Mesocortical dopaminergic neurons. 2. Electrophysiological consequences of terminal autoreceptor activation.
Measurement of drug- and stimulation-induced changes in the electrical excitability of dopaminergic terminals was employed to assess the effects of stimulation of dopamine terminal autoreceptors in the prefrontal cortex in urethane-anesthetized rats. Systemic or local administration of amphetamine decreased, whereas systemic administration of haloperidol increased the excitability of prefrontal cortical dopaminergic terminals of ventral tegmental area dopaminergic neurons. Mesoprefrontal dopaminergic terminal excitability was also responsive to spontaneous and stimulation-induced alterations in the rate of impulses reaching the terminal fields. These results are comparable to those previously reported for nigrostriatal and mesoaccumbens dopaminergic neurons, and are discussed with regard to the operational characteristics of autoinhibition in the mesocortical dopaminergic system.


Repeat self-harm: an 18-month follow-up.
An 18-month follow-up of cases of deliberate self-harm (DSH) revealed that 30% had repeated the act. Of a large number of items recorded at index DSH only one, a past history of self-harm, was associated with repetition. It is suggested that some factors not predictive of longer term repeat DSH may be important in the assessment of risk for immediate further self-harm.


Single-nucleotide polymorphism rs2290692 in the 3'UTR of ITPKC associated with susceptibility to Kawasaki disease in a Han Chinese population.
Kawasaki disease (KD) is characterized by acute systemic vasculitis and frequently is complicated by coronary artery lesions (CALs). The inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene rs28493229 was recently found to be associated with the risk for KD in the Japanese population, suggesting that the ITPKC gene may contribute to KD susceptibility. This study investigated the association of ITPKC polymorphisms with KD in a Han Chinese population. Five ITPKC Single-nucleotide polymorphisms, including rs28493229, were genotyped in 223 unrelated patients who had KD and 318 non-KD control subjects. The allele, genotype, and haplotype frequencies were compared between the patients and the control subjects, between the patients with and those without CALs, and between patients resistant to intravenous immunoglobulin treatment and those responsive to such treatment. Multiple alleles were observed for rs28493229 and rs2290692. No significant differences in the frequencies of the C allele, the CC genotype, or the C carriers of rs28493229 were observed in the comparisons. Interestingly, significantly higher frequencies of the C allele (p < 0.001), the CC genotype (p = 0.001), and the C carriers (p = 0.003) were observed for rs2290692 among the patients than among the control subjects, and similar differences were observed between the patients with and those without CALs. The GC haplotype for rs28493229 and rs2290692 was more common among the patients than among the control subjects. The results indicate that the C allele of the ITPKC gene rs2290692 is linked to a significantly higher risk for KD in the studied population, which provides new evidence to support the importance of the ITPKC gene in the occurrence of KD. More notably, this finding suggests that there may be an unidentified ITPKC polymorphism in strong linkage disequilibrium to rs2290692, significantly affecting susceptibility to KD in the Han population.


Polyphosphorylated glycerolipids mimic adrenocorticotropin-induced stimulation of mitochondrial pregnenolone-synthesis.
As with adrenocorticotropin pretreatment in vivo, addition of cardiolipin in vitro enhances adrenal mitochondrial pregnenolone synthesis and apparent binding of cholesterol to cytochrome P-450scc. These effects are relatively specific for glycerolipids containing two or more phosphate radicals in the polar head group, and changes in such phospholipids or comparably acting substances may play a role in mediating adrenocorticotropin- or other hormone-induced effects on membrane-associated enzymes.


Corrigendum: Malnutrition leads to increased inflammation and expression of tuberculosis risk signatures in recently exposed household contacts of pulmonary tuberculosis.
[This corrects the article DOI: 10.3389/fimmu.2022.1011166.].


Active commuting reduces sociodemographic differences in adherence to recommendations derived from leisure-time physical activity among Brazilian adults.
To investigate the consequences of including active commuting, compared with the leisure domain only, in the prevalence and sociodemographic factors associated with attending the physical activity recommendations, in Brazilian adults. Population-based cross-sectional study. Adults between 20 and 59 years of age (n = 1720) were face-to-face interviewed from September 2009 to January 2010. Sociodemographic indicators and leisure-time and commuting physical activity were assessed by a validated questionnaire. Poisson regression was used to estimate crude and adjusted prevalence ratio (PR) and 95% confidence interval (95% CI). The prevalence of adherence to recommendations when only leisure-time physical activity was considered was 15.5% (95% CI: 13.6; 17.4) and was associated with men (PR: 1.57, 95% CI: 1.25; 1.96), adults without a partner (PR: 1.38 95% CI: 1.05; 1.81) and higher educational level and income. The prevalence of adherence to physical activity recommendations after the combination of leisure-time and commuting was 29.1% (95% CI: 26.5; 31.6). Percentages differences in favor of men, white adults and those with higher educational level and income were no longer significant after the inclusion of active commuting. The inclusion of active commuting expands the percentage of adults who achieved the health-related physical activity recommendations and reduced important sociodemographic differences derived from the analysis of leisure-time physical activity alone. Public health strategies should consider the different domains of physical activity in the monitoring and promotion of a more active lifestyle.


Influence of fissure integrity on quantitative CT and emphysema distribution in emphysema-type COPD using a dedicated COPD software.
Fissure integrity (FI) plays a key role in selecting patients for interventional emphysema therapy. We investigated its interference with automated lobar segmentation in quantitative computed tomography (CT) and emphysema distribution. CT was available for 50 patients with chronic obstructive pulmonary disease (COPD). Lobe segmentation was performed fully automated by software and corrected manually. FI was evaluated visually using a %-scale. The influence of FI on emphysema ratio (ER=percentage of lung volume with density values<-950 HU), mean lung density (MLD), emphysema and total volume of adjacent lobes was analyzed. Lobe-based results were compared with respect to FI. Differences in ER in adjacent lobes for complete vs. incomplete fissures were 12.4% for the right horizontal, 0.2% and 3% for the right oblique and 4.4% for the left oblique fissure (all p>0.05). Results for emphysema comparing automated vs. manually corrected segmentation exceeded clinically acceptable values, but were not significantly affected by FI (p>0.05). The widest limits of agreement for ER and MLD were noted in the right middle lobe ([-14, 17.4%], [-22.4, 32.4 Hounsfield Units]). Automated lobe segmentation and emphysema distribution are not significantly affected by FI. Manual correction of automated lobar segmentation is still recommended in severe emphysema.


Paclitaxel derivative-based liposomal nanoplatform for potentiated chemo-immunotherapy.
The combination of chemotherapy with the immune checkpoint blockade (ICB) therapy is bringing a tremendous hope in the treatment of malignant tumors. However, the treatment efficacy of the existing chemo-immunotherapy is not satisfactory due to the high cost and immunogenicity of ICB antibodies, low response rate to ICB, off-target toxicity of therapeutic agents, and low drug co-delivery efficacy. Therefore, a high-efficient nanosystem combining the delivery of chemotherapeutics with small molecule ICB inhibitors may be promising for an efficient cancer therapy. Herein, a novel reactive oxygen species (ROS)-activated liposome nanoplatform was constructed by the loading of a ROS-sensitive paclitaxel derivative (PSN) into liposomes to overcome the difficulties on delivering paclitaxel mostly represented by premature drug release and a low amount accumulated into the tumor. The innovative liposomal nanosystem was rationally designed by a remote loading of BMS-202 (a small molecule PD-1/PD-L1 inhibitor) and PSN into the liposomes for a ROS-sensitive paclitaxel release and sustained BMS-202 release. The co-loaded liposomes resulted in a high co-loading ability and improved pharmacokinetic properties. An orthotopic 4 T1 breast cancer model was used to evaluate the efficiency of our nanoplatform in vivo, resulting in a superior antitumor activity. The antitumor immunity was activated by paclitaxel-mediated immunogenic cell death, while BMS-202 continuously blocked PD-L1 which could be up-regulated by paclitaxel in tumors to increase the response to ICB and further recover the host immune surveillance. These results revealed that this dual-delivery liposome might provide a promising strategy for a high-efficient chemo-immunotherapy, exhibiting a great potential for clinical translation.


Routes of Theophylline Monohydrate Dehydration Process Proposed by Mid-Frequency Raman Difference Spectra.
Two routes of the dehydration process of theophylline monohydrate have been proposed in this work from mid-frequency Raman difference spectra (MFRDS) results and experiments. MFRDS can establish short-range order correlations among various theophylline crystal forms. MFRDS results indicate that the short-range order of metastable Form III is most similar to that of monohydrate, which explains that Form III is the main dehydration products in the mild dehydration process. The phenomenon that unstable amorphous theophylline intermediate phase would appear during the dehydration process of theophylline monohydrate was confirmed indirectly by Powder X-ray Diffraction (PXRD) and optical microscope and reported in the previous reports, which could cause the nucleation of Form II, as MFRDS results indicate short-range order of amorphous solid dispersion of theophylline is most similar to that of Form II. MFRDS analysis shows the advantages in studying the phase transformation of small organic molecule crystals.


Esophageal motility disorders.
Esophageal motility disorders consist of a complex array of disturbances in normal esophageal function associated with dysphagia, gastroesophageal reflux, and noncardiac chest pain. A thorough knowledge of normal esophageal anatomy and physiology is important to a full understanding of these motility derangements. Through a complicated interaction of neuromuscular and hormonal influences, the voluntary act of swallowing transforms into an automated sequence of peristaltic waves propelling food and liquids into the stomach in concert with coordinated relaxation of the sphincters. Anatomic and physiologic barriers exist within the esophagus protecting against gastroesophageal reflux and aspiration. With improvements in diagnostic tools such as barium contrast radiography, scintigraphy, pH measurements, and esophageal manometrics with provocative testing, motility disorders have become better defined and understood. Primary motility disorders consist of achalasia, diffuse esophageal spasm (DES), "nutcracker esophagus," hypertensive lower esophageal sphincter, and nonspecific esophageal motility dysfunction (NEMD). A host of secondary and miscellaneous motility disorders also affect the esophagus, including scleroderma and other connective tissue diseases, diabetes mellitus, Chagas' disease, chronic idiopathic intestinal pseudo-obstruction, and neuromuscular disorders of striated muscle. Gastroesophageal reflux disease (GERD) may also be promoted by associated motility disturbances. Treatment modalities include surgical myotomy; dilatation; and pharmacologic manipulations, including use of nitrates, calcium-channel blockers, H2-blockers, and psychotropic drugs where appropriate.


