Detection of Helicobacter rodentium-like DNA in the liver tissue of patients with chronic liver diseases by polymerase chain reaction-denaturing gradient gel electrophoresis and DNA sequence analysis.
Many Helicobacter spp. were isolated from the stomach, intestinal tract, and liver of different animals and humans. The association between Helicobacter spp. and hepatobiliary diseases, including hepatocellular carcinoma, was thoroughly examined, indicating a potential role of the bacteria in the progression toward cancer. In our work, we screened 97 liver biopsies from patients with chronic liver diseases for the presence of Helicobacter spp. DNA. With the use of genus-specific polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and subsequent sequencing, we found that the majority of Helicobacter spp. DNA detected was similar to Helicobacter rodentium DNA (71%). The DNA of other detected Helicobacter spp. was similar to Helicobacter pylori DNA. This is the first indication of H. rodentium-like DNA presence in human liver tissue. We also conclude that PCR-DGGE is a useful screening method for assigning species designation and heterogeneity.


Phosphatidylinositol 4-phosphate is a major source of GPCR-stimulated phosphoinositide production.
Phospholipase C (PLC) enzymes hydrolyze the plasma membrane (PM) lipid phosphatidylinositol 4,5-bisphosphate (PI4,5P2) to generate the second messengers inositol trisphosphate (IP3) and diacylglycerol (DAG) in response to receptor activation in almost all mammalian cells. We previously found that stimulation of G protein-coupled receptors (GPCRs) in cardiac cells leads to the PLC-dependent hydrolysis of phosphatidylinositol 4-phosphate (PI4P) at the Golgi, a process required for the activation of nuclear protein kinase D (PKD) during cardiac hypertrophy. We hypothesized that GPCR-stimulated PLC activation leading to direct PI4P hydrolysis may be a general mechanism for DAG production. We measured GPCR activation-dependent changes in PM and Golgi PI4P pools in various cells using GFP-based detection of PI4P. Stimulation with various agonists caused a time-dependent reduction in PI4P-associated, but not PI4,5P2-associated, fluorescence at the Golgi and PM. Targeted depletion of PI4,5P2 from the PM before GPCR stimulation had no effect on the depletion of PM or Golgi PI4P, total inositol phosphate (IP) production, or PKD activation. In contrast, acute depletion of PI4P specifically at the PM completely blocked the GPCR-dependent production of IPs and activation of PKD but did not change the abundance of PI4,5P2 Acute depletion of Golgi PI4P had no effect on these processes. These data suggest that most of the PM PI4,5P2 pool is not involved in GPCR-stimulated phosphoinositide hydrolysis and that PI4P at the PM is responsible for the bulk of receptor-stimulated phosphoinositide hydrolysis and DAG production.


Breathing pattern and kinematics in normal subjects during speech, singing and loud whispering.
We used for the first time a non-invasive optoelectronic plethysmography to assess breathing movements and to provide a quantitative description of chest wall kinematics during phonation. Volumes of different chest wall compartments (abdomen and lung apposed to rib cage and abdomen) were assessed using optoelectronic plethysmography in 16 normal Italians (eight men) during reading, singing and high-effort whispering (HW). During phonation the breathing pattern was different from quiet breathing and exercise. (1) During phonation, tidal volume and expiratory time increased while inspiratory time decreased. The expiratory volume changes and flows during HW were considerably greater than during vocalization. During HW, the overall end-expiratory thoracic volume significantly decreased as a result of decreased volume of all compartments and essentially impinged on the maximal expiratory flow-volume curve. (2) While, as previously shown, during exercise the expired volume is due entirely to the abdomen, during phonation all three chest wall compartments contribute to it. Under all conditions studied breathing was, on average, more costal in females than in males but this was mainly related to different size rather than gender per se. Physical characteristics have a greater importance than gender in determining breathing pattern and chest wall kinematics during phonation. The activity of the control of expiration during phonation is more complex than during exercise.


Clinical feasibility of CS-VIBE accelerates MRI techniques in diagnosing intracranial metastasis.
Our objective was to evaluate and compare the diagnostic performance of post-contrast 3D compressed-sensing volume-interpolated breath-hold examination (CS-VIBE) and 3D T1 magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) in detecting intracranial metastasis. Additionally, we analyzed and compared the image quality between the two. We enrolled 164 cancer patients who underwent contrast-enhanced brain MRI. Two neuroradiologists independently reviewed all the images. The signal-to-noise ratio (SNR), contrast-to noise ratio (CNR) were compared between two sequences. For patients with intracranial metastasis, we measured enhancement degree and CNRlesion/parenchyma of the lesion. The overall image quality, motion artifact, gray-white matter discrimination and enhancing lesion conspicuity were analyzed. Both MPRAGE and CS-VIBE showed similar performance in diagnosing intracranial metastasis. Overall image quality of CS-VIBE was better with less motion artifact; however conventional MPRAGE was superior in enhancing lesion conspicuity. Overall, the SNR and CNR of conventional MPRAGE were higher than those of CS-VIBE. For 30 enhancing intracranial metastatic lesions, MPRAGE showed a lower CNR (p = 0.02) and contrast ratio (p = 0.03). MPRAGE and CS-VIBE were preferred in 11.6 and 13.4% of cases, respectively. In comparison with conventional MPRAGE, CS-VIBE achieved comparable image quality and visualization, with the scan time being half of that of MPRAGE.


Automated Tracking Systems for the Assessment of Farmed Poultry.
The world's growing population is highly dependent on animal agriculture. Animal products provide nutrient-packed meals that help to sustain individuals of all ages in communities across the globe. As the human demand for animal proteins grows, the agricultural industry must continue to advance its efficiency and quality of production. One of the most commonly farmed livestock is poultry and their significance is felt on a global scale. Current poultry farming practices result in the premature death and rejection of billions of chickens on an annual basis before they are processed for meat. This loss of life is concerning regarding animal welfare, agricultural efficiency, and economic impacts. The best way to prevent these losses is through the individualistic and/or group level assessment of animals on a continuous basis. On large-scale farms, such attention to detail was generally considered to be inaccurate and inefficient, but with the integration of artificial intelligence (AI)-assisted technology individualised, and per-herd assessments of livestock became possible and accurate. Various studies have shown that cameras linked with specialised systems of AI can properly analyse flocks for health concerns, thus improving the survival rate and product quality of farmed poultry. Building on recent advancements, this review explores the aspects of AI in the detection, counting, and tracking of poultry in commercial and research-based applications.


Effects of Hominis placenta on LPS-induced cell toxicity in BV2 microglial cells.
Hominis placenta (HP) dried placenta extracted from pregnant women after delivery has been widely used to treat chronic inflammatory diseases. HP has been reported to be effective to alleviate the arthritic symptoms by modulating the expression of inflammatory factors in adjuvant-induced arthritis rats. However, the mechanism of action of HP is unknown. Neuroinflammation has been implicated in the pathogenesis of several neurodegenerative disease, including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotropic lateral sclerosis (ALS). Activated microglia produce large amounts of toxic soluble factors, which can be responsible for the neurodegenerative disease. Chronic microglial activation leads to neuroinflammation, which contributes to neuronal dysfunction, injury and loss in these diseases. Lipopolysaccharide (LPS) is widely used for neuroinflammation caused by microglial activation of immune cells in the central nervous system (CNS) and subsequent release of inflammatory or neurotoxic factors. In the present study, we investigated the effects and signaling pathway of HP in the LPS induced BV2 microglial cells. BV2 microglial cells were pretreated with 50 μM HP for 2h prior to 2 μg/ml LPS for 15 min. Cell viability was determined by MTT assay. The level of protein expression was analyzed by western blot. Immunofluorescence was performed with an anti-COX2 antibody in BV2 cells. HP decreased LPS-induced microglial cell death by 24% and inhibited LPS-induced activation of c-Jun N-terminal kinase (JNK) by 23% and p42/44MAP kinase (ERK) by 34% treatment of LPS. In addition, HP attenuated LPS-induced pro-inflammatory proteins such as iNOS and COX2 in microglial cells 34% and 28% respectively. Our data shows that HP has a protective role against LPS stimulation through inhibition of MAPK signaling and suppression of inflammation caused by neurotoxin including LPS. These findings suggest that HP could be a potential therapeutic agent of neurodegenerative diseases which accompanied with microglial activation.


Demographic and sociocultural characteristics of sickle anaemia children with positive hepatitis B surface antigenaemia in a tertiary health facility in Enugu.
Hepatitis B virus) infection is contracted through contact with body fluid of infected persons. Patients with sickle cell anaemia (SCA), a common haematological disorder in Nigeria, have tendencies to visit traditional healers who administer scarifications and ritual marks that may expose them to HBV infection. To determine the demographic and socio-cultural characteristics of children with SCA infected with HBV at the University of Nigeria Teaching Hospital Enugu. Two hundred and twenty one children aged 6 months to 17 years with SCA were recruited consecutively from October 2004 to April 2005. They were screened for HBsAg using ELISA method. There was no statistically difference in hepatitis B surface antigenaemia among different age group (P = 0.907). Social class did not significantly influence the prevalence of HBsAg among subjects (p = 0.887). Socio-cultural practices like circumcision and scarification did not influence the prevalence of HBsAg, (p = 0.636) (p = 0.771) respectively. Significantly higher number of people from lowest socioeconomic class practice scarification (p = 0.0001). Demographic and sociocultural factors do not appear to influence the prevalence of HBsAg among children with SCA in Enugu, Nigeria.


Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial.
The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.


