Skin tests in Nigerian asthmatics from the equatorial forest zone in Benin, Nigeria.
Forty-two patients with bronchial asthma from the Benin area and 32 control subjects were subjected to skin prick tests for groups of allergens. There was a significant excess of reactions of 5 mm or over to Dermatophagoides farinae amongst the asthmatics. This was the most commonly detected allergen. There was an overall excess in asthmatics of positive reactions of over 5 mm in the other groups although there was no significant excess in any single group. There was no significant difference in the weaker skin reactions (less than 5 mm between) asthmatics and controls. From clinical histories most precipitating factors known to patients were probably non-allergic in origin, exercise, irritant odours, dust and climatic changes being the commonest. Sets of allergens specially prepared for West Africa would be valuable for skin testing asthmatics in this environment.


Local variation in diapause characteristics of Tetranychus urticae Koch (Acarina: Tetranychidae).
Diapause characteristics of nine local populations of Tetranychus urticae Koch (Acarina: Tetranychidae) occurring on rose in central Japan were investigated. The percentage of females that entered diapause at 18° C and 9L: 15D photoperiod ranged between 0 and 77%. In addition, both photoperiodic and temperature responses varied widely among these populations. We suggest that temperature response might be a better trait than photoperiodic response for selection among local populations. Females in diapause survived -24° C better than those that were not. However, no difference in cold hardiness among these populations was found. The mite responded rapidly to artificial selection for low and high diapause percentage. The response was asymmetrical, being easier in the direction of low diapause percentage. Reciprocal and back crosses using selected low and high diapause percentage cultures showed that the genetic control of diapause was complicated. Neither the "lowdiapause" nor the "high-diapause" trait dominated over the other. However, the "low-diapause" trait seemed to be stronger. The results of this study suggest that variation in diapause response is maintained by (1) adaptation to local environments and (2) the complexity of the genetics of diapause. Such variation may provide the genetic raw material for natural selection and is a prerequisite for the extension of ecological range.


Immunogenicity, safety and inter-lot consistency of a meningococcal conjugate vaccine (MenACYW-TT) in adolescents and adults: A Phase III randomized study.
MenACYW-TT is an investigational quadrivalent (serogroups A, C, W and Y) meningococcal conjugate vaccine that is being developed for protection against invasive meningococcal disease. In this Phase 3, blinded, randomized study, 3344 meningococcal vaccine-naïve 10-55-year-olds were randomized (3:3:3:2) to receive one of three lots of MenACYW-TT or licensed quadrivalent meningococcal conjugate vaccine, MCV4-DT (NCT02842853). Antibody titers were assessed by human and rabbit complement serum bactericidal antibody assays. The co-primary objectives were to demonstrate lot-to-lot consistency of MenACYW-TT by the between-lot geometric mean titer ratios (GMTR) at Day 30, and non-inferiority of Day 30 vaccine seroresponses (titers ≥ 1:16 if pre-vaccination titers < 1:8, or ≥ 4-fold increase if pre-vaccination titers ≥ 1:8) with MenACYW-TT vs MCV4-DT. Further objectives included safety and immunogenicity. Lot consistency was demonstrated for all three lots, with GMTRs ranging from 0.87 to 1.1. The proportion of participants achieving seroresponse in the MenACYW-TT group (data pooled from the 3 lots) was non-inferior to MCV4-DT (A: 74% vs 55%; C: 89% vs 48%; W: 80% vs 61%; Y: 91% vs 73%, respectively). MenACYW-TT and MCV4-DT had similar safety profiles; no safety concerns were identified. The study met both co-primary endpoints, demonstrating lot-to-lot consistency and non-inferiority of MenACYW-TT vs MCV4-DT in adolescents and adults.


Severe autosomal recessive retinitis pigmentosa maps to chromosome 1p13.3-p21.2 between D1S2896 and D1S457 but outside ABCA4.
A severe form of autosomal recessive retinitis pigmentosa (arRP) was identified in a large Pakistani family ascertained in the Punjab province of Pakistan. All affected individuals in the family had night blindness in early childhood, early complete loss of useful vision, and typical RP fundus changes plus macular degeneration. After exclusion of known arRP loci, a genome-wide scan was performed using microsatellite markers at about 10 cM intervals and calculating two-point lod scores. PCR cycle dideoxynucleotide sequencing was used to sequence candidate genes inside the linked region for mutations. RP in this family shows linkage to markers in a 10.5 cM (8.9 Mbp) region of chromosome 1p13.3-p21.2 between D1S2896 and D1S457. D1S485 yields the highest lod score of 6.54 at theta=0. Sequencing the exons and intron-exon boundaries of five candidate genes and six ESTs in this region, OLFM3, GNAI3, LOC126987, FLJ25070, DKFZp586G0123, AV729694, BU662869, BU656110, BU171991, BQ953690, and CA397743, did not identify any causative mutations. This novel locus lies approximately 4.9 cM (7.1 Mbp) from ABCA4, which is excluded from the linked region. Identification and study of this gene may help to elucidate the phenotypic diversity of arRP mapping to this region.


The hemostatic effect of hot saline irrigation in endoscopic sinus surgery: a systematic review and meta-analysis.
A good control of intraoperative bleeding is key for adequate anatomical visualization during endoscopic sinus surgery (ESS). The objective of this review was to assess the practice of hot intranasal saline irrigation (HSI) in achieving intraoperative hemostasis and good surgical field quality during ESS. An electronic search was performed via PubMed, SCOPUS, Google Scholar, and Cochrane from inception to June 2022. The included trials were evaluated according to the recommendations of the Cochrane Handbook for Systematic Reviews. The primary outcome assessed was the intraoperative bleeding score of the surgical field. The mean arterial pressure, duration of the surgery, amount of blood loss and surgeon's satisfaction score were assessed as the secondary outcomes. The risk of bias for each study was evaluated using the Cochrane risk of bias tool. A total of 254 records were identified after removal of duplicates. Based on the title and abstract 246 records were excluded, leaving seven full texts for further consideration. Five records were excluded following full text assessment. Three trials with a total of 212 patients were selected. Hot saline irrigation was superior to control in the intraoperative bleeding score (MD - 0.51, 95% CI - 0.84 to - 0.18; P < 0.001; I2 = 72%; very low quality of evidence) and surgeon's satisfaction score (RR 0.18, 95% CI 0.09 to 0.33; P < 0.001; I2 = 0%; low quality of evidence). The duration of surgery was lengthier in control when compared to HSI (MD - 9.02, 95% CI - 11.76 to - 6.28; P < 0.001; I2 = 0; very low quality of evidence). The volume of blood loss was greater in control than HSI (MD - 56.4, 95% CI - 57.30 to - 55.51; P < 0.001; I2 = 0%; low quality of evidence). No significant difference between the two groups for the mean arterial pressure was noted (MD - 0.60, 95% CI - 2.17 to 0.97; P = 0.45; I2 = 0%; low quality of evidence). The practice of intranasal HSI during ESS is favorable in controlling intraoperative bleeding and improving the surgical field quality. It increases the surgeon's satisfaction, reduces blood loss, shortens operative time and has no effect on intraoperative hemodynamic instability. PROSPERO registration number: CRD42019117083.


CCL5 protein level: influence on breast cancer staging and lymph nodes commitment.
Many tumor cells express chemokines and chemokine receptors, and these molecules can contribute to distinct modes of metastasis processes. It is known that they play a crucial role in breast cancer (BC) tumorigenesis and progression. Considering this, it was investigated a possible role for C-Chemokine receptor type 5(CCR5) polymorphism (rs333/delta32) by conventional polymerase chain reaction (PCR) and CCL5 (C-C motif chemokine ligand 5) protein level by immunosorbent assay (ELISA) in 47 BC patients (resulting in 47 tumoral tissue samples and 47 adjacent normal tissue samples). There was a significant difference between CCL5 level in tumoral and adjacent normal tissues for the same BC patients (p < 0.0001). A significant association was also found for CCL5 level in relation to lymph nodes commitment (p = 0.03). Likewise, there was a significant difference in CCL5 level from tumor tissue of stage III in relation to stage I (p < 0.02). On the other hand, it was verified that CCR5-delta32 polymorphism presented no significant association in relation to CCL5 protein level. Considering the present findings, we suggest that CCL5 may be involved in BC staging and metastasis process.


Characterization of purinoceptors present on human liver plasma membranes.
Using ATP alpha 35S as radioligand, we have detected the presence of specific purinoceptors on human liver plasma membranes. They are characterized by a Kd value of 0.19 microM and a Bmax of 24 pmol/mg membrane protein. These purinoceptors belong to the P2Y subclass as demonstrated by the high degree of similarity with rat liver purinoceptors, previously shown to be P2Y [(1986) Biochem. J. 240, 367-371] and known to be involved in the control of liver glycogenolysis.


Partial stereochemical assignment of quartromicins A3 and D3.
[structure: see text]. A partial stereochemical assignment of quartromicins A3 (R = alpha-D-galactosyl) and D3 (R = H, M+ = Na+, K+, Ca+) is presented.


Development of hepatocellular carcinoma associated with increases in DNA synthesis in the surrounding cirrhosis.
The relationship between DNA synthesis activity in hepatocytes from cirrhotic tissue and development of hepatocellular carcinoma was studied in 33 posthepatitic patients with Child's grade A cirrhosis. DNA synthesis activity was measured by a bromodeoxyuridine (a thymidine analogue) labeling index, using the bromodeoxyuridine-antibromodeoxyuridine in vitro method, and the patients were followed up prospectively with frequent liver ultrasonography for 2 years. During the 2-year follow-up, 11 of the 33 cirrhotic patients developed hepatocellular carcinoma; they included 8 of the 15 patients (53%) in the high labeling index (greater than 1.5%) group compared with only 3 of the 18 patients (17%) in the low labeling index (less than 1.5) group (P less than 0.05). Five of the latter 18 subsequently had increased synthesis activity. Of these 20 patients who showed high synthesis activities either initially or subsequently, 10 (50%) developed hepatocellular carcinoma, in contrast to 1 of 13 (8%) with persistently low activities (P less than 0.05). Thus, hepatocellular carcinoma seems to develop or may become detectable when DNA synthesis in the background cirrhosis is increasing or remains high.


Preoperative angiographic embolization for large hemorrhagic Wilms' tumor.
Preoperative angiographic embolization of the renal artery is a surgical adjunct not necessary for the majority of Wilms' tumors. However, on the basis of early experience, we would recommend this technique for those large vascular tumors with preoperative hemorrhage in which the risk of embolization is likely to outweight the risk of intraoperative disruption and hemorrhage.


Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy.
Most solid tumor cells adapt to their heterogeneous microenvironment by depending largely on aerobic glycolysis for energy production, a phenomenon called the Warburg effect, which is a hallmark of cancer. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generate essential metabolic intermediates that play a pivotal role in the biosynthesis of macromolecules, to support cell proliferation, invasiveness, and chemoresistance. The cellular metabolic reprogramming in cancer is regulated by several oncogenic proteins and tumor suppressors such as hypoxia-inducible factor (HIF-1), Myc, p53, and PI3K/Akt/mTOR pathway. A better understanding of the mechanisms involved in the regulation of aerobic glycolysis can help in developing glycolytic inhibitors as anticancer agents. These metabolic antiglycolytic agents could be more effective if used in drug combinations to combat cancer. Several preclinical and early clinical studies have shown the effectiveness of targeting the glycolytic pathway as a therapeutic approach to suppress cancer progression. This review aimed to present the most recent data on the emerging drug candidate targeting enzymes and intermediates involved in glucose metabolism to provide therapeutic opportunities and challenges for antiglycolytic cancer therapy.


A few-shot sample augmentation algorithm based on SCAM and DEPS for pump fault diagnosis.
In recent years, pumps have become critical components in agriculture, industry, and the military, necessitating extensive development and implementation of the fault diagnosis method. In the majority of existing fault classification models, the connection between performance improvement and the amount of training data remains high, yet real-world samples are difficult to obtain. Combining domain migration theory and sample expansion method, this paper introduces a few-shot learning fault diagnosis method. Employing the T-SNE visualization algorithm, we examine the validity of the self-calibration attention mechanism (SCAM) and distribution edge prediction strategy (DEPS). The accomplishment demonstrated that the proposed algorithm could effectively map the expanded sample space within a separate interval, thereby avoiding the problem of feature aliasing caused by the overlap of sample features among similar categories and significantly enhancing the quality and quantity of training samples. The experimental analysis indicates that the proposed methodology can effectively increase the accuracy of few-shot tasks, especially in the 9way-15shot task, where it maintains a performance of 72 %, which leading the mean accuracy calculated from the others of about 30%. It is believed that much of the work has superior applicability to other few-shot diagnosis cases.


Provision of immobilization or ice by paramedics in Southwestern Ontario.
Pain is the most common reason for prehospital transport. As emergency wait times increase, timely pain management is essential. In children, there is abundant evidence that prehospital pharmacologic analgesia is suboptimal, but little is known about non-pharmacologic therapies. We sought to characterize documentation by paramedics of non-pharmacologic (immobilization and ice) and pharmacologic analgesia in children with musculoskeletal injuries. We reviewed all ambulance call reports for children 0-17 years transported to Southwestern Ontario regional hospitals from January 1, 2017, to December 31, 2019, with a musculoskeletal injury (Ontario Ministry of Health and Long-Term Care problem codes 66 and 67). Primary and secondary outcomes were documented immobilization or ice and pharmacologic analgesia, respectively. In a multivariable analysis, we explored the relationship between immobilization or ice and the following a priori covariates: age, sex, visible deformity, crew type, pain severity, and analgesia. Of 40,692 ambulance call reports reviewed, 4445 met inclusion criteria. There were 2584/4441 (58.2%) males, with a median (IQR) age of 14 (10, 16) years. In ambulance call reports with documented pain scores, 2106/3048 (69.1%) ambulance call reports reported "moderate or severe" pain. Immobilization or ice were documented in 1605/4445 (36.1%) and 385/4445 (8.7%) of ambulance call reports. Pharmacologic analgesia was documented in 275/1983 (13.9%) and 125/991 (12.6%) of ambulance call reports for primary care paramedics and advanced care paramedics, respectively. An increased odds of documented immobilization or ice was associated with moderate or severe pain [OR: 2.4; 95% CI 1.84-3.17; p < 0.01] and visible deformity [OR: 2.5; 95% CI 1.97-3.12; p < 0.01]. Documented immobilization and ice and pharmacologic analgesia to children by paramedics is suboptimal. Our findings underscore an important need for enhanced education surrounding the benefits of non-pharmacologic options for children with musculoskeletal injuries.


Outcomes of stepping down asthma medications in a guideline-based pediatric asthma management program.
Little is known about outcomes after stepping down asthma medications within an asthma management program. To determine outcomes of stepping down asthma medications in a pediatric asthma management program. We performed a retrospective study of 5- to 18-year-old children with asthma in an integrated primary care practice in the United States. Data were included on participants from March 1, 2009, until December 31, 2011. We first determined whether a child was eligible for step down and next recorded whether a step-down attempt was made and if the attempt was successful. In addition to descriptive statistics for the sample demographics and the outcomes of stepping down, univariate and multivariate analyses were performed to determine predictors of successful asthma medication step-down attempts. Of the 477 children sampled for this study, 264 (55.3%) had a guideline-eligible opportunity to step down asthma medications. An attempted step down occurred in only 89 (33.7%) of children who had guideline-eligible opportunities. A total of 166 children (34.8%) attempted a step down of asthma medication at least once (including those guideline ineligible to step down). Of children with follow-up, 96 (71.6%) of step-down attempts were successful. Time of year (any season except fall) when the step down was attempted predicted successful step down in univariate and multivariate analysis (odds ratio = 3.81; 95% confidence interval, 1.23-11.85; P = .02). Being guideline eligible for step down predicted successful step down in univariate analysis only (odds ratio = 2.51; 95% confidence interval, 1.16-5.43; P = .02). Our findings from this sample of children participating in an asthma management program suggest that stepping down asthma medication based on National Asthma Education and Prevention Program 3 guidelines is frequently successful.


Amino acid sequence of the light chain of bovine protein C.
The amino acid sequence of the light chain of the vitamin K-dependent protein C from bovine plasma is reported together with the supporting data. The sequence was determined by sequenator analysis of intact light chain, which contains 155 amino acid residues, and fragments obtained by chemical and enzymatic degradation of the light chain. All 11 glutamyl residues up to position 44 are carboxylated as gamma-carboxyglutamic acid residues. This part of the molecule proved very homologous to the other vitamin K-dependent plasma proteins. The remaining part (111 residues) is homologous to the corresponding parts in factor IX and factor X but not to prothrombin.


The L444P Gba1 mutation enhances alpha-synuclein induced loss of nigral dopaminergic neurons in mice.
Mutations in glucocerebrosidase 1 (GBA1) represent the most prevalent risk factor for Parkinson's disease. The molecular mechanisms underlying the link between GBA1 mutations and Parkinson's disease are incompletely understood. We analysed two aged (24-month-old) Gba1 mouse models, one carrying a knock-out mutation and the other a L444P knock-in mutation. A significant reduction of glucocerebrosidase activity was associated with increased total alpha-synuclein accumulation in both these models. Gba1 mutations alone did not alter the number of nigral dopaminergic neurons nor striatal dopamine levels. We then investigated the effect of overexpression of human alpha-synuclein in the substantia nigra of aged (18 to 21-month-old) L444P Gba1 mice. Following intraparenchymal injections of human alpha-synuclein carrying viral vectors, pathological accumulation of phosphorylated alpha-synuclein occurred within the transduced neurons. Stereological counts of nigral dopaminergic neurons revealed a significantly greater cell loss in Gba1-mutant than wild-type mice. These results indicate that Gba1 deficiency enhances neuronal vulnerability to neurodegenerative processes triggered by increased alpha-synuclein expression.


Do practicing clinicians agree with expert ratings of neonatal intensive care unit quality measures?
To assess the level of agreement when selecting quality measures for inclusion in a composite index of neonatal intensive care quality (Baby-MONITOR) between two panels: one comprised of academic researchers (Delphi) and another comprised of academic and clinical neonatologists (clinician). In a modified Delphi process, a panel rated 28 quality measures. We assessed clinician agreement with the Delphi panel by surveying a sample of 48 neonatal intensive care practitioners. We asked the clinician group to indicate their level of agreement with the Delphi panel for each measure using a five-point scale (much too high, slightly too high, reasonable, slightly too low and much too low). In addition, we asked clinicians to select measures for inclusion in the Baby-MONITOR based on a yes or no vote and a pre-specified two-thirds majority for inclusion. In all, 23 (47.9%) of the clinicians responded to the survey. We found high levels of agreement between the Delphi and clinician panels, particularly across measures selected for the Baby-MONITOR. Clinicians selected the same nine measures for inclusion in the composite as the Delphi panel. For these nine measures, 74% of clinicians indicated that the Delphi panel rating was 'reasonable'. Practicing clinicians agree with an expert panel on the measures that should be included in the Baby-MONITOR, enhancing face validity.


Recurrent laryngeal nerve injury in thyroid surgery: Clinical pathways and resources consumption.
The impact of recurrent laryngeal nerve (RLN) injury management in thyroid surgery seems to be relevant to patients, National Healthcare System (NHS), and society. We studied resource consumption in the management of patients with RLN injury versus noninjured patients investigating 3 perspectives (patients, NHS, and society) in 5 clinical pathways. Direct medical costs supported by the NHS range from a minimum of euro (€) 79.46 to a maximum of € 3261.95. From the patient's perspective, the direct medical costs supported by the patient increased from a minimum of € 3.60 to a maximum of € 499.45. Productivity losses were accounted in € 156 per day per patient. From the NHS perspective, the percentage increase ranged from 43.25% to 98.14%. From the patient's perspective, it ranged from 51.52% to 80.60%. The analysis shows a significant economic impact of RLN injury management, which varies depending on the damage, duration, and severity. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.


Correlation of intralesional in vivo chemotherapy of line 10 hepatoma with in vitro drug sensitivity.
The effects of intralesional chemotherapy with 7 different drugs on line 10 hepatoma grown in strain 2 guinea pigs were compared with the sensitivity of line 10 tumor cells in vitro, using a micro modification of the tumor stem assay with capillary tubes. A modified method was used to evaluate the in vitro dose-response curves. The correlation for in vivo/in vitro resistance was found to be 100% and for in vivo/in sensitivity it was 80%.


