The acute and chronic effects of wastes associated with offshore oil and gas production on temperate and tropical marine ecological processes.
A review of the acute and chronic effects of produced formation water (PFW), drilling fluids (muds) including oil-based cutting muds, water-based cutting muds, ester-based cutting muds and chemical additives, and crude oils associated with offshore oil and gas production was undertaken in relation to both temperate and tropical marine ecological processes. The main environmental effects are summarized, often in tabular form. Generally, the temporal and spatial scales of these studies, along with the large levels of inherent variation in natural environments, have precluded our ability to predict the potential long-term environmental impacts of the offshore oil and gas production industry. A series of critical questions regarding the environmental effects of the offshore oil and gas production industry that still remain unanswered are provided for future consideration.


Work-relatedness of carpal tunnel syndrome: Systematic review including meta-analysis and GRADE.
Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome with a high prevalence among workers. Insights on the physical work-related risk factors is necessary to develop appropriate preventative methods. The objective of this systematic review, including meta-analyses, is to assess which physical work-related risk factors are associated with carpal tunnel syndrome. Systematic literature searches were carried out using PubMed and Embase until September 6, 2021. Studies were included if: (1) CTS was clinically assessed, (2) the studies were prospective cohort studies, and (3) the exposure was reported using terms of exposed/less or nonexposed. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). In total, 9270 patients with CTS from a population of 1,051,707 workers were included from 17 studies. Meta-analyses revealed high-quality evidence for associations between CTS and high exposures to repetition (hazard ratio [HR] 1.87, 95% CI 1.42-2.46), force intensity (HR 1.84, 95%CI 1.22-2.79), exposures above hand activity level of ACGIH (HR 1.75, 95%CI 1.40-2.17), and the Strain Index >10 (HR 1.58, 95% CI 1.09-2.30). No significant associations were found for pinch gripping, hand-arm vibration or force duration. High computer-use exposure was significantly associated with a decreased rate of work-related CTS (HR 0.28, 95% CI 0.12-0.64). This systematic review of prospective cohort studies found high certainty for an increased rate of CTS due to a high Strain Index, exposures exceeding the Activity Level of ACGIH, and high force intensity and high repetition. Workers performing tasks requiring both high force and high repetition even have a higher rate of developing CTS.


The effect of diet on tissue levels of kinin-forming enzyme in blood-free rat gastro-intestinal tract.
1. Kallikreins, kinin-forming enzymes, are present in the wall of the gastro-intestinal tract. The role of the kinin-forming system in the gut is unknown. In the present study, a modified bio-assay technique was used to detect the presence of tissue concentration gradients of kinin-forming enzyme (KFE) at different levels of the rat gastro-intestinal tract and the effect on them of diet.2. Segments of rat gut, perfused free of blood, were homogenized in 0.1 N-HCl and activated by autolytic processes. Total KFE content was then determined by incubation of extract with standard kinin-forming substrate, followed by bio-assay of the released kinin using superfused oestrous rat uterus. Acid extraction of the KFE gave a recovery of 127.4% when compared with simple water extraction.3. Tissue concentrations of KFE were determined in stomach, duodenum, jejunum, terminal ileum, caecum and proximal and distal colon. Concentrations were determined after (A) normal diet, (B) water ad libitum for 24 hr and (C) isotonic glucose ad libitum for 60 hr.4. All the gut tissues contained KFE. After diet A there was least (19.5 +/- 1.0 ng bradykinin equivalent formed per minute (KU) per gram wet weight) in the stomach and a single large peak (504 +/- 92 KU .g(-1) wet weight) in the caecum.5. The different dietary states produced changes only in the duodenum, the caecum and the distal colon. The duodenal level was raised when the organ was empty after diet B (140 +/- 29 KU .g(-1)) and fell when filled with solid or fluid after diets A (57 +/- 14 KU .g(-1)) and C (80 +/- 17 KU .g(-1)) respectively. The caecal KFE level, which was high when the lumen was full after diet A, fell progressively as it was increasingly emptied after diets B (213 +/- 41 KU .g(-1)) and C (105 +/- 42 KU .g(-1)) respectively. The KFE concentration in the distal colon was low when the lumen was full after diets A (58 +/- 10 KU .g(-1)) and B (66 +/- 17 KU .g(-1)) and rose when the lumen was nearly empty after diet C (118 +/- 17 KU .g(-1)).6. Kinin-forming activity in rat intestinal extracts had a pH optimum at pH 8.5 and formed a bradykinin-like spasmogen. The increased activity in the fasted rat duodenum was not significantly inhibited by soybean trypsin inhibitor (100 mug/ml.) while that in caeci from fed rats was inhibited by 17% (P < 0.05).7. These changes may indicate physiological involvement of the kallikrein-kinin system in these organs.


Cardiorespiratory Fitness, Smoking Status, and Risk of Incidence and Mortality From Cancer: Findings From the Veterans Exercise Testing Study.
To assess the joint and stratified associations between cardiorespiratory fitness (CRF), incidence, and mortality from cancer in never, former, and current male smokers. CRF (treadmill exercise test) was assessed in 4694 men (never smokers [n = 1715]; former smokers [n = 1602], 32.4 [30.5] pack-years; and current smokers [n = 1377], 40.3 [26] pack-years) aged 58.1 (17.3) years, and prospectively followed for 12.7 (7.5) years. Multivariable Cox hazard models were analyzed. In joint analyses, where high CRF in never smokers was used as a reference, hazard ratios and 95% (confidence intervals) for cancer incidence and cancer mortality were as follows: moderate CRF 1.41 (1.0-1.9) and 3.0 (1.7-5.5) in never smokers, 1.65 (1.3-2.2) and 3.7 (2.1-6.6) in former smokers, and 1.3 (0.9-1.7) and 3.4 (1.9-6.1) in current smokers, respectively. The corresponding values for low CRF were 1.53 (1.1-2.2) and 5.1 (2.7-9.5), 1.84 (1.3-2.5) and 6.6 (3.7-11.8), and 1.5 (1.1-2.2) and 5 (2.7-9.3), respectively. In stratified analyses by smoking status, compared with low CRF, moderate and high CRF were associated with a 32% to 78% reduction in cancer mortality risk (P trend for all <.001). Higher CRF is associated with lower risk of incidence and mortality from cancer regardless of smoking status, supporting the potential preventive benefits for public health.


Preliminary results of the certification study for the determination of zearalenone in maize.
Twenty-six laboratories from the EU participated in the final interlaboratory comparison study of the Standard Measurement and Testing (SMT) project of the European Commission for the preparation and certification of reference materials for the determination of the Fusarium mycotoxin zearalenone (ZON) in maize.Two different maize materials were distributed to the participants, naturally contaminated maize and 'blank' maize material. Additionally, a common ZON calibrant was provided for the quantification.The participating laboratories employed mainly immuno-affinity column techniques for the clean-up and high performance liquid chromatography (HPLC) followed by fluorescence detection for the final separation and quantification.A good mean recovery of 95.5% and trueness was obtained for the maize samples spiked at 99.5 μg/kg ZON. The relative between-laboratory standard deviations (RSDR) ranged from 6 to 12% for naturally ZON contaminated and spiked maize.


Using Cognitive Behavior Therapy and Mindfulness Techniques in the Management of Chronic Pain in Primary Care.
Chronic pain and its associated syndrome have become increasingly prevalent in primary care. With the increase in narcotic use and subsequent adverse events, primary care physicians often seek safer alternatives to treating this condition. Prescribing narcotics necessitates using methods to screen for high abuse risk and protect against misuse. With the understanding of how chronic pain is related to mental illnesses such as depression and posttraumatic stress disorder, mindfulness techniques and behavioral therapy can be used to help decrease the dependence on dangerous opioid medications and help patients understand, accept, and cope with their chronic pain.


Geographic isolation and elevational gradients promote diversification in an endemic shrew on Sulawesi.
Phylogeographic research on endemic primates and amphibians inhabiting the Indonesian island of Sulawesi revealed the existence of seven areas of endemism (AoEs). Here, we use phylogenetic and population genetic analyses of one mitochondrial gene and 15 nuclear loci to assess geographic patterns of genetic partitioning in a shrew (Crocidura elongata) that is endemic to Sulawesi, but occurs across the island. We uncover substantial genetic diversity in this species both between and within AoEs, but we also identify close relationships between populations residing in different AoEs. One of the earliest divergences within C. elongata distinguishes a high-elevation clade from low-elevation clades. In addition, on one mountain, we observe three distinct genetic groups from low, middle, and high elevations, suggesting divergence along a single elevational gradient. In general, our results show that C. elongata, like several other Sulawesi endemic taxa, harbors extensive genetic diversity. This diversity is structured in part by known AoE boundaries, but also by elevational gradients and geographic isolation within AoEs.


A new technique for dissection of the pulmonary vessels.
The conventional method for dissection of the pulmonary artery and vein has been described repeatedly [1-4]. However these sources have only presented dissection of the sheaths of vessels by exfoliation [1-3]. This article describes a new technique for the safe and rapid dissection of these vessels.


[In vitro cultivation of Plasmodium cynomolgi bastianelli in hepatocytes of the Macaca rhesus].
Primary cultures of Rhesus monkey were infected with sporozoites of P. c. bastianelli. Despite a high level of contamination, two schizonts were seen at days 6 and 11.


Mendelian randomization.
Mendelian randomization (MR) is a term that applies to the use of genetic variation to address causal questions about how modifiable exposures influence different outcomes. The principles of MR are based on Mendel's laws of inheritance and instrumental variable estimation methods, which enable the inference of causal effects in the presence of unobserved confounding. In this Primer, we outline the principles of MR, the instrumental variable conditions underlying MR estimation and some of the methods used for estimation. We go on to discuss how the assumptions underlying an MR study can be assessed and give methods of estimation that are robust to certain violations of these assumptions. We give examples of a range of studies in which MR has been applied, the limitations of current methods of analysis and the outlook for MR in the future. The difference between the assumptions required for MR analysis and other forms of non-interventional epidemiological studies means that MR can be used as part of a triangulation across multiple sources of evidence for causal inference.


