Migraine and Risk of Ocular Motor Cranial Nerve Palsies: A Nationwide Cohort Study.
To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). Nationwide retrospective cohort study. Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score-matched controls (n = 138 907). Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts. After a mean follow-up period of 3.1 years (range, 1-6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P < 0.001; HR, 4.23, P < 0.001; HR, 3.37; P < 0.001). This finding was maintained after excluding potential confounders during sensitivity tests. Moreover, the significant association between migraine and OMCNP remained after we adjusted for potential risk factors of microvascular ischemia. However, different migraine subtypes showed no significant differences. Migraine is an unrecognized risk factor for OMCNP development in adults. Further studies are needed to validate our findings and to delineate the exact pathophysiologic mechanisms linking migraine and OMCNP.


Lack of efficacy of pomegranate supplementation for glucose management, insulin levels and sensitivity: evidence from a systematic review and meta-analysis.
The potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. In this paper, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the precise effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans. Comprehensive electronic searches were conducted in PubMed, Embase, and the Cochrane Library. Studies included were RCTs that evaluated the changes in diabetes biomarkers among adults (≥18 years) following pomegranate interventions. The predefined outcomes included fasting blood glucose (FBG), fasting blood insulin (FBI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR). Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using a random-effects model. Publication bias, subgroup analyses, sensitivity analysis and random-effects meta-regression were also performed to explore the influence of covariates on the net changes in fasting glucose and insulin concentrations. Sixteen eligible trials with 538 subjects were included. The pooled estimates suggested that pomegranate did not significantly affect the measures of FBG (WMD, -0.6 mg/dL; 95% CI, -2.79 to 1.58; P=0.59), FBI (WMD, 0.29 μIU/mL; 95% CI, -1.16 to 1.75; P=0.70), HOMA-IR (WMD, -0.04; 95% CI, -0.53 to 0.46; P=0.88) or HbA1c (WMD, -0.11%; 95% CI, -0.39 to -0.18; P=0.46). Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found in the current meta-analysis. Pomegranate intake did not show a notably favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results.


In vitro and in vivo ligand binding to the 5HT(3) serotonin receptor characterised by time-resolved fluorescence spectroscopy.
The binding of the fluorescein-labelled antagonist GR-flu ([1,2,3,9-tetrahydro-3-[(5-methyl-1H-imidazol-4-yl)methyl]-9-(3-amino-(N-fluoresceinthiocarbamoyl)propyl)-4H-carbazol-4-one]) to a purified, detergent-solubilised ligand-gated ion channel, the type-3 serotonin (5-hydroxytryptamine, 5HT) receptor (5HT(3)R), was characterised by frequency-domain time-resolved fluorescence spectroscopy (TRFS). Detailed understanding of how ligands interact with the homopentameric receptor was obtained. While a 1:1 stoichiometry was observed for the GR-flu-receptor complex, the agonist quipazine bound cooperatively to the receptor, suggesting multiple binding sites for this ligand. The GR-flu-binding site of the receptor was proven to provide an acidic environment as shown by determining the fraction of bound GR-flu in the protonated state. Fluorescence anisotropy relaxation experiments indicated a hindered but still high mobility for the receptor-bound GR-flu. Hence, the binding site is expected to present a wide opening to the ligand. Finally, we succeeded in measuring the binding of GR-flu to 5HT(3) receptors in live cells. These results show that the purified and the native receptor behave identically and demonstrate that time-resolved fluorescence measurements are suited to selectively investigate biomolecular interactions in live cells.


Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception.
In humans, gamma-band oscillations in the primary somatosensory cortex (S1) correlate with subjective pain perception. However, functional contributions to pain and the nature of underlying circuits are unclear. Here we report that gamma oscillations, but not other rhythms, are specifically strengthened independently of any motor component in the S1 cortex of mice during nociception. Moreover, mice with inflammatory pain show elevated resting gamma and alpha activity and increased gamma power in response to sub-threshold stimuli, in association with behavioral nociceptive hypersensitivity. Inducing gamma oscillations via optogenetic activation of parvalbumin-expressing inhibitory interneurons in the S1 cortex enhances nociceptive sensitivity and induces aversive avoidance behavior. Activity mapping identified a network of prefrontal cortical and subcortical centers whilst morphological tracing and pharmacological studies demonstrate the requirement of descending serotonergic facilitatory pathways in these pain-related behaviors. This study thus describes a mechanistic framework for modulation of pain by specific activity patterns in the S1 cortex.


Exploring the perspectives and preferences for HTA across German healthcare stakeholders using a multi-criteria assessment of a pulmonary heart sensor as a case study.
Health technology assessment and healthcare decision-making are based on multiple criteria and evidence, and heterogeneous opinions of participating stakeholders. Multi-criteria decision analysis (MCDA) offers a potential framework to systematize this process and take different perspectives into account. The objectives of this study were to explore perspectives and preferences across German stakeholders when appraising healthcare interventions, using multi-criteria assessment of a heart pulmonary sensor as a case study. An online survey of 100 German healthcare stakeholders was conducted using a comprehensive MCDA framework (EVIDEM V2.2). Participants were asked to provide i) relative weights for each criterion of the framework; ii) performance scores for a health pulmonary sensor, based on available data synthesized for each criterion; and iii) qualitative feedback on the consideration of contextual criteria. Normalized weights and scores were combined using a linear model to calculate a value estimate across different stakeholders. Differences across types of stakeholders were explored. The survey was completed by 54 participants. The most important criteria were efficacy, patient reported outcomes, disease severity, safety, and quality of evidence (relative weight >0.075 each). Compared to all participants, policymakers gave more weight to budget impact and quality of evidence. The quantitative appraisal of a pulmonary heart sensor revealed differences in scoring performance of this intervention at the criteria level between stakeholder groups. The highest value estimate of the sensor reached 0.68 (on a scale of 0 to 1, 1 representing maximum value) for industry representatives and the lowest value of 0.40 was reported for policymakers, compared to 0.48 for all participants. Participants indicated that most qualitative criteria should be considered and their impact on the quantitative appraisal was captured transparently. The study identified important variations in perspectives across German stakeholders when appraising a healthcare intervention and revealed that MCDA can demonstrate the value of a specified technology for all participating stakeholders. Better understanding of these differences at the criteria level, in particular between policymakers and industry representatives, is important to focus innovation aligned with patient health and healthcare system values and constraints.


[Localised aspergillosis and oxalosis of the lung caused by aspergillus niger: soil of ornamental plants as a reservoir of aspergilli (case report) (author's transl)].
Haemoptysis occurred in a 64-year-old man with a history of pulmonary tuberculosis, negative for M. tuberculosis. Precipitating antibodies to Aspergillus niger were found in serum and the fungus found in sputum. Autopsy revealed aspergilloma, colonization of the pulmonary cavity by A. niger and local oxalosis if the cavity wall. Ornamental plant soil containing A. niger conidia, as well as the air in the patient's living-room, was the probable source of infection.


Effects of orally administered oestradiol decanoate on plasma oestradiol, oestrone and gonadotrophin levels, vaginal cytology, cervical mucus and endometrium in ovariectomized women.
Six ovariectomized women with the uterus left in situ were given a daily oral dose of 0.5 mg of oestradiol decaneoate in oil for 14 days. After a single dose of oestradiol decanoate mean plasma oestradiol rose from 26.8 pg/ml to 66.8 pg/ml within 30 min. There was a further rise to 100-110 pg/ml (P less than 0.001) remaining at the same level over a 24 h period. On repeated daily administration of oestradiol decanoate this rise continued reaching the mean value of 187.1 pg/ml (P less than 0.001) at 2 weeks, while plasma oestrone remained at the same level (147.1 pg/ml) as it was at 24 h. The ratio of plasma oestrone:oestradiol was less than 1 at 2 weeks. Plasma FSH and LH fell progressively during the medication. Changes of the Maturation Index, cervical mucus Ferning and Spinnbarkeit demonstrated the strong 'peripheral' activity of this dose of oestradiol decanoate. All endometrial specimens showed late proliferative changes at 2 weeks. It was concluded that the favourable properties of oestradiol decanoate offer new possibilities for a more physiological oestrogen supplementation therapy.


Maximum power extraction and DC-Bus voltage regulation in grid-connected PV/BES system using modified incremental inductance with a novel inverter control.
Low ripples and variations in the DC-Bus voltage in single-phase Photovoltaic/Battery Energy Storage (PV/BES) grid-connected systems may cause significant harmonics distortion, instability, and reduction in power factor. The use of short-life electrolytic capacitor on the DC-Bus is considered a standard way for reducing these ripples and variations because of its large capacitance but results in short lifetime of the inverter. Replacing large electrolytic capacitors with small film capacitors can extend the lifetime of a PV/BES grid-connected system because small film capacitors have longer lifetime than large electrolytic capacitors. These film capacitors have low capacitance, which causes severe oscillations in the output current, and voltage drop due to huge ripples on the DC-Bus voltage. In this research, the main goal is to eliminate the output current ripples and voltage fluctuations associated with employing film capacitors. First, a modified incremental conductance (MIC) technique is proposed for tracking the maximum power by controlling the duty ratio of the DC-DC boost converter. Second, for the first time, a simple and novel d-q current regulation technique, which employs flowchart decision logic, is used in the DC-Bus control system for both the PV power system and the state of charge (SOC) of the BES. In this case, the DC-Bus controller is characterized by a cost-effective implementation because of its low sampling frequency. Although the presented approaches are successful in eliminating voltage distortion and fluctuations, they have unacceptable dynamic performance. Therefore, to improve the dynamic performance, BES was used to maintain a reliable and stable harvest from PV modules for varying loads while also increasing the dynamic performance of the overall system. The proposed PV/BES grid-connected systems, which employs a small 10-µF bus capacitor, is simulated and connected to the grid (230 V, 50 Hz). The DC-Bus voltage overshoot, undershoot and the total harmonics distortion (THD) of the output current for the proposed MIC are (1 V), (2.5 V) and (less than 5%), respectively. The average time response under rising radiation to track the global peak for MIC, traditional incremental conductance and variable step size incremental conductance are 1.403 s, 1.501 s and 1.113 s respectively. The obtained findings demonstrated the efficacy and superiority of the proposed d-q current control and MIC technique.