MSC-EV therapy for bone/cartilage diseases.
Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality has been shown to vary from batch to batch and preparation to preparation. As the consistency and reproducibility of therapeutic effects rely on the quality of EVs, it is necessary to establish techniques to manufacture scalable amounts of EVs with the same quality. In this manuscript, we discuss the potential factors that affect EV quality. We then introduce pre-clinical studies of EV therapy for bone/cartilage diseases such as osteoarthritis, rheumatoid arthritis, and osteoporosis.


Cigarette Smoking and ARDS After Blunt Trauma: The Influence of Changing Smoking Patterns and Resuscitation Practices.
Cigarette smoking is associated with an increased risk of developing ARDS. However, whether changes in smoking patterns or processes of care impact this relationship is unclear. Are changes in smoking and resuscitation patterns associated with changes in the relationship between smoking and ARDS? We conducted a prospective cohort study of critically injured adults with blunt trauma from 2005 to 2015. Plasma cotinine, a tobacco biomarker, was measured to categorize patients by smoking status. We used regression to assess the relationship between smoking, resuscitation practices, and ARDS over time. In the overall cohort, active (OR, 1.9; 95% CI, 1.0-3.5; P = .046) and passive (OR, 2.6; 95% CI, 1.4-4.8; P = .002) smoking were associated with an increased risk of developing ARDS in multivariate analyses. In contrast to the dose-response relationship in patients enrolled from 2005 to 2008, passive cigarette smoke exposure was associated with the highest risk of developing ARDS in patients enrolled from 2009 to 2015, suggesting a threshold effect. Packed RBC (pRBC) and fresh frozen plasma (FFP) transfusions were associated with an increased risk of developing ARDS, particularly in active smokers (pRBC: OR, 5.6; P < .001; FFP: OR, 4.5; P < .001) compared with passive smokers or nonsmokers. Blood product transfusion and smoking patterns changed over time. Despite changes in resuscitation and smoking patterns, cigarette smoking remains associated with an increased risk of developing ARDS. However, this relationship changed over time, with passive smokers at particularly increased risk of developing ARDS in later years, which may be related to changes in smoking patterns or transfusion practices over time. These findings highlight the need for additional mechanistic and epidemiologic studies of the effects of low levels of cigarette smoke exposure on lung health.


Impact of catalytic iron on mortality in patients with acute coronary syndrome exposed to iodinated radiocontrast-The Iscom Study.
Catalytic iron (CI) mediates vascular injury by generating reactive oxygen species. We evaluated role of CI in predicting mortality in patients with acute coronary syndrome (ACS) and studied association of contrast nephropathy with CI levels. We investigated 806 patients with ACS undergoing contrast exposure for a cardiac procedure who were followed up for 30 days. Overall mortality was 1.6% at 30 days. Catalytic iron at baseline predicted mortality with CI levels significantly higher in those who died, 0.45 μmol/L (0.37, 0.68) compared with survivors 0.31 μmol/L (0.21, 0.40); P = .004. Catalytic iron was associated with increased risk of death in the highest quartile compared with lower 3 quartiles (hazard ratio 7.88, P = .001) after adjustment for age, diabetes, ST deviation, Killip class, ejection fraction, baseline creatinine, hemoglobin level, and troponin. Fifty-five patients (6.8%) developed contrast nephropathy. Patients with contrast nephropathy had a 27% increase in median CI levels from baseline up to 48 hours compared with a marginal 2.9% increase in those without contrast nephropathy (0.37, 0.14 μmol/L to 0.47, 0.20 μmol/L versus 0.35, 0.12 μmol/L to 0.36, 0.14 μmol/L, P < .0001). Patients with contrast nephropathy had significantly higher mortality compared with those without contrast nephropathy (9.1% vs 1.1%, P = .001). High baseline CI levels predicted mortality in patients with ACS. Occurrence of contrast nephropathy was associated with rise in CI levels and higher mortality. Therapeutic options to buffer or chelate CI may have beneficial effects on mortality in this setting.


[Information storage by the French blood banking community in 1988].
This report presents the results of a survey about computerization of the French Blood Bank Community. Questionnaires issued on the behalf of the French Automation Working Party (G.A.I.T.S.) were sent, then analysed during the second term of 1988. The answers allowed us to obtain a picture of the advance of computerization in the French Blood Transfusion Services.


Sensitivity of sensor-based sit-to-stand peak power to the effects of training leg strength, leg power and balance in older adults.
Increasing leg strength, leg power and overall balance can improve mobility and reduce fall risk. Sensor-based assessment of peak power during the sit-to-stand (STS) transfer may be useful for detecting changes in mobility and fall risk. Therefore, this study investigated whether sensor-based STS peak power and related measures are sensitive to the effects of increasing leg strength, leg power and overall balance in older adults. A further aim was to compare sensitivity between sensor-based STS measures and standard clinical measures of leg strength, leg power, balance, mobility and fall risk, following an exercise-based intervention. To achieve these aims, 26 older adults (age: 70-84 years) participated in an eight-week exercise program aimed at improving leg strength, leg power and balance. Before and after the intervention, performance on normal and fast STS transfers was evaluated with a hybrid motion sensor worn on the hip. In addition, standard clinical tests (isometric quadriceps strength, Timed Up and Go test, Berg Balance Scale) were performed. Standard clinical tests as well as sensor-based measures of peak power, maximal velocity and duration of normal and fast STS showed significant improvements. Sensor-based measurement of peak power, maximal velocity and duration of normal STS demonstrated a higher sensitivity (absolute standardized response mean (SRM): ≥ 0.69) to the effects of training leg strength, leg power and balance than standard clinical measures (absolute SRM: ≤ 0.61). Therefore, the presented sensor-based method appears to be useful for detecting changes in mobility and fall risk.


In vitro comparison of tension and stiffness between hamstring tendon and patella tendon grafts.
Following anterior cruciate ligament reconstruction, grafts relax and warm from the temperature of the operating room to body temperature. The current study compared graft tension and stiffness between patella tendon and hamstring tendon grafts. Six quadruple strand hamstring tendon grafts and six patella tendon grafts were preconditioned and loaded to 105 N while at 20 degrees C. Graft tension and stiffness were measured after 15 min, after an additional 4 h, and after increasing the temperature to 34 degrees C. A two-way repeated-measures analysis of variance and a post hoc test were used to compare the measurements between the two types of graft and identify significant (p < 0.05) changes for each type of graft. Tension was significantly larger for the patella tendon grafts, although the stiffness values were not significantly different (p > 0.8). For both types of graft, tension and stiffness decreased significantly with time and the temperature increase. The lowest tension and stiffness measurements were 50 +/- 11 N and 129 +/- 35 N/mm, respectively, for the patella tendon grafts, compared to 18 +/- 5 N and 115 +/- 11 N/mm, respectively, for the hamstring tendon grafts. Both types of graft lose tension to relaxation and a temperature increase, but the tension loss is larger for hamstring tendon grafts.


Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature.
Obstructive sleep apnea (OSA) is a highly prevalent condition with few therapeutic options. To date there is no approved pharmacotherapy for this disorder, but several attempts have been made in the past and are currently ongoing to find one. The recent identification of multiple endotypes underlying this disorder has oriented the pharmacological research towards tailored therapies targeting specific pathophysiological traits that contribute differently to cause OSA in each patient. In this review we retrospectively analyze the literature on OSA pharmacotherapy dividing the medications tested on the basis of the four main endotypes: anatomy, upper airway muscle activity, arousal threshold and ventilatory instability (loop gain). We show how recently introduced drugs for weight loss that modify upper airway anatomy may play an important role in the management of OSA in the near future, and promising results have been obtained with drugs that increase upper airway muscle activity during sleep and reduce loop gain. The lack of a medication that can effectively increase the arousal threshold makes this strategy less encouraging, although recent studies have shown that the use of certain sedatives do not worsen OSA severity and could actually improve patients' sleep quality.


Effects of intermittent inhalation exposures to mixed atmospheres of NO2 and H2SO4 on rabbit alveolar macrophages.
Rabbits were exposed (2h/d) to atmospheres consisting of 0.5 mg/m3 (0.3 micron) H2SO4 plus NO2 at either 0.3 (low) or 1 ppm (high). Animals were sacrificed 24 h after 2, 6, or 13 exposures, and cells were recovered from the lungs by bronchopulmonary lavage. Exposure to high NO2 with acid resulted in an increase in neutrophils at all time points and an increase in phagocytic capacity of macrophages after two or six exposures. On the other hand, exposure to the low NO2 with acid resulted in depressed phagocytic capacity and mobility. The results were compared with those for NO2 or H2SO4 given alone.


Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta-Analysis.
Chorioamnionitis has recently been reported as a risk factor for various neonatal diseases, including cerebral palsy, bronchopulmonary dysplasia, and necrotizing enterocolitis, but its effect on patent ductus arteriosus (PDA) is unclear. We performed a systematic review and meta-analysis to evaluate the effect of chorioamnionitis on PDA. We searched PubMed, EMBASE, Cochrane Library, and KoreaMed databases using the terms: "intrauterine infection" or "maternal infection" or "antenatal infection" or "chorioamnionitis" or "placenta inflammation" or "placenta pathology" or "neonatal outcome" or "neonatal morbidity" or "PDA or patent ductus arteriosus" or "ductus arteriosus," and "prematurity" or "very low birth weight infant." Studies were included if they were randomized controlled trials, case-control studies, or cohort studies that included information relating to chorioamnionitis and PDA. Among 1,571 studies, a total of 23 studies (17,708 cases) were included in the meta-analysis to analyze the relationship between chorioamnionitis and PDA, except one study that only included PDA requiring surgical ligation. The association between chorioamnionitis and PDA was statistically significant (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.19, 1.72; P < 0.0001). In subgroup analysis, clinical chorioamnionitis was not associated with PDA (OR 1.28; 95% CI 1.00, 1.64, 1.790; P = 0.05), whereas histologic chorioamnionitis (OR 1.54; 95% CI 1.10, 2.15; P = 0.01) and chorioamnionitis diagnosed from both clinical and histologic findings (OR 1.75; 95% CI 1.07, 2.86; P = 0.03) showed significant associations with PDA. Chorioamnionitis did not increase the risk of PDA requiring surgical ligation (OR 1.23; 95% CI 0.69, 2.17; P = 0.48), and antenatal steroid use reduced the risk of PDA (OR 0.62; 95% CI 0.42, 0.90; P = 0.01) after chorioamnionitis. The results from this meta-analysis support an association between maternal chorioamnionitis and PDA in offspring.