An fMRI study of theory of mind in schizophrenic patients with "passivity" symptoms.
Several studies have shown that patients with schizophrenia underactivate brain regions involved in theory of mind relative to controls during functional brain imaging. However, in most studies the samples were fairly heterogeneous in terms of clinical symptomatology. We examined a group of nine patients with first episode or recurrent episodes, who clinically presented with predominant "passivity" symptoms such as third-person auditory hallucinations or delusion of control, using a cartoon-based theory of mind task and compared activation patterns with a group of 13 healthy controls. All patients responded well to antipsychotic treatment and were only mildly symptomatic at the time of testing. The patient group showed significantly less activation of the right anterior cingulate cortex (ACC) and right insula compared with controls, but greater activation in dorsal areas of the medial prefrontal cortex, right temporal areas and left temporo-parietal junction. Patients with schizophrenia with predominant "passivity" symptoms and good response to antipsychotic treatment show a markedly diverging pattern of brain activation during theory of mind task performance compared with healthy controls. These findings suggest abnormal activation of those brain areas involved in the evaluation of self-reference during mental state attribution.


Phenology, activity and regulation of radiation load in the desert isopod, Hemilepistus reaumuri.
The phenology and activity of the isopod H. reaumuri has been studied since 1972, in the Negev desert; five distinct phenophases were identified in the annual life cycle of the isopod. From the relationship between activity pattern, phenophases, and microclimatic data it was concluded that H. reaumuri's principal strategy of compensating for its' physiological constraints is through behavioural regulation of energy inflow. (850-1000 cal. cm-2 day-1).


[Silver staining of the nucleolus organizer regions in the interphase cells of an embryonic pig kidney culture during and after administration actinomycin D].
Silver staining of nucleolus organizer regions was used for studying their structural alterations during inhibition of ribosomal RNA synthesis by actinomycin D and after its removal in pig kidney cells. Three nuclear types were revealed from the pattern of restored silver grains distribution in the nuclei. When the inhibitor was removed, nuclear multitype gradually disappeared for 24 hours and nuclear RNA synthesis became normal.


Single-bolus injection of local anesthetic, with or without continuous infusion, for interscalene brachial plexus block in the setting of multimodal analgesia: a randomized controlled unblinded trial.
Previous trials favored a continuous interscalene brachial plexus block over a single injection for major shoulder surgery. However, these trials did not administer a multimodal analgesic regimen. This randomized, controlled unblinded trial tested the hypothesis that a continuous infusion of local anesthetic for an interscalene brachial plexus block still provides superior analgesia after major shoulder surgery when compared with a single injection in the setting of multimodal analgesia, inclusive of intravenous dexamethasone, magnesium, acetaminophen and ketorolac. Sixty patients undergoing shoulder arthroplasty or arthroscopic rotator cuff repair were randomized to receive a bolus of ropivacaine 0.5%, 20 mL, with or without a continuous infusion of ropivacaine 0.2% 4-8 mL/hour, for an interscalene brachial plexus block. Patients were provided with intravenous morphine patient-controlled analgesia. The primary outcome was cumulative intravenous morphine consumption at 24 hours postoperatively. Secondary outcomes included pain scores at rest and on movement, and functional outcomes, measured over 48 hours after surgery. Median (IQR) cumulative intravenous morphine consumption at 24 hours postoperatively was 10 mg (4-24) in the continuous infusion group and 14 mg (8-26) in the single injection group (p=0.74). No significant between-group differences were found for any of the secondary outcomes. A continuous infusion of local anesthetic for an interscalene brachial plexus block does not provide superior analgesia after major shoulder surgery when compared with a single injection in the setting of multimodal analgesia, inclusive of intravenous dexamethasone, magnesium, acetaminophen and ketorolac. The findings of this study are limited by performance and detection biases. NCT04394130.


The epithelial calcium channel TRPV5 is regulated differentially by klotho and sialidase.
The transient receptor potential vanilloid type 5 (TRPV5) Ca(2+) channel facilitates transcellular Ca(2+) transport in the distal convoluted tubule (DCT) of the kidney. The channel is glycosylated with a complex type N-glycan and it has been postulated that hydrolysis of the terminal sialic acid(s) stimulate TRPV5 activity. The present study delineates the role of the N-glycan in TRPV5 activity using biochemical assays in Human Embryonic Kidney 293 cells expressing TRPV5, isoelectric focusing and total internal reflection fluorescent microscopy. The anti-aging hormone klotho and other glycosidases stimulate TRPV5-dependent Ca(2+) uptake. Klotho was found to increase the plasma membrane stability of TRPV5, via the TRPV5 N-glycan. Sialidase mimicked this stimulatory action. However, this effect was independent of the N-glycosylation state of TRPV5, since the N-glycosylation mutant (TRPV5(N358Q)) was activated to the same extent. We showed that the increased TRPV5 activity after sialidase treatment is caused by inhibition of lipid raft-mediated internalization. In addition, sialidase modified the N-glycan of transferrin, a model glycoprotein, differently from klotho. Previous studies showed that after klotho treatment, galectin-1 binds the TRPV5 N-glycan and thereby increases TRPV5 activity. However, galectin-3, but not galectin-1, was expressed in the DCT. Furthermore, an increase in TRPV5-mediated Ca(2+) uptake was detected after galectin-3 treatment. In conclusion, two distinct TRPV5 stimulatory mechanisms were demonstrated; a klotho-mediated effect that is dependent on the N-glycan of TRPV5 and a sialidase-mediated stimulation that is lipid raft-dependent and independent of the N-glycan of TRPV5.


The velo-cardio-facial syndrome: the otorhinolaryngeal manifestations and implications.
The velo-cardio-facial syndrome (VCFS), due to a deletion in chromosome 22 on its long arm (22q11), is a leading cause of velopharyngeal dysfunction and cleft palate. With the recent finding of a deletion on chromosome 22q11 in these patients with velopharyngeal dysfunction, a routine test is available making the diagnosis of VCFS much more frequent than previously thought.


Performance of Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Using Fluorine-18-Fluorodeoxyglucose for the Diagnosis, Staging, and Recurrence Assessment of Bone Sarcoma: A Systematic Review and Meta-Analysis.
To investigate the performance of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the diagnosis, staging, restaging, and recurrence surveillance of bone sarcoma by systematically reviewing and meta-analyzing the published literature.To retrieve eligible studies, we searched the MEDLINE, Embase, and the Cochrane Central library databases using combinations of following Keywords: "positron emission tomography" or "PET," and "bone tumor" or "bone sarcoma" or "sarcoma." Bibliographies from relevant articles were also screened manually. Data were extracted and the pooled sensitivity, specificity, and diagnostic odds ratio (DOR), on an examination-based or lesion-based level, were calculated to appraise the diagnostic accuracy of F-FDG PET and PET/CT. All statistical analyses were performed using Meta-Disc 1.4.Forty-two trials were eligible. The pooled sensitivity and specificity of PET/CT to differentiate primary bone sarcomas from benign lesions were 96% (95% confidence interval [CI], 93-98) and 79% (95% CI, 63-90), respectively. For detecting recurrence, the pooled results on an examination-based level were sensitivity 92% (95% CI, 85-97), specificity 93% (95% CI, 88-96), positive likelihood ratio (PLR) 10.26 (95% CI, 5.99-17.60), and negative likelihood ratio (NLR) 0.11 (95% CI, 0.05-0.22). For detecting distant metastasis, the pooled results on a lesion-based level were sensitivity 90% (95% CI, 86-93), specificity 85% (95% CI, 81-87), PLR 5.16 (95% CI, 2.37-11.25), and NLR 0.15 (95% CI, 0.11-0.20). The accuracies of PET/CT for detecting local recurrence, lung metastasis, and bone metastasis were satisfactory. Pooled outcome estimates of F-FDG PET were less complete compared with those of PET/CT.F-FDG PET and PET/CT showed a high sensitivity for diagnosing primary bone sarcoma. Moreover, PET/CT demonstrated excellent accuracy for the staging, restaging, and recurrence surveillance of bone sarcoma. However, to avoid misdiagnosis, pathological examination or long-term follow-up should be carried out for F-FDG-avid lesions in patients with suspected bone sarcoma.


Treatment and post-treatment effects of functional therapy on the sagittal pharyngeal dimensions in Class II subjects.
To evaluate the craniofacial changes induced by functional appliances with special regard to the oro and nasopharyngeal sagittal airway dimensions in subjects with dentoskeletal Class II malocclusions when compared with an untreated Class II control group immediately after therapy and at long-term observation. A group of 40 patients (21 females and 19 males) with Class II malocclusion treated consecutively either with a Bionator or an Activator followed by fixed appliances was compared with a matched control group of 31 subjects (16 females and 15 males) with untreated Class II malocclusion. The treated sample was evaluated at T1, start of treatment (mean age: 9.9 ± 1.4 years); T2, end of functional treatment and prior to fixed appliances (mean age: 11.9 ± 1.3 years); and T3, long-term observation at the end of growth (mean age: 18.2 ± 2.1 years). Statistical comparisons were performed with independent sample t tests at T1 (baseline characteristics) and for the T1-T2, T2-T3, and T1-T3 changes. During active treatment the treated group showed a significant increment in lower airway dimension (PNS-AD1), as well as a significant improvement in the upper airway dimension (PNS-AD2). A significant decrease in the upper adenoid size (AD2-H) was also found. In the longterm evaluation, a significant increase in both lower and upper airway thickness (PNS-AD1; PNS-AD2) and a significant decrease in the upper adenoid thickness were still present in the treated group. The treatment with functional appliances produced significant favorable changes during active treatment in the oro- and nasopharyngeal sagittal airway dimensions in dentoskeletal Class II subjects when compared with untreated controls, and these changes were stable in the long-term.