Evidence for dissociation of ferrihemoglobin by poly-L-lysine.
Circular dichroism and absorption spectra of ferrihemoglobin were shown to be altered upon binding with poly-L-lysine at alkaline pH. When ferrihemoglobin immobilized to Sepharose gel was treated with poly-L-lysine, hemoglobin subunits were released from the gel. These results suggest that ferrihemoglobin was dissociated into subunits by poly-L-lysine.


Skin manifestations of Kikuchi-Fujimoto disease: case report and review.
Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotising lymphadenitis, which is a benign disease of unknown aetiology. Misdiagnosing KFD as lymphoma or systemic lupus erythematosus is not uncommon due to the similarity of clinical and histopathological features of these diseases. A 12-year-old female suffered from cervical lymphadenopathy, leukocytopenia, fever and especially skin rash. The biopsy of the lymph node was compatible with KFD. The skin biopsy showed interface alterations with vacuolar degeneration of the basal cells suggesting lupus erythematosus; however, the patient did not fulfill the diagnostic criteria for systemic lupus erythematosus. After treatment with acetaminophen, fever subsided and the skin rashes disappeared without relapse during a 10-month follow-up period. The histopathological findings of cutaneous lesions in KFD are usually similar to those observed in the involved lymph nodes. This report suggests that interface change might be one of the pathological features of the cutaneous manifestations of KFD.


[The future of teleradiology: results of Teleradiology Expert Meeting of the Health Network Congress 2001].
Legal prerequisites have substantial influence on the development of teleradiology. At an expert meeting (Mannheim, 8.6.2001) a proposal for a teleradiology article in the new German x-ray ordinance has been set up. An exception of the demand for a doctor trained in radiation protection at the point of examination shall be established for emergency cases. To realize the intended improvement of patient care measurements for quality assurance concerning the medical personnel and processes are necessary. Along with other current developments the basis of secure regional teleradiology networks is now built up.


Skilled reaching training promotes astroglial changes and facilitated sensorimotor recovery after collagenase-induced intracerebral hemorrhage.
Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke and a leading cause of disability and mortality worldwide. Although rehabilitation improves recovery after ICH the cellular mechanisms involved are poorly understood. We decided to examine if skilled (SK) and unskilled (US) training after sham or intracerebral hemorrhage (ICH) surgeries would induce GFAP+ astrocytic changes and whether these modifications can be associated with functional improvement. A 4-week course of motor training, involving either skilled and unskilled training began seven days after surgery; sensorimotor recovery was evaluated using Staircase, ladder walk and cylinder tests. Histological and morphometric analyses were used to assess GFAP+ cell bilaterally in forelimb sensorimotor cortex and dorsolateral striatum. All behavioral tests showed that ICH-SK rats experienced a greater degree of recovery when compared to ICH no task or ICH-US groups; no behavioral differences were found among all sham groups. Astrocytic density was increased in all analyzed structures for ICH no task, ICH-SK and ICH-US rats. Morphological analysis revealed an increased number of primary processes in ipsilateral (to lesion) sensorimotor cortex for all ICH groups. Present results also revealed that both ICH and SK induced an increased length of GFAP+ primary process; there was a further increase in length processes for ICH-SK group in sensorimotor cortex and ipsilateral striatum. We suggest that skilled reaching is an effective intervention to promote astrocytic plasticity and recovery after ICH.


WH1fungin a surfactin cyclic lipopeptide is a novel oral immunoadjuvant.
WH1fungin, a surfactin lipopeptide from Bacillus amyloliquefaciens WH1, can be used as an adjuvant for eliciting strong immune response by parenteral immunization. In this study, WH1fungin was firstly reported as an oral immunoadjuvant. In mice, WH1fungin markedly enhanced the immune response to co-administered protein antigens (OVA or GST), similar to levels elicited by CTB, but no immune response was elicited to itself. Both IgG1 and IgG2a antibodies elicited from the immunizations indicating a mixed Th1/Th2 response. Splenocytes from mice immunized with OVA plus WH1fungin responded to OVA CTL peptide stimulation resulting in an increase in CD8(+)TNF-α(+) and CD8(+)IFN-γ(+) T cell populations. These results further suggested that WH1fungin helps to elicit both humoral and cellular responses to OVA. More studies revealed that the potential mechanism as oral immunoadjuvant was that WH1fungin could form co-precipitates with antigens in a pH value similar to gastric juice. The precipitation protected the antigens from degradation by pepsin providing an explanation for the antigens to withstand the acidic and proteolytic environments of the gastrointestinal tract when co-administered with WH1fungin. Moreover, WH1fungin promoted the uptake of OVA by the intestine and by cultured DC2.4 cells, and increased the expression of cell surface markers and cytokines in DC2.4 cells. Taken together, WH1fungin is a potent oral immunoadjuvant with the ability of protecting protein antigens from acidic and proteolytic degradation, suggesting its potential usage in oral vaccine development.


Behavior of natural radionuclides in wastewater treatment plants.
56 samples, including influent, primary effluent, secondary effluent and final effluent wastewater from two Spanish municipal wastewater treatment plants (WWTPs), were analyzed to assess both the occurrence and behavior of natural radioactivity during 12 sampling campaigns carried out over the period 2007-2010. Influent and final effluent wastewaters were sampled by taking into account the hydraulic residence time within the WWTP. A wide range of gross alpha activities (15-129 mBq/L) and gross beta activities (477-983 mBq/L) in liquid samples were obtained. A correlation analysis between radioactivity in liquid samples and the performance characteristics of the WWTPs was performed. The results in liquid samples showed that gross beta activities were not influenced by treatment in the studied WWTPs. However, gross alpha activities behave differently and an increase was detected in the effluent values compared with influent wastewater. This behavior was due to the increase in the total dissolved uranium produced during secondary treatment. The results indicate that the radiological characteristics of the effluents do not present a significant radiological risk and make them suitable for future applications.


9-(Phosphonoalkyl)guanine derivatives as substrates or inhibitors of guanylate kinase.
Several 9-(phosphonoalkyl)guanines (Gua(CH2)nCH2-PO3H2; n = 4-6) and 9-(difluorophosphonoalkyl)guanines (Gua(CH2)nCF2PO3H2; n = 3-7) were studied as potential substrates and inhibitors of guanylate kinase. These compounds are inhibitors of the enzyme except 9-(5-phosphonopentyl)guanine (n = 4) which is a substrate with an efficiency of phosphorylation of about 0.3% that of GMP, as estimated from the Vmax/Km ratios. The phosphonate and difluorophosphonate derivatives with n = 5 produce optimal inhibition. These two compounds have similar affinity, both being competitive inhibitors with respect to GMP and noncompetitive inhibitors with respect to ATP. pH-dependence studies indicate that the dianionic rather than the monoanionic form of these compounds bind to the enzyme. The lack of phosphorylation of 9-(5,5-difluoro-5-phosphonopentyl)guanine by guanylate kinase is explained by the decreased nucleophilic character of the oxygen atoms of the phosphonate group rather than by inadequate binding to the GMP-binding site.


Basal Cell-derived WNT7A Promotes Fibrogenesis at the Fibrotic Niche in Idiopathic Pulmonary Fibrosis.
Loss of epithelial integrity, bronchiolarization, and fibroblast activation are key characteristics of idiopathic pulmonary fibrosis (IPF). Prolonged accumulation of basal-like cells in IPF may impact the fibrotic niche to promote fibrogenesis. To investigate their role in IPF, basal cells were isolated from IPF explant and healthy donor lung tissues. Single-cell RNA sequencing was used to assess differentially expressed genes in basal cells. Basal cell and niche interaction was demonstrated with the sLP-mCherry niche labeling system. Luminex assays were used to assess cytokines secreted by basal cells. The role of basal cells in fibroblast activation was studied. Three-dimensional organoid culture assays were used to interrogate basal cell effects on AEC2 (type 2 alveolar epithelial cell) renewal capacity. Perturbation was used to investigate WNT7A function in vitro and in a repetitive bleomycin model in vivo. We found that WNT7A is highly and specifically expressed in basal-like cells. Proteins secreted by basal cells can be captured by neighboring fibroblasts and AEC2s. Basal cells or basal cell-conditioned media activate fibroblasts through WNT7A. Basal cell-derived WNT7A inhibits AEC2 progenitor cell renewal in three-dimensional organoid cultures. Neutralizing antibodies against WNT7A or a small molecule inhibitor of Frizzled signaling abolished basal cell-induced fibroblast activation and attenuated lung fibrosis in mice. In summary, basal cells and basal cell-derived WNT7A are key components of the fibrotic niche, providing a unique non-stem cell function of basal cells in IPF progression and a novel targeting strategy for IPF.


Efficacy of contrast-enhanced ultrasound for diagnosis of cesarean scar pregnancy type.
We compared the clinical efficacy of contrast-enhanced ultrasound (CEUS) to transvaginal ultrasound (TVS) for diagnosing cesarean scar pregnancy (CSP). A total of 485 cases of suspected CSP were recruited from January 2017 to March 2018. All received TVS and CEUS by two sonologists blinded to diagnosis by the other. Diagnostic features of CSP that significantly differed between modalities by univariate analysis (P < .05) were included in a logistic regression model. The sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), and accuracy (ACC) of CSP diagnosis by TVS and CEUS were compared according to operational and pathological outcomes as the reference standard. There were 220 CSP cases (including 85 cases of type I, 93 of type II, and 42 of type III). The sensitivities of CEUS for detection of types I - III CSP were 94.1%, 92.5%, and 97.6%, respectively, and corresponding sensitivities of TVS were 82.4%, 80.6%, and 95.2%. Compared to TVS, CEUS yielded significantly better overall sensitivity (97.27% vs 88.18%), specificity (96.60% vs 75.47%), +LR (28.60 vs 3.59), -LR (0.03 vs 0.16), and diagnostic ACC (96.9% vs 81.23%) (all P < .001). CEUS is superior to TVS for detecting cesarean scar pregnancy and distinguishing among CSP types.


Thyroid carcinoma, cataract and hearing loss in a patient after irradiation for facial hemangioma.
Thyroid carcinoma and cataract are well established complications of irradiation treatment to the head and neck region. Hearing loss is also a documented complication though less frequently reported. A rare case of a patient suffering from all three complications due to irradiation of the face by 24,000 rads for a hemangioma is reported. The pertinent literature is reviewed.


Residues of dioxin in egg samples collected from west zone of India.
The residues of the congeners of dioxin and furan have been identified in the egg samples collected from the western zone of the India. The samples were collected from the chicken grown in sites where Municipal Corporation incinerates the municipal and hazardous wastes. All the samples showed the presence of the residues of PCDDs/Fs. The mean TEQ of dioxin and furan were 7.10 pg/g and 0.39 pg/g respectively.


