Synthesis and physical properties of perovskite Sm1-xSrxNiO3(x= 0, 0.2) and infinite-layer Sm0.8Sr0.2NiO2nickelates.
Recently, superconductivity at about 9-15 K was discovered in Nd1-xSrxNiO2(Nd-112,x≈ 0.125-0.25) infinite-layer thin films, which has stimulated enormous interests in related rare-earth nickelates. Usually, the first step to synthesize this 112 phase is to fabricate theRNiO3(R-113,R: rare-earth element) phase, however, it was reported that the 113 phase is very difficult to be synthesized successfully due to the formation of unusual Ni3+oxidation state. And the difficulty of preparation is enhanced as the ionic radius of rare-earth element decreases. In this work, we report the synthesis and investigation on multiple physical properties of polycrystalline perovskites Sm1-xSrxNiO3(x= 0, 0.2) in which the ionic radius of Sm3+is smaller than that of Pr3+and Nd3+in related superconducting thin films. The structural and compositional analyses conducted by x-ray diffraction and energy dispersive x-ray spectrum reveal that the samples mainly contain the perovskite phase of Sm1-xSrxNiO3with small amount of NiO impurities. Magnetization and resistivity measurements indicate that the parent phase SmNiO3undergoes a paramagnetic-antiferromagnetic transition at about 224 K on a global insulating background. In contrast, the Sr-doped sample Sm0.8Sr0.2NiO3shows a metallic behavior from 300 K down to about 12 K, while below 12 K the resistivity exhibits a slight logarithmic increase. Meanwhile, from the magnetization curves, we can see that a possible spin-glass state occurs below 12 K in Sm0.8Sr0.2NiO3. Using a soft chemical reduction method, we also obtain the infinite-layer phase Sm0.8Sr0.2NiO2with square NiO2planes. The compound shows an insulating behavior which can be described by the three-dimensional variable-range-hopping model. And superconductivity is still absent in the polycrystalline Sm0.8Sr0.2NiO2.


Measuring health-related quality of life in patients treated for substance dependence: differences among instruments and methods of eliciting preferences.
Measuring the health-related quality of life is an essential estimation in cost-utility studies. In this research, we provide new evidence about comparing utility scores - in the field of substance dependence. Although the main objective is to compare the EQ-5D-5L and SF-6D with paired gamble, evidence about the SF-6D with standard gamble is also provided. Ninety-four patients with substance dependence were recruited; the SF-6D and the EQ-5D-5L were administered at the beginning of treatment and 6 months thereafter. Differences in treatment effect were estimated by comparing utility gains. All analyses were reproduced for two subgroups of severity. Both the baseline scores and the treatment effect are sensitive to the instrument used. For severe states, the SF-6D with paired gamble (SF-6D with standard gamble) estimates the lowest (highest) utility. With regard to the impact of treatment, the EQ-5D-5L and SF-6D with paired gamble estimate strongly similar effects for severe states (and both estimate greater effects than does the SF-6D with standard gamble). These findings have implications for cost-utility analyses. The incremental cost-utility ratio of treatments intended for severe states is barely sensitive to the choice of EQ-5D-5L or SF-6D with paired gamble.


RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.
Necroptosis facilitates cell death in a controlled manner and is employed by many cell types following injury. It plays a significant role in various liver diseases, albeit the cell-type-specific regulation of necroptosis in the liver and especially hepatocytes, has not yet been conceptualized. We demonstrate that DNA methylation suppresses RIPK3 expression in human hepatocytes and HepG2 cells. In diseases leading to cholestasis, the RIPK3 expression is induced in mice and humans in a cell-type-specific manner. Overexpression of RIPK3 in HepG2 cells leads to RIPK3 activation by phosphorylation and cell death, further modulated by different bile acids. Additionally, bile acids and RIPK3 activation further facilitate JNK phosphorylation, IL-8 expression, and its release. This suggests that hepatocytes suppress RIPK3 expression to protect themselves from necroptosis and cytokine release induced by bile acid and RIPK3. In chronic liver diseases associated with cholestasis, induction of RIPK3 expression may be an early event signaling danger and repair through releasing IL-8.


Can thermal intensification be considered a sustainable way for greening Fenton processes?
Life cycle assessment and kinetic modeling were used to elucidate the impact of thermal intensification (TI) on resource consumption and the techno-economic feasibility of a Fenton process at laboratory scale. Increasing temperature from 25 to 55 °C lowers treatment time (96.5%) and electricity use (67.8%) due to the positive impact of temperature on the reaction rate; however, beyond 50 °C no significant diminution in energy use, emissions, and operating cost was observed. The environmental footprint of the process is linked with energy use, operating pH, and the electricity share of the country; nevertheless, the impact of transport and infrastructure materials was lower. At 55 °C and pH of 2.8, emissions of precursors of freshwater and marine eutrophication, particulate matter formation, and ionizing radiation were reduced more than half; besides, in most of the midpoint categories, pondered by the ReCiPe-2016 method, emissions were lowered ca. 43.3%. The endpoint categories human health, ecosystem quality, and resource availability had a significant decline in disability-adjusted life years (46.0%), time-integrated species loss (42.0%), and surplus cost (33.1%). Harnessing the energy present in the wastewater itself decreased 41.9% global warming potential (GWP), but the use of steam for heating raised it 718.8%. In countries where electricity generation is dependent on fossil fuels, GWP could increase (2.0-20.0%) whereas GWP would decrease (8.8-9.4%) when renewable energy sources dominate. Operating at 55 °C and pH of 5.5 rose the reaction time (1835.5%), GWP (29.3%), particulate matter formation (44.3%), terrestrial acidification (21.8%), marine (48.9%), and freshwater eutrophication (66.7%). TI of Fenton processes could increase their treatment capacity with a small reduction in the quality of the effluent; furthermore, they can be made affordable for low-to-medium scale industries in emerging economies due to decreased resources consumption and emissions, leading to a lower treatment cost (US$0.49/m3).