Role of Endogenous Bone Marrow Stem Cells Mobilization in Repair of Damaged Inner Ear in Rats.
The utilization of the stem cells is widely used in the last few years in different fields of medicine, either by external transplantation or endogenous mobilization, most of these studies still experimental on animals; few were tried on human as in the spinal cord injury or myocardial infarction. As regard its use in the inner ear, stem cell transplantation was examined in many previous studies, while the mobilization idea is a new method to be experimented in inner ear hair cell regeneration. The present work assessed the possibility of mobilizing endogenous bone marrow derived stem cells (SCs) in rats using granulocyte colony stimulating factor (G-CSF) to induce regeneration and repair to experimentally damaged inner ear hair cells by Amikacin injection. The study included thirty adult Sprague Dawley male rats. Experimental induction of inner ear damage was done by repeated intratympanic injection of amikacin sulfate. Mobilization of bone marrow SCs was provoked by subcutaneous injection of GCSF. Cochlear integrity, induction of hearing loss and functional recovery of sensory hearing loss were assessed using Distortion Product Otoacoustic Emission (DPOAEs). The morphological alteration and recovery of the organ of Corti was assessed histologically using the light and scanning electron microscopes. After six month duration, there was improvement in 50% of the sensorineural DPOAE results. Functional recovery coincided with the repair of structural components of organ of Corti. SCs mobilization by G-CSF is a promising alternative method for replacement therapy in sensorineural hearing loss.


Failure to demonstrate parent-of-origin effect in transmission of bipolar II disorder.
Parent-of-origin effect (POE) is suggested in transmission of bipolar disorder. Bipolar II disorder (BPII) should be considered separately. The gender difference of transmitting parents, prevalence rate in children, and age at onset of patients in relation to the sex of the transmitting parent, were examined in 220 BPII patients. No evidence suggesting involvement of POE was found. POE is not involved in transmission of BPII. Number of subjects is not sufficient. Rate of interviewed subjects differs between mothers and fathers. Female BPII patients do not transmit the disease more often than male patients.


Diagnostic accuracy of silica clotting time method for lupus anticoagulant in a clinical population with various symptoms of antiphospholipid syndrome.
Correct interpretation of lupus anticoagulant (LA) tests is crucial for diagnosis of antiphospholipid syndrome (APS). This study assessed diagnostic accuracy of the SCT method in a clinical population with various symptoms of APS. Altogether 60 APS patients were consecutively recruited from a relevant clinical population. All cases had stable positivity of at least one of the reference tests (two other LA methods; anticardiolipin- and anti-β2-glycoprotein-I antibodies). Controls (n = 62) with negative reference tests were also consecutively recruited from the same clinical population. Receiver operator characteristic (ROC) analysis for the SCT test to identify the APS cases showed area under the curve of 0.82 (95% CI 0.75-0.90). The positive cut-off defined by a non-parametric method (99 percentile in a healthy population) had specificity of 92%, but low sensitivity of 53%. The optimal cut-off corresponded to the 97.5 percentile (67% sensitivity and 92% specificity). Combined sensitivity of the positive diluted Russell Viper Venom time (dRVVT) and SCT tests was 73%, while specificity remained 92%. The sensitivity of the SCT method varied in different clinical subgroups and was highest in patients with rheumatic diseases and in patients with triple positivity of three reference methods.


Arthrodesis of the thumb metacarpophalangeal joint: Conventional open technique with a locking plate or compression pins versus minimally invasive technique with compression pins or screws.
Arthrodesis of the thumb metacarpophalangeal (MCP) joint usually leads to satisfying results when performed with an open technique. The main complication is adhesion of the extensor tendons that sometimes requires hardware removal associated with tenolysis. The goal of this study was to assess whether a minimally invasive technique could reduce the risk of this complication. Arthrodesis of the thumb MCP was performed using an open technique with a locking plate or compression pins in 12 cases (group I) and using a minimally invasive technique with compression pins or screws in 12 cases, for a total of 24 patients aged 48.9 years on average, among which 15 were women. At the last follow-up, the average pain level was rated at 2/10 in group I and 2.3/10 in group II. The QuickDASH was 40.70/100 in group I and 36.24 in group II, grip strength was 79% of the contralateral side in group I and 51% in group II. Pinch strength was 81% of the contralateral side in group I and 45% in group II. Fusion was achieved in all cases in group I and in 7 of 12 cases in group II. Surgical revision for non-union was needed in 5 cases in group II, with hardware removal and tenolysis performed in 2 cases. The non-unions were observed in non-rheumatoid cases. While the two groups were not identical, arthrodesis of the thumb MCP using a minimally invasive technique with compression pins or screws seems to give satisfying results for rheumatoid cases in which no cartilage remains.


Visible persistence in paranoid schizophrenics.
A visual temporal integration (i.e., visible persistence) task was performed by normal controls and paranoid schizophrenics. The task evaluated the critical duration (CD), which approximates the duration of peripheral persistence duration and post-CD persistence, which is possibly more associated with central processes. Subjects were required to report when temporally modulated spatial frequency patterns, which are known to have characteristic temporal processing rates, were pulsing "on-off" with a distinct "off" period. The dependent measure was the duration of visible persistence. An analysis of groups X spatial frequency duration (50, 75, 150, 300 msec) X spatial frequency (high, medium, low), with repeated measures on the last two variables, revealed that the second-order interaction was significant (p less than 0.05). Schizophrenics had shorter visible persistence only for the 300-msec presentation for the high spatial frequency pattern. Also, the CD of schizophrenics did not conform to the duration of normals on the high spatial frequency. The results are discussed in terms of the role high spatial frequencies plays in visual information processing and how shorter visible persistence by paranoid schizophrenics may reflect a premature termination of information necessary for synthesis into accurate percepts.


Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).
Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL). The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness. Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59). We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases.


Structural evolution and tissue-specific expression of tetrapod-specific second isoform of secretory pathway Ca2+-ATPase.
Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2 gene radiated from ATP2C1 (encoding SPCA1) during adaptation of tetrapod ancestors to terrestrial habitats.


Model systems in SDHx-related pheochromocytoma/paraganglioma.
Pheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and sympathetic and parasympathetic ganglia outside the adrenal gland, respectively. Many follow germline mutations in genes coding for subunits of succinate dehydrogenase (SDH), a tetrameric enzyme in the tricarboxylic acid (TCA) cycle that both converts succinate to fumarate and participates in electron transport. Germline SDH subunit B (SDHB) mutations have a high metastatic potential. Herein, we review the spectrum of model organisms that have contributed hugely to our understanding of SDH dysfunction. In Saccharomyces cerevisiae (yeast), succinate accumulation inhibits alpha-ketoglutarate-dependent dioxygenase enzymes leading to DNA demethylation. In the worm Caenorhabditis elegans, mutated SDH creates developmental abnormalities, metabolic rewiring, an energy deficit and oxygen hypersensitivity (the latter is also found in Drosophila melanogaster). In the zebrafish Danio rerio, sdhb mutants display a shorter lifespan with defective energy metabolism. Recently, SDHB-deficient pheochromocytoma has been cultivated in xenografts and has generated cell lines, which can be traced back to a heterozygous SDHB-deficient rat. We propose that a combination of such models can be efficiently and effectively used in both pathophysiological studies and drug-screening projects in order to find novel strategies in PPGL treatment.


Cytotoxic and apoptosis-inducing activity of C21 steroids from the roots of Cynanchum atratum.
Two new (1-2) and two known C21 steroids (3-4) were isolated from the roots of Cynanchum atratum. Their structures were elucidated by detailed 1D and 2D spectroscopic. The MTT assay showed that compounds 1-4 displayed obvious cytotoxic activities against HepG2 cells with IC50 values ranging from 10.19μM to 76.12μM. Compounds 1-3 also exhibited cytotoxic effects in A549 cells with IC50 values of 30.87-95.39μM. Compound 3 showed the antiproliferative activity via G0/G1 cell cycle arrest and proapoptosis in HepG2 cells by Flowcytometry analysis. Western blotting analysis revealed that compound 3 could induce HepG2 cell apoptosis via the mitochondrial pathway by downregulating Bcl-2 expression, upregulating Bax protein expression, and activating caspase-9 and caspase-3.


The microbiome during pregnancy and early postnatal life.
We are changing our concept that the newborn infant emerges from a sterile environment. In-utero colonization may have major impacts on the developing mammal in terms of development of immunity and metabolism that, with epigenetic modifications, will lead to diseases in later life. In addition, the microbial profile that develops during and after birth depends on mode of delivery, type of feeding (human milk versus formula) and various other environmental factors to which the newborn is exposed. The goal of this review is to clarify that the microbiome in the maternal fetal unit as well as the immediate changes that occur as new microbes are acquired postnatally play major roles in subsequent health and disease. Rapidly developing technologies for multi-omic analyses and systems biology are shifting paradigms in both scientific knowledge and clinical care.


Childhood Symptoms of ADHD and Impulsivity in Abstinent Heroin Users.
Heroin dependence is associated with deficits in impulsivity, which is also a core feature of attention deficit hyperactivity disorder (ADHD). This study aimed to explore the association between childhood ADHD symptoms and cognitive and motor impulsivity among abstinent individuals with a history of heroin dependence. Thirty-two abstinent Bulgarian males with a history of heroin dependence participated in the study. Self-rated childhood ADHD symptoms were obtained using the Wender-Utah Rating Scale. Cognitive impulsivity was measured using the Iowa Gambling Task (IGT), an index of impulsive decision making, and the Delayed Reward Discounting Task (DRDT), a measure of intertemporal choice. Motor impulsivity was indexed with the Stop Signal Task (SST), a measure of response inhibition. Participants, whose average age was 27.66 years (SD = 2.7), had an average ADHD symptom score of 36.6 (SD = 18.6), had roughly 7 years (SD = 2.9) of heroin use, and had been abstinent for just over a year (M = 402.5 days, SD = 223.8). Linear regression analyses revealed that self-reported ADHD symptoms predicted impulsive decision making (IGT), but not delayed discounting (DRDT) or response inhibition (SST). Self-reported childhood ADHD symptoms do not uniformly predict impulsivity among abstinent individuals with heroin dependence. Results suggest the IGT may be more sensitive to externalizing psychopathology among individuals with heroin dependence than other measures of impulsivity.