Matching design to use: a task analysis comparison of three cognitive aid designs used during simulated crisis management.
Intraoperative critical events typically include vital sign instability that requires a specific and time-sensitive response. Although cognitive aids can improve clinical performance during critical events, their design may not be optimized for real-world use. For example, during a critical event, health practitioners may be familiar with the treatment pathway and only require specific information from an aid-a behaviour described as "sampling". We hypothesized that use of cognitive aids designed to facilitate sampling behaviour would reduce the time required to extract information during simulated critical events. We designed two experimental cognitive aids, based on cognitive science research on human performance, to facilitate sampling behaviour. Design principles included content clusters that were specifically located, colour-coded and labelled, the elimination of distractors such as numbering, and a key features summary. In a simulated low-fidelity study, we compared the time required for anesthesia care providers to identify and extract specific information from these two experimental cognitive aids and from a traditional step-by-step "linear/control" aid. An eye-tracking device was used to assess how information was accessed from the cognitive aids. When all response times were pooled, participants identified and extracted information more quickly using either experimental aid (median [interquartile range] 6.3 [4.0-9.7] sec, P = 0.006 and 4.7 [3.3-6.3] sec, P < 0.001) than the "linear/control" cognitive aid (12.7 [9.3-14.7] sec). Eye-tracking data revealed that participants spent more time looking at the "linear/control" design cognitive aid [mean (standard deviation) 10.9 (7.1) sec] than at either experimental cognitive aid [6.7 (4.6) and 3.8 (2.5) sec, P = 0.020, P < 0.001], respectively. Cognitive aids designed to enhance sampling behaviour may facilitate rapid retrieval of specific information during crisis management.


Application of the crypt-isolation technique to flow-cytometric analysis of DNA content in colorectal neoplasms.
Conventional flow-cytometric analysis of colorectal tumor DNA content includes both tumor and stromal cell DNA. To improve the method, we evaluated the DNA content of purified epithelial cells using the crypt-isolation technique. Normal and neoplastic crypts were isolated from fresh resected colorectum nonenzymatically. Isolated crypts were digested into single nuclei suspensions and examined by flow cytometry (FCM). Internal controls from normal crypts were used to define diploidy. The neoplastic nuclei in the same individual and mixtures of both normal and neoplastic nuclei in various ratios were analyzed. Tumors having both diploid and aneuploid stemlines were found more frequently than that reported using conventional FCM. Near-diploid DNA stemlines with DNA indices ranging between 0.90 and 1.10 were detectable. The cases of advanced cancer in which the DNA index was between 0.90 and 0.95 were associated significantly with Dukes' stage C. This is the first reported analysis of the DNA content of "pure" neoplastic colorectal epithelia using FCM. Multiploid and near-diploid stemlines were more accurately analyzed than that using conventional FCM.


Chronic inflammation and CD16+ natural killer cell zeta-chain downregulation in hemodialysis patients.
Natural killer (NK) cell activity is decreased in hemodialysis (HD) patients. Zeta-chain phosphorylation is an early event that follows the triggering of some NK cell-activating receptors. NK cell zeta-chain is downregulated in patients with cancer due to chronic inflammation. HD is also a chronic inflammatory state. NK cell zeta-chain expression in HD was evaluated. Thirty-three HD patients and 30 healthy volunteers were enrolled into the study. The CD3-CD16+ subpopulation was examined, since it corresponds to 90% of all NK cells and has the highest cytotoxicity.NK cell count and zeta-chain mean fluorescence intensity were evaluated with flow cytometry. The inflammatory markers C-reactive protein, IL-6 and tumor necrosis factor-alpha were measured with ELISA. The inflammatory markers were increased in HD patients. NK cell count did not differ between HD patients and healthy volunteers. NK cell zeta-chain mean fluorescence intensity was decreased in the patient group. Chronic inflammation could be responsible for the NK cell zeta- chain downregulation in HD patients, contributing to the decreased NK cell activity.


Sonographic evaluation of immobility of normal and endometriotic ovary in detection of deep endometriosis.
To examine the association between ovarian immobility and presence of endometriomas and assess the diagnostic accuracy of transvaginal sonographic (TVS) ovarian immobility in the detection of deep infiltrating endometriosis (DIE). This was a multicenter prospective observational study of women presenting with chronic pelvic pain from January 2009 to March 2015. Women with or without history of endometriosis who were scheduled to undergo laparoscopic surgery for endometriosis gave a detailed history and underwent specialized TVS in a tertiary referral unit prior to laparoscopy. During TVS, ovarian mobility and the presence of endometriomas were assessed. The relationship between TVS ovarian mobility, with or without endometriomas, and DIE was correlated with the gold standard, diagnosis of endometriosis at laparoscopy. Included in the analysis were 265 women with preoperative TVS and laparoscopic outcomes. Ovarian immobility on TVS was significantly associated with presence of endometriomas at surgery, with a prevalence of 12.2%, 10.8% and 52.7% for fixation of the left ovary only, the right ovary only and bilateral ovaries, respectively, compared with 4.2%, 3.7% and 7.3% for normal ovaries. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and positive and negative likelihood ratios of TVS ovarian immobility for diagnosis at surgery of immobility of ovaries with endometriomas in the left ovary only were 44.4%, 92.3%, 44.4%, 92.3%, 5.8, 0.6, in the right ovary only were 50.0%, 98.5%, 80.0%, 94.2%, 33.0, 0.5 and bilaterally were 74.4%, 68.6%, 72.5%, 70.6%, 2.4, 0.4, while those for diagnosis of immobility of normal ovaries were 25.0%, 87.9%, 8.3%, 96.4%, 2.1, 0.9 for left ovary only, 14.3%, 92.9%, 7.1%, 96.6%, 2.0, 0.9 for right ovary only and 35.7%, 97.2%, 50.0%, 95.0%, 12.6, 0.7 bilaterally, respectively (P < 0.05 except for normal left and right ovaries with P = 0.2 and 0.4, respectively). The sensitivity, specificity, PPV and NPV for performance of ovarian immobility in the prediction of DIE for all women were 58.3%, 74.1%, 60.6%, 72.2% and in the prediction of need for bowel surgery were 78.2%, 71.1%, 41.3%, 92.6%, respectively. There is a significant association between ovarian immobility and the presence of endometriomas. Ovarian immobility as a sonographic 'soft marker' of DIE performs better in the presence of endometriomas compared with in normal ovaries. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Differential expression of leukemia inhibitory factor and insulin like growth factor-1 between normal pregnancies, partial hydatidiform moles and complete hydatidiform moles.
Leukemia inhibitory factor (LIF) and insulin like growth factor-1 (IGF-1) are two of the most important growth factors mediating trophoblast actions. We hypothesized that the localization and expression patterns of LIF and IGF-1 in partial and complete hydatidiform moles (HM) compared with normal first trimester placentas may provide an understanding of the proliferative processes in HMs. The study population included curettage material of women diagnosed as complete or partial HM as a result of histopathological and immunohistochemical examination (complete HM group, n = 8; partial HM group, n = 8) and women undergoing dilatation&curettage for unwanted pregnancies (control group, n = 8). Expression of LIF and IGF-1 among placental cell groups was evaluated immunohistochemically and given a score depending on immunostaining intensity. In normal chorionic villi strong expression of LIF and IGF-1 was present. Both LIF and IGF-1 expressions were weaker in the chorionic villi of complete HMs. In complete mole decidua there was a significant decrease in glandular and endothelial IGF-1 expression along with a decrease in decidual cell LIF expression compared to normal first trimester decidua. LIF expression in extravillous trophoblasts was stronger in complete molar placentas compared to normal placentas. LIF and IGF-1 are important regulators of trophoblast proliferation and invasion. Differential expression of LIF and IGF-1 in molar trophoblasts and chorionic villi might have a role in regulation of trophoblasts in complete moles. Decreased expression of glandular IGF-1 and decidual LIF might be related to the decidual changes during trophoblastic proliferation and invasion of decidua in complete HMs.


The prevalence of physical activity and its associated factors among Malaysian adults: findings from the National Health and Morbidity Survey 2011.
Despite the health-enhancing benefits of physical activity, a large segment of the Malaysian population does not engage in regular physical activity at the recommended level. This study aimed to determine physical activity patterns and the associated sociodemographic correlates of physical activity. Data on physical activity were obtained from the National Health and Morbidity Survey (NHMS) 2011, a nationally representative, population-based cross-sectional study. A two-stage stratified sampling method was used to select a representative sample of Malaysian adults aged 16 years and above. A total of 19,145 adults aged 16 years and above were recruited, and face-to-face interviews were conducted using the International Physical Activity Questionnaire (IPAQ), short version. The correlates for physical activity were identified using multivariate analysis. In this study, 64.3% (95%CI: 63.1-65.5) of Malaysian adults aged 16 and above were physically active, but overall physical activity levels decreased with advancing age. Men, rural residents, 'other' ethnic groups, and married women were more likely to demonstrate higher levels of physical activity. Approximately 65% of Malaysian adults were physically active. However, it is recommended that health promotions for active lifestyles should be targeted to the least active segments, which constitute more than a quarter of the Malaysian population.


