic response to pain. Berliner's work on the origin of moral masochism, as well as the work of Steele on generational repetition, suggest the processes through which the infant's attachment to a sadistic mother gives rise to masochistic tendencies which may be reenacted throughout life in an effort to reproduce the affective feelings associated with mother's love and affection.


Hypouricemia and malignant neoplasms. A new case of xanthinuria.
An 80-year-old man with squamous cell carcinoma of the parotid gland was noted to have persistent severe hypouricemia with serum uric acid values of 0.5 to 1.0 mg/dL. Urinary excretion of uric acid was very low and a diagnosis of xanthinuria was made.


EEG repetition and change detection responses in infancy predict adaptive functioning in preschool age: a longitudinal study.
Neurodevelopmental disorders (NDDs) are mostly diagnosed around the age of 4-5 years, which is too late considering that the brain is most susceptive to interventions during the first two years of life. Currently, diagnosis of NDDs is based on observed behaviors and symptoms, but identification of objective biomarkers would allow for earlier screening. In this longitudinal study, we investigated the relationship between repetition and change detection responses measured using an EEG oddball task during the first year of life and at two years of age, and cognitive abilities and adaptive functioning during preschool years (4 years old). Identification of early biomarkers is challenging given that there is a lot of variability in developmental courses among young infants. Therefore, the second aim of this study is to assess whether brain growth is a factor of interindividual variability that influences repetition and change detection responses. To obtain variability in brain growth beyond the normative range, infants with macrocephaly were included in our sample. Thus, 43 normocephalic children and 20 macrocephalic children were tested. Cognitive abilities at preschool age were assessed with the WPPSI-IV and adaptive functioning was measured with the ABAS-II. Time-frequency analyses were conducted on the EEG data. Results indicated that repetition and change detection responses in the first year of life predict adaptive functioning at 4 years of age, independently of head circumference. Moreover, our findings suggested that brain growth explains variability in neural responses mostly in the first years of life, so that macrocephalic children did not display repetition suppression responses, while normocephalic children did. This longitudinal study demonstrates that the first year of life is an important period for the early screening of children at risk of developing NDDs.


Complications, urinary continence, and oncologic outcome of 1000 laparoscopic transperitoneal radical prostatectomies-experience at the Charité Hospital Berlin, Campus Mitte.
Laparoscopic transperitoneal radical prostatectomy (LRP) is an alternative to open radical prostatectomy, but data based on large populations are not frequently available. This study was initiated to evaluate LRP with regard to complications, urinary continence, and oncologic outcome. We retrospectively reviewed 1000 consecutive patients with a mean age of 62 yr (SD+/-6 yr) and clinically localized prostate cancer. Between May 1999 and October 2004, all 1000 patients underwent LRP performed by eight urologists at one institution (Charité Hospital Berlin, Campus Mitte). The review procedure was based on complete patient documents (hospital stay, n=1000) and an interview by one physician. Histopathologic results, intraoperative and early and late complications, continence rate, and time to first PSA increase (n=952) were recorded. Erectile function was not part of this review. Twenty-two patients received neoadjuvant treatment for >2 mo. The median follow-up was 28.8 mo (range: 7.2 to 69.7). Intraoperative and early complications occurred in 11.8% of patients. In 77.6% the urethrovesical anastomosis tested by cystography at day 5 or 6 after LRP was intact; 76% used none or not more than one pad per 24h. The overall PSA-free survival was more than 90% for pT2, 80.3% for pT3a, and 72.4% for pT3b until July 2005. The mortality rate was 0.3%. In the present series of 1000 patients, a specific disadvantage of LRP compared with the open approach, as reported in the literature, could not be shown. On the basis of short-term follow-up data, our retrospective evaluation confirms that LRP provides satisfactory results. We believe that laparoscopic radical prostatectomy can be the technique of choice in the future.