(S)-4C3HPG reduces infarct size after focal cerebral ischemia.
This study investigated whether the metabotropic glutamate receptor ligand (S)-4C3HPG can reduce brain damage after focal ischemia in rats. Application of 1 micromol of (S)-4C3HPG (intracerebroventricularly) 5 min after occlusion of the middle cerebral artery significantly reduced the infarct size by 72.3% of the saline control.


miR-29a/b1 Inhibits Hair Follicle Stem Cell Lineage Progression by Spatiotemporally Suppressing WNT and BMP Signaling.
Hair follicle stem cells (HFSCs) and subsequent generations of matrix progeny make lineage choices by responding to spatiotemporal signals; however, the cues driving that specification are not well understood. Here, we demonstrate that the dynamics of microRNA (miR)-29 expression are inversely proportional to HFSC lineage progression. Furthermore, we show that sustained miR-29a/b1 overexpression in anagen or telogen in mice causes a short-hair phenotype and eventual hair loss by inhibiting the proliferation of HFSCs and matrix cells and likely preventing their differentiation. Conversely, in a loss-of-function in vivo model, miR-29a/b1 deficiency accelerates HFSC lineage progression in telogen. Mechanistically, miR-29a/b1 blocks HFSC lineage specification by spatiotemporally targeting Ctnnb1, Lrp6, Bmpr1a, and Ccna2. We further show that skin-specific Lrp6 or Bmpr1a ablation partially accounts for the short-hair phenotype. Overall, these synergistic targets reveal miR-29a/b1 as a high-fidelity antagonist of HFSC lineage progression and a potential therapeutic target for hair loss.


Molecular simulation of dendrimers and their mixtures under shear: comparison of isothermal-isobaric (NpT) and isothermal-isochoric (NVT) ensemble systems.
Flow properties of dendrimers are studied with the aid of nonequilibrium molecular dynamics techniques. Simulations are performed in the NpT ensemble using the NpT-SLLOD algorithm [P. J. Davis and D. J. Evans, J. Chem. Phys. 100, 541 (1994)] and are compared to the results from simulations performed in the NVT ensemble reported earlier [J. T. Bosko, B. D. Todd, and R. J. Sadus, Chem. Phys. 121, 12050 (2004)]. Shear thickening observed at high strain rates vanishes in systems kept under constant pressure. Also the exponents in the power-law dependencies of the viscosity and the normal stress coefficients change. The variations are significant only at high strain rates and do not affect largely microscopic properties such as shape, alignment, or rotation of molecules. The NpT-SLLOD algorithm has been applied to study various systems including dendrimers in solution and their blends with linear chain molecules of the same molecular mass, and some results for these systems are presented.


Protein import into mitochondria: a paradigm for the translocation of polypeptides across membranes.
The translocation of proteins across membranes usually requires specific transport systems composed of membrane-bound and soluble components. A combination of biochemical and genetic approaches has led to the identification and preliminary characterization of some of these components.


Effects of limestone addition and sintering on heavy metal leaching from hazardous waste incineration slag.
Hazardous waste incineration (HWI) in rotary kilns and the disposal of the residual slag on landfills play an important role in German waste treatment. In order to save disposal costs the elution behaviour of HWI-slag should be further optimised. Quality-improved slag may be disposed off on cheaper landfill sites still applying to landfill regulations. In a new process-integrated approach hazardous waste is mixed with limestone, which initiates chemical reactions with heavy metals in the rotary kiln yielding new compounds of different solubility. In this work HWI-slag/limestone mixtures are thermally treated and then examined by elution tests. Experimental data indicate that the heavy metals pertinent to landfill class assignment of a HWI-slag share a solubility minimum at a CaO-content of about 15%. Such improved HWI-slags are allowed to be disposed off on cheaper landfill sites. Furthermore, a new combination of thermodynamic calculation methods is applied to predict heavy metal solubility for different process conditions. Used models hold the opportunity to explain the tendencies of heavy metal leaching and propose plausible chemical reactions. With it, a new tool to examine the impact of temperature treatment and slag composition on heavy metal elution from HWI-slag is presented.


Co-staining human PBMCs with fluorescent antibodies and antibody-oligonucleotide conjugates for cell sorting prior to single-cell CITE-Seq.
The dual interrogation of the transcriptome and proteome with single-cell resolution provides exquisite insights into immune mechanisms in health and disease. Here, we describe a cutting-edge protocol wherein we combine Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), a technique utilizing antibody-oligonucleotide conjugates (AOCs), with fluorescence-activated cell sorting to enrich rare cell populations. Our protocol incorporates co-staining of cells with both fluorescent antibodies and AOCs simultaneously for subsequent input into the cell sorting and CITE-Seq pipeline. For complete details on the use and execution of this protocol, please refer to Mair et al. (2020).


Intracellular pH regulation in mantle epithelial cells of the Pacific oyster, Crassostrea gigas.
Shell formation and repair occurs under the control of mantle epithelial cells in bivalve molluscs. However, limited information is available on the precise acid-base regulatory machinery present within these cells, which are fundamental to calcification. Here, we isolate mantle epithelial cells from the Pacific oyster, Crassostrea gigas and utilise live cell imaging in combination with the fluorescent dye, BCECF-AM to study intracellular pH (pHi) regulation. To elucidate the involvement of various ion transport mechanisms, modified seawater solutions (low sodium, low bicarbonate) and specific inhibitors for acid-base proteins were used. Diminished pH recovery in the absence of Na+ and under inhibition of sodium/hydrogen exchangers (NHEs) implicate the involvement of a sodium dependent cellular proton extrusion mechanism. In addition, pH recovery was reduced under inhibition of carbonic anhydrases. These data provide the foundation for a better understanding of acid-base regulation underlying the physiology of calcification in bivalves.


Differential activation of afferent neuronal and inflammatory pathways during small bowel obstruction (SBO).
Small bowel obstruction (SBO) is a potentially life-threatening condition which may be caused by a variety of pathologies such as postoperative adhesions or malignant diseases. Little is known on alterations in gut physiology during SBO, although its comprehension is essential to improve treatment which may help to prevent subsequent organ failure prior to surgical resolution. We aimed to investigate afferent nerve sensitivity and intestinal inflammatory response during SBO to identify possible targets of treatment. C57Bl6 mice were anesthetized, and a midline laparotomy was performed. A small bowel loop was ligated 5 cm proximal to ileo-cecal valve to induce SBO. Control animals received a sham midline laparotomy. SBO animals and controls were sacrificed after 3, 9, or 24 h (each n = 6). A dilated segment of small intestine located 1.5 cm oral to the ligature was prepared for multi-unit mesenteric afferent nerve recordings in vitro. Histological assessment of leukocyte infiltration was performed by myeloperoxidase (MPO). Pro-inflammatory cytokine expression was quantified by RT-PCR. Data are mean ± SEM. Afferent firing to serosal 5-HT (500 μM) peaked at 3.9 ± 0.2 impulse/s 24 h after induction of SBO compared to 2.4 ± 0.1 impulse/s in sham controls (p < 0.05). Serosal bradykinin (0.5 μM) led to an increase in peak afferent firing of 5.3 ± 0.5 impulse/s in 24 h SBO animals compared to 3.5 ± 0.2 impulse/s in sham controls (p < 0.05). No differences in 5-HT and BK sensitivity were observed in 3 and 9 h SBO animals compared to controls. Continuous mechanical ramp distension of the intestinal loop was followed by a pressure-dependent rise in afferent nerve discharge that was reduced in 3 h SBO animals compared to sham controls (p < 0.05). MPO stains showed a rise in leukocyte infiltration of the intestine in SBO animals at 9 and 24 h (p < 0.05). Il-6 but not TNF-a gene expression was increased at 9 and 24 h in SBO animals compared to sham controls (p < 0.05). Afferent nerve sensitivity is increased 24 h after induction of SBO. SBO led to a delayed onset intestinal inflammatory response. Inflammatory mediators released during this inflammatory response may be responsible for a later increase in afferent sensitivity. Agents with anti-inflammatory action may, therefore, have a beneficial effect during SBO and may subsequently help to prevent possible organ dysfunction.


Hormone action during aging: alterations and mechanisms.
The ability to respond to certain hormones is altered during the aging process. Attempts to elucidate the mechanisms involved in such changes have focused primarily on the various molecular components which mediate hormone actions. These include chromatin, the nucleus, cytoplasmic factors, adenylate cyclase and hormone receptors. Age related changes have been observed at all of these levels, and in some cases have been correlated with changes in biological responsiveness to particular hormones. This review attempts to summarize the data obtained in these studies. Possible interpretations are discussed and future directions for such research are suggested.


Publishing Outside the Box: Popular Press Books.
Writing and publishing popular press books requires a set of skills, not natural to basic and applied researchers trained to publish in peer-referred behavior analytic journals or to practice behavior analysis in applied settings. This article provides suggestions and examples. These include finding a distinctive idea, securing a contract, hiring an agent (or not), deciding on a publisher, and writing engagingly for a broad audience. The last is the greatest challenge. Among my recommendations are to read good prose, good models, and good books about publishing; talk to experienced colleagues; read aloud to judge the appropriateness of your vocabulary and style; and interject humor, imagery, and drama. Book publishing is a long and difficult process, but it is possible. It has a great potential for bringing behavior analytic research, practice and theory to the attention of the general public.