Thiopental requirements may be increased in children reanesthetized at least one year after recovery from extensive thermal injury.
Clinical observations suggested that children long recovered from burn injury required larger doses of thiopental for a smooth anesthetic induction. A prospective randomized study examined children 6-16 yr old, with greater than 15% burn, and more than 1 year after injury, for loss of lid reflex (LR), corneal reflex (CR), and acceptance of the anesthesia mask (AM) 60 sec after administration of thiopental. Children were unpremedicated, received the thiopental (2.5%) through a rapidly running peripheral intravenous line, and received either 2, 3, 4, 5, 6, 7, or 8 mg/kg. LR, CR, and AM were examined at 30, 60, and 90 sec. Blood pressure and heart rate were recorded for those patients receiving 7 or 8 mg/kg thiopental. The mean age was 12.0 +/- 0.5 yr, weight 43.9 +/- 2.9 kg, % burn 44.7 +/- 2.9, time since burn 68.4 +/- 7.7 months, and time since previous thiopental 25.1 +/- 6.6 months. The estimated ED50 (95% confidence limits) for loss of LR was 4.78 (3.95-5.78) mg/kg; for loss of CR was 7.04 (4.87-10.10) mg/kg; and for AM was 6.74 (4.68-9.71) mg/kg. These doses of thiopental were significantly greater for LR and AM (P less than 0.001) but not CR (P = 0.15) compared to non-thermally injured children. There were no clinically important or statistically significant decreases in blood pressure while heart rate did increase 11 beats/min (P less than 0.05) in children who received 7 or 8 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)


Rebalancing Immune Homeostasis to Treat Autoimmune Diseases.
During homeostasis, interactions between tolerogenic dendritic cells (DCs), self-reactive T cells, and T regulatory cells (Tregs) contribute to maintaining mammalian immune tolerance. In response to infection, immunogenic DCs promote the generation of proinflammatory effector T cell subsets. When complex homeostatic mechanisms maintaining the balance between regulatory and effector functions become impaired, autoimmune diseases can develop. We discuss some of the newest advances on the mechanisms of physiopathologic homeostasis that can be employed to develop strategies to restore a dysregulated immune equilibrium. Some of these designs are based on selectively activating regulators of immunity and inflammation instead of broadly suppressing these processes. Promising approaches include the use of nanoparticles (NPs) to restore Treg control over self-reactive cells, aiming to achieve long-term disease remission, and potentially to prevent autoimmunity in susceptible individuals.


Alcohol policy changes and 22-year trends in individual alcohol consumption in a Swiss adult population: a 1993-2014 cross-sectional population-based study.
Evidence on the impact of legislative changes on individual alcohol consumption is limited. Using an observational study design, we assessed trends in individual alcohol consumption of a Swiss adult population following the public policy changes that took place between 1993 and 2014, while considering individual characteristics and secular trends. Cross-sectional study. Swiss general adult population. Data from 18 963 participants were collected between 1993 and 2014 (aged 18-75 years). We used data from the 'Bus Santé' study, an annual health survey conducted in random samples of the adult population in the State of Geneva, Switzerland. Individual alcohol intake was assessed using a validated food frequency questionnaire. Individual characteristics including education were self-reported. 7 policy changes (6 about alcohol and 1 about tobacco) that occurred between 1993 and 2014 defined 6 different periods. We predicted alcohol intake using quantile regression with multivariate analysis for each period adjusting for participants' characteristics and tested significance periods. Sensitivity analysis was performed including drinkers only, the 10th centile of highest drinkers and smoker's status. Between 1993 and 2014, participants' individual alcohol intake decreased from 7.1 to 5.4 g/day (24% reduction, p<0.001). Men decreased their alcohol intake by 34% compared with 22% for women (p<0.001). The decrease in alcohol intake remained significant when considering drinkers only (28% decrease, p<0.001) and the 10th centile highest drinkers (24% decrease, p<0.001). Consumption of all alcoholic beverages decreased between 1993 and 2014 except for the moderate consumption of beer, which increased. After adjustment for participants' characteristics and secular trends, no independent association between alcohol legislative changes and individual alcohol intake was found. Between 1993 and 2014, alcohol consumption decreased in the Swiss adult population independently of policy changes.


HER-2 amplification is highly homogenous in gastric cancer.
Her-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-Her-2 therapy is currently investigated in several other HER-2-amplified cancers including gastric cancer. Although HER-2 amplification occurs in more than 10% of gastric cancers, potential heterogeneity of HER-2 amplification and overexpression could represent a major drawback for anti-Her-2 therapy. To address the potential applicability of trastuzumab in gastric cancer, tissue microarray sections of 166 gastric adenocarcinomas and 69 lymph node metastases were analyzed for Her-2 overexpression and amplification using Food and Drug Administration-approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 27 (16%) of 166 gastric adenocarcinomas. Amplification was typically high level with more than 20 HER-2 copies per tumor cell and a HER-2/centromere 17 ratio >3. Amplification was associated with intestinal tumor phenotype but unrelated to survival, grading, pT, pN, or pM. Identical HER-2 status was found in primary tumor and their matched lymph node metastases. Moreover, HER-2 and Topoisomerase IIalpha coamplification analysis of 3 to 16 large sections from 8 Her-2-positive gastric cancers did not reveal any heterogeneity of the amplicon site. The high level of HER-2 amplification in combination with the homogeneity of its expression in primary and metastatic tumors argues for a possible therapeutic utility of trastuzumab in HER-2-amplified gastric adenocarcinomas.


Antibodies reacting with the glomerular mesangium. Isolation and immunopathology.
Antigens of porcine lung were prepared by homogenization and ultrasonic treatment of lung tissue. The antigens were digested by collagenase and trypsin and chromatographed on Sephadex G 200. After immunization of rabbits with certain fractions of the chromatographed material, antibodies could be obtained in rabbits which fixed in vitro and in vivo in the glomerular mesangium of rats, hogs and the human, but not in the basement membrane of glomeruli of these species. Following intravenous injection into rats, the antibodies could be observed in the mesangial area without an apparent loss of antigenicity for 55 days. While 5 days after the application of 20 mg of the anti-mesangial IgG-preparation, there were no glomerular changes histologically demonstrable, after 55 days small amounts of rat-IgG could be demonstrated histochemically within the mesangium. Deposits of rat-complement (C3) could not be demonstrated with certainty. Severe morphological lesions were absent. Rats injected with the same doses of antibody and simultaneously immunized with rabbit-IgG showed a substantially greater deposit of autologous rat-IgG and rat-complement within the mesangial area after 55 days. By histological examination focal and segmental scleroses of the mesangium were determined. A significant pathological proteinuria did not occur. The present model constitutes a new possibility for studying the function of the glomerular mesangium.


Gold nanoparticle formation as an indicator of enzymatic methods: colorimetric L-phenylalanine determination.
An enzymatic-colorimetric method has been developed based on the reaction between L-phenylalanine (L-Phe) and the L-amino acid oxidase (LAAO) in the presence of Au(III), which has led to the formation of gold nanoparticles. The intensity of the localized surface plasmon resonance (LSPR) band of the generated nanoparticles (550 nm) can be related to the concentration of L-Phe in the sample. The mechanism of the LAAO-L-Phe enzyme reaction in the presence of Au(III) has been studied through the evaluation and optimization of experimental conditions. These studies have reinforced the hypothesis that the catalytic center of the enzyme helps the Au(III) reduction and, thanks to the protein, the Au0 form is stabilized as gold nanoparticles (AuNPs). In the calibration study, a sigmoidal relationship between the concentration of the substrate and the LSPR of the nanoparticles was observed. The linearization of the signal has allowed the determination of L-Phe in the range from 17 to 500 µM with an RSD% (150 μM) of 4.8% (n = 3). The method is free of other amino acid interference normally found in blood plasma. These highly competitive results open the possibility of further development of a rapid method for L-Phe determination based on colorimetry.