Chemical Vapor Deposition for Atomically Dispersed and Nitrogen Coordinated Single Metal Site Catalysts.
Atomically dispersed and nitrogen coordinated single metal sites (M-N-C, M=Fe, Co, Ni, Mn) are the popular platinum group-metal (PGM)-free catalysts for many electrochemical reactions. Traditional wet-chemistry catalyst synthesis often requires complex procedures with unsatisfied reproducibility and scalability. Here, we report a facile chemical vapor deposition (CVD) strategy to synthesize the promising M-N-C catalysts. The deposition of gaseous 2-methylimidazole onto M-doped ZnO substrates, followed by an in situ thermal activation, effectively generated single metal sites well dispersed into porous carbon. In particular, an optimal CVD-derived Fe-N-C catalyst exclusively contains atomically dispersed FeN4 sites with increased Fe loading relative to other catalysts from wet-chemistry synthesis. The catalyst exhibited outstanding oxygen-reduction activity in acidic electrolytes, which was further studied in proton-exchange membrane fuel cells with encouraging performance.


Cognitive markers for efficacy of neurofeedback for attention-deficit hyperactivity disorder - personalized medicine using computational psychiatry in a randomized clinical trial.
Exploring whether cognitive components (identified by baseline cognitive testing and computational modeling) moderate clinical outcome of neurofeedback (NF) for attention-deficit hyperactivity disorder (ADHD). 142 children (aged 7-10) with ADHD were randomly assigned to either NF (n = 84) or control treatment (n = 58) in a double-blind clinical trial (NCT02251743). The NF group received live, self-controlled downtraining of electroencephalographic theta/beta ratio power. The control group received identical-appearing reinforcement from prerecorded electroencephalograms from other children. 133 (78 NF, 55 control) children had cognitive processing measured at baseline with the Integrated Visual and Auditory Continuous Performance Test (IVA2-CPT) and were included in this analysis. A diffusion decision model applied to the IVA2-CPT data quantified two latent cognitive components deficient in ADHD: drift rate and drift bias, indexing efficiency and context sensitivity of cognitive processes involving information integration. We explored whether these cognitive components moderated the improvement in parent- and teacher-rated inattention symptoms from baseline to treatment end (primary clinical outcome). Baseline cognitive components reflecting information integration (drift rate, drift bias) moderated the improvement in inattention due to NF vs. control treatment (p = 0.006). Specifically, those with either the most or least severe deficits in these components showed more improvement in parent- and teacher-rated inattention when assigned to NF (Cohen's d = 0.59) than when assigned to control (Cohen's d = -0.21). Pre-treatment cognitive testing with computational modeling identified children who benefitted more from neurofeedback than control treatment for ADHD.


Stress levels and coping strategies among Jordanian parents caring for newly diagnosed children with leukemia: A cross sectional descriptive correlational study.
The purpose of this study was to describe the stress experienced and coping approaches exhibited by Jordanian parents of children recently diagnosed with leukemia. This cross-sectional study collected data from parents of children who had been diagnosed with leukemia within the previous three months (N = 130; 57 fathers (43.8%) and 73 mothers (56.2%), age (Mean = 37.5, SD = 8.4)). The Parenting Stress Index-Short Form was used. Similarly, parents' coping approaches were assessed with the Coping Health Inventory for Parents. Parents' mean total stress and coping strategies scores were 108 (± 26.8) and 93.9 (± 15.6), respectively. There were significant negative relationships between parents' stress levels and age (r = -0.46, p = .01), education level (f = 28.5, p < .05), and income (r = -0.65, p = .01). Additionally, there were significant positive relationships between parents' coping strategies and age (r = 0.34, p = .01) and income (r = 0.53, p < .01). There were non-significant differences between fathers' and mothers' stress levels and coping strategies. Parents of children with leukemia experienced high stress. The findings also confirmed the negative relationship between parents' stress, age, education level, and income; and the positive relationship between parents' coping strategies, age, and income. Several strategies are needed to manage said stress; for example, respite care for parents who spend long hours at the hospital. Volunteers to care for children at home or hospital might also relieve parents' stress.