Repositioning and optimization of left ventricular lead position in nonresponders to cardiac resynchronization therapy is associated with improved ejection fraction, lower NT-proBNP values, and fewer heart failure symptoms.
Observational data suggest that an anterior or apical left ventricular (LV) position in cardiac resynchronization therapy (CRT) is associated with worse outcome and higher likelihood of "nonresponse." It is not known whether the benefits of optimizing LV lead position in a second procedure outweighs the procedural risks. To evaluate the clinical effects of LV lead repositioning. During the period 2015-2020, we identified all patients in whom the indication for the procedure was LV lead repositioning owing to "nonresponse" in combination with suboptimal LV lead position. All patients were followed with a structured visit 6 months post LV lead revision. Heart failure hospitalization and mortality data were gathered from the medical records and cross-checked with the population registry. A total of 25 patients were identified who fulfilled the inclusion criteria. All procedures were successful in establishing LV lead pacing in a lateral mid or basal location. Median follow-up was 2.5 years [1.1-3.7]. There were improvements in NYHA class (mean -0.5 ± 0.5 class, P < .001), LV ejection fraction (+5 [interquartile range 2-11] absolute %, P = .01), QRS duration (-36 [-44 to -8], P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (-615 [-2837 to +121] ng/L, P = .03). Clinical outcome was similar to a reference population with CRT (P = ns). In nonresponders to CRT with either an anterior or inferior LV lead position, it was feasible to perform LV lead repositioning in all cases, with a low complication rate. Changing the LV lead position was associated with improved LV ejection fraction, larger QRS reduction, and larger NT-proBNP reduction.


[Abduction/external rotation immobilization after primary traumatic anterior shoulder dislocation: which ortheses are suitable?].
Immobilization of the shoulder in 60 ° external rotation and 30 ° abduction after primary anterior shoulder dislocation has been shown to allow anatomical reduction and potential healing of the capsule-labrum complex. The purpose of the present study was to evaluate commercially available shoulder braces concerning functionality and comfort as well as for potential problems. In this study ten healthy subjects (6 female, 4 male and average age 23 years) tested four braces: 1. Omo Immobil (Ottobock), 2. Quadrat (DJO Global), 3. MP Airplane Axilla (Horst Rattenhuber GmbH) and 4. ARC XR (Bledsoe Brace Systems) with respect to functionality and comfort. Each subject completed simulated activities of daily living (ADLs) and a the end of each ADL the subject evaluated comfort, difficulty of the activities and potential pain on a points scale. The position or the change of the position were controlled by digital photographs. Additionally it was checked whether the subjects could actively change the position of the brace contrary to the desired position. Braces 3 and 4 were rated significantly more comfortable (p < 0.05). Even the difficulty of the activities was rated lower and in particular putting on and taking off the braces was assessed to be significantly easier in comparison to braces 1 and 2. In addition, differences of potential pain were statistically significant and pain was experienced only with braces 1 and 2. The measuring of the position showed no significant differences (p > 0.05). For braces 1 and 2 the active change of the position by subjects was significantly higher and the arm could be rotated more against the favored position (p < 0.05). Between braces 3 and 4, there were no statistical differences during the whole evaluation. Ortheses where the main joint is positioned in and not in front of the axilla or which can ensure a jointless stabilization of the shoulder or which allow an improved position by an additional sling on the opposite shoulder, are most qualified for immobilization of the shoulder in an external rotation/abduction position with respect to functionality and comfort.


A Data Science Approach for the Identification of Molecular Signatures of Aggressive Cancers.
The main hallmarks of cancer include sustaining proliferative signaling and resisting cell death. We analyzed the genes of the WNT pathway and seven cross-linked pathways that may explain the differences in aggressiveness among cancer types. We divided six cancer types (liver, lung, stomach, kidney, prostate, and thyroid) into classes of high (H) and low (L) aggressiveness considering the TCGA data, and their correlations between Shannon entropy and 5-year overall survival (OS). Then, we used principal component analysis (PCA), a random forest classifier (RFC), and protein-protein interactions (PPI) to find the genes that correlated with aggressiveness. Using PCA, we found GRB2, CTNNB1, SKP1, CSNK2A1, PRKDC, HDAC1, YWHAZ, YWHAB, and PSMD2. Except for PSMD2, the RFC analysis showed a different list, which was CAD, PSMD14, APH1A, PSMD2, SHC1, TMEFF2, PSMD11, H2AFZ, PSMB5, and NOTCH1. Both methods use different algorithmic approaches and have different purposes, which explains the discrepancy between the two gene lists. The key genes of aggressiveness found by PCA were those that maximized the separation of H and L classes according to its third component, which represented 19% of the total variance. By contrast, RFC classified whether the RNA-seq of a tumor sample was of the H or L type. Interestingly, PPIs showed that the genes of PCA and RFC lists were connected neighbors in the PPI signaling network of WNT and cross-linked pathways.


Arterial pseudoaneurysms of the shoulder mimicking other entities: utilization of pulsation artifact on musculoskeletal MR for accurate diagnosis in 2 cases.
We present two cases of pseudoaneurysm (PSA) about the shoulder mimicking more common clinical entities-soft tissue neoplasm and septic arthritis-for which biopsy of the mass and joint aspiration were requested respectively. We review the imaging findings of PSA with emphasis on findings in musculoskeletal protocol MRI, including the identification of pulsation artifact in both cases, which was critical to establishing the correct diagnosis. In the proper clinical setting, with imaging findings demonstrating a complex mass or fluid collection, MR images should be scrutinized for the presence of pulsation artifact, which can help diagnose a high-flow vascular lesion and avoid a potentially harmful invasive procedure such as biopsy.


[The significance of pattern electroretinogram in detecting retinal function in primary open angle glaucoma].
To evaluate the clinical significance of pattern electroretinogram (PERG) in primary open angle glaucoma (POAG). Thirty-six patients (59 eyes) with POAG and 32 persons (59 eyes) as age-matched normal controls were tested by PERG. The changes of PERG in POAG included reduction of amplitudes of P(1), N(2), P(1) + N(2) and N(2)/P(1). Using the criteria of AN(2) + AP(1) < 2.7 and AN(2)/AP(1) < 0.7 (A = amplitude), the positive rate was 90% in 59 eyes with POAG, and no eye from the normal control group was considered as abnormal. The amplitudes of PERG had already been abnormal before the early visual field loss occurred in POAG eyes. The amplitudes of P(1) and N(2) waves decreased with the enlargement of visual field defect, were positively correlated to the patient's visual acuity and negatively correlated to the cup/disc ratio of optic nerve papilla, and linear regression equations between them were respectively established. PERG is an useful method in detecting the retinal functions in POAG.


Bioaugmentation of intertidal sludge enhancing the development of salt-tolerant aerobic granular sludge.
Three parallel bioreactors were operated with different inoculation of activated sludge (R1), intertidal sludge (ItS) (R2), and ItS-added AS (R3), respectively, to explore the effects of ItS bioaugmentation on the formation of salt-tolerant aerobic granular sludge (SAGS) and the enhancement of COD removal performance. The results showed that compared to the control (R1-2), R3 promoted a more rapid development of SAGS with a cultivation time of 25 d. Following 110-day cultivation, R3 exhibited a higher granular diameter of 1.3 mm and a higher hydrophobic aromatic protein content than that in control. Compared to the control, the salt-tolerant performance in R3 was also enhanced with the COD removal efficiency of 96.4% due to the higher sludge specific activity of 14.4 g·gVSS-1·d-1 and the salinity inhibition constant of 49.3 gL-1. Read- and genome-resolved metagenomics together indicated that a higher level of tryptophan/tyrosine synthase gene (trpBD, tyrBC) and enrichment of the key gene hosts Rhodobacteraceae, Marinicella in R3, which was about 5.4-fold and 1.4-fold of that in control, could be the driving factors of rapid development of SAGS. Furthermore, the augmented salt-tolerant potential in R3 could result from that R1 was dominated by Rhodospirillaceae, Bacteroidales, which carried more trehalose synthase gene (otsB, treS), while the dominant members Rhodobacteraceae, Marinicella in R3 were main contributors to the glycine betaine synthase gene (ectC, betB, gbsA). This study could provide deeper insights into the rapid development and improved salt-tolerant potential of SAGS via bioaugmentation of intertidal sludge, which could promote the application of hypersaline wastewater treatment.


Acute upper airway obstruction caused by Stenotrophomonas maltophilia soft tissue infection.
A previously healthy 71-y-old male developed acute upper airway obstruction caused by a Stenotrophomonas maltophilia infection of the mucocutaneous and soft tissue of the neck. Ventilator support was provided via a small-calibre endotracheal tube. Stenotrophomonas was susceptible only to levofloxacin and cotrimoxazole. Antibiotic therapy rapidly improved the soft tissue oedema, allowing extubation and discharge from the intensive care unit.


Single-cell transcriptomics reveals variable trajectories of CSPCs in the progression of osteoarthritis.
Osteoarthritis (OA) is characterised by cartilage destruction; however, there are no specific drugs available for its treatment. Cartilage-derived stem/progenitor cells (CSPCs) are multipotent cells that play an essential role in cartilage renewal and may provide critical insights into the medical needs for OA treatment. However, alterations in cell function and fate of CSPCs during OA progression have seldom been analysed, especially at the single-cell level. Additionally, it has been reported that CSPCs can migrate to the cartilage injury area, although the mechanism of migration remains elusive. Thus, understanding the changing patterns of CSPCs in the pathological process of OA is important in the effort to develop stem cell therapy for OA. Here, we downloaded single-cell transcriptomic data of patients with OA from the Gene Expression Omnibus (GEO) database and performed unbiased clustering of the cells based on gene expression patterns using the Seurat package. Using common stem cell markers and chondrogenic transcription factors, we traced CSPCs throughout all stages of OA. We further explored the dynamics of CSPCs in OA progression and validated the single-cell RNA sequencing data in vitro using qPCR, immunofluorescence, and western blotting. Specifically, we primarily explored the heterogeneity of CSPCs at the single-cell level and found that it was closely associated with OA progression. Our results indicate significantly reduced chondrogenic differentiation capacity in CSPCs during the late stage of OA, while their proliferation capacity tended to increase. We also found that genes implicated in fibrosis, cell motility, and extracellular matrix remodelling were upregulated in CSPCs during the progression of OA. Our study revealed the dynamics of stem cells in OA progression and may inform the development of stem cell therapy for OA.


