Neuroendoscopic-assisted versus mini-open craniotomy for hypertensive intracerebral hemorrhage: a retrospective analysis.
To compare outcomes in neuroendoscopic-assisted vs mini-open craniotomy for hypertensive intracerebral hemorrhage (HICH), so as to provide reasonable surgical treatment. Clinical data of 184 patients with HICH in the hospital from January 2019 to May 2021 were analyzed retrospectively. The patients were divided into mini-open craniotomy group and neuroendoscopic-assisted group. The operation time, hematoma clearance rate, intraoperative blood loss, neurological function recovery, and postoperative mortality of the two groups were compared by retrospective analysis. The operation time and intraoperative blood loss in the mini-open craniotomy group were more than those in the neuroendoscopic-assisted group, but there was no significant difference between the two groups. There was no significant difference in hematoma clearance rate between the two groups, but for the rugby hematoma, the hematoma clearance rate in the neuroendoscopic-assisted group was higher than in the mini-open craniotomy group, the difference was statistically significant. Within 1 month after the operation, there was no significant difference in mortality between the two groups. 6 months after the operation, there was no significant difference in the recovery of neurological function between the two groups. Neuroendoscopic-assisted and mini-open craniotomy for the treatment of HICH has the advantages of minimal trauma with good effects, and its main reason for short operation time, reduced bleeding, and high hematoma clearance rate. Although the two surgical methods can improve the survival rate of patients, they do not change the prognosis of patients. Therefore, the choice of surgical methods should be adopted based on the patient's clinical manifestations, hematoma volume, hematoma type, and the experience of the surgeon.


Bi-coordinate sound localization by the barn owl.
1. Binaurally time-shifted and intensity-unbalanced noise, delivered through earphones, induced owls to respond with a head-orienting behavior similar to that which occurs to free field auditory stimuli. 2. Owls derived the azimuthal and elevational coordinates of a sound from a combination of interaural time difference (ITD) and interaural intensity difference (IID). 3. IID and ITD each contained information about the azimuth and elevation of the signal. Thus, IID and ITD formed a coordinate system in which the axes were non-orthogonal. 4. ITD was a strong determinant of azimuth, and IID was a strong determinant of elevation, of elicited head turn.


Crystalline silica-induced macrophage pyroptosis interacting with mitophagy contributes to pulmonary fibrosis via modulating mitochondria homeostasis.
Environmental exposure to crystalline silica (CS) can lead to silicosis. Alveolar macrophages (AMs) play a crucial role in the pathogenesis of silicosis. Previously, we demonstrated that enhancing AMs mitophagy exerted protective effects on silicosis with a restrained inflammatory response. However, the exact molecular mechanisms are elusive. Pyroptosis and mitophagy are two different biological processes that determine cell fate. Exploring whether there were interactions or balances between these two processes in AMs would provide new insight into treating silicosis. Here we reported that crystalline silica induced pyroptosis in silicotic lungs and AMs with apparent mitochondria injury. Notably, we identified a reciprocal inhibitory effect between mitophagy and pyroptosis cascades in AMs. By enhancing or diminishing mitophagy, we demonstrated that PINK1-mediated mitophagy helped clear damaged mitochondria to negatively regulate CS-induced pyroptosis. While constraining pyroptosis cascades by NLRP3, Caspase1, and GSDMD inhibitors, respectively, displayed enhanced PINK1-dependent mitophagy with lessened CS-injured mitochondria. These observed effects were echoed in the mice with enhanced mitophagy. Therapeutically, we demonstrated abolishing GSDMD-dependent pyroptosis by disulfiram attenuated CS-induced silicosis. Collectively, our data demonstrated that macrophage pyroptosis interacting with mitophagy contributes to pulmonary fibrosis via modulating mitochondria homeostasis, which may provide potential therapeutic targets.


Mechanisms of persistence and impact of ordinary heterotrophic organisms in aerobic granular sludge.
The stability of granules, contaminant removal and microbial structure of an aerobic granular sludge (AGS) process were investigated with a focus on ordinary heterotrophic organisms (OHOs). Long-term stable granules and high removals of COD (97 %), NH4+ (98 %), P (85 %) and total N (77 %) were achieved. Sequencing analyses identified 6.6 % of phosphorus-accumulating organisms in the sludge, concordant with the observed bio-P removal capacity. However, OHOs were the most abundant bacteria in the sludge (70-93 %) without resulting in unstable aggregates. Under current dogmas of microbial competition in activated sludge, it seemed contradictory that OHOs could persist in the long term in the AGS where COD was depleted beginning in the anaerobic phase. Microbial analyses showed that OHOs could survive in granules by micropredation, proteolysis, fermentation and EPS consumption. Heterotrophic-nitrification/ aerobic-denitrification was an active pathway in the AGS. These findings contribute to a better understanding of microbial competition in AGS and its stability.


Does gender influence outcomes from a multidisciplinary intervention for quality of life designed for patients with advanced cancer?
Cancer treatment can profoundly impact the patient's quality of life (QOL). It has been well documented that there are gender differences in the symptoms associated with cancer treatment. This study explores the impact of gender on QOL for patients with newly diagnosed advanced cancer. A randomized, controlled clinical trial in patients receiving radiotherapy for advanced cancer demonstrated maintenance of QOL with a six session multidisciplinary structured intervention compared to controls. This current study reports the gender differences in that trial. Outcome measures included the functional assessment of cancer therapy-general (FACT-G), linear analog self-assessment (LASA), and profile of mood states (POMS) at baseline and weeks 4, 27, and 52. Kruskal-Wallis was used to compare QOL scores. One hundred thirty-one patients (45 women and 86 men, mean age 58.7) participated in the clinical trial. At week 4 postintervention, women in the intervention group had statistically significant improvement in their FACT-G score, FACT-G physical well-being subscale, LASA fatigue, POMS total score, POMS fatigue-inertia subscale, and POMS confusion-bewilderment subscale (p < 0.05). Men receiving the intervention had a smaller decrease in FACT-G score compared to controls (p = 0.048) and also worsened on the LASA financial (p = 0.02). At week 27, the only gender difference was that intervention group men had more POMS anger-hostility (p = 0.009). By week 52, there were no statistically significant gender differences in any of the QOL measures. Gender-based differences appear to play a role in the early, but not late, response to a multidisciplinary intervention to improve QOL for patients with advanced cancer, suggesting that early interventions can be tailored for each gender.


Prostaglandin D2 toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites.
Prostaglandin D2 (PGD2) is the most abundant prostaglandin in brain but its effect on neuronal cell death is complex and not completely understood. PGD2 may modulate neuronal cell death via activation of DP receptors or its metabolism to the cyclopentenone prostaglandins (CyPGs) PGJ2, Δ(12)-PGJ2 and 15-deoxy-Δ(12,14)-PGJ2, inducing cell death independently of prostaglandin receptors. This study aims to elucidate the effect of PGD2 on neuronal cell death and its underlying mechanisms. PGD2 dose-dependently induced cell death in rat primary neuron-enriched cultures in concentrations of ≥10μM, and this effect was not reversed by treatment with either DP1 or DP2 receptor antagonists. Antioxidants N-acetylcysteine (NAC) and glutathione which contain sulfhydryl groups that can bind to CyPGs, but not ascorbate or tocopherol, attenuated PGD2-induced cell death. Conversion of PGD2 to CyPGs was detected in neuronal culture medium; treatment with these CyPG metabolites alone exhibited effects similar to those of PGD2, including apoptotic neuronal cell death and accumulation of ubiquitinated proteins. Disruption of lipocalin-type prostaglandin D synthase (L-PGDS) protected neurons against hypoxia. These results support the hypothesis that PGD2 elicits its cytotoxic effects through its bioactive CyPG metabolites rather than DP receptor activation in primary neuronal culture.


Correction of Severe Secondary Cleft Lip Nasal Deformity.
The lower lateral cartilages (LLCs) are key elements for alar and tip support. Repositioning of both LLCs is an effective procedure for correcting a laterally spreading dome of LLCs and drooping nasal tip in cleft lip nasal deformity (CLND). The alar contour graft has become an essential component of rhinoplasty for correcting the concave or collapsed and retracted alar. Herein, onlay cartilage graft was combined with nasal tip plasty to correct hypoplastic cleft lateral crus or alar rim retraction, and with columella strut to obtain better aesthetic outcomes in patients with severe CLND. Seven patients with severe secondary unilateral CLND, including hypoplastic cleft lateral crus or alar rim retraction, underwent rhinoplasty from October 2013 to April 2020. Both LLCs were isolated and repositioned approximated medially using tip suture technique combined with columella strut. A septal cartilage onlay graft was applied on the hypoplastic cleft lateral crus. Cartilage graft on the nasal tip was performed to further project and enhance the nasal tip. Photogrammetric evaluation of the operated patients and statistical analysis of the obtained data were performed. The average age at operation was 23.5 (range: 17-36) years. The follow-up period was 6-36 (mean, 14.3) months. All patients were enrolled by photogrammetric evaluation. Height of the medial nostril and short axis of the nostril on the cleft side were increased with a statistical significance of P < 0.05, indicating that depressed ala on the cleft side, which is a feature of CLND, was corrected similar to that of the noncleft side. The alar contour cartilage graft, as an effective adjunctive technique, improves the alar margin, prevents the alar rim from collapsing, and provides supports to the cleft-side alar rim. It can be a prophylactic measure to prevent postoperative retraction in patients with weakened LLCs. Lower lateral cartilage repositioning, columellar strut, and nasal tip plasty are useful for correcting severe secondary unilateral CLND.