Antisynthetase syndrome - much more than just a myopathy.
The aim of the study was to summarize current knowledge on antisynthetase syndrome (ASS), including its epidemiology, pathogenesis, proposed so far diagnostic criteria, heterogeneity of clinical manifestations, prognostic factors and therapeutic possibilities. PubMed database was screened for "antisynthetase syndrome" OR "antisynthetase antibodies" between February and April 2020. Aminoacyl-tRNA synthetases participate in the immune system activation as antigens, but also serve chemoattractive and cytokine-resembling roles, initiating innate and adaptive pathways. Exposure to various inhaled antigens may induce the autoimmune cascade leading to ASS. NK cells with its impaired INF-y production as well as formation of NETs by neutrophils contribute to pathogenesis. The prevalence of symptoms vary significantly depending on the study with muscular, articular and pulmonary involvement being the most frequently observed. Although classified as subtype of idiopathic inflammatory myopathies, myositis may not necessarily be the prominent manifestation. Since clinical presentation is heterogeneous and symptoms can emerge gradually, ASS could be considered as a heterogeneous spectrum rather than a homogenous disease entity. The currently available classification criteria do not fully correspond with the clinical patterns of the disease. Therapy is based on glucocorticosteroids and other immunosuppressive agents. Randomized controlled trials, dedicated for patients with ASS, are needed to form treatment algorithms.


Remote real-time control of aerosol continuous monitoring for high radon concentration environments.
In this study, we developed a new continuous aerosol monitoring device, which can be controlled by a remote server and transmit data over the Internet according to the TCP protocol. The user can remotely control the device and obtain the data measured in real time, which can be used to send alarms related to the concentrations of radioactive aerosols. This new device was applied to remotely measuring the concentrations of nuclides (uranium, plutonium, and beta) in radioactive aerosols and for reducing the effects of high radon in the environment based on the measurements. The experimental results demonstrated that this novel device can provide accurate test results and transmit the results to the administrator's location, and it can be remotely controlled in order to remain at a safe distance away from a dangerous measurement area.


Diagnostic application of mitochondrial enzymes and isoenzymes.
Evolutionary, topological and metabolic aspects of mitochondrial enzymes and isoenzymes are reviewed, and the structural and functional heterogeneity of mitochondria is demonstrated. Primary deficiencies of mitochondrial enzymes are described and the need for their proper recognition is illustrated. Species differences of secondary dysfunction of mitochondrial enzymes are shown. The release of mitochondrial enzymes is compared to that of cytosolic enzymes from liver and heart muscle cells and the diagnostic significance of assays of mitochondrial enzymes in serum is evidenced. Possible mechanisms of mitochondrial enzyme release from cells and unresolved questions pertaining to this process are discussed in light of potential diagnostic utility of mitochondrial enzymes in serum.


The management of histologically unverified presumed cerebral gliomas with radiotherapy.
To define the natural history, and prognostic factors of patients with histologically unverified presumed gliomas diagnosed on CT or MR imaging, and treated with external beam radiotherapy. Retrospective review of 111 adults with histologically unverified presumed cerebral glioma treated with radiotherapy between 1974 and 1990. Using CT or MRI criteria alone 41 were presumed low grade, 63 high grade gliomas and 7 were unclassified. Survival results were compared to a cohort of 82 adults with histologically verified low grade gliomas treated over the same period with surgery and radiotherapy. The 5 year survival probability of the whole cohort was 31%. Age, performance status, and the degree of contrast enhancement were independent prognostic factors for survival. Patients with presumed low grade glioma had a 5 year survival of 41% compared to 52% for patients with verified low grade glioma. After correction for prognostic factors no significant difference was found in the survival between patients with verified and unverified low grade tumors. One of 15 cases with subsequent histology, obtained at autopsy or salvage surgery, had nonglial pathology. Patients diagnosed on the basis of clinical features and imaging as having presumed glioma have similar natural history and clinical behavior after treatment with radiotherapy to those with histologically confirmed gliomas. However, the results should not be taken as justification for avoiding biopsy. A proportion of patients may have nonglial pathology and new more effective treatment strategies for patients with glial tumors can only evolve on the basis of full diagnostic information including pathology.


Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions.
The human T-cell leukemia/lymphoma virus (HTLV) genome, in addition to the structural Gag and Env proteins and retroviral enzymes, carries a region at its 3' end originally designated pX. To date, we know that this region encodes two essential transcriptional and post-transcriptional positive regulators of viral expression, the Tax and Rex proteins, respectively (reviewed elsewhere in this issue). Here, we will review current knowledge of the functions of three additional proteins encoded in the pX region, p12I, p13II, and p30II.


An improved coating for the isolation and quantitation of interferon-gamma in spiked plasma using surface plasmon resonance (SPR).
A study was initiated to investigate the use of surface plasmon resonance (SPR) for the detection in plasma of a high pI model protein, recombinant human interferon-gamma (IFN-gamma). Initially a number of self-assembled monolayers (SAMs) and hydrogel-derivatised SAM-coatings were characterised for the adsorptive and desorptive properties of plasma components. Next a monoclonal anti-IFN-gamma antibody, MD-2, was covalently attached to dextran-modified mercaptoundecanoic acid surfaces that performed best. On coatings consisting of carboxyl-modified dextran (CMD) a difference in interaction behaviour was observed when IFN-gamma was injected in either buffer or diluted plasma. During the injection of IFN-gamma in buffer, an acceleration of the interaction process was observed and the signal continued to increase after the injection plug had passed. Upon injection of diluted plasma spiked with IFN-gamma, the response increased without acceleration of the binding process. After the injection was finished, some of the bound material desorbed as expected, resulting in a signal decrease. On non-charged dextrans, the interaction between the antibody-modified surface and IFN-gamma in either plasma or buffer was similar. During sample injection the response increased with a binding rate depending on the concentration of IFN-gamma present in solution. When the injection was finished, some of the bound material was washed away from the surface and only a minor contribution of non-specific adsorbed plasma components was noticeable. From the coatings tested, the non-modified dextran-coated SPR sensor disks prove to be best suited for the detection of IFN-gamma in complex matrices like plasma. The interaction of IFN-gamma in both diluted plasma and buffer is comparable and concentrations of IFN-gamma of 250 ng ml-1 and higher can be detected in both buffer and 100x-diluted plasma. The non-specific adsorption of plasma components is low, whereas the specific IFN-gamma response is relatively high.


Relationship between attentional bias and stimulus control: An observational study of real-world eating patterns.
Attentional bias towards food related stimuli has been proposed as a potential target for dieting intervention, however the evidence supporting a relationship between attentional bias and food intake is mixed. Theory holds that food related attentional bias should be positively associated with measures of stimulus-controlled eating, and that implicit processes such as impulsivity moderate this association. The aim of the present study was to examine whether the proposed relationship between food-related attentional bias and stimulus control exists, and whether it is moderated by impulsivity. A community sample of 68 participants completed a food-related attentional bias task and impulsiveness scale during a laboratory visit, after which they recorded their real-world eating in real-time over 14 days using Ecological Momentary Assessment (EMA). During this time, participants also responded to 4-5 randomly timed assessments per day. Food outlet presence (e.g., fast food restaurants, cafes, corner stores etc.) was assessed during both eating and non-eating assessments. EMA data was then used to determine levels of stimulus controlled eating for each participant. Substantial variation was seen in both our measure of both food-related attentional bias (Range: 33.9 to 80.0) and in the degree to which the participant's eating could be categorised as being under stimulus control (Range: 0.50 to 0.93). However, food-related attentional bias scores were not a significant independent predictor of stimulus control and nor was this relationship moderated by impulsivity. Contrary to theoretical predictions, we found no evidence that of an association between attentional bias, impulsivity, and stimulus control. More work is needed to better understand the implicit processes underlying eating behaviour in the real-world.


Intracellular ionic activities and transmembrane electrochemical potential differences in gallbladder epithelium.
Intracellular ion activities in Necturus gallbladder epithelium were measured with liquid ion-exchanger microelectrodes. Mean values for K, Cl and Na activities were 87, 35 and 22 mM, respectively. The intracellular activities of both K and Cl are above their respective equilibrium values, whereas the Na activity is far below. This indicates that K and Cl are transported uphill toward the cell interior, whereas Na is extruded against its electrochemical gradient. The epithelium transports NaCl from mucosa to serosa. From the data presented and the known Na and Cl conductances of the cell membranes, we conclude that neutral transport driven by the Na electrochemical potential difference can account for NaCl entry at the apical membrane. At the basolateral membrane, Na is actively transported. Because of the low Cl conductance of the membrane, only a small fraction of Cl transport can be explained by diffusion. These data suggest that Cl transport across the basolateral membrane is a coupled process which involves a neutral NaCl pump, downhill KCl transport, or a Cl-anion exchange system.


A clinical study of visualization on depressed white blood cell count in medical patients.
This psychoneuroimmunological study examined the effects of visualization, or mental imagery, on immune system response, specifically, on depressed white blood cell (WBC) count in 20 medical patients. Subjects were 10 females and 10 males and included medical patients diagnosed with cancer, AIDS, viral infections, and other medical problems associated with depressed WBC count. Results indicated significant increases in WBC count for all patients over a 90-day period, after a predicted initial decrease in WBC count. No significant age or sex differences were found.