On-surface synthesis of disilabenzene-bridged covalent organic frameworks.
Substituting carbon with silicon in organic molecules and materials has long been an attractive way to modify their electronic structure and properties. Silicon-doped graphene-based materials are known to exhibit exotic properties, yet conjugated organic materials with atomically precise Si substitution have remained difficult to prepare. Here we present the on-surface synthesis of one- and two-dimensional covalent organic frameworks whose backbones contain 1,4-disilabenzene (C4Si2) linkers. Silicon atoms were first deposited on a Au(111) surface, forming a AuSix film on annealing. The subsequent deposition and annealing of a bromo-substituted polyaromatic hydrocarbon precursor (triphenylene or pyrene) on this surface led to the formation of the C4Si2-bridged networks, which were characterized by a combination of high-resolution scanning tunnelling microscopy and photoelectron spectroscopy supported by density functional theory calculations. Each Si in a hexagonal C4Si2 ring was found to be covalently linked to one terminal Br atom. For the linear structure obtained with the pyrene-based precursor, the C4Si2 rings were converted into C4Si pentagonal siloles by further annealing.


ATP-ADP compartmentation in storage pool deficient platelets: correlation between granule-bound ADP and the bleeding time.
Platelets contain two major compartments of ATP and ADP, the cytosol and the dense granules. We separated the two compartments by controlled digitonin-induced cell lysis and measured both fractions directly in the platelets of 16 patients with storage pool deficiency. The total contents of ATP and ADP in the platelets of these patients was significantly lower than in normal controls. This was primarily caused by decreased amounts of ATP and ADP in the granule compartment, but also cytosolic ADP was low in these patients. In contrast, cytosolic ATP was not significantly decreased. The lower the amount of granule-bound ATP and ADP, the longer was the bleeding time in these patients. The best correlation was found with granule ADP. These data may indicate that ADP stored in platelet dense granules plays a role in the arrest of bleeding.


Polarization contrast and motion detection.
Form and motion perception rely upon the visual system's capacity to segment the visual scene based upon local differences in luminance or wavelength. It is not clear if polarization contrast is a sufficient basis for motion detection. Here we show that crayfish optomotor responses elicited by the motion of images derived from spatiotemporal variations in e-vector angles are comparable to contrast-elicited responses. Response magnitude increases with the difference in e-vector angles in adjacent segments of the scene and with the degree of polarization but the response is relatively insensitive to the absolute values of e-vector angles that compose the stimulus. The results indicate that polarization contrast can support visual motion detection.


Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility.
Genetic studies elucidate a link between testis-specific serine/threonine kinases (TSSKs) and male infertility in mammals, but the underlying mechanisms are unclear. Here, we identify a TSSK homolog in Drosophila, CG14305 (termed dTSSK), whose mutation impairs the histone-to-protamine transition during spermiogenesis and causes multiple phenotypic defects in nuclear shaping, DNA condensation, and flagellar organization in spermatids. Genetic analysis demonstrates that kinase catalytic activity of dTSSK, which is functionally conserved with human TSSKs, is essential for male fertility. Phosphoproteomics identify 828 phosphopeptides/449 proteins as potential substrates of dTSSK enriched primarily in microtubule-based processes, flagellar organization and mobility, and spermatid differentiation and development, suggesting that dTSSK phosphorylates various proteins to orchestrate postmeiotic spermiogenesis. Among them, the two substrates, protamine-like protein Mst77F/Ser9 and transition protein Mst33A/Ser237, are biochemically validated to be phosphorylated by dTSSK in vitro, and are genetically demonstrated to be involved in spermiogenesis in vivo. Collectively, our findings demonstrate that broad phosphorylation mediated by TSSKs plays an indispensable role in spermiogenesis.


Metal release from gold-containing jewelry materials: no gold release detected.
Metal release from 13 different gold-containing jewelry alloys stored for 1 and 3 weeks in artificial sweat was analysed. For chemical analysis, inductively-coupled plasma detection (ICP) and atomic absorption spectrophotometry (AA), with flame and with furnace, were used. No release of gold was detected. It is unlikely that skin contact with gold-containing metallic items such as jewelry is responsible for inducing contact allergy to gold or allergic contact dermatitis due to the gold. The patch-test reactivity to gold sodium thiosulfate needs to be explained by some other mechanism(s).


Bedside electrical impedance tomography in early diagnosis of pneumothorax in mechanically ventilated ICU patients - a single-center retrospective cohort study.
This study aimed to evaluate the routine use of electrical impedance tomography (EIT) to diagnose pneumothorax (PTX) in mechanically ventilated patients in the intensive care unit (ICU). A retrospective cohort study was conducted including mechanically ventilated supine patients who received EIT examinations. The EIT-based tidal variation was divided into ventral and dorsal regions of interest (ROIs): upper right (UR, ROI1), upper left (UL, ROI2) lower right (LR, ROI3), and lower left (LL, ROI4), and the ventilation defect score (DS) was calculated in each quadrant. Furthermore, horizontal ventral ventilation index (HVVI) was defined as ROI1% / ROI2% in the two ventral quadrants if ROI1% > ROI2%, otherwise HVVI = ROI2% / ROI1%. A total of 203 patients were included, 25 of them with confirmed PTX. In the PTX patients, preceding cardiac surgery was the most common cause of PTX. Compared with the patients without PTX, the PTX patients had a higher DS in the ventral quadrants [median and interquartile range (IQR): 1.00 (0.00, 2.00) vs. 0.00 (0.00, 0.00), P < 0.001] respectively, but similar in the dorsal quadrants [median and IQR: 1.00 (0.00, 1.00) vs. 0.00 (0.00, 1.00), P = 0.722]. Moreover, a higher HVVI was found in the PTX group [median and IQR: 2.51 (1.58, 3.52) vs. 1.36 (1.15, 1.77), P < 0.001]. The area under the receiver operating characteristic curve of the HVVI to differentiate PTX from non-PTX was 0.88, with a sensitivity of 70% and a specificity of 90% when the cut-off value was 2.57. The ventilation defect in the ventral regions and a high HVVI on EIT were observed in mechanically ventilated patients with PTX, which should trigger further diagnostics to confirm it.


Rhodium(iii)-catalyzed synthesis of phthalides by cascade addition and cyclization of benzimidates with aldehydes.
We herein report the Rh(iii)-catalyzed C-H bond activation and addition of benzimidates to aldehydes to afford biologically important phthalides in a single step. The imidate is a novel and unexplored directing group that not only enables C-H bond activation and addition to aldehydes, but also serves to capture the reversibly formed alcohol intermediate. The reaction shows broad scope with a high level of functional group compatibility and is applicable to both aromatic and aliphatic aldehydes.


Which is More Effective and Safer? Comparison of Propensity Score-Matched Microhook Ab Interno Trabeculotomy and iStent Inject.
The purpose of this study was to compare the surgical outcomes between ab interno trabeculotomy (LOT) and iStent inject W implantation (iStent) both combined with cataract surgery, matching the background factors including age, intraocular pressure (IOP), medication score, central corneal thickness (CCT), and axial length. A total of 100 eyes from 75/79 patients with primary open-angle glaucoma were included in the LOT/iStent groups. The background factors were matched between the two groups using the propensity score. There were no significant differences in age, IOP, medication score, CCT, and axial length, preoperatively. The postoperative medication scores were 1.3 ± 1.2 and 1.2 ± 1.2 in the LOT and iStent groups. The postoperative IOPs were 12.8 ± 2.8 and 13.1 ± 2.4 mmHg in the LOT and iStent groups, respectively. The changes in the medication score were - 0.64 ± 1.4 and - 0.44 ± 1.6 in the LOT and iStent groups, respectively. The changes in the IOP were - 2.1 ± 3.3 and - 1.5 ± 3.0 mmHg in the LOT and iStent groups, respectively. These values were not significantly different between the two groups. The postoperative IOP and changes in the IOP were significantly associated with preoperative IOP and CCT. There was no significant difference in the occurrence of postoperative complications (hyphema, 11.0% and 6.0%, and transient ocular hypertension, 8.0% and 5.0%, in the LOT and iStent groups, respectively). LOT and iStent have similar surgical outcomes with sufficient safety. Postoperative IOP was significantly associated with preoperative IOP and CCT in both groups.


Predictors of cigarette smoking in pregnant women with substance use disorders.
Cigarette smoking is common among pregnant women with substance use disorders (SUD) and may contribute to more adverse health consequences for the infant than alcohol and illicit drug use. However, most studies focused on stopping illicit drug use and paid little attention to cigarette smoking in pregnant women with SUD. To identify predictors of current smoking among pregnant women with SUD, given past-month psychological distress, alcohol use and illicit drug use, the receipt of past-year mental health and substance use treatment controlling for potential confounders. Secondary analysis of cross-sectional data from the National Survey on Drug Use and Health (NSDUH) 2015-2019 was conducted. The NSDUH included 3,540 pregnant women aged 18-44 years; among them were 195 lifetime smokers with SUD. Multiple logistic regression modeling was used to examine the probability of prenatal smoking. Sixty-one percent of pregnant women with SUD reported current cigarette smoking. The likelihood of prenatal smoking increased with a higher level of past-month psychological distress (Adjusted Odds Ratio [AOR] 1.14; 95% Confidence Interval [CI]: 1.02-1.28), past-month illicit drug use (AOR: 5.68; 95% CI: 1.59-20.21), and past-year substance use treatment receipt (AOR: 5.73; 95% CI: 1.88-17.45). The receipt of substance use treatment markedly increased the probability of smoking in pregnant women with SUD. Treatment and policy initiatives are required to address and integrate cigarette smoking within other substance use treatment modalities for pregnant women with SUD.


Effects of yeast-derived postbiotic supplementation in late gestation and lactation diets on performance, milk quality, and immune function in lactating sows.
This experiment was conducted to determine the effects of yeast-derived postbiotic (YDP) supplementation in sow diets during late gestation and lactation on the performance of sows and their offspring. At 90-d gestation, 150 sows (Landrace × Large White, parity: 3.93 ± 0.11) were allocated to three dietary treatments (n = 50 per treatment): 1) basal diet (control [CON]), 2) basal diet with 1.25 g/kg YDP (0.125 group), and 3) basal diet with 2.00 g/kg YDP (0.200 group). The experiment continued until the end of weaning (day 21 of lactation). Supplementation with YDP resulted in greater deposition of backfat in sows during late gestation and an increasing trend in average weaning weight of piglets than observed in the CON group (P < 0.01, P = 0.05). Supplementation with YDP decreased piglet mortality and diarrhea index in piglets (P < 0.05). In farrowing sows' serum, the glutathione peroxide content in the YDP group was lower than that in the CON group (P < 0.05); the content of immunoglobulin A (IgA) in the 0.200 group or YDP group was higher than that in the CON group (P < 0.05). In lactating sows' serum, malondialdehyde content was higher in the YDP group (P < 0.05). In day 3 milk of sows, the 0.200 group tended to increase the lactose content (P = 0.07), and tended to decrease the secretory immunoglobulin A (sIgA) content (P = 0.06) with respect to that in the CON group. The sIgA content in the YDP group was lower than that in the CON group (P < 0.05). In the milk of sows, the 0.200 group tended to increase the lactose content with respect to that in the CON group (P = 0.08); the immunoglobulin G (IgG) content in the 0.125 group or YDP group was higher than that in the CON group (P < 0.05). YDP supplementation increased the IgA content in the milk (P < 0.01). In sow placenta, the content of total anti-oxidant capacity in the YDP group was higher than that in the CON group (P = 0.05); and the content of transforming growth factor-β in the YDP group was higher than that in the CON group (P < 0.05). In piglet serum, the content of IgG and immunoglobulin M in the 0.125 group was higher than that in the CON and 0.200 groups (P < 0.05). In summary, this study indicated that feeding sows diets supplemented with YDP from late gestation through lactation increased sows' backfat deposition in late gestation and piglets' weaning weight; decreased piglet mortality and diarrhea index in piglets; and improved maternal and offspring immunity.