Genetic characterization of gliomas arising in patients with multiple sclerosis.
The co-occurrence of gliomas and multiple sclerosis (MS) in the same patient is uncommon, but a well-reported phenomenon. Most have been high grade astrocytic tumors that developed after the diagnosis of MS, leading authors to postulate that chronic gliosis in demyelinative plaques might be the underlying substrate for secondary induction of a glial neoplasm. Until recently, however, genetic tools have not been available to test the hypothesis that high grade gliomas might arise from longstanding chronic gliosis, with transformation to low grade glioma, and eventually GBM, i.e., be secondary GBMs. We searched our surgical neuropathology and MS Brain Bank databases over the past 25 years (1987-2011) and identified eight cases of co-occurring MS and glioma. After careful review to guarantee both diagnoses, cases were studied by fluorescence in situ hybridization for genetic markers appropriate to diagnosis, as well as by direct sequencing for IDH1/2 and P53. No unusual genetic features were detected in our cohort; further, the 4 GBMs we did identify did not have clinical features of secondary glioblastomas nor did any of the four manifest IDH-1 immunohistochemical expression or IDH1/2 mutations, as might be expected in secondary GBMs. Conversely, PTEN loss and EGFR expression, features often found in primary GBMs, but seldom identified in secondary GBMs, were found in 3 of 4 GBMs. We conclude that gliomas in MS patients have genetic features paralleling counterparts in non-MS patients. There is no strong genetic evidence for GBMs to be secondary GBMs.


Bagging survival tree procedure for variable selection and prediction in the presence of nonsusceptible patients.
For clinical genomic studies with high-dimensional datasets, tree-based ensemble methods offer a powerful solution for variable selection and prediction taking into account the complex interrelationships between explanatory variables. One of the key component of the tree-building process is the splitting criterion. For survival data, the classical splitting criterion is the Logrank statistic. However, the presence of a fraction of nonsusceptible patients in the studied population advocates for considering a criterion tailored to this peculiar situation. We propose a bagging survival tree procedure for variable selection and prediction where the survival tree-building process relies on a splitting criterion that explicitly focuses on time-to-event survival distribution among susceptible patients. A simulation study shows that our method achieves good performance for the variable selection and prediction. Different criteria for evaluating the importance of the explanatory variables and the prediction performance are reported. Our procedure is illustrated on a genomic dataset with gene expression measurements from early breast cancer patients. In the presence of nonsusceptible patients among the studied population, our procedure represents an efficient way to select event-related explanatory covariates with potential higher-order interaction and identify homogeneous groups of susceptible patients.


A study to compare Hematopoietic Progenitor Cell count determined on a next-generation automated cell counter with flow cytometric CD34 count in peripheral blood and the harvested peripheral blood stem cell graft from autologous and allogenic donors.
A successful bone marrow transplant requires a minimum of 2-4 × 106 cells/kg patient body weight of CD 34+ cells to be transfused, where peripheral blood CD34+ cell count being and ideal predictor. We compared the correlation and predictive capacity of both hematopoietic progenitor cell count (HPC) determined on the Sysmex XN-9000 and flow cytometric CD34 in autologous and allogenic donors. Autologous and allogenic donors were taken as per criteria. TLC (Total Leukocyte Count), MNC (Mononuclear cell count), HPC, and CD34 assay were done in both the peripheral blood prior to apheresis, and the harvest product postapheresis. Sysmex XN-9000 was used for TLC, MNC, and HPC tests, and a modified ISH-AGE protocol was used to enumerate CD34 by flow cytometry. Statistical analysis was done using SPSS 16.0. Sixty-seven allogenic and 35 autologous donors were enrolled. 45% were females, and 55% were males. Correlation between HPC and CD34 was found to be 0.887 with P value < .01 in peripheral blood and 0.847 with P value < .01 in the harvested product. On the other hand, TLC had a correlation of 0.424 and 0.520 in peripheral blood and harvested, respectively. MNC had a weak association. The cutoff value for a target dose of 2 × 106 CD34 cells/kg was 37 × 106 /L for pre-HPC. For a target of 4 × 106 CD34 cells/kg, the cutoff value calculated to be 54 × 106 /L (Sensitivity: 85%, Specificity: 89%) for peripheral blood HPC. We conclude that HPC is comparable to CD34 in predicting harvest product's adequacy.