Prognostic role of Mini-Mental State Pediatric Examination (MMSPE) on neuropsychological functioning.
The aim of this study was to evaluate the ability of the Mini-Mental State Pediatric Examinations (MMSPE) in the individuation of neuropsychological impairments. MMSPE was administered to 60 children attending a primary or lower secondary school suffering from neurological diseases, admitted to our neuropsychology services. All children performed both a MMSPE examination and a neuropsychological evaluation. Results of neuropsychological evaluation and MMSPE were dichotomized. Positive predictive value (PPV), negative predictive value (NPV), and accuracy were also calculated. The diagnostic performance of MMSPE showed a good overall accuracy (0.83, CI 95% 0.64-0.91), NPV (0.81, CI 95% 0.73-1.00), PPV (0.87, CI 95% 0.68-0.94), specificity (0.91, CI 95% 0.81-1.00), sensitivity (0.74, CI 95% 0.57-0.90), and odds ratio of 28.5 (CI 95% 6.6-123), p < 0.001. MMSPE has a good prognostic ability in predicting neuropsychological problems in the context of different neurological pediatric diseases. We suggest that this instrument could greatly improve pediatric clinical practice in identifying high-risk children.


Chemoprotective effects of plasma derived from mice of different ages and genders on ovarian failure after cyclophosphamide treatment.
Premature ovarian failure is one of the major side effects of chemotherapy drugs. Blood plasma contains several factors that might lead to the repair of different tissues. The chemoprotective effects of plasma derived from mice with different ages and genders were assessed on ovarian tissue in cyclophosphamide-treated mice. Forty-two adult female mice were divided into six groups as follows: (A) control; (B) 0.9% sodium chloride as vehicle; (C) cyclophosphamide; (D) cyclophosphamide + young male blood plasma; (E) cyclophosphamide + old male blood plasma; (F) cyclophosphamide + young female blood plasma. Ovarian failure was induced by injecting cyclophosphamide. On the 1st day, three groups received simultaneous injections of 150 μL intraperitoneal and 70 μL intravenous plasma derived from mice of different ages and genders. Each plasma type (150 μL) was then injected intraperitoneally every other 3 days for 19 days. On day 21, the dissected ovaries were stained for stereological analysis. Also, estrogen and progesterone levels were measured. Cyclophosphamide had damaging effects on ovarian parameters and led to reduced hormone levels in comparison with the control group. However, treating with young female and, old male blood plasma, to a lesser degree, showed beneficial effects on the number of primordial follicles, pre-antral follicles, and granulosa cells. Also, these two treatments had protective effects on the volume of ovarian parameters as well as estrogen and progesterone levels in comparison with the cyclophosphamide group (P < 0.05). Plasma derived from mice of different ages and genders can ameliorate premature ovarian failure against the adverse effects of cyclophosphamide.


Bias and Modality in Conditionals: Experimental Evidence and Theoretical Implications.
The concept of bias is familiar to linguists primarily from the literature on questions. Following the work of Giannakidou and Mari (Truth and Veridicality in Grammar and Thought: Modality, Mood, and Propositional Attitudes, University of Chicago Press, Chicago, 2021), we assume "nonveridical equilibrium" (implying that p and ¬p as equal possibilities) to be the default for epistemic modals, questions and conditionals. The equilibrium of conditionals, as that of questions, can be manipulated to produce bias (i.e., reduced or higher speaker commitment). In this paper, we focus on three kinds of modal elements in German that create bias in conditionals and questions: the adverb wirklich 'really', the modal verb sollte 'should', and conditional connectives such as falls 'if/in case'. We conducted two experiments collecting participants' inference about speaker commitment in different manipulations, Experiment 1 on sollte/wirklich in ob-questions and wenn-conditionals, and Experiment 2 on sollte/wirklich in wenn/falls/V1-conditionals. Our findings are that both ob-questions and falls-conditionals express reduced speaker commitment about the modified (antecedent) proposition in comparison to wenn-conditionals, which did not differ from V1-conditionals. In addition, sollte/wirklich in the antecedent of conditionals both create negative bias about the antecedent proposition. Our studies are among the first that deal with bias in conditionals (in comparison to questions) and contribute to furthering our understanding of bias.


Production of high-energy 6-Ah-level Li | |LiNi0.83Co0.11Mn0.06O2 multi-layer pouch cells via negative electrode protective layer coating strategy.
Stable lithium metal negative electrodes are desirable to produce high-energy batteries. However, when practical testing conditions are applied, lithium metal is unstable during battery cycling. Here, we propose poly(2-hydroxyethyl acrylate-co-sodium benzenesulfonate) (PHS) as negative electrode protective layer. The PHS contains soft poly (2-hydroxyethyl acrylate) and poly(sodium p-styrene sulfonate), which improve electrode flexibility, connection with the Cu current collector and transport of Li ions. Transmission electron cryomicroscopy measurements reveal that PHS induces the formation of a solid electrolyte interphase with a fluorinated rigid and crystalline internal structure. Furthermore, theoretical calculations suggest that the -SO3- group of poly(sodium p-styrene sulfonate) promotes Li-ion motion towards interchain migration through cation-dipole interaction, thus, enabling uniform Li-ion diffusion. Electrochemical measurements of Li | |PHS-coated-Cu coin cells demonstrate an average Coulombic efficiency of 99.46% at 1 mA/cm2, 6 mAh/cm2 and 25 °C. Moreover, when the PHS-coated Li metal negative electrode is paired with a high-areal-capacity LiNi0.83Co0.11Mn0.06O2-based positive electrode in multi-layer pouch cell configuration, the battery delivers an initial capacity of 6.86 Ah (corresponding to a specific energy of 489.7 Wh/kg) and, a 91.1% discharge capacity retention after 150 cycles at 2.5 mA/cm2, 25 °C and 172 kPa.


Alcohol dependence and the ventral hippocampal influence on alcohol drinking in male mice.
Examining neural circuits underlying persistent, heavy drinking provides insight into the neurobiological mechanisms driving alcohol use disorder. Facilitated by its connectivity with other parts of the brain such as the nucleus accumbens (NAc), the ventral hippocampus (vHC) supports many behaviors, including those related to reward seeking and addiction. These studies used a well-established mouse model of alcohol (ethanol) dependence. After surgery to infuse DREADD-expressing viruses (hM4Di, hM3Dq, or mCherry-only) into the vHC and position guide cannula above the NAc, male C57BL/6J mice were treated in the CIE drinking model that involved repeated cycles of chronic intermittent alcohol (CIE) vapor or air (CTL) exposure alternating with weekly test drinking cycles in which mice were offered alcohol (15% v/v) 2 h/day. Additionally, smaller groups of mice were evaluated for either cFos expression or glutamate release using microdialysis procedures. In CIE mice expressing inhibitory (hM4Di) DREADDs in the vHC, drinking increased as expected, but CNO (3 mg/kg intraperitoneally [i.p.]) given 30 min before testing did not alter alcohol intake. However, in CTL mice expressing hM4Di, CNO significantly increased alcohol drinking (∼30%; p < 0.05) to levels similar to the CIE mice. The vHC-NAc pathway was targeted by infusing CNO into the NAc (3 or 10 μM/side) 30 min before testing. CNO activation of the pathway in mice expressing excitatory (hM3Dq) DREADDs selectively reduced consumption in CIE mice back to CTL levels (∼35-45%; p < 0.05) without affecting CTL alcohol intake. Lastly, activating the vHC-NAc pathway increased cFos expression and evoked significant glutamate release from the vHC terminals in the NAc. These data indicate that reduced activity of the vHC increases alcohol consumption and that targeted, increased activity of the vHC-NAc pathway attenuates excessive drinking associated with alcohol dependence. Thus, these findings indicate that the vHC and its glutamatergic projections to the NAc are involved in excessive alcohol drinking.


Silent thyroiditis: a histologic and immunohistochemical study.
Twenty-six specimens obtained from 23 patients with clinically and laboratory-proven silent thyroiditis were examined histologically; 11 specimens were obtained during the thyrotoxic phase, and 15 specimens during the early or late recovery phase. All specimens showed chronic thyroiditis, focal or diffuse type; and lymphoid follicles were present in about half of the specimens. Most specimens showed neither stromal fibrosis nor oxyphilic cell changes. The follicular disruptions, which varied from moderate to severe and involved nearly all the visible follicles, were characteristic and common histologic features of this disorder. Giant cells were present in about two thirds of specimens. Six of the 7 specimens taken during the late recovery phase showed no follicular disruption. In 3 patients who had follow-up biopsies, the histologic involvement in the initial biopsy specimens clearly had disappeared in the second biopsy specimens. These histologic features indicate that silent thyroiditis may be a form of chronic thyroiditis, i.e., "chronic thyroiditis with marked follicular destruction." Thyroid biopsy is recommended as a useful tool in differentiating this disease from other thyroid diseases causing hyperthyroidism. In addition to the histologic analysis, intrathyroidal lymphocyte subsets were examined immunohistochemically and compared to those in chronic thyroiditis (Hashimoto's thyroiditis). In both silent and chronic thyroiditis, a great majority of lymphocytes infiltrating between thyroid follicles showed a T-cell phenotype, and no significant differences in T-cell and B-cell distribution between the diseases were observed.