International Classification of Functioning, Disability and Health (ICF) and correlation between disability and finance assets in chronic stroke patients.
Stroke is the third cause of long term disability worldwide and its rehabilitation program must to have into account all aspects of disability. International research and politics increasingly study the relationship between disability and the direct costs associated with living with a disability. Using the ICF, this article provides a correlation between financial assets and disability in participation and activities, in a context such as the Italian one where there is a twenty-year decentralization of the national health system Methods. At the University of Catanzaro, in southern Italy, n=130 ICF checklists of stroke patients were analyzed at 6 months from the end of the rehabilitation treatment. Financial assets domains in environment and nine domains in participation and activities were correlated, in order to evaluate the relationship between familiar economic condition and disability. Pearson's r test (t = -6.6515, df = 25, p-value<0.05) showed a significant correlation of 0.79. Multiple R-squared was 0.639 and an we reported an Adjusted R-squared of 0.6245 (p<0.05). Thus, about 62% of the increase of the all considered disability qualifiers in participation and activities in ICF checklist can be explained by a lower financial income. In a regional context (Calabria) of an European country (Italy) with a national health system, thanks to the ICF it can be assumed that with the decrease of the financial income, the gap in participation of activities increases.


Ionized o-, m-, and p-difluorobenzene dissociate through ring-opened intermediates: a TPEPICO investigation.
Threshold photoelectron photoion coincidence (TPEPICO) experiments have shown that o-, m-, and p-difluorobenzene ions dissociate via a common, ring-opened intermediate and not via ionized p-difluorobenzene. Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of the experimental breakdown curves yields activation energies for the initial isomerization of 4.48 +/- 0.05, 4.55 +/- 0.05, and 4.68 +/- 0.05 eV for o-, m-, and p-difluorobenzene, respectively. These values place each ion at a similar absolute energy and thus similar transition states. A large positive DeltaS(double dagger) for each ion (ca 100 J K(-1) mol(-1)) suggests a ring-opened structure for these transition states.


Assessment of individual changes in body fatness in boys during early pubertal period.
In order to know whether the changes in indexes of overweight, body mass index (BMI; kg/m2) and percentage of overweight (POW) (%), really represent the tendency toward obesity, we examined longitudinal individual changes in these indexes, and the change in body composition in boys during early pubertal period. The subjects were 50 school boys who lived in Shizuoka, Japan. Standing height and weight were measured, and BMI and POW were obtained. Body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) were estimated by bioelectrical impedance method. The influence of predictive variables (LBM, FM) on the changes in BMI and POW was investigated by multiple regression analysis. We examined the 3-year changes in BMI, POW and predictive variables in each individual, from 9 to 12 years of age. The mean change of BMI was 1.7 +/- 0.3 (mean +/- SEM) kg/m2 and that of POW was 2.2 +/- 1.9%. The influence of predictive variables on the changes in BMI and POW was determined. The variance of the change in POW could be explained by that in FM (r(2) = 0.737, P < 0.0001), while the change in BMI was influenced by both LBM and FM (r2 = 0.891, P < 0.0001). Based on the definition of obesity, POW is the better index of body fatness to assess its individual change for boys during early pubertal period, because the index independent from the change in LBM is supposed to be the appropriate index for obesity in practical use.


A novel anti-CD47-targeted blockade promotes immune activation in human soft tissue sarcoma but does not potentiate anti-PD-1 blockade.
The treatment options for metastatic soft tissue sarcomas (STSs) are limited. In most cases, immunotherapy with immune checkpoint inhibitors has not been successful so far. Macrophages dominate the immune landscape of STSs; thus, combinatorial strategies aiming at both tumor-infiltrating lymphocytes and macrophages may represent a particularly relevant treatment approach for metastatic or recurrent STSs. In this cohort study, 66 patients who underwent surgery for STSs were enrolled. Tumor cells and tumor-infiltrating immune cells were analyzed using flow cytometry and immunohistochemistry. In cell suspensions obtained from surgical resections, human T cells were activated by superparamagnetic polymer beads and cultured at a concentration of 0.3 × 106/µl in the absence or presence of therapeutic monoclonal antibodies (anti-PD-1, anti-CD47, and anti-PD-1 + anti-CD47). Supernatants from cell suspensions were analyzed using multiplex Luminex cytokine bead-based immunoassays. The most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma which also displayed high expression of CD47 in the tumor microenvironment. Both anti-PD-1 and anti-CD47 therapies drastically increased the production of pro-inflammatory cytokines in the tumor microenvironment of STSs, but co-administration of both agents did not further increase cytokine secretion. Furthermore, all patient samples treated with a combination of both anti-PD-1 and anti-CD47 antibodies showed a dramatic reduction in cytokine secretion. Our findings suggest that anti-PD-1 and anti-CD47 therapies do not enhance each other, and the combined application of anti-PD-1 and anti-CD47 agents in vitro limits rather than potentiates their efficacy.


Cannabinoid CB2 receptor orthologues; in vitro function and perspectives for preclinical to clinical translation.
Cannabinoid CB2 receptor agonists are in development as therapeutic agents, including for immune modulation and pain relief. Despite promising results in rodent preclinical studies, efficacy in human clinical trials has been marginal to date. Fundamental differences in ligand engagement and signalling responses between the human CB2 receptor and preclinical model species orthologues may contribute to mismatches in functional outcomes. This is a tangible possibility for the CB2 receptor in that there is a relatively large degree of primary amino acid sequence divergence between human and rodent. Here, we summarise CB2 receptor gene and protein structure, assess comparative molecular pharmacology between CB2 receptor orthologues, and review the current status of preclinical to clinical translation for drugs targeted at the CB2 receptor, focusing on comparisons between human, mouse and rat receptors. We hope that raising wider awareness of, and proposing strategies to address, this additional challenge in drug development will assist in ongoing efforts toward successful therapeutic translation of drugs targeted at the CB2 receptor.


A unique patient with epilepsy with cinematographic visual hallucinations.
The purpose of this case report is to document a patient with cinematographic hallucinations, with corresponding right temporal lobe seizures on electroencephalogram (EEG). The results showed that the patient's EEG was normal. The patient subsequently reported hallucinations, which had been occurring for the last several months. During monitoring, no interictal EEG abnormalities were identified, but a total of 11 partial seizures were captured originating from the right posterior temporal area. They either were subclinical or corresponded with his visual hallucinations. The present study demonstrates focal seizures of temporal lobe origin producing complex visual hallucinations without a corresponding lesion on MRI brain imaging.


Quantitative assessment of contact and non-contact lateral force calibration methods for atomic force microscopy.
Atomic Force Microscopy (AFM) has been widely used for measuring friction force at the nano-scale. However, one of the key challenges faced by AFM researchers is to calibrate an AFM system to interpret a lateral force signal as a quantifiable force. In this study, five rectangular cantilevers were used to quantitatively compare three different lateral force calibration methods to demonstrate the legitimacy and to establish confidence in the quantitative integrity of the proposed methods. The Flat-Wedge method is based on a variation of the lateral output on a surface with flat and changing slopes, the Multi-Load Pivot method is based on taking pivot measurements at several locations along the cantilever length, and the Lateral AFM Thermal-Sader method is based on determining the optical lever sensitivity from the thermal noise spectrum of the first torsional mode with a known torsional spring constant from the Sader method. The results of the calibration using the Flat-Wedge and Multi-Load Pivot methods were found to be consistent within experimental uncertainties, and the experimental uncertainties of the two methods were found to be less than 15%. However, the lateral force sensitivity determined by the Lateral AFM Thermal-Sader method was found to be 8-29% smaller than those obtained from the other two methods. This discrepancy decreased to 3-19% when the torsional mode correction factor for an ideal cantilever was used, which suggests that the torsional mode correction should be taken into account to establish confidence in Lateral AFM Thermal-Sader method.


In Vivo Nitric Oxide Synthase Inhibitors Can Be Deprived of This Activity: Unexpected Influence of the Tetrachloroplatinate(II) Counteranion. Crystal Structures of Bis(S-Methyl-Isothiouronium)-N,N'-Bis(3-Guanidinopropyl)Piperazinium and Hexamidinium Tetrachloroplatinates(II) Salts.
The synthesis and crystal structures of bis(S-methylisothiouronium) (MSTUH)(+), N,N'-bis((3- guanidinopropyl)piperazinium (PipeC3GuaH4)(4+) and hexamidinium (HexaH2)(2+) tetrachloro platinate(ll) salts ( called hereafter PtMSTU, PtPipeC3Gua and PtHexa respectively ) were investigated. These compounds contain the "amidine" function ( - C(=NH)NH(2) ) in which the H atoms supplied by the acid have become attached to the imino group of each terminal amidino function. Moreover, in PtPipeC3Gua, the nitrogen atoms of the chair-piperazine moiety are also protonated. The influence of tetrachloroplatinate(ll) counteranion ( versus sulfate, nitrate and diisethionate ) in the in vivo nitrite inhibition by the (MSTUH)(+), (PipeC3GuaH4)(4+) and (HexaH2)(2+) cations was investigated. The three tetrachloroplatinate(ll) salts, unexpectedly, do not inhibit significantly the in vivo nitrite production in comparison with the other salts (sulfate, nitrate and diisethionate and their corresponding previous countercations) which exhibit NO synthase inhibition, especially bis(S-methylisothiouronium) sulfate, a selective and potent inducible NO synthase (iNOS) inhibitor commonly used as standard.


Cardiopulmonary bypass after cardiac arrest and prolonged closed-chest CPR in dogs.
We studied a clinically realistic field-to-hospital scenario in dogs with four-minute ventricular fibrillation (VF) cardiac arrest followed by 30-minute standard external CPR basic life support (BLS). At the end of this 34-minute insult, cardiopulmonary bypass (CPB) was used for early defibrillation and assisted circulation for one hour (n = 10). Recovery was compared with that of control dogs (n = 10) in which standard CPR with advanced life support (ALS) for another 30 minutes was used for restoration of spontaneous circulation (ROSC). Both groups had hemodilution and heparinization; controlled blood pressure, blood gases, ventilation, and other parameters for 20 hours; and intensive care to 72 hours. During CPR-BLS of 30 minutes in both groups signs of cerebral viability returned. CPB achieved ROSC more successfully (ten of ten vs five of ten CPR-ALS controls) (P less than .02); and more rapidly, with less defibrillation energy (first countershock in eight of ten) and with less epinephrine (P less than .01). CPB improved 72-hour survival (seven of ten vs three of ten controls) (P less than .05). Between two and 24 hours, of those with ROSC, cardiac complications killed three of ten CPB dogs (after weaning), and two of five CPR-ALS dogs (NS). All seven CPB survivors to 72 hours were neurologically normal; of the three CPR-ALS survivors, one remained with severe neurologic deficit and two were neurologically normal (seven of ten CPB vs two of ten controls, P = .025). Starting CPR-BLS within four minutes of arrest can maintain cerebral viability.(ABSTRACT TRUNCATED AT 250 WORDS)


Temporomandibular joint arthrography: dynamic study by videorecording.
Temporomandibular joint symptoms are common. Patients not successfully treated by conservative methods require accurate assessment of the internal derangements of the joint. Temporomandibular joint arthrography using only videorecorded intensifier fluorography displays the anatomy and function accurately with a low radiation dose.