Conventional treatment integrated with Chinese herbal medicine improves the survival rate of patients with advanced non-small cell lung cancer.
The main objective of this study was to assess whether treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with Chinese herbal medicine (CHM), can improve the five-year survival rate in patients suffering from advanced non-small cell lung cancer (NSCLC), compared to patients treated by EGFR-TKIs alone. The study is based on information in the sub-dataset of the National Health Insurance Research Database (NHIRD) from years 2000 to 2010, during which time a total of 14,244 patients were diagnosed with NSCLC in Taiwan. After selection by exclusion criteria and matching process, 2,616 NSCLC patients were included in the study. Statistical analysis was utilized to evaluate the differences in characteristic distribution, and to compare the survival rates between the CHM cohort and non-CHM cohort. Patients with advanced NSCLC using CHM as an adjunct therapy exhibited a significantly improved survival rate [hazard ration (HR) = 0.8; 95% confidence interval (CI): 0.73-0.87, p value<0.001], compared with non-CHM users. Based on a survival analysis by Kaplan-Meier method, the 5-year survival rate of CHM users was 4.9% higher, with the most notable difference being an elevated 2-year survival rate of up to 12.75%. In addition to the survival rate analysis, we provide the ten most used single herbs and herbal formulas prescribed for patients with advanced NSCLC. This nationwide retrospective cohort study provides evidence supporting CHM as an effective adjunctive therapy to ameliorate the side effects of target therapy and prolong the five-year survival rate of patients with advanced NSCLC.


Enhancement of UDPgalactose: glycoprotein galactosyltransferase in cultured human skin fibroblasts by cationic polypeptides.
UDPgalactose : glycoprotein galactosyltransferase in normal human skin fibroblast homogenates has been assayed using ovalbumin as an acceptor. The activity in the homogenate fraction sedimenting between 51 300 X g and 105 000 X g was enhanced by the addition of a number of catonic polypeptides of L-configuration but not by those of D-configuration. In contrast to the enhancing effect of poly(L-lysine), poly(L-glutamic acid) inhibited the activity. Poly(D-glutamic acid) had no effect. Cationic or anionic amino acid derivatives, spermine or spermidine had no effect on activity. The enhancement of transferase activity by poly(L-arginine) is probably due to an increase in V for UDPgalactose and ovalbumin. The implication of these results for the regulation of glycoprotein synthesis in cultivated skin fibroblasts and for the pathogenesis of cystic fibrosis is discussed.


Contribution of large genomic rearrangements in PALB2 to familial breast cancer: implications for genetic testing.
PALB2 is the most important contributor to familial breast cancer after BRCA1 and BRCA2. Large genomic rearrangements (LGRs) in BRCA1 and BRCA2 are routinely assessed in clinical testing and are a significant contributor to the yield of actionable findings. In contrast, the contribution of LGRs in PALB2 has not been systematically studied. We performed targeted sequencing and real-time qPCR validation to identify LGRs in PALB2 in 5770 unrelated patients with familial breast cancer and 5741 cancer-free control women from the same Australian population. Seven large deletions ranging in size from 0.96 kbp to 18.07 kbp involving PALB2 were identified in seven cases, while no LGRs were identified in any of the controls. Six LGRs were considered pathogenic as they included one or more exons of PALB2 and disrupted the WD40 domain at the C terminal end of the PALB2 protein while one LGR only involved a partial region of intron 10 and was considered a variant of unknown significance. Altogether, pathogenic LGRs identified in this study accounted for 10.3% (6 of 58) of the pathogenic PALB2 variants detected among the 5770 families with familial breast cancer. Our data show that a clinically important proportion of PALB2 pathogenic mutations in Australian patients with familial breast cancer are LGRs. Such observations have provided strong support for inclusion of PALB2 LGRs in routine clinical genetic testing.


Insulin-loaded hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid hydrogels used as rectal suppositories to regulate the blood glucose of diabetic rats.
The purpose of this study was developing a novel hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid (HPMC-co-PAM-co-PMAA) hydrogel, which was used as rectal suppository to regulate the blood glucose of diabetes. HPMC-co-PAM-co-PMAA hydrogel was fabricated via free-radical polymerization. Fourier transform infrared spectroscopy (FTIR) and Raman spectra were used to confirm the fabrication of HPMC-co-PAM-co-PMAA hydrogel. Their inner morphology was observed with scanning electron microscope (SEM). The extracts of hydrogel were applied to study their cell viability. The hypoglycemic effects of insulin (INS)-loaded HPMC-co-PAM-co-PMAA hydrogels were investigated by rectal administration. FTIR and Raman spectra confirmed the obtaining of HPMC-co-PAM-co-PMAA hydrogels. Many micro-pores were found in the SEM photograph of HPMC-co-PAM-co-PMAA hydrogels. Cell experiments indicated that HPMC-co-PAM-co-PMAA hydrogel was out of cytotoxicity. In vitro release profiles showed that INS-loaded hydrogel could release INS at a continuous manner in pH 7.4 buffer (rectal conditions). Animal experiments suggested that INS-loaded hydrogel had an obvious hypoglycemic effect. Therefore, as a convenient and economic method of administration, INS-loaded HPMC-co-PAM-co-PMAA hydrogels could be used as rectal suppositories to regulate blood glucose.


Evaluation and treatment planning for patients with cleft lip and cleft palate.
The Oral-Facial and Communicative Disorders Program of the University of North Carolina has provided comprehensive diagnostic evaluation and inpatient and outpatient treatment for patients with cleft lip, cleft palate, and related problems for 22 years. A major aspect of the program is the initial diagnostic evaluation of patients and long-term follow-up evaluation of the results of treatment. The Oral-Facial and Communicative Disorders Program acts as both a consultant in providing requested information to referring professionals and agencies and also as a multi- and interdisciplinary treatment center. The nature of the evaluation process and the manner in which findings and recommendations are agreed upon in order that a comprehensive and coherent treatment plan can be established has been presented. It has been stressed that the needs of the patient can best be met by representatives from disciplines important to the diagnosis and management of patients with cleft lip and cleft palate who can meet together, and after discussion and negotiation arrive at a consensus for every aspect of treatment that is required, as well as a time that is most desirable for each patient.


Venous thromboembolism after shoulder arthroplasty: a systematic review.
Shoulder arthroplasty (SA) is a common orthopaedic procedure that is being performed on a more and more frequent basis. Venous thromboembolism (VTE) as a complication has received little attention when it occurs after SA. The literature lacks a comprehensive summary of the incidence, risk factors, and prophylaxis of VTE in this population of patients. Literature on VTE after SA has been identified from 5 scientific databases: EMBASE, MEDLINE, Web of Science, CINAHL, and Cochrane. All primary full-text articles reporting at least 1 case of deep vein thrombosis or pulmonary embolism after SA were included. Articles were critically appraised and systematically analyzed to determine the incidence, risk factors, thromboprophylaxis, diagnosis, and management of VTE after SA. This study included 14 articles. The reported incidence of VTE after SA was 0.2% to 16.0%. The most serious risk factors for development of VTE included history of VTE, thrombophilia, major surgery, advanced age, current malignant disease, immobility, and bed confinement. Diagnosis was typically determined by duplex scan and chest computed tomography scan. VTE prophylaxis was used in 6 (43%) of the included studies, with the ideal method of prophylaxis unknown. Although variability exists in the reported incidence of VTE, surgeons should still be aware of the potential for this serious complication after SA. We recommend assessing the risk factors and estimating the VTE risk status for all patients undergoing SA. The ideal method of prophylaxis for this population of patients remains unknown and should be investigated in future high-quality clinical studies.


Health-related quality of life in children and adolescents: subjective well being.
The main objective of this study was to build a model, which includes personal and social factors, that helps to highlight factors that promote health-related quality of Life (HRQoL) in children and in adolescents. A sample of 3195 children and adolescents was acquired from 5th and 7th graders from all five Portuguese regions. In this study three independent latent variables were specified--Physical, Psychological and Social and two dependent latent variables were measured: Health behavior and Quality of Life. The integrative model was composed by different components: (1) health-related quality of life, integrated by 8 dimensions from KIDSCREEN-52; (2) health behavior, (3) variables related to physical health; (4) variables related to social health; (5) variables related to psychological health. As results were found strong correlation between psychological dimensions and self-esteem and other factors and a structural equation model was developed. The model presented a RMSEA index of .08. Similarly, adjustment levels for the CFI, NFI and IFI vary above or around .90, which suggests a good adjustment for the hypothesized model. The model presented significant qui-square. This study showed that in all the samples studied, the psychological variables were those that contributed at a superior level to HRQoL.


Reduced cortical serotonin 5-HT2A receptor binding and glutamate activity in high compulsive drinker rats.
Serotonin2A receptors and glutamate signaling have been implicated in the pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced Polydipsia (SIP), characterized by excessive drinking under intermittent food reinforcement schedules, is a valid model for studying the compulsive phenotype in rats. We explored the expression, function, and neurochemistry of 5-HT2A receptors in the frontal cortex (FC) of rats with individual differences to compulsivity. Rats were selected for high (HD) versus low (LD) drinking on SIP. First, we measured 5-HT2A, 5-HT1A, and mGlu2/3 receptors and serotonin transporter binding in different brain regions. Second, we assessed the effect of microinfusion into the medial prefrontal cortex (mPFC) of the 5-HT2A/C receptor agonist DOI, the mGlu2/3 agonist LY379268, and the combination of DOI with the 5-HT2A receptor antagonist M100907 and the 5-HT2C receptor antagonist SB242084. Finally, we measured the serotonin and glutamate efflux in mPFC in basal condition and after DOI local application. The compulsive HD rats showed a specific reduction of 5-HT2A receptor binding in FC compared to LD rats. The highest dose of DOI reduced compulsive drinking in HD rats on SIP, whereas LY379268 did not induce any significant effect. The 5-HT2A receptor antagonist M100907 reversed the DOI induced reduction on compulsive drinking in HD rats while blocking the 5-HT2C receptor did not affect SIP. Compulsive HD rats showed increased serotonin and decreased glutamate efflux in basal conditions that were modified by the DOI application. These findings indicate that reduced 5-HT2A receptor binding and glutamate neurochemical mechanisms may underlie compulsive behavior vulnerability.