Hair-growth promoting effect and anti-inflammatory mechanism of Ginkgo biloba polysaccharides.
The aim of this study was to optimize the separation and purification technology of water-soluble Ginkgo biloba leaves polysaccharides (WGBP), analyze its composition characteristics, observe its hair-growth promoting effect in alopecia areata mice, clarify the polysaccharide fraction with bioactive activities, and explore its anti-inflammation mechanism. We isolated acidic polysaccharides (WGBP-A2) and purified a RG-I type polysaccharide (WGBP-A2b) with a molecular weight of 44 kDa. Results showed that WGBP-A2 could significantly increase the contents of VEGF and HGF in the skin tissue of alopecia areata mice, decrease the contents of Inflammatory factors in the serum. On a cellular level, the expressions of p-p65 and p-IκBα, TNF-α and IL-1β in HUVECs treated with WGBP-A2b were down-regulated. The bioinformatic analysis showed that the inflammation signaling pathway was significantly changed. Its specific mechanism may be related to its regulating the expression of p-p65 p-IκBα, TNF-α and IL-1β proteins in the inflammation signaling pathway.


Antidromic activation of spikes with bimodal and trimodal latencies in the olfactory bulb of rabbits.
Spikes with bimodal and occasional trimodal latencies were recorded from neurons in the olfactory bulb of rabbits in response to lateral olfactory tract (LOT) stimulation at one site. Among neurons with bimodal spike latencies, two types have to be distinguished. In the case of type I neurons long-latency second-mode spikes were suppressed by short-latency first-mode spikes. Due to this suppression the long-latency second-mode spike could be investigated only, when its threshold was lower than that of the short-latency spike. In the case of type II neurons the long-latency second-mode spike was not suppressed. The collision test was applied to type I bimodal spikes. All short-latency first-mode and long-latency second-mode spikes were suppressed by spontaneous spikes. The suppression time indicated the likelihood of collision in most cases, but one could not entirely exclude the possibility, that short-latency first-mode spikes were suppressed due to refractoriness and long-latency second-mode spikes due to inhibition. To allow a more definite interpretation of collision a multiple collision test was applied, by stimulating axons at several LOT sites. A parallel rise of latency values and suppression time values was measured for 3 and more axonal spikes with different latencies, indicating collision and antidromic activation more definitely. Antidromically activated short-latency first-mode spikes were interpreted to be due to axonal stimulation and antidromically activated long-latency second-mode spikes to be due to axon collateral stimulation. No evidence for any postsynaptic activation of type I short-latency first-mode or long-latency second-mode spikes was gained. An indicator for collision of an antidromic spike with a spontaneous spike is the value collision time minus latency (c-l). The c-l values of axonal spikes ranged from 0.2 to 1.8 ms with a mean of 0.7 ms (n = 25), and c-l values of axon collateral spikes from 0.2 to 2.5 ms, with a mean of 1.1 ms (n = 13). The interpretation of c-l values is discussed. In the multiple collision test the c-l deviations from the lowest c-l value of each neuron ranged for axonal spikes between 0.0 and 0.7 ms (n = 25), with 38% not exceeding 0.1 ms and 81% not exceeding 0.4 ms. Spikes activated via axon collaterals had c-l deviations between 0.0 and 2.0 ms (n = 13). The c-l deviations above 2 ms were remote from other values and considered to be possibly inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)


Cerebellar metastases from epithelial ovarian carcinoma. A case report.
Central nervous system metastases are an unusual sequela of epithelial ovarian neoplasms, occurring in less than 1% of reported autopsy cases. A case of cerebellar metastatic disease occurred following combination chemotherapy and a negative second-look operation for a stage III poorly differentiated adenocarcinoma of the ovary. The single metastatic tumor was resectable, and the patient had resolution of her symptoms following surgery. This is the fourth report of an epithelial ovarian carcinoma metastatic to the cerebellum.


The Allium test--an alternative in environmental studies: the relative toxicity of metal ions.
Among the test systems suitable for toxicity monitoring, the Allium test (A. cepa) is well known and commonly used in many laboratories. The onions are easy to store and to handle, and the root tip cells constitute a convenient system for macroscopic (growth, EC50 values) as well as for microscopic parameters (c-mitosis, stickiness, chromosome breaks). Since the cells possess important plant activation enzymes, the Allium test has a wide area of application. Furthermore, results from the Allium test have shown good agreement with results from other test systems, eukaryotic as well as prokaryotic. A modified version of the test method, comprising series of onions for each concentration of the test liquids, was applied to salts of eight metals: Hg (as methyl mercury chloride (MMC) and as HgCl2), Cu, Ni, Cd, Be, Al (diluted in tap water and distilled water), Mn and Li. The highest toxicity, in EC50 values, was caused by Hg (for MMC 9.0 X 10(-7) M, for HgCl2 3.3 X 10(-6) M), Cu (2.7 X 10(-6) M), Ni (1.7 X 10(-5) M) and Cd (3.1 X 10(-5) M); medium toxicity was caused by Be (4.8 X 10(-4) M) and Al (in tap water 8.0 X 10(-4) M, in distilled water 2.8 X 10(-5) M), and low toxicity by Mn (5.2 X 10(-3) M) and Li (2.0 X 10(-2) M). Some of the metals induced specific microscopic effects, requiring particular mention: thus, Ni treatment induced an unusual form of c-mitosis with the c-mitotic chromosomes remaining on the equatorial plate, Be treatment induced a type of 'banded' or 'fragmented' chromosomes. Treatment with Al led to the development, in the cytoplasm of certain root tip cells, of two oblong hyaline structures formed by material extruded from the nucleus. Chromosome breaks were mainly observed as fragments at mitotic anaphase. The metal ions tested here caused only low amounts of fragments, usually in less than 1% of the cells; only Be caused a higher frequency (4.1%). It was not possible to group the few metals tested here according to their cytological effects. The standard parameters, such as the most commonly occurring c-mitosis or stickiness, showed no correlation to atomic weight or to ion charge of the metals. Still, they gave valuable information in relation to environmental screening; thus, the finding of c-mitosis may indicate risks of aneuploidy. Generally speaking, the Allium test is a very useful tool for evaluating and ranking environmental chemicals with reference to their toxicity.


Corrigendum on: Wang H, Chen C, Li J, Yang X, Zhang H and Wang Z. Modified first dorsal metacarpal artery island flap for sensory reconstruction of thumb pulp defects. J Hand Surg Eur. 2016, 41: 177-84.
The authors apologise for an error in the presentation of the affiliations of the authors of this published paper. The correct details are:Hui Wang(1,2*), Chao Chen(3*), Jun Li(4), Xiaoxi Yang(5), Hui Zhang(1,6), Zhiqiang Wang(1,7) (1)Graduate School, Southern Medical University, Guangzhou, Guangdong, PR China(2)The department of Hand Surgery, The Second Hospital of Tangshan, Tangshan, Hebei, PR China(3)The department of Orthopedics, Chinese PLA General Hospital, Beijing, PR China(4)The emergency department, The Second Hospital of Tangshan, Tangshan, Hebei, PR China(5)The department of traditional Chinese Medicine, College of traditional Chinese Medicine, North China University of Technology, Tangshan, Hebei, PR China(6)The department of Joint Surgery, The Second Hospital of Tangshan, Tangshan, Hebei, PR China(7)The department of Orthopaedics, Affiliated Hospital, North China University of Technology, Tangshan, Hebei, 063000, PR China*Hui Wang and Chao Chen contributed equally to this work.


Insufficiency fractures of the sternum.
Insufficiency fractures occur within weakened bones that are unable to withstand the stress of every day normal activities. The spine, pelvis, and lower long-bone extremities are common sites of insufficiency fractures. Spontaneous sternal insufficiency fracture (SIF) has rarely been reported in elderly patients. To recognise a sternal insufficiency fracture is important in selecting the adequate diagnostic procedures.


Translation and validation of Sinhala version of modified EORTC QLQ-OH15 in oral cancer patients who receive radiotherapy with or without chemotherapy in Sri Lanka.
The recognition of patient-reported outcomes for oral cancer is important in improving patients' quality of life. The aim of this study was to translate and validate the modified Sinhala version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oral Health Module (EORTC QLQ-OH15). A cross-sectional study was conducted to validate the EORTC QLQ-OH15 that was modified after adding two questions to the original questionnaire. The two questions added were 'difficulty in opening the mouth wide' and 'trouble with talking' which affect oral health related quality of life (OHRQOL) of oral cancer patients receiving radiotherapy. The Sinhala translated modified EORTC QLQ-OH15 and already validated the core questionnaire EORTC QLQ-C30 were self-completed by 85 adult oral cancer patients who received initial anti-cancer treatment with radiotherapy with or without chemotherapy. Content and face validity were examined by an expert panel. Construct validity was confirmed by using factor analysis, multi-trait scaling analysis, and known group comparison. Reliability was assessed by internal consistency, test-retest reliability by Wilcoxon Signed Ranks Test and intra class correlation coefficient. Responsiveness to change was assessed. The majority of participants (58%) were aged 50-69 years and 84% were males. Nearly 32% had cancer of the anterior two thirds of the tongue. Of the sample, 66% received chemo radiotherapy. Thirteen items were included for the factor analysis. They were loaded for four factors. Three scales 'Eating problem', 'Gum and Speech problem' and 'Soreness' loaded with 5, 4 and 3 items respectively and single item 'teeth' to a one factor with the total variance explained was 72.74%. Mann-Whitney U tests for all three scales were statistically significant confirming the ability of the modified EORTC QLQ-OH15 to detect expected differences in OHRQOL in clinically different groups. Cronbach's alpha for all the scales were more than 0.8. Wilcoxon Matched Paired Sign Rank Test showed highly significant results (p < 0.05) for all three scales revealing high responsiveness. The modified Sinhala version of the EORTC QLQ-OH15 is a valid, reliable tool that can be used to measure OHRQOL in oral cancer patients who receive radiotherapy with or without chemotherapy.