Molecular insights into the differential efflux mechanism of Rv1634 protein, a multidrug transporter of major facilitator superfamily in Mycobacterium tuberculosis.
Currently, multidrug-resistant tuberculosis (MDR-TB) is a public health crisis and a major health security threat globally. In Mycobacterium tuberculosis (Mtb), major facilitator superfamily (MFS) is the largest group of secondary active transporters. Along with the transport of their natural substrates, MFS proteins were involved in a drug efflux mechanism that ultimately lead to resistance against available anti-TB drugs in Mtb. In the present study, the three-dimensional structure model of an MFS protein, Rv1634, a probable multidrug transporter from Mtb, was generated using homology modeling. The protein structure model was found in inward-open conformation having 14 transmembrane helices. In addition, a central transport channel was deduced across the protein, and a single binding pocket was identified halfway through the central cavity by structural alignment with the homologous protein structures. Further, Rv1634 protein was studied based on the differential structural behavior of apo and ligand-bound forms. All the protein systems were inserted into a phospholipid bilayer to characterize the conformational dynamics of the protein using molecular dynamics (MD) simulations. Detailed analysis of the MD trajectories showed the diverse substrate specificity of the binding pocket for the antibiotics that caused differential movement in the ciprofloxacin and norfloxacin, to which Mtb strains have now become resistant. The expulsion of the drugs outside the bacterial cell occurs through the alternating-access mechanism of N and C-terminal domains, which is intriguing and essential to the understanding the drug resistance mechanism in pathogenic bacteria.


Oral reconstruction with hybrid implant-supported fixed prostheses in cases of mandibular defect using two methods along with 3 years of follow-up: A case report.
Ameloblastoma is an invasive odontogenic tumor, and for reconstruction, iliac graft and dental implants play an important role. This article evaluates the application of hybrid prostheses, clinical steps, and complications related to this treatment.


Risk factors of perforation in gastric stromal tumors during endoscopic resection: a retrospective case-control study.
Perforation is a common complication during endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) associated with secondary infections, sepsis, hospitalization time and cost. However, the risk factors of perforation remain controversial. This study aimed to investigate the risk factors for perforation during ER of gGISTs. This retrospective case-control study included consecutive patients with gGISTs who underwent ER between June 2009 and November 2021 at the Nanjing Drum Tower Hospital. Univariate and multivariate analyses were performed to investigate the risk factors for perforation. Sensitivity analyses with propensity scoring (PS) were performed to evaluate the stability of the independent effects. In total, 422 patients with gGISTs were included. The following factors were associated with perforation during ER: in the non-intraluminal growth patterns (all confounders adjusted odds ratio [aOR]: 5.39, 95% CI 2.99-9.72, P < 0.001), in the gastric fundus (aOR 2.25, 95% CI 1.40-3.60, P = 0.007), sized ≥ 2 cm (aOR 1.70, 95% CI 1.04-2.77, P = 0.035), in the lesser curvature (aOR 0.12, 95% CI 0.05-0.27, P < 0.001), and in the gastric cardia (aOR 0.13, 95% CI 0.04-0.50, P = 0.003). The PS analysis confirmed the stable independent effects of these identified risk factors. ERs of gGISTs in non-intraluminal growth patterns, in the gastric fundus, and with larger tumor size were independent risk factors for perforation. While tumors in the lesser curvature or gastric cardia were independent protective factor for perforation.


Lack of tumorigenic activity of 1,1-dimethylhydrazine in Syrian golden hamsters treated by subcutaneous injection.
Syrian golden hamsters were treated throughout their lifespan by weekly subcutaneous injections of 1,1-dimethylhydrazine (1,1-DMH) at doses of 0, 8, 17 and 35 mg/kg body weight. In contrast to our previous study using European hamsters, no treatment-related tumors occurred in this study.


Youth in group home care: youth characteristics and predictors of later functioning.
This paper presents the findings of an exploratory research study of foster care youth residing in group homes in a mid-Atlantic state in the USA. The aims of the present study were to (1) describe youth characteristics, (2) explore whether baseline functioning differed by gender or ethnicity, (3) explore predictors of cross-time differences in psychosocial functioning, and (4) explore predictors of later functioning, specifically age, gender, and length of stay. Psychosocial functioning at two time points (i.e., T1 = admission into group home; T2 = current or discharge) in 180 charts from 29 randomly selected group homes were reviewed. Youth were on average 14.86 years of age, predominantly male (71%; n = 128), and predominantly African American (79%). Findings suggest that group home placement may benefit some youth but not others, particularly girls and younger children with lower initial level of need. Findings underscore the potential complexity of intervention impact in the context of unique youth, family, and environment factors.


Reconstitution of rapid and asymmetric assembly of M13 procoat protein into liposomes which have bacterial leader peptidase.
The leader peptidase of Escherichia coli cleaves a 23-residue leader sequence from M13 procoat to yield mature coat protein in virus-infected cells. We have reconstituted pure leader peptidase into vesicles of E. coli lipids and found that these liposomes are active in the conversion of procoat to coat. Trypsin removes all but 10% of the leader peptidase, yet the vesicles retain nearly full capacity to convert procoat to coat, suggesting that only procoat which inserts across the liposomal membrane is a substrate for leader peptidase. This is confirmed by the finding that over 70% of the coat protein produced by these liposomes spans the membrane. The rate at which leader peptidase inside protease-treated liposomes cleaves externally added procoat is comparable to the rate of procoat cleavage by the same amount of leader peptidase in detergent micelles. Thus, procoat can rapidly integrate across a liposomal membrane and be cleaved to coat protein. These findings confirm the central part of the membrane trigger hypothesis that certain proteins (such as procoat) can cross a bilayer without the aid of a proteinaceous pore or transport system.


Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.
Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic.


Heralds of global transparency: Remote sensing, nuclear fuel-cycle facilities, and the modularity of imagination.
How has commercial remote sensing influenced the framing of public narratives about nuclear programs and weapons of mass destruction? This article examines an early and formative case: In 2002, a Washington-based nongovernmental organization used commercial satellite images to publicly identify the Natanz nuclear facility in Iran. The episode helped inaugurate the 'Iran nuclear crisis' as we have known it since. But it also played a role in fomenting a commercial market for remote sensing, adjusting the role of 'citizen scientist' in the nuclear arms-control community, visualizing a new television journalism beat of 'covering the intelligence community', legitimizing a transforming role of nuclear safeguards inspectors at the International Atomic Energy Agency, and solidifying Iran's nuclear program as 'clandestine'. This article follows the images as they pass through these social worlds and examines how heterogenous actors incorporated remote sensing into their identities and commitments to global transparency.


