Determinants of assemblage size for the parasitoids of Cecidomyiidae (Diptera).
The parasitoids known to attack 191 phytophagous species of gall midges (Cecidomyiidae) were used to examine factors influencing parasitoid assemblage size. The number of parasitoid species a midge species supports was tested against nine variables describing geographical, biological and ecological attributes of hosts. The apparency of midge larvae was found to have the greatest influence on parasitoid assemblage size; highly visible species support more parasitoids than less visible ones. Pupation site and midge voltinism also significantly affect associated parasitoids, at least for highly apparent hosts. Biogeographic region, host-plant architecture and the plant parts infested were found to be of secondary importance. The surface texture of infested plant parts, the number of midge larvae occupying galls and the diversity of plant tissues infested have minimal apparent effects on parasitoid richness. Parasitoid assemblage size and total parasitism rates were also found to be positively correlated for 73 galling and nongalling midge species, and gallers typically suffer higher levels of parasitism than non-gallers. Using these data to test the "enemy hypothesis", which proposes that the galling habit has evolved to escape attack from parasitoids, we conclude that parasitoid pressure cannot account for the presence of galls in the Cecidomyiidae.


Exploring the associations between driving volatility and autonomous vehicle hazardous scenarios: Insights from field operational test data.
With the promising development and deployment trends of autonomous vehicles (AVs), AVs' operation safety has become a key issue worldwide. Studies have been conducted to reveal the risk factors of AV operation safety based upon AV-involved crash reports. However, the crash data sample size was limited and the crash reports only recorded static information, thus it failed to identify crash contributing factors and further provide feedbacks to AV algorithm development. In this study, the risk factors were investigated based upon hazardous scenarios, which were claimed to possess consistent causal mechanisms with crash events. First, contributing factors were extracted from both vehicle kinematics and traffic environment aspects, and their volatility features were obtained. Then, path analysis models were developed to reveal the concurrent relationships between scenario volatility and hazardous scenario occurrence probability. Besides, to understand the varying risk factors for hazardous scenarios caused by human drivers and AVs, a logit regression model was further established. The modeling results showed that large volatility of space headway held direct impacts on increasing the AV driving risks. And the volatility of the drivable road area had no significant impacts on AV driving risks while it indirectly influenced human driving risks. Finally, result implications for AV driving behavior improvements have been discussed.


Direct-Current Generator Based on Dynamic PN Junctions with the Designed Voltage Output.
The static PN junction is the foundation of integrated circuits. Herein, we pioneer a high current density generation by mechanically moving N-type semiconductor over P-type semiconductor, named as the dynamic PN junction. The establishment and destruction of the depletion layer causes the redistribution and rebounding of diffusing carriers by the built-in field, similar to a capacitive charge/discharge process of PN junction capacitance during the movement. Through inserting dielectric layer at the interface of the dynamic PN junction, output voltage can be improved and designed numerically according to the energy level difference between the valence band of semiconductor and conduction band of dielectric layer. Especially, the dynamic MoS2/AlN/Si generator with open-circuit voltage of 5.1 V, short-circuit current density of 112.0 A/m2, power density of 130.0 W/m2, and power-conversion efficiency of 32.5% has been achieved, which can light up light-emitting diode timely and directly. This generator can continuously work for 1 h, demonstrating its great potential applications.


In vitro digestion with proteases producing MHC class II ligands.
Proteases generate peptides that bind to MHC class II molecules to interact with a wide diversity of CD4(+) T cells. They are expressed in dedicated organelles: endosomes and lysosomes of professional antigen presenting cells (pAPCs) such as B cells, macrophages, and dendritic cells. The identification of endosomal proteases which produce antigenic peptides is important, for example, for better vaccination and to prevent autoimmune diseases. Here, we describe a panel of technics (in vitro digestion assays of protein with recombinant proteases or purified endosomes/lysosomes, T cell stimulation) to monitor the production of MHC class II ligands.


The IMGT/HLA database.
The human leukocyte antigen (HLA) complex is located within the 6p21.3 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and include many highly polymorphic HLA genes. The naming of new HLA genes and allele sequences and their quality control is the responsibility of the WHO Nomenclature Committee for Factors of the HLA System. The IMGT/HLA Database acts as the repository for these sequences and is recognized as the primary source of up-to-date and accurate HLA sequences. The IMGT/HLA website provides a number of tools for accessing the database: these include allele reports, sequence alignments, and sequence similarity searches. The website is updated every 3 months with all the new and confirmatory sequences submitted to the WHO Nomenclature Committee. Submission of HLA sequences to the committee is possible through the tools provided by the IMGT/HLA Database.


42 months of experience with the Mentor inflatable penile prosthesis.
The Mentor inflatable penile prosthesis is a hydraulic device that was introduced in May 1983 for the treatment of erectile dysfunction. Since its introduction further technical modifications and improvements have been made on the product. From the onset the reliability, function and cosmetic effect of this physiological device have been excellent. The modifications have served to improve the ease of operation and to increase further the reliability as demonstrated by our progressive decrease in the incidence of mechanical failures. From May 1983 to November 1986 we implanted 137 Mentor inflatable penile prostheses. Our over-all mechanical failure rate was 7.3 per cent. As a result of the modifications, however, the mechanical failure rate decreased to 3.1 per cent during the last 38 months of that period when 129 (94 per cent) of the prostheses were implanted, and during the last 24 months of that period when 86 (63 per cent) of the prostheses were implanted the mechanical failure rate was only 1.2 per cent.


Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial.
Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%. This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN. Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test. RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible. A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects. A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible.


Distribution and ecological risk of substituted and parent polycyclic aromatic hydrocarbons in surface waters of the Bai, Chao, and Chaobai rivers in northern China.
Like their parent polycyclic aromatic hydrocarbons (PAHs), substituted polycyclic aromatic hydrocarbons (SPAHs), including methyl PAHs (MPAHs), oxygenated PAHs (OPAHs), and chlorinated PAHs (ClPAHs), exist ubiquitously in urban and agricultural rivers. Although laboratory studies have found the biological toxicities of certain SPAHs to be higher than that of their parent PAHs, the ecological risk of SPAHs in rivers has been largely ignored. Here, we studied the distribution, source and transport of PAHs and SPAHs as well as ecological risks in the Chaobai River System, which experiences a high level of anthropogenic activity. The results show that the concentration of ΣOPAHs (321 ± 651 ng/L) was higher than that of ΣPAHs (158 ± 105 ng/L), ΣMPAHs (28 ± 22 ng/L), and ΣClPAHs (30 ± 12 ng/L). We also found that (S)PAHs in Chaobai River mainly originated from Beiyun River (53%-65%), which receives considerable municipal wastewater treatment plant effluent from Beijing. The major transport pathway of (S)PAHs from Chaobai River was likely for irrigation (83%-86%) and transportation into Yongdingxin River (13%-16%), which finally merged into the Bohai Sea. The mixed chronic risk of (S)PAHs (risk quotient = 45 ± 53) was higher than the mixed acute risk (risk quotient = 1.9 ± 1.4), with all sites facing chronic risk and 90% of sites experiencing acute risk. Although the chronic and acute risks of (S)PAHs to plants, invertebrates, and vertebrates were mainly from PAHs (97.5% to chronic risk and 96.5% to acute), SPAHs still posed a chronic risk to invertebrates and vertebrates (risk quotient > 1). Accordingly, the ecological risk of (S)PAHs in Chaobai River should be taken into consideration for ecosystem protection. The transmission of PAHs and SPAHs from Chaobai River may also pose potential risks to farmland through irrigation, as well as to the Bohai Sea via river water discharge.


Application of Ionic Liquid-Based Ultrasonic-Assisted Extraction of Flavonoids from Bamboo Leaves.
Ionic liquids (ILs), known as environmentally benign "green" solvents, were developed as an optimal solvent for the green extraction and separation field. In this paper, an ionic liquid-based ultrasonic-assisted extraction (IL-UAE) of flavonoids (FVs) from bamboo leaves of Phyllostachys heterocycla was developed for the first time. First, 1-butyl-3-methylimidazolium bromide ([Bmim] Br), with the best extraction efficiency, was selected from fifteen ionic liquids with diverse structure, like carbon chains or anions. Then, the influencing parameters of ionic liquid (IL) concentration, liquid-solid ratio, ultrasonic time, and ultrasonic power, were investigated by single factor tests, and further optimized using response surface methodology (RSM). In the optimization experiment, the best conditions were 1.5 mol/L [BMIM]Br aqueous solution, liquid-solid ratio 41 mL/g, ultrasonic time 90 min, and ultrasonic power 300 W. Furthermore, the microstructures of bamboo leaves and the recovery of FVs and [BMIM]Br were also studied. Therefore, this simple, green and effective IL-UAE method has potentiality for the extraction of FVs from bamboo leaves for the large-scale operations.


In vivo comparison of the optiflow and EZ glide aortic dispersion cannulas.
Morbidity associated with coronary artery bypass grafts and embolization during aortic cannulation is strongly related to patient characteristics/comorbidities, arterial cannulation site used and the shape of arterial cannulae tips. The desired features of an arterial cannula should be to mitigate the morbid effects of these cannulas and to focus on achieving higher blood flows with lower cannula pressures (CPs). To evaluate the in vivo performance of two aortic dispersion flow cannulas: the Optiflow (Sorin Group, Italy) and EZ Glide (Edwards Lifesciences). They were evaluated for CPs, pump-flow rates (FRs), and plasma-free hemoglobin (Hb) over a 12-month period. Data were collected in a prospective, randomized (1:1), nonblinded, monocentric study with a cohort of 30 patients (optiflow group N = 15; EZ Glide group N = 15). The optiflow cannula was found to have decreasing CPs as the pump FRs were increased (112.3 ± 10.9 vs 131.1 ± 11.4 mm Hg; P < .001). Results indicated no significant differences between groups for increases in plasma free Hb (P = .41) and total microembolic signals counts during the period of cardiac surgery (P = .63). Both optiflow and EZ Glide dispersion flow arterial cannulas performed well, but the optiflow cannula demonstrated an ability to increase pump FRs with lower arterial line and CPs than the EZ Glide cannula. This implies an ability to improve peripheral perfusion while reducing cannula shear stress and the risk of endothelial damage, thereby having the potential to reduce the risk of atherosclerotic plaque dislodgement.