Confirmatory validation of the factor structure and psychometric properties of the Difficulties in Emotion Regulation Scale-Positive.
Emotion dysregulation is a transdiagnostic factor central to the etiology and treatment of various clinical difficulties. Yet, research in this area has focused almost exclusively on emotion dysregulation stemming from negative emotions. The current study confirmed the factor structure of the Difficulties in Emotion Regulation Scale-Positive (DERS-P) and further examined its reliability and validity. Participants in Study 1 were 229 college students (M age = 19.37 years; 66.8% female; 67.2% White). Participants in Study 2 were 353 trauma-exposed community individuals ( M age = 35.77 years; 57.8% female; 71.2% White). Findings supported the three-factor structure of the DERS-P. Mean levels of the DERS-P scales demonstrated convergent and discriminant validity and differentiated individuals with (vs. without) probable posttraumatic stress disorder, depression, alcohol use, and drug use disorders. Findings provide additional support for the factor structure, reliability, and validity of the DERS-P, thereby adding to its clinical utility.


Association between lipid-lowering agents and severe hyponatremia: a population-based case-control study.
Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. This was a register-based case-control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22-1.35) for statins, 1.09 (0.79-1.47) for ezetimibe, 1.38 (0.88-2.12) for fibrates, and 2.12 (1.31-3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64-0.74) for statins, 0.60 (0.41-0.86) for ezetimibe, 0.87 (0.51-1.42) for fibrates, and 1.21 (0.69-2.06) for resins. Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias.


States of contra-lateral rotator cuff - Based on bilateral shoulder ultrasound results of 401 patients.
For patients with rotator cuff tear (RCT), the contra-lateral shoulders have higher risk of RCT than general population. It has been proved by several previous studies. The focus of this study is to obtain the data of contra-lateral rotator cuff tear in Chinese population, and to find the rules of contra-lateral rotator cuff tear through statistical analysis. From March 2016 to January 2020, patients who underwent shoulder arthroscopic surgery were included in the study, we conduct bilateral shoulder ultrasound before surgery, patients information collection include gender, age, occupation and whether received contra-lateral rotator cuff surgery within 1-3 years. The above information was statistically analyzed. According to the inclusion and exclusion criteria, 401 patients were included. The incidence of contra-lateral rotator cuff tear was 24.3%, 5.58% of them underwent contra-lateral rotator cuff repair surgery within 3 years. The degree of contra-lateral rotator cuff tear was positively correlated with the degree of the primary side; Patients with full-thickness rotator cuff tear were more likely to have contra-lateral rotator cuff tear than patients with partial rotator cuff tear. For patients with supraspinatus tendon tear, the contra-lateral rotator cuff tear risk increases, For patients with subscapularis muscle tear, the contra-lateral rotator cuff tear risk doesn't increases. Contra-lateral rotator cuff tear is related to age, the risk of contra-lateral rotator cuff tear is higher in elderly patients. The contra-lateral RCT data obtained in our study was 24.3%, significantly lower than that of previous studies. The reasons may include ethnic variation, lifestyle, and proportion of heavy physical labor. The condition of contra-lateral rotator cuff is closely related to affected side rotator cuff tear.


Four-color multiplex reverse transcription polymerase chain reaction--overcoming its limitations.
Quantitative reverse transcription polymerase chain reaction (qRT-PCR) conducted in real time is a powerful tool for measuring messenger RNA (mRNA) levels in biological samples. Multiplex PCR is defined as the simultaneous amplification of two or more DNA (cDNA) targets in a single reaction vessel and may be carried out only using uniquely labeled probes for each target. Up to four genes can be detected in a multiplex 5' nuclease assay when using the appropriate instrument and the right combination of fluorophores. One of the more important advantages of multiplexing is a reduced sample requirement, which is especially important when sample material is scarce. Additional benefits are saving time on reaction setup and lower cost compared to singleplex reactions. Although multiplexing has several advantages over singleplex qRT-PCR, limited work has been done to show its feasibility. Few publications on four-color multiplex qRT-PCR have been reported, and to our knowledge no work has been done to explore the assay's limitations. In this paper, we report the first in-depth analysis of a four-gene multiplex qRT-PCR. To achieve a better understanding of the potential limitations of the qRT-PCR assay, we used in vitro transcribed RNA derived from four human genes. To emulate gene expression experiments, we developed a model system in which the in vitro transcripts were spiked with plant total RNA. This model allowed us to develop an artificial system closely resembling differential gene expression levels varying up to a million fold. We identified a single "universal" reaction condition that enabled optimal amplification in real time of up to four genes over a wide range of template concentrations. This study shows that multiplexing is a feasible approach applicable to most qRT-PCR assays performed with total RNA, independent of the expression levels of the genes under scrutiny.


Numerical and temporal relationships in a three-level food chain.
Densities were examined in natural populations consisting of horsenettle (Solanum carolinense), larvae of a horsenettle-specific phytophagous moth (Frumenta nundinella), and a polyphagous parasitoid wasp (Scambus pterophori), that parasitized the moth. Herbivore and parasitoid densities were both positively associated with fruit density, but moth larval density was linear while parasitoid density increased parabolically; thus, optimum moth survivorship was at intermediate moth densities. There was no evidence of escape from herbivory in time by plant populations due to either mean flowering date or a spread of flowering in seasonal time. However, one plant population and one moth population apparently escaped in space due to isolated location. Although plant reproductive success is reduced whether or not moth larvae are parasitized, both presence of a numerical herbivore refuge and parasitoid attack at high fruit and moth densities would be expected to stabilize long-term temporal dynamics of this simple food chain.


Societal awareness on neonatal hyperbilirubinemia: A systematic review and meta-analysis.
Early recognition of neonatal hyperbilirubinemia is essential for prevention of bilirubin neurotoxicity and its long-term sequelae. High rates of home delivery in low- and middle-income countries (LMICs) as well as early discharge post-delivery (within 24hours) make community surveillance for neonatal hyperbilirubinemia highly important. Here, we performed a literature review to estimate the level of societal awareness of neonatal hyperbilirubinemia. We searched several databases for studies assessing the knowledge and awareness of neonatal hyperbilirubinemia. We retrieved 211 citations from 206 databases with five being in the grey literature. 52 selected articles were further reviewed. Data from these studies were then analyzed using Stata software (Statacorp® LLC Texas USA). We found that the pooled estimate of societal awareness of neonatal hyperbilirubinemia was 67% (95% confidence interval [CI]: 60, 74). There however was a publication bias (Begg test: P ≤ 0.01; Egger P = 0.06). Studies that scored or graded knowledge reported lower estimates [adjusted odds ratio (aOR) = -0.17; 95% CI: -0.32-0.02; P = 0.03]. Hospital location was an important determinant of awareness of complications [aOR = 0.30; 95% CI: 0.30-0.57; P = 0.03]. We therefore concluded that there is a significant need to improve societal awareness of neonatal hyperbilirubinemia.


Physical activity growth curves relate to adiposity in adolescents.
Findings from prospective studies on associations between physical activity and adiposity among youth are inconsistent. Our aim was to describe physical activity trajectories during secondary school and examine the association with change in adiposity in youth. Physical activity was measured in 20 survey cycles from 1999 to 2005; anthropometrics were measured in survey cycles 1, 12, and 19. Individual growth curves modeling moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) were estimated. Estimates of initial level and rate of decline in MVPA and VPA bouts per week were included as potential predictors of body fat% and body mass index using age- and sex-specific linear regression. Complete data were available for 840 and 760 adolescents aged 12-13 years at baseline, followed from survey cycles 1-12 and 12-19, respectively. Among girls, yearly declines of one MVPA and one VPA bout per week during earlier adolescence were associated with increases of 0.19 (95% confidence interval [CI], 0.02-0.36) and 0.47 (95% CI, 0.015-0.92) units of body fat%, respectively. In boys, a yearly decline of one MVPA bout per week was associated with an increase of 0.38 (95% CI, 0.05-0.70) units of body fat% during later adolescence. Obesity prevention programs should include strategies to prevent declines in physical activity.


[Impact of a motivational intervention on coping with chronic pain: results of a controlled efficacy study].
For effective self-management of chronic pain changes of cognitive and behavioral attitudes are required. The readiness to change can be described within the framework of the transtheoretical model (TTM) and is facilitated through motivational interviewing. This prospective study evaluated the effectiveness of brief motivational interviewing by telephone for the variables self-efficacy, cognitive and behavioral coping and psychological strain through chronic pain over a period of 9 months. Different questionnaires, the self-efficacy expectations (ASES-D), cognitive, behavioral coping and psychological strain through chronic pain (FESV) and the German version of the pain stages of change questionnaires (PSOCQ), the FF-STABS were distributed to 147 patients at a rehabilitation clinic (indications: fibromyalgia syndrome, rheumatoid arthritis, ankylosing spondylitis). The intervention group participants received 3 telephone calls at intervals of 2 months with a follow-up time of 9 months after first study admission. At the end of the study 91 patients were enrolled for analysis (drop out rate 38%). To evaluate the effects of treatment nonparametric-analysis for longitudinal data was used. The analysis showed significant positive effects in the intervention group for cognitive coping (U-value -2.423; p=0.015 group x time-effect) and for coping with emotional strains of chronic pain (subscale anxiety: U-value -2.3618; p=0.018; subscale anger: U-value 2.8638; p=0.004; group x time-effect). No significant effects were shown for self-efficacy expectations and behavioral coping with pain. Further explorative analysis of subgroups revealed slightly better treatment effects for patients with rheumatoid arthritis and ankylosing spondylitis than for those with fibromyalgia syndrome.