Housing dampness and health amongst British Bengalis in east London.
The paper describes a survey that was undertaken to investigate the possible associations between damp public sector housing in London (U.K.) and the health of British Bengali tenants. The problems of establishing epidemiological evidence in this field and the accurate assessment of dampness and health are addressed, and the relative importance of housing and lifestyle factors in the prevalence of damp in the home is considered. The results show that there are significant relationships between reported and measured damp, cold and mould in the home and various aspects of reported health. It is also apparent that it is aspects of housing, in particular the provision of a good heating system rather than lifestyle that determine the degree of dampness in a home.


Moderate-Intensity Continuous Training or High-Intensity Interval Training with or without Resistance Training for Altering Body Composition in Postmenopausal Women.
This study aimed to compare body composition changes induced by moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), or HIIT + resistance training (RT) programs (3 d·wk, 12 wk) in overweight/obese postmenopausal women, and to determine whether fat mass reduction is related to greater fat oxidation (FatOx). Participants (n = 27) were randomized in three groups: MICT (40 min at 55%-60% of peak power output), HIIT (60 × 8 s at 80%-90% of peak HR, 12 s active recovery), and HIIT + RT (HIIT + 8 whole-body exercises: 1 set of 8-12 repetitions). Dual-energy x-ray absorptiometry was used to measure whole-body and abdominal/visceral fat mass (FM) and fat-free mass. FatOx was determined at rest, during a moderate-intensity exercise (40 min at 50% of peak power output), and for 20 min postexercise, before and after training. Overall, energy intake and physical activity levels did not vary from the beginning to the end of the intervention. Body weight and total FM decreased in all groups over time, but significant abdominal/visceral FM losses were observed only in HIIT and HIIT + RT groups. When expressed in percentage, total FM, fat-free mass, and muscle mass were significantly modified only by HIIT + RT training. FatOx did not change at rest but increased similarly in the three groups during and after exercise. Therefore, the HIIT-induced greater FM loss was not related to higher FatOx during or after exercise. MICT or HIIT ± RT could be proposed to nondieting postmenopausal women who are overweight/obese to decrease weight and whole-body FM. The HIIT programs were more effective than MICT in reducing abdominal/visceral FM. RT addition did not potentiate this effect but increased the percentage of muscle mass.


Critical care illness and rehabilitation.
Critical care illness is often followed by protracted, slow and incomplete recovery. Survivors given access to specialized rehabilitation achieve a higher level of recovery, with greater independence and less need for social or health-care support long-term.


[Effects of Triptolide on Tc and Th Cell Excursion in Peripheral Blood of Nude Mice with Systemic Lupus Erythematosus BALB/c-un].
To investigate the effect of triptolide on the excursion of Tc and Th cells in peripheral blood of systemic lupus erythematosus (SLE) BALB/c-un nude mice induced by pristane. Eighteen female BALB/c-un nude mice were randomly divided into blank, SLE and triptolide group, each with 6 mice by random table method. Group SLE and group triptolide were established by single intraperitoneal injection of pristane, and blank group was used as blank control group. SLE model was established by single intraperitoneal injection. Triptolide group was fed with triptolide at the dose of 5 mg/(kg·d), and the blank group and SLE group were fed normally. Blood samples were collected from the caudal vein before treatment and 1, 3 and 6 months after treatment respectively. Fluorescence labeled flow cytometry was used to delect Tc and Th lymphocyte subsets at different stages of treatment. After treatment for 3 and 6 moths, the percentages of Tcl, Thl cells and CD8+, Tcl/Tc2, Thl/Th2 and CD4+/CD8+ all decreased in the group of triptolide, and the percentage of CD4+, Tc2 and Th2 cells increased (P<0.05). The mechanism of triptolide in the treatment of SLE may be related with the excursion of Tc and Th cells to Tcl and Tc2 to maintain the relative homeostasis of Tc and Th cells at different stage, thus affecting the immune response and the inflammatory reaction.


Suppression of NADPH oxidase 2 substantially restores glucose-induced dysfunction of pancreatic NIT-1 cells.
Defects in insulin secretion by pancreatic cells and/or decreased sensitivity of target tissues to insulin action are the key features of type 2 diabetes. It has been shown that excessive generation of reactive oxygen species (ROS) is linked to glucose-induced β-cell dysfunction. However, cellular mechanisms involved in ROS generation in β-cells and the link between ROS and glucose-induced β-cell dysfunction are poorly understood. Here, we demonstrate a key role of NADPH oxidase 2 (NOX2)-derived ROS in the deterioration of β-cell function induced by a high concentration of glucose. Sprague-Dawley rats were fed a high-fat diet for 24 weeks to induce diabetes. Diabetic rats showed increased glucose levels and elevated ROS generation in blood, but decreased insulin content in pancreatic β-cells. In vitro, increased ROS levels in pancreatic NIT-1 cells exposed to high concentrations of glucose (33.3 mmol·L(-1)) were associated with elevated expression of NOX2. Importantly, decreased glucose-induced insulin expression and secretion in NIT-1 cells could be rescued via siRNA-mediated NOX2 reduction. Furthermore, high glucose concentrations led to apoptosis of β-cells by activation of p38MAPK and p53, and dysfunction of β-cells through phosphatase and tensih homolog (PTEN)-dependent Jun N-terminal kinase (JNK) activation and protein kinase B (AKT/PKB) inhibition, which induced the translocation of forkhead box O1 and pancreatic duodenal homeobox-1, followed by reduced insulin expression and secretion. In conclusion, NOX2-derived ROS could play a critical role in high glucose-induced β-cell dysfunction through PTEN-dependent JNK activation and AKT inhibition.


Electron microscopic immunocytochemical demonstration of separate neurophysin-vasopressinergic and neurophysin-oxytocinergic nerve fibres in the neural lobe of the rat hypophysis.
By means of the unlabeled antibody peroxidase-antiperoxidase (PAP) technique at the electron microscopic level, it was demonstrated that the hormones of the neural lobe of the rat hypophysis are located in separate neurophysin-vasopressinergic and neurophysin-oxytocinergic nerve fibres. These observations confirm the results of our previous immunocytochemical studies at the light microscopic level.


Pit picking vs. Limberg flap vs. primary open method to treat pilonidal sinus disease - A cohort of 327 consecutive patients.
Minimally invasive methods in pilonidal sinus disease (PSD) surgery are becoming standard. Although long-term results are available for some techniques, long-term outcome data of patients after pit picking is lacking. We aimed at investigating perioperative and long-term outcomes of patients undergoing pit picking, Limberg flap or primary open surgery to treat PSD. In a single-centre observational study, we evaluated the outcomes of 327 consecutive patients undergoing PSD surgery between 2011 and 2020. PSD had recurred in 22% of Limberg flap patients and 62% of pit picking patients at 5 years (p=0.0078; log rank test). Previous pilonidal surgeries, smoking, body mass index, immunodeficiency, and diabetes did not significantly influence the long-term recurrence rate. Primary open treatment was performed for 72% of female patients presenting with primary disease. Due to its especially dismal long-term results, pit picking should be abandoned, and Limberg flap should be promoted instead, even for primary disease and in females.


DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients.
Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD. After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis. The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD. Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers.


A simple method for "reference range" estimation from routine laboratory data.
A simplified method is presented to estimate reference ranges from hospital laboratory data. It is based on a combination of graphical estimation of relative sizes of normal and abnormal populations and the "mode-center" concept in which the mode of the total population centers on the 50% cumulative frequency of the normal population. This method can be applied to determine reference ranges even though the data source contains abnormally high and/or low values. The reference ranges obtained for BUN and calcium from in-patient and out-patient sources by this method were found to be similar to those reported for "healthy" subjects.


Evaluation of the DNA damaging effect of the heat-induced food toxicant 5-hydroxymethylfurfural (HMF) in various cell lines with different activities of sulfotransferases.
5-Hydroxymethylfurfural (HMF), a heat-induced food toxicant present in a vast number of food items, has been suggested to be genotoxic after being bioactivated by the sulfotransferase SULT1A1. The comet assay was used to evaluate the DNA damaging effect of HMF in cell lines with different activities of SULT1A1: two human cell lines (Caco-2, low activity; and HEK293, higher activity), one cell line from mouse (L5178Y, no activity) and two cell lines from Chinese hamster (V79, negligible activity; and V79-hP-PST, high activity of human SULT1A1). HMF induced significant DNA damage in all cell lines after 3 h exposure to 100 mM. Most sensitive were V79 and V79-hP-PST where HMF induced significant DNA damage at 25 mM. Consequently, in the present study we have shown that HMF is a DNA damaging agent in vitro independent of the activity of SULT1A1 in the cells. The HMF-induced DNA damage was only observed at rather high concentrations which usually was associated with a concomitant decrease in cell viability.


Speech pathology telepractice intervention during the COVID-19 pandemic for Spanish-speaking children with cleft palate: A systematic review.
Due to the lockdown and quarantines caused by the COVID-19 pandemic, the need to study and use telepractice for providing speech pathology interventions for children with cleft palate has arisen. To carry out a systematic review of the use of telepractice during the COVID-19 pandemic for providing speech pathology interventions for Spanish-speaking children with cleft palate. In July and August 2020, the authors searched the electronic databases Medline, LILACS, SciELO, and the Cochrane Library using the following keywords in English (MeSH): Cleft palate combined with Early intervention, Speech therapy, Rehabilitation of speech and language disorders, Speech production measurement, Speech articulation tests and Telemedicine. Original articles were selected and analyzed, complemented by an analysis of flowcharts and recommendations by the GES Clinical Guide of Cleft Lip and Palate of Chile's Government and the authors' expert opinions. A total of 2680 articles were retrieved, of which 23 were critically analyzed and used to adapt the early stimulation, evaluation, and treatment of children with CP to speech therapy telepractice at the Gantz Foundation, a Hospital in Santiago de Chile. Only three researchers carried out a quick review, which limited the depth of individual analysis of the studies included. Also, the suggestions and material presented should be evaluated in future investigations. This systematic review provides useful guidelines for providing speech pathology interventions through telepractice for children with cleft palate. Audiovisual materials seem to be extremely useful for families receiving the interventions. The use of interactive videos for Spanish-speaking children and educational videos for parents is manifest.


Gestational diabetes: a reappraisal of HBA1c as a screening test.
Recent technological advances have made HBA1c a more standardized and user-friendly test with wide availability. This study evaluated HBA1c as a screening test for gestational diabetes mellitus (GDM) in a high-risk population. A total of 442 pregnant women were assessed by HBA1c. Two thresholds were used to "rule in or rule out" GDM, which was confirmed by the "gold-standard" 75-g OGTT (World Health Organization criteria). Eighty-four (19%) women had GDM while 358 (81%) women were normal; there was a complete overlap of the HBA1c histograms of the two populations. The area under receiver operating characteristic curve of HBA1c to detect GDM was 0.54 (95% CI 0.48-0.61). Using a value of <5.5% to rule out GDM; a sensitivity of 82.1% was achieved, with 15 (16.7%) of 90 women below the threshold being false-negatives (NPV = 83.3%). Using a threshold of HBA1c > or = 7.5% to rule-in GDM; the specificity was 95.8% with 15 (71.4%) of 21 patients over the threshold being false-positives (PPV = 28.6%). HBA1c would eliminate the need for an OGTT in 25.1% (111/442) of whom 27% (30/111) women would be misclassified. At any HBA1c threshold with an acceptable sensitivity, the false-positive rate remained high making it necessary for too many healthy women to undergo the confirmatory OGTT. Despite all the progress in methodology, HBA1c remains a poor test to screen for GDM.


Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) μmol/kg]>propranolol [9.21 (9.08-9.42) μmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 μmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 μmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 μmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.


Abelchia: inability to belch/burp-a new disorder? Retrograde cricopharyngeal dysfunction (RCPD).
This is retrospective case series involving 72 patients who presented with symptoms associated with inability to burp. The following symptoms was described by almost all the patients; retrosternal pain after eating or drinking, bloating feeling in the stomach, gurgling noise in the throat, excessive flatulence. These symptoms are worse with fizzy/carbonated drinks and beer. A full clinical history and examination plus endoscopic and in some cases barium a swallow radiological investigation was done. The surgery was performed under a general anaesthesia for all cases. Suspension pharyngoscopy in supine position using a Weerda diverticuloscope to identify the cricopharyngeal bar muscle. High dose of botulinum toxin A (botox) 100 iu was injected into the cricopharynxgeus muscle under a general anaesthesia. A total of 72 patients were diagnosed and undergone surgery between November 2016 and December 2020. There were 50 male and 22 female patients. Their average age was 30 (range 18-68 years old). All patients were able to burp again within first 4 weeks of the injection. This persisted even after the Botox worn off beyond the 3 months in 96% of cases. The average follow-up was 24 months post injection with longest follow-up 48 months (range 1-48 months). The author reported a new condition of inability to burp due to failure of the cricopharyngeal sphincter to relax spontaneously and outcome of treatment using botulinum toxin A injection into the cricopharyngeus muscle. It is expected that the paralysing action of botulinum toxin injection last approximately 3 months. However, this group of patients seem to be cured even after the effect of the botox is worn off. The author therefore postulated that there might me some neural dysfunction that inhibits the brain to send signals to the cricopharyngeal sphincter to initiate burping. Once burping is re-established with the help of botox injection, spontaneous burping seems to occur and sustained even after the botox is worn off.