P62 and the sequestosome, a novel mechanism for protein metabolism.
In addition to selecting proteins for degradation by the 26S proteasome, ubiqitination appears to serve other regulatory functions, including for endosomal/lysosomal targeting, protein translocation, and enzyme modification. Currently, little is known how multiubiquitin chains are recognized by these cellular mechanisms. Within the 26S proteasome, one subunit (Mcb1/S5a) has been identified that has affinity for multiubiquitin chains and may function as a ubiquitin receptor. We recently found that a non-proteasomal protein p62 also preferentially binds multiubiquitin chains and forms a novel cytoplasmic structure "sequestosome" which serves as a storage place for ubiquitinated proteins. In the present manuscript, the role and regulation of p62 in relation to the sequestosomal function will be reviewed.


Higher dietary magnesium and potassium intake are associated with lower body fat in people with impaired glucose tolerance.
Obesity and diabetes are public health concerns worldwide, but few studies have examined the habitual intake of minerals on body composition in people with prediabetes. In this prospective cross-sectional study, 155 Chinese subjects with IGT [median age: 59 (53-62) years, 58% female] had an assessment of body composition including body fat percentage, oral glucose tolerance tests (OGTT), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and 3-day food records from nutritional programme analysis. Dietary intake of minerals was negatively correlated with body fat. People with obesity had the lowest daily consumption of iron median (IQR) 10.3 (6.9-13.3) mg, magnesium 224 (181-282) mg, and potassium 1973 (1563-2,357) mg when compared to overweight [10.5 (8.0-14.5) mg, 273 (221-335) mg, and 2,204 (1720-2,650) mg] and normal weight individuals [13.2 (10.0-18.6) mg, 313 (243-368) mg, and 2,295 (1833-3,037) mg] (p = 0.008, <0.0001, and 0.013 respectively). Amongst targeted minerals, higher dietary magnesium and potassium intake remained significantly associated with lower body fat after the adjustment of age, gender, macronutrients, fibre, and physical activity. Dietary magnesium and potassium intake may be associated with lower body fat in people with impaired glucose tolerance. Inadequate dietary mineral intake may play contribute to obesity and metabolic disorders independent of macronutrients and fibre consumption.


(Un)intended consequences? The impact of the 2017 tax cuts and jobs act on shareholder wealth.
We study the stock market reactions to the Tax Cuts and Jobs Act (TCJA), the most significant structural U.S. tax reform in over 30 years. In line with the stated intent of TCJA proponents, we find that the Act benefited highly taxed firms. However, the Act hindered firms with international operations as well as firms with high interest expense and tax losses. Counter to claims that the TCJA would quickly spur economic growth, we find that financially constrained and high growth opportunity firms did not benefit. Rather, market participants anticipate that most of the TCJA's benefits will be passed on to shareholders via higher corporate payouts. We confirm these market expectations by documenting that firms did increase payouts via repurchases after the TCJA, but did not increase their corporate investments.


Tolerance develops to the haloperidol-induced increase in the efflux of dopamine metabolites from the brains of unanesthetized, freely-moving rats.
The lateral cerebral ventricles of freely moving rats were perfused by means of chronically implanted push-pull cannulae every second day for 2 weeks. Perfusates were analyzed for metabolites of dopamine [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] and of 5-hydroxytryptamine [5-hydroxyindoleacetic acid (5HIAA)] using high performance liquid chromatography and an amperometric detector. Rats received daily subcutaneous injections of haloperidol (1 mg/kg) or its vehicle. After the first injection of haloperidol the concentrations of DOPAC and HVA were markedly increased while that of 5HIAA was unchanged. Complete tolerance developed to the haloperidol-induced increased efflux of dopamine metabolites by day 9, although a higher dose of haloperidol (2 mgf/kg) on day 15 was still capable of eliciting a modest increase in the efflux of DOPAC and HVA.


Role of survivin in acute lung injury: epithelial cells of mice and humans.
Survivin, an inhibitor of apoptosis, regulates cell division and is a potential target for anticancer drugs because many cancers express high survivin levels. However, whether survivin would be toxic to human lung cells and tissues has not been determined. This report clarified the involvement of survivin in acute lung injury. We used immunohistochemical analysis, immunoelectron microscopy, and real-time reverse transcription-quantitative polymerase chain reaction to study survivin expression and localization in injured mouse and human lungs. We also used cultured human lung epithelial cells (BEAS-2B and A549) to study survivin cytoprotection. Nuclei and cytoplasm of epithelial cells in day 3 and day 7 models of bleomycin-injured lung showed survivin-positive results, which is consistent with upregulated survivin mRNA expression. These nuclei also evidenced double positive findings for proliferating cell nuclear antigen and survivin. Day 7 models had similar Smac/DIABLO-positive and survivin-positive cell distributions. The cytoplasm and nuclei of epithelial cells in lesions with diffuse alveolar damage manifested strong survivin-positive findings. Bleomycin stimulation in both epithelial cell lines upregulated expression of survivin and apoptosis-related molecules. Suppression of survivin expression with small interfering RNA rendered human lung epithelial cells susceptible to bleomycin-induced damage, with markedly upregulated activation of caspase-3, caspase-7, poly (ADP-ribose) polymerase, and lactate dehydrogenase activity and an increased number of dead cells compared with mock small interfering RNA-treated cells. Overexpression of survivin via transfection resulted in these epithelial cells being resistant to bleomycin-induced cell damage, with reduced activation of apoptosis-related molecules and lactate dehydrogenase activity and fewer dead cells compared with results for mock-transfected cells. Survivin, acting at the epithelial cell level that depends partly on apoptosis inhibition, is therefore a key mediator of cytoprotection in acute lung injury. Understanding the precise role of survivin in normal lung cells is required for the development of therapeutic survivin.


Genetic Diversity, Population Structure and Phylogeny of Indigenous Goats of Mongolia Revealed by SNP Genotyping.
Mongolian goats are of great interest for studying ancient migration routes and domestication, and also represent a good model of adaptability to harsh environments. Recent climatic disasters and uncontrolled massive breeding endangered the valuable genetic resources of Mongolian goats and raised the question of their conservation status. Meanwhile, Mongolian goats have never been studied on genomic scale. We used Illumina Goat SNP50 to estimate genetic risks in five Mongolian goat breeds (Buural, Ulgii Red, Gobi GS, Erchim, Dorgon) and explored phylogenic relationships among these populations and in the context of other breeds. Various clustering methods showed that Mongolian goats grouped with other Asian breeds and were especially close to some neighboring Russian and Chinese breeds. The Buural breed showed the lowest estimates of inbreeding and exhibited the shortest genetic distances within the other Mongolian breeds, especially, to Ulgii Red and Gobi GS. These three breeds formed a single core group, being weakly differentiated from each other. Among them, Gobi GS displayed obvious signs of inbreeding probably resulted from artificial selection pressure. Dorgon and especially Erchim goats stand apart from the other Mongolian breeds according to various types of analyses, and bear unique features pointing to different breeding histories or distinct origins of these breeds. All populations showed strong decline in effective population size. However, none of them met formal criteria to be considered as endangered breeds. The SNP data obtained in this study improved the knowledge of Mongolian goat breeds and could be used in future management decisions in order to preserve their genetic diversity.


Factors influencing parentage ratio in canine dual-sired litters.
Breeding a bitch with two different sires during a single estrous cycle has the potential to facilitate rapid genetic gain and improve reproductive performance within a canine breeding colony. There is limited data regarding the factors that contribute to the success of dual-sired litters in domestic dogs, and only anecdotal evidence suggesting that these litters rarely produce offspring from more than one sire. The objective of this prospective clinical study was to investigate multiple factors that likely affect the success of dual-sired litters on whelping rate, litter size and parentage ratio. These factors include: timing of artificial insemination (AI), order of sires, number of AI's per cycle, semen type, sperm quality and age of sire and bitch. Data collected over a 10 year period from twenty-nine estrous cycles (28 individual bitches of 10 different breeds) were evaluated after an initial AI with frozen semen from the 'genetically desired' sire and followed up with a second AI with either fresh (n = 9) or frozen (n = 16) semen or natural mating (n = 4) from a different, 'back up', sire. DNA parentage of each pup born was determined by using a primary panel of 288 SNPs. The whelping rate and litter size from previous single sire inseminations per estrous cycle, in the same bitches, (n = 16) over 25 estrous cycles using either fresh (n = 4) or frozen-thawed (n = 21) semen, were analyzed as controls. Of the 29 dual-sired breedings, 26 bitches whelped (89.7%), and 8 litters (30.8%) were of mixed parentage. In the litters of mixed parentage after a dual-sired breeding, a greater proportion of the offspring were from the second sire than the first sire (73.0% and 27.0% respectively; P < 0.05). Interestingly, in litters where all pups were of single sire parentage after a dual-sired breeding, 50.0% of the offspring were by the first sire and 50.0% were by the second sire. For litters of mixed or single paternity produced by dual-sired breeding there was no difference in average litter size. However, on a per estrous cycle basis for each bitch the whelping rate (89.7% v. 76.0%.) and litter size (5.5 ± 2.5 v. 4.0 ± 2.78) of all dual-sired breedings were greater (P < 0.05) compared to previous single-sired breedings (controls) respectively. This study demonstrates that offspring of mixed parentage derived from dual-sired breedings may be achieved. Furthermore, insemination with semen from two different sires may increase the whelping rate and litter size, which is an important consideration when using genetically valuable, or older individuals with potentially reduced fertility.