Brain dynamics, psychophysiological uncertainty and behavioral learning.
The present paper takes a first step toward the integration of recent findings on brain dynamics and learning into established fields of psychophysiological science. Leading-edge studies of brain dynamics have shown that the brain manifests an inherent variability and that, when new stimuli (i.e., "problems") are presented to the organism, brain chaos increases. Similarly, many previous studies using a wide variety of physiological and behavioral measures have shown that "psychophysiological uncertainty" is associated with novel stimuli, novice behavioral performance, and new stimulus-stimulus and response-stimulus contingencies. Such uncertainty may ultimately be resolved through some form of learning. Along with the general changes in physiological and behavioral activity, increases in brain chaos may usher the organism into an exploratory mode which serves as a catalyst for learning.


Answers and questions from the KvAP structures.
The recent landmark structures of KvAP, a voltage-gated potassium (Kv) channel, provide the first high-resolution experimental structural models of this class of proteins. Previous extensive studies of Kv channels provide a means to evaluate and interpret the KvAP structures. In this minireview, we survey different experimental approaches to Kv channels and map these findings to KvAP, showing that the relationship between the KvAP structures and other Kv channels is uncertain.


Pronounced lipoprotein lipid reduction obtained by combined lipid-lowering treatment in patients with atherosclerotic disease.
The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.


Myostatin inhibits proliferation of human urethral rhabdosphincter satellite cells.
Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti-neural cell adhesion molecule antibody. The cells were transfected with simian virus-40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real-time reverse transcription polymerase chain reaction and immunoneutralization using an anti-myostatin antibody was also evaluated. Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.


Patient safety: break the silence.
A culture of patient safety requires commitment and full participation from all staff members. In 2008, results of a culture of patient safety survey conducted in the perioperative division of the Lehigh Valley Health Network in Pennsylvania revealed a lack of patient-centered focus, teamwork, and positive communication. As a result, perioperative leaders assembled a multidisciplinary team that designed a safety training program focusing on Crew Resource Management, TeamSTEPPS, and communication techniques. The team used video vignettes and an audience response system to engage learners and promote participation. Topics included using preprocedural briefings and postprocedural debriefings, conflict resolution, and assertiveness techniques. Postcourse evaluations showed that the majority of respondents believed they were better able to question the decisions or actions of someone with more authority. The facility has experienced a marked decrease in the number of incidents requiring a root cause analysis since the program was conducted.


Global establishment threat from a major forest pest via international shipping: Lymantria dispar.
The global shipping network is widely recognised as a pathway for vectoring invasive species. One species of particular concern is Lymantria dispar (gypsy moth). Two subspecies, L. d. asiatica and L. d. japonica (herein referred to as Asian Gypsy Moth - AGM) are of considerable concern as ships arriving to a number of countries have been found carrying AGM egg masses. However, ships carrying AGM eggs can only threaten a country at ports located in a climatically suitable region. We present a CLIMEX model of climate suitability and combine this with international shipping to estimate the global threat from AGM. We find that for the USA more than half of international ships (approximately 18,000 ships) arrive to climatically suitable ports. Other countries with a large number of ships arriving to ports with suitable climates include Canada and Brazil. This is the first global analysis of the invasion threat from AGM, and we recommend countries focus AGM-inspection programs towards ships arriving at ports found within climatically suitable regions.


Barrel cortical neurons and astrocytes coordinately respond to an increased whisker stimulus frequency.
Nerve cells program the brain codes to manage well-organized cognitions and behaviors. It remains unclear how a population of neurons and astrocytes work coordinately to encode their spatial and temporal activity patterns in response to frequency and intensity signals from sensory inputs. With two-photon imaging and electrophysiology to record cellular functions in the barrel cortex in vivo, we analyzed the activity patterns of neurons and astrocytes in response to whisker stimuli with increasing frequency, an environmental stimulus pattern that rodents experience in the accelerated motion. Compared to the resting state, whisker stimulation caused barrel neurons and astrocytes to be activated more synchronously. An increased stimulus frequency up-regulated the activity strength of neurons and astrocytes as well as coordinated their interaction. The coordination among the barrel neurons and astrocytes was fulfilled by increasing their functional connections. Our study reveals that the nerve cells in the barrel cortex encode frequency messages in whisker tactile inputs through setting their activity coordination.


An examination of the factors influencing the bioaccumulation of methylmercury at the base of the estuarine food web.
Estuarine systems have received ongoing mercury (Hg) inputs from both point sources and regional contamination and have high legacy Hg in sediments. This is an environmental concern given that coastal seafood is an important vector for human exposure to methylmercury (MeHg). The base of the food chain represents the most important trophic steps for MeHg bioaccumulation. The magnitude of the uptake by phytoplankton, and their consumers, is influenced by many factors, in addition to sediment and water MeHg concentrations, that impact MeHg assimilation into phytoplankton and the trophic transfer to higher trophic levels, both benthic and pelagic. For forage fish, such as mummichogs (Fundulus heteroclitus), abiotic and biotic (bioenergetic) factors can influence their MeHg content, and diet is also important as they feed both on benthic and pelagic prey. Given that the importance of sediment MeHg versus pelagic MeHg sources has been debated, we updated a phytoplankton bioaccumulation model, and coupled this with a bioaccumulation model for MeHg concentration in mummichog tissue to examine the controlling factors for sites, from Maine to Maryland, USA, ranging widely in their Hg concentrations and other variables. The study highlighted the importance of DOC in modulating uptake into the pelagic food web, but also demonstrated the importance of diet in controlling mummichog MeHg. Finally, the relative importance of MeHg source - sediment or water column - was correlated with the level of Hg contamination. Sediment-derived MeHg was a more important source for highly Hg contaminated systems. As water column and sediment MeHg are not strongly correlated for the studied ecosystems, their importance as a source of MeHg to mummichogs varies with location. The study highlights the differences across ecosystems in MeHg bioaccumulation pathways, and that uptake into phytoplankton is an important variable controlling forage fish concentration.


Influence of Physical Activity on Blood Pressure in Children With Overweight/Obesity: A Randomized Clinical Trial.
The prevalence of childhood hypertension (HT) is growing exponentially, influenced by environmental factors such as foods with high salt content, sedentary lifestyles, and poor-quality food. The incidence of HT is about 10.4% in well-nourished children, but when associated with obesity or overweight, this can rise to 38% and 68%, respectively. To assess the influence of physical activity on the blood pressure (BP) of children who are overweight or obese. This randomized clinical trial was carried out in Granada (Spain), from October 2015 to June 2016. The sample consisted of 98 children, all of whom were overweight or obese. The intervention group (IG) (n = 49) practised physical activity and received nutritional advice, while the control group (n = 49) only received theoretical-practical sessions on nutrition. Body composition was measured, a nutritional assessment was made and BP was determined (in percentiles, to avoid the misclassification of children who are located at the extremes of normal growth). Before the physical activity intervention, 85.7% of the children in the IG (with overweight/obesity) were in the 95th or higher percentile for BP, a situation representative of high BP (HT). However, by the end of the study period, this value had decreased significantly (P = 0.001), to 16.13%. Childhood obesity is a risk factor for HT. Physical activity, together with nutritional advice, effectively reduces BP in children who are overweight or obese. The use of percentiles, according to age, weight, and height, is an effective means of measuring BP. This study is registered at https://www.clinicaltrials.gov (identifier NCT02779647).


Use of angio computed tomography to evaluate extent of endometrial carcinoma.
Patients with endometrial carcinoma underwent angio computed tomography (CT) prior to surgery to evaluate the extent of the carcinoma. The subjects of the study were 87 patients operated on at the Cancer Institute Hospital during the period 1983 to 1986. After preoperative bilateral internal iliac angiography, angio CT was performed using the already inserted catheters. Although the intact uterine wall was enhanced by the angio CT, the cancerous lesion was not, which permitted easy recognition of the cancerous lesion as a low-density area. To evaluate the degree of myometrial invasion, the minimal thickness of intact uterine wall was measured in the CT image, and was compared later with findings from the operative materials. The comparison showed that for all the patients, the minimal thickness of the intact uterine wall as shown in the CT image was comparable to the actual minimal thickness of the operative materials. Because depth of myometrial invasion is known as an important prognostic factor, measurement of the minimal thickness of the intact uterine wall as shown in the CT image is useful as an objective prognostic factor. Angio CT facilitates recognition of myometrial invasion preoperatively.


Functional properties and structural changes of rice proteins with anthocyanins complexation.
This study investigated the functional properties and structural changes associated with the complexation of rice protein (RP) with anthocyanins (ACN). Furthermore, fractions (i.e., albumin, globulin, prolamin and glutelin) isolated from RP complexed with anthocyanins were examined. The interactions with ACN altered the structure of RP, leading to an increase in the β-sheet and spectral shift of the amide Ⅱ band. Additionally, fluorescence spectroscopy suggested that the hydrophobic and hydrogen bonds were the dominant forces in the formation of RP-ACN complexes. It was interesting to find that the RP-ACN particles exhibited the best functional properties at pH 3, likely due to the specific conformational changes upon interaction. In addition, the combination of RP and ACN increased the antioxidant ability of RP. Overall, this research suggested that RP-ACN particles at pH 3 can be designed to form and stabilize mesostructures such as foams and emulsion, which can lead to health benefits.


The effects on merino lambs of chronic infection with Trichostrongylus rugatus.
Four groups of six 5-month-old merino lambs were exposed to infection with 12,000 larvae of Trichostrongylus rugatus per week and one group was killed at each of 3, 6, 9 and 12 weeks. Numbers of adult worms increased in an approximately linear manner throughout the experiment; the percentage of larvae developing to adults remained between 35 and 25% throughout the course of the experiment. Sub-total villus atrophy was evident in the anterior small intestine of each group of infected sheep and significant reductions occurred in the plasma concentrations of albumin and phosphate. Serum globulin and calcium concentrations rose in infected animals. No clinical signs were observed in infected sheep, no alteration in bone histology was detected and no decrease in growth rate occurred.