Rapid identification of Branhamella catarrhalis. A comparison of five rapid methods.
Five methods for the rapid identification and differentiation of Branhamella catarrhalis from other Neisseria species in 86 respiratory specimens were compared. These tests included the 4-methylumbelliferyl butyrate (MUB), API quadFerm, B.CAT.Confirm, Gonochek II, and the Tributyrin disc. All five tests reliably and accurately identified 31 B. catarrhalis isolates. However, the MUB test was the least expensive, least labor intensive, and did not require overnight purity plates for performance. The MUB test provided same-day identification of B. catarrhalis isolates from the initial primary isolation culture.


Anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis patients in Cotonou, Benin.
To assess the current anti-tuberculosis drug resistance situation in Cotonou, at the largest anti-tuberculosis centre of Benin. A total of 470 isolates of Mycobacterium tuberculosis complex from pulmonary tuberculosis (TB) patients were analysed: 244 from new cases and 226 from previously treated cases. Drug susceptibility testing of isolates against first-line drugs was performed using the proportion method. Primary multidrug resistance (MDR) depends on the patients' origin: MDR in new cases is relatively high (1.6%) when all patients are considered, but low (0.5%) and comparable to 1994 national survey results when only patients residing in Benin are considered. MDR in previously treated patients (11.1%) remains comparable to the study performed in Benin in 1994. No relation was found between human immunodeficiency virus co-infection and anti-tuberculosis drug resistance. This study shows the great importance of correct patient identification in epidemiological surveys, where results may vary according to the population(s) studied.


Community health service programs in academe: unique learning opportunities for students.
Services provided by a college of nursing allow students to participate in unique clinical experiences in nurse-managed healthcare. The authors describe the use of a nursing center, wellness program, and home health program of a college of nursing to provide clinical experiences for nursing students.


Recovery of impaired pretreatment spermatogenesis in testicular cancer.
Light microscopic sperm analysis was done 24 months after treatment or later in 25 patients with testicular cancer with azoospermia or severe oligospermia (sperm cell count less than 10 x 10(6)/mL) after orchiectomy before further treatment. Treatment after orchiectomy consisted of abdominal irradiation, cisplatin-based chemotherapy, retroperitoneal surgery, a combination of the former treatment modalities, or a surveillance policy. At the time of post-treatment reassessment, 15 of the 25 patients had sperm cell concentrations of at least 10 x 10(6)/ml (7 of 14 patients in the azoospermia group; 8 of 11 patients in the oligospermia group). Eight patients fathered a child after discontinuation of treatment for testicular cancer. Recovery of spermatogenesis could be seen after all types of treatment. A highly increased pretreatment serum follicle-stimulating hormone was correlated with lack of sperm cell production recovery.


Corrigendum to "Self-reported face recognition abilities moderately predict face-learning skills: Evidence from Italian samples" [Heliyon 9 (3) (March 2023) Article e14125].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14125.].