Exophytic interstitial ectopic pregnancy removal: novel use of Endoloop for uterine cavity preservation.
To demonstrate the unique use of Endoloop during laparoscopic removal of an exophytic interstitial ectopic pregnancy to ensure hemostasis, provide counter traction against a uterine manipulator, and reduce the likelihood of entry into the endometrium. Case report with intraoperative surgical footage. Tertiary care referral center operating room. Single patient case report. A single patient with an ectopic pregnancy suspected using ultrasound and confirmed during surgery. Laparoscopic removal of the interstitial ectopic pregnancy via a wedge resection cornuectomy without endometrial involvement using a monopolar hook, Endoloop, and a William's cystoscopic needle for the injection of vasopressin. The patient was a 32-year-old G7P1051 with a history of a left tubal ectopic pregnancy status post a laparoscopic left salpingectomy, 1 full-term vaginal delivery, 2 elective terminations, 2 early pregnancy losses, smoking (1 pack per day), and marijuana use (6 blunts per day). She initially presented in November 2020 with intermittent but worsening left lower quadrant abdominal pain and was found to have a left adnexal mass, raising concern for an ectopic pregnancy in the setting of a β-human chorionic gonadotropin (β-hCG) level of 6,411 mIU/mL, and no intrauterine pregnancy identified using transvaginal ultrasound. She was counseled on medical vs. surgical management and she elected to receive an injection of methotrexate in the emergency department (ED) before discharge with a scheduled follow-up visit at the clinic for standard β-hCG trends. The patient did not attend her scheduled day 4 and 7 visits for β-hCG levels or her 2-week appointment for ultrasound; so, she was called over the phone and asked to come to the ED as soon as possible for evaluation. Approximately 3 weeks after the injection of methotrexate, the patient was still experiencing intermittent left lower quadrant abdominal pain. A repeat ultrasound in the ED showed no intrauterine gestational sac, an endometrial thickness of 0.6 cm, a normal right ovary, a normal left ovary with a corpus luteum cyst, a small amount of free fluid in the cul-de-sac, and a left adnexal extraovarian complex cystic structure measuring 2.9 × 2.4 cm with a fetal pole. The fetal pole corresponded with a gestation period of 6 weeks and 3 days, based on a crown-rump length of 0.59 cm, and lacked cardiac activity. The β-hCG level at this time was 1,124 mIU/mL, and the patient strongly desired surgical management for her ongoing abdominal pain and unresolved ectopic pregnancy. The patient's vital signs and complete blood count were within normal limits. The patient desired future fertility. A repeat transvaginal ultrasound before surgery showed the extraovarian nature of the ectopic pregnancy but could not specify whether it was intrauterine or intra-abdominal in the left adnexa; so, the decision was made to proceed with a diagnostic laparoscopy. After laparoscopic entry through Palmer's point using the Veress needle and then insertion of a 5-mm trocar under direct visualization, the left exophytic interstitial ectopic pregnancy was discovered, as depicted in the video. Given the patient's desire for future fertility, a wedge resection cornuectomy without the involvement of the endometrium was the ideal surgical approach. Subsequent trocar placement consisted of a 10-mm trocar in the umbilicus and a 5-mm trocar in the left lower quadrant. The Endoloop was initially inserted into the umbilical 10-mm trocar to allow for placement around the interstitial ectopic pregnancy to achieve hemostasis and act as a tourniquet. The Endoloop suture was passed into the abdomen and then pulled laterally using an atraumatic grasper through the left lower quadrant trocar to provide counter traction against a uterine manipulator that was deviating the uterus to the patient's right side. This created an excellent plane for dissection along the myometrial base of the interstitial pregnancy to prevent the removal of excess uterine tissue and decrease the likelihood of entry into the endometrial cavity. Injection of 4 units vasopressin (20u in 50 mL of normal saline) using a William's cystoscopy catheter through the umbilical port further ensured hemostasis along the base of the ectopic pregnancy during removal using a monopolar hook. The cystoscopy catheter was chosen for its length and flexible body to maximize maneuverability. Electrocautery was used as needed for hemostasis. After the removal of the ectopic pregnancy using the monopolar hook, the myometrium and serosa were reapproximated in a running 2-layered fashion using a V-Loc suture. The ectopic pregnancy was removed from the abdomen in a specimen retrieval bag through the 10-mm umbilical port. The 10-mm port was closed using a standard fascial closure device and then the skin of all the port sites was reapproximated using 4-0 Monocryl suture. Two important factors that favored this surgical technique over hysterectomy or standard cornuectomy included the patient's strong desire for future fertility and the exophytic nature of the interstitial pregnancy. Nevertheless, as the pregnancy increases in distance from the cornua, so does the likelihood that the pregnancy will be a normal intrauterine pregnancy, which greatly impacts counseling and management if the pregnancy is desired. Postoperative care was routine and the recommendation was made to wait at least 3 months to attempt another pregnancy and to undergo saline-infused sonography for the evaluation of the endometrial cavity; however, the patient never followed up. This video demonstrates the unique use of Endoloop and vasopressin through a William's cystoscopy injection needle during the laparoscopic removal of an exophytic interstitial ectopic pregnancy. The Endoloop helped to ensure hemostasis, provide counter traction against the uterine manipulator, and optimize visualization to reduce the likelihood of endometrial involvement in a patient who desired future fertility.


Misoprostol for intrauterine fetal death.
The frequency of intrauterine fetal death (IUFD) with retained fetus varies, but is estimated to occur in 1% of all pregnancies. The vast majority of women will spontaneously labor and deliver within three weeks of the intrauterine death. The complexity in medical management increases significantly when the cervix is unripe or unfavorable, or when the woman develops disseminated intravascular coagulation. Misoprostol regimens for the induction of labor for second and third trimester IUFDs, range from 50 to 400 microg every 3 to 12 h, and are all clinically effective. Nevertheless, the current scientific evidence supports vaginal misoprostol dosages, which are adjusted to gestational age: between 13-17 weeks, 200 microg 6-hourly; between 18-26 weeks, 100 microg 6-hourly; and more than 27 weeks, 25-50 microg 4-hourly. In women with a previous cesarean, lower doses should be used and doubling of doses should not occur. Clinical monitoring should continue after delivery or expulsion because of the risk of postpartum atony and/or placenta retention.


Measuring readiness to change and locus of control belief among male alcohol-dependent patients in Taiwan: comparison of the different degrees of alcohol dependence.
The purpose of the present study was to evaluate the Drinking-Related Health Locus of Control scale (DRIE) and the three aspects of readiness to change (i.e. ambivalence, recognition, and taking action), in response to the degree of dependence. This study was carried out based on data collected from 160 male alcohol-dependent patients, and the degree of alcohol dependence was divided into three categories: light, moderate, and severe, on the basis of the total scores of the short-form Severity Degree Alcohol Dependence Data questionnaire (SADD). There were significant differences between the different degrees of dependence on drinking-related locus of control, feelings of ambivalence toward drinking, recognition of problematic drinking, and readiness to take action to change. Patients with more severe dependence usually had higher scores of drinking-related locus of control, indicating a tendency toward external locus of control, feelings of ambivalence, and recognition of their drinking problem; patients with light dependence usually had higher scores for taking action. Clinicians can strengthen readiness to change problematic drinking if the importance of degree of dependence and drinking-related locus of control are taken into consideration when devising interventions.


Investments in research infrastructure on the project level: Problems, methods and mechanisms.
Evaluation of infrastructure projects usually involves the separate application of financial or economic analysis to assess return on investment. In this paper we have developed a modified approach that includes additional public effects and their distribution between project participants in the financial and economic model of the research infrastructure project. Evaluation methods are based on the transition from financial to economic efficiency by adjusting cash flows and including indirect effects (impact of technological spillovers), externalities (knowledge spillovers and ecological effects) and tax effects. Policy and practical implications are closely examined with a focus on the distributional effects for the Core Facility Project of the Catalyst Center in Novosibirsk Academic Town. The results show that a significant excess of economic returns compared to financial returns is determined mainly by the indirect benefits of private participants who use the results of the project, but are not direct participants in this project. The main impact on the financial efficiency arises at the investment stage through direct support measures, complemented by private funding. Indirect support measures only work successfully during the operational stage. Stimulation of the investments in research infrastructure through government support essentially depends on the choice of a certain combination of government support instruments and project financing.


Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data.
Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.


A revised version of the Iwaoka's assay: Application of hyphenated techniques.
Assessing the effects of glutathione peroxidase (GPx)-like catalytic activities of natural, semi-synthetic, and synthetic compounds is nowadays well recognized of importance for the preliminary screening of potential anti-inflammatory, neuroprotective, and anti-cancer agents. To this aim the Iwaoka's assay, relying on 1H NMR data recording, has been the most exploited test. In this short communication we propose an efficient and easy to perform methodology to accomplish the same process based on the application of hyphenated techniques like gas-chromatography coupled to mass spectrometry (GC-MS) and high-performance liquid chromatography with diode array detection (HPLC-DAD). The assay consisted in monitoring and quantifying the oxidation at different times of 1,4-dithiothreitol to 4,5-dihydroxy-1,2-dithiane in the presence of H2O2 and 2-phenyl-1,2-benzoselenazol-3(2H)-one (Ebselen) as the catalyst in EtOAc or MeOH as the solvents. The results we recorded by the application of both GC-MS and HPLC-DAD, showed that the GPx-like activity of Ebselen, used as the reference compound, can be effectively monitored in a time-course manner, and compare favorably to the NMR-based test.


Advanced oxidation of bisphenols by peracetic acid activated by light and ultrasound.
Light and ultrasound have been tested as physical factors activating peracetic acid (PAA) to oxidize bisphenols (BPs). Based on the chemometric approach of the Taguchi method, UV irradiation with a wavelength of 254 nm was selected as the optimal type of PAA activator. The effectiveness of the UV/PAA system was also compared with other oxidation methods. Under optimal conditions ([BPs]0 = 1 mg/L, 1 mM PAA, pH 9, UV 254 nm) the tested bisphenols are completely degraded within 15-60 min. The influence of the matrix on the process of organic micropollutants removal in the UV/PAA system was also investigated. Toxicity assessment leads to the conclusion that the reaction mixture shows limited toxicity towards living organisms.


Cosmetic regulatory activities in the United States: past, present and future.
To protect consumers from unsafe or decptively labeled cosmetics, the Food and Drug Administration promulgates regulations, conducts factory inspections, investigates mardeted products, evaluates consumer complaints, maintains registries of voluntarily submitted formulation and adverse reaction information, and carries out analytical, microbiological and toxicological studies. There has been a significant shift in program priorities from surveillance activities to scientific research and the determination of systemic hazards to health. Major scientific efforts involve studies to determine the dermal toxicity of cosmetics, develop methods for predicting the efficacy of preservatives, and answer questions about the skin penetration and carcinogenicity of nitrosodiethanolamine. A further issue of concern is the carcinogenic hazard of hair dyes.