Supporting Evidence of Human Enteric Nervous System Adult Neurogenesis: Presence of Primary Cilia and Adult Neurogenesis Markers.
Adult neurogenesis has been profusely studied in central nervous system. However, its presence in enteric nervous system remains elusive although it has been recently demonstrated in mice and intimately linked to glial cells. Moreover, primary cilium is an important organelle in central adult neurogenesis. In the present study, we analysed some parallelisms between central and enteric nervous system (ENS) in humans based on ultrastructural and immunohistochemical techniques. Thus, we described the presence of primary cilia in some subtypes of glial cells and Interstitial Cells of Cajal (ICCs) and we performed 3-D reconstructions to better characterise their features. Besides, we studied the expression of several adult neurogenesis-related proteins. Immature neuron markers were found in human ENS, supporting the existence of adult neurogenesis. However, only ICCs showed proliferation markers. Hence, we propose a new paradigm where ICCs would constitute the original neural stem cells which, through asymmetrical cell division, would generate the new-born neurons.


Genital tuberculid in a female child: a new entity (childhood vulval tuberculid).
Localized tuberculid has been infrequently reported in the literature. Most of these reports are of papulonecrotic tuberculids localized to the penis, an entity designated as "penis tuberculid." In females, such a localized genital tuberculid has not been documented till date. We report an 11-year-old girl with lichen scrofulosorum confined to the vulva, associated with cervical and inguinal tubercular lymphandenitis.


Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk.
The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case-control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (ORMet allele vs. Thr allele=1.17, 95 % CI 0.97-1.42, P OR=0.102; ORMetMet vs. ThrThr =1.32, 95 % CI 0.93-1.87, P OR=0.121; ORThrMet vs. ThrThr =1.17, 95 % CI 0.94-1.45, P OR=0.150; ORMetMet + ThrMet vs. ThrThr =1.20, 95 % CI 0.96-1.51, P OR=0.114; ORMetMet vs. ThrThr + ThrMet =1.37, 95 % CI 0.98-1.93, P OR=0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case-control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.


Induction of LTP in rat primary visual cortex: tetanus parameters.
Long-term potentiation (LTP), intensively studied in the hippocampus as a possible mnemonic device, has begun to be studied in the neocortex. In this study the effects of varying tetanic stimulus parameters on LTP of field potentials recorded from layer II/III induced by white matter stimulation in the in vitro rat visual cortical slice were examined. Low intensity tetanus was more effective in producing LTP than high-intensity tetanus, although single pulses of very high intensity reliably resulted in LTP. LTP consistently occurred following 2 Hz-60 min, or 100 Hz-10 min tetanus; whereas, 10 min of 7 and 25 Hz tetanus usually resulted in long-lasting depression. Although no obvious rule related tetanus frequency and duration to the incidence of LTP, an inverted-U relationship was found between tetanus frequency and LTP magnitude.


Anhedonia in Depression and Bipolar Disorder.
Anhedonia is a hallmark feature of depression and is highly prevalent among individuals with mood disorders. The history and neurobiology of anhedonia has been most extensively studied in the context of unipolar Major Depressive Disorder (MDD), with converging lines of evidence indicating that marked anhedonia heralds a more chronic and treatment-refractory illness course. Furthermore, findings from neuroimaging studies suggest that anhedonia in MDD is associated with aberrant reward-related activation in key brain reward regions, particularly blunted reward anticipation-related activation in the ventral striatum. However, the ongoing clinical challenge of treating anhedonia in the context of Bipolar Disorder (BD) also highlights important gaps in our understanding of anhedonia's prevalence, severity, and pathophysiology along the entire mood disorder spectrum. In addition, although current theoretical models posit a key role for reward hyposensitivity in BD depression, unlike studies in MDD, studies in BD do not clearly show evidence for reduced reward-related activation in striatal or other brain regions. Although further research is needed, the evidence to date hints at a divergent pathophysiology for anhedonia in unipolar and bipolar mood disorders, which, if better understood, could lead to significant improvements in the diagnosis and treatment of MDD and BD.


Knowledge self-monitoring, efficiency, and determinants of self-confidence statement in multiple choice questions in medical students.
Multiple-choice question (MCQ) tests are commonly used to evaluate medical students, but they do not assess self-confidence nor penalize lucky guess or harmful behaviors. Based on a scoring method according to the appropriateness of confidence in answers, the study aimed at assessing knowledge self-monitoring and efficiency, and the determinants of self-confidence. A cross-sectional study of 842 s- and third-year medical students who were asked to state their level of confidence (A: very confident, B: moderately confident and C: not confident) during 12 tests (106,806 events). A bonus was applied if the level of confidence matched with the correctness of the answer, and a penalty was applied in the case of inappropriate confidence. Level A was selected more appropriately by the top 20% students whereas level C was selected more appropriately by the lower 20% students. Efficiency of higher-performing students was higher when correct (among correct answers, rate of A statement), but worse when incorrect compared to the bottom 20% students (among incorrect answers, rate of C statement). B and C statements were independently associated with female and male gender, respectively (OR for male vs female = 0.89 [0.82-0.96], p = 0.004, for level B and 1.15 [1.01-1.32], p = 0.047, for level C). While both addressing the gender confidence gap, knowledge self-monitoring might improve awareness of students' knowledge whereas efficiency might evaluate appropriate behavior in clinical practice. These results suggest differential feedback during training in higher versus lower-performing students, and potentially harmful behavior in decision-making during clinical practice in higher-performing students.


SIM-ELM: Connecting the ELM model with similarity-function learning.
This paper moves from the affinities between two well-known learning schemes that apply randomization in the training process, namely, Extreme Learning Machines (ELMs) and the learning framework using similarity functions. These paradigms share a common approach involving data remapping and linear separators, but differ in the role of randomization within the respective learning algorithms. The paper presents an integrated approach connecting the two models, which ultimately yields a new variant of the basic ELM. The resulting learning scheme is characterized by an analytical relationship between the dimensionality of the remapped space and the learning abilities of the eventual predictor. Experimental results confirm that the new learning scheme can improve over conventional ELM in terms of the trade-off between classification accuracy and predictor complexity (i.e., the dimensionality of the remapped space).


Erythropoietin levels can be used to determine tissue oxygenation in critically ill patients.
Critically ill patients often require pharmacological support to maintain blood pressure and cardiac output, and mechanical ventilation to ensure adequate oxygenation. Current methods of measurement of oxygen delivery do not necessarily reflect tissue oxygenation. Levels of circulating erythropoietin reliably reflect the adequacy of renal oxygen supply under physiological and many pathological conditions. It is proposed that the measurement of circulating erythropoietin can be used as a measure of tissue oxygenation in critically ill patients.


Treatment of disseminated granuloma annulare with a 5-lipoxygenase inhibitor and vitamin E.
Histologically, granuloma annulare (GA) is a common non-infectious necrobiotic granulomatous reaction pattern that correlates with a number of different, but relatively specific clinical presentations. The cause or causes of GA are unknown: when localized, it is usually self-limiting, but it may be persistent when disseminated. We present three women who had had disseminated GA for more than 1 year. One patient had previously been treated with isotretinoin with no response. All three patients were treated with vitamin E 400 IU daily and zileuton 2400 mg daily. All responded within 3 months with complete clinical clearing. The anti-inflammatory and immune regulatory effects of vitamin E and zileuton may be an effective treatment in some patients with prolonged disseminated/generalized GA.


Ca2+-induced pancreatic cell death: roles of the endoplasmic reticulum, zymogen granules, lysosomes and endosomes.
Alcohol induces Ca(2+)-dependent intracellular trypsinogen activation in the apical granular area via non-oxidative metabolites, such as fatty acid ethyl esters and fatty acids. Intracellular trypsinogen activation is a crucial initiating event in the development of acute pancreatitis, but the specific organelle in which this process takes place has been unknown. Recent data demonstrate that the Ca(2+)-dependent trypsinogen activation occurs in postexocytotic endocytic vacuoles. These vacuoles are acid due to a bafilomycin-sensitive vacuolar H(+) ATPase and have a very Ca(2+)-permeable membrane. Acid endocytic structures, together with lysosomes, zymogen granules and elements of the endoplasmic reticulum, also play an important role in the physiological Ca(2+) signal generation that normally regulates enzyme and fluid secretion from the exocrine pancreas.


The impact of elevated blood pressure upon 10-year mortality among Japanese men in Hawaii: the Honolulu Heart Program.
The impact of blood pressure upon total and cause-specific mortality during 10 years of follow-up was studied for 7610 Japanese men in Hawaii, aged 45-68 at baseline examination. The age adjusted rate of total mortality for men with definite hypertension (WHO criteria) was twice that for normotensive men. The relative risk of mortality was five for all cardiovascular diseases (CVD), four for coronary heart disease (CHD), and six for stroke. Men with borderline hypertension also had significantly high mortality rates intermediate between the definite hypertensives and the normotensives. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were the most important independent predictors of total, CVD, CHD and stroke mortality in multivariate analysis, taking account of 11 other known risk factors. However, SBP was more strongly related to total, CVD and CHD mortality than was DBP, whereas the reverse was true for stroke mortality. There was no significant association of either SBP or DBP with cancer and other non-cardiovascular mortality in multivariate analysis. Men who were receiving antihypertensive medication at baseline examination had a higher mortality from CVD, CHD and stroke as compared to untreated men in every category of blood pressure status. This apparently paradoxical finding probably reflects more advanced status of hypertension existing before treatment rather than adverse effects of drugs per se; however, this latter possibility cannot be dismissed.