Effect of the Macintosh curved blade size on direct laryngoscopic view in edentulous patients.
In the present study, we compared the laryngoscopic view depending on the size of the Macintosh curved blade in edentulous patients. Thirty-five edentulous adult patients scheduled for elective surgery were included in the study. After induction of anesthesia, two direct laryngoscopies were performed alternately using a standard-sized Macintosh curved blade (No. 4 for men and No. 3 for women) and smaller-sized Macintosh curved blade (No. 3 for men and No. 2 for women). During direct laryngoscopy with each blade, two digital photographs of the lateral view were taken when the blade tip was placed in the valleculae; the laryngoscope was lifted to achieve the best laryngeal view. Then, the best laryngeal views were assessed using the percentage of glottic opening (POGO) score. On the photographs of the lateral view of direct laryngoscopy, the angles between the line extending along the laryngoscopic handle and the horizontal line were measured. The POGO score was improved with the smaller-sized blade compared with the standard-sized blade (87.3% [11.8%] vs. 71.3% [20.0%], P<0.001, respectively). The angles between the laryngoscopic handle and the horizontal line were greater with the smaller-sized blade compared to the standard-sized blade when the blade tip was placed on the valleculae and when the laryngoscope was lifted to achieve the best laryngeal view (both P<0.001). Compared to a standard-sized Macintosh blade, a smaller-sized Macintosh curved blade improved the laryngeal exposure in edentulous patients.


Human rotavirus strains circulating among children in the capital of China (2018-2022)_ predominance of G9P[8] and emergence ofG8P[8].
This study aimed to update the genetic diversity of Rotavirus (RV) infections in children under five years old in Beijing, China. A 5-year active hospital-based surveillance for sporadic acute gastroenteritis (AGE) from January 2018 to December 2022 in the capital of China was performed. A total of 748 fecal samples from AGE patients were collected for followed by RV antigen detection by ELSIA, RNA detection by reverse transcription PCR, G/P genotyping and phylogenetic analyzing. RV antigen was detected in 11.0% of the collected samples, with 54 samples confirmed to be RV RNA positive. G9 and G8 genotypes were identified in 43 (79.6%) and 7 (13.0%) samples, respectively, all of which were allocated to P[8]. The predominant G/P combination was G9P[8] (79.6%), following by G8P[8] (13.0%), G4P[8] (5.6%) and G3P[8] (1.9%). A significant change in G/P-type distribution was observed, with the G9P[8] being predominant from 2018 to 2021, followed by the emergence of an uncommon G8P[8] genotype, which was first reported in 2021 and became predominant in 2022. Blast analysis showed that one G1 isolate had a high similarity of 99.66% on nucleotide acid with RotaTeq vaccine strain with only one amino acid difference L150V. Additionally, one P[8] isolate was clustered into a branch together with RotaTeq vaccine strain G6P[8]. The study reveals that G8P[8] has become the predominant genotype in pediatric outpatients in China for the first time, indicating a significant change in the composition of RV genetic diversity. The importance of RVA genotyping in surveillance is emphasized, as it provides the basis for new vaccine application and future vaccine efficacy evaluation.


Age-associated accumulation of heat-labile aminoacyl-tRNA synthetases in mice and rats.
Age-related changes of two aminoacyl-tRNA synthetases in BDF1 mouse and Fischer 344 rat tissues were investigated. The proportions of heat-labile enzymes in the brain and liver were 5 to 10% in young animals, but 25 to 40% in old animals. The proportions began to increase markedly with increase in the mortality rate of the animals. Significant correlations were found between the proportions of heat-labile tyrosyl- and leucyl-tRNA synthetases in the brain and liver of individual animals. Moreover, the proportions of the heat-labile enzymes in the brain were also significantly correlated with those in the liver. Thus, it appears that when one enzyme is heat-labile in one tissue other enzymes are also heat-labile in the same tissue and the same enzyme is also heat-labile in other tissues. Analysis of the size-distribution of partially purified leucyl-tRNA synthetase complexes indicated that, while enzyme preparations from young animals tended to consist of complexes of larger sizes, those from older animals contained smaller complexes, a 10S complex being a major component. On heating preparations from old animals, the activity in the 10S peak disappeared most rapidly. This finding suggests that the heat-stability of the enzyme depended on its molecular form.


Pneumococcal keratitis at the flap interface after laser in situ keratomileusis.
A 28-year-old woman had uneventful laser in situ keratomileusis in the right eye. Six days postoperatively, she reported ocular pain and a large corneal stromal infiltrate was observed at the flap interface. A second surgery including lifting and excising the flap and scraping the stromal bed was performed. Topical antibiotics were prescribed. A bacterial culture revealed Streptococcus pneumoniae. The keratitis responded well to topical vancomycin. Twelve days after the second surgery, the stromal infiltrate had regressed, the hypopyon had resolved, and visual acuity was hand movements at 0.5 m.


METTL3-mediated m6A modification of lnc RNA RHPN1-AS1 enhances cisplatin resistance in ovarian cancer by activating PI3K/AKT pathway.
Cisplatin resistance is a big challenge for ovarian cancer (OC) therapy. The abnormal expression of long noncoding RNAs (lncRNAs) regulated by N6-methyladenosine (m6A) modification has been confirmed to play the crucial roles in OC. The aim of this study is to explore the regulatory mechanism of lncRNA RHPN1-AS1 on OC with cisplatin resistance. The real-time reverse transcription-polymerase chain reaction was carried out to confirm the expression of RHPN1-AS1 and methyltransferase-like 3 (METTL3) in OC. The effects of RHPN1-AS1 on cisplatin-resistant OC cells were identified by cell functional experiments and animal experiment. Western blotting was performed to detect the effect of RHPN1-AS1 on PI3K/AKT pathway. Moreover, methylated RNA immunoprecipitation and RNA stability assays confirmed the interaction between RHPN1-AS1 and METTL3. RHPN1-AS1 and METTL3 were confirmed to be overexpressed in OC. After transfecting RHPN1-AS1 overexpression or RHPN1-AS1 knockdown vectors into cisplatin-resistant OC cells, it was found that upregulating RHPN1-AS1 contributed to cell viability, migration, invasion, and tumor growth in vivo. In addition, RHPN1-AS1 could enhance the protein levels of PI3K and phosphorylated AKT in cisplatin-resistant OC cells, and METTL3 could enhance the stability of RHPN1-AS1 by the m6A modification. Overall, this study revealed that METTL3-mediated m6A modification of RHPN1-AS1 accelerates cisplatin resistance in OC by activating PI3K/AKT pathway.


Role play. Providing care to children and their families in the emergency center.
The collaborative model has many benefits for children and families, physicians, nurses, staff, and NPs. The model of care can be structured to charge lower fees for nonacute problems, thereby saving money. Various studies have reported savings of 20% to 38% in the cost of visits when patients were seen by NPs instead of physicians (Salkever, Skinner, Steinwach, & Katz, 1982). With appropriate triaging, waiting time may be reduced for children and families with nonacute problems. Perhaps the most important benefit is the teaching that the NP is able to provide for families in terms of managing particular health problems, safety needs, and preventive interventions and maintenance of wellness for children.


Reducing Inappropriate Lumbar Spine MRI for Low Back Pain: Radiology Support, Communication and Alignment Network.
The aim of this study is to evaluate the impact of educational sessions on reducing lumbar spine MRI inappropriateness for uncomplicated low back pain and to present our institutional experience on the use of ACR's Radiology Support, Communication and Alignment Network (R-SCAN) program toward achieving appropriateness. The R-SCAN web portal was accessed to register a project. Using order entry data, the number of lumbar spine MRI orders placed per month at three family medicine clinics was assessed over a 10-month period. After educational presentations were given at those three clinics highlighting the American College of Physicians and Choosing Wisely campaign imaging guidelines, the number of MRI orders placed was reassessed over an additional 10 months. For a subset of these exams, the ACR Appropriateness Criteria rating of the lumbar spine MRIs were compared between the pre- and posteducation periods. A P value < .05 was considered statistically significant. The average number of monthly MRIs ordered from all three clinics combined was 6.3 during the posteducation period, which was significantly less than during the pre-education period of 10.0 (P = .009). The combined average ACR Appropriateness Criteria rating made at all three clinics was 5.8 after educational sessions, which was significantly higher than the rating of 4.7 before educational sessions (P = .014). Clinician education, facilitated by R-SCAN, resulted in a reduced number of MRI lumbar spine studies performed for uncomplicated low back pain and improved appropriateness of those studies as measured by the ACR Appropriateness Criteria rating.


Bilateral multiple oncocytic cysts of the parotid gland in type 2 diabetes patients.
The hallmarks of type 2 diabetes (T2D) are hyperglycaemia and insulin resistance. These factors, at the cellular level, are associated with mitochondrial dysfunction and increased glucose uptake. Such events are poorly explored in the context of the salivary glands. In this study, we present a series of eight cases of a distinct salivary gland lesion characterised by multiple oncocytic cysts, and we provide new pathological insights regarding its pathogenesis. Seven patients (87.5%) had confirmed T2D, and obesity was identified in five (62.5%) patients. Clinically, the patients showed bilateral parotid gland swelling with recurrent episodes of pain and enlargement. Imaging examination revealed multiple cystic lesions in both parotid glands. Microscopically, the parotid glands showed multiple cysts of different sizes, lined by oncocytic epithelial cells. Intraluminally, strongly eosinophilic glass-like crystalloid material was observed. Immunohistochemical studies were performed, and the most notable finding was glucose transporter 1 (GLUT1) overexpression in the oncocytic cysts which is not observed in any other oncocytic lesion of patients without T2D. In addition, high expressions of mitochondrial antigen, fission 1 protein and mitofusin-2 were observed in the oncocytic epithelium of the cysts. Furthermore, most of the oncocytic cysts showed a pattern of cytokeratin expression consistent with striated ducts. These results strongly suggest that T2D is associated with alterations in GLUT1 expression in the cells of striated ducts with mitochondrial dysfunction, causing a hyperplastic process characterised by multiple oncocytic cysts. For this lesion, the designation of 'diabetes-associated-bilateral multiple oncocytic cysts of the parotid gland' is proposed.