Antigenotoxic and anticytotoxic effect of camel milk in mice treated with cisplatin.
Camel milk (CM) has good nutritive value, in addition to its antigenotoxic and anticytotoxic effects. Therefore the aim of this investigation was to evaluate the capacity of CM to inhibit the micronucleated polychromatic erythrocytes (MnPCEs) in the bone marrow and improve the mitotic activity produced by cisplatin. Cisplatin is one of the most widely used antineoplastic drugs in the treatment of cancer. The 70 adult male Swiss albino mice were divided into seven groups:Gr. I: treated with distilled water and considered as a control group.Gr. II: treated with camel milk (33 ml/kg, b.w).Gr. III: treated previously with cisplatin (0.5 mg/kg, b.w).Gr. IV: treated with camel milk and followed after 2 h. with cisplatin (33 ml/kg → 0.5 mg/kg, b.w).Gr. V: treated with camel milk and cisplatin at the same time (33 ml/kg + 0.5 mg/kg, b.w).Gr. VI: treated with an acute single dose of cisplatin (2.5 mg/kg, b.w).Gr. VII: treated with camel milk prior and followed with an acute single dose of cisplatin (33 ml/kg → 2.5 mg /kg, b.w). The animals were sacrificed 24 h after cisplatin injection. The pretreatment with CM dose caused a significant decrease (P < 0.001) in the frequency of MnPCEs and increase (P < 0.001) in the mitotic index (MI) induced by cisplatin when compared with the groups treated with cisplatin alone. The possible explanation for the antigenotoxic and anticytotoxic effects observed in the pretreatment with CM is ascribed to its contents. In conclusion, from the findings we suggest that this milk has some antioxidant effect, and the antigenotoxic mechanism of this milk needs to be explored further before their use during cisplatin chemotherapy.


A serial section Golgi analysis of the primate claustrum.
The cellular composition of the primate claustrum was analyzed using serially sectioned Golgi impregnated neurons. The tissue used in this study was embedded in a soft resin mixture and cut with 25 mm long glass knives. The resin embedding allowed the sections to be cut serially at a thickness of only 3 micrometers. A camera lucida was employed for drawing the cellular processes from selected impregnated neurons; these drawings were later incorporated into a single composite picture of the neuron. Three types of neurons were observed in the primate claustrum. The largest of these neurons (Type 1) had a cell body and spine-laden dendritic arborization that varied in size and shape according to the neuron's position in the claustrum. The axons of Type I neurons were successfully impregnated in 25-day-old animals and were found to form collaterals within the claustrum. The collaterals from the axons of these cells appeared to leave the claustrum through both the external and extreme capsules. A second neuron found in the claustrum (Type II) had a round cell body with smooth beaded dendrites which radiated in all directions. The axon of the Type II neuron appeared to give off numerous collaterals that were not observed to leave the claustrum. A third type of neuron (Type III) had a small pear shaped cell body and a sparse dendritic tree. The axon and its collaterals appeared to remain within the dendritic circumference of the Type III neuron.


Hydrochlorothiazide binding to human serum albumin induces some compactness in the molecular structure of the protein: A multi-spectroscopic and computational study.
The interaction between hydrochlorothiazide (HCTZ), a diuretic drug, with human serum albumin (HSA) was investigated by different biophysical approaches such as UV absorption, circular dichroism (CD), Fourier transform infrared (FT-IR), and fluorescence spectroscopy in 50 mM sodium phosphate buffer, pH 7.4. The results of fluorescence titration experiments revealed that HCTZ strongly quenches the intrinsic fluorescence of HSA through a static quenching mechanism. Binding constants and the number of binding sites were calculated using Stern-Volmer plots. Thermodynamic analysis of the binding data elucidated that hydrogen bonding and van der Waals interactions played the major role in the binding process. Computation of the protein surface hydrophobicity (PSH) index using 1-anilinonaphtalene-8-sulfonate indicated that considerable decrement in PSH value of the protein happened upon drug binding. The binding site of HCTZ in HSA was identified using warfarin and ibuprofen as site markers, a result confirmed by molecular docking study. The results of CD experiments showed that some alterations occurred in the structure of the protein upon ligation. Also, the results of FT-IR experiments were in good agreement with CD experiments. It looks like that both secondary and tertiary structures of HSA have been affected upon HCTZ binding.


Active mitochondrial respiration in cancer: a target for the drug.
The relative contribution of mitochondrial respiration and subsequent energy production in malignant cells has remained controversial to date. Enhanced aerobic glycolysis and impaired mitochondrial respiration have gained more attention in the metabolic study of cancer. In contrast to the popular concept, mitochondria of cancer cells oxidize a diverse array of metabolic fuels to generate a majority of the cellular energy by respiration. Several mitochondrial respiratory chain (MRC) subunits' expressions are critical for the growth, metastasis, and cancer cell invasion. Also, the assembly factors, which regulate the integration of individual MRC complexes into native super-complexes, are upregulated in cancer. Moreover, a series of anti-cancer drugs function by inhibiting respiration and ATP production. In this review, we have specified the roles of mitochondrial fuels, MRC subunits, and super-complex assembly factors that promote active respiration across different cancer types and discussed the potential roles of MRC inhibitor drugs in controlling cancer.


Evaluation of left ventricular systolic and diastolic function in patients with atrioventricular re-entrant tachycardia treated by radiofrequency current ablation.
Little is known about the long-term influence of radiofrequency current ablation (RFCA) on left ventricular (LV) systolic and diastolic function in patients with atrioventricular re-entrant tachycardia (AVRT). The study group consisted of 65 patients (33 M, mean age 39 +/- 11 y) with WPW syndrome and recurrent episodes of AVRT without any concomitant diseases. The control group consisted of 50 age-matched healthy volunteers. In both study and control groups transthorasic echocardiography (TTE) and Doppler were performed in order to assess LV systolic and diastolic function. In WPW patients TTE was followed by electrophysiology study and RFCA. TTE was repeated in 6-months time in the study group. At 6-month follow-up a decrease in LV end-systolic diameters (1.77 +/- 0.22 vs. 1.67 +/- 0.22 cm/m2, P < 0.001) and volumes (20 +/- 6 vs. 17 +/- 5 ml, P < 0.001) and an increase in LV FS (33 +/- 6 vs. 37 +/- 5%, P < 0.001), EF (54 +/- 6 vs. 60 +/- 5%, P < 0.001), IVS (44 +/- 13 vs. 49 +/- 14%, P < 0.05) and LV PW thickening (58 +/- 19 vs. 62 +/- 16%, P < 0.05) was found. Doppler analysis revealed an increase in E wave (78 +/- 17 vs. 82 +/- 14 cm/s, P < 0.001), E/A ratio (1.14 +/- 0.37 vs. 1.33 +/- 0.24, P < 0.001) and a decrease in A wave (68 +/- 19 vs. 63 +/- 12 cm/s, P < 0.05), DT (219 +/- 33 vs. 180 +/- 20 ms, P < 0.001 ), IVRT (105 +/- 13 vs. 88 +/- 13 ms, P < 0.001), AR (26 +/- 8 vs. 18 +/- 12 cm/s, P < 0.001 ) and difference between duration of AR and A waves (5 +/- 24 vs. -12 +/- 21 ms, P < 0.001). No significant differences in regard to LV systolic and diastolic variables were found between patients and controls post RFCA. RFCA of accessory pathway in patients with WPW syndrome and AVRT is associated with improvement of LV systolic and diastolic function.


Heterologous gshF gene expression in various vector systems in Escherichia coli for enhanced glutathione production.
Glutathione (GSH), an important bioactive product, is widely used in production of pharmaceuticals and foods. In this study, four different vector systems, pET28a, pUC18, pUC19-P32, and pUC19-Pabb, were applied for expression of gshF, encoding the bifunctional glutathione synthetase of Streptococcus thermophiles. These four constructs were named as pET28a-gshF, pUC18-gshF, pUC19-P32-gshF and pUC19-Pabb-gshF, respectively, and then introduced into Escherichia coli strain BL21(DE3) for further investigation of protein expression and GSH production. The expression levels of the GshF in BL21(pUC19-P32-gshF) and BL21(pUC19-Pabb-gshF) were much lower than those of BL21(pET28a-gshF) and BL21(pUC18-gshF). In the fed-batch fermentation, the GSH accumulated by BL21(pUC18-gshF) reached 15.21 g/L, which was the highest level of GSH biosynthesis ever reported. Although BL21(pUC19-Pabb-gshF) produced less GSH compared to BL21(pUC18-gshF), the final GSH concentration produced by BL21 (pUC19-Pabb-gshF) still accumulated to 5.09 g/L, which indicated the potential application of the constitutive promoter in GSH production.


Consecutive incorporation of functionalized nucleotides with amphiphilic side chains by novel KOD polymerase mutant.
Recently, 7-substituted 7-deazapurine nucleoside triphosphates and 5-substituted pyrimidine nucleoside triphosphates (dN(am)TPs) were synthesized to extend enzymatically using commercially available polymerase. However, extension was limited when we attempted to incorporate the substrates consecutively. To address this, we have produced a mutant polymerase that can efficiently accept the modified nucleotide with amphiphilic groups as substrates. Here we show that the KOD polymerase mutant, KOD exo(-)/A485L, had the ability to incorporate dN(am)TP continuously over 50nt, indicating that the mutant is sufficient for generating functional nucleic acid molecules.


Vascular patterning in human heterotopic ossification.
Heterotopic ossification (HO, also termed myositis ossificans) is the formation of extra-skeletal bone in muscle and soft tissues. HO is a tissue repair process gone awry, and is a common complication of surgery and traumatic injury. Medical strategies to prevent and treat HO fall well short of addressing the clinical need. Better characterization of the tissues supporting HO is critical to identifying therapies directed against this common and sometimes devastating condition. The physiologic processes of osteogenesis and angiogenesis are highly coupled and interdependent. However, few efforts have been made to document the vascular patterning within heterotopic ossification. Here, surgical pathology case files of 29 human HO specimens were examined by vascular histomorphometric analysis. Results demonstrate a temporospatial patterning of HO vascularity that depends on the "maturity" of the bony lesion. In sum, human HO demonstrates a time- and space-dependent pattern of vascularization suggesting a coupled pathophysiologic process involving the coordinate processes of osteogenesis and angiogenesis. Further imaging studies may be used to further characterize vasculogenesis within HO and whether anti-angiogenic therapies are a conceivable future therapy for this common condition.