A case of pyometra treated with endoscopic ultrasound-guided drainage.
A 90-year-old woman was admitted to our hospital because of a high-grade fever and appetite loss. On computed tomography scan, a huge cystic lesion about 10 cm in diameter was observed in the pelvic cavity, attached to the vagina and the neck of uterus. Pyometra was strongly suspected; however, a probe could not be inserted into the opening of the uterus because of atrophic changes. Therefore, we decided to perform endoscopic ultrasound (EUS)-guided drainage of the pyometra using the transrectal route. Foul-smelling yellow-brown pus was aspirated. A guide-wire was inserted and a 7 Fr catheter was inserted into the pyometra through an external fistula. We thus completed the treatment of pyometra without surgical resection.


The actual and anticipated effects of restrictions on flavoured electronic nicotine delivery systems: a scoping review.
To synthesize the outcomes of policy evaluations of flavoured electronic nicotine delivery systems (ENDS) restrictions. PubMed, Scopus, Embase and Web of Science before May 3, 2022. Studies that report sales, behaviour, or compliance outcomes related to implemented or hypothetical ENDS flavour restrictions. Restriction details, whether implemented or hypothetical, whether additional products were restricted, jurisdictional level, study locations, and outcomes classified by sales, behaviour, and compliance. We included 30 studies. Of those, 26 were conducted exclusively in the US, two in India, and two surveyed respondents in multiple countries, including the US. Twenty-one evaluated implemented restrictions, while nine considered hypothetical restrictions. Five studies evaluated product sales, 17 evaluated behaviour, and 10 evaluated compliance, with two studies reporting multiple outcomes. Two studies reported an increase and one a reduction in cigarette sales following restrictions, while three reported reductions in ENDS sales. Behavioural studies presented a mixed view of the impacts of regulations on ENDS and cigarette use. However, the use of disparate outcomes limits the comparability of studies. Studies of hypothetical restrictions suggest decreased ENDS use, increased cigarette use, and increased use of illicit markets. Studies of compliance with flavoured product restrictions that included ENDS found that 6-39% of stores sold restricted flavoured products post-restrictions. Online stores remain a potential source of restricted products. Our findings highlight the need for additional research on the impacts of ENDS restrictions. Research should further evaluate the impact of restrictions on youth and adult use of nicotine and tobacco products in addition to the effects of restrictions in countries beyond the US to enable a robust consideration of the harm-benefit trade-off of restrictions.


Liver X receptor biology and pharmacology: new pathways, challenges and opportunities.
Nuclear receptors (NRs) are master regulators of transcriptional programs that integrate the homeostatic control of almost all biological processes. Their direct mode of ligand regulation and genome interaction is at the core of modern pharmacology. The two liver X receptors LXRα and LXRβ are among the emerging newer drug targets within the NR family. LXRs are best known as nuclear oxysterol receptors and physiological regulators of lipid and cholesterol metabolism that also act in an anti-inflammatory way. Because LXRs control diverse pathways in development, reproduction, metabolism, immunity and inflammation, they have potential as therapeutic targets for diseases as diverse as lipid disorders, atherosclerosis, chronic inflammation, autoimmunity, cancer and neurodegenerative diseases. Recent insights into LXR signaling suggest future targeting strategies aiming at increasing LXR subtype and pathway selectivity. This review discusses the current status of our understanding of LXR biology and pharmacology, with an emphasis on the molecular aspects of LXR signaling that constitute the potential of LXRs as drug targets.


Neural networks modelling of streamflow, phosphorus, and suspended solids: application to the Canadian Boreal forest.
Sediment has long been identified as an important vector for the transport of nutrients and contaminants such as heavy metals and microorganisms. The respective nutrient loading to water bodies can potentially lead to dissolved oxygen depletion, cyanobacteria toxin production and ultimately eutrophication. This study proposed an artificial neural network (ANN) modelling algorithm that relies on low cost readily available meteorological data for simulating streamflow (Q), total suspended solids (TSS) concentration, and total phosphorus (TP) concentration. The models were applied to a 130-km2 watershed in the Canadian Boreal Plain. Our results demonstrated that through careful manipulation of time series analysis and rigorous optimization of ANN configuration, it is possible to simulate Q, TSS, and TP reasonably well. R2 values exceeding 0.89 were obtained for all modelled data cases. The proposed models can provide real time predictions of the modelled parameters, can answer questions related to the impact of climate change scenarios on water quantity and quality, and can be implemented in water resources management through Monte Carlo simulations.


Complex chromosomal rearrangement involving chromosomes 11, 13, 14 and 18 resulting in monosomy for 13q32----qter.
A five-year-old boy with speech delay, minor facial abnormalities and borderline psychomotor retardation was found to have a complex de novo double translocation involving four chromosomes resulting in monosomy for the segment 13q32----qter. Chromosomes involved were 11, 13, 14, and 18. The translocation between chromosome 11 and 13 was unbalanced with the loss of the segment 13q32----qter. The second translocation between 14 and 18 was apparently balanced.


A fast-screening procedure for testing the effects of pollutants in mammals.
A compartmental analysis of r the radiorespirometric study of the metabolism of [14C]glucose is described. The model is applied to the study of the effects of CH3HgCl on this metabolism. Implications of the agreement between experiment and the mathematical model for the development of fast-screening experiments for detecting in vivo effects of pollutants and toxins are discussed.


Primary Repair of Peroneus Longus Myofascial Herniation With Symptomatic Superficial Peroneal Nerve Compression.
Symptomatic myofascial herniations of the extremities occur infrequently; however, they can contribute to significant pain, weakness, and neuropathy with activity. Muscle herniation typically occurs through either a traumatic or congenital focal defect in the deep overlying fascia. Patients may present with an intermittently palpable subcutaneous mass and may have neuropathic symptoms, depending on the degree of nerve involvement. Patients are initially treated with conservative modalities, whereas surgery is reserved for patients who demonstrate persistent functional limitations and neurologic symptoms. Here, we demonstrate a technique for primary repair of a symptomatic lower-leg fascial defect.


Modeling of asthma, COPD and cystic fibrosis in sheep.
Sheep naturally allergic to Ascaris suum antigen have been used to study the pathophysiology of asthma and more recently allergic rhinitis, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. The utility of the model as it relates to the study of these diseases is discussed.


Widespread hematite at high latitudes of the Moon.
Hematite (Fe2O3) is a common oxidization product on Earth, Mars, and some asteroids. Although oxidizing processes have been speculated to operate on the lunar surface and form ferric iron-bearing minerals, unambiguous detections of ferric minerals forming under highly reducing conditions on the Moon have remained elusive. Our analyses of the Moon Mineralogy Mapper data show that hematite, a ferric mineral, is present at high latitudes on the Moon, mostly associated with east- and equator-facing sides of topographic highs, and is more prevalent on the nearside than the farside. Oxygen delivered from Earth's upper atmosphere could be the major oxidant that forms lunar hematite. Hematite at craters of different ages may have preserved the oxygen isotopes of Earth's atmosphere in the past billions of years. Future oxygen isotope measurements can test our hypothesis and may help reveal the evolution of Earth's atmosphere.


Sex differences and structural brain maturation from childhood to early adulthood.
Recent advances in structural brain imaging have demonstrated that brain development continues through childhood and adolescence. In the present cross-sectional study, structural MRI data from 442 typically developing individuals (range 8-30) were analyzed to examine and replicate the relationship between age, sex, brain volumes, cortical thickness and surface area. Our findings show differential patterns for subcortical and cortical areas. Analysis of subcortical volumes showed that putamen volume decreased with age and thalamus volume increased with age. Independent of age, males demonstrated larger amygdala and thalamus volumes compared to females. Cerebral white matter increased linearly with age, at a faster pace for females than males. Gray matter showed nonlinear decreases with age. Sex-by-age interactions were primarily found in lobar surface area measurements, with males demonstrating a larger cortical surface up to age 15, while cortical surface in females remained relatively stable with increasing age. The current findings replicate some, but not all prior reports on structural brain development, which calls for more studies with large samples, replications, and specific tests for brain structural changes. In addition, the results point toward an important role for sex differences in brain development, specifically during the heterogeneous developmental phase of puberty.


Sexual Quality of Life and Association With HIV and Sexually Transmitted Infections Among a Cohort of Heterosexual Couples in Kenya.
Sexual quality of life (SQoL) is a critical component of sexual health and is understudied in Sub-Saharan African settings with endemic HIV and sexually transmitted infection (STI). We sought to assess SQoL among heterosexual couples in Kisumu, Kenya, and how this was associated with HIV status, STIs, and sexual practices. This was a prospective cohort study of community-recruited couples. SQoL, HIV status, herpes simplex virus (HSV)-2 status, bacterial vaginosis (BV), sexual practices, and sociodemographics were measured at baseline, 6 months, and 12 months. Multivariable linear regression with random intercept was fitted separately for females and males, accounting for partner characteristics. SQoL was assessed with an 18-item female and 11-item male survey. From April 2014 through July 2016, 252 couples were enrolled, and followed up through September 2017. At baseline, women were median age 23 years, 10% HIV positive, 53% HSV-2 seropositive, and 22% with BV. At baseline men were median age 26 years, 12% HIV positive, 47% HSV-2 seropositive, and 56% circumcised. Mean SQoL was higher for men (88) than women (78), with consistent scores over time. In multivariable analysis (P < .05 each), SQoL Questionnaire-Female (SQoL-F) score was reduced with: male partner report that sex felt rougher than he would have liked (9.5-point decrease), female HSV-2 seropositivity (5.15-point decrease), female reported having dry vaginal sex (5.27-point decrease); among women with BV, SQoL-F score declined with recent sexual activity (8.27-point decrease) and increasing age (0.75-point decrease per 1 year increase in age). Age and recent sex did not affect SQoL-F for women without BV. SQoL Questionnaire-Male score was decreased 4.99 points if male was employed, 4.52 points if male reported multiple recent sex partners, and 29.5 points for HIV positive men whose female partner reported having sex when not in the mood. Men's SQoL increased by 0.84 points for each 1-U increase in female partner body mass index and 17.6 points for HIV positive men whose female partner reported recent sex with him. Within sexual partnerships, men had greater SQoL than women, and the adverse impact of BV and STIs on SQoL was greater for women than men. Research is needed to ensure relevant domains are measured in settings where measure of SQoL has not been validated, along with robust measures of physiologic and psychologic correlates. More attention to SQoL as an outcome may strengthen interventions aimed at preventing HIV and STIs and improving sexual health holistically. Mehta SD, Nordgren RK, Agingu W, et al. Sexual Quality of Life and Association With HIV and Sexually Transmitted Infections Among a Cohort of Heterosexual Couples in Kenya. J Sex Med 2018;15:1446-1455.