Acetylcholine content in different regions of the rat brain.
Acetylcholine content of different rat brain regions was measured. A correlation between acetylcholine content and cholineacetyltransferase (ChAc) activity in discrete brain regions was found. However there are regions such as cerebellar nuclei, cerebellar hemisphere, caudal medial forebrain bundle, zone incerta, nucleus vestibularis lateralis where the acetylcholine content is relatively much higher than the ChAc activity, and regions such as n.cochleares, n.motor n.V., N.motor N.VII., n.motor, n.XII where ChAc activity was high and the content of acetylcholine is relatively low.


A comparison between different models of the relation between recorded intradental nerve impulse activity and reported pain in man.
In this study three different models of the relation between intradental nerve impulse activity (INA) and pain report, expressed by finger-span (FS), in man were investigated. The techniques were (i) a previously described mathematical model, (ii) the relation between the Areas of INA and FS and (iii) the relation between the Peaks of INA and FS. Their usefulness in 533 clinical experiments on 15 subjects were evaluated by means of a statistical analysis of the variability and accuracy of the models. It was shown that the mathematical model was the most accurate and stable method of the three different methods investigated. This was indicated by, among other things, a significantly smaller variability for the mathematical model within experimental sessions than between sessions. The two other methods were found to be of less scientific value since they had an undesired high variability within sessions, and also showed contradicting results during control conditions.


A wake-up call for social epidemiologists studying health inequalities: Response to Dijkstra & Horstman.
In their paper, published in this journal, Dijkstra & Horstman critically reflect on a selection of social epidemiological articles and examine how low socioeconomic status populations are constructed in these articles. They identify four components which they argue represent the "dominant thought style" of this literature: 1) proliferation, 2) generalization, 3) problematization and 4) individualization. We largely agree with their first two points, but strongly disagree with the other two, and explain why in our reply. All in all, we believe that their analysis is a wake-up call for social epidemiologists, rightly pointing to the risk that the relevance and moral origins of the use and study of categories, like 'low socioeconomic status', can easily become less visible, and therefore should be articulated and explained every time.


Relationship between filtration coefficients of microvasculature and levels of atrial natriuretic peptide or echocardiographic measurements.
Assessing the volume status of hemodialysis (HD) patients and determining their adequate dry weight (DW) present great challenges for physicians involved in HD. In this study the relationship between standardized filtration coefficients of microvasculature (Lpst) and the plasma atrial natriuretic peptide (ANP) levels or echocardiographic measurements (UCGm) were clarified. The aim of this study was to evaluate the possibility of utilizing Lpst as one of the tools for assessing volume status of patients undergoing HD. 52 patients on maintenance HD were examined. Lpst was calculated by utilizing continuous measurements of blood volume during HD by means of monitoring changes of hematocrit with CRIT-LINE(TM). Plasma ANP levels were measured shortly after HD. Plasma ANP levels were elevated beyond the normal limit in 32 patients (Hi group) and were within the normal range in the remaining 20 patients (Lo group). UCGm were performed within 1 month prior to the study. Inferior vena cava diameters in quiet expiration (IVCe) were dilated in 21 patients (Hivc group) and were within the normal range in the remaining 31 patients (Livc group). Lpst was compared with plasma ANP level and UCGm. Lpst in Lo group were significantly lower than those in the Hi group (0.83+/-0.19 vs. 2.64+/-2.73 ml/mm Hg/min; p<0.001). Lpst correlated significantly with plasma ANP levels (r=0.613; p<0.001). Lpst in the Livc group were significantly lower than those in the Hivc group (1.33+/-1.61 vs. 2.85+/-2.88 ml/mm Hg/min; p<0.001). Lpst also correlated with IVCe (r=0.630; p<0.001). The receiver operating characteristic (ROC) curves for high plasma ANP level and for dilated IVCe were significant for Lpst. Area under the ROC curve for elevated ANP was 0.909 (95% confidence interval (CI) 0.834-0.985) and for dilated IVCe was 0.833 (95% CI 0.724-0.941). We conclude that there exists a significant association between Lpst and plasma ANP levels at the end of a dialysis session. There is a possibility that high plasma ANP levels cause elevation of Lpst. Besides ANP, Lpst significantly correlated with IVCe. These results suggested that Lpst can be utilized as one of the tools for assessing volume status of patients undergoing HD.


Studies of the 5' exonuclease and endonuclease activities of CPSF-73 in histone pre-mRNA processing.
Processing of histone pre-mRNA requires a single 3' endonucleolytic cleavage guided by the U7 snRNP that binds downstream of the cleavage site. Following cleavage, the downstream cleavage product (DCP) is rapidly degraded in vitro by a nuclease that also depends on the U7 snRNP. Our previous studies demonstrated that the endonucleolytic cleavage is catalyzed by the cleavage/polyadenylation factor CPSF-73. Here, by using RNA substrates with different nucleotide modifications, we characterize the activity that degrades the DCP. We show that the degradation is blocked by a 2'-O-methyl nucleotide and occurs in the 5'-to-3' direction. The U7-dependent 5' exonuclease activity is processive and continues degrading the DCP substrate even after complete removal of the U7-binding site. Thus, U7 snRNP is required only to initiate the degradation. UV cross-linking studies demonstrate that the DCP and its 5'-truncated version specifically interact with CPSF-73, strongly suggesting that in vitro, the same protein is responsible for the endonucleolytic cleavage of histone pre-mRNA and the subsequent degradation of the DCP. By using various RNA substrates, we define important space requirements upstream and downstream of the cleavage site that dictate whether CPSF-73 functions as an endonuclease or a 5' exonuclease. RNA interference experiments with HeLa cells indicate that degradation of the DCP does not depend on the Xrn2 5' exonuclease, suggesting that CPSF-73 degrades the DCP both in vitro and in vivo.


Donor B-type natriuretic peptide predicts early cardiac performance after heart transplantation.
Decision processes in heart donation remain difficult and are often based on subjective evaluation. We measured B-type natriuretic peptide (BNP) in heart donors and analyzed its value as a discriminator for early post-transplant cardiac performance. Blood samples were prospectively obtained in 94 brain-dead patients, among whom 56 were scheduled for heart donation. BNP values were not available prior to donor selection. BNP of heart donors was related to invasively measured cardiac output and hemodynamic parameters, early after transplantation. BNP, expressed as median (interquartile range), was 65 (32 to 149) pg/ml in brain-dead donors scheduled for heart donation. BNP was higher (287 pg/ml, range 65 to 457; p = 0.0001) in donors considered ineligible for heart donation. In 45 heart recipients, cardiac output (CO) of 5.6 (4.8 to 6.2) liters/min was measured at Day 12 (10-15). In the univariate analysis, recipient CO correlated significantly with donor BNP (r = -0.34, p = 0.025). Stepwise multiple regression, including donor variables such as body mass index, age, BNP, norepinephrine dose, gender and total ischemic time, identified donor BNP and age as the best independent predictors of CO in recipients (p = 0.02 and p = 0.005, respectively, R(2) of the model = 0.27). Donor BNP of >160 pg/ml had 89% accuracy to predict poor cardiac performance in the recipient (cardiac index <2.2 liters/min/m(2)). High donor BNP was independently correlated with a longer hospital stay. Donor BNP was found to be related to cardiac performance, early after cardiac transplantation. BNP measurement in heart donors could become a useful tool in the evaluation of donor hearts.


The presence of autoantibodies specific for NZB serum factors in adult NZB mice and the establishment of monoclonal autoantibodies against these humoral factors.
Humoral factors in serum of young NZB mice enhance maturation of B-lymphocyte precursors in vitro. A blot ELISA assay identified autoantibodies against the serum factors. NZB-SFs (designated NZB-SF alpha, pI 3.5-4.0, and NZB-SF beta, pI 7.8) were purified by sequential steps. Both had a molecular weight (MW) of approximately 23,000 in SDS-PAGE. NZB mice develop autoantibodies against NZB-SFs by 2 months of age; titers increased progressively with age. Non-autoimmune-prone mice did not produce autoantibodies against NZB-SFs. We then developed two hybridoma clones, IIC1C1 and IIC1M4, which produce monoclonal autoantibodies against NZB-SF alpha and NZB-SF beta, respectively. Both IgM autoantibodies could be affinity purified with a column of CNBr-Sepharose 4B gel conjugated with anti-mouse IgM antibody. Neither IIC1C1 nor IIC1M4 abolished bioactivity of recombinant mouse IL-1 alpha, human IL-1, mouse, rat, or human IL-2, mouse IL-3, or colony-stimulating factor. Neither antibody reacted to recombinant mouse IL-1 alpha, IL-4, TNF alpha, or IFN gamma in blot ELISA assays. Monoclonal autoantibodies IIC1C1 and IIC1M4 were used to purify NZB-SFs. SDS-PAGE of the affinity-purified NZB-SFs revealed bands of 23 and 60 kDa, and proteins extracted from the bands were reactive to our monoclonal autoantibodies.