Effect of biotin on ribonucleic acid synthesis.
A single injection of biotin to biotin-deficient rats produces a two-fold increase in the incorporation, both in vivo and in vitro of precursors into nucleic acids as early as 2 h after the biotin treatment. The specific activity of the precursor pool is not affected by biotin. Analysis of the polysome profile at various times following biotin treatment and a kinetic study of the effect of excess poly(U) on the incorporation of phenylalanine by cell-free amino acid incorporation experiments indicate a marked decrease in messenger-free ribosomes in rat liver after biotin administration.


Selective anti-Markovnikov cyclization and hydrofluorination reaction in superacid HF/SbF5: a tool in the design of nitrogen-containing (fluorinated) polycyclic systems.
The selective synthesis of tetrahydroquinolines and fluorinated arylamines was performed in superacid HF/SbF5 through a superelectrophilic ammonium-carbenium activation process. This anti-Markovnikov oriented reaction was applied to the straightforward synthesis of highly valued (fluorinated) nitrogen-containing heterocyclic compounds.


Cutaneous pleomorphic T-cell lymphoma coexisting with myelodysplastic syndrome transforming into acute myeloid leukemia: successful treatment with a fludarabine-containing regimen.
The coexistence of a primary myelodysplastic syndrome (MDS) and a T-cell cutaneous non-Hodgkin's lymphoma is an extremely rare event, which has so far only been reported in a single instance in the literature. We describe herein an additional case in which the lymphoid disease was combined with an MDS at the time of its evolution into acute myeloid leukemia (AML). Both diseases were successfully treated with a regimen containing fludarabine. We discuss possible pathogenetic mechanisms and suggest the use of nonalkylating drugs, such as fludarabine, for the treatment of this rare association of malignancies usually characterized by a very poor response to therapy.


The use of multi b values diffusion-weighted imaging in patients with acute stroke.
The purpose of this paper is to study the mechanism of apparent diffusion coefficient reduction after stroke by using multi b value diffusion-weighted imaging. Ten healthy people and 25 patients with acute stroke were enrolled. In healthy volunteers, region of interests were put in the semioval center and in the precentral gyrus. In patients with acute stroke, region of interests were put in lesions and contralateral normal brain regions. ADC(fast) and ADC(slow) are thought of as a fast and a slow apparent diffusion coefficient, which result from the extracellular and intracellular compartments, respectively. p (fast) and p (slow) are regarded as the percentage of signal intensities deriving from water diffusion of the extracellular and intracellular compartments, separately. All data were analyzed using paired, two-tailed t tests. Statistical analyses were performed using SPSS 15.0. In patients with acute stroke, p (fast) in lesions (0.54 ± 0.11) is lower than that in normal regions (0.75 ± 0.09), while p (slow) is on the contrary. ADC(fast) and ADC(slow) values in lesions are less than those in normal areas. Compared with those in normal regions, p (fast) of lesions decreases by 28 %, and ADC(fast) and ADC(slow) of lesions went down by 27 and 36 %, respectively. There are statistically significant differences (P < 0.05) in ADC(fast), ADC(slow), and p (fast) between lesions and normal regions. The increase in the volume of extracellular space and the decrease in ADC(slow) are the primary reasons that lead to the decrease in apparent diffusion coefficient of lesions after stroke.


Case for an RNA-prion world: a hypothesis based on conformational diversity.
Prions and other misfolded proteins can impart their structure and functions to normal molecules. Based upon a thorough structural assessment of RNA, prions and misfolded proteins, especially from the perspective of conformational diversity, we propose a case for co-existence of these in the pre-biotic world. Analyzing the evolution of physical aspects of biochemical structures, we put forward a case for an RNA-prion pre-biotic world, instead of, merely, the "RNA World".


An international multicenter survey reveals health care providers' knowledge gap in childhood central nervous system tumors.
Childhood central nervous system (CNS) tumors have longer delays in diagnosis than do other pediatric malignancies because health care providers (HCPs) lack awareness about clinical presentation of these tumors. To evaluate the knowledge gap among HCPs, we conducted a global cross-sectional survey. The survey consisted of a set of CNS tumor knowledge questions focused on symptoms, signs, and imaging indications. The survey was disseminated to HCPs via email (November 2018-March 2020). Participants had to complete a pre-test survey, attend an education seminar on CNS tumors, and complete a post-test survey. The knowledge gap was evaluated using pre-test and post-test scores. We received 889 pre-test and 392 post-test responses. Most respondents were from Asia (73.1% of pre-test responses; 87.5% of post-test responses). The median pre-test score was 40.0% (range: 13.1-92.9%). A high percentage of correct answers were given in post-test responses (median score: 77.1%, range: 14.9-98.2%). In the pre-test, 18.7% of participants accurately responded that Cushing's triad was a less common symptom, and 15.0% recognized that children aged > 10 years are at risk of late diagnosis. Surprisingly, 21.9% falsely reported that patients with malignancy experienced the longest pre-diagnostic symptom interval, and 54.5% of respondents wrongly selected medulloblastoma as the most common CNS tumor. Overall, pediatricians demonstrated a greater knowledge gap on both surveys than did other specialties. Conclusion: Pre- and post-test surveys revealed significant knowledge gaps in childhood CNS tumors among HCPs. Thus, raising professional awareness on clinical presentations of CNS tumors through educational strategies is important to address this knowledge deficit. What is Known: • Diagnostic delay in childhood central nervous system (CNS) tumors continues to be a significant problem that negatively impacts the quality of life and treatment sequelae. • Lack of medical education on CNS tumors is a contributing factor to this problem. What is New: • Most health care providers do not realize that low-grade tumors are the most common neoplasm in children. • Health care providers fail to recognize that teenagers and adolescents are a vulnerable age group for diagnostic delays, with the longest pre-diagnostic symptom interval.


The comparison of intraincisional bupivacaine infiltration and intravenous paracetamol administration for pain alleviation after cesarean section: a double-blinded randomized placebo controlled clinical trial.
This study aimed to compare the analgesic effect of subcutaneous (SC) bupivacaine and intravenous (IV) paracetamol on postoperative pain and opioid requisites in patients undergoing cesarean delivery. One hundred and five women were allocated into 3 groups in this prospective, double-blind, placebo-controlled, randomized trial. Group 1 received SC bupivacaine, Group 2 received IV paracetamol following surgery and every 6 hours for 24 hours in the postoperative period, Group 3 received SC 0.9% saline and IV 0.9% saline at similar periods. Visual analogue scale (VAS) pain scores at rest and coughing, at 15 and 60 minutes, and 2, 6 and 12 hours, and total opioid necessity were measured. VAS scores at rest were higher in placebo group than in bupivacaine and paracetamol groups at 15 minutes (p=0.047) and 2 hours (p=0.004). VAS scores at coughing were higher in placebo group than in bupivacaine and paracetamol groups at 2 hour (p=0.001) and 6 hours (p=0.018). Placebo group needed higher (p<0.001) doses of morphine than paracetamol or bupivacaine groups. Intravenous paracetamol decreases pain scores similar to SC bupivacaine in the postoperative period compared to placebo. Patients taking bupivacaine or paracetamol need fewer opioids than placebo.


Monitoring for target objects: activation of right frontal and parietal cortices with increasing time on task.
The right prefrontal and parietal cortices have been implicated in attentional processing in both neuropsychological and functional neuroimaging literature. However, attention is a heterogeneous collection of processes, each of which may be underpinned by different neural networks. These attentional networks may interact, such that engaging one type of attentional process could influence the efficiency of another via overlapping neural substrates. We investigated the hypothesis that right frontal and parietal cortices provide the neuroanatomical location of the functional interaction between sustained attention and the process of selectively monitoring for target objects. Six healthy volunteers performed one of two tasks which required either selective or non-selective responding. The task lasted continuously for 18 min, during which time 3 Positron Emission Tomography (PET) scans were acquired for each task. This was repeated to obtain 12 PET measurements of regional cerebral blood flow (rCBF) for each subject. The right inferior frontal and parietal cortices were differentially activated by increasing time on task during the selective (S) vs non-selective (NS) task. Specifically, rCBF decreased with increasing time spent performing the NS task but not the S task. This result suggests that the normal deactivation in these areas as time on task increases is counteracted by the extra cognitive demands of selectively responding to target objects. Therefore, we have confirmed our hypothesis that right frontal and parietal cortices provide the neuroanatomical location for the modulation of object selection by sustained attention. We also identified the neuroanatomical correlates of each process separately, and confirmed earlier reports of prefrontal cortex and anterior cingulate activation associated with selective responding, and a fronto-parietal-thalamic network associated with sustained attention.


Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise.
Mitochondrial respiratory sensitivity to ADP is thought to influence muscle fitness and is partly regulated by cytosolic-mitochondrial diffusion of ADP or phosphate shuttling via creatine/phosphocreatine (Cr/PCr) through mitochondrial creatine kinase (mtCK). Previous measurements of respiration in vitro with Cr (saturate mtCK) or without (ADP/ATP diffusion) show mixed responses of ADP sensitivity following acute exercise vs. less sensitivity after chronic exercise. In human muscle, modelling in vivo 'exercising' [Cr:PCr] during in vitro assessments revealed novel responses to exercise that differ from detections with or without Cr (±Cr). Acute exercise increased ADP sensitivity when measured without Cr but had no effect ±Cr or with +Cr:PCr, whereas chronic exercise increased sensitivity ±Cr but lowered sensitivity with +Cr:PCr despite increased markers of mitochondrial oxidative capacity. Controlling in vivo conditions during in vitro respiratory assessments reveals responses to exercise that differ from typical ±Cr comparisons and challenges our understanding of how exercise improves metabolic control in human muscle. Mitochondrial respiratory control by ADP (Kmapp ) is viewed as a critical regulator of muscle energy homeostasis. However, acute exercise increases, decreases or has no effect on Kmapp in human muscle, whereas chronic exercise surprisingly decreases sensitivity despite greater mitochondrial content. We hypothesized that modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate-shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp ) after acute and chronic exercise. The Kmapp was determined in vitro with 20 mm Cr (+Cr), 0 mm Cr (-Cr) or 'in vivo exercising' 20 mm Cr/2.4 mm PCr (Cr:PCr) on vastus lateralis biopsies sampled from 11 men before, immediately after and 3 h after exercise on the first, fifth and ninth sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training, whereby the first session did not change Kmapp with in vivo Cr:PCr despite increases in -Cr. The fifth session decreased sensitivity with Cr:PCr or +Cr despite no change in -Cr. Chronic exercise increased sensitivity ±Cr in association with increased electron transport chain content (+33-62% complexes I-V), supporting classic proposals that link increased sensitivity to oxidative capacity. However, in vivo Cr:PCr reveals a perplexing decreased sensitivity, contrasting the increases seen ±Cr. Functional responses occurred without changes in fibre type or proteins regulating mitochondrial-cytosolic energy exchange (mtCK, VDAC and ANT). Despite the dynamic responses seen with ±Cr, modelling in vivo phosphate-shuttling conditions in vitro reveals that ADP sensitivity is unchanged after high-intensity exercise and is decreased after training. These findings challenge our understanding of how exercise regulates skeletal muscle energy homeostasis.