Physical activity or food intake prior to testing did not affect the reproducibility of GH secretion elicited by GH releasing hormone plus GH-releasing hexapeptide in normal adult subjects.
Growth hormone deficiency (GHD) in adults is a defined syndrome of which the adverse effects on different areas of body function are reversed under replacement therapy with GH. The diagnosis of GHD is controversial in adults, relying on the GH secretion elicited by the so-called provocative tests of GH reserve. Most of the tests in use, including the widely employed insulin tolerance test, have been shown to be blunted after daily activities, such as mild exercise, heat or food intake, which makes stringent testing conditions mandatory in order to assure reproducibility. The combined administration of GH releasing hormone (GHRH) and GH-releasing hexapeptide (GHRP-6) is a very effective test for the diagnosis of GH deficiency in adults. In the present study, the perturbatory action of mild physical activity and food intake on the reproducibility of this combined test was assessed. Seventeen healthy volunteers of both sexes were tested twice on separate occasions with the sequential administration of GHRH (90 microg i.v.) plus GHRP-6 (90 microg i.v.) as bolus. Eleven subjects underwent the first combined test in the morning under basal conditions and the second test was performed in the afternoon of the same day after a morning of habitual working activity and after a standard lunch. Another group of six subjects underwent similar double testing in the morning and in the afternoon after morning activity followed by lunch; however, both tests were separated by a period of 6 months. GH levels were analysed by time-resolved fluoroimmunoassay, with sampling every 15 minutes. The reproducibility of the GHRH + GHRP-6 test performed on the same day was high, with the mean GH peak being 65.4 +/- 8.0 microg/l in the basal state and 51.2 +/- 9.6 microg/l after lunch, while the area under the curve (AUC) was 2287 +/- 288 microg/l per 45 minutes in the morning and 1759 +/- 350 after lunch. When a period of 6 months had elapsed between the first and the second test, the reproducibility was well maintained with a mean GH peak of 42.7 +/- 6.2 microg/l in the basal state and 34.3 +/- 3.6 microg/l in the after lunch test, with the AUC 1463 +/- 209 and 1164 +/- 106 microg/l per 45 minutes in the morning and after lunch, respectively. When analysed individually, physical activity, lunch or time elapsed between the two tests did not significantly change the GH peak in the subjects tested. The GHRH + GHRP-6 test of GH reserve is a highly reproducible test in adult subjects over time, and is not perturbed by common daily activities, such as mild physical exercise or food intake. Considering that stringent testing conditions are not required and the whole test may be performed in 30 minutes, it may be useful in the clinical setting for the diagnosis of GH deficiency in adults.


Gadolinium contrast dose in the evaluation of central nervous system tumors.
Many factors affect the ability to detect a CNS lesion. There is no single contrast dose that is optimal for all diseases. By understanding these factors that may affect lesion detection, the appropriate dose for specific pathologic processes may be determined.


Adverse childhood experiences, problematic internet use, and health-related quality of life in Chinese adolescents.
Background: The influence of adverse childhood experiences (ACEs) on an individual's health is substantial. However, the associations between ACEs, problematic internet use (PIU), and health-related quality of life (HRQOL) in adolescents remain underexplored.Objective: To assess the association between ACEs and HRQOL in Chinese adolescents and to evaluate the mediating role of PIU in this association.Method: A sample of 6,639 adolescents (3,457 boys and 3,182 girls) aged between 11-20 years (mean [SD] age: 14.5 [1.6] years) were recruited from 6 junior and senior middle schools using a proportional sampling approach in a cross-sectional study. Data on ACE exposure was collected through the short form of Childhood Trauma Questionnaire, the ACE-International Questionnaire, and two additional questions. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0. The associations between ACEs and HRQOL were estimated using linear regression models. Mediation analysis was further conducted to explore the possible mediating role of PIU in the association between ACEs and HRQOL.Results: Our study collected 13 different ACEs. We found that adolescents exposed to any ACE had significantly lower scores in all HRQOL dimensions, psychosocial health summary scale, and total scale, than those without such exposure. Specifically, adolescents with ≥ 3 ACE exposure had a total scale score that was 14.70 (95%CI: 15.53 to 13.87) points lower than their non-exposed counterparts. Mediation analysis identified PIU as a significant mediator, with the proportion of the total effect attributable to PIU ranging from 14.38% for social functioning to 17.44% for physical functioning.Conclusions: Exposure to ACEs was associated with poorer HRQOL in Chinese adolescents, underscoring the importance to prevent ACEs and their negative impacts on adolescent well-being. These findings also highlighted the need of promoting appropriate internet use among adolescents exposed to ACEs, in order to avert potential impairment in their HRQOL.HIGHLIGHTSAdolescents with adverse childhood experiences have poorer health-related quality of life.The association between adverse childhood experiences and health-related quality of life shows a dose-response pattern.Problematic internet use partially mediates the associations between adverse childhood experiences and health-related quality of life in adolescents.


Deficient copper availability on organoleptic and nutritional quality of tomato fruit.
Copper (Cu) is an essential micronutrient for plants because it functions as a redox-active cofactor in vital processes inside the cells. Arable lands are often deficient in micronutrient contents and require the application of enriched fertilisers, whose overuse poses a high risk for human health, the environment and the food safety. Here, we aimed to decipher the effects of Cu deficiency during fruit growth on Cu and other micronutrients contents and on the fruit nutritional value and quality of tomato, the most consumed fruit worldwide, throughout the maturation process. Changes in the contents of important micronutrients for fruit physiology and human health, such as Fe and Mn, occurred in response to Cu deficient growing conditions at different fruit ripening stages, while lower Cu levels were detected in those fruit along the whole maturation process. Cu deficiency delayed changes in lycopene content and fruit colour, but increased acidity, and advanced the rise in antioxidant capacity and vitamin C content during fruit colour change from green to light red in the Moneymaker tomato; although this time lag eventually caught up in the most mature fruit stage. Cu deficiency also increased total phenolic and flavonoid contents only in green fruit.


Return to Play After Thumb Ulnar Collateral Ligament Injuries Managed Surgically in Athletes-A Systematic Review.
The purpose of this systematic review was to summarize the available data on how surgical management of injuries to the thumb ulnar collateral ligament (UCL) complex affects athletes and their return-to-play (RTP) and postinjury performance metrics in addition to evaluating rehabilitation guidelines. A systematic search was performed on PubMed and Embase databases for articles on outcomes of surgical treatment of thumb UCL injuries in athletes. Articles with expert recommendations on postoperative management and RTP guidelines were also included separately. Study characteristics were recorded, including sport, RTP rates, and data on performance. Recommendations were summarized by sport. The Methodological Index for Non-Randomized Studies (MINORS) criteria was used to assess methodological quality. The authors also present their recommended return-to-sport algorithm. Twenty-three articles were included, including 11 with reports on patients and 12 expert opinions on guiding RTP. The mean MINORS score for the applicable studies was 9.4. In the 311 patients included, RTP was 98.1% in aggregate. No performance detriments were noted in athletes after surgery. Thirty-two (10.3%) patients had postoperative complications. The recommendations on timing to RTP vary by sport and author, but all recommended initial thumb protection when returning to sport. Newer techniques, such as suture tape augmentation, suggest the permission for earlier motion. Return-to-play rates after surgical treatment of thumb UCL injuries are high, with reassuring return to preinjury level of play with few complications. Recommendations for surgical technique have trended toward suture anchors and, now, suture tape augmentation with earlier motion protocols, although rehabilitation guidelines vary by sport and author. Current information on thumb UCL surgery in athletes is limited by the low quality of evidence and expert recommendations. Prognostic IV.


Prefrontal and posterior parietal contributions to the perceptual awareness of touch.
Which brain regions contribute to the perceptual awareness of touch remains largely unclear. We collected structural magnetic resonance imaging scans and neurological examination reports of 70 patients with brain injuries or stroke in S1 extending into adjacent parietal, temporal or pre-/frontal regions. We applied voxel-based lesion-symptom mapping to identify brain areas that overlap with an impaired touch perception (i.e., hypoesthesia). As expected, patients with hypoesthesia (n = 43) presented lesions in all Brodmann areas in S1 on postcentral gyrus (BA 1, 2, 3a, 3b). At the anterior border to BA 3b, we additionally identified motor area BA 4p in association with hypoesthesia, as well as further ventrally the ventral premotor cortex (BA 6, BA 44), assumed to be involved in whole-body perception. At the posterior border to S1, we found hypoesthesia associated effects in attention-related areas such as the inferior parietal lobe and intraparietal sulcus. Downstream to S1, we replicated previously reported lesion-hypoesthesia associations in the parietal operculum and insular cortex (i.e., ventral pathway of somatosensory processing). The present findings extend this pathway from S1 to the insular cortex by prefrontal and posterior parietal areas involved in multisensory integration and attention processes.


Anthocyanins and other flavonoids as flower pigments from eleven Centaurea species.
Anthocyanins and other flavonoids were isolated from the flowers of eleven Centaurea species, C. macrocephala, C. rupestotilis and C. suaveolens, which produce yellow flowers, and C. achtarovii, C. dealbata, C. montana, C. nigra, C. scabiosa, C. simplicicaulis, C. hypoleuca and C. triumfetti, which have cyanic flowers. Four anthocyanins, cyanidin 3,5-di-O-glucoside, cyanidin 3-O-(6"-malonylglucoside)-5-O-glucoside, cyanidin 3-O-(6"-succinylglucoside)-5- O-glucoside and cyanidin glycoside, were detected in the cyanic flowers of seven Centaurea species. Of these anthocyanins, the first two were found as major anthocyanins. In the cyanic species, four other flavonoids, apigenin 7-O-glucuronide-4'-O-glucoside, malonylated apigenin 7,4'-di-O-glucoside, apigenin 7-0- glucuronide and kaempferol glycoside, were also isolated. On the other hand, nine flavonols and four flavones were isolated from the three yellow-flowered species, and identified as quercetagetin, quercetagetin 7-O-glucoside, quercetagetin 3'-methyl ether 7-O-glucoside, patuletin, patuletin 7-O-glucoside, quercetin 7-O-glucoside, kaempferol 3-methyl ether, kaempferol 3-methyl ether 4'-O-glucuronide and isorhamnetin 3-O-galactoside, and apigenin, apigenin 7- O-glucuronide, luteolin 7-O-glucoside and apigenin 6,8-di-C-glucoside (vicenin-2). Of these flavonoids, the former five flavonols are "yellow flavonols", and it was shown that their flower colors are due to these compounds.


Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain.
A growing body of evidence in humans implicates chronic activation of the innate immune response in the brain as a major cause of neuropathology in various neurodegenerative conditions, although the mechanisms remain unclear. In an unbiased genetic screen for mutants exhibiting neurodegeneration in Drosophila, we have recovered a mutation of dnr1 (defense repressor 1), a negative regulator of the Imd (immune deficiency) innate immune-response pathway. dnr1 mutants exhibit shortened lifespan and progressive, age-dependent neuropathology associated with activation of the Imd pathway and elevated expression of AMP (antimicrobial peptide) genes. To test the hypothesis that overactivation of innate immune-response pathways in the brain is responsible for neurodegeneration, we demonstrated that direct bacterial infection in the brain of wild-type flies also triggers neurodegeneration. In both cases, neurodegeneration is dependent on the NF-κB transcription factor, Relish. Moreover, we found that neural overexpression of individual AMP genes is sufficient to cause neurodegeneration. These results provide a mechanistic link between innate immune responses and neurodegeneration and may have important implications for the role of neuroinflammation in human neurodegenerative diseases as well.


An investigation of internalized stigma and recovery levels of patients registered in a Community Mental Health Center.
This study was carried out to investigate the internalized stigma and recovery levels of patients registered in a Community Mental Health Center (CMHC). This descriptive study was completed with 230 psychiatric patients to a registered Community Mental Health Center is located in Turkey. Data were collected using a sociodemographic characteristics' form, the Internalized Stigma of Mental Illness Scale (ISMI), and the Maryland Assessment of Recovery in Serious Mental Illness (MARS). A statistically significant negative relationship was found between total ISMI and MARS scores (p < 0.05). The internalized stigma and recovery levels of individuals diagnosed with mental illness registered at the CMHC were found to be normal.


The effect of educational information about treatments for schizophrenia on stigmatizing perceptions.
A promising strategy for reducing stigmatizing perceptions towards people with schizophrenia is education about treatment and recovery. The effects of different kinds of treatment information on stigmatizing perceptions, however, have yet to be compared directly. This study compared three different educational interventions focusing on medication, CBT, and psychodynamic psychotherapy in their potential to reduce stigmatizing perceptions towards people with schizophrenia. In an online experiment 178 participants received one of three psychoeducation texts that focused on medication, CBT or psychodynamic therapy. The effects on stereotypical beliefs about psychosis (dangerousness, unpredictability, blame, prognostic pessimism) and emotional responses towards people with schizophrenia (anxiety, anger, sympathy) were tested. Perceptions of dangerousness, unpredictability, and anxiety towards people with schizophrenia were reduced in all conditions. Prognostic pessimism was reduced only after reading the CBT information. No neutral control group was included. The sample was not representative with respect to level of education or gender. Stigmatizing perceptions may be reduced by receiving information about any type of treatment for psychosis and without producing negative side-effects, although this needs to be replicated in a controlled study. However, information on CBT seems most suitable to reduce stigma, since it was able to reduce prognostic pessimism.


Potentials of biodegraded cashew pomace for cake baking.
The use of biodegraded cashew pomace processed into flour for cake baking was investigated. The physico-chemical changes during the submerged fermentation of the pomace and the organoleptic qualities of the composite cake were also monitored. There was an increase of about 50% in protein content of the pomace after 96 h of fermentation. However, a reduction of about 61% in the total microbial count after 24 h was due to the toxic effect of the organic acids on the microbial cells during fermentation. The cashew flour had high crude fibre (ca. 20-33%) and carbohydrate (ca. 16-47%) values. The composite cake made from a 10:90 combination of 96 h-degraded cashew flour/wheat flour respectively was the most accepted. The cake which had a specific volume of 0.53 ml/g lost 11.1% moisture when 38 g of its batter was exposed to 190 degrees C for 10 minutes. This cake had a calorie value of 293.8/100 g and may be useful in feeding diabetic patients who require low carbohydrate foods.


Experiences and opinions of multi-professional non-medical oncology prescribers on post-qualification training: a qualitative study.
Within the UK, a non-medical prescriber is a non-medical healthcare professional who has undertaken post-registration training to gain prescribing rights. Lack of post-qualification NMP training has previously been identified as a barrier to the development of oncology non-medical prescribing practice. To explore the experiences and opinions of multi-professional non-medical oncology prescribers on post-qualification training. Nine out of 30 oncology non-medical prescribers (three nurses, three pharmacists and three radiographers) from a single cancer centre in Wales, were selected from a study site NMP database using randomisation sampling within Microsoft® Excel. Participants were interviewed using a validated and piloted semi-structured interview design on the topic of post-qualification training for non-medical prescribers. Participants were invited via organisational email. Interviews were audio-recorded and transcribed verbatim. Anonymised data were thematically analysed aided by NVivo® software. Main themes identified: experience related to training, competency, support and training methods. Competency assessment methods discussed were the annual non-medical prescriber appraisal, peer review and a line manager's overarching appraisal. Support requirements identified included greater consultant input to help non-medical prescribers identify training and peer support opportunities. Organisational support was requested regarding regular study leave and governance around clinical judgement and errors. The need for regular structured in-house training related to non-medical prescriber's level of experience was identified. Development of organisation-led governance strategies and in-house training programmes will support training equity for all non-medical prescribers within the organisation.


An assessment of adjunctive behavior in a safety-signal paradigm.
Three groups of rats were exposed to 0.4 mA shock presentations on a VT 30-sec schedule. Behavior was monitored during 35-sec shock-free periods inserted randomly after 15 of the 60 shocks per session. In the no-signal and random-signal control groups the behavior patterns which developed were similar to defense or fear reactions. In the safety-signal group, in which a tone signalled the 35-sec no-shock periods, a pattern of adjunctive and facultative behaviors developed including marked increases in grooming and rearing behaviors. No evidence of adjunctive drinking was found in any of the three groups.


Locus coeruleus and substantia nigra: involvement in morphine-induced behavior.
Cats pretreated with morphine (5 mg/kg, IP) received naloxone into the area of the locus coeruleus (LC) or the area of the substantia nigra (SN). The LC-treated animals stopped the morphine-induced stereotyped behavior and showed normal but hyperactive behavior. The SN-treated animals, however, ceased their movements of the head and the forelegs, adopted a rigid posture with extended forelegs and became hypoactive. It is concluded that both the LC area, which contains noradrenergic cell bodies, and the SN area, which contains dopaminergic cell bodies, are sites of action of morphine on behavior.


14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils.
14-Deoxyandrographolide (14-DAP) is a labdane diterpene isolated from Andrographis paniculata with previously reported calcium channel blocking activity. Its potential platelet activating factor (PAF) antagonistic activity in bovine neutrophils was assessed. 14-DAP, in concentrations between 10-100 microM, reduced the extracellular acidification rate and the intracellular alkalinization in a dose-dependent manner. In addition, 14-DAP reduced PAF-induced calcium flux in the presence of extracellular calcium, and tyrosine phosphorylation of a 44 kDa protein corresponding to the MAPK(ERK1). However, 14-DAP reduced the 3H-PAF binding with a Ki of 7.8 x 10 (- 9)M, and a Hill slope of 0.63, suggesting that there is more than one binding site for 14-DAP. We concluded that 14-DAP is an effective antagonist of PAF-mediated processes in bovine neutrophils, probably by virtue of its calcium channel blocking property.


Lanolin and derivatives chemistry: relationship to allergic contact dermatitis.
This paper summarizes lanolin, the composition of its esters, acids and alcohols, its chemical and physical modifications, and refining. It discusses lanolin, its constituents and derivatives, and their relationship to allergic contant dermatitis.


Cerebral embolization during percutaneous valve implantation does not occur during balloon inflation valvuloplasty: prospective diffusion-weighted brain MRI study.
The study aim was to define the timing of cerebral embolization events during transcatheter aortic valve implantation (TAVI), and to determine if events were more closely associated with valve implantation or with balloon inflation. Between January 2008 and November 2011, a total of 114 patients underwent TAVI at the author's institution. Of these patients, 44 had previously undergone imaging before and after TAVI, and were included in the study (26 transfemoral (TF); 18 transapical (TA)). Eleven patients who had only balloon valvuloplasty (BV) during the same period were included, as were 22 patients who had open aortic valve replacement (AVR), as controls. All 77 patients underwent neurological examination, and all had cerebral MRIs before and after their procedures. Fifty of the 77 patients who underwent postprocedural MRI had new cerebral lesions, as follows: 24/26 (92%) in TF patients; 17/18 (94%) in TA patients; 3/11 (27%) in BV patients; and 6/22 (27%) in AVR patients (TF and TA versus BV and AVR, p < 0.0001). The mean number and volume of embolic lesions per patient were respectively 5.4/438 mm3 for TF, 11.6/3414 mm3 for TA, 0.7/46 mm3 for BV, and 0.4/48 mm3 for AVR (TF versus TA and BV versus AVR, p = NS; TF and TA versus BV and AVR, p < 0.0001). No association was found between either the EuroSCORE or patient age and the number of events. In the present study, an incidence of silent cerebral embolic lesions after TAVI was identified which was significantly higher than that for BV or AVR. This indicated an association of embolism with valve implantation rather than with balloon inflation.


High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease.
Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises, chronic inflammation, and activation of coagulation. The clinical complications such as painful crisis, stroke, pulmonary hypertension, nephropathy and venous thromboembolism lead to cumulative organ damage and premature death. High molecular weight kininogen (HK) is a central cofactor for the kallikrein-kinin and intrinsic coagulation pathways, which contributes to both coagulation and inflammation. We hypothesize that HK contributes to the hypercoagulable and pro-inflammatory state that causes end-organ damage and early mortality in sickle mice. We evaluated the role of HK in the Townes mouse model of SCD. We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves survival of sickle mice.