Silencing of lncRNA MALAT1 Prevents Inflammatory Injury after Lung Transplant Ischemia-Reperfusion by Downregulation of IL-8 via p300.
Ischemia-reperfusion injury is a common early complication after lung transplantation. It was reported that long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in ischemia-reperfusion injury and regulates inflammation. This study aimed to explore the role of MALAT1 in inflammatory injury following lung transplant ischemia-reperfusion (LTIR). A LTIR rat model was successfully established, with the expression of MALAT1 and interleukin-8 (IL-8) in lung tissues detected. Then, in vitro loss- and gain-of-function investigations were conducted to evaluate the effect of MALAT1 on pulmonary epithelial cell apoptosis and IL-8 expression. The relationship among MALAT1, p300, and IL-8 was tested. Moreover, a sh-MALAT1-mediated model of LTIR was established in vivo to examine inflammatory injury and chemotaxis infiltration. Both IL-8 and MALAT1 were highly expressed in LTIR. MALAT1 interacted with p300 to regulate the IL-8 expression by recruiting p300. Importantly, silencing of MALAT1 inhibited the chemotaxis of neutrophils by downregulating IL-8 expression via binding to p300. Besides, MALAT1 silencing alleviated the inflammatory injury after LTIR by downregulating IL-8 and inhibiting infiltration and activation of neutrophils. Collectively, these results demonstrated that silencing of MALAT1 ameliorated the inflammatory injury after LTIR by inhibiting chemotaxis of neutrophils through p300-mediated downregulation of IL-8, providing clinical insight for LTIR injury.


Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity.
Immunotherapy has transformed cancer treatment. However, current immunotherapy modalities face various limitations. In the present study, we developed multiplexed activation of endogenous genes as an immunotherapy (MAEGI), a new form of immunotherapy that elicits antitumor immunity through multiplexed activation of endogenous genes in tumors. We leveraged CRISPR activation (CRISPRa) to directly augment the in situ expression of endogenous genes, and thereby the presentation of tumor antigens, leading to dramatic antitumor immune responses. Deploying this as a cell-based vaccination strategy showed efficacy in both prophylactic and therapeutic settings. Intratumoral adeno-associated virus delivery of CRISPRa libraries elicited strong antitumor immunity across multiple cancer types. Precision targeting of mutated gene sets eradicated a large fraction of established tumors at both local and distant sites. This treatment modality led to alterations in the tumor microenvironment, marked by enhanced T cell infiltration and antitumor immune signatures. Multiplexed endogenous gene activation is a versatile and highly scalable strategy to elicit potent immune responses against cancer, distinct from all existing cancer therapies.


Serum chromogranin A correlated with albuminuria in diabetic patients and is associated with early diabetic nephropathy.
The kidney is the main site for the removal of chromogranin A (CgA). Previous studies have found that patients with renal impairment displayed elevated concentrations of CgA in plasma and that CgA concentrations reflect a deterioration of renal function. In this study, we aimed to estimate serum CgA levels and to evaluate the role of serum CgA in the early diagnosis of diabetic nephropathy (DN). A total of 219 patients with type 2 diabetes mellitus (T2DM) were included in this cross-sectional study. These patients were classified into normoalbuminuria (n = 121), microalbuminuria (n = 73), or macroalbuminuria (n = 25) groups based on their urine albumin to creatinine ratios (UACRs). The degree of DN is reflected by UACR. A control group consisted of 45 healthy subjects. The serum CgA levels were measured by ELISA, and other key parameters were assayed. Serum CgA levels were higher in patients with T2DM than in control subjects, and a statistically significant difference among the studied subgroups regarding CgA was found (P < 0.05). The levels of serum CgA increased gradually with the degree of DN (P < 0.001). Serum CgA levels showed a moderate-intensity positive correlation with UACRs (P < 0.001). A cutoff level of 3.46 ng/ml CgA showed 69.86% sensitivity and 66.12% specificity to detect DN in the early stage. The levels of serum CgA increased gradually with the degree of DN and can be used as a biomarker in the early detection of DN.


Employment Condition Modifies the Using Patterns of Screening Mammography in Workers Insured by the Mexican Government: A Case-Control Study.
Our main aim was to investigate whether the employment condition modifies the use patterns of the screening mammography in workers insured by the Mexican government (Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, ISSSTE; medical facilities of the Mexican government). A case-control study age-matched was done in women insured by the Mexican government, aged 40-69 years, attending a general hospital (ISSSTE). All subjects were submitted to an interview and anthropometric data registry. In the interview were obtained: demographic data, of schooling, breast cancer family history, and reproductive history; besides, mammography history during the past 2 years and place of performance (in or outside of the ISSSTE). Finally, it was evaluated whether the mammography use in the ISSSTE was related to their employment condition: Active workers (cases) vs. dependents or retired workers (controls). The sample was of 252 women: 126 cases and 126 controls. Cases obtained less mammograms in the ISSSTE (P = 0.03, odds ratio = 0.54, 95% confidence interval, CI 0.30-0.96), than their dependents or the retired workers. Furthermore, cases with high education (university or higher) also obtained fewer mammograms in the ISSSTE (P = 0.03, odds ratio = 0.26, 95% CI 0.05-0.93). Women active workers with higher education are obtaining less screening mammograms in the ISSSTE than their dependents or the retired workers.


Validating the GCP data hypothesis using internet search data.
The Global Consciousness Project (GCP) operates under the hypothesis that events that elicit widespread emotion or draw the simultaneous attention of a large number of people could affect the output of hardware-generated random numbers. The hypothesis thus suggests that the mind, in some sense, can interact with matter at a distance, a controversial suggestion because such a mechanism could challenge some current understandings. Testing the validity of the hypothesis thus carries substantial merit as negative results would reinforce already established scientific perceptions, whereas positive results would point in the direction of a needed update. In this paper, it is hypothesized that events inflicting a strong emotional response should also trigger the need for information. As such, global internet search trends should correlate with the GCP data, allowing for the hypothesis to be objectively tested. In practice, Google Trends search data is used to construct several search indexes that are correlated with GCP data aggregates using time series statistics. It is found that the GCP data significantly correlates with the indexes and can be used to improve the statistical model's in-sample fit. Furthermore, it is found that out-of-sample forecasts can be made more accurate if the GCP data is used. The results thus point toward the validity of the GCP data hypothesis and that the data produced by the GCP can be put to practical use by, for example, forecasters.


Sudden death due to isolated acute infarction of the His bundle.
A 29 year old black man considered to be in good health died suddenly and unexpectedly. At postmortem examination there were no significant gross abnormalities, all drug screens were normal and sicklemia was not present. Special studies of the cardiac conduction system demonstrated isolated acute infarction of the His bundle, with no similar evidence of myocardial infarction anywhere else in the heart. The atrioventricular (AV) node artery was moderately narrowed, but its branch supplying the His bundle was occluded greater than 95% by focal fibromuscular dysplasia. There were no other significant coronary lesions or other abnormalities in the heart.