Operator independent focused high frequency ISM band for fat reduction: porcine model.
Selective fat reduction has been clearly shown for various methods and energy modalities including cryolipolysis and high intensity focused thermal ultrasound. Mathematical modeling of focused high frequency of the EM spectrum has indicated that selective heating of fat is possible using wavelengths not previous explored. The purpose of this study was to demonstrate in the porcine model that selective heating of fat is possible with a non-contact, operator independent device. High frequencies of the Industrial, Scientific and Medical (ISM) RF band were utilized to reduce abdominal fat in a porcine model. Practical application of mathematical modeling allowed an auto-feedback loop to be developed to allow operator independent adjustment of energy to maintain subcutaneous fat at 45-46°C while overlying skin remained at 40-41°C. Treatments of three Vietnamese pigs were performed under anesthesia in a certified veterinary facility. Gross and microscopic histologic results demonstrated a marked reduction in adipocytes of the treated area after 4 treatments of a total of 30 minutes each, with incremental fat diminution after each treatment. A final 70% reduction of the abdominal fat layer was seen in the treated areas. Duplex ultrasound revealed a reduction of fat layer from 7.6 to 2.9 mm. Histologic evaluation revealed that epidermis, dermis, and adnexal structures such as hair follicles were unaffected by the treatment, while adipocytes were significantly affected. A new model of fat reduction using high frequency RF has been successfully achieved in a porcine model. This has very positive implications in the development of an operator independent, contact free device for reduction of fat in clinical practice.


Platelet-rich plasma (PRP) in oncological patients: long-term oncological outcome analysis of the treatment of subcutaneous venous access device scars in 89 breast cancer patients.
Platelet-rich plasma (PRP) is widely used product, and meta-analyses showed this product to be beneficial when applied to a wound area. This study group has already demonstrated increased patient satisfaction and lower complication rates in breast cancer patients who received PRP after removal of their subcutaneous venous access device. This work is a follow-up analysis focusing on oncologic safety. Currently, there is no long-term data on the use of PRP products in cancer patients available yet. Between the years 2012-2016, venous access device removal was supported with the application of Arthrex ACP® (Autologous Conditioned Plasma)-a PRP product to improve the wound-healing process. All surgeries were performed in the breast cancer center of the municipal hospital of Cologne, Holweide, Germany. 35 patients received an application of Arthrex ACP® after port removal compared to the control group of 54 patients. Endpoints were local recurrence-free, distant recurrence-free as well as overall survival. Median follow-up was 45 months. No (0) adverse events were shown for cancer recurrence within the subcutaneous venous access device scar area. Thus, there seems to be no local oncogenic potential of the PRP product. All other endpoints as well as any-cause death numerically favor PRP use. PRP products such as Arthrex ACP® seem to be oncological inert when applied after removal of subcutaneous access devices. This is the first study providing long-term data about overall survival, distant recurrence-free and local recurrence-free survival after applying PRP in high-risk cancer patients.


An Experience Sampling Measure of the Key Features of Rumination.
Research indicates that rumination can be viewed as a dynamic process that fluctuates over time, within hours and days. An increasing number of intensive longitudinal studies on rumination are accordingly being conducted and published using experiencing sampling methodology (ESM), a technique with measurements in everyday life. Yet, this literature suffers from a profound caveat: rumination has so far been conceptualized and measured as a unitary construct in these ESM studies. This is unfortunate, since such a unitary view contrasts with prominent contemporary models that regard rumination as a multifaceted construct, wherein the key features are not interchangeable and should therefore be measured separately. Moreover, no validated ESM measure of the key features of rumination has yet been developed. Therefore, we developed and validated an ESM protocol and the first ESM questionnaire to assess rumination as a multifaceted construct, measuring five features of rumination. We conducted an ESM study in a community sample of 40 French-speaking participants. They answered the five rumination ESM items in French four times a day for fourteen days. At the end of the ESM assessment period, participants completed trait-like questionnaires of rumination, depression, and general anxiety. The ESM rumination items exhibited good psychometric properties, including excellent within-person variability and convergent validity with corresponding trait-like constructs. Although further validation is warranted, this novel ESM assessment protocol of rumination as a multifaceted construct (validated in French and translated into English) will allow future researchers to study how rumination's features fluctuate and interact with other constructs over time.


HER-2 overexpression in female genital tract clear cell carcinomas: Evaluation of different scoring guidelines, clinicopathological features and prognostic impact.
Clear cell carcinoma (CCC) is a rare high-grade adenocarcinoma associated with poor response to platinum-based chemotherapy agents in the female genital tract. Human epidermal growth factor receptor 2 (HER2) overexpression is routinely used as a biomarker for targeted therapy in breast and gastric carcinomas, but its role in CCC remains unclear. In this study, HER2 overexpression was evaluated by immunohistochemistry (IHC) using College of American Pathologists (CAP) HER2 scoring guidelines for breast and endometrial serous carcinoma (ESC) on tissue microarray blocks. In equivocal and positive cases, fluorescence in situ hybridization (FISH) was performed. IHC score 3, and all amplified cases on FISH test were considered positive. Thirty-six cases of ovarian (OCCC), 36 endometrial (ECCC), and 2 cervical CCC were included. According to ESC and breast scoring guidelines, 20 % and 15.1 % of ECCC and 14.7 % and 6 % of OCCC were HER2 positive, respectively. Both cases of cervical CCC were negative. Scoring based on breast carcinoma guideline showed higher concordance (100 %) with gene amplification results, in comparison with ESC guideline (82.7 %). On multivariate survival analysis, HER2 positive ECCC and OCCC (based on ESC scoring methods) had significantly lower overall and disease-free survivals (OS, DFS) (P < 0.05). HER2 immunoscoring based on ESC guideline can yield a higher sensitivity with relevant clinical and prognostic features in OCCC and ECCC. HER2 can be considered a potential biomarker for targeted therapy and future clinical trials.


Publication standards in infancy research: Three ways to make Violation-of-Expectation studies more reliable.
The Violation-of-Expectation paradigm is a widespread paradigm in infancy research that relies on looking time as an index of surprise. This methodological review aims to increase the reliability of future VoE studies by proposing to standardize reporting practices in this literature. I review 15 VoE studies on false-belief reasoning, which used a variety of experimental parameters. An analysis of the distribution of p-values across experiments suggests an absence of p-hacking. However, there are potential concerns with the accuracy of their measures of infants' attention, as well as with the lack of a consensus on the parameters that should be used to set up VoE studies. I propose that (i) future VoE studies ought to report not only looking times (as a measure of attention) but also looking-away times (as an equally important measure of distraction); (ii) VoE studies must offer theoretical justification for the parameters they use, and (iii) when parameters are selected through piloting, pilot data must be reported in order to understand how parameters were selected. Future VoE studies ought to maximize the accuracy of their measures of infants' attention since the reliability of their results and the validity of their conclusions both depend on the accuracy of their measures.


Transcriptional mechanisms that regulate T helper 1 cell differentiation.
Recent research has made great strides in uncovering the mechanisms by which the T helper 1 (Th1) cell gene expression program is established. In particular, studies examining the transcription factors T-bet, STAT1, and STAT4 have elucidated their roles in regulating Th1 signature genes, including Ifng, and have started to address their contributions to the epigenetic states in Th1 cells. Additionally, new findings have provided information about how the co-expression of T helper cell lineage-defining transcription factors impacts the phenotype of the cell. In this review, we will briefly highlight the research from the last few years examining the epigenetic states in T helper cells and the mechanisms by which they are established. We will then discuss how this new information contributes to our understanding of the flexibility of T helper cell genetic programs.


A novel pentavalent vaccine candidate completely protects against Acinetobacter baumannii in a mouse model of peritonitis.
Acinetobacter baumannii is considered as one of the most virulent and infectious organisms that have an increased ability to both evade host immune response and resist various classes of antibiotics, leading to life-threatening infections. Multiple virulence factors have been implicated in the high prevalence rate of A. baumannii in hospitalized and immunocompromised patients. Moreover, improper use of antibiotics has led to the emergence of extensive drug-resistant strains that urgently require alternative strategies to control this superbug. Unfortunately, the availability of a licensed vaccine against A. baumannii infections is still challenged by the vast diversity among A. baumannii strains. Here, we report the development of a novel pentavalent vaccine candidate composed of two recombinant proteins (Wza and YiaD) and a pool of capsular polysaccharides isolated from 3 clinical isolates. We tested this new vaccine in vivo in a mouse model of peritonitis against the standard strain ATCC 19606 in addition to 3 clinical isolates of A. baumannii. Immunization with this vaccine completely protected the challenged mice with 100% survival rate in the case of all the tested bacteria. Further clinical studies are urgently needed to evaluate the efficacy and safety of this proprietary vaccine to protect patients from A. baumannii lethal infections. KEY POINTS: • Recombinant proteins pool (Wza and YiaD) immunization led to a synergistic immune response. • Capsular polysaccharides pool induced up to 90% protection of tested clinical isolates. • The pentavalent pool showed superiority with 100% survival of immunized mice.


Hilar Inflammatory Pseudotumour with Hepatic Artery Atheroma- mimicker of Klatskin Tumour.
Inflammatory pseudotumour of hilar biliary structures is an extremely rare benign lesion that can mimic hilar cholangiocarcinoma. Clinical presentation and imaging findings often pose diagnostic difficulties. Main histopathological findings are the presence of myofibroblastic spindle cells, plasma cells, macrophages, and lymphocytes without cellular atypia or atypical mitotic figures. We describe a case of 62 year old male who presented with surgical obstructive jaundice. Imaging revealed a mass lesion involving the biliary confluence with upstream dilatation of biliary tree. Diagnosis of hilar cholangiocarcinoma with type III hilar block was made. Intraoperately hilar mass lesion was found which was encasing right hepatic artery with no evidence of metastasis. The patient underwent Right hepatectomy with caudate lobectomy with complete common bile duct (CBD) excision with Roux en Y hepaticojejunostomy. Unexpectedly histopathological examination showed no evidence of malignancy and revealed hilar inflammatory pseudotumour with hepatic artery atherosclerosis. Preoperative imaging, operative management, pathologic diagnosis and literature review are being presented in view of rarity of the case.