Acute cholestasis-induced renal failure: effects of antioxidants and ligands for the thromboxane A2 receptor.
Acute biliary obstruction is associated with the development of renal impairment and oxidative stress. The F2-isoprostanes, formed during oxidant injury, are renal vasoconstrictors acting via thromboxane (TX)-like receptors. We determined whether the formation of F2-isoprostanes is increased in experimental cholestasis and whether thiol containing antioxidants or ligands for the TXA2 receptor could improve renal function. The effects on renal function of acute bile duct ligation (BDL) in the rat were studied for two days. The consequences of administration of N-acetylcysteine (NAC), alpha-lipoic acid (LA), the TX receptor antagonist (TXRA) BAYu3405, or placebo were then examined. BDL caused a reduction in creatinine clearance from 1.10 +/- 0.05 to 0.55 +/- 0.05 ml/min and sodium excretion from 52 +/- 3 to 17 +/- 3 micromol/hr. Urinary F2-isoprostanes increased from 14 +/- 2 to 197 +/- 22 pg/ml following BDL. Renal functional changes were ameliorated by NAC (creatinine clearance 0.73 +/- 0.05 ml/min), LA (0.64 +/- 0.03 ml/min), and a TXRA (0.90 +/- 0.15 ml/min); P < 0.05. Similarly, sodium excretion was increased from 17 +/- 3 micromol/hr (placebo) to 34 +/- 3 micromol/hr (NAC), 29 +/- 3 micromol/hr (LA), and 38 +/- 5 micromol/hr (TXRA); P < 0.005. Hepatic glutathione concentrations increased from 6.5 +/- 0.3 micromol/g (normal liver) to 8.8 +/- 0.5 micromol/g (NAC) and 7.7 +/- 0.3 micromol/g (LA), P < 0.01. However, only LA markedly inhibited F2-isoprostane formation (197 +/- 22 to 36 +/- 11 pg/ml creatinine clearance; P < 0.05). Urinary TXB2 excretion was elevated after BDL (2.2 +/- 0.5 to 111.1 +/- 20.3 pg/min) but was unaffected by NAC and LA. NAC, LA, and TXRA can partially prevent renal dysfunction in experimental cholestasis. The effects of the antioxidants are independent of their ability to inhibit lipid peroxidation or TX synthesis.


Wild-type APC Is Associated with Poor Survival in Metastatic Microsatellite Stable Colorectal Cancer.
The prognostic implication of wild-type APC (APC-WT) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) is not well defined. APC prognostic value was evaluated retrospectively in two independent cohorts of patient with MSS mCRC with a confirmatory analysis from a public data set from Memorial Sloan Kettering Cancer Center (MSKCC). In comparison with the APC-mutant (APC-MT) population (n = 255), APC-WT patients (n = 86) tended to be younger (59% of age < 40 vs. 26% of age > 50), right-sided (41.7% vs. 27%), BRAFV600E mutated (23.3% vs. 0.8%), and KRAS wild type (65.1% vs. 49.8%). Alternative WNT pathway alterations, RNF43 and CTNNB1, were over-represented in the APC-WT versus APC-MT population (7% vs. 0.4% and 4.7% vs. 0.4%, respectively). APC-WT patients had a worse overall survival (OS) than APC-MT patients (22.6 vs. 45.6 months, p < .0001). Using a multivariate model correcting for primary tumor location, RAS and BRAF status, APC-WT was predictive of poor survival (APC-MT vs. APC-WT, hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44-0.86, p = .0037). The prognostic implication of APC-WT on OS was confirmed further in a similar multivariate model of 934 stage IV patients from MSKCC public database (APC-MT vs. APC-WT, HR, 0.63, 95% CI, 0.49-0.81, p < .0001). APC-WT is associated with poor OS in MSS mCRC regardless of RAS and BRAF status. Compared with APC-MT mCRC tumors, APC-WT tumors were associated with other Wnt activating alterations, including RNF43 and CTNBB1. Our data suggest alternative therapy needs to be investigated in APC-WT patients. Patients with microsatellite stable metastatic colorectal cancer with wild-type APC had a worse overall survival than patients with mutated APC regardless of RAS/RAF status. APC status should be considered as a stratification factor in prospective trials, and novel therapeutic strategies need to be developed for this subgroup of patients.


SURF: A Screening Tool (for Sponsors) to Evaluate Whether Using Real-World Data to Support an Effectiveness Claim in an FDA Application Has Regulatory Feasibility.
Based on recent guidance and publicly available approvals, the US Food and Drug Administration (FDA) has demonstrated its openness to considering evidence of effectiveness from real-world data (RWD) and nonrandomized studies (or "real-world evidence (RWE)") in its decision making. Through analysis of the FDA approvals, several authors have identified methodologic issues commonly discussed by FDA reviewers. However, in our analysis of FDA guidance and use cases, acceptability of RWE also critically depends on whether the characteristics of the clinical development program align with circumstances in which the FDA may have flexibility in considering evidence from real-world study designs relative to more robust designs. Successful use of RWD requires advance planning to allocate the necessary resources and time to undertake principled epidemiology approaches to study design, data selection, and implementation of analyses as well as address regulatory feedback. Thus, sponsors benefit from early identification of programs in which successful RWD use is more likely, to ensure efficient use of resources required for the next steps of scientific feasibility assessment. We developed SURF, a screening tool intended to help a sponsor decide whether to prioritize resources for further exploring the feasibility of using an RWD approach to meet the FDA's effectiveness evidentiary standards for a particular clinical development program. Here, we provide an analysis of FDA guidance, highlighting the circumstances in which RWD approaches may be most acceptable, and demonstrate the use of this screening tool, including the rationale for its construction, types of evidence needed, and application to publicly available approvals as support of concept.


Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents.
The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.


Bilateral spontaneous dislocation of IOLs within the capsular bag to the anterior chamber in a retinitis pigmentosa patient.
The aim of the paper is to present a case of 82 year old man suffering from retinitis pigmentosa, who over the period of 10 years developed partial, bilateral spontaneous dislocation of IOLs within the capsular bag to the anterior chamber. Complexes of IOLs in the capsular bags with severe capsule contraction were removed and AC IOLs were implanted in both eyes. Vision improved significantly in both eyes. Reported complications can be related to coexisting retinitis pigmentosa in described patient.


Systemic iron status.
Iron is one of the essential micronutrients, and as such, is required for growth, development, and normal cellular functioning. In contrast to some other micronutrients such as water-soluble vitamins, there is a significant danger of toxicity if excessive amounts of iron accumulate in the body. A finely tuned feedback control system functions to limit this excessive accumulation by limiting absorption of iron. This chapter will discuss systemic and brain iron homeostasis.


[Diagnosis, treatment and follow-up of community-acquired bacterial infections of the urinary system of men and women (acute cystitis and acute pyelonephritis) and of the genital system of men (acute prostatitis): general remarks].
Urinary tract infections are frequent. The aim of these guidelines is to improve the management of urionary tract infections. Increasing antibiotic prescriptions may increase bacterial drug resistance. Asymptomatic bacteriuria, bacterial count, pyuria are defined and the clinical value of the bacterial culture and urinary dipstick test are discussed. The good antibiotic use depends on bacteriological, pharmaceutical, patient characteristics and economic findings which are precised in these guidelines.


Investigation of the awareness of the students of shiraz dental school concerning the patients' rights and the principles of ethics in dentistry.
Deliberating the patients' rights is one of the major human ethical and legal principles which can be investigated through the agenda of professional and medical ethics.accordingly , the students of dentistry have to be educated about this issue and achieve the necessary skills in deliberating and concerning the patients' rights. The present study aimed to investigate Shiraz dental students' awareness and attitude regarding the patients' rights as well as the principles of dental ethics in order to design methods for organizing and improving the ethics in dentistry. The present descriptive-analytical study was conducted on 111 students of different departments of Shiraz Dental School. The study data were collected through a questionnaire designed based on the patients' rights charter in Iran, ADA ethical codes which are internationally acceptable in the field of dentistry, and the guidelines of the ministry of health, treatment, and medical education (No. 140588). Then, the data were entered into the SPSS statistical software and analyzed. Of all participants, 21.6% were men and 78.4% were women. According to the results, 71% of the students were acquainted with the patients' rights. In addition, the patients' characteristics, including gender and nationality, were not important for 58.6% of the students. The study findings showed that 71% of the participants were acquainted with the patients' rights Establishment of a comprehensive, integrated charter in Iran is needed. With rapid development of medical sciences, new issues appear which necessitate taking into account the mutual rights of the physicians, people, and patients.


A girl with Takayasu arteritis associated with possible systemic lupus erythematosus.
Takayasu arteritis is an inflammatory disease that affects the aorta and its main branches. Its etiology is obscure. Its association with systemic lupus erythematosus has been reported in the English literature in about 20 cases worldwide, and a relationship with a positive tuberculin test, either with or without tuberculosis, has also been mentioned. We report a pediatric patient who presented with renovascular hypertension secondary to Takayasu arteritis associated with a strongly positive tuberculin test and who subsequently developed possible systemic lupus erythematosus 8 months later.


Mutations in genes cnc or dKeap1 modulate stress resistance and metabolic processes in Drosophila melanogaster.
The transcription factor Nrf2 and its negative regulator Keap1 play important roles in the maintenance of redox homeostasis in animal cells. Nrf2 activates defenses against oxidative stress and xenobiotics. Homologs of Nrf2 and Keap1 are present in Drosophila melanogaster (CncC and dKeap1, respectively). The aim of this study was to explore effects of CncC deficiency (due to mutation in the cnc gene) or enhanced activity (due to mutation in the dKeap1 gene) on redox status and energy metabolism of young adult flies in relation to behavioral traits and resistance to a number of stressors. Deficiency in either CncC or dKeap1 delayed pupation and increased climbing activity and heat stress resistance in 2-day-old adult flies. Males and females of the ∆keap1 line shared some similarities such as elevated antioxidant defense as well as lower triacylglyceride and higher glucose levels. Males of the ∆keap1 line also had a higher activity of hexokinase, whereas ∆keap1 females showed higher glycogen levels and lower values of respiratory control and ATP production than flies of the control line. Mutation of cnc gene in allele cncEY08884 caused by insertion of P{EPgy2} transposon in cnc promotor did not affect significantly the levels of metabolites and redox parameters, and even activated some components of antioxidant defense. These data suggest that the mutation can be hypomorphic as well as CncC protein can be dispensable for adult fruit flies under physiological conditions. In females, CncC mutation led to lower mitochondrial respiration, higher hexokinase activity and higher fecundity as compared with the control line. Either CncC activation or its deficiency affected stress resistance of flies.