Genomic structures and characterization of the 5'-flanking regions of acyl carrier protein and Delta4-palmitoyl-ACP desaturase genes from Coriandrum sativum.
The seed-specific or seed-predominant promoters of acyl carrier protein (Cs-ACP1) and Delta4-palmitoyl-acyl carrier protein desaturase (Cs-4PAD) genes, which are involved in the biosynthesis of petroselinic acid, were isolated from coriander (Coriandrum sativum) and analyzed in coriander endosperms and transgenic Arabidopsis. The expression of Cs-ACP1 and Cs-4PAD genes was coordinately regulated during seed development.


Suppression of NLRP3 and NF-κB signaling pathways by α-Cyperone via activating SIRT1 contributes to attenuation of LPS-induced acute lung injury in mice.
α-Cyperone is the volatile oil component in Cyperus rotundus L. The previous reports had shown the inhibition of α-Cyperone on NF-κB signaling in LPS-stimulated RAW264.7 cells. However, it is still unclear whether α-Cyperone could suppress inflammatory response in acute lung injury (ALI) induced by LPS. The aim of this study is to investigate the suppression of α-Cyperone on LPS-induced ALI in mice. In this study, we established the LPS-induced ALI model and compared different doses of α-Cyperone with the control group and LPS group. Accordingly, the following indexes would be compared, including lung wet/dry ratio, MPO activity, inflammatory cell number, histopathological changes, levels of inflammatory cytokines, NF-κB and NLRP3 signaling pathways activation. The results demonstrated that α-Cyperone had the effect on reducing the wet/dry ratio and MPO activity. Furthermore, the increase of inflammatory cells and inflammatory cytokines could be inhibited by α-Cyperone. Meanwhile, α-Cyperone could downregulate NF-κB and NLRP3 signaling pathways. Finally, we found α-Cyperone could up-regulate the expression of SIRT1 and SIRT1 inhibitor could reverse the protective effects of α-Cyperone on ALI. In conclusion, α-Cyperone showed the protective effect on LPS-induced ALI in mice by suppressing the NF-κB and NLRP3 signaling pathways, mainly via up-regulating SIRT1. This provides a potential drug for the treatment of LPS-induced ALI.


Socioeconomic status is not associated with the delivery of care in people with diabetes but does modify HbA1c levels: An observational cohort study (Elzha-cohort 1).
Structured primary diabetes care within a collectively supported setting is associated with better monitoring of biomedical and lifestyle-related target indicators amongst people with type 2 diabetes and with better HbA1c levels. Whether socioeconomic status affects the delivery of care in terms of monitoring and its association with HbA1c levels within this approach, is unclear. This study aims to understand whether, within a structured care approach, (1) socioeconomic categories differ concerning diabetes monitoring as recommended; (2) socioeconomic status modifies the association between monitoring as recommended and HbA1c. Observational real-life cohort study with primary care registry data from general practitioners within diverse socioeconomic areas, who are supported with the implementation of structured diabetes care. People with type 2 diabetes mellitus were offered quarterly diabetes consultations. "Monitoring as recommended" by professional guidelines implied minimally one annual registration of HbA1c, systolic blood pressure, LDL, BMI, smoking behaviour and physical activity. Regarding socioeconomic status, deprived, advantageous urban and advantageous suburban categories were compared to the intermediate category concerning (a) recommended monitoring; (b) association between recommended monitoring and HbA1c. Aim 1 (n = 13 601 people): Compared to the intermediate socioeconomic category, no significant differences in odds of being monitored as recommended were found in the deprived (OR 0.45 (95% CI 0.19-1.08)), advantageous urban (OR 1.27 (95% CI 0.46-3.54)) and advantageous suburban (OR 2.32 (95% CI 0.88-6.08)) categories. Aim 2 (n = 11 164 people): People with recommended monitoring had significantly lower HbA1c levels than incompletely monitored people (-2.4 (95% CI -2.9; -1.8) mmol/mol). SES modified monitoring-related HbA1c differences, which were significantly higher in the deprived (-3.3 (95% CI -4.3; -2.4) mmol/mol) than the intermediate category (-1.3 (95% CI -2.2; -0.4) mmol/mol). Within a structured diabetes care setting, socioeconomic status is not associated with recommended monitoring. Socioeconomic differences in the association between recommended monitoring and HbA1c levels advocate further exploration of practice and patient-related factors contributing to appropriate monitoring and for care adjustment to population needs.


Human placental glucose transport in fetoplacental growth and metabolism.
While efficient glucose transport is essential for all cells, in the case of the human placenta, glucose transport requirements are two-fold; provision of glucose for the growing fetus in addition to the supply of glucose required the changing metabolic needs of the placenta itself. The rapidly evolving environment of placental cells over gestation has significant consequences for the development of glucose transport systems. The two-fold transport requirement of the placenta means also that changes in expression will have effects not only for the placenta but also for fetal growth and metabolism. This review will examine the localization, function and evolution of placental glucose transport systems as they are altered with fetal development and the transport and metabolic changes observed in pregnancy pathologies.


Arthrodesis Versus Arthroplasty in Thumb Carpometacarpal Osteoarthritis: Impact on Maximal Voluntary Force, Endurance, and Accuracy of Pinch.
To investigate differences in pinch strength recovery among patients with first carpometacarpal joint osteoarthritis treated with either arthrodesis or suspension arthroplasty. Thirty-seven subjects who underwent arthrodesis or suspension arthroplasty for carpometacarpal osteoarthritis were included. Force exerted during maximal voluntary contraction (MVC) in a pinch task was measured. Maximal voluntary contraction was recorded using a haptic device equipped with a load cell from which an analog signal was acquired and digitized for visual feedback. Dynamic force was assessed by a task consisting of 10 repetitions, with a target of 70% of MVC. Endurance was assessed by the length of sustained pinch task at 30% of MVC. Task performance was quantified by mean distance and offset error from the target force as error indices, and standard deviation of force was used as index of force steadiness. The arthrodesis group obtained considerably higher MVC values than the arthroplasty group. No notable differences were found for pinch endurance. The standard deviation for dynamic force was lower for arthroplasty, indicating greater force steadiness. Arthrodesis is associated with greater pinch strength. Arthroplasty is associated with better pinch precision. Therapeutic IV.


betagamma subunits of heterotrimeric G-proteins contribute to Ca2+ release at fertilization in the sea urchin.
A cytoplasmic Ca2+ transient is required for egg activation at fertilization in all animals. The pathway leading to release of Ca2+ from the endoplasmic reticulum in echinoderms includes activation of a SRC homolog, followed by phospholipase Cgamma activation, and formation of inositol trisphosphate. However, the upstream activators or modulators of this signaling pathway are not known. We recently identified four Galpha subunits of heterotrimeric G-proteins present in the sea urchin egg, and here we find that activation of G-proteins of the Galphas and Galphaq type, but not Galphai or Galpha12 type, is required for normal Ca2+ dynamics at fertilization. The effects of these G-proteins are mediated by the Gbetagamma subunits, occur upstream of the cytoplasmic Ca2+ release, and influence both the amplitude of Ca2+ release and the duration of the lag phase. We propose integration of the G-protein input into the framework of signaling at sea urchin fertilization.