Properties of the nicotinamide adenine dinucleotide phosphate-dependent aldehyde reductase from pig kidney. Amino acid composition, reactivity of cysteinyl residues, and stereochemistry of D-glyceraldehyde reduction.
Some physical and chemical properties of the monomeric NADP+-dependent aldehyde reductase (previously called TPN-L-hexonate dehydrogenase or D-glucuronate reductase) from pig kidney have been examined. The amino acid composition has been determined. Four of the five thiol groups react with p-mercuribenzoate at pH 7, with no resulting loss of catalytic activity. High concentrations of p-mercuribenzoate cause complete enzyme inhibition, which can be partly reversed by addition of aldehyde reductase is low (9%, estimated from the ellipticity at 208 nm), and 70 to 80% of the tyrosine and tryptophan residues aare buried within the molecule. One molecule of NADPH binds to the enzyme (Kp equal 25 muM), causing a blue shift and enhancement of the coenzyme fluorescence, and suggesting that the environment of the active site is hydrophobic. In the reduction of D-glyceraldehyde, catalyzed by aldehyde reductase, the pro-4R "A" hydrogen of NADPH attacks the re face of the carbonyl group. This stereospecificity is the same as in the reductions of D-glyceraldehyde and acetaldehyde effected by rabbit muscle dehydrogenase and liver alcohol dehydrogenase, respectively.


Nuclear proteins binding to a cauliflower mosaic virus 35S truncated promoter.
Proteins present in tobacco nuclear extracts bind to a truncated cauliflower mosaic virus (CaMV) 35S promoter fragment (from -90 to +2 relative to the transcription start site) in a sequence specific manner. Gel mobility shift assays show the presence of two protein-DNA complexes that are not competed by a -47/+2 promoter fragment. DNAse I protection and DNA methylation interference reveal two protected sites in the slower migrating complex; both include the pentamer TGACG, separated by a stretch of eight nucleotides where G methylation does not prevent the binding of the proteins. The faster complex is the prevalent form at low protein concentrations. As the protein concentration increases a non-linear rise in the amount of the slower migrating complex relative to the faster one is seen suggesting that cooperative effects are involved in the binding to the second site.


Ethnopharmacological survey on medicinal plants used in herbal drinks among the traditional communities of Pakistan.
There is very limited information regarding medicinal plants used by traditional healers in Pakistan, for treating wide-ranging diseases. Current study provides significant ethnopharmacological information, both qualitative and quantitative on medical plants in Pakistan and the pharmacological importance of herbal drinks, especially in the discovery of new drugs. The current ethnomedicinal field study was conducted from various traditional communities of Pakistan to document usage of medicinal plants as herbal drinks. Data was collected through field interviews from local people and using semi-structured questionnaires. Data was analyzed using quantitative indices such as UV (use value), RFC (Relative frequency of citation), and FL (Fidelity level). The present study recorded 217 plant species belonging to 174 genera and 69 families used in herbal drinks preparations. Major herbal preparations include decoctions, infusions and juice. According to use reports, significant species were Aloe vera, Artemisia fragrans, Allium cepa, Senegalia catechu, Alternanthera sessilis, Malva ludwigii, Arnebia benthamii, Cichorium intybus, Coccinia grandis, Dalbergia sissoo. Major ailment treated with herbal drinks include heartburn, fever, diarrhea, hypertension, and others. Use value (UV) varies from 0.23 to 0.02, with Mentha arvensis (0.23) having the highest value of UV followed by Mentha longifolia (0.22), Plantago lanceolate (0.19), Achillea millefolium (0.18), Coriandrum sativum (0.18), Justicia adhatoda and Malva sylvestris (0.17). Values of RFC varies from 0.28 to 0.09 while Fidelity level (FL) among plants varies from 37.5 to 100. Alternanthera sessilis, Oxytropis lapponica, Millettia pinnata and Salvia bucharica had the highest FL value (100). The use of medicinal plants is prevalent in traditional communities of Pakistan. Different herbal preparations are in common practice including various herbal drinks a common tradition and much favoured herbal preparation in terms of its results and regarded as reciprocal to modern drugs. Therefore, suggesting further pharmacological, phytochemical evaluation for essential metabolites and chemical constituents.


How strong should my anchor be for estimating group and individual level meaningful change? A simulation study assessing anchor correlation strength and the impact of sample size, distribution of change scores and methodology on establishing a true meaningful change threshold.
Treatment benefit as assessed using clinical outcome assessments (COAs), is a key endpoint in many clinical trials at both the individual and group level. Anchor-based methods can aid interpretation of COA change scores beyond statistical significance, and help derive a meaningful change threshold (MCT). However, evidence-based guidance on the selection of appropriately related anchors is lacking. A simulation was conducted which varied sample size, change score variability and anchor correlation strength to assess the impact of these variables on recovering the simulated MCT for interpreting individual and group-level results. To assess MCTs derived at the individual-level (i.e. responder definitions; RDs), Receiver Operating Characteristic (ROC) curves and Predictive Modelling (PM) analyses were conducted. To assess MCTs for interpreting change at the group-level, the mean change method was conducted. Sample sizes, change score variability and magnitude of anchor correlation affected accuracy of the estimated MCT. For individual-level RDs, ROC curves were less accurate than PM methods at recovering the true MCT. For both methods, smaller samples led to higher variability in the returned MCT, but higher variability still using ROC. Anchors with weaker correlations with COA change scores had increased variability in the estimated MCT. An anchor correlation of around 0.50-0.60 identified a true MCT cut-point under certain conditions using ROC. However, anchor correlations as low as 0.30 were appropriate when using PM under certain conditions. For interpreting group-level results, the MCT derived using the mean change method was consistently underestimated regardless of the anchor correlation. Sample size and change score variability influence the necessary anchor correlation strength when recovering individual-level RDs. Often, this needs to be higher than the commonly accepted threshold of 0.30. Stronger correlations than 0.30 are required when using the mean change method. Results can assist researchers selecting and assessing the quality of anchors.


The impact of sprint interval training with or without weight loss on substrate oxidation in adults: A secondary analysis of the i-FLEX study.
Endurance exercise training and weight loss (WL) have been associated with changes in fat oxidation. However, there is limited evidence investigating the impact of sprint interval training (SIT)-induced WL on fat oxidation in adults. To investigate the impact of SIT with or without WL on fat oxidation, 34 adults aged 19-60 years (males, n = 15) took part in 4-week SIT. SIT consisted of 30-s Wingates starting with two intervals and working up to four interspersed with 4 min of active recovery. Fat oxidation was estimated via indirect calorimetry using a metabolic cart during submaximal cycling. Following the intervention, participants were classified into a WL group (weight change >0 kg) or a non-WL group (weight change ≤0 kg). No difference in resting fat oxidation (p = 0.642) and respiratory exchange ratio (RER) (p = 0.646) were observed between the groups. There was a significant interaction for the WL group with increased submaximal fat oxidation usage (p = 0.005) and decreased submaximal RER over the duration of the study (p = 0.017). When adjusted for baseline weight and sex, submaximal fat oxidation usage remained significant (p < 0.05), while RER did not (p = 0.081). The WL group had higher work volume, relative peak power, and mean power than the non-WL group (p < 0.05). Short-term SIT elicited significant improvements in submaximal RER and fat oxidation (FOx) in adults that lost weight, which may be explained by an increase in work volume throughout SIT training.


A case report of two male siblings with autism and duplication of Xq13-q21, a region including three genes predisposing for autism.
Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.


Bioaccumulation and function analysis of glutathione S-transferase isoforms in Manila clam Ruditapes philippinarum exposed to different kinds of PAHs.
This study analyzed the function of different glutathione S-transferase (GST) isoforms and detoxification metabolism responses in Manila clam, Ruditapes philippinarum, exposed to 4 kinds of polycyclic aromatic hydrocarbons (PAHs) single, and their mixtures for 15 days under laboratory conditions. 13 kinds of GSTs in R. philippinarum were classified, and the results of tissue distribution indicated that 12 kinds of GSTs (except GST sigma 3) expressed most in digestive glands. We detected the mRNA expression levels of aryl hydrocarbon receptor signaling pathway, and detoxification system in digestive glands of clams exposed to benzo[a]pyrene (BaP), chrysene (CHR), benzo[a]anthracene (BaA), benzo[b]fluoranthene (BbF), and BaP + CHR + BaA + BbF, respectively. Among these genes, we selected GST-sigma, GST-omega and GST-pi as potential indicators to BaP; GST-sigma, GST-A and GST-rho to CHR; GST-pi, GST-sigma, GST-A, GST-rho and GST-microsomal to BaA; GST-theta and GST-mu to BbF; while GST-pi and GST-mu to the mixture of BaP, CHR, BaA and BbF. Additionally, the bioaccumulation of PAHs in tissues increased remarkably over time, and showed an obvious dose-effect. Under the same concentration, the bioaccumulation in single exposure group was higher than that in mixture group, and the bioaccumulation of PAHs in tissues with different concentrations of stress was irregular. The results revealed the metabolic differences and bioaccumulation rules in clams exposed to four kinds of PAHs, and provided more valuable information for the PAHs risk assessment.


Effect of microspheres in intra-arterial chemotherapy. A study of arterio-venous shunting and passage of a labelled marker.
Degradable starch microspheres (DSM) mixed and injected with a cytostatic drug might improve intra-arterial chemotherapy by increasing the local drug concentration. Several factors are of importance for an optimal effect of the microspheres, e.g. size and vascularity of the tumour, arterial blood flow and arterio-venous shunts. Therefore, the dose of DSM has to be individualized. A method for continuous monitoring of the effect of DSM was developed. A radiolabelled marker was injected intra-arterially mixed with DSM and mitomycin C. Two kinetic parameters--Passing Fraction and Marker Flow Rate--were found to be influenced by the microspheres and thus seemed to be useful for monitoring the DSM-treatment. Arterio-venous shunting was measured as passage of 99Tcm-labelled macroaggregated albumin through the liver to the lungs. Significant increase of shunting after injection of DSM was demonstrated in 15 out of 19 patients. Almost no effect of the microspheres was seen in patients with marked arterio-venous shunting or minimal reduction of the marker flow rate, but in others the passage of the labelled marker could generally be significantly reduced.