The U.S. medicine chest: Understanding the U.S. pharmaceutical supply chain and the role of the pharmacist.
The U.S. capacity to manufacture key essential medications has diminished. The U.S. pharmaceutical supply chain (USPSC) has diversified and now relies on international sources of active pharmaceutical ingredients and finished drug products (FDPs). Despite years of effort raising concerns about the USPSC, pharmacists and pharmacy technicians continue to spend a substantial amount of time and energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes related to low-quality medications. The extent of U.S. reliance on foreign sources of medications is largely unknown. Pharmacists do not have a reliable way to determine the country of origin (i.e., source), capacity, or geographic location of pharmaceutical manufacturers, limiting our ability to anticipate challenges or mitigate risks to our Nation's drug supply. The U.S. Food and Drug Administration's task of regulating quality and safety is challenging and will likely require additional safeguards and resources. In addition to pharmacists' engagement, solutions will likely need to leverage a mix of policy, economic incentives, and expanded objective surveillance testing. The U.S. pharmaceutical supply chain is complex, global, and goes beyond FDPs. The 2020 American Pharmacists Association House of Delegates has rightly asserted that "The quality and safety of pharmaceutical and other medical products and the global pharmaceutical and medical product supply chain are essential to the United States national security and public health." Pharmacy professionals on the front line engage with patients, identify medication-related issues, and engage in drug-procurement decisions. Pharmacists are essential to our nation's overall health and must be engaged in the development and implementation of strategies to safeguard the USPSC.


FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer.
Estrogen receptor α (ERα) is a transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast cancers. The molecular mechanisms underlying the up-regulation of ERα activity, however, remain poorly understood. We identified FK506-binding protein 52 (FKBP52) as a factor associated with poor prognosis of individuals with ERα-positive breast cancer. We found that FKBP52 interacts with breast cancer susceptibility gene 1 and stabilizes ERα, and is essential for breast cancer cell proliferation. FKBP52 depletion resulted in decreased ERα expression and proliferation in breast cancer cell lines, including MCF7-derived fulvestrant resistance (MFR) cells, suggesting that inhibiting FKBP52 may provide a therapeutic effect for endocrine therapy–resistant breast cancer. In contrast, FKBP51, a closely related molecule to FKBP52, reduced the stability of ERα. Consistent with these findings, FKBP51 was more abundantly expressed in normal tissues than in cancer cells, suggesting that these FKBPs may function in the opposite direction. Collectively, our study shows that FKBP52 and FKBP51 regulate ERα stability in a reciprocal manner and reveals a regulatory mechanism by which the expression of ERα is controlled.


Blood and brain ethanol concentrations during absorption and distribution in long-sleep and short-sleep mice.
It is often assumed that blood ethanol content accurately reflects brain ethanol content. In previous studies we have found that at the time of regaining the righting response blood and brain ethanol levels were identical, and blood ethanol could be used to predict brain ethanol level. It is likely, however that shortly after the administration of ethanol, blood and brain ethanol levels would differ. For this study, venous blood (orbital sinus) and brain ethanol levels were measured in long-sleep and short-sleep mice within the first 30 min following ethanol administration (2.5-6.0 g/kg). Ethanol was administered intraperitoneally or intragastrically. For both lines of mice and for every dose, brain ethanol concentrations were significantly greater (as much as 100 mg/dl) than blood ethanol levels for the first 6 min, and peak blood and brain ethanol levels were reached 4 to 6 min after dosing. Approximately 6 to 10 minutes (depending on dose and line of mouse) was required for blood and brain concentrations to reach equilibrium. At the time of loss of the righting response, brain ethanol levels were significantly higher than blood ethanol levels. These results indicate that within the first 6 min after administration of ethanol, blood ethanol level is not suitable for the assessment of brain ethanol content.


Separation of rat liver lysosome membrane adenosine triphosphatase activities by polyacrylamide gel electrophoresis.
Solubilization of rat liver lysosome membranes with octyl glucoside or lauryl sarcosinate and analysis of ATPase activities in sections of polyacrylamide gels after electrophoresis revealed one major peak at pH 8 and two peaks at pH 5. The pH 8 ATPase peak was not localized in the same peak with pH 5 ATPase activity, suggesting that these were catalyzed by different proteins. Ca2+- and Mg2+-ATPase activities at pH 8 were present in the same major peak, with Ca2+ activity predominating. The pH 8 Ca2+-ATPase was also not present in the same area of the gels as Ca2+-ADPase.


A Comparison of Methods for Identifying Informal Carers: Self-Declaration Versus a Time Diary.
Two main methods for identifying whether an individual is an informal carer are self-declaration and the use of a time diary. We analysed the level and predictors of agreement between these two methods among co-residential informal carers of adult recipients. We used the 2014/15 UK Time Use Survey, which is a large-scale household survey for those aged 8 years old and over. It contains an individual questionnaire for self-declaration and a time diary for activity-based identification that records all activity in 10-min slots for two 24-h periods. Our analysis: (i) assesses the degree of overlap across approaches; (ii) explores the differences in characteristics between carers identified via one approach relative to non-carers using a bivariate probit estimator; and (iii) shows what factors are associated with being identified by both approaches using two independent probit estimators. Out of 6301 individuals, we identified 545 carers (8.6%) by at least one method and only 104 (19.1% of 545 carers) by both methods. We found similar factors predicted caregiving using either method but the magnitudes of the effects of these factors were larger for self-declared carers. Activity-based carers who provided more activities to a dependent adult and spent more time caregiving were more likely to also self-declare. Our results show low levels of agreement between the two main methods used to identify informal carers. Any assessment of current caregiving research or future means to collect caregiving information should pay particular attention to the identification method as it may only relate to certain carer groups.


Co-occurrence of sexual risk behaviors and substance use across emerging adulthood: evidence for state- and trait-level associations.
Prior research has suggested that problematic alcohol and drug use are related to risky sexual behaviors, either due to trait-level associations driven by shared risk factors such as sensation seeking or by state-specific effects, such as the direct effects of substance use on sexual behaviors. Although the prevalence of both high-risk sexual activity and alcohol problems decline with age, little is known about how the associations between substance use disorder symptoms and high-risk sexual behaviors change across young adulthood. Using a community sample (n = 790) interviewed every 3 years from age 21 to age 30 years, we tested trait- and state-level associations among symptoms of alcohol and drug abuse and dependence and high-risk sexual behaviors across young adulthood using latent growth curve models. We utilized diagnostic interviews to obtain self-report of past-year drug and alcohol abuse and dependence symptoms. High-risk sexual behaviors were assessed with a composite of four self-reported behaviors. Results showed time-specific associations between alcohol disorder symptoms and risky sexual behaviors (r = 0.195, P < 0.001), but not associations between their trajectories of change. Conversely, risky sexual behaviors and drug disorder symptoms were associated only at the trait level, not the state level, such that the levels and rate of change over time of both were correlated (r = 0.35, P < 0.001). High-risk sexual behaviors during young adulthood seem to be driven both by trait and state factors, and intervention efforts may be successful if they are either aimed at high-risk individuals or if they work to disaggregate alcohol use from risky sexual activities.


Oral calcium promotes pigment gallstone formation.
Dietary calcium supplementation has been recommended for prevention of osteoporosis and has become a standard component of most "health food" diets. Biliary calcium has been recognized to play a central role in the formation of pigment gallstones. We have recently demonstrated that 5 days of oral calcium supplementation significantly increases biliary calcium in the prairie dog (K. D. Lillemoe, T. H. Magnuson, G. E. Peoples, et al., Gastroenterology 94: A563, 1988). We hypothesized, therefore, that long-term oral calcium supplementation would promote pigment gallstone formation. Sixteen adult male prairie dogs were maintained on a standard nonlithogenic diet. Eight animals received calcium supplementation (2.5 x control levels) in their water, while the remaining eight animals served as controls. After 8 weeks, cholecystectomy was performed, and the common bile duct was cannulated. Bile was examined microscopically and analyzed for ionized calcium, bilirubin, glycoprotein, and biliary lipids. The cholesterol saturation index (CSI) was calculated. Pigment stones and calcium bilirubinate sludge were present in all animals receiving calcium supplementation. Only one control animal had evidence of pigment stones (P less than 0.001). Biochemical analysis of gallbladder bile demonstrated a significant increase in total bilirubin and bilirubin monoglucuronide (P less than 0.01) as well as bile glycoprotein content (P less than 0.05) after oral calcium supplementation. Gallbladder bile ionized calcium was also increased although not significantly. These data suggest that oral calcium supplementation promotes gallbladder sludge and pigment gallstone formation in the prairie dog. This observation raises concern that oral calcium supplementation, especially in the older female population, may enhance gallstone formation.


Repression precedes independent evolutionary gains of a highly specific gene expression pattern.
Highly specific expression patterns can be caused by the overlapping activities of activator and repressor sequences in enhancers. However, few studies illuminate how these sequences evolve in the origin of new enhancers. Here, we show that expression of the bond gene in the semicircular wall epithelium (swe) of the Drosophila melanogaster male ejaculatory bulb (EB) is controlled by an enhancer consisting of an activator region that requires Abdominal-B driving expression in the entire EB and a repressor region that restricts this expression to the EB swe. Although this expression pattern is independently gained in the distantly related Scaptodrosophila lebanonensis and does not require Abdominal-B, we show that functionally similar repressor sequences are present in Scaptodrosophila and also in species that do not express bond in the EB. We suggest that during enhancer evolution, repressor sequences can precede the evolution of activator sequences and may lead to similar but independently evolved expression patterns.


Manual asymmetries of motor sequencing in boys with reading disability.
Boys with reading disability were asked to tap two mechanical keys in time to the beat of a metronome, with left and right hand alone, and with alternating hands. On the single hand trials these boys tapped as well as normal boys with both left and right hands, but when asked to alternate hands, their tapping stability, particularly of the left hand, deteriorated significantly and was worse than that of much younger normal boys. It is argued from evidence from patients with surgical commissurotomies that the motor deficiency in synchronizing left and right hands may be due to a disturbance in interhemishperic cooperation in the boys with reading disability, and it is suggested that the reading problems of these children may be the consequence of a developmental delay in interhemispheric cooperation.