Preservation of erythrocytes using metabolic regulators and mutrients. V. Inosine and methylene blue.
Methylene blue and inosine have been shown to stimulate glycolytic metabolism in the erythrocytes, increasing the concentration of 2.3-diphosphoglycerate (2,3-DPG), which is necessary for hemoglobin function, by regulating oxidative metabolism and providing a five-carbon nutrient for glycolysis, respectively. However, a recent study suggested that the methylene blue effect was dependent on the presence of inosine. This study was designed to establish, if possible, the existence of a methylene blue effect and to confirm the usefulness of inosine. The optimal concentration of inosine for increasing 2,3-DPG synthesis in a CPD-adenine preservative is confirmed to be 10--15 mM. Concentrations of 2,3-DPG were maintained in the erythrocytes at normal or higher levels for 21 days of storage with 10 or 15 mM inosine, whether the methylene blue was present or not. However, when methylene blue was present, 2,3-DPG concentrations were significantly better maintained.


Accuracy of thoracic pedicle screw placement in adolescent idiopathic scoliosis patients using the entry point identified by new landmarks: a computed tomography study.
Although thoracic pedicle (TP) screw has gained increasingly popularity in the surgical treatment of adolescent idiopathic scoliosis (AIS) patients, questions remain about the accurate selection of entry point for TP screw placement in these patient. The main objective of the present study was to evaluate the accuracy of TP screw placement in AIS patients using the entry point identified by new landmarks. Thirty-four thoracic AIS patients treated with posterior TP screw instrumentation were included. All these TP screws were inserted through the entry point identified by new landmarks with free-hand technique. Postoperative CT scans were obtained to evaluate the screw position. The perforations of the pedicle were classified as grade 0 (no perforation), grade 1 (≤ 2 mm), grade 2 (2.1-4 mm), grade 3 (4.1-6 mm) and grade 4 (6.1-8.0 mm). Screws in grade 0, displaced either medially or anteriorly in grade 1 and displaced laterally in grades 1 to 2 were considered acceptable. Of the 495 TP screws inserted, 34 (6.9%) screws were displaced with 7 screws (1.4%) displaced medially, 20 screws (4.1%) displaced laterally and 7 screws (1.4%) displaced anteriorly (P < 0.05). Among the 34 displaced screws, 11 screws (32.4%) were considered as grade 1, 14 screws (38.2%) as grade 2 and 9 screws (29.4%) as grade 3 (P < 0.05). The overall rate of acceptable screws was 97.8%. No screw-related complication was noted. Our new method for selecting the entry point of TP screw in AIS patients is convenient and can achieve high accuracy of screw placement, which is worthy of being widely popularized.


Impacting Health Disparities in Urban Communities: Preparing Future Healthcare Providers for "Neighborhood-Engaged Care" Through a Community Engagement Course Intervention.
It is well known that health disparities exist and that a significant majority of patients who suffer disproportionately from them are lower income, non-white residents of dense, and diverse urban neighborhoods. It is our belief that factors hindering the reduction of health disparities in these neighborhoods are a lack of a framework and preparation needed to engage these communities in identifying specific health care needs. This paper describes one curricular intervention, a graduate level community engagement course, developed within an academic medical center located in an urban setting, that demonstrates promise in effecting change in the extent to which clinicians are able to engage communities and practice "neighborhood-engaged care" with the central goal of mitigating disparities.


Relationship between 1H and 13C NMR chemical shifts and the secondary and tertiary structure of a zinc finger peptide.
Essentially complete assignments have been obtained for the 1H and protonated 13C NMR spectra of the zinc finger peptide Xfin-31 in the presence and absence of zinc. The patterns observed for the 1H and 13C chemical shifts of the peptide in the presence of zinc, relative to the shifts in the absence of zinc, reflect the zinc-mediated folding of the unstructured peptide into a compact globular structure with distinct elements of secondary structure. Chemical shifts calculated from the 3D solution structure of the peptide in the presence of zinc and the observed shifts agree to within ca. 0.2 and 0.6 ppm for the backbone C alpha H and NH protons, respectively. In addition, homologous zinc finger proteins exhibit similar correlations between their 1H chemical shifts and secondary structure.