Variation in the costs and benefits of mutualism: the interaction between yuccas and yucca moths.
Yucca moths are both obligate pollinators and obligate seed predators of yuccas. I measured the costs and net benefits per fruit arising for eight species of yuccas from their interaction with the yucca moth Tegeticula yuccasella. Yucca moths decrease the production of viable seeds as a result of oviposition by adults and feeding by larvae. Oviposition through the ovary wall caused 2.3-28.6% of ovules per locule to fail to develop, leaving fruit with constrictions, and overall, 0.6-6.6% of ovules per fruit were lost to oviposition by yucca moths. Individual yucca moth larvae ate 18.0-43.6% of the ovules in a locule. However, because of the number of larvae per fruit and the proportion of viable seeds, yucca moth larvae consumed only 0.0-13.6% of potentially viable ovules per fruit. Given both oviposition and feeding effects, yucca moths decreased viable seed production by 0.6-19.5%. The ratio of costs to (gross) benefits varied from 0% to 30%, indicating that up to 30% of the benefits available to yuccas are subsequently lost to yucca moths. The costs are both lower and more variable than in a similar pollinator-seed predator mutualism involving figs and fig wasps.There were differences between species of yuccas in the costs of associating with yucca moths. Yuccas with baccate fruit experienced lower costs than species with capsular fruit. There were also differences in costs between populations within species and high variation in costs between fruit within populations. High variability was the result of no yucca moth larvae being present in over 50% of the fruit in some populations, while other fruit produced up to 24 larvae. I present hypotheses explaining both the absence and high numbers of larvae per fruit.


Comparison of One-day Combined versus Staged Anterior and Posterior Cervical Decompression, Fixation, and Fusion.
To compare the perioperative outcomes between single-day combined or separate-day staged surgeries for cervical spinal stenosis. A retrospective cohort analysis was conducted on consecutive patients admitted at a single institution between July 2015 and April 2019, who underwent either single-day combined or separate-day staged surgeries during the same hospitalization period. Demographics, comorbidities, hospital length of stay, and perioperative complications were compared between the patient groups. Eighty patients (combined surgery: n=68, staged surgery: n=12) were included. Dysphagia was the most commonly reported postoperative complication in 44/80 patients (55%). There were no significant differences in the baseline demographics between the two groups. The staged surgery group had significantly longer total time in the operating room (7.2 vs. 8.5 hours, p=0.002), longer duration of general anesthesia (6.7 vs. 7.6 hours, p=0.006), and higher incidence of postoperative delirium (12.1% vs. 50% p=0.005) than the combined surgery group. The mean hospital length of stay was similar in the two groups (combined surgery: 7.5 days vs. staged surgery: 15.1 days, p=0.09). Staged anterior and posterior cervical decompressions, stabilizations, and fusions are associated with longer total time in the operating room, longer duration of general anesthesia, and higher incidence of postoperative delirium than combined surgeries.


Pathophysiology and clinical evaluation of acute heart failure.
Acute heart failure (AHF) is a complex syndrome characterized by worsening heart failure (HF) symptoms that requires escalation of therapy. Intrinsic cardiac abnormalities and comorbid conditions, including lung and renal disease, and sleep-disordered breathing, can contribute to the development of AHF. In this Review, we summarize and discuss the literature on the clinical evaluation and underlying pathophysiology of AHF. Important features of AHF evaluation include identification of precipitating factors to the disease, and assessment of circulatory-renal limitations associated with use of HF medications, prior HF hospitalizations, congestion and perfusion profiles, and end-organ dysfunction. The pathophysiological contributions of endothelial dysfunction, neurohormonal activation, venous congestion, and myocardial injury to the development of AHF are also discussed. These potential causative mechanisms provide a framework for clinicians to evaluate and manage patients with AHF and highlight possible future targets for therapies designed to improve clinical outcomes.


ESTIV questionnaire on the acquisition and use of primary human cells and tissue in toxicology.
The ability to use human cells and tissues in toxicology research and testing has the benefit that it obviates the need to undertake species extrapolation when assessing human hazard. However, obtaining and using human cells and tissues is logistically difficult, ethically complex and is a potential source of infections to those coming into contact with human cell material. The issue is also controversial, with the recent EU legislation draft on tissue engineering, and also due to some instances of human material being obtained and used without informed consent. There are also varying regulations and attitudes relating to the use of human cells and tissues throughout Member States of the EU, and there is a need for harmonisation. The European Society of Toxicology in Vitro (ESTIV) Executive Board and the European Network of Human Research Tissue Banks (ENRTB) have conducted a survey to ascertain the extent to which human cells and tissues are used by its members, how these are obtained, what local regulations are in force, how the material is used, and the advantages and disadvantages experienced by members in using such material, as opposed to cell lines. The results obtained have been compared with the results from a previous survey conducted in 2000. It is hoped that this information will help to facilitate the process of acquiring and using human cells and tissues in a safe and effective way to promote the use of non-animal approaches for investigating the mechanisms of toxicity, and for predicting the toxic hazard of substances.


Investigating the Relationship between the Dimensions and Morphology of Sella Turcica with the Long-Face Growth Pattern and the Vertical Growth Pattern.
The sella turcica is one of the important landmarks of lateral cephalometry, which is used in orthodontics for the diagnosis, treatment plan, and evaluation of skeletal development and maturity. The purpose of the present study is to investigate the relationship between the dimensions and morphology of sella turcica with the long-face growth pattern and people with an open bite. This study also examines the relationship between sella turcica bridging (STB) and the vertical growth pattern. As many as 153 radiographs were analyzed using the Romexis software, considering the basal, gonial, and FMA angles to determine the vertical growth pattern of the face. The basal angle was also used to check for an open bite. Of these patients, 80 had a long vertical face growth pattern, and 73 had a normal face growth pattern. The four landmarks of tuberculum sellae, dorsum sellae, sellae floor, and posterior clinoid were determined on the cephalograms to measure the length, depth, and anteroposterior diameter of the sella turcica. In this study, it was found that the chance of developing a long face in people with partial and complete bridging is 8.37 and 1.92, respectively. An increase in the length of the sella turcica for one unit decreases the chance of a long face, and as the depth of the sella turcica increases, the chance of a long face increases. STB is frequently seen in people with long faces. However, this finding should be considered in relation to other diagnostic parameters. The shorter the length and higher the depth of sella turcica, the higher the chance of developing a long face.


Functional impairment in alcoholic liver disease and non-alcoholic fatty liver disease is significant and persists over 3 years of follow-up.
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are common and increasing in prevalence. We examined prevalence and predictors of functional impairment in biopsy-proven ALD and NAFLD. Change in function over 3 years was explored. Validated functional, cognitive, autonomic, and fatigue symptom assessment tools were completed by patients who had attended our liver clinic. Totals of 224 NAFLD and 107 ALD patients returned the assessment tools. NAFLD and ALD demonstrated comparable functional difficulties, which were significantly worse than controls (p < 0.001) with the proportion of participants experiencing difficulty significantly higher [x (2) 8.93(3), (p = 0.01)]. No significant functional difficulty was demonstrated between those participants who were pre-cirrhotic or cirrhotic. Independent associations were present between difficulty with function in ALD and higher burden of autonomic and cognitive symptoms (p = 0.02) and in NAFLD-increased cognitive difficulty (p < 0.0001), age (p = 0.001), fatigue (p = 0.01), lower albumin (p = 0.02), and bilirubin (p = 0.04). PHAQ scores increased 21 % 2008-2011 {(3.2/15.6) [15.6 (0-93.8)] to 18.75 (0-90.6)}. Functional difficulty of participants alive [15.6 (0-96.9)] was significantly less compared to those who died [40.6 (0-100)] (p = 0.02). NAFLD and ALD patients experience significant functional impairment affecting activities of daily living that persists over time. This has implications for the management of liver disease and service provision.


Premature mortality attributable to PM2.5 pollution in China during 2008-2016: Underlying causes and responses to emission reductions.
Long-term exposure to fine particulate matter (PM2.5) poses a great threat to public health in China. To this end, the Chinese government promulgated the Air Pollution Prevention and Control Action Plan (the Action Plan) in 2013. However, the health benefits of the Action Plan have not been well explained. In this paper, the underlying causes of changes in premature mortality attributable to PM2.5 pollution and the response of this mitigation policy in China were explored using sensitivity analysis. The simulated annual average PM2.5 concentration reduced by 24.9% over mainland China from 2008 to 2016. Subsequently, national premature mortality would decrease by 14.4% from 1.14 million (95% CI: 0.54, 1.55) in 2008 to 0.98 million (95% CI: 0.44, 1.38) in 2016. Specifically, premature mortality reduced by 209,600 cases (-18.3%) owing to PM2.5 reduction during 2008-2016, of which 188,500 cases were from 2014 to 2016 due to the Action Plan in 2013. Note that the health benefits were limited when compared with air quality improvements, mainly due to that the IER functions have a stable curve at higher concentration intervals. Meanwhile, premature mortality would have increased by 14.2% from 2008 to 2016 owing to demographic changes, substantially weakening the impact of the decrease in PM2.5 and baseline mortality. The effectiveness of China's new air pollution mitigation policy was proved through the research. However, considering the non-linear response of mortality to PM2.5 changes and the aggravation of demography trends, stronger emission control steps should be further taken to protect public health in China.


Clinical heterogeneity in familial congenital ptosis: analysis of fourteen cases in one family over five generations.
This report describes a proband and his family consisting of 14 patients affected with simple congenital ptosis. Pedigree suggests an autosomal dominant pattern with 70-90% penetrance. The family includes patients with both unilateral and bilateral involvement, and cases with and/or without complex synkinesia. Left unilateral preponderance is striking, and pedigree analysis suggests the possibility of a modifier gene determining laterality. This study represents the first report of a large family with congenital autosomal dominant simple ptosis which demonstrates the full clinical spectrum of this condition.