Mucoadhesive properties of cross-linked high amylose starch derivatives.
Acetate (Ac-), aminoethyl (AE-) and carboxymethyl (CM-)derivatives of cross-linked high amylose starch (HASCL-6) were previously shown to control, over more than 20h, the release of drugs from highly loaded (up to 60% drug) monolithic tablets. It was now of interest to evaluate their mucoadhesive characteristics in view of further utilization in buccal or vaginal transmucosal delivery. The present study shows that ionic AE-HASCL-6 and CM-HASCL-6 derivatives exhibit higher mucoadhesive properties than neutral HASCL-6 and Ac-HASCL-6, suggesting that the ionic groups introduced on cross-linked starch chains play a role in the bioadhesion process. The adhesiveness seemed related to capillary attraction forces. Surface adhesion parameters were calculated for slabs based on the mentioned polymers and corroborated with their swelling behavior at various pH changes. The positively charged AE-derivatives presented a higher adhesion at acidic pH, being thus recommended for vaginal delivery, whereas the negatively charged derivatives (CM-HASCL-6) exhibited a better adhesion at neutral pH, being thus more appropriate for buccal delivery.


Bacterial Growth: Cell-Cycle Dependent Growth-Rate Homeostasis.
In the study of bacterial growth, the prevailing conclusion is that cells grow exponentially at a constant rate throughout the cell cycle. Using a new approach, Nordholt et al. reveal that bacterial growth is biphasic; immediately after division, the cell grows linearly, transitioning to exponential growth towards the end of the cell cycle.


Bruising in non-accidental head injured children; a retrospective study of the prevalence, distribution and pathological associations in 24 cases.
Non-accidental head injury, be it shaking, impact(s) or a combination of the two, is characterised by subdural and/or subarachnoid haemorrhages with retinal haemorrhages, but minimal or absent external cranio-facial trauma. The classical assault scenario depicts the infant being gripped around the head, face, chest and abdomen and shaken or being gripped by a limb and swung. This gripping might be expected to leave physical evidence in the form of bruising. A study was undertaken to establish the prevalence, distribution and pathological association of external bruising in 24 cases of fatal non-accidental head injury in children. At autopsy, 17 cases had new external bruises, 15 old external bruises and 13, a combination of both. However, seven (29%) cases showed no fresh external bruising and five (21%) showed no external bruising at all. Thus, external bruising may be absent in children with fatal intracranial injury. The face was shown to be the commonest site of bruising followed by the forehead and buttocks. Limb, chest and abdominal bruising were found to be uncommon. Retinal haemorrhages were confirmed in 23 (96%) cases. It is hypothesised that bruising, when present, may be a result of abuse in the form of punches and slaps rather than due to gripping during the assault. We discuss why gripping does not necessarily result in external bruising.


[Resection of malignant tumors of the anterior skull base and the fronto-orbito-ethmoidal region by overturn of frontonasal flap].
To introduce a better surgical approach for the resection of malignant tumors in the anterior skull base and in the fronto-orbito-ethmoidal region. A "U" form incision on the bilateral superciliary arch was made and connected with the unhealthy nasal side incision. Then the frontal musculocutaneous flap was over-turned upward. The nasal pyramid was over-turned to the healthy side. The malignant tumors in the anterior skull base and the fronto-orbito-ethmoidal region were fully exposed and resected. From december 1986 to december 1996, 50 patients received tumour resection through this approach. Postoperatively, the one-year survival rate was 86.0% (43/50), the three-year survival rate was 62.0% (31/50), and the five-year survival rate was 44.0% (22/50). The frontonasal flap overturn approach provided good exposure of surgical field, avoided the coronal incision, and the reaction of brain was mild. We believe this surgical approach is superior to traditional combined craniofacial approach.


Reversible cytotoxic edema in the splenium of the corpus callosum related to antiepileptic treatment: report of two cases and literature review.
Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology. We report two cases including a 25-year-old male patient and a 12-year-old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation. Comprehensive MRIs, including diffusion tensor imaging-based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient. On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion.


Detection of main urinary metabolites of β2-agonists clenbuterol, salbutamol and terbutaline by liquid chromatography high resolution mass spectrometry.
Clenbuterol, terbutaline and salbutamol are B2-agonists drugs included in the list of banned substances of the World Anti Doping Agency (WADA) prohibited in and out of competition. In this article, the excretion of urinary metabolites of clenbuterol, terbutaline and salbutamol have been studied using liquid chromatography electrospray time-of-flight mass spectrometry (LC-TOFMS), after a single therapeutic dose administration in rats. Urine collected was processed with solid-phase extraction prior to LC-TOFMS analyses using electrospray in the positive ion mode and pseudo MS/MS experiments from in-source collision induced dissociation (CID) fragmentation (without precursor ion isolation). The strategy applied for the identification of metabolites was based on the search of typical biotransformations with their corresponding accurate mass shift and the use of common diagnostic fragment ions from the parent drugs. The approach was satisfactory applied, achieving the identification of 11 metabolites (5 from clenbuterol, 4 from salbutamol and 3 from terbutaline), 4 of them not previously reported in urine. Novel metabolites identified in rat urine included N-oxide-salbutamol, hydroxy-salbutamol, methoxy-salbutamol glucuronide and terbutaline N-oxide, which are all reported here for the first time.


Sequential deposition of latent TGF-beta binding proteins (LTBPs) during formation of the extracellular matrix in human lung fibroblasts.
Latent TGF-beta binding proteins (LTBPs) mediate the targeting of latent TGF-beta complexes into ECM structures, which is important for TGF-beta activation and functions. LTBPs-1, -3 and -4 associate with and regulate the bioavailability of TGF-betas. We investigated whether LTBP-3 and -4 are associated with pericellular fibrillar structures of human lung fibroblast ECM, and which of their domains are important for this function. Immunoblotting analyses of isolated insoluble matrices as well as immunofluorescence analyses and confocal microscopy indicated that both LTBP-3 and -4 get assembled into the ECM. Interestingly, LTBP-4 was not detected until 7-10 days of culture and LTBP-3 until 14 days of culture. This was a major difference from the deposition kinetics of LTBP-1, which was detected already within 2 days of culture. Expression analyses by real time RT-PCR indicated that the slow appearance of LTBP-3 and -4 was due to the low expression levels soon after subculture. Recombinant N-terminal fragments of LTBP-3 and -4 bound readily to fibroblast ECM. The C-terminal domain of LTBP-4, but not of LTBP-3, also associated with the matrix structures. The levels of ECM-associated latent complexes of TGF-beta1 increased in parallel with the increased production and deposition of the LTBPs. The amount of active TGF-beta in the conditioned medium decreased during extended culture. Our results suggest that ECM is an important site of deposition also for LTBP-3 and -4 and that the temporal and spatial targeting of the TGF-beta complexes are associated with ECM maturation.


Dilated cardiomyopathy complicating a case of epidermolysis bullosa dystrophica.
A child with epidermolysis bullosa dystrophica, recessive type (EBDR) developed significant anemia at 9 years of age and was treated with long-term transfusion therapy. At age 17 he had symptoms of congestive heart failure secondary to dilated cardiomyopathy. Treatment with digoxin and vasodilators for the past year has failed to improve his cardiomyopathy significantly. Chronic iron overload and secondary hemosiderosis may have contributed to his problems, and we propose that chelation therapy be used in any child receiving long-term transfusion therapy.


Sub-optimal modulation of gain by the cognitive control system in young adults with early psychosis.
Executive dysfunctions in early psychosis (EP) are subtle but persistent, hindering recovery. We asked whether changes in the cognitive control system (CCS) disrupt the response to increased cognitive load in persons with EP. In all, 30 EP and 30 control participants undertook multimodal MRI. Computational models of structural and effective connectivity amongst regions in the CCS were informed by cortical responses to the multi-source interference task, a paradigm that selectively introduces stimulus conflict. EP participants showed greater activation of CCS regions, including the superior parietal cortex, and were disproportionately slower at resolving stimulus conflict in the task. Computational models of the effective connectivity underlying this behavioral response suggest that the normative (control) group resolved stimulus conflict through an efficient and direct modulation of gain between the visual cortex and the anterior insula (AI). In contrast, the EP group utilized an indirect path, with parallel and multi-region hops to resolve stimulus conflict at the AI. Individual differences in task performance were dependent on initial linear gain modulations in the EP group versus a single nonlinear modulation in the control group. Effective connectivity in the EP group was associated with reduced structural integration amongst those connections critical for task execution. CCS engagement during stimulus conflict is hampered in EP owing to inefficient use of higher-order network interactions, with high tonic gain impeding task-relevant (phasic) signal amplification.