Interaction of the conceptus and endometrium to establish pregnancy in mammals: role of interleukin 1β.
Implantation and the establishment of pregnancy in mammals involves an intricate interplay of hormones, cytokines, growth factors, proteins, lipids, ions and the extracellular matrix between the uterine epithelium, stroma, immune cells and the conceptus trophectoderm. The divergent nature of implantation in the mouse, human and pig provides not only an interesting contrast in the establishment of pregnancy and early embryonic development but also intriguing similarities with regard to early endometrial-conceptus signaling. An interesting pro-inflammatory cytokine expressed in a number of mammalian species during the period of implantation is interleukin-1β (IL1B). The presence of IL1B might be involved with immunotolerance at the maternal-placental interface and has been proposed as one of the mediators in placental viviparity. The production of IL1B and other proinflammatory cytokines might play a role in establishing pregnancy through modulation of the nuclear factor kappa-B (NFKB) system in a number of species. A model for the regulation of cellular progesterone receptor expression and NFKB activation for endometrial receptivity and conceptus attachment is continuing to evolve and is discussed in the present review.


Soluble complement receptor 1 is increased in patients with leukemia and after administration of granulocyte colony-stimulating factor.
Complement receptor type 1 is expressed by erythrocytes and most leukocytes. A soluble form is shed from the leukocytes and found in plasma (sCR1). sCR1 is a powerful inhibitor of complement. We report an increased sCR1 in the plasma of leukemia patients, up to levels producing measurable complement inhibition. Half of the 180 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) had sCR1 levels above the normal range. The highest levels were observed in T-ALL (17 patients). The complement function of a T-ALL serum was improved by blocking sCR1 with a specific mAb (3D9). Measurements in 16 peripheral stein cell donors before and after granulocyte colony-stimulating factor (G-CSF) administration showed an increase in sCR1 (before, 43.8+/-15.4; at day 5, 118.3+/-44.7 ng/mL; P < 0.0001). This increase paralleled the increase in total leukocyte counts and was concomitant with de novo leukocyte mRNA CR1 expression in all three individuals tested. Whether pharmacological intervention may be used to up-regulate sCR1 so as to inhibit complement in vivo should be further investigated.


Diffusion and perfusion quantified by Magnetic Resonance Imaging are markers of human placenta development in normal pregnancy.
To investigate the potential of bi-exponential model of diffusion-weighted (DW) signal decay to quantify diffusion and perfusion changes in human placenta of normal pregnancies due to its development. 26 normal pregnancies at 19-37 weeks of gestation underwent Magnetic Resonance Imaging (MRI) examination at 1.5 T. DW Spin-Echo Echo Planar Imaging with diffusion gradients applied along 3 no-coplanar directions at seven different b-values (0,50,100,150,400,700,1000 s/mm2) was used. Apparent diffusion coefficient (ADC), pseudodiffusion (D*) and perfusion fraction (f) were extracted in selected placenta regions: umbilical (U-ROI), central (C-ROI) and peripheral (P-ROI). The relation between ADC, D*, f and mother age, gestational age (GA), Body-Mass Index (BMI), basal Glycaemia (bG), were evaluated. Pearson correlation with Bonferroni correction was used. A significant negative correlation was found between ADC and GA, for GA≥30w in P-ROI, while no-dependence of ADC on GA was observed in GA range 19-29 weeks. A positive linear correlation was found between f and GA in the C-ROI and between f and GA in P-ROI for GA≥30 week. No significant correlations were found between ADC, D*, f and age, BMI, bG. ADC measurements in P-ROI of normal placenta reflects tissue changes occurring in the third trimester of gestation. Specifically, ADC decreases with GA increase. Besides, f increases with the GA increase in the C-ROI and during the third trimester of pregnancy in the P-ROI. These results suggest the potential of diffusion and perfusion parameters extracted by using a biexponential model to provide information about placenta changes during its development.