Pulmonary embolism treatment. Detection of chronic thromboembolic pulmonary hypertension.
The correct stratification of pulmonary embolism risk (PE) is essential for decision-making, regarding treatment and defining the patient's place of admission. In high-risk PE, urgent re-establishment of pulmonary circulation and admission to a critical unit is required. The reperfusion treatment of choice is systemic thrombolysis, although in certain situations, especially when there is a contraindication for it, we will evaluate a surgical embolectomy or one of the catheter-guided therapies. In the rest of PE, the treatment of choice will be anticoagulation. Currently, direct oral anticoagulants have become the treatment of choice for the treatment of PE, due to their better safety profile. However, low molecular weight heparins and subsequently antivitamins K, remain the most used treatment, because they are funded by the public system. In cases of PE with cardiorespiratory arrest and / or cardiogenic shock, whenever available at our center, we must consider the indication of extracorporeal membrane oxygenation. The recent creation of PE response teams (PERT team), have meant an improvement in the care of patients with intermediate-high and high risk PE. During the follow-up of patients with PE, it is essential to perform a correct screening of chronic thromboembolic pulmonary hypertension, in order to perform a correct diagnostic and therapeutic approach.


Respect and Autonomy in Children's Observation and Participation in Adults' Activities.
This chapter examines Peruvian Quechua children's learning by observing and pitching in. The children concentrate attentively when they observe the activities of the adults and they exercise autonomy in the context of adults' encouragement of measured behaviors while always showing respectful silence in the presence of their elders.


Immune-instructive materials as new tools for immunotherapy.
Immune instructive materials, are materials with the ability to modulate or mimic the function of immune cells, provide exciting opportunities for developing new therapies in many areas including medical devices, chronic inflammation, cancer, and autoimmune diseases. In this review we highlight some of the latest research involving material-based strategies for modulating macrophage phenotype and dendritic cell function, as well as a brief description on biomaterial use in T cell and natural killer cell engineering. We highlight studies on material topography, size, shape and surface chemistry to reduce inflammation, along with scaffold and hydrogel delivery systems that are used for modulating DC phenotype and influencing T cell polarization. Artificial antigen presenting cells are also reviewed as a promising approach to cancer immunotherapy.


A HER2-targeted RNA aptamer molecule labeled with 99mTc for single-photon imaging in malignant tumors.
A modified RNA aptamer with HER2-specific binding was conjugated to hynic and labeled with (99m)Tc, for potential use as a radiopharmaceutical for diagnostic imaging of ovarian cancer cells (SKOV-3) with high HER2 expression. The aptamer was radiolabeled with (99m)Tc by using hynic as the chelator and tricine as the co-ligand. Stability testing of the radioconjugated aptamer was performed via ITLC and SDS-PAGE in normal saline and serum. The aptamer-radionuclide conjugate was evaluated for cellular HER2-specific binding, saturation affinity, and cellular internalization in SKOV-3 and MCF-7 cells, and its biodistribution properties were assessed in normal and SKOV-3 tumor-bearing mice. Radiolabeling of the aptamer was achieved with high yield and radiochemical purity, and the (99m)Tc-hynic-RNA aptamer was highly stable in normal saline and serum. Cellular experiments showed specific binding of the aptamer to the HER2 receptor with a dissociation constant of 27 nM. Rapid blood clearance was observed after injection of the (99m)Tc-hynic-RNA aptamer, and the main excretion route was via the hepatobilary system. While the radioconjugated aptamer bound specifically to the HER2 receptor on cells in vitro, it did not show any significant tumor-to-blood or tumor-to-muscle ratios in mice. Modifications to radiolabeled aptamer will require improving its pharmacokinetic properties and tumor uptake in vivo.


Prognostic value of blood pressure and resting heart rate in patients with tricuspid regurgitation.
The prognostic value of blood pressure (BP) and resting heart rate (RHR) in tricuspid regurgitation (TR) patients is unknown. This study aimed to investigate the associations of BP and RHR with all-cause mortality in patients with TR. A total of 2,013 patients with moderate or severe TR underwent echocardiography and BP measurement. The associations of routinely measured BP and RHR with 2-year all-cause mortality were analyzed. The cohort had 45.9% male patients and a mean age of 62.5 ± 15.9 years. At the 2-year follow-up, 165 patient deaths had occurred. The risk of death decreased rapidly, negatively correlating with systolic blood pressure (SBP) up to 120 mmHg and diastolic blood pressure (DBP) up to 70 mmHg. For RHR, the risk increased in direct proportion, starting at 80 beats per min. After adjusting for age, sex, body mass index (BMI), diabetes, coronary heart disease, pulmonary hypertension, estimated glomerular filtration rate (eGFR), and NYHA class, SBP [hazard ratio (HR):0.89; 95% CI:0.823-0.957 per 10 mmHg increase; P =0.002], DBP (HR:0.8; 95% CI:0.714-0.908 per 10 mmHg increase; P < 0.001), and RHR (HR: 1.1; 95% CI: 1.022-1.175 per 10 beats per min increase; P = 0.011) were independently associated with all-cause mortality. These associations persisted after further adjustments for echocardiographic indices, medications, serological tests, and etiologies. In this cohort of patients with TR, routinely measured BP and RHR were associated with all-cause mortality independently. However, further large-scale, high-quality studies are required to validate our findings.


Suppression of Th1 cytokine production by a peptide derived from C4b.
The complement system has been proposed to play a significant role in the regulation of T-cell responses. However, the precise mechanism underlying C4-induced immune tolerance remains to be clarified. We recently reported that monomeric C4b inhibits CXCL10 production from blood cells. The purpose of this study was to verify the active site of monomeric C4b. We investigated the in vitro effects of a C4b-derived peptide (VPAGSARPVAFSVVPTAAA), named HP2 (highly homologous peptide 2), on the IFN-β-induced production of CXCL10 in human blood and the in vivo effects of the administration of HP2 on Th1/2 cytokine production in the spleen in mice. We also tested whether the administration of HP2 influences symptoms of experimentally induced ulcerative colitis in mice. HP2 inhibited CXCL10 production in human blood, and the administration of HP2 significantly suppressed the production of Th1 cytokines, such as IL-2, IFN-γ, and TNF-α, in spleen cells isolated from mice. The administration of HP2 in the mice significantly improved the symptoms of colitis, with down-regulation of colitogenic CD4(+)CD45RB(high) T cells and up-regulation of CD4(+)LAP/TGF-β1(+) T cells. The amino acid sequence described above is suggested to be the active site in C4b for the inhibition of Th1 cytokine production. These results should contribute to the development of new drugs suppressing autoimmune responses.


In vitro binding of cefovecin to plasma proteins in Australian marsupials and plasma concentrations of cefovecin following single subcutaneous administration to koalas (Phascolarctos cinereus).
Cefovecin has a long duration of antibiotic activity in cats and dogs, somewhat attributable to its high plasma protein binding. To determine the cefovecin binding to plasma proteins in vitro in selected Australian marsupials and to quantify the change in cetovecin concentration over time following subcutaneous injection in koalas. Various cefovecin concentrations were incubated with plasma and quantified using HPLC. The median (range) bound percentages when 10 μg/mL of cefovecin was incubated with plasma were 11.1 (4.1-20.4) in the plasma of the Tasmanian devil, 12.7 (5.8-17.3) in the koala, 18.9 (14.6-38.0) in the eastern grey kangaroo, 16.9 (15.7-30.2) in the common brush-tailed possum, 37.6 (25.3-42.3) in the eastern ring-tailed possum and 36.4 (35.0-38.3) in the red kangaroo, suggesting that cefovecin may have a shorter duration of action in these species than in cats and dogs. Cefovecin binding to plasma proteins in thawed, frozen equine plasma was also undertaken for assay quality control and the median (range) plasma protein binding (at 10 μg/mL) was 95.6% (94.9-96.6%). Cefovecin was also administered to six koalas at 8 mg/kg subcutaneously and serial blood samples were collected at 3, 6, 24, 48, 72, 96 h thereafter. Cefovecin plasma concentrations were not quantifiable in four koalas and in the other two, the mean plasma concentration at t = 3 h was 1.04 ± 0.01 μg/mL. Because of the limited pharmacokinetic data generated, no further pharmacokinetic analysis was performed; however, a single injected bolus of cefovecin is likely to have a short duration of action in koalas (hours, rather than days).


Chitosan inhibits prostaglandin E2 formation and cyclooxygenase-2 induction in lipopolysaccharide-treated RAW 264.7 macrophages.
Chitosan, a deacetylated chitin, has been reported to accelerate the wound healing and exert anti-inflammatory effect but the possible mechanisms involved are still unclear. Enhanced production of prostaglandin E2 (PGE2) and pro-inflammatory cytokines has been shown to contribute to immunosuppression and cytotoxicity during wound healing. In this study, we examined the effect of chitosan on cyclooxygenase pathway and cytokines production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results first demonstrated that chitosans (MW=50,000, 150,000 or 300,000) significantly inhibit the overproduction of PGE2 as well as cyclooxygenase-2 (COX-2) protein expression and activity accompanied by attenuation of pro-inflammatory cytokines production such as tumor necrosis factor-alpha and interleukin-1beta formation but increase of the anti-inflammatory cytokine, IL-10, formation in LPS-treated RAW 264.7 macrophages. These results suggest that the beneficial effect of chitosan on wound healing may be associated, at least partly, with the inhibition of PGE2 production by suppressing COX-2 induction and activity as well as attenuation of pro-inflammatory/anti-inflammatory cytokines ratio in activated macrophages.


An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.
Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.


Ultrastructural observations on antennal sensilla of Coleophora obducta (Meyrick) (Lepidoptera: Coleophoridae).
Coleophora obducta (Meyrick) is an important defoliator of larch in northeast China. To further describe the mechanism of insect-plant chemical communication, we observed the antennae and their sensilla of C. obducta by scanning and transmission electron microscopy. In both sexes, antennae were threadlike, and in total there were eight types of sensilla found on the antennae: Sensilla placodea, Sensilla basiconica, Sensilla coeloconica, Sensilla styloconica, Sensilla trichodea, Sensilla squamiformia, Sensilla furcatea and Böhm bristles, respectively. We described ultrastructures and discussed possible functions. We inferred from their ultrastructures as chemoreceptors that S. placodea, S. basiconica and S. trichodea were innervated by sensory neurons. The neuron of S. styloconica terminated in a tubular structure which suggested gustatory/mechanosensory function, and the terminal sensory pegs might function as contact-chemoreceptors depending on their locations.