Anti-inflammatory effects of a SERP 30 polysaccharide from the residue of Sarcandra glabra against lipopolysaccharide-induced acute respiratory distress syndrome in mice.
Sarcandra glabra (Thunb.) Nakai, a valuable dietetic Chinese herb, is still widely used today. Multiple ingredients of S. glabra with a variety of activities such as anti-inflammatory, antiviral, and antitumor were studied. However, the Sarcandra glabra (Thunb.) Nakai polysaccharide hasn't been reported for its anti-inflammatory effect. In this study, the anti-inflammatory activity of Sarcandra glabra (Thunb.) Nakai polysaccharide was assessed in LPS-induced ARDS mice. A polysaccharide coded as SERP 30 was obtained by water extraction, alcohol precipitation, and gel filtration. After the physicochemical properties determination and structural characterization, LPS induced-mice ARDS model was used to evaluate the anti-inflammatory and associated antioxidant activities of SERP 30. H&E staining was used to observe the seriousness of lung injury in mice. The ELISA method was used to measure the expression of inflammatory factors (TNF-α and IL-6) in the serum of the mice. The TBA method and the WST-1 method were used to evaluate the oxidative stress injury. Immunohistochemistry was used to distinguish the expression of metalloproteinase-9 (MMP-9), heparinase (HPA), syndecan-1, and decorin in ARDS-mice lung tissue. Western blotting was used to confirm the expression of related proteins in mouse lung tissue. SERP 30 had a potential role in improving lung damage, reducing inflammation, and preventing oxidative stress. Moreover, SERP 30 significantly attenuated the damage to the endothelial glycocalyx and maintained the integrity of the glycocalyx. The western blotting result implied that the main anti-inflammatory mechanism is directed towards NF-κB and MAPK signaling pathways with inhibiting the activation of associated proteins. This research provides a theoretical basis for treating ARDS by using a byproduct from food resource.


'I just hope they take it seriously': homeless men talk about their health care.
Objective Men who experience homelessness in Australia often have complex health and social issues, including the trimorbidity of concurrent mental illness, substance use disorders and physical health conditions. These men tend to have poor health outcomes, and present challenges to healthcare systems. To improve system responsiveness and patient outcomes, the perspectives of marginalised groups need to be understood. Methods Five focus groups were conducted with 20 men in a homeless men's hostel, exploring their experiences of seeking and receiving health care, and views about improving these. An inductive thematic analysis was undertaken. Results Several participants expressed gratitude for care provided for life-threatening physical illness and trauma. However, negative experiences of health system responses were more frequently reported. Four emerging themes all made securing effective 'tickets of entry' to health care more difficult: dismissive care, care fragmentation, inconsistent medical management of pain and inadequate acknowledgement of psychological distress. Conclusions Improvements are needed in care integration and the de-escalation of potentially confrontational interactions. Effective, safe and compassionate system responses to presentations of psychological distress and pain should be collaboratively developed. Some current responses may entrench stigma, further traumatising vulnerable patients. What is known about the topic? Men who experience homelessness have poor health outcomes and present challenges to healthcare systems. What does this paper add? This paper describes healthcare experiences and insights of men who are experiencing homelessness in Australia. These men reported experiencing dismissive care, care fragmentation, inconsistent, inadequate and/or unsafe prescribing for pain and inconsistent and/or ineffective responses to psychological distress. What are the implications for practitioners? Changes are needed in health system responses, informed by the experiences and insights of marginalised people, to break cycles of trauma and exclusion.


Highly preferred site of insertion of Tn7 into the chromosome of Vibrio anguillarum.
The possible usefulness of Tn7 as a tool for genetic studies in Vibrio anguillarum was examined. Using the plasmid pRK2073 as the transposon donor, Tn7 transposes at high frequency into the chromosome of V. anguillarum. However, hybridization analysis of the mutants DNA digested with different enzymes revealed that all isolates have the insertions in the same site. This indicates that like in many other gram-negative bacteria, Tn7 shows a specificity of transposition in the chromosome of V. anguillarum. Plasmid pRK2013 proved to be a very useful delivery vector for transposon mutagenesis in V. anguillarum.


Neonatal posterior cerebral artery stroke: clinical presentation, MRI findings, and outcome.
To report the clinical presentation, magnetic resonance imaging (MRI) findings, and follow-up data of newborn infants with perinatal arterial ischemic stroke in the territory of the posterior cerebral artery (PCA). Data on 18 newborn infants from three neonatal intensive care units (11 males, seven females) with an MRI-confirmed PCA stroke were analysed and reported. Infants were born at a mean gestational age of 38.7 weeks (SD 3.4) with a mean birthweight of 3244g (SD 850). Fourteen infants presented with clinical seizures. Five of these had associated hypoxic-ischemic encephalopathy, four had hypoglycaemia, and five had neither hypoxic-ischemic encephalopathy nor hypoglycaemia. Subclinical seizures were present in one infant with hypoxic-ischemic encephalopathy and one with meningitis. One preterm infant presented with apnoeas and one had hypoxic-ischemic encephalopathy without seizures. Neurodevelopmental follow-up of 17 children at a median age of 36 months (SD 28, range 12-120mo) showed five with a global delay. Two children with additional injury developed postneonatal epilepsy and one child with extensive injury developed hemiplegia. A visual field defect was observed in nine children (six hemianopia, three quadrantanopia). In the 11 children with a second MRI at 3 months, the asymmetry of the optic radiation correlated with the development of a visual field deficit. Outcome after PCA stroke is fairly good, depending on additional brain injury. Follow-up is required, as subsequent visual field defects are frequently observed. Further research will be needed to clarify the role of hypoglycaemia in perinatal arterial ischemic stroke.


The surgical management of vertebrobasilar insufficiency.
Vertebrobasilar insufficiency may result from structural lesions anywhere along the vertebrobasilar system. Recently developed techniques in angiography and microsurgery have made the vertebrobasilar system more accessible to surgical therapy. The syndrome of vertebrobasilar insufficiency is discussed, and our experience with the surgical treatment of lesions from the vertebral origin to the distal basilar region is reviewed.


Rumination as a transdiagnostic process: The role of rumination in relation to antisocial and borderline symptoms.
The present study examined the influence of several forms of repetitive negative thinking on antisocial and borderline symptoms to identify underlying mechanisms that may contribute to the presentation and cooccurrence of these symptoms. Participants (N = 403), completed the Personality Assessment Inventory, the Personality Diagnostic Questionnaire-4, and several measures of rumination/worry. Path analyses were conducted in which different forms of rumination/worry predicted antisocial and borderline symptoms across two personality disorder measures. Across both models tested, anger rumination emerged as the strongest predictor of both antisocial and borderline symptoms while worry negatively predicted antisocial symptoms. Rumination and worry explained substantially more variance in borderline symptoms compared to antisocial symptoms. This study is the first study to examine antisocial symptoms in relation to forms of rumination/worry and highlights the differential relations of rumination/worry to antisocial and borderline symptoms using a multi-measure approach. Further, this study highlights the importance of examining types of repetitive negative thinking, specifically rumination, as potential transdiagnostic processes.


The central action of various arecaidine esters (arecoline derivatives) on blood pressure and heart rate in the cat. Comparison with the peripheral effects.
The central action of various arecaidine esters (arecoline derivatives) on the cardiovascular system has been studied. Central injection of these cholinergic drugs into the vertebral artery of the cat gives rise to a hypotensive effect, whereas heart rate is not affected. It is concluded that the blood pressure lowering effect is brought about by stimulating central muscarinic receptors. Moreover, the experimental results indicate that the central muscarinic receptors behave in the same way towards their agonists as do the peripheral muscarinic receptors.


Two mixed-ligand lanthanide-hydrazone complexes: [Pr(NCS)3(pbh)2]·H2O and [Nd(NCS)(NO3)(pbh)2(H2O)]NO3·2.33H2O [pbh is N'-(pyridin-2-ylmethylidene)benzo-hydrazide, C13H11N3O].
The gel-mediated syntheses and crystal structures of [N'-(pyridin-2-ylmethylidene-κN)benzohydrazide-κ(2) N',O]tris(thiocyanato-κN)praseodymium(III) mono-hydrate, [Pr(NCS)3(C13H11N3O)2]·H2O, (I), and aqua(nitrato-κ(2) O,O')[N'-(pyri-din-2-ylmethylidene-κN)benzohydrazide-κ(2) N',O](thiocyanato-κN)neo-dym-ium(III) nitrate 2.33-hydrate, [Nd(NCS)(NO3)(C13H11N3O)2(H2O)]NO3·2.33H2O, (II), are reported. The Pr(3+) ion in (I) is coordinated by two N,N,O-tridentate N'-(pyridin-2-ylmethylidene)benzohydrazide (pbh) ligands and three N-bonded thio-cyanate ions to generate an irregular PrN7O2 coordination polyhedron. The Nd(3+) ion in (II) is coordinated by two N,N,O-tridentate pbh ligands, an N-bonded thio-cyanate ion, a bidentate nitrate ion and a water mol-ecule to generate a distorted NdN5O5 bicapped square anti-prism. The crystal structures of (I) and (II) feature numerous hydrogen bonds, which lead to the formation of three-dimensional networks in each case.


Bioreduction of hexavalent chromium by a novel haloalkaliphilic Salipaludibacillus agaradhaerens strain NRC-R isolated from hypersaline soda lakes.
A novel Cr(VI)-resistant haloalkaliphilic bacterial strain NRC-R, identified as Salipaludibacillus agaradhaerens, was isolated from hypersaline soda lakes and characterized for its Cr(VI) bioreduction efficiency. Strain NRC-R grew well and effectively reduced Cr(VI) under a wide range of sodium chloride, pH, shaking velocity and temperature, showing maximum Cr(VI) reduction at 8% NaCl, pH 10, 150 rpm and 35 °C, respectively. Strain NRC-R was able to grow and reduce Cr(VI) effectively in the presence of different heavy metals and oxyanions (Pb2+, Zn2+, Co2+, Mn2+, Ni2+, Mo2+, HPO4 -, NO3 -, SO4 2- and HCO3 -). Furthermore, Fe3+ and Cu2+ significantly enhanced the Cr(VI) removal by about 1.5 fold. Strain NRC-R could reduce Cr(VI) using a variety of electron donors, exhibiting a maximum reduction in the presence of NADH and fructose. The bioremoval of Cr(VI) using strain NRC-R was due to direct enzymatic reduction and the chromate reductase activity was mainly detected in the bacterial cell membrane. Under the optimized conditions, strain NRC-R showed a remarkable Cr(VI) bioreduction with highest reduction rate of 240 uM/h. Cr(VI) concentrations of up to 3 mM (888.5 mg/L) and 4 mM (1177 mg/L) were completely reduced within 16 h and 32 h, respectively. TEM and SEM-EDX analyses confirmed the biosorption of chromium species into the cells. To the best of our knowledge, this is the first report about Cr(VI) reduction by S. agaradhaerens. In conclusion, S. agaradhaerens NRC-R was a highly efficient Cr(VI) reducing haloalkaliphilic bacterium that has a significant potential in the bioremediation of Cr(VI)-contaminated environments. The online version contains supplementary material available at 10.1007/s13205-021-03082-2.