Comparison of survival and post-operation outcomes for minimally invasive versus open hepatectomy in hepatocellular carcinoma: A systematic review and meta-analysis of case-matched studies.
With the rapid development of minimally invasive techniques and instruments, more and more patients begin to accept minimally invasive surgery. Minimally invasive hepatectomy (MIH) has obvious advantages in terms of surgical incision, but there is still no strong evidence of its long-term survival effect. The primary objective of this study was to compare long-term survival outcomes between MIH and Open hepatectomy (OH) in hepatocellular carcinoma based on high-quality case-control studies. The study on the comparison of MIH (including RH or LH) and OH in the treatment of HCC from the date of establishment to June 1, 2022 was searched through PubMed, Web of Science, Embase and Cochrane Library databases. The main results were long-term overall and disease-free survival and short-term postoperative effect; All studies were conducted according to PRISMA guidelines, and meta-analysis of random effect models was adopted. 43 articles included 6673 patients. In these studies, the data from 44 studies need to be extracted and pooled in the meta-analysis. Our results showed that compared with OH group, OS (HR 1.17; 95%CI 1.02, 1.35; P=0.02) and DFS (HR 1.15; 95%CI 1.05, 1.26; P=0.002) in MIH group were slightly lower than those in OH group. The operation time (Z=2.14, P=0.03, MD8.01, 95% CI: 2.60-13.42) was longer than OH group. In terms of length of hospital stay (Z=10.76, p<0.00001, MD -4.0, 95% CI: -4.72 to -3.27), intraoperative blood loss (Z=5.33, P<0.00001, MD -108.33, 95% CI: -148.15 to -68.50), blood transfusion rate (Z=5.06, p<0.00001, OR=0.64, 95% CI 0.54 to 0.76, I2 = 0%), postoperative complications (Z=9.24, p<0.00001, OR = 0.46, 95% CI 0.39 to 0.55, I2 = 21%), major morbidity (Z=6.11, p<0.00001, OR=0.46, 95% CI 0.39 to 0.59,I2 = 0%), R0 resection (Z=2.34, P=0.02, OR=1.46, 95% CI 1.06 to 2.0, I2 = 0%) and mortality(Z=2.71,P=0.007, OR=0.56, 95% CI 0.37 to 0.85), the MIH group was significantly better than the OH group. The meta-analysis showed no significant difference in terms of major hepatectomy Z=0.47, P=0.64, OR=1.04, 95% CI 0.89 to 1.22, I2 = 0%), anatomical resection (Z=0.48, P=0.63, OR=0.92, 95%CI 0.67 to 1.27), satellite nodules (Z=0.54, P=0.59, OR=0.92, 95%CI 0.69 to 1.23, I2 = 0%), microvascular invasion (Z=1.15, P=0.25, OR=1.11, 95%CI 0.93 to 1.34, I2 = 0%) and recurrence (Z=0.71, p=0.48, OR=0.94, 95% CI 0.78 to 1.12, I2 = 19%). This study is the first to compare the clinical efficacy of MIH and OH in the treatment of HCC based on a high-quality propensity score matching study. The results show that in terms of long-term survival outcomes (OS and DFS), although the gap between MIH and OH is not obvious, OH was better than MIH on the whole. However, in terms of short-term postoperative outcomes (post-operation outcomes), MIH was slightly better than OH. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022332556.


Treatment Pattern for Advanced Gastric Cancer in Japan and Factors Associated with Sequential Treatment: A Retrospective Administrative Claims Database Study.
Clinical trials have proven the efficacy and safety of new therapies for advanced gastric cancer (AGC), but how those therapies are used in the real world is poorly described. Real-world treatment patterns of antitumor therapies and factors associated with overall therapy duration in patients with AGC in Japan were investigated. This retrospective cohort study used a Japanese administrative claims database (June 2014 to September 2019). Patients with AGC who started the guideline-recommended first-line combination regimens with platinum and fluoropyrimidine agents between June 2015 and July 2019 were included. Cox regression analysis was performed to identify factors associated with overall therapy duration (first line to last administration of guideline-listed agent). Of the 10,581 patients included, the most common first-line combination regimen without trastuzumab was S-1 plus oxaliplatin (4327/9069 patients; 47.7%) and with trastuzumab was capecitabine plus cisplatin (608/1512 patients; 40.2%). Most common second- and third-line regimens were ramucirumab plus taxane (3650/5358 patients; 68.1%) and nivolumab (1229/2390 patients; 51.4%), respectively. Factors positively associated with longer overall therapy duration were: oral fluoropyrimidine in first line (hazard ratio [95% confidence interval]: 0.63 [0.57-0.69]); trastuzumab in any line (0.73 [0.68-0.78]); treatment at a designated cancer hospital (0.89 [0.84-0.94]); dietary consultation within 1 month before/after start of first line (0.92 [0.86-0.98]); and treatment at a surgical department (0.94 [0.89-0.99]). Negatively associated factors were: edema (1.21 [1.07-1.37]); physical therapy (1.21 [1.12-1.31]); nutritional intervention (1.21 [1.14-1.28]) within 1 month before/after start of first line; thrombosis (1.13 [1.04-1.23]); renal disease (1.11 [1.02-1.21]); age (1.07 [1.02-1.13]); and peritoneal metastasis/ascites (1.06 [1.01-1.13]). In real-world treatment practice for AGC in Japan, therapy choice after the recommended first-line chemotherapy was consistent with guidelines. Factors associated with overall therapy duration were identified, which may assist in optimizing treatment sequence.


A fatal fecaloma.
Fecal impaction may complicate chronic constipation. We report a fatal case of fecal impaction in a patient treated with long-term neuroleptic treatment. A 70-year-old man with a history of severe chronic psychosis treated with olanzapine was admitted to the emergency department for acute abdominal pain and increased abdominal perimeter. Abdominal computed tomography revealed a severe fecal impaction with no sign of peritonitis or acute mesenteric ischemia. The patient eventually died from multi-organ failure 2 days after his admission to the intensive care unit. Chronic constipation with fecal impaction is a well-known complication of long-term neuroleptic treatment. Severe forms may be life-threatening. Prevention with systematic administration of laxatives appears of paramount importance.


The role of formate in combatting oxidative stress.
The interaction of keto-acids with reactive oxygen species (ROS) is known to produce the corresponding carboxylic acid with the concomitant formation of CO2. Formate is liberated when the keto-acid glyoxylate neutralizes ROS. Here we report on how formate is involved in combating oxidative stress in the nutritionally-versatile Pseudomonas fluorescens. When the microbe was subjected to hydrogen peroxide (H2O2), the levels of formate were 8 and two-fold higher in the spent fluid and the soluble cell-free extracts obtained in the stressed cultures compared to the controls respectively. Formate was subsequently utilized as a reducing force to generate NADPH and succinate. The former is mediated by formate dehydrogenase (FDH-NADP), whose activity was enhanced in the stressed cells. Fumarate reductase that catalyzes the conversion of fumarate into succinate was also markedly increased in the stressed cells. These enzymes were modulated by H2O2. While the stressed whole cells produced copious amounts of formate in the presence of glycine, the cell-free extracts synthesized ATP and succinate from formate. Although the exact role of formate in anti-oxidative defence has to await further investigation, the data in this report suggest that this carboxylic acid may be a potent reductive force against oxidative stress.


Inhibition of lysophosphatidic acid receptor 1 relieves PMN recruitment in CNS via LPA1/TSP1/CXCR2 pathway and alleviates disruption on blood-brain barrier following intracerebral haemorrhage in mice.
The frequencies of morbidity and impairment associated with spontaneous intracerebral haemorrhage (ICH) are comparatively high. Blood-brain barrier (BBB) integrity was compromised due to subsequent brain injury induced by ICH, which is crucial for a poor prognosis. Polymorphonuclear leukocyte (PMN) strongly modulate the disruption of BBB in the central nervous system (CNS). The lysophosphatidic acid receptor 1 (LPA1) mediated thrombospondin-1 (TSP1) regulation in astrocytes, which induce macrophage inflammatory protein 2(MIP2) secretion. MIP2 enhance PMN recruitment through CXC chemokine type 2 (CXCR2) activation. The purpose of this study was to investigate whether the LPA1-mediated inhibition of PMN recruitment and BBB protection after ICH is regulated by TSP1 and CXCR2 networks. ICH induction was performed in CD1 mice using collagenase administration. AM966, a targeted LPA1 antagonist, was orally administered 1 and 12 h following ICH. further identify possible LPA1-mediated BBB protection mechanisms, we intracerebroventricularly (ICV) administered a CXCR2 ligand MIP2, as well as TSP1 CRISPR activation (ACT) with AM966. Consequently, we performed neurobehavioral, brain water content (BWC), Evans blue staining (EBS), immunofluorescence (IF), and western blot (WB) analyses. After ICH, astrocytes showed signs of LPA1, which peaked after 24 h, while PMN\ displayed evidence of CXCR2. The AM966-mediated LPA1 suppression relieved PMN recruitment, diminished brain oedema, demonstrated extravasation (as evidenced by EBS), protected BBB integrity, and enhanced neurologic activity following ICH. AM966 treatment strongly reduced TSP1, CXCR2, Occludin, and Claudin-5 expressions and PMN recruitment following ICH, and their expressions were restored by MIP2 and TSP1 CRISPR (ACT). This study shows that LAP1 suppression reduced PMN recruitment after ICH in mice via TSP1/CXCR2 signalling, which minimized BBB disruption and improved the CNS's neurobehavioral functioning. Hence, LPA1 is a strong candidate for therapy to reduce PMN recruitment and offer protection of BBB integrity after ICH.


Update on prevalence of Babesia canis and Rickettsia spp. in adult and juvenile Dermacentor reticulatus ticks in the area of Poland (2016-2018).
Ornate dog tick, Dermacentor reticulatus is an important vector of Babesia canis, and Rickettsia spp. and other pathogens of veterinary and public health interest. The current study is the first to investigate the long-term changes in prevalence of these pathogens in expanding tick populations in Central Europe. Molecular techniques (PCR, sequencing) were applied for the detection of pathogen DNA in adult (n = 2497) and juvenile ticks (1096 larvae and 410 nymphs). DNA of Rickettsia spp. was identified in 35% of adults and 12.6% of juvenile ticks. DNA of B. canis was detected in 3% of adult ticks and only in ticks from the Eastern region (regional prevalence 6%). As previously, no B. canis-positive ticks were found in Western Poland, including ticks from Wrocław area (n = 298). DNA of B. canis was identified in 0.33% of juvenile ticks (in 3 pools of larvae and 2 nymphs) from the Eastern region. In the current study we confirmed high occurrence of R. raoultii in adults ticks from all four zones and relatively high prevalence of B. canis in the Eastern population of D. reticulatus, corresponding well with high incidence of canine babesiosis in this area of Poland. Finally, we confirmed R. raoultii and B. canis infection in all life stages of D. reticulatus ticks.