Immunoperoxidase anti-keratin staining of epidermal and pilar cysts.
Epidermal and pilar cysts have been stained with anti-keratin antibodies raised from human hair and human callus. The staining properties of the two cysts are different and, in general, support the idea that they originate from epidermis and trichilemmal hair follicle layer respectively.


Quality of Life Differences in Children and Adolescents With 0, 1 to 2, or 3+ Persistent Postconcussion Symptoms.
Persistent postconcussion symptoms (PPCSs) are associated with lower health-related quality of life (HRQoL) in children and adolescents. Despite commonly cited criteria for PPCSs involving 3 or more complaints, many individuals experience just 1 or 2 symptoms that may still negatively affect HRQoL. To determine differences in HRQoL between children and adolescents with 0, 1 to 2, or 3+ parent-reported persistent symptoms at 1 month postconcussion. Prospective cohort study. Community practice clinics. Individuals aged 8 to 18 years presented for the initial visit within 3 days of a sport- or recreation-related concussion. One month later, parents or guardians reported persistent symptoms using the Rivermead Post Concussion Symptoms Questionnaire (RPQ). Individuals with complete symptom data were analyzed (n = 236/245, n = 97 females, age = 14.3 ± 2.1 years). Participants were grouped by the number of discrete RPQ symptoms reported as worse than preinjury (0, 1-2, or 3+). Total summary and subscale scores on the Pediatric Quality of Life Inventory (PedsQL) 23-item HRQoL inventory and 18-item Multidimensional Fatigue Scale (MDFS). Kruskal-Wallis rank sum tests highlighted differences in PedsQL HRQoL and MDFS total scores across symptom groups (PedsQL HRQoL: χ22 = 85.53, P < .001; MDFS: χ22 = 93.15, P < .001). Dunn post hoc analyses indicated all 3 groups were statistically significantly different from each other (P < .001). The median (interquartile range) values for the Peds QL Inventory HRQoL totals were 93.5 (84.2-98.8) for those with 0 symptoms; 84.8 (73.9-92.4) for those with 1 to 2 symptoms; and 70.7 (58.7-78.0) for those with 3+ symptoms. The median (interquartile range) values for the MDFS totals were 92.4 (76.4-98.6) for those with 0 symptoms; 78.5 (65.6-88.9) for those with 1 to 2 symptoms; and 54.2 (46.2-65.3) for those with 3+ symptoms. Similar group differences were observed for each PedsQL HRQoL and MDFS subscale score. Children and adolescents whose parents reported 1 to 2 PPCSs had lower HRQoL and more fatigue than those with 0 symptoms. Across all 3 groups, those with 3+ persistent symptoms had the lowest HRQoL and most fatigue. These findings indicate the continued need for intervention in this age group to prevent and address PPCSs.


Fully automated registration of vibrational microspectroscopic images in histologically stained tissue sections.
In recent years, hyperspectral microscopy techniques such as infrared or Raman microscopy have been applied successfully for diagnostic purposes. In many of the corresponding studies, it is common practice to measure one and the same sample under different types of microscopes. Any joint analysis of the two image modalities requires to overlay the images, so that identical positions in the sample are located at the same coordinate in both images. This step, commonly referred to as image registration, has typically been performed manually in the lack of established automated computational registration tools. We propose a corresponding registration algorithm that addresses this registration problem, and demonstrate the robustness of our approach in different constellations of microscopes. First, we deal with subregion registration of Fourier Transform Infrared (FTIR) microscopic images in whole-slide histopathological staining images. Second, we register FTIR imaged cores of tissue microarrays in their histopathologically stained counterparts, and finally perform registration of Coherent anti-Stokes Raman spectroscopic (CARS) images within histopathological staining images. Our validation involves a large variety of samples obtained from colon, bladder, and lung tissue on three different types of microscopes, and demonstrates that our proposed method works fully automated and highly robust in different constellations of microscopes involving diverse types of tissue samples.


Frequency gradient in the autorhythmicity of the pyeloureteral pacemaker system.
The pacemaker properties of the various regions of isolated segments of the rabbit renal pelvis were examined. The results show that pacemaker frequency and waveform of contraction change significantly within the renal pelvis. The highest frequency was encountered at the fornix, while the ureteropelvic junction is lowest.


Wide-field Intensity Fluctuation Imaging.
The temporal intensity fluctuations contain important information about the light source and light-medium interaction and are typically characterized by the intensity autocorrelation function, g2(τ). The measurement of g2(τ) is a central topic in many optical sensing applications, ranging from stellar intensity interferometer in astrophysics, to fluorescence correlation spectroscopy in biomedical sciences and blood flow measurement with dynamic light scattering. Currently, g2(τ) at a single point is readily accessible through high-frequency sampling of the intensity signal. However, two-dimensional wide-field measurement of g2(τ) is still limited by camera frame rates. We propose and demonstrate a 2-pulse within-exposure modulation approach to break through the camera frame rate limit and obtain the quasi g2(τ) map in wide field with cameras of only ordinary frame rates.


A systematic review of the treatment for abdominal cutaneous nerve entrapment syndrome.
Abdominal cutaneous nerve entrapment syndrome (ACNES) is a frequently overlooked cause of chronic abdominal pain. We aim to outline the current available literature concerning the treatment of patients diagnosed with ACNES. A systematic search in PubMed, EMBASE, CINAHL, and Cochrane databases was performed. Seven studies were included; describing trigger point injection (TPI) or anterior neurectomy as stand-alone procedure, TPI followed by anterior neurectomy as stepwise regimen, and nerve stimulation and phenolization. After TPI, 86% of the patients showed successful response, 76% at long-term follow-up. Two other studies report successful treatment in 50% of patients. In the included trial using anterior neurectomy, 73% vs 18% of the patients demonstrate a successful pain response in the neurectomy and sham group, respectively. Two cohort studies showed that 69% and 61% of the neurectomy group reported to be satisfied at 18 months and 32 months follow-up, respectively. There is significant pain relief after injections and anterior neurectomy. Awareness of the diagnosis is important. The validity of currently used diagnostic criteria needs to be evaluated in additional studies.


The Effect of Different Doses of Ciprofol in Patients with Painless Gastrointestinal Endoscopy.
Ciprofol is currently used for painless gastrointestinal endoscopy and anesthesia induction. However, whether it is superior to propofol and its optimal dose remains unknown. A total of 149 patients, 63 males and 86 females, aged 18-80 years, BMI 18-28 kg/m2, ASA I-III, were divided randomly into four groups: propofol group (group P, n = 44), ciprofol 0.2mg/kg group (group C2, n = 38), ciprofol 0.3mg/kg group (group C3, n = 36) and ciprofol 0.4 mg/kg group (group C4, n = 31). Groups C2, C3 and C4 had injected IV with ciprofol 0.2, 0.3 and 0.4 mg/kg, respectively. Group P had injected IV with propofol 1.5mg/kg. The time for disappearance of the eyelash reflex, gastrointestinal endoscopy time, recovery time, and the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at awakening (T1), 15 minutes after awakening (T2) and 30 minutes after awakening (T3) were recorded. Compared with group P, the time to fall asleep was significantly shortened, and the incidence of nausea and vomiting and injection pain was significantly lower in groups C2, C3 and C4 (P < 0.05). There was no significant difference in recovery time and recovery quality between each group (P > 0.05). Compared with group P and C4, the incidence of hypotension and respiratory depression was significantly lower in groups C2 and C3 (P < 0.05). The appropriate dose of ciprofol for painless gastrointestinal endoscopy is more advantageous than propofol in hemodynamics and respiratory stability, with less injection pain and nausea and vomiting, which is worthy of clinical promotion.


Prevention of T2DM in women with a previous history of GDM.
Women with a history of gestational diabetes mellitus (GDM) have a high risk of progression to type 2 diabetes mellitus (T2DM). Risk factors are similar for GDM and T2DM and include, among others, obesity, family history, and ethnic background. GDM is also associated with the metabolic syndrome. Women with impaired glucose tolerance or "prediabetes" postpartum have the highest risk of progression. In women with impaired glucose tolerance, lifestyle modification or pharmacologic therapy may prevent or delay the onset of T2DM.


Production of Poly-3-Hydroxybutyrate (P3HB) with Ultra-High Molecular Weight (UHMW) by Mutant Strains of Azotobacter vinelandii Under Microaerophilic Conditions.
Poly-3-hydroxybutyrate (P3HB) is a biopolymer, which presents characteristics similar to those of plastics derived from the petrochemical industry. The thermomechanical properties and biodegradability of P3HB are influenced by its molecular weight (MW). The aim of the present study was to evaluate the changes of the molecular weight of P3HB as a function of oxygen transfer rate (OTR) in the cultures using two strains of Azotobacter vinelandii, a wild-type strain OP, and PhbZ1 mutant with a P3HB depolymerase inactivated. Both strains were grown in a bioreactor under different OTR conditions. An inverse relationship was found between the average molecular weight of P3HB and the OTRmax, obtaining a polymer with a maximal MW (8000-10,000 kDa) from the cultures developed at OTRmax of 5 mmol L-1 h-1 using both strains, with respect to the cultures conducted at 8 and 11 mmol L-1 h-1, which produced a P3HB between 4000 and 5000 kDa. The increase in MW of P3HB was related to the activity of enzymes involved in the synthesis and depolymerization. Overall, our results show that it is possible to modulate the average molecular weight of P3HB by manipulating oxygen transfer conditions with both strains (OP and PhbZ1 mutant) of A. vinelandii.


Sex change in plants: Old and new observations and new hypotheses.
Evidence is presented that individuals of a large number of dioecious and subdioecious plant species are able to alter their sexual state in response to changes in the ambient environment and/or changes in size or age. We suggest that lability of sexual expression probably has survival value where a significant portion of the females must otherwise bear the cost of fruit production in unfavorable environments. We demonstrate that in patchy environments of the proper scale and variability in quality, labile sexual expression will enhance an individual's genetic contribution to the next generation.