Benign/malignant classifier of soft tissue tumors using MR imaging.
This article presents a pattern-recognition approach to the soft tissue tumors (STT) benign/malignant character diagnosis using magnetic resonance (MR) imaging applied to a large multicenter database. To develop and test an automatic classifier of STT into benign or malignant by using classical MR imaging findings and epidemiological information. A database of 430 patients (62% benign and 38% malignant) from several European multicenter registers. There were 61 different histologies (36 with benign and 25 with malignant nature). Three pattern-recognition methods (artificial neural networks, support vector machine, k-nearest neighbor) were applied to learn the discrimination between benignity and malignancy based on a defined MR imaging findings protocol. After the systems had learned by using training samples (with 302 cases), the clinical decision support system was tested in the diagnosis of 128 new STT cases. An 88-92% efficacy was obtained in a not-viewed set of tumors using the pattern-recognition techniques. The best results were obtained with a back-propagation artificial neural network. Benign vs. malignant STT discrimination is accurate by using pattern-recognition methods based on classical MR image findings. This objective tool will assist radiologists in STT grading.


Identification and partial characterization of common seal (Phoca vitulina) and grey seal (Haliochoerus grypus) interleukin-6-like activities.
Interleukin-6 (IL-6) is a pleiotropic molecule with many important immune modulatory actions. We have investigated the production of biological activity of this cytokine in two species of European seal. IL-6-like activity was detected in supernatants from cultured peripheral blood leucocytes. This IL-6-like activity had an apparent molecular weight of 17-26 kDa, similar to that of human IL-6. IL-6-like activity was also detected in plasma taken from seals with symptoms of systemic infection, but not from apparently healthy seals. Inhibition of this plasma and leucocyte derived activity was accomplished with both rabbit and goat antisera raised against recombinant human IL-6. Further investigation using polymyxin-B showed that this activity was not due to residue LPS present in the supernatants or infected plasmas.


Enhanced visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid over ZnIn2S4/g-C3N4 photocatalyst.
ZnIn2S4/g-C3N4 heterojunction photocatalyst was successfully synthesized via a simple hydrothermal method and applied to visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous phase. The flower-like ZnIn2S4 particles were dispersed on the surface of g-C3N4 nanosheets in the ZnIn2S4/g-C3N4 composite. The composite showed higher separation rate of electron-hole pairs as compared to ZnIn2S4 and g-C3N4. Consequently, the ZnIn2S4/g-C3N4 composite exhibited enhanced visible light photocatalytic decomposition efficiency of 2,4-D, within 20% ZnIn2S4/g-C3N4 composite owning the highest photocatalytic efficiency and initial rate. The initial rates of 2,4-D degradation on g-C3N4, ZnIn2S4, and 20% ZnIn2S4/g-C3N4 were 1.23, 0.57 and 3.69mmol/(gcath), respectively. The h(+) and O2(-) were found to be the dominant active species for 2,4-D decomposition. The photocatalytic degradation pathways of 2,4-D by ZnIn2S4/g-C3N4 under visible light irradiation were explored. The ZnIn2S4/g-C3N4 composite displayed high photostability in recycling tests, reflecting its promising potential as an effective visible light photocatalyst for 2,4-D treatment.


Biochemical, histological, and memory impairment effects of chronic copper toxicity: a model for non-Wilsonian brain copper toxicosis in Wistar rat.
Animal models of copper toxicosis rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content. The aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper and zinc levels in the liver and hippocampus, on biochemical parameters, and on neurobehavioral functions (by Morris water maze) of male Wistar rats. Copper-administered animals exhibited significantly decreased serum acetylcholinesterase (AChE) activity and impaired neuromuscular coordination and spatial memory compared to control rats. Copper-intoxicated rats showed significant increase in liver and hippocampus copper content (99.1 and 73 % increase, respectively), 40.7 % reduction in hepatic zinc content, and interestingly, 77.1 % increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive grade 4 copper depositions and grade 1 copper-associated protein in hepatocytes of copper-intoxicated rats were substantiated by rhodanine and orcein stains, respectively. Copper-intoxicated rats demonstrated swelling and increase in the number of astrocytes and copper deposition in the choroid plexus, with degenerated neurons showing pyknotic nuclei and dense eosinophilic cytoplasm. In conclusion, the present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory and neuromuscular coordination, swelling of astrocytes, decreased serum AChE activity, copper deposition in the choroid plexus, neuronal degeneration, and augmented levels of copper and zinc in the hippocampus of male Wistar rats.


Growing corticospinal axons by-pass lesions of neonatal rat spinal cord.
The anterograde transport of horseradish peroxidase was used to label newly growing corticospinal axons after they had entered lesioned regions of the neonatal rat spinal cord. Two types of lesions were made at thoracic and lumbar levels before the arrival of the first corticospinal axons. (1) Thermal lesions were produced by the brief application of a heated rod to the vertebral column and could destroy the normal growth path over several spinal segments. Corticospinal axons, when successful in growing distal to thermal lesions, did so at the same rate as in normal controls and retaining their normal relative positions and morphology, especially fasciculation. (2) Surgical lesions were produced by cutting the spinal cord and were limited to one segment but could result in a barrier in the normal growth path composed of a cyst or glial scar. Corticospinal axons that succeeded in growing distal to a surgical lesion did so by being deflected to unusual positions, became defasciculated, and sometimes their normal growth rate was slowed. That corticospinal axons could in many instances grow past the two types lf lesion suggests that a morphologically stereotyped glial scaffolding is not necessary for axon growth. The role of fasciculation in normal axon growth is highlighted by the disparate effects of the two types of lesion.


Characterization by array-CGH of an interstitial de novo tandem 6p21.2p22.1 duplication in a boy with epilepsy and developmental delay.
We report on a 6-years-old boy with psychomotor retardation, mild dysmorphic features and behavioral disturbances associated with epilepsy. Conventional cytogenetic analysis concluded to an interstitial de novo 6p21.2p22.3 duplication. Molecular cytogenetic analysis, including array-CGH technology, allows characterization of this 7.3Mb interstitial tandem duplication. The phenotype of this small 6p duplication reported to date is compared to other cases in the literature. Presence of epilepsy, although rare in patients with 6p duplication may be linked to genes involved in brain function and synaptic transmission in the 6p21.2p22.1 duplicated region (GABBR1, BRD2 and GRM4).


SN 2 versus E2 Competition of Cyclic Ethers.
We have quantum chemically studied the influence of ring strain on the competition between the two mechanistically different SN 2 and E2 pathways using a series of archetypal ethers as substrate in combination with a diverse set of Lewis bases (F- , Cl- , Br- , HO- , H3 CO- , HS- , H3 CS- ), using relativistic density functional theory at ZORA-OLYP/QZ4P. The ring strain in the substrate is systematically increased on going from a model acyclic ether to a 6- to 5- to 4- to 3-membered ether ring. We have found that the activation energy of the SN 2 pathway sharply decreases when the ring strain of the system is increased, thus on going from large to small cyclic ethers, the SN 2 reactivity increases. In contrast, the activation energy of the E2 pathway generally rises along this same series, that is, from large to small cyclic ethers. The opposing reactivity trends induce a mechanistic switch in the preferred reaction pathway for strong Lewis bases from E2, for large cyclic substrates, to SN 2, for small cyclic substrates. Weak Lewis bases are unable to overcome the higher intrinsic distortivity of the E2 pathway and, therefore, always favor the less distortive SN 2 reaction.


Pleiotrophin induces nitric oxide dependent migration of endothelial progenitor cells.
Pleiotrophin (PTN) is produced under ischemic conditions and has been shown to induce angiogenesis in vivo. We studied whether or not PTN exerts chemotaxis of pro-angiogenic early endothelial progenitor cells (EPCs), a population of circulating cells that have been reported to participate in and stimulate angiogenesis. Chemotaxis of EPCs, isolated from blood of healthy humans (n = 5), was measured in transwell assays. PTN at 10-500 ng/ml elicited dose-dependent chemotaxis of both EPCs and human umbilical vein endothelial cells (HUVECs), but not of human coronary artery smooth muscle cells (CASMCs) and T98G glioblastoma cells that lack PTN receptors. The degree of chemotaxis was comparable to that induced by the angiogenic factors VEGF and SDF-1alpha. Chemotaxis to PTN was blocked by the NOS inhibitors L-NNA and L-NMMA, the NO scavenger PTIO, the phosphoinositide-3 kinase inhibitor wortmannin, and the guanylyl cyclase inhibitor ODQ, suggesting dependence of EPC chemotaxis on these pathways. PTN induced NOS-dependent production of NO to a similar degree as did VEGF, as indicated by the NO indicator DAF-2. PTN increased proliferation in EPCs and HUVECs to a similar extent as VEGF, but did not induce proliferation of CASMCs. While L-NNA abolished PTN-induced migration in EPCs and HUVECs, it did not inhibit PTN- and VEGF-enhanced proliferation and also caused proliferation by itself. These data suggest that PTN may mediate its pro-angiogenic effects by increasing the local number of not only endothelial cells but also early EPCs at angiogenic sites.


Improved results of delayed-type hypersensitivity skin testing in HIV-infected patients treated with topical dinitrochlorobenzene.
Infection with HIV results in progressive deterioration of cell-mediated immunity, with consequent impairment of delayed-type hypersensitivity (DTH) skin reactivity. Topical dinitrochlorobenzene (DNCB) is thought to increase cellular immune function in HIV infection. Our goal was to evaluate changes in DTH skin reactivity of HIV-infected patients who were given DNCB therapy. DTH skin testing and lymphocyte subset analysis were performed in five HIV-infected patients before the start of DNCB treatment and after 3 months of therapy. Topical DNCB application was carried out by the patients according to a standardized protocol. DNCB therapy enhanced DTH skin test responses in four of five patients. Three patients who were anergic before the start of treatment reacted to skin test antigens while using DNCB. The skin test results did not correlate with lymphocyte subset changes. DNCB treatment improves DTH skin test responses in HIV-infected patients, indicating a positive effect on cellular immune function.