LncRNA-XIST/microRNA-126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma.
Abnormal glucose metabolism may contribute to cancer progression. Glioma represents a cancer resulting from an imbalance between glucose metabolism and tumor growth. However, the molecular mechanisms responsible for dysregulated brain glucose metabolism and lactate accumulation in glioma remain to be elucidated. The present study identified a long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) as a candidate to mediate glucose metabolism in glioma. Cell viability, migration, invasion, and resistance to apoptosis were evaluated in lncRNA-XIST-depleted glioblastoma cells by short hairpin RNA. Glucose uptake, lactate production, as well as levels of glucose transporter 1 (GLUT1) and GLUT3, were measured. Luciferase assay, RNA pull-down, and RNA immunoprecipitation were performed to validate the interactions among lncRNA-XIST, microRNA-126 (miR-126), and insulin receptor substrate 1 (IRS1). An in vivo analysis was carried out in nude mice bearing glioblastoma cell xenografts. The study found that lncRNA-XIST knockdown inhibited cell viability, migration, invasion, resistance to apoptosis, and glucose metabolism of glioblastoma cells. LncRNA-XIST functioned as a competing endogenous RNA of miR-126 and then regulated IRS1/PI3K/Akt pathway in glioblastoma cells. In vivo results demonstrated lncRNA-XIST knockdown reduces the tumorigenicity of glioblastoma cells. Taken together, we demonstrated a novel cellular mechanism that was dependent of the lncRNA-XIST/miR-126/IRS1/PI3K/Akt pathway in enhanced glucose metabolism in glioma.


Thin film poly(vinyl alcohol)-polysulfone composite membranes based on recycled polysulfone: salt separation performances.
Poly(vinyl alcohol) (PVA)-coated membranes on polysulfone (Ps) (Memb-Pv) were cross-linked using the dibasic maleic acid. The tailoring of membrane properties (viz. hydrophilicity, permeability) develops through the ester linkage due to cross-linking of PVA and maleic acid (MA). Series of Ps asymmetric membranes were prepared using the successive stages of phase inversion of Ps materials. The recyclability approaches of polysulfone (Ps) pertained. The characteristics and transport properties of all the membranes are evaluated. FTIR-ATR, scanning electron (SEM), and atomic force microscopy (AFM) are used for the structural characterization of the membranes. The salient features of Memb-Pv composite membranes support promising results in desalination. The work aimed to highlight the trade-off between the flux and selectivity of composite membranes' salts (bi-/monovalent) through the recycled Ps matrix. The number of recycling stages influences the salt separation performance. The sulfate rejection differs from Memb-IPv (93.26%) to Memb-IVPv (86.70%) for water-I matrix using 2500 mg/L. The defluoridation potential of the membranes is also convincing. The defluoridation performance of Memb-IPv is 87% for 10 mg/L. A significant dimension is added regarding salt separation performance's dependence on the water matrices' nature. The decrease in fluoride separation is ~ 1-3% for the water-2 matrix as the TDS increases.


Estrogen-induced sequential changes in avian bone metabolism.
Medullary bone was induced in male Japanese quail by administration of estradiol valerate. An increase in the organic weight of the femur was observed by 36 h after estrogen and an increase in ash weight was observed by 96 h. A complex sequence of metabolic changes in the femur occurred after estrogen treatment. A large increase in uptake of 3H-proline associated with enhanced collagen formation began 36 h after estrogen and reached a peak 3.5 times the control rate at 60 h. The onset of mineralization of the newly formed bone matrix, as determined by 45Ca uptake, began about 24 h after onset of collagen synthesis indicating that synthesis of the bone matrix and its mineralization occur sequentially. Large increases in the rates of uptake of 3H-uridine and 3H-thymidine occurred prior to the onset of medullary bone formation and appear to reflect the differentiation of osteogenic precursors to bone-forming cells.


Human Amniotic Membrane Mesenchymal Stem Cells inhibit Neutrophil Extracellular Traps through TSG-6.
The mesenchymal stem cells obtained from human amniotic membrane (hAMSC) possess immunosuppressive functions through soluble factors such as prostanoids and proteins; thus, they have been proposed to ameliorate inflammatory processes. On the other hand, activated neutrophils are cells of the first line of immune defense that are able to release extracellular traps (NETs). NETs are formed of DNA and granular components; however, the excessive release of NETs is associated with the development of autoimmune and chronic inflammatory diseases. In this study, we identified that conditioned medium (CM) from hAMSC was able to diminish NETs release, as well as the production of reactive oxygen species (ROS) and the mitochondrial membrane potential from LPS-stimulated mouse bone marrow-derived neutrophils (BMN). Interestingly, NETs inhibition, ROS levels decrease and mitochondrial membrane potential loss were reverted when LPS-stimulated murine derived BMN were exposed to the CM from hAMSC transfected with TSG-6-siRNA. Finally, rhTSG6 was able to significantly diminish NETs release in BMN. These data suggest an inhibition mechanism of NETs ROS-dependent in which TSG-6 participates. Consequently, we propose the hAMSC use as a therapeutic candidate in the treatment of inflammatory diseases in which NETs are involved.


A reexamination of the stopped-flow measured hydrogen-deuterium exchange rates in nucleic acid double helices.
Using the deuteration labelling method in conjunction with an improved stopped-flow instrument, we have reexamined the proton exchange process in poly(dA-dT).poly(dA-dT). A single proton exchange class is found with a rate constant at 20 degrees C of 0.4 S-1. This exchange rate is independent of buffer concentration. From the comparison of these results with those obtained in a former study where two rates were measured, it is concluded that the present deuteration signal corresponds to the exchange of the amino protons, whereas the imino proton exchange is not detected.


In vitro evaluation of regional nasal drug delivery using multiple anatomical nasal replicas of adult human subjects and two nasal sprays.
Quantifying drug delivery to the site of action using locally-acting nasal suspension sprays is a challenging but important step toward understanding bioequivalence (BE) between test and reference products. The main objective of this study was to investigate the in vitro deposition pattern of two common but different locally-acting nasal suspension sprays using multiple nasal cavities. Twenty anatomically accurate nasal replicas were developed from high-resolution sinonasal computed tomography scans of adults with healthy nasal airways. The airways were segmented into two regions of anterior and posterior to the internal nasal valve. Both sides of the septum were considered separately; hence, 40 nasal cavities were studied. The positioning of the spray nozzle in all 40 cavities was characterized by the head angle, coronal angle, and the insertion depth. Despite using a controlled protocol to minimize the anterior losses, a wide range of variability in posterior drug delivery was observed. The observed intersubject variability using this in vitro method may have important implications for understanding BE of locally-acting nasal suspension sprays.


Teachers' interpersonal styles and fear of failure from the perspective of physical education students.
A growing body of research-based knowledge has been generated for the purpose of better understanding the reciprocal and dynamic relationship between teachers' instructional characteristics and students' psychosocial and learning outcomes. This study specifically examined the relationship between teachers' interpersonal styles and fear of failure outcomes in physical education students. Five hundred sixty-two middle school and high school students in Physical Education classes (PE) participated in the study. Students completed questionnaires that assessed instructors' autonomy-supportive and controlling teaching styles and students' own fear of failure. A person-centered analysis was used to test the hypotheses. The results revealed that higher teacher autonomy support was associated with lower student fear of failure. To the contrary, a controlling teaching style was associated with fear of failure in these students. Two profiles emerged in which moderate fear of failure was associated with a stronger perception of a controlling teacher style and lower levels of fear of failure were associated with greater perceived instructor support for autonomy.


Application of microsatellite primers developed for Polistes in the independent-founding wasp Polists satan Bequaert (Hymenoptera: Vespidae).
Microsatellite primers developed for a given species are sometimes useful for another in the same genus and in other genera within the same family, making possible to search for pre-existing suitable primers in the databanks such as GenBank. We examined whether existing primers developed for Polistes could be used for Polistes satan Bequaert. We tested 50 microsatellite primers from three Polistes species and found that six microsatellite loci show polymorphism in size in P. satan. These six loci were highly polymorphic, having four to 15 alleles in P. satan with an expected heterozygosity of 0.525-0.832. These loci can be used to study parameters concerning genetic relatedness such as social interactions in colonies and genetic conflicts of interest among nestmate individuals.


Liberation of oligosaccharides from glycosphingolipids on PC12 cell surface with endoglycoceramidase.
Endoglycoceramidase (EGCase) cleaves the linkage between the oligosaccharide and ceramide of glycosphingolipids (Ito, M., and Yamagata, T., J. Biol. Chem. 261, 14278-14282, ibid, 264, in press). Intact cells of rat pheochromocytoma line PC12 were treated with the highly purified EGCase I and the oligosaccharides released were analyzed by HPLC. Cleavage of the oligosaccharides with the enzyme reached a plateau as the amount of the enzyme was increased. At maximum, 42% of the oligosaccharides from globoside, 40% from GalGb3Cer, and 60% from Gb3Cer were liberated during 1h of incubation without impairing the viability of cells. The only partial liberation indicates that not all oligosaccharides of cell surface glycosphingolipids are accessible to the enzyme. The use of EGCase offers an important new method to access the functions of glycosphingolipids on cell surface in situ.


CHD: a major burden in type 2 diabetes.
Patients with type 2 diabetes have a two- to four-fold greater risk of cardiovascular mortality than non-diabetic individuals. In order to prevent coronary events in the diabetic population, it is important to treat modifiable cardiovascular risk factors. Data from the Multiple Risk Factor Intervention Trial (MRFIT) show that serum cholesterol level, systolic blood pressure level and cigarette smoking were significant predictors of cardiovascular disease mortality in men with and without diabetes. At every risk factor level, the absolute risk of age-adjusted coronary death rate was three times greater for diabetic men than non-diabetic men (p<0.0001). Patients with diabetes have an abnormal (dyslipidaemic) lipoprotein profile with high levels of very low density lipoprotein cholesterol and triglycerides, and a low level of high density lipoprotein cholesterol. Although levels of total cholesterol or low density lipoprotein (LDL) cholesterol do not differ significantly between patients with and without diabetes, those with diabetes have higher levels of atherogenic small dense LDL particles. MRFIT data show that at any serum cholesterol level, diabetes confers two-three times the risk for a coronary event. These findings constitute the rationale for considering hypolipaemic therapy, e.g. with HMG-CoA reductase inhibitors (statins), in diabetic patients with dyslipidaemia, particularly in those with evidence of coronary heart disease. Evidence shows that statins significantly lower cholesterol, exhibit beneficial effects on many components of atherosclerosis, and can significantly reduce the incidence of stroke.