Characteristics of Women With Gestational Diabetes From Non-Caucasian Compared With Caucasian Ethnic Groups.
Short- and long-term outcomes in women after gestational diabetes mellitus (GDM) vary by ethnicity. Understanding differences in baseline diabetes risk factors is important for informing choice of risk-reducing interventions. We aimed to compare maternal and pregnancy-related characteristics in Caucasian and non-Caucasian women with GDM. Using a large multicentre Canadian cohort of women diagnosed with GDM and recruited between 2009 and 2013, we compared demographic, clinical and behavioural characteristics in women with GDM across 7 ethnic groups. Data were obtained from chart reviews and surveys, and logistic and linear regression models were used to compare binary and continuous variables, respectively, between Caucasian and non-Caucasian ethnic groups. Of the 1,332 women with GDM, 911 were eligible for inclusion. Of these, 41.4% were white Caucasian, 17.1% were South Asian, 18.4% were East Asian, 5.8% were black, 8.8% were Filipina, 5.2% were Middle Eastern and 3.3% were Hispanic. Non-Caucasian women were diagnosed with GDM at a younger age and were more likely to have a family history of diabetes compared with Caucasian women. With the exception of East Asians, non-Caucasian women were more likely to be overweight using ethnicity-specific body mass index cutoffs and have higher oral glucose tolerance test values than Caucasian women. Prepregnancy smoking and alcohol consumption prevalence were highest in Caucasian women. Several important ethnicity-specific differences in clinical and behavioural characteristics of women with GDM were identified. These differences need to be considered when offering interventions for reducing risk of adverse perinatal outcomes and subsequent type 2 diabetes.


Endodontic Rotary Systems: Comparison between Gentlefile and Pro Taper Universal for removal of Enterococcus faecalis.
As a resistant bacterium species in infected root canals, Enterococcus faecalis needs to be removed in any endodontic treatment. So, we aimed to compare the effectiveness of two rotary systems, Gentlefile and Pro Taper Universal, in removing Enterococcus faecalis (E. faecalis) from the infected root canal system. Forty single-root premolar teeth were collected and randomly divided into two groups: Gentlefile (n=18) and Pro Taper Universal (n=18). In addition, four teeth were used as a negative control. The root canals were prepared and infected with E. faecalis and incubated for 4 weeks. Samples were obtained from the root canal immediately before and after instrumentation. A reduction in bacteria was determined by the colony count method. Colony numbers of E. faecalis were significantly different before and after instrumentation in all groups (p<0.001). Furthermore, Gentlefile group illustrated a higher percentage of bacterial reduction (96.1%) compared to Pro Taper Universal group (90%). Accordingly, Gentlefile group was found to be significantly (p<0.001) more effective in decreasing bacterial populations than Pro Taper Universal group. Although both rotary systems were highly effective in bacterial reduction from root canals, Gentlefile demonstrated better bacterial reduction percentage from root canals than Pro Taper Universal. Key words:Enterococcus faecalis, Gentlefile, Pro Taper Universal, Rotary systems.


The Effect of Standardized Hospitalist Information Cards on the Patient Experience: a Quasi-Experimental Prospective Cohort Study.
Communication with clinicians is an important component of a hospitalized patient's experience. To test the impact of standardized hospitalist information cards on the patient experience. Quasi-experimental study in a U.S. tertiary-care center. All-comer medicine inpatients. Standardized hospitalist information cards containing name and information on a hospitalist's role and availability vs. usual care. Patients' rating of the overall communication as excellent ("top-box" score); qualitative feedback summarized via inductive coding. Five hundred sixty-six surveys from 418 patients were collected for analysis. In a multivariate regression model, standardized hospitalist information cards significantly improved the odds of a "top-box" score on overall communication (odds ratio: 2.32; 95% confidence intervals: 1.07-5.06). Other statistically significant covariates were patient age (0.98, 0.97-0.99), hospitalist role (physician vs. advanced practice provider, 0.56; 0.38-0.81), and hospitalist-patient gender combination (female-female vs. male-male, 2.14; 1.35-3.40). Eighty-seven percent of patients found the standardized hospitalist information cards useful, the perceived most useful information being how to contact the hospitalist and knowing their schedule. Hospitalized patients' experience of their communication with hospitalists may be improved by using standardized hospitalist information cards. Younger patients cared for by a team with an advanced practice provider, as well as female patients paired with female providers, were more likely to be satisfied with the overall communication. Assessing the impact of information cards should be studied in other settings to confirm generalizability.


Reversible minimal change nephrotic syndrome and glomerular IgA deposition associated with nonparenteral heroin abuse: a case report.
To report for the first time a case of reversible minimal change nephrotic syndrome with immunoglobulin A (IgA) deposition associated with heroin. A 29-year-old male heroin abuser who developed nephrotic syndrome was admitted to our clinic. Renal biopsy revealed minimal change disease with IgA deposition. Because spontaneous complete remission was observed after cessation of heroin, a diagnosis of minimal change nephrotic syndrome with IgA deposition associated with heroin abuse was considered. This case showed minimal change nephrotic syndrome with IgA deposition that had a benign clinical course.


Treating psychological problems in medical settings: primary care as the de facto mental health system and the role of hypnosis.
Psychological comorbidity with medical illness is associated with poor health status, complicated medical management, and increased utilization and greater costs of medical services. Hypnosis practitioners in specialty psychological or psychiatric treatment settings infrequently treat such patients, since there is a greater likelihood of patients' psychological problems being treated solely in primary medical care. Referring patients from primary care to the mental health system will most likely not result in patients initiating psychological or hypnotic treatment. At the same time, integrated provision of medical and psychological treatment in the medical office has demonstrated much higher rates of initiation of treatment and improved medical outcomes. Although hypnosis has been found to be an empirically effective treatment for many medical problems, when hypnosis practitioners do not practice in these medical sites then patients do not have access to effective hypnotic interventions for cotreatment of medical problems.


Influence of Not-for-Profit Hospital Ownership Type on Community Benefit and Charity Care.
Non-profit hospitals are expected to provide charity care and other community benefits to adjust their tax exemption status. Using the Medicare Hospital Cost Report, American Hospital Association Annual Survey, and the American Community Survey datasets, we examined if church-affiliated hospitals spent more on charity care and community benefit. For this analysis, we defined five main categories of community benefits were measured: total community benefit; charity care; Medicaid shortfall; unreimbursed other means-tested services; and the total of unreimbursed education and unfunded research. Multiple regression was used to examine the effect of church ownership, controlling for other factors, on the level of community benefit in 2644 general acute care non-profit hospitals. Descriptive analyses and multiple regression were used to show the relationship between the provision of community benefits and church affiliation including Catholic (CH), other church-affiliated hospitals (OCAH), and non-church affiliated hospitals (NCAH). The non-profit hospital on average spent 6.5% of its total expenses on community benefits. NCAH spent 6.09%, CH spent 7.5%, and OCAH spent 9.4%. Non-profits spent 2.8% of their total expenses on charity care, with the highest charity care spending for OCAH (5.2%), followed by CH (3.9%), and NCAH (2.4%). Regression results showed that CH and OCAH, on average, spent 1.08% and 2.16% more on community benefits than NCAHs. In addition, CH and OCAH spent more on other categories of community benefits except for education and research. Church-affiliated hospitals spend more on community benefits and charity care than non-church affiliated nonprofit hospitals.


Gammaherpesvirus targets peritoneal B-1 B cells for long-term latency.
Gammaherpesviruses establish life-long infection in most adults and are associated with the development of B cell lymphomas. While the interaction between gammaherpesviruses and splenic B cells has been explored, very little is known about gammaherpesvirus infection of B-1 B cells, innate-like B cells that primarily reside in body cavities. This study demonstrates that B-1 B cells harbor the highest frequency of latently infected cells in the peritoneum throughout chronic infection, highlighting a previously unappreciated feature of gammaherpesvirus biology.


[Development of the curvature of the cervical spine in utero. Attempted interpretation].
It is conventional saying that the fetal rachis shows only one ventral concavity. An echographic study allowed to observe in utero the rachis of more than a hundred live fetuses. The radius of this curvature gradually increases according to the development, revealed by the disappearance of the cervical curvature under the influence of the weight of the head and the uterine constraints. The sagittal curvatures of the vertebral column explains mans adaptability to the erected position. The authors think that the conventional conception, in which ontogenetic development is comparable with phylogenetic development, needs to be reconsidered: the cervical curvature is a prime curvature setting the evolutionist question about the origins of the rachidian curvatures.


SNP genotyping of enterohemorrhagic Escherichia coli O157:H7 isolates from China and genomic identity of the 1999 Xuzhou outbreak.
Enterohemorrhagic Escherichia coli O157:H7 is a well-known pathogen as a cause of diarrhea, hemorrhagic colitis (HC), and hemolytic uremic syndrome (HUS). Single nucleotide polymorphisms (SNPs) have been widely used to determine genetic relatedness and epidemiological relationship of O157:H7. Little is known of genetic diversity of Chinese O157:H7 isolates and their relationships with global isolates. The minimum sets of 32 SNPs each from Manning et al. and Clawson et al. were used to type 325 Chinese O157:H7 isolates. The 64 SNPs divided the Chinese O157:H7 isolates into 5 SNP genotypes (SG-1-SG-5). The most common SGs were SG-5 (79.69%) and SG-1 (14.46%). Human isolates concentrated in SG-1 and SG-5, and there is only 1 human isolates in SG-3. The 47 isolates in SG-1 were further divided by an additional SNP sourced from Xuzhou21 genome into 2 subtypes (SG-1.1 and SG-1.2). Strains in SG-1.1 caused the 1999 Xuzhou deadly outbreak. Our Chinese isolates have been found to belong to a limited number of SNP genotypes and are represented by distantly related clades in Manning et al. and lineages in Claswon et al., suggesting parallel spread of these SNP genotypes in China.


Developmental expression of prion protein gene in brain.
Synthesis of the cellular isoform of the prion protein (PrPC) was found to be regulated during development of the hamster brain. PrP poly A(+) RNA was readily detectable 10 days postpartum; after 20 days of age, no change in its level could be detected through 13 months of age. Low levels of PrP poly A(+) RNA were detectable 1 day after birth. By contrast, myelin basic protein poly A(+) RNA was found at high levels in brain at 30 days of age and thereafter declined steadily. Using monospecific PrP antisera, immunoprecipitable cell-free translation products were detected at low levels 2 days after birth and increased progressively through 10 days of age. How the levels of PrP mRNA participate in brain development and function remains to be established.