Prediction of monthly dry days with machine learning algorithms: a case study in Northern Bangladesh.
Dry days at varied scale are an important topic in climate discussions. Prolonged dry days define a dry period. Dry days with a specific rainfall threshold may visualize a climate scenario of a locality. The variation of monthly dry days from station to station could be correlated with several climatic factors. This study suggests a novel approach for predicting monthly dry days (MDD) of six target stations using different machine learning (ML) algorithms in Bangladesh. Several rainfall thresholds were used to prepare the datasets of monthly dry days (MDD) and monthly wet days (MWD). A group of ML algorithms, like Bagged Trees (BT), Exponential Gaussian Process Regression (EGPR), Matern Gaussian Process Regression (MGPR), Linear Support Vector Machine (LSVM), Fine Trees (FT) and Linear Regression (LR) were evaluated on building a competitive prediction model of MDD. In validation of the study, EGPR-based models were able to better capture the monthly dry days (MDD) over Bangladesh compared to those by MGPR, LSVM, BT, LR and FT-based models. When MDD were the predictors for all six target stations, EGPR produced highest mean R2 of 0.91 (min. 0.89 and max. 0.92) with a least mean RMSE of 2.14 (min. 1.78 and max. 2.69) compared to other models. An explicit evaluation of the ML algorithms using one-year lead time approach demonstrated that BT and EGPR were the most result-oriented algorithms (R2 = 0.78 for both models). However, having a least RMSE, EGPR was chosen as the best model in one year lead time. The dataset of monthly dry-wet days was the best predictor in the lead-time approach. In addition, sensitivity analysis demonstrated sensitivity of each station on the prediction of MDD of target stations. Monte Carlo simulation was introduced to assess the robustness of the developed models. EGPR model declared its robustness up to certain limit of randomness on the testing data. The output of this study can be referred to the agricultural sector to mitigate the impacts of dry spells on agriculture.


Assessment of the accuracy of pharmacy students' compounded solutions using vapor pressure osmometry.
OBJECTIVE. To assess the effectiveness of using a vapor pressure osmometer to measure the accuracy of pharmacy students' compounding skills. DESIGN. Students calculated the theoretical osmotic pressure (mmol/kg) of a solution as a pre-laboratory exercise, compared their calculations with actual values, and then attempted to determine the cause of any errors found. ASSESSMENT. After the introduction of the vapor pressure osmometer, the first-time pass rate for solution compounding has varied from 85% to 100%. Approximately 85% of students surveyed reported that the instrument was valuable as a teaching tool because it objectively assessed their work and provided immediate formative assessment. CONCLUSIONS. This simple technique of measuring compounding accuracy using a vapor pressure osmometer allowed students to see the importance of quality control and assessment in practice for both pharmacists and technicians.


Aetiology and pathogenesis of paraneoplastic autoimmune disorders.
Paraneoplastic autoimmune disorders (PAD) represent a group of autoimmune diseases associated with neoplasms. As a consequence of a remote autoimmunity-mediated effect, PAD are found in multiple organs or tissues, including the skin, blood and nervous system. Compared with non-paraneoplastic autoimmune diseases, PAD have different aetiologies, pathologies, disease symptoms and treatment responses. There are two main origins of autoimmunity in PAD: neoplasm-mediated dysregulated homeostasis in immune cells/organs and in autoantigens. Pathologically, PAD are mediated predominantly by either autoantibodies or autoreactive T-cells. In the past decade, significant progress has been achieved in increasing our understanding of the aetiology and pathology of PAD. In this review article, we aim to provide a comprehensive overview of the recent advances in this field.


Antiplatelet drug resistance is associated with early neurological deterioration in acute minor ischemic stroke in the Chinese population.
To evaluate the prevalence and risk factors of antiplatelet drug resistance and its association with early neurological deterioration (END) and recurrent ischemic stroke (RIS) in patients with acute minor stroke. Antiplatelet drug resistance was assessed by platelet aggregation assay in 426 patients with minor stroke who were receiving combined treatment of aspirin and clopidogrel. All patients were followed up for 90 days. The primary endpoint of the study was END within 10 days after admission. The secondary endpoints included RIS, myocardial infarction and death during 90 days of treatment. The safety endpoints were intracerebral or extracranial hemorrhagic events. Cox proportional hazard regression analysis was performed to determine the risk factors for the primary endpoint and secondary endpoints. Among the 426 patients, 24.4 % exhibited aspirin resistance, 35.9 % exhibited clopidogrel resistance, and 19.2 % displayed concomitant aspirin and clopidogrel resistance. In multivariate analysis, diabetes mellitus and high level of low density lipoprotein-cholesterol were independent risk factors for aspirin resistance, while diabetes mellitus was the only independent risk factor for clopidogrel resistance. END was observed in 93 (21.8 %) patients. Diabetes mellitus, high fasting blood glucose level, and concomitant aspirin and clopidogrel resistance were independent risk factors for END. RIS was observed in 40 (9.4 %) patients. Diabetes mellitus, hypertension, and concomitant aspirin and clopidogrel resistance were independent risk factors for RIS. Antiplatelet drug resistance is common in acute minor ischemic stroke patients and is associated with END and RIS after acute minor ischemic stroke in the Chinese population. http://www.chictr.org/ . Unique Identifier: ChiCTR-OCH-14004724.


Impact of Sex, Sleep, Symptoms of Central Sensitization, and Psychosocial Factors in Adolescents with Chronic Musculoskeletal Pain: An Exploratory Study.
This study aimed to explore and compare the associations of psychosocial factors, sleep, and central sensitization with chronic neck, back, limb, and multiregional pain and disability. One thousand seven hundred thirty (n = 1,730) adolescents responded to an online questionnaire containing questions about sociodemographic data, as well as the Nordic Musculoskeletal Questionnaire; the International Physical Activity Questionnaire; the Functional Disability Inventory; the Depression, Anxiety, and Stress Scale; the Basic Scale on Insomnia Complaints and Quality of Sleep; the Pain Catastrophizing Scale; the Tampa Scale of Kinesiophobia; the Child Self-Efficacy Scale; and the Central Sensitization Inventory. Univariable and multivariable regression analysis were used to assess the associations between these variables and pain and disability. Groups were categorized into those with neck (n = 54), back (n = 80), upper limb (n = 52), lower limb (n = 109), or multiregional (n = 1,140) pain. Multivariable analysis showed that symptoms of central sensitization increased the odds of neck, back, and multiregional pain; depression, anxiety and stress, and physical activity increased the odds of multiregional pain; and fear of movement increased the odds of lower limb pain. Female gender increased the odds of pain in all groups, except in the lower limb group. Depression, anxiety, and stress also remained associated with disability in neck, back, upper limb, and multiregional pain; poorer sleep remained associated with disability in neck, upper limb, and multiregional pain; catastrophizing remained associated with back and multiregional pain; and fear of movement and symptoms of central sensitization were associated with disability only in multiregional pain. There are similar but also different variables associated with the presence of pain and disability in the neck, back, limbs, and multiregional pain.


Resolution of peptide antibiotics, cerexins and tridecaptins, by high performance liquid chromatography (studies on antibiotics from the genus Bacillus. XXVI).
By high performance liquid chromatography, cerexin B was separated into four components (B1, B2, B3 and B4), cerexin D into four components (D1, D2, D3 and D4), tridecaptin A into components (A alpha and A beta), tridecaptin B into four components (B alpha, B beta, B gamma and B delta) and tridecaptin C into three components (C alpha 1, C alpha 2 and C beta 1). All components were preparatively isolated, and their fatty acid and amino acid compositions determined for structural elucidation.


Cells intermediate between mucous neck cells and chief cells in rat stomach.
Morphological and histochemical methods revealed cells intermediate between mucous neck cells and chief cells in rat stomach. The secretory granules of mucous neck cells and chief cells were homogeneous. However, some cells resembling mucous neck cells in shape and size yet contained heterogeneous granules. One type of cell contained mucous granules showing a bipartite structure. The inner cores of these granules resembled the granules of mucous neck cells morphologically and after staining by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) procedure and lectin-ferritin methods. The outer layer of these granules, however, resembled the granules of chief cells and failed to stain by these methods. Another type of cell also contained bipartite granules, but these showed a dense cap and lucent matrix. The cap of the granules did not stain with the PA-TCH-SP and lectin methods, but the remaining matrix was reactive. These presumed transitional cells were located in a layer between the mucous neck cells and the chief cells. Immature chief cells with sparse granular reticulum were found near these intermediate cells in some cases. Many similar intermediate type cells were also found in early developmental stages of the gastric mucosa in rat. These results suggest a close relationship between chief cells and mucous neck cells; chief cells may develop from undifferentiated stem cells via mucous neck cells in adult rat stomach.


Replication of the bovine immunodeficiency-like virus in diploid and aneuploid cells: permanent, latent and virus-productive infections in vitro.
Bovine immunodeficiency-like virus (BIV) is an infectious and leukotropic retrovirus, the sole lentivirus candidate which has been isolated from cattle. Although BIV has recently been shown to be related to the human immunodeficiency virus, there is very limited information on the replication and the pathogenesis of BIV. It is reported here that BIV can permanently infect diploid and aneuploid cells from four different species: bovine, canine, ferret and ovine. With the exceptions of a bovine diploid and a canine aneuploid cell line, all lines were virus non-productive. However, BIV was rescued by co-cultivation of virus non-productive cells with homologous BIV-free or canine cells (Cf2Th). A permanent and BIV-productive infection was established for 90-serial subcultures in a canine cell line. A BIV titre of 1 x 10(6)/0.1 ml was observed in stationary culture and 1 x 10(10)/0.1 ml in suspension culture. The canine cell line above was used for production of BIV antigens, whereas BIV-free canine cells were routinely used to isolate BIV from BIV non-productive cells infected in vitro and from blood from experimentally BIV-infected cattle. The different steps of virus maturation were similar by electron microscopy to those of lentiviruses. BIV results are compared to those of lentiviruses.


Normal Development of the Corpus Callosum and Evolution of Corpus Callosum Sexual Dimorphism in Infancy.
The aim of this study was to establish reference ranges for the corpus callosum in infancy and to clarify how sexual dimorphism evolves between the fetal stage and infancy. Normal sonograms from cerebral ultrasonographic examinations of 1- to 6-month-old healthy full-term infants were selected. The length and thickness of the corpus callosum were determined, and the effect of sex on these values was analyzed. Studies on corpus callosum sexual dimorphism were reviewed. In total, sonograms from 236 1- to 6-month-old infants (120 male and 116 female) were collected, and the typical values (5th-95th percentiles) of the corpus callosum were determined for each group. During the first 2 months, with and without brain size adjustment, the corpus callosum in female infants was significantly thicker than that in male infants (mean thickness ± SD: 1 month, male infant, 1.8 ± 0.3 mm; female infant, 2.1 ± 0.3 mm; P = .005; 2 months, male infant, 1.8 ± 0.2 mm; female infant, 2.0 ± 0.3 mm; P = .002). The corpus callosum thickness of male and female infants had no significant differences after 2 months of age. Sexual dimorphism was not detected in corpus callosum length. Our study provides reference data on typical corpus callosum development in infants. In the fetal period and early infancy, the corpus callosum in female infants is thicker than that in male infants. From 3 months onward, the corpus callosum sexual dimorphism becomes insignificant throughout childhood. The evolvement of corpus callosum sexual dimorphism suggests that maternal factors may influence brain development.