Evaluation of the Gastrointestinal Tract as Potential Route of Primary Polyomavirus Infection in Mice.
Detection of Polyomavirus (PyV) DNA in metropolitan rivers worldwide has led to the suggestion that primary viral infection can occur by the oral route. The aim of this study was to test this notion experimentally. Mouse PyV (MPyV) was used to infect C57BL/6J mice by the nasal or intragastric route. Viral load kinetics was studied 3, 7, 10, 14, 21 and 28 days post-infection (dpi) using quantitative PCR. Following nasal infection, MPyV DNA was readily detected in many organs including lung, heart, aorta, colon, and stool with viral loads in the range of 10(3)-10(6) copies/mg wet weight that peaked 7-10 dpi. Complete viral clearance occurred in the serum and kidney by 28 dpi, while clearance in other organs was partial with a 10-100 fold decrease in viral load. In contrast, following intragastric infection peak detection of PyV was delayed to 21 dpi, and viral loads were up to 3 logs lower. There was no detectable virus in the heart, colon, or stool. The intragastric route of MPyV infection is successful, not as efficacious as the respiratory route, and associated with delayed viral dissemination as well as a lower peak MPyV load in individual organs.


A scheme for the evaluation of methods in clinical chemistry with particular application to those measuring enzyme activities. Part II: analysis of data and performance assessment.
Recommendations are made concerning the editing of day-to-day reproducibility data for establishment of precision in the evaluation of a clinical chemistry method. The concept of diagnostic and equalized diagnostic indices is introduced together with formulae for their generation from the usual precision and accuracy data acquired in method evaluations. These indices allow direct comparison of data obtained from procedures for measuring enzyme activities which employ a variety of experimental conditions and units in their protocols. The equalized diagnostic index permits assessment of the suitability of the normal range assignment. Permissible limits of variation (PLV) and permissible limits of discrepancy (PLD) have been developed empirically from detailed examination of data from method evaluations and proficiency testing surveys in the published literature. The application of the diagnostic indices and the two permissible limits of criteria have been illustrated using data from the assessment of 19 kits measuring CPK activity. The inconsistency of the correlation coefficient in method comparisons is confirmed.


Caring for children who die unexpectedly: patterns that emerge out of chaos.
Despite medical advances in technology, improved socioeconomics, and medical knowledge, an estimated 55,000 children die every year in the United States. A phenomenological study was conducted at a tertiary-quaternary children's hospital to determine the emerging patterns amidst the chaos with nurses caring for children dying unexpectedly. Implications for nursing practice include a progression of caring, a set of patterns that emerge out of the seeming chaos of a coding patient. These patterns shed light on the interactive relationships within the hospital and can foster collaboration among bedside nurses, advanced practice nurses, inter-professional team members, directors, and hospital administrators.


Distributions and Reference Ranges for Automated Pupillometer Values in Neurocritical Care Patients.
Automated pupillometry is becoming widely accepted as an objective measure of pupillary function, especially in neurocritical care units. Normative reference values and thresholds to denote a significant change are necessary for integrating automated pupillometry into practice. Providing point estimates of normal ranges for pupillometry data will help clinicians intuit meaning from these data that will drive clinical interventions. This study used a planned descriptive analysis using data from a multicenter registry including automated pupillometry assessments in 2140 subjects from 3 US hospitals collected during a 3-year period. We provide a comprehensive list of admission pupillometry data. Our data demonstrate significant differences in pupillary values for Neurological Pupil Index, latency, and constriction velocity when stratified by age, sex, or severity of illness defined by the Glasgow Coma Scale score. This study provides a greater understanding of expected distributions for automated pupillometry values in a wide range of neurocritical care populations.


Phytochemical Screening of Nyctanthes arbor-tristis Plant Extracts and Their Antioxidant and Antibacterial Activity Analysis.
Nyctanthes arbor-tristis, alias "Vishnu Parijat," is a medicinal plant used to treat various inflammation-associated ailments and to combat innumerable infections in the traditional system of medicine. In the present study, we collected the samples of N. arbor-tristis from the lower Himalayan region of Uttarakhand, India, and carried out their molecular identification through DNA barcoding. To examine the antioxidant and antibacterial activities, we prepared the ethanolic and aqueous extracts (from flowers and leaves) and performed their phytochemical analysis by using different qualitative and quantitative approaches. The phytoextracts showed marked antioxidant potential, as revealed by a comprehensive set of assays. The ethanolic leaf extract showed marked antioxidant potential towards DPPH, ABTS, and NO scavenging (IC50 = 30.75 ± 0.006, 30.83 ± 0.002, and 51.23 ± 0.009 μg/mL, respectively). We used TLC-bioautography assay to characterize different antioxidant constituents (based on their Rf values) in the chromatograms ran under different mobile phases. For one of the prominent antioxidant spots in TLC bioautography, GC-MS analysis identified cis-9-hexadecenal and n-hexadecanoic acid as the major constituents. Furthermore, in antibacterial study, the ethanolic leaf extract showed marked activity against Aeromonas salmonicida (113.40 mg/mL of extract was equivalent to 100 μg/mL of kanamycin). In contrast, the ethanolic flower extract showed considerable antibacterial activity against Pseudomonas aeruginosa (125.85 mg/mL of extract ≡100 μg/mL of kanamycin). This study presents the phylogenetic account and unravels the antioxidant-related properties and antibacterial potential of N. arbor-tristis.


Novel cationic-modified salep as an efficient flocculating agent for settling of cement slurries.
A new cationic flocculant was synthesized by graft copolymerization of acrylamide (AM) and 3-(methacryloylamino)propyl]trimethylammonium chloride (MAPTAC) onto salep using free radical polymerization initiated by ammonium persulfate (APS) to produce cationic salep [S-g-P(AM-co-MAPTAC)]. Reaction parameters (monomers/salep ratio, concentration of reactants, MAPTAC/AM ratio, and APS) were optimized using a full factorial experimental design to obtain the highest settling rate for cement suspensions. The best performing product was characterized by gel permeation chromatography (GPC), FTIR, (1)H NMR spectroscopy, and thermogravimetric analysis (TGA). The resulted cationic flocculant may be introduced as a promising candidate for the green production of asbestos-free fiber cement products by Hatschek process.


Molecular structure, spectral studies, intra and intermolecular interactions analyses in a novel ethyl 4-[3-(2-chloro-phenyl)-acryloyl]-3,5-dimethyl-1H-pyrrole-2-carboxylate and its dimer: A combined DFT and AIM approach.
A newly synthesized chalcone, Ethyl 4-[3-(2-chloro-phenyl)-acryloyl]-3,5-dimethyl-1H-pyrrole-2-carboxylate (ECPADMPC) has been characterized by (1)H NMR, (13)C NMR, UV-Vis, FT-IR, Mass spectroscopy and elemental analysis. Quantum chemical calculations have been performed by DFT level of theory using B3LYP functional and 6-31G(d,p) as basis set. The time dependent density functional theory (TD-DFT) is used to find the various electronic transitions within molecule. A combined theoretical and experimental wavenumber analysis confirms the existence of dimer. Topological parameters-electron density (ρ(BCP)), Laplacian of electron density (∇(2)ρ(BCP)), energetic parameters-kinetic electron energy density (G(BCP)), potential electron density (V(BCP)) and the total electron energy density (H(BCP)) at the bond critical points (BCP) have been analyzed by 'Atoms in molecules' AIM theory in detail. The intermolecular hydrogen bond energy of dimer is calculated as -12.3kcal/mol using AIM calculations. AIM ellipticity analysis is carried out to confirm the presence of resonance assisted intermolecular hydrogen bonds in stabilization of dimer. The analysis clearly depicts the presence of different kind of interactions in dimer. This dimer may work as model system to understand the H-bonding interaction in biomolecules. The local reactivity descriptor analysis is performed to find the reactive sites within molecule.


A gene prognostic index from cellular senescence predicting metastasis and radioresistance for prostate cancer.
Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages. We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50-23.93, p < 0.001), consistent with the results in the TCGA database (HR: 1.60, 95% CI 1.03-2.47, p = 0.038). Furthermore, CSGPI had high diagnostic accuracy distinguishing radioresistance from no radioresistance (AUC: 0.938, 95% CI 0.834-1.000). GSEA showed that high-risk patients were highly associated with apoptosis, cell cycle, ribosome, base excision repair, aminoacyl-tRNA biosynthesis, and mismatch repair. For immune checkpoint analysis, we found that PDCD1LG2 and CD226 were expressed at significantly higher levels in patients with metastasis than in those without metastasis. In addition, higher expression of CD226 significantly increased the risk of metastasis (HR: 3.65, 95% CI 1.58-8.42, p = 0.006). We observed that AZD7762, PHA-793887, PI-103, and SNX-2112 might be sensitive to ALDH2 and ALCAM, and PC3 could be the potential cell line used to investigate the interaction among ALDH2, ALCAM, and the above drugs. We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.


Exosome proteomics study of the effects of traditional cigarettes and electronic cigarettes on human bronchial epithelial cells.
Electronic cigarette (e-Cig) has been promoted as a safer alternative to traditional cigarette (t-Cig) recently. However, there are limited scientific data on the potential health effects of e-Cig use. In this study, we evaluated the cytotoxicities of e-Cig and t-Cig condensate solutions (e-CigCS and t-CigCS) on human bronchial epithelial cells (16HBE cells) in vitro, and employed the exosome proteomic technique to systematically assess the effects of e-CigCS and t-CigCS on 16HBE cells. Cytotoxicity assay showed 16HBE cells were more sensitive to t-CigCS than e-CigCS. Proteomic analysis demonstrated that there are 431 differential expressed exosomal proteins (DEEPs) in test groups compared to the control air group (P-value<0.05) and t-CigCS has a greater influence than e-CigCS on exosomal protein expression. Bioinformatic analysis showed the DEEPs from the t-Cig group were significantly enriched in pathways in cancer while tobacco-flavored e-Cig (e-Cigt) and menthol-flavored e-Cig (e-Cigm) groups were not. Further validations of some DEEPs, such as NF-κB p65, Sulfiredoxin-1(SRXN1) and Thioredoxin-interacting protein (TXNIP), were carried out using immunoblot and Real-time PCR analysis, showing that t-Cig may have a greater influence than e-Cig on tumor development and metastasis. Taken together, the finding reported here strongly support our hypothesis that electronic cigarettes are significantly less toxic compared with traditional cigarette.