Spectrophotometric determination of titanium with o-carboxyphenylfluorone in cationic micellar media, and its equilibrium and kinetic studies.
Spectrophotometric determination of titanium(IV) was accomplished with o-carboxyphenylfluorone (OCPF) in the presence of hexadecyltrimethyl ammonium chloride (HTAC) under strongly acidic media. In the determination of titanium(IV), Beer's law was obeyed in the range of 24-340 ng mL(-1) with an effective molar absorption coefficient (at 530 nm) and relative standard deviation of 2.24 × 10(5)dm(3)mol(-1)cm(-1) and 0.64% (n=8), respectively. The severe interference of iron ions was easily eliminated by the addition of ethylenediaminetetraacetic acid (EDTA); the effects of other foreign substances were low. Equilibrium and kinetic studies under analytical conditions were investigated to quantitatively evaluate the reaction mechanism. The obtained orange complex is considered to be Ti(OCPF)(4). Its stability log K(f) and rate constant K(obs) are 16.88 and 1.65 × 10(-2)s(-1), respectively. It is suggested that the color of the complex is related to the species of OCPF in the solution.


Increasing antituberculosis drug resistance in the United Kingdom: analysis of National Surveillance Data.
To identify recent trends in, and factors associated with, resistance to antituberculosis drugs in England, Wales, and Northern Ireland. Cohort of tuberculosis cases reported to the enhanced tuberculosis surveillance system matched to data on drug susceptibility and national strain typing data. England, Wales, and Northern Ireland 1998-2005. Unadjusted and adjusted odds ratios for drug resistance and associated factors. Proportion of multidrug resistant tuberculosis cases clustered. 28 620 culture confirmed cases were available for analysis. The proportion of cases resistant to isoniazid increased from 5% to 7%. Rifampicin resistance increased from 1.0% to 1.2% and multidrug resistance from 0.8% to 0.9%. Ethambutol and pyrazinamide resistance remained stable at around 0.4% and 0.6%, respectively. Regression analyses showed a significant increase in isoniazid resistance outside London (odds ratio 1.04, 95% confidence interval 1.01 to 1.07, a year, associated with changes in age (0.98, 0.98 to 0.99, a year), place of birth (1.49, 1.16 to 1.92), and ethnicity (P<0.05). In London, the rise (1.05, 1.02 to 1.08, a year) was related mainly to an ongoing outbreak. Increases in rifampicin resistance (1.06, 1.01 to 1.11, a year) and multidrug resistance (1.06, 1.00 to 1.12, a year) were small. A fifth of patients with multidrug resistant tuberculosis in 2004-5 had indistinguishable strain types, and one case was identified as extensively drug resistant. The rise in isoniazid resistance reflects increasing numbers of patients from sub-Saharan Africa and the Indian subcontinent, who might have acquired resistance abroad, and inadequate control of transmission in London. The observed increases highlight the need for early case detection, rapid testing of susceptibility to drugs, and improved treatment completion.


Effects of diurnal variations in temperature on non-accidental mortality among the elderly population of Montreal, Québec, 1984-2007.
The association between ambient temperature and mortality has been studied extensively. Recent data suggest an independent role of diurnal temperature variations in increasing daily mortality. Elderly adults-a growing subgroup of the population in developed countries-may be more susceptible to the effects of temperature variations. The aim of this study was to determine whether variations in diurnal temperature were associated with daily non-accidental mortality among residents of Montreal, Québec, who were 65 years of age and over during the period between 1984 and 2007. We used distributed lag non-linear Poisson models constrained over a 30-day lag period, adjusted for temporal trends, mean daily temperature, and mean daily concentrations of nitrogen dioxide and ozone to estimate changes in daily mortality with diurnal temperature. We found, over the 30 day lag period, a cumulative increase in daily mortality of 5.12% [95% confidence interval (CI): 0.02-10.49%] for a change from 5.9 °C to 11.1 °C (25th to 75th percentiles) in diurnal temperature, and a 11.27% (95%CI: 2.08-21.29%) increase in mortality associated with an increase of diurnal temperature from 11.1 to 17.5 °C (75th to 99th percentiles). The results were relatively robust to adjustment for daily mean temperature. We found that, in Montreal, diurnal variations in temperature are associated with a small increase in non-accidental mortality among the elderly population. More studies are needed in different geographical locations to confirm this effect.


Epinephrine and sodium bicarbonate during CPR following asphyxial cardiac arrest in rats.
Although high-dose epinephrine during CPR improves coronary perfusion pressure (CoPP) and rate of return of spontaneous circulation (ROSC) in some models, its impact on long term outcome (> or = 72 h) has not been evaluated. Previous studies of sodium bicarbonate (NaHCO3) therapy during CPR indicate that beneficial effects may be dependent on epinephrine (EPI) dose. We hypothesized that EPI and NaHCO3 given during CPR have a significant impact on long term outcome. One hundred male Sprague-Dawley rats were prospectively studied in a block randomized placebo controlled trial. Rats were anesthetized, paralyzed, mechanically ventilated, instrumented, and each underwent 10 min of asphyxia, resulting in 6.8 +/- 0.4 min of circulatory arrest. Resuscitation was performed by mechanical ventilation and manual external chest compressions. EPI 0.0 (placebo), 0.01, 0.1, or 1.0 mg/kg IV was given at the onset of CPR, followed by NaHCO3 0.0 (placebo) or 1.0 mEq/kg IV. Successfully resuscitated rats were monitored and ventilated for 1 h without hemodynamic support. Neurologic deficit scores (NDS), cerebral histopathologic damage scores (CHDS) and myocardial histopathologic damage scores (MHDS) were determined in rats that survived 72 h. EPI improved CoPP and ROSC in a dose-dependent manner up to 0.1 mg/kg. Rats receiving EPI 0.1 and 1.0 mg/kg during CPR exhibited prolonged post-ROSC hypertension and metabolic acidemia, increased A-a O2 gradient, and an increased incidence of post-ROSC ventricular tachycardia or fibrillation. Overall survival was lower with EPI 0.1 and 1.0 mg/kg compared to 0.01 mg/kg. Although NDS was significantly less with EPI 0.1 mg/kg compared to placebo, there was no difference in CHDS between groups. In contrast, MDS was significantly higher with EPI 0.1 mg/kg compared to placebo or EPI 0.01 mg/kg. There was an overall trend toward improved survival at 72 h in rats that received NaHCO3 which was most evident in the EPI 0.1 mg/kg group. We conclude that (1) EPI during CPR has a biphasic dose/response curve in terms of survival, when post-resuscitation effects are left untreated and (2) NaHCO3 doses greater than 1.0 mEq/kg may be necessary to treat the side-effects of high-dose EPI. Further work is needed to determine if treating the immediate post-resuscitation effects of high-dose EPI can prevent detrimental effects on long-term outcome.


Ultrasound-assisted facile one-pot synthesis of ternary MWCNT/MnO2/rGO nanocomposite for high performance supercapacitors with commercial-level mass loadings.
Commercial application of supercapacitors (SCs) requires high mass loading electrodes simultaneously with high energy density and long cycle life. Herein, we have reported a ternary multi-walled carbon nanotube (MWCNT)/MnO2/reduced graphene oxide (rGO) nanocomposite for SCs with commercial-level mass loadings. The ternary nanocomposite was synthesized using a facile ultrasound-assisted one-pot method. The symmetric SC fabricated with ternary MWCNT/MnO2/rGO nanocomposite demonstrated marked enhancement in capacitive performance as compared to those with binary nanocomposites (MnO2/rGO and MnO2/MWCNT). The synergistic effect from simultaneous growth of MnO2 on the graphene and MWCNTs under ultrasonic irradiation resulted in the formation of a porous ternary structure with efficient ion diffusion channels and high electrochemically active surface area. The symmetric SC with commercial-level mass loading electrodes (∼12 mg cm-2) offered a high specific capacitance (314.6 F g-1) and energy density (21.1 W h kg-1 at 150 W kg-1) at a wide operating voltage of 1.5 V. Moreover, the SC exhibits no loss of capacitance after 5000 charge-discharge cycles showcasing excellent cycle life.


Clinical prognostic value of the SMYD2/3 as new epigenetic biomarkers in solid cancer patients: a systematic review and meta-analysis.
SET and MYND domain-containing protein (SMYD) family with methyltransferase activity is involved in cancer progression. This novel meta-analysis aimed to evaluate the association of SMYD family with the clinical and survival outcomes in solid cancer patients. We systematically searched Embase, PubMed, Scopus and Web of Science to select relevant articles. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals were extracted. Heterogeneity was evaluated by chi-square-based Q and I2 tests, while publication bias by funnel plots and Egger's test. Thirty-two articles (4,826 patients) met inclusion criteria. SMYD2/3 overexpression was statistically associated with poor overall survival (HR = 1.794, P < 0.001), disease/relapse/progression-free survival (HR = 2.114, P < 0.001), disease/cancer-specific survival (HR = 3.220, P = 0.003), larger tumor size (OR = 1.963, P < 0.001), advanced TNM stage (OR = 2.066, P < 0.001), lymph node metastasis (OR = 2.054, P < 0.001), and distant metastasis (OR = 1.978, P = 0.004). Subgroup analysis showed more significant association between SMYD2 overexpression and reduced survival outcomes than that in SMYD3. Conversely, the relationship between SMYD3 and various clinicopathologic factors was stronger compared to SMYD2. Enhanced SMYD2/3 expression may be an unfavorable clinical prognostic factor in different solid cancer types.