Beta-Ketoacyl-acyl carrier protein synthetase. Characterization of the acyl-enzyme intermediate.
Beta-Ketoacyl-acyl carrier protein (ACP) synthetase catalyzes the condensation reaction of fatty acid synthesis in Escherichia coli. The homogeneous enzyme reacts with hexanoyl-CoA to form hexanoyl-enzyme which was isolated and characterized. Hexanoyl-enzyme contains 2 mol of hexanoate/mol of enzyme (molecular weight 66,000); it is liable at alkaline pH, and it reacts with neutral hydroxylamine to form hexanoyl hydroxamic acid. Hexanoate was cleaved from the enzyme when hexanoyl-enzyme was subjected to performic acid oxidation. These properties indicate that hexanoyl-enzyme is a thioester. Studies of the circular dichroism spectra of fully acylated and nonacylated forms of the enzyme indicated that the secondary structure of the enzyme is relatively unperturbed by the presence of the hexanoyl groups. An alpha helical content of 65% was estimated for the enzyme from the circular dichroism spectrum. Hexanoyl-enzyme is active in both partial reactions that comprise the beta-ketoacyl-ACP synthetase reaction; it reacts with ACP to form hexanoyl-ACP and with malonyl-ACP to form beta-ketooctanoyl-ACP. Although the hexanoate of hexanoyl-enzyme is transferred very rapidly to ACP, the physiological acceptor in this reaction, it is also transferred very slowly to CoA, dithiothreitol, and 2-mercaptoethanol, indicating that the enzyme can react nonspecifically with a number of unrelated mercaptans.


Proliferative dermatitis in a loggerhead turtle, Caretta caretta, and a green turtle, Chelonia mydas, associated with novel papillomaviruses.
A subadult loggerhead turtle, Caretta caretta, presented with generalized small, white, raised lesions over its neck, shoulders, and all four flippers. A juvenile green turtle, Chelonia mydas, recently treated for fibropapillomatosis, presented with four similar localized lesions on one flipper. To diagnose the conditions, biopsies of the lesions were taken for histopathology, electron microscopy, and molecular diagnostics. Histopathologic findings were similar in the two turtles and skin lesions were characterized by multifocal areas of epidermal hyperplasia accompanied by variation and abnormalities in the nuclear morphology of keratinocytes and a few intranuclear inclusions in some cells. Transmission electron microscopy revealed multiple epithelial cells with large intranuclear aggregates of virions consistent in morphology with papillomavirus. Papillomavirus was detected in samples from both turtles by polymerase chain reaction (PCR). Sequence analysis of the partial sequence of the papillomavirus E1 gene revealed two viruses (CcPV and CmPV) that were distinct from each other and from other species in Papillomaviridae, and likely represent two novel species and perhaps a new genus.


Mapping of B cell epitopes on desmoglein 3 in pemphigus vulgaris patients by the use of overlapping peptides.
Pemphigus vulgaris (PV) is a severe autoimmune blistering disease associated with autoantibodies to desmoglein 3 (Dsg 3), a transmembrane glycoprotein of the cadherin family. Previous studies mainly focused on the mapping of conformational epitopes of Dsg 3 using recombinant fragments of Dsg 3 and competition ELISA. Here, we performed a mapping of linear B cell epitopes on Dsg 3 in PV patients by the use of overlapping synthetic peptides. A set of 254 overlapping synthetic peptides of 14 amino acids length covering the entire Dsg 3 extracellular domain was generated. Sera of patients with active PV (n=10) and healthy volunteers (n=10) were tested for IgG reactivity with the 254 peptides by ELISA. Testing each peptide separately, 7 major antigenic sites were identified. In order to validate these reactivities, 7 corresponding peptides of 13-33 amino acids in length were generated and employed by ELISA. Additional sera of active PV patients (n=17) and healthy volunteers (n=20) were tested and the most reactive peptide was used to specifically purify anti-Dsg 3 antibodies from PV sera (n=3). The major autoantibody reactivity in PV sera was mapped to amino acids 333-356 within the EC3 domain. Purifying patients IgG using the identified peptide, however, failed to induce acantholysis in keratinocyte dissociation assay. We conclude that linear epitopes do not play a major pathogenic role in human PV.


A Novel Assay for Investigating the Role of Exosomes in Tumor Cell-Endothelial Cell Crosstalk.
Exosomes have critical role in regulating the tumor development and progression and resistance following antiangiogenesis therapies (AATs). Exosomes could be released by both tumor cells and surrounding endothelial cells (ECs). Here, we describe the methods to explore the cargo transfer between tumor cells and ECs by a novel four-compartment co-culture methods and to investigate the effect of tumor cells on angiogenic ability of ECs by Transwell co-culture methods.


A back-propagation programmed network that simulates response properties of a subset of posterior parietal neurons.
Neurons in area 7a of the posterior parietal cortex of monkeys respond to both the retinal location of a visual stimulus and the position of the eyes and by combining these signals represent the spatial location of external objects. A neural network model, programmed using back-propagation learning, can decode this spatial information from area 7a neurons and accounts for their observed response properties.


Application of Machine Learning to Assess Interindividual Variability in Rapid-Acting Insulin Responses After Subcutaneous Injection in People With Type 1 Diabetes.
Circulating insulin concentrations mediate vascular-inflammatory and prothrombotic factors. However, it is unknown whether interindividual differences in circulating insulin levels are associated with different inflammatory and prothrombotic profiles in type 1 diabetes (T1D). We applied an unsupervised machine-learning approach to determine whether interindividual differences in rapid-acting insulin levels associate with parameters of vascular health in patients with T1D. We re-analyzed baseline pretreatment meal-tolerance test data from 2 randomized controlled trials in which 32 patients consumed a mixed-macronutrient meal and self-administered a single dose of rapid-acting insulin individualized by carbohydrate counting. Postprandial serum insulin, tumour necrosis factor (TNF)-alpha, plasma fibrinogen, human tissue factor (HTF) activity and plasminogen activator inhibitor-1 (PAI-1) were measured. Two-step clustering categorized individuals based on shared clinical characteristics. For analyses, insulin pharmacokinetic summary statistics were normalized, allowing standardized intraindividual comparisons. Despite standardization of insulin dose, individuals exhibited marked interpersonal variability in peak insulin concentrations (48.63%), time to peak (64.95%) and insulin incremental area under the curve (60.34%). Two clusters were computed: cluster 1 (n=14), representing increased serum insulin concentrations; and cluster 2 (n=18), representing reduced serum insulin concentrations (cluster 1: 389.50±177.10 pmol/L/IU h-1; cluster 2: 164.29±41.91 pmol/L/IU h-1; p<0.001). Cluster 2 was characterized by increased levels of fibrinogen, PAI-1, TNF-alpha and HTF activity; higher glycated hemoglobin; increased body mass index; lower estimated glucose disposal rate (increased insulin resistance); older age; and longer diabetes duration (p<0.05 for all analyses). Reduced serum insulin concentrations are associated with insulin resistance and a prothrombotic milieu in individuals with T1D, and therefore may be a marker of adverse vascular outcome.


Light-induced fluorescence changes in Phycomyces: evidence for blue light-receptor associated flavo-semiquinones.
Light-induced fluorescence changes (LIFCs) were detected in sporangiophores of the blue-light-sensitive fungus Phycomyces blakesleeanus (Burgeff). The LIFCs can be utilized as a spectrophotometric assay for blue-light photoreceptors and for the in vivo characterization of their photochemical primary reactions. Blue-light irradiation of sporangiophores elicited a transient decrease and subsequent regeneration of flavin-like fluorescence emission at 525 nm. The signals recovered in darkness in about 120 min. In contrast to blue light, near-UV (370 nm) caused an increase in the fluorescence emission at 525 nm. Because the LIFCs were altered in a light-insensitive madC mutant with a defective photoreceptor, the fluorescence changes must be associated with early photochemical events of the transduction chain. Action spectra for the fluorescence changes at 525 nm showed major peaks near 470 and 600 nm. Double-pulse experiments involving two consecutive pulses of either blue and near-UV, blue and red, or near-UV and red showed that the responses depended on the sequence in which the different wavelengths were applied. The results indicate a blue-light receptor with intermediates in the near-UV, blue and red spectral regions. We explain the results in the framework of a general model, in which the three redox states of the flavin photoreceptor, the oxidized flavin (Fl), the flavo-semiquinone (FlH*), and the flavo-hydroquinone (FlH2) are each acting as chromophores with their own characteristic photochemical primary reactions. These consist of the photoreduction of the oxidized flavin generating semiquinone, the photoreduction of the semiquinone generating hydroquinone, and the photooxidation of the flavo-hydroquinone regenerating the pool of oxidized flavins. The proposed mechanism represents a photocycle in which two antagonistic photoreceptor forms, Fl and FlH2, determine the pool size of the biological effector molecule, the flavo-semiquinone. The redox changes that are associated with the photocycle are maintained by redox partners, pterins, that function in the near-UV as secondary chromophores.