Population pharmacokinetics and pharmacogenomics of tacrolimus in Chinese children receiving a liver transplant: initial dose recommendation.
In order to improve the precision of treatment with tacrolimus in Chinese patients undergoing pediatric liver transplantation, the optimum initial dose of tacrolimus was determined based on population pharmacokinetics and pharmacogenomics. Demographic data, clinical parameters, drug combinations and pharmacogenomics were integrated to build a population pharmacokinetic model using NONMEM. Additionally, Monte Carlo simulations were used to optimize the recommended initial dose. Weight, patient cytochrome 450 3A (CYP3A)5 genotype, and co-administration with wuzhi-capsule (WZ) were incorporated into the final model. For children with a CYP3A5*3/*3 genotype not co-administered WZ, 0.10 mg/kg/day split into two doses was recommended for patients weighing 5-17 kg, and 0.05 mg/kg/day split into two doses was recommended for patients weighing 17-60 kg. For children with a CYP3A5*1 allele not co-administered WZ, 0.25 mg/kg/day for patients weighing 5-10 kg, 0.20 mg/kg/day for patients weighing 10-17 kg, 0.15 mg/kg/day for patients weighing 17-36 kg, and 0.10 mg/kg/day for patients weighing 36-60 kg; all split into two doses was recommended. For children with a CYP3A5*3/*3 genotype co-administered WZ, 0.10 mg/kg/day for patients weighing 5-11 kg, and 0.05 mg/kg/day for patients weighing 11-60 kg; both split into two doses was recommended. For children with a CYP3A5*1 allele who were co-administered WZ, 0.20 mg/kg/day for patients weighing 5-10 kg, 0.15 mg/kg/day for patients weighing 10-22 kg, and 0.10 mg/kg/day for patients weighing 22-60 kg all split into two doses was recommended. The optimal initial dose of tacrolimus was determined based on population pharmacokinetics and pharmacogenomics in Chinese patients undergoing pediatric liver transplantation.


Gonadectomy affects brain derived neurotrophic factor in rats after chronic constriction nerve injury.
To assess the effect of gonadectomy on brain derived neurotrophic factor (BDNF) expression in neuropathic pain. Using chronic constriction injury (CCI) model, we detected BDNF mRNA in dorsal root ganglion and protein content in spinal cord by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay respectively. The time point we chose was post CCI operation d 0, 3, 7, 14, and 21. After CCI surgery, BDNF mRNA in ipsilateral DRGs was upregulated and reached its maximum on post operation d 7. BDNF protein level in ipsilateral spinal cord was also increased and reached its maximum on post operation d 14. The magnitude of this increase in gonadectomy (GDX) rats was significantly smaller than the GDX-sham rats at each time point. Gonadectomy reduced the BDNF increment after CCI surgery. Estrogen may affect nociceptive processing by its effect on BDNF.


Tissue uptake, distribution, and healing response after delivery of paclitaxel via second-generation iopromide-based balloon coating: a comparison with the first-generation technology in the iliofemoral porcine model.
This study sought to evaluate vascular drug uptake, distribution and response of second-generation paclitaxel coated balloon (PCB) (Cotavance, MEDRAD Interventional, Indianola, Pennsylvania) and compare it with first-generation technology, containing identical excipient and drug concentration. Original PCB technologies displayed a heterogeneous deposition of crystalline paclitaxel-iopromide inside the balloon folds, whereas second-generation PCBs consisted of more homogeneous, circumferential coatings. Paclitaxel tissue uptake was assessed in 20 iliofemoral arteries of a domestic swine. Vascular healing response was assessed in the familial hypercholesterolemic model of iliofemoral in-stent restenosis. Three weeks after bare-metal stent implantation, vascular segments were randomly revascularized with first-generation PCBs (n = 6), second-generation PCBs (n = 6), or plain balloon angioplasty (PBA) (n = 6). At 28 days, angiographic and histological evaluation was performed in all treated segments. One-hour paclitaxel tissue uptake was 42% higher in the second-generation PCBs (p = 0.03) and resulted in more homogeneous segment-to-segment distribution compared with first-generation PCBs. Both angiography (percentage of diameter stenosis: second-generation 11.5 ± 11% vs. first-generation 21.9 ± 11% vs. PBA 46.5 ± 10%; p < 0.01) and histology (percentage of area stenosis: second-generation 50.5 ± 7% vs. first-generation 54.8 ± 18% vs. PBA 78.2 ± 9%; p < 0.01) showed a decrease in neointimal proliferation in both PCB groups. Histological variance of the percentage of area stenosis was lower in second-generation compared with first-generation PCBs (51.7 vs. 328.3; p = 0.05). The presence of peristrut fibrin deposits (0.5 vs. 2.4; p < 0.01) and medial smooth muscle cell loss (0 vs. 1.7; p < 0.01) were lower in the second-generation compared with first-generation PCBs. In the experimental setting, second-generation PCB showed a comparable efficacy profile and more favorable vascular healing response when compared to first-generation PCB. The clinical implications of these findings require further investigation.


Noble metal nanoparticles (Mx = Ag, Au, Pd) decorated graphitic carbon nitride nanosheets for ultrafast catalytic reduction of anthropogenic pollutant, 4-nitrophenol.
We report an effective facile immobilization of noble nanoparticles (Mx = Ag, Au and Pd) assembled on g-C3N4 (g-CN) prepared via a simple ultra-sonication strategy. The Mx assembled g-CN nanocomposites were applied for the effective conversion of 4-nitrophenol (4-NP). As prepared nanocomposites were characterized by techniques of XRD, SEM-EDS, TEM, XPS, and FT-IR analysis to gain crystallographic structural, and morphological insights. The Pd@g-C3N4 (Pd@g-CN) nanocomposite exhibited best catalytic performance (kapp = 1.141 min-1) toward the conversion of 4-NP to 4-aminophenol (4-AP), almost 100% within 4 min using aqueous sodium borohydride (NaBH4). The higher catalytic efficiency of Pd@g-CN could be attributed to the surface electron density on the Pd and rapid electron transfer capacity. Interestingly, g-CN not only role as a stabilizer but also provided compatibility for noble metal deposition, which improves the chemical and morphological stability of noble metal nanoparticles. Different reaction parameters including concentrations of 4-NP, and catalyst amount were studied. These unique combinations make noble metal nanoparticles anchored g-CN nanosheets an ideal platform for catalysis applications and environmental remediation.


The expression of poly(A)-binding protein gene is translationally regulated in a growth-dependent fashion through a 5'-terminal oligopyrimidine tract motif.
Poly(A)-binding protein (PABP) is an important regulator of gene expression that has been implicated in control of translation initiation. Here we report the isolation and the initial structural and functional characterization of the human PABP gene. Delineation of the promoter region revealed that it directs the initiation of transcription at consecutive C residues within a stretch of pyrimidines. A study of the translational behavior of the corresponding mRNA demonstrates that it is translationally repressed upon growth arrest of cultured mouse fibroblasts and translationally activated in regenerating rat liver. Furthermore, transfection experiments show that the first 32 nucleotides of PABP mRNA are sufficient to confer growth-dependent translational control on a heterologous mRNA. Substitution of the C residue at the cap site by purines abolishes the translational control of the chimeric mRNA. These features have established PABP mRNA as a new member of the terminal oligopyrimidine tract mRNA family. Members of this family are known to encode for components of the translational apparatus and to contain an oligopyrimidine tract at the 5' terminus (5'TOP). This motif mediates their translational control in a growth-dependent manner.


Techno-economic assessment of co-production of edible bioplastic and food supplements from Spirulina.
Large amount of plastic wastes harming the environment have raised concerns worldwide on finding alternatives to non-biodegradable plastics. Microalgae has been found as a potential source for bioplastic production, besides its more common application in the pharmaceutical and nutraceutical industry. In this study, the objective was to techno-economically evaluate the large-scale co-production of Spirulina powder as food supplements and edible bioplastic for food packaging. The scale of production was large enough to satisfy 1% of local (Thailand) plastic demand (i.e., approx. 1200 MT y-1), and 1% of the global Spirulina demand (approx. 1000 MT y-1) as food supplements. Results showed that the co-production of the Spirulina powder and bioplastic revealed an attractive venture with a payback time (PBT) as low as 2.6 y and ROI as high as 38.5%. This was because the revenues generated were as high as US$ 55.6 million y-1, despite high capital (US$ 55.7 million) and operating (US$ 34.9 million y-1) costs. Sensitivity analysis showed differences in the profitability based on variations of major parameters in the study, where the split ratio of biomass used for food supplement versus bioplastic production and the bioplastic's selling price were found to be the most sensitive.


Determination of carboxymethyl-D-glucoses in the product of hydrolytic depolymerization of carboxymethylcellulose by isotachophoresis.
Optimal conditions for isotachophoretic separation of carboxymethyl-D-glucoses formed by acidic depolymerization of carboxymethylcellulose were found. 6-O-carboxymethyl-D-glucose, 2-O-carboxymethyl-D-glucose and 3-O-carboxymethyl-D-glucose were identified and determined in the reaction mixture after carboxymethylcellulose hydrolysis. Relative reactivity of hydroxy groups in the glucopyranose unit of cellulose decreased in the following order: O(6)H greater than O(2)H much greater than O(3)H. This was found to be in agreement with the data published by other authors.


Regulation of the cytoskeleton in mesothelial cells: reversible loss of keratin and increase in vimentin during rapid growth in culture.
Human mesothelial cells grew rapidly in culture when provided with serum, EGF, and hydrocortisone, adopting a fibroblastoid shape and forming parallel, multilayered arrays at saturation density. In the absence of EGF, the cells grew slowly to a flat, epithelioid monolayer similar to their normal pattern in vivo. Mesothelial cells normally have a high keratin and a low vimentin content in vivo. In culture, rapidly growing cells greatly reduced synthesis and content of their four major keratins to levels undetectable by immunofluorescence in most cells, but keratin synthesis and content returned to high levels whenever growth slowed. Vimentin synthesis and content was high during serial culture, but decreased several-fold in nondividing cells. The unique ability of the mesothelial cell to reversibly alter its morphology and intermediate filament composition is of unknown function and mechanism, but accounts for the morphological heterogeneity and the presence of keratin-negative cells in mesotheliomas.


Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes.
Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p <0.001). After adjustment for potential confounders including glycated hemoglobin, hypertension and body mass index, advanced fibrosis, but not liver steatosis, was associated with increased risk of albuminuria (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.28; p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m2. The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07-2.20; p = 0.021). Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.