Incidence and risk factors associated with progression to severe pneumonia among adults with non-severe Legionella pneumonia.
Legionella species are important causative organisms of severe pneumonia. However, data are limited on predictors of progression to severe Legionella pneumonia (LP). Therefore, the risk factors for LP progression from non-severe to the severe form were investigated in the present study. This was a retrospective cohort study that included adult LP patients admitted to a 2,700-bed referral center between January 2005 and December 2019. A total of 155 patients were identified during the study period; 58 patients (37.4%) initially presented with severe pneumonia and 97 (62.6%) patients with non-severe pneumonia. Among the 97 patients, 28 (28.9%) developed severe pneumonia during hospitalization and 69 patients (71.1%) recovered without progression to severe pneumonia. Multivariate logistic regression analysis showed platelet count ≤150,000/mm3 (odds ratio [OR], 2.923; 95% confidence interval [CI], 1.100-8.105; P=0.034) and delayed antibiotic treatment >1 day (OR, 3.092; 95% CI, 1.167-8.727; P=0.026) were significant independent factors associated with progression to severe pneumonia. A low platelet count and delayed antibiotic treatment were significantly associated with the progression of non-severe LP to severe LP.


The pharmaco-toxicological conundrum of oleander: Potential role of gut microbiome.
Nerium oleander L., commonly known as oleander, is a toxic shrub and also a medicinal plant. All parts of oleander are rich in cardiac glycosides that inhibits Na+/K+-ATPase and induce inotropic effect on the cardiomyocytes. Several pre-clinical and clinical reports indicate acute toxicity due to intentional, accidental and suicidal oleander consumption. Contrarily, oleander is used for the treatment of diverse ailments in traditional medicinal practices around the globe and several evidence-based pre-clinical studies indicated metabolic and immunological health benefits of polyphenol-rich oleander extracts. Thus, the current review aims to address this pharmaco-toxicological conundrum of oleander by addressing the possible role of gut microflora in the differential oleander toxicity. Additionally, a comprehensive account of ethnopharmacological usage, metabolic and immunological health benefits has been documented that supplement the conflicting arguments of pharmaco-toxicological properties of oleander. Finally, by addressing the gap of knowledge of ethnomedicinal, pharmacological and toxicological reports of oleander, the current review is expected to pave the way to address the differential pharmaco-toxicological effects of oleander.


A new approach to absorptive function of gallbladder.
To investigate the mechanism of concentration of bile, the normal canine gallbladders were cannulated through the cystic duct into the gallbladder neck with polyethylene tube, and hypotonic, isotonic and hypertonic salines as well as hepatic and gallbladder biles were placed in the gallbladder. Low molecular electrolytes such as Na+ and Cl- were transported across the epithelial membrane against water flux. The hepatic bile was decreased markedly in volume and each level of electrolytes including bile acids approached that in the gallbladder bile. The different results were obtained by concentration of the hepatic bile in the gallbladder with chemically induced cholecystitis.


Effects of Cl- channel blockers on beta-adrenoceptor-mediated decreases in resting potential and intracellular Cl- activity in guinea-pig heart.
In order to find a more specific blocker of the cardiac Cl- channel, we examined the effects of anthracene-9-carboxylic acid (9AC) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) on the beta-adrenoceptor-mediated decreases in resting potential and intracellular chloride ion activity (aiCl) in guinea-pig papillary muscles by using Cl- ion selective microelectrodes. 9AC (1 mM) significantly inhibited the isoproterenol (1 microM)-induced decreases in resting potential and aiCl in quiescent preparations. However, 1 mM DIDS did not significantly affect the changes in aiCl and resting potential during beta-adrenergic stimulation. Thus, in cardiac cells, 9AC is a more potent blocker of the Cl- channels activated by beta-adrenergic stimulation than DIDS.


Decrease of cholesterol and free fatty acids in cortisone-resistant lymphoid cells incubated with allogeneic tumor cells.
A marked decrease of cholesterol and free fatty acids was found in the cortisone-resistant lymphoid cells from thymus or spleen of mice immunized with Ehrlich carcinoma cells when incubated with the tumor cells.


Regular walking improves plasma protein concentrations that promote blood hyperviscosity in women 65-74 yr with type 2 diabetes.
The purpose of the present study was to investigate the effects of regular treadmill walking on plasma factors that increase low-shear blood viscosity and red blood cell aggregation in older women with type 2 diabetes. Eighteen women with type 2 diabetes (age: 69±3 yr; body mass index: 30.5±5.0 kg⋅m-2) performed 12-wk of 120 min⋅wk-1 of supervised treadmill walking at an intensity equivalent to the gas-exchange threshold. Peak exercise values, anthropometry and blood indices of diabetic status, markers of inflammation, and plasma fibrinogen were analysed during a 6-wk pre-training 'control' period, and then after 6 and 12-wk of regular walking. Regular walking significantly increased peak oxygen uptake (p = 0.01). Body mass, waist to hip ratio, and glycaemic control did not change. Systolic and diastolic blood pressures decreased by 8.5% (p < 0.01) and 7.2% (p < 0.01) respectively, cholesterol to high-density lipoprotein (HDL) ratio decreased by 9.6% (p = 0.01), and HDL concentration significantly increased (p = 0.01). While 12 wk of regular walking did not significantly alter plasma concentrations of interleukin-6 (IL-6), tumour necrosis factor-α, or C-reactive protein, plasma fibrinogen concentration decreased by 6.9% (p < 0.01) and plasma interleukin-10 (IL-10) concentration increased from 1.15±0.32 to 1.62±0.22 mmol⋅L-1 (p < 0.04). Improved plasma inflammatory profile and decreased plasma fibrinogen concentration is induced by regular walking, independent of glycaemic control. These factors may mediate the improved haemorheology associated with exercise training in metabolic disorders.


Acute pyelonephritis causing acute renal allograft dysfunction.
In renal transplant recipients, acute pyelonephritis may cause acute deterioration of renal function. We report a case with acute allograft failure due to acute pyelonephritis, which was confirmed by graft biopsy. After appropriate antimicrobial therapy, allograft function recovered.


Non-contact characterization of compound optical elements using reflectance confocal microscopy, low-coherence interferometry, and computational ray-tracing.
Advances in microscopy have enabled us to see at unprecedented depths and resolutions, even breaking the diffraction-limit by several fold. These improvements have come at the expense of system complexity with microscopes routinely employing multiple objective lenses and custom optical relays. Optimal system design is paramount for imaging performance, but research systems are limited by the use of commercial components because optical prescriptions are often inaccessible. System performance can be further degraded when these components are implemented in nonstandard configurations outside of manufacturer specifications. Here, we describe a method for characterization of compound optical elements including curvatures, material and air-gap thicknesses, and glass types. We present validation data for doublets and a commercial broadband scan lens. Our method is both non-contact and non-destructive, and we believe it addresses a unique gap in optical design that may be extended to broad applications in both research and industrial manufacturing.


Effects of dimethylnitrosamine on metabolism of N,N-dimethylaniline by rat liver microsomes. A comparative study of treatment in vivo, in isolated liver perfusion and in the microsomal system.
The effect of dimethylnitrosamine (DMN) on rat liver microsomal detoxication was studied, using the non-carcinogenic aromatic amine N,N-dimethylaniline (dimethylaniline) as substrate. Prior to the preparation of microsomes, the rat liver was exposed to DMN either in vivo (by i.p. injection) or in the isolated liver perfusion system (by addition to the perfusion medium). DMN treatment in vivo (20 mg/kg body wt.) caused a 40% increase in dimethylaniline N-oxygenation and a 30% decrease in dimethylaniline C-oxygenation. When DMN was added to the perfusion medium to a final concentration of 5 or 25 mM, a similar effect was observed. With the 5 mM dose, C-oxygenation was decreased by 20% with a non-significant increase in N-oxygenation. The higher dose caused a 50% increase in N-oxygenation, whereas the decrease in C-oxygenation remained at 20%. When microsomes were incubated with both DMN (5 mM) and dimethylaniline (5 mM) in the system, a small but significant decrease in both N- and C-oxygenation of dimethylaniline was observed. The effect of DMN on the amino acid incorporation into liver and plasma proteins was also studied in the liver perfusion system. The synthesis of both liver and plasma proteins was reduced by DMN.


Why cholesterol as a central theme in coronary artery disease?
Evidence from epidemiologic studies and clinical trials have conclusively demonstrated a direct association between coronary artery disease and levels of total and low-density lipoprotein (LDL) cholesterol. Data from a number of studies suggest that even "average" or "normal" cholesterol levels are too high with respect to coronary artery disease risk. Low levels of high-density lipoprotein (HDL) cholesterol have also emerged as a coronary artery disease risk. A recent meta-analysis has eliminated much of the controversy surrounding triglyceride's contribution to coronary artery disease risk, establishing triglyceride levels as an independent risk factor. Lowering lipid levels by any means-including pharmacologic, surgical, and dietary/lifestyle changes--decreases coronary artery disease risk.


Genetic relationships between high blood eosinophil count, asthma susceptibility, and asthma severity.
Genetic relationships between blood eosinophil count (BEC), asthma susceptibility, and severity are unclear. We sought to identify the genetic difference between type 2 (T2) and nontype 2 (non-T2) asthma (defined by BEC) and investigate genetic relationships between high BEC, asthma susceptibility, and severity. Genome-wide association studies (GWASs) were performed for T2 (n = 9,064; BEC ≥ 300 cells/μL) versus non-T2 asthma (n = 14,379; BEC < 150 cells/μL) and asthma susceptibility (37,227 asthmatics vs. 124,132 nonasthma controls) in the UK Biobank and asthma severity (moderate-to-severe asthma [n = 2,153] vs. mild asthma [n = 5165]) in the All of Us Research Program (AoURP). Genetic causality between BEC, asthma susceptibility, and severity were dissected using Mendelian randomization (MR). High BEC was associated with asthma and decreased pulmonary function. GWASs revealed four sets of genetic variants (p < 5 × 10-8): genes associated with only BEC or asthma and genes associated with high BEC and asthma in the same or opposite direction. The C allele of rs653178 in ATXN2 was associated with high BEC, risk for autoimmune diseases, and protection for asthma. Genetic variants associated with BEC or asthma were not associated with asthma severity. MR indicated high BEC and asthma were in bidirectional causal relationship (p < .001); however, they were not causal for asthma severity. Genetic variants associated with asthma or BEC and asthma severity are distinctive. High BEC is a risk factor for asthma; however, it is neither necessary nor sufficient for asthma susceptibility and severity.