Weight loss surgery and subsequent emergency care use: a population-based cohort study.
This study assessed long-term emergency care utilization after weight loss surgery. We conducted a self-matched longitudinal cohort analysis of weight loss surgery patients in Ontario operated between April 1, 2006, and March 31, 2011. Using population-wide registries, we compared emergency visits in the 3-year interval after surgery to the 3 years before surgery using incidence rate ratios with 95% confidence intervals. The study excluded patients with repeat surgeries, and the analysis excluded visits in the immediate perioperative interval (ie, 3 months before and after surgery). A total of 8815 patients were identified of whom most were women (81%), living in an urban area (84%), and treated with gastric bypass (99%). Approximately half (53%) were aged 25 to 45 years. Approximately half of the patients 4364 (49%) had at least 1 emergency in both preoperative and postoperative intervals, 1417 (16%) in the preoperative interval only and 1661 (19%) in the postoperative interval only. Total emergencies significantly increased from 852 per 1000 patient-years to 1000 per 1000 patient-years, equal to an incidence rate ratio of 1.17 (95% confidence interval, 1.13-1.21; P<.001). Compared to baseline, emergencies from gastrointestinal, genitourinary, substance misuse, trauma, and miscellaneous complaints increased significantly after surgery. Conversely, emergencies due to cardiovascular, ear, respiratory, and dermatology complaints decreased significantly after surgery. Ambulance use, triage urgency, and hospitalizations were significantly higher for emergencies after surgery. Persistent and resource-intensive emergency care utilization after weight loss surgery underscores the need of long-term patient support.


Dislocation of the shoulder joint with ipsilateral humeral shaft fracture: two case reports.
A combination of the shaft fracture of the humerus with shoulder dislocation is a rarely documented injury. Moreover, few reports describe a long-term outcome after a follow-up period over 10 years. The present article is the first report of long-term clinical results obtained with this combined injury. We present two cases of the dislocation of the shoulder joint with ipsilateral humeral shaft fracture. One is an anterior dislocation and the other is posterior. The anterior dislocation was closely reduced on the date of injury, but the posterior dislocation required open reduction 6 weeks after the injury because it was missed at the initial diagnosis and identified 4 weeks after the injury. In the latter case, shoulder pain and limitation of the motion persisting after the first surgery had to be treated by anterior acromioplasty and arthrolysis of the shoulder. In both cases, the humeral fracture was fixed by retrograde intramedullary nailing using a Küntscher nail and successful bone union was achieved. At over 10-year follow-up examination, both patients had no limitation in activities of daily living and no restrictions to their normal occupation. The radiographs of the shoulder joint demonstrated good clinical results, with no degenerative change or osteonecrosis. We have experienced two cases of dislocation of the shoulder joint with ipsilateral humeral shaft fracture and reported long-term results over 10 years. Good clinical results were demonstrated in both cases.


The rs3743205 SNP is important for the regulation of the dyslexia candidate gene DYX1C1 by estrogen receptor β and DNA methylation.
Estrogen is involved in numerous physiological processes such as growth, differentiation, and function of the male and female reproductive tissues. In the developing brain, estrogen signaling has been linked to cognitive functions, such as learning and memory; however, the molecular mechanisms underlying this phenomenon are poorly understood. We have previously shown a link between developmental dyslexia and estrogen signaling, when we studied the functional interactions between the dyslexia candidate protein DYX1C1 and the estrogen receptors α (ERα) and β (ERβ). Here, we investigate the 17β-estradiol (E2)-dependent regulation of dyslexia susceptibility 1 candidate 1 (DYX1C1) expression. We demonstrate that ERβ, not ERα, binds to a transcriptionally active cis-regulatory region upstream of DYX1C1 transcriptional start site and that DYX1C1 expression is enhanced by E2 in a neuroblastoma cell line. This regulation is dependent on transcription factor II-I and liganded ERβ recruitment to this region. In addition, we describe that a single nucleotide polymorphism previously shown to be associated with dyslexia and located in the cis-regulatory region of DYX1C1 may alter the epigenetic and endocrine regulation of this gene. Our data provide important molecular insights into the relationship between developmental dyslexia susceptibility and estrogen signaling.


Danish translation and adaptation of Loewenstein Occupational Therapy Cognitive Assessment 2nd Edition (LOTCA-II).
To translate and adapt the English version of the Loewenstein Occupational Therapy Cognitive Assessment 2nd Edition (LOTCA-II) to Danish. The translation process followed the overall guidelines of the World Health Organization (WHO) with forward translation, expert panel discussion, pre-tests and interviews with patients and laymen, and back-translation. The translation was successful and minor corrections and adaptations were made. In total three versions were produced before the final Danish version LOTCA-II/D was drafted. The Danish version of LOTCA-II was successfully translated and adapted based on the WHO guidelines. Before implementation in clinical practice further research of the reliability and validity of the LOTCA-II/D are needed.


A Review on Interface Engineering of MXenes for Perovskite Solar Cells.
With an excellent power conversion efficiency of 25.7%, closer to the Shockley-Queisser limit, perovskite solar cells (PSCs) have become a strong candidate for a next-generation energy harvester. However, the lack of stability and reliability in PSCs remained challenging for commercialization. Strategies, such as interfacial and structural engineering, have a more critical influence on enhanced performance. MXenes, two-dimensional materials, have emerged as promising materials in solar cell applications due to their metallic electrical conductivity, high carrier mobility, excellent optical transparency, wide tunable work function, and superior mechanical properties. Owing to different choices of transition elements and surface-terminating functional groups, MXenes possess the feature of tuning the work function, which is an essential metric for band energy alignment between the absorber layer and the charge transport layers for charge carrier extraction and collection in PSCs. Furthermore, adopting MXenes to their respective components helps reduce the interfacial recombination resistance and provides smooth charge transfer paths, leading to enhanced conductivity and operational stability of PSCs. This review paper aims to provide an overview of the applications of MXenes as components, classified according to their roles as additives (into the perovskite absorber layer, charge transport layers, and electrodes) and themselves alone or as interfacial layers, and their significant importance in PSCs in terms of device performance and stability. Lastly, we discuss the present research status and future directions toward its use in PSCs.


Publishing on the WWW. Part 3 - Scanning medical images for screen presentation.
The purpose of this article is to remove the myths and black art surrounding electronic imaging and prove beyond doubt that any mind competent in the workings of the human body is capable of producing good on-screen images from adequate equipment. Note that in this day and age of SI units imaging still uses inches to describe diagonal screen size and pixels per inch to describe resolution.


Effect of seasonal abiotic conditions and field margin habitat on the activity of Pandora neoaphidis inoculum on soil.
The ability of the aphid pathogenic fungus Pandora neoaphidis to remain active in the absence of a resting stage through a combination of continuous infection and as conidia deposited on soil was assessed alongside the potential for planted field margins to act as a refuge for the fungus. P. neoaphidis was able to infect the pea aphid, Acyrthosiphon pisum, when maintained under controlled conditions that simulated those that occur seasonally in the UK. Although there was a significant inverse relationship between temperature and time-to-kill, with death occurring after 4.2, 6.9 and 13.6 days when maintained under fluctuating summer, autumn and winter temperatures, respectively, there were no additional statistically significant effects of photoperiod. The activity of inoculum on soil was indirectly assessed by baiting with A. pisum. Under controlled conditions P. neoaphidis remained active on soil and was able to infect aphids for up to 80 days. However, the percentage of aphids that became infected decreased from 76% on day 1 to 11% on day 80. Whereas there was little difference in the activity of conidia that had been maintained at 4 degrees C and 10 degrees C, activity at 18 degrees C was considerably reduced. Under field conditions the activity of inoculum was strongly influenced by season. On day 49 there was little or no activity during spring, summer or winter. However, during autumn a mean proportion of 0.08 aphids still became infected with P. neoaphidis. Margin type did not affect the activity of conidia nor was there a difference in activity between blocks that had regenerated naturally and those that had been planted. These results suggest that P. neoaphidis can infect aphids and remain active on soil under the abiotic conditions that occur seasonally in the UK and that this fungus may be able to persist annually without a resting stage.


Noncovalent Self-Assembled Monolayers on Graphene as a Highly Stable Platform for Molecular Tunnel Junctions.
Monolayer graphene is used as the bottom electrode to fabricate stable and high-quality self-assembled monolayer (SAM)-based tunnel junctions. The SAMs are formed on graphene via noncovalent bonds without altering the structure of the graphene. This work paves the way to new types of molecular electronic junctions based on 2D materials.


Implications of age of onset for delinquency risk.
A substantial body of research suggests that age of onset is a viable discriminator of risk for chronic versus transient delinquency. Also, a multivariate model of psychosocial variables (demographics, individual, school, and family functioning) appears likely to provide a comparatively accurate and useful discriminatory model for prediction. These two findings were applied to a normal sample of male adolescents (N = 199, ages 15-18) to study the relationship of age of onset to delinquent behavior (as opposed to use of legal status to denote delinquency) and legal status. Additionally, the efficiency and improvement over chance accuracy of a multivariate model developed as part of a larger research project was tested. Results indicated that age of onset is an important and accurate discriminator of extent of subsequent delinquency. Subjects with an early age of onset reported more delinquent behavior, were more likely to be adjudicated, and showed different patterns of delinquency. A combination of demographic, individual, school, and family variables predicted age of onset.


A comprehensive assessment of upgrading technologies of wastewater treatment plants in Taihu Lake Basin.
To meet the increasingly stringent discharge standards of wastewater treatment plants (WWTPs) in the Taihu Lake Basin, the Chinese government successively established the National Special Water Project Program to develop new technologies to retrofit and upgrade existing wastewater treatment processes during the 11th, 12th, and 13th Five-Year Plans. However, there is a lack of systematic sorting of the existing research outcomes, and thus hinders the application and promotion of the upgrade technologies. Based on the outcomes of the National Special Water Project and a field survey, this research analyzed the current status of wastewater treatment in the Taihu Lake Basin and systematically integrated the retrofitting measures of WWTPs in terms of achieving the Grade IA of the national standard and local stricter discharge standards (DB 32/1072-2018 and DB 33/2169-2018). In particular, the boundary conditions, design parameters, specific recommendations of the technologies, and some typical engineering cases were provided accordingly. Finally, this study discussed the future development directions of WWTPs during the upgrade process from the perspective of carbon neutrality and digitalization. The present work will hopefully assist in retrofitting and constructing WWTPs to achieve the stricter effluent discharge criteria and help optimize the design and construction of WWTPs in the best way.