[Further developments in disaster control: goal, strategy and tactic using the example of the 2021 flood disaster in the Ahr valley].
In July 2021, the Medical Task Force 47 was deployed to the flood disaster in western Germany as part of the cross-regional disaster relief system. With the aim of deriving possible improvements in disaster management, it was scientifically evaluated. The focus of this study was the strategy to build up and to maintain a responsive and efficient rescue system. After defining an evaluation process, an interdisciplinary panel of experts reviewed operational documents and relevant concepts of the Bavarian Red Cross. Based on these, strategies and tactics were developed to achieve predefined goals. The performance of the emergency units could be increased by modern vehicles and equipment (eBikes, drones, all-terrain vehicles). To improve the response capability, new rapid response groups could be required that can take over the function of an advance command and can process mission assignments in impassable terrain autonomously. These could be integrated and synchronized into regional and cross-regional disaster relief. In future, it could be difficult for Germany's largely volunteer-organised disaster management to safely deploy the multitude of possible state-of-the-art resources in the highly complex environment of a disaster. Partial professionalization by full-time command and control staff could be one solution for this problem.


Effect of ultrasound irradiation on asphaltene aggregation and implications to rheological behavior of bitumen.
The present work investigates the contribution of asphaltene aggregation to bitumen viscosity subject to ultrasound irradiation. A West-African bitumen with a viscosity of 12043cP at room temperature was sonicated at low (38 kHz) and mild frequency (200 kHz) under controlled gas environment including air, nitrogen (N2) and carbon dioxide (CO2). The rheology of the bitumen, asphaltene content analyses as well as spectral studies were conducted. Herein was found that sonicating the bitumen at 200 kHz under air-environment reduces the initial viscosity up to 2079cP, which was twice larger than that obtained when a low frequency was used. In respect of the gas environment, it was shown that ultrasound irradiation under N2 environment could lower the bitumen viscosity up to 3274cP. A positive correlation between the asphaltene content and the viscosity reduction was established. The results from the spectral analyses including Fast Fourier Infrared and the observations from Scanned Electron Microscope were consistent with the rheological studies and led to the argument that the viscosity reduction results from either the scission of long chain molecules attached to the aromatic rings (when the applied frequency was altered under fixed gas environment) or the self-aggregation of asphaltene monomers (when gas environment was changed at fixed frequency).


Understanding Effects of Alkyl Side-Chain Density on Polaron Formation Via Electrochemical Doping in Thiophene Polymers.
Polarons exist when charges are injected into organic semiconductors due to their strong coupling with the lattice phonons, significantly affecting electronic charge-transport properties. Understanding the formation and (de)localization of polarons is therefore critical for further developing organic semiconductors as a future electronics platform. However, there are very few studies reported in this area. In particular, there is no direct in situ monitoring of polaron formation and identification of its dependence on molecular structure and impact on electrical properties, limiting further advancement in organic electronics. Herein, how a minor modification of side-chain density in thiophene-based conjugated polymers affects the polaron formation via electrochemical doping, changing the polymers' electrical response to the surrounding dielectric environment for gas sensing, is demonstrated. It is found that the reduction in side-chain density results in a multistep polaron formation, leading to an initial formation of localized polarons in thiophene units without side chains. Reduced side-chain density also allows the formation of a high density of polarons with fewer polymer structural changes. More numerous but more localized polarons generate a stronger analyte response but without the selectivity between polar and non-polar solvents, which is different from the more delocalized polarons that show clear selectivity. The results provide important molecular understanding and design rules for the polaron formation and its impact on electrical properties.


Point-of-Care Ultrasound for Pediatric Endotracheal Tube Placement Confirmation by Advanced Practice Transport Nurses.
This study aimed to identify which point-of-care ultrasound (POCUS) techniques and sonographic signs were reliably acquired and interpreted by transport nurses for the confirmation of endotracheal tube placement in children. We developed and assessed a multimodal POCUS training curriculum for transport nurses that evaluated 5 sonographic signs using 3 scanning techniques. Twenty-one transport nurses were enrolled in the curriculum. The mean scores (95% confidence interval [CI]) of the knowledge test were 82% (95% CI, 63%-93%), 88% (95% CI, 68%-95%), and 74% (95% CI, 53%-87%) for tracheal, lung, and hemidiaphragmatic scans, respectively. For the simulation image evaluation, 94% (95% CI, 77%-99%) of tracheal scan images, 97% (95% CI, 81%-99%) of lung scan images, and 88% (95% CI, 69%-96%) of hemidiaphragmatic scan images were determined clinically useful. For the pediatric intensive care unit image evaluation, 100% (95% CI, 86%-100%) of tracheal scan images, 100% (95% CI, 86%-100%) of lung scan images, and 79% (95% CI, 59%-91%) of hemidiaphragmatic scan images were determined clinically useful. A tracheal dilation sign was rarely captured by POCUS. Transport nurses can acquire POCUS skills to confirm endotracheal tube placement in children. A combination of a double trachea sign, a lung sliding sign, and a lung pulse sign could be a feasible POCUS approach.


Halotolerant Citrobacter sp. remediates salinity stress and promotes the growth of Vigna radiata (L) by secreting extracellular polymeric substances (EPS) and biofilm formation: a novel active cell for microbial desalination cell (MDC).
To address soil salinization and its impact on crop production, microbial desalination cells (MDCs) offer a promising solution. These bioelectrochemical systems integrate desalination and wastewater treatment through microbial activity. A halotolerant beneficial bacterial strain called Citrobacter sp. strain KUT (CKUT) was isolated from India's salt desert Run of Kutch, Gujrat, highlighting its potential application in combating soil salinization. CKUT exhibits high salt tolerance and has the ability to produce extracellular polymeric substances (EPS) at a concentration of 0.04 mg/ml. It forms biofilm that enable it to withstand up to 10% NaCl concentration. Additionally, CKUT shows promise in remediating salinity levels, reducing it from 4.5 to 2.7 gL-1. These characteristics are driven by biofilm formation and EPS production. In an experiment where V. radiata L. seedlings were inoculated with CKUT, the treated plants exhibited enhanced chlorophyll content, growth, and overall plant characteristics compared to seedlings treated with sodium chloride (NaCl). These improvements included increased shoot length (150 mm), root length (40 mm), and biomass. This indicates that CKUT treatment has the potential to enhance the suitability of V. radiata and other crops for cultivation in saline lands, effectively addressing the issue of soil salinization. Furthermore, integrating CKUT into microbial desalination cells (MDCs) offers an opportunity for freshwater production from seawater, contributing to sustainable agriculture by promoting improved crop growth and increased yield in areas prone to salinity. HIGHLIGHTS : • Soil salinization reduces crop yield, including Vigna radiata L. • Citrobacter sp. strain KUT (CKUT) is a halotolerant bacterium isolated from the salt desert Run of Kutch, Gujarat, which can tolerate high salt concentrations. • CKUT mitigates salinity by producing extracellular polymeric substances (EPS) and forming biofilms. • CKUT treatment demonstrated increased plant growth, biomass, and chlorophyll content under salinity stress, showcasing its potential in microbial desalination cell (MDC) for enhancing crop yield in salinized soils.


Structure of rearranged and germ-line rabbit V kappa genes indicated that the CDR3 is encoded by the V kappa gene.
The third complementary-determining regions (CDR3) of rabbit kappa chains are unusually long and the length is more heterogeneous when compared to those of the mouse and the human kappa chains. To study how the rabbit kappa light (L) chain genes create diversity and generate CDR3, we analyzed the structure of a rearranged variable kappa gene (Vr) and the variable (Vg) and joining (Jg) regions of the putative precursor genes. Alignment of the Vr gene sequence with that of the Vg and Jg regions allowed precise determination of the recombination event. Five nucleotides between the recombination point and the J2 heptamer were deleted, indicating flexibility in the recombination producing rabbit kappa chains. The entire Vg is contained in the rearranged product demonstrating that neither a D element nor an N sequence addition are required for the CDR3 formation. Comparison of the Vr and the Vg gene sequences show base substitutions suggesting that somatic mutations may contribute to rabbit kappa L chain diversity.


Role of Protein Kinase Akt Activation in Protective Effect of Ganglioside GM1 on PC12 Cells Exposed to H2O2.
Micro- and nanomolar concentrations of ganglioside GM1 improved viability of neuronal PC12 cells under conditions of oxidative stress and reduced H2O2-induced ROS accumulation in these cells. These effects were more pronounced at micromolar concentrations. GM1 in concentrations of 100 nM and 10 μM significantly and substantially increased basal activity of protein kinase B (Akt) (the level of phosphorylated Akt form), but had virtually no effect on its expression in PC12 cells. In the presence of PI3K inhibitor LY294002 preventing protein kinase Akt activation, the protective effect of GM1 significantly decreased. These findings suggest that activation of protein kinase Akt by GM1 contributes to improvement of PC12 cell viability by this ganglioside.


Characterization of NiONPs synthesized by aqueous extract of orange fruit waste and assessed their antimicrobial and antioxidant potential.
This research was performed to evaluate the nickel oxide nanoparticles (NiONPs) fabricating potential of orange fruit waste (OFW) aqueous extract. Moreover characterize the synthesized OFW-NiONPs through standard techniques such as UV-vis. spectrophotometer, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and Scanning Electron Microscope (SEM) analyses. Furthermore, the antimicrobial and antioxidant potential of OFW-NiONPs were studied against most common microbial pathogens (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, and Aspergillus niger) and free radicals (2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, OH, and FRAP). A sharp absorbance peak was obtained at 324 nm under UV-vis spectrum analysis that confirmed that the synthesis of OFW-NiONPs and it has been capped and stabilized by numbers of active functional groups studied through FTIR analysis. SEM and DLS analyses revealed that the cubic and triangle shaped OFW-NiONPs with the size intensity distribution was ranging from 21 nm to 130 nm. Interestingly, the OFW-NiONPs showed remarkable antimicrobial activity against the common microbial pathogens in the order of E. coli > A. niger > K. pneumoniae > B. subtilis > S. aureus at increased concentration of 200 μg mL-1. Similarly, the synthesized OFW-NiONPs also possess significant free radicals scavenging activity against DPPH, OH, and FRAP. These results conclude that this OFW-NiONPs can be considered for some biomedical applications after the investigations of some in-vivo research.


An ultrastructural study of cultured human meningioma cells.
Ultrastructural alterations in human meningioma cells growth in vitro are reported. In early passages the cells retain some of the characteristic features of the original tumors. These include interdigitations associated with intercellular junctional devices (e.g., desmosomes, gap junctions). However, with repeated subculture these features tend to be less frequent. Typical whorl formations are observed only in primary cultures. The number of cytoplasmic filaments, lipid inclusions and other dense bodies increases with time in culture. Cytoplasmic invaginations into nuclei and the appearance of very large cells become more frequent in repeatedly transferred cultures.