Revealing cholesterol effects on PEGylated HSPC liposomes using AF4-MALS and simultaneous small- and wide-angle X-ray scattering.
Liposome development is of great interest owing to increasing requirements for efficient drug carriers. The structural features and thermal stability of such liposomes are crucial in drug transport and delivery. Reported here are the results of the structural characterization of PEGylated liposomes via small- and wide-angle X-ray scattering and an asymmetric flow field-flow fractionation (AF4) system coupled with differential refractive-index detection, multi-angle light scattering (MALS) and dynamic light scattering. This integrated analysis of the exemplar PEGylated liposome formed from hydrogenated soy phosphatid-yl-choline (HSPC) with the addition of cholesterol reveals an average hydro-dynamic radius (R h) of 52 nm with 10% polydispersity, a comparable radius of gyration (R g) and a major liposome particle mass of 118 kDa. The local bilayer structure of the liposome is found to have asymmetric electronic density profiles in the inner and outer leaflets, sandwiched by two PEGylated outer layers ca 5 nm thick. Cholesterol was found to effectively intervene in lipid chain packing, resulting in the thickening of the liposome bilayer, an increase in the area per lipid and an increase in liposome size, especially in the fluid phase of the liposome. These cholesterol effects show signs of saturation at cholesterol concentrations above ca 1:5 cholesterol:lipid molar ratio.


Engineering microenvironment for expansion of sensitive anchorage-dependent mammalian cells.
Tissue engineering involves ex vivo seeding of anchorage-dependent mammalian cells onto scaffolds, or transplanting cells in vivo. The cell expansion currently requires repeated cell detachment from solid substrata by enzymatic, chemical or mechanical means. The report here presents a high yield three-dimensional culture and harvest system circumventing the conventional detachment requirements. Cells mixed with dilute cationic collagen were microencapsulated within an ultra-thin shell of synthetic polymers. The cationic collagen could rapidly form a conformal layer of collagen fibers around cells to support cell proliferation and functions. The collagen could be readily removed from cells with a buffer rinse after harvesting from the fragile microcapsules. The cells harvested from this system demonstrate improved attachment, morphology and functions over conventionally cultured cells, upon binding to ligand-conjugated polymer surfaces. The harvested cells can be re-encapsulated and allowed to proliferate again, or used immediately in applications.


The fibrotic and immune microenvironments as targetable drivers of metastasis.
Although substantial progress has been made over the past 40 years in treating patients with cancer, effective therapies for those who are diagnosed with advanced metastatic disease are still few and far between. Cancer cells do not exist in isolation: rather, they exist within a complex microenvironment composed of stromal cells and extracellular matrix. Within this tumour microenvironment exists an interplay between the two main stromal cell subtypes, cancer-associated fibroblasts (CAFs) and immune cells, that are important in controlling metastasis. A complex network of paracrine signalling pathways between CAFs, immune cells and tumour cells are involved at multiple stages of the metastatic process, from invasion and intravasation at the primary tumour site to extravasation and colonisation in the metastatic site. Heterogeneity and plasticity within stromal cell populations also contribute to the complexity. Although many of these processes are likely to be common to a number of metastatic sites, we will describe in detail the interplay within the liver, a preferred site of metastasis for many tumours. A greater understanding of these networks provides opportunities for the design of new therapeutic approaches for targeting the metastatic disease.


Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells.
Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we show that Dcaf11 (Ddb1- and Cul4-associated factor 11) participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs). The deletion of Dcaf11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is also greatly compromised. Mechanistically, Dcaf11 targets Kap1 (KRAB-associated protein 1) for ubiquitination-mediated degradation, leading to the activation of Zscan4 downstream enhancer and the removal of heterochromatic H3K9me3 at telomere/subtelomere regions. Our study therefore demonstrates that Dcaf11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.


Back Muscle Mass as a Predictor of Postoperative Complications in Posterior Lumbar Interbody Fusion Surgery.
There is a lack of studies on utilising skeletal muscle mass via preoperative lumbar computed tomography or magnetic resonance imaging as a predictor of postoperative complications of posterior lumbar interbody fusion (PLIF) surgery in elderly patients. Patients aged >65 years who underwent PLIF were enrolled. The sum of the cross-sectional areas of the erector spinae muscles (CSABoth) was presented as the skeletal muscle mass. Postoperative complications were assessed using CSABoth, pulmonary function testing, and prognostic nutritional index (PNI). Patients with postoperative complications showed significantly lower values of CSABoth (median 2266.70 (2239.73-2875.10) mm2 vs. 3060.30 (2749.25-3473.30) mm2, p < 0.001), functional vital capacity, forced expiratory volume at 1 s, and PNI. However, multiple logistic regression analysis identified American Society of Anaesthesiologists Physical Status (ASA PS) I (odds ratio 0.307 (95% confidence interval 0.110-0.852), p = 0.023), ASA PS III (4.033 (1.586-10.254), p = 0.003), CSABoth (0.999 (0.999-1.000), p < 0.001), and postoperative red blood cell (RBC) transfusion (1.603 (1.193-2.152), p = 0.002) as risk factors for postoperative complications after PLIF surgery. CSABoth, ASA PS III, and postoperative RBC transfusion might be used as predictors of postoperative complications after PLIF in patients aged >65 years.


Fatal soft-tissue infection complicating pulmonary arteriovenous fistulae.
A patient with pulmonary arteriovenous (AV) fistulae presented with an ultimately fatal anaerobic soft tissue infection. This represents the first report of such a complication, but the association of intracerebral anaerobic abscess with pulmonary AV fistulae suggests the possibility of a common pathophysiologic mechanism.


Progressive pseudorheumatoid dysplasia with new-found gene mutation of Wntl inducible signaling pathway protein 3.
As one kind of osteochondrodysplasia, progressive pseudorheumatoid dysplasia (PPD) is also known as spondyloepiphyseal dysplasia tarda with progressive arthropathy or arthropathy progressive pseudorheumatoid of childhood. PPD is a very rare disease, especially in China, and has an estimated prevalence of 1/1000000 due to lacking definite prevalence survey. It is an autosomal recessive disorder caused by gene mutation of Wntl inducible signaling pathway protein 3 (WISP3). Its basic pathological change is persistent degeneration and loss of articular cartilage in multiple joints. Its clinical appearances include bone enlargement, platyspondyly, irregular endplate, secondary osteoarthritis, extensive osteoporosis, joint rigidity and function loss. Clinical diagnosis of PPD is made based on clinical appearance and imaging examinations, whereas its definite diagnosis depends on gene sequencing. PPD has no severe effect on life span, but causes high disability rate and very poor prognosis. There are only case reports with limited information in China. One female patient was diagnosed as PPD and secondary osteoarthritis. She had typical clinical appearance and imaging examinations, and received individualized therapeutic regimens. She had a gene mutation (c.72delT, p.T24TfsX4) of WISP3. This gene mutation has not been reported by previous literatures and included in Single Nucleotide Polymorphism Database. As the first time, this paper reported a patient with PPD caused by new-found gene mutation (c.72delT, p.T24TfsX4) of WISP3.


Industrial eco-efficiency of resource-based cities in China: spatial-temporal dynamics and associated factors.
Promoting the greening of industry is the key to achieving high-quality and sustainable development of the urban economy. It is particularly important for resource-based cities (RBCs) that exploit natural resources as the leading industries. In this paper, the Windows-Bootstrap-DEA model was used to calculate the industrial eco-efficiency (IEE) of 114 RBCs in China from 2003 to 2016, and the regional differences and dynamic evolution characteristics of the IEE were analyzed. The panel Tobit model was used to explore the factors associated with IEE in RBCs. The results showed that the IEE of RBCs in China was at a low level during the study period, and the resource utilization process had not reached an optimal state. There were large regional differences in IEE, and there was a significant degree of spatial agglomeration. The results of conditional probability density estimation showed that the distribution of IEE had strong internal stability on the whole, and the distributions of IEE of RBCs in different regions, different resource types, and different development stages showed significant differences. The results of the panel Tobit model showed that per capita GDP, ownership structure, science and technology input, and industrial agglomeration had significant positive effects on IEE, while industrial structure and employment structure showed significant negative effects. The conclusions of this paper can provide a scientific decision-making basis for industrial transformation planning of RBCs.


Effects of 1,2,4-trichlorobenzene on the enzyme activities and ultrastructure of earthworm Eisenia fetida.
Adult Eisenia fetida earthworms were exposed to sub-lethal concentrations of 1,2,4-trichlorobenzene to assess the toxicity of contaminated soils. The LC₅₀ of 1,2,4-TCB at 7 and 14 d were 945±175 and 890±169 mg kg⁻¹. A lower dose of 1,2,4-TCB (25 mg g⁻¹) had stimulatory effects on SOD and AChE activities, but AChE activities were significantly inhibited at higher treatment levels (100 and 400 mg g⁻¹). SOD activities increased after 2, 7, and 14 d of exposure, but AChE activities were significantly inhibited at 400 mg/kg 1,2,4-TCB after 2, 7, and 14 d of exposure, and the inhibition rates were 25.41%, 28.65%, and 25.05%. Ultrastructural observation of the intestinal epithelium at three concentrations (control, 50, and 400 mg g⁻¹) revealed that the epicuticle, cuticle layer, and microvilli were damaged with increasing 1,2,4-TCB concentration. At 400 mg kg⁻¹, mitochondria were seriously injured and the smooth endoplasmic reticulum was seriously dilated.