High-performance liquid chromatography of amino acids, peptides and proteins. XCVIII. The influence of different displacer salts on the bandwidth properties of proteins separated by gradient elution anion-exchange chromatography.
The influence of eight different displacer salts on the bandwidth properties of four globular proteins separated by a high-performance anion-exchange chromatography has been investigated. Proteins were eluted under gradient conditions with a range of alkali metal halide salts, in which the anion and cation were varied in the series F-, Cl- and Br- and Li+, Na+ and K+, respectively. The experimentally observed bandwidths (sigma v,exp) were found to deviate significantly from peak widths (sigma v,calc) predicted on the basis of plate theory for small molecules. For data accumulated under conditions of varied gradient time and constant flow-rate the solute bandwidth ratios (sigma v,exp/sigma v,calc) increased in the order Br- less than Cl- less than F- at low values of the gradient steepness parameter, b, or increasing column residence times. In addition, systematic changes in the cation influenced the bandwidth ratios (sigma v,exp/sigma v,calc) in the order K+ less than Na+ less than Li+. Significant deviations between predicted and observed bandwidth values were also observed under elution conditions of constant gradient time and varied flow-rate. The results of the present study further demonstrate the complex nature of the interaction between protein solutes and coulombic chromatographic surfaces.


Neurobiological Bases of Alcohol Consumption After Social Stress.
The urge to seek and consume excessive alcohol is intensified by prior experiences with social stress, and this cascade can be modeled under systematically controlled laboratory conditions in rodents and non-human primates. Adaptive coping with intermittent episodes of social defeat stress often transitions to maladaptive responses to traumatic continuous stress, and alcohol consumption may become part of coping responses. At the circuit level, the neural pathways subserving stress coping intersect with those for alcohol consumption. Increasingly discrete regions and connections within the prefrontal cortex, the ventral and dorsal striatum, thalamic and hypothalamic nuclei, tegmental areas as well as brain stem structures begin to be identified as critical for reacting to and coping with social stress while seeking and consuming alcohol. Several candidate molecules that modulate signals within these neural connections have been targeted in order to reduce excessive drinking and relapse. In spite of some early clinical failures, neuropeptides such as CRF, opioids, or oxytocin continue to be examined for their role in attenuating stress-escalated drinking. Recent work has focused on neural sites of action for peptides and steroids, most likely in neuroinflammatory processes as a result of interactive effects of episodic social stress and excessive alcohol seeking and drinking.


Association of HIV and malaria with mother-to-child transmission, birth outcomes, and child mortality.
To assess the impact of HIV and malaria coinfection on mother-to-child HIV transmission (MTCT) and adverse birth outcomes. One hundred nine HIV-positive mother-infant pairs with a malaria diagnosis were identified in a community cohort and followed up postpartum. Maternal malaria was diagnosed by a rapid immunochromatographic test (ICT) on sera and histopathologic examination of placenta. Infant HIV was diagnosed within 6 weeks of birth using polymerase chain reaction (PCR) to capture in-utero and intrapartum HIV transmission. Log binomial models were used to assess the relative risk of MTCT, low birth weight, and preterm birth associated with malaria. Approximately 17.4% of infants were HIV positive at or around birth, and the prevalence of serologic and placental malaria were 31% and 32%, respectively. HIV-positive mothers with serological ICT malaria were significantly more likely to have low-birth-weight infants, and low-birth-weight infants had significantly higher risk of MTCT compared with infants of normal birth weight. Although placental and serologic ICT malaria were significantly associated with MTCT, after adjusting for maternal HIV viral load, the risk of MTCT was significantly increased only for mothers coinfected with placental malaria (relative risk [RR] = 7.9, P = 0.025). Placental malaria increases the risk of MTCT after adjustment for viral load. Programs should focus on enhanced malaria prevention during pregnancy to decrease the risk of adverse birth outcomes and MTCT.


Feasibility of a pharmacist-led symptom monitoring and management intervention to improve breast cancer endocrine therapy adherence.
Adjuvant endocrine therapy (AET) for breast cancer reduces mortality, but one-third to one-half of patients discontinue it early or are nonadherent. We developed a pilot single-site study of patients with evidence of early nonadherence to AET to assess the feasibility of a novel, clinical pharmacist-led intervention targeting symptom and medication management. Patients with prescription fill records showing nonadherence were enrolled in a single-arm feasibility study. Automated reminders were sent by e-mail or text with a link to symptom monitoring assessments weekly for 1 month and monthly until 6 months. Clinical oncology pharmacists used guideline-based symptom management and other medication management tools to support adherence and ameliorate symptoms reported on the assessments. Patient-reported outcome assessments included physical, mental, and social health domains and self-efficacy to manage symptoms and medications. Feasibility outcomes included completion of symptom reports and pharmacist recommendations. Of 19 participants who were nonadherent who enrolled and completed initial assessments, 18 completed all final study procedures, with 14 completing all assessments and no patient missing more than 3 assessments. All 18 participants reported at least one of 3 symptom types, and the majority reported attempting pharmacist recommendations. Patient-reported measures of physical, mental, and social health and self-efficacy improved, and 44% of the patients became adherent. An intervention using pharmacists in an oncology practice to systematically monitor and manage symptoms shows promise to reduce symptoms, enhance support and self-efficacy, and improve adherence to AET.


[Percutaneous fibrin gluing in subcutaneous cerebrospinal fluid fistulas following operations on the brain and spinal cord].
In spite of a careful operation technique subcutaneous CSF fistulae may occur after operations to the central nervous system, which will then require repeated puncture treatment in combination with compression bandages and draining of the cerebrospinal fluid or a surgical treatment. The originally obtained result of the operation may in this way become doubtful. The percutaneous fibrin sealing of the fistulous opening and the tissue layers of the fistulous cavity after complete puncturing of its content is a safe and riskless procedure with which the therapy of this complication can be decisively improved. The indications and the technique are described. Contraindications are pointed out. The chances to obtain good results are shown on the basis of various cases.


Hepatitis B virus e antigen and viral persistence.
Hepatitis B virus (HBV) e antigen (HBeAg) was discovered in the sera of HBV patients nearly 50 years ago. It is not essential for HBV to infect or replicate in hepatocytes. Earlier clinical studies suggested that this antigen might play an important role for HBV to establish persistence in babies after its mother-to-child transmission. Subsequent clinical studies also suggested that HBeAg might have immunomodulatory activities. In recent years, a large body of information on how HBeAg might modulate host immunity was published. In this review, we summarize recent research progresses on the immunomodulatory activities of HBeAg and discuss how these activities of HBeAg may promote HBV persistence.


Metabolic activity of odontoblast-like cells irradiated with blue LED (455 nm).
Blue light emitting diodes (LEDs) are frequently used in dentistry for light activation of resin-based materials; however, their photobiostimulatory effects have not yet been fully investigated. This study aimed to investigate the effect of blue LED (455 nm) on the metabolism of odontoblast-like cells MDPC-23. Energy doses of 2 and 4 J/cm(2) were used at 20 mW/cm(2) fixed power density. MDPC-23 cells were seeded at 10,000 cells/cm(2) density in Dulbecco's modified Eagle's medium (DMEM) containing 10 % fetal bovine serum (FBS). After 12 h, the culture medium was replaced with new DMEM supplemented with 0.5 % of FBS, and the cells were incubated for further 12 h. After that, single irradiation was performed to the culture, under selected parameters. Cell viability evaluations (Alamar Blue Assay, n = 12), number of viable cells (Trypan Blue Assay, n = 12), morphological analysis by scanning electron microscopy (SEM, n = 2), gene expression (n = 6) of alkaline phosphatase (Alp), collagen (Col-1a1), and dental matrix protein (Dmp-1) (quantitative polymerase chain reaction (qPCR)) were performed 72 h after irradiation. Data were analyzed by Kruskal-Wallis, ANOVA, and Tukey tests (p < 0.05). Direct light application at 4 J/cm(2) energy dose had no negative effects on cell viability, while irradiation with 2 J/cm(2) reduced cell metabolism. None of doses affected the number of viable cells compared with the control group. The two energy doses downregulated the expression of Alp; however, expression of Col-1a1 and Dmp-1 had no alteration. Cells presented change in the cytoskeleton only when irradiated with 2 J/cm(2). In conclusion, the blue LED (455 nm) irradiation, under the evaluated parameters, had no biostimulatory effects on MDPC-23 cells.


Watershed-scale assessment of surface water-related risks from shale gas development in mountainous areas, China.
Water risks are one of the key issues dominating environmental debates on shale gas development. Water withdrawals and wastewater discharges in shale gas fields of mountainous areas are more complicated than in plain areas due to different climatic, topographical and hydrological conditions, which would impact water resources. This research identifies the surface water-related risks from shale gas development in mountainous areas as water shortage and water pollution. Conceptions of accessibility for both water supply and water pollution are proposed to describe the vulnerability of water resources and the exposure to water pollution. Based on a risk probability model, a water risk assessment method for mountainous areas is constructed from the perspectives of dangers, exposures and vulnerabilities. Finally, the assessment method is applied in Chongqing, China. The results show that, from 2010 to 2020, the water consumption of shale gas development has a little impact on regional water resources in total, but more significant impacts are seen in a few areas, including the seasonal water-deficient areas in Western Chongqing, the urban and suburban areas with high pollutant loadings in Midwest Chongqing, and other areas with high pollutant accessibility and vulnerable water environments. The surface water-related risks of the shale gas development in Chongqing are principally composed of low and relatively low levels of risks, which cover 60% of the total area of Chongqing and display a spatial difference of west > northeast > southeast areas. Based on Monte Carlo method, the results of uncertainty analyses show the model is reliable. This research provides a reference for water comprehensive risk assessment of shale gas development in mountainous areas.


Human cysticercosis: a probable case of cerebral cysticercosis with generalized subcutaneous nodular lesions.
A case is reported in Montreal of human cysticercosis in a 44-year-old man who emigrated from Italy in 1956. Numerous subcutaneous nodules were found throughout his body. X-ray of his thighs and chest showed oblong calcific densities measuring 1 x 0.5 cm in size. Examination of an excised nodule from the right biceps revealed a cysticercus larva morphologically similar to Cysticercus cellulosae although the scolex lacked hooks. On the basis of the intensity of infection, focal and generalized epileptic seizures, changes in the CSF, and well demarcated lucencies observed in brain scan, cerebral cysticercosis was considered the most likely diagnosis.