Mass spectrometry and the amyloid problem--how far can we go in the gas phase?
A number of proteins are capable of converting from their soluble, monomeric form into highly-ordered, insoluble aggregates known as amyloid fibrils. In vivo, these fibrils, which accumulate in organs and tissues, are associated with a wide range of amyloid diseases for which there are currently no therapeutic solutions. The molecular details of the pathway from native monomer through oligomeric intermediates to the final amyloid fibril remain a challenging enigma. Over the past few years, mass spectrometry has been applied to investigate the various stages of amyloid fibril formation, and this report summarizes the key steps achieved to date.


Establishing pediatric reference intervals for 13 biochemical analytes derived from normal subjects in a pediatric endocrinology clinic in Korea.
Defining pediatric reference intervals is one of the most difficult tasks for laboratory physicians. The continuously changing physiology of growing children makes their laboratory values moving targets. In addition, ethnic and behavioral differences might also cause variations. The aim of this study was to establish age- and sex-specific partitioned reference intervals for 13 serum biochemical analytes in Korean children. A total of 2474 patients, girls aged 2-14 years and boys aged 2-16 years, who underwent a short stature workup but were diagnosed as normal at the Pediatric Endocrinology Clinic of Severance Hospital (Seoul, Korea) between September 2010 and June 2012 were included in this study. The levels of serum calcium, inorganic phosphorus, blood urea nitrogen, creatinine, uric acid, glucose, total cholesterol, total protein, albumin, alkaline phosphatase, aspartic aminotransferase, alanine aminotransferase, and total bilirubin were measured using a Hitachi 7600 analyzer (Hitachi High-Technologies Corporation, Tokyo, Japan). Reference intervals were partitioned according to sex or age subgroups using the Harris and Boyd method. Most analytes except calcium and albumin required partitioning either by sex or age. Age-specific partitioned reference intervals for alkaline phosphatase, creatinine, and total bilirubin were established for both males and females after being partitioned by sex. Additional age-specific partitioning of aspartic aminotransferase in females and total protein and uric acid in males was also required. Inorganic phosphorus, total cholesterol, alanine aminotransferase, blood urea nitrogen, and glucose were partitioned only by sex. This study provided updated age- and sex-specific pediatric reference intervals for 13 basic serum chemistry analytes from a sufficient number of healthy children by using a modern analytical chemistry platform.


Continuous monitoring of noise levels in the Gulf of Catania (Ionian Sea). Study of correlation with ship traffic.
Acoustic noise levels were measured in the Gulf of Catania (Ionian Sea) from July 2012 to May 2013 by a low frequency (<1000Hz) hydrophone, installed on board the NEMO-SN1 multidisciplinary observatory. NEMO-SN1 is a cabled node of EMSO-ERIC, which was deployed at a water depth of 2100m, 25km off Catania. The study area is characterized by the proximity of mid-size harbors and shipping lanes. Measured noise levels were correlated with the passage of ships tracked with a dedicated AIS antenna. Noise power was measured in the frequency range between 10Hz and 1000Hz. Experimental data were compared with the results of a fast numerical model based on AIS data to evaluate the contribution of shipping noise in six consecutive 1/3 octave frequency bands, including the 1/3 octave frequency bands centered at 63Hz and 125Hz, indicated by the Marine Strategy Framework Directive (2008/56/EC).


Improving access to otolaryngology-head and neck surgery expert advice through eConsultations.
Prolonged wait times have become common. Electronic consultations (eConsults) have been shown in previous studies to reduce unnecessary face-to-face consultations to specialists, but no prior study has investigated the feasibility or efficacy of eConsults in an otolaryngology-head and neck surgery (OTO-HNS) practice. Prospective observational study. The Champlain BASE eConsult system is a secure web portal allowing primary care physicians (PCPs) to communicate asynchronously with specialists about a patient, without requiring a formal face-to-face consult. The data from all eConsults sent through this portal to OTO-HNS practices between July 2011 and January 2015 were collected and analyzed. Response time was rapid; over 40% of eConsults received a response within 24 hours, and nearly all eConsults were answered within 7 calendar days. The median response time was nearly 29 times faster than traditional face-to-face consultation. Unnecessary face-to-face referrals were avoided in 33.4% of all eConsults, and in nearly 50% of cases where the PCP initially planned a formal referral. PCPs reported adopting a new or additional course of action over 50% of the time following an eConsult. Eighty-eight percent of PCPs reported the service to be valuable for their patients, and 92% found it valuable for themselves. eConsults require only a limited time commitment from specialists, with over 75% taking less than 10 minutes to complete. eConsultation is a cost-effective system that can lead to decreased wait times, improved communication between PCPs and otolaryngologists, and help guide the development of targeted continuing professional development modules for PCPs. 4. Laryngoscope, 128:350-355, 2018.


Ionic signaling in plant responses to gravity and touch.
Touch and gravity are two of the many stimuli that plants must integrate to generate an appropriate growth response. Due to the mechanical nature of both of these signals, shared signal transduction elements could well form the basis of the cross-talk between these two sensory systems. However, touch stimulation must elicit signaling events across the plasma membrane whereas gravity sensing is thought to represent transformation of an internal force, amyloplast sedimentation, to signal transduction events. In addition, factors such as turgor pressure and presence of the cell wall may also place unique constraints on these plant mechanosensory systems. Even so, the candidate signal transduction elements in both plant touch and gravity sensing, changes in Ca2+, pH and membrane potential, do mirror the known ionic basis of signaling in animal mechanosensory cells. Distinct spatial and temporal signatures of Ca2+ ions may encode information about the different mechanosignaling stimuli. Signals such as Ca2+ waves or action potentials may also rapidly transfer information perceived in one cell throughout a tissue or organ leading to the systemic reactions characteristic of plant touch and gravity responses. Longer-term growth responses are likely sustained via changes in gene expression and asymmetries in compounds such as inositol-1,4,5-triphosphate (IP3) and calmodulin. Thus, it seems likely that plant mechanoperception involves both spatial and temporal encoding of information at all levels, from the cell to the whole plant. Defining this patterning will be a critical step towards understanding how plants integrate information from multiple mechanical stimuli to an appropriate growth response.


Reduced expression of regeneration associated genes in chronically axotomized facial motoneurons.
Chronically axotomized motoneurons progressively fail to regenerate their axons. Since axonal regeneration is associated with the increased expression of tubulin, actin and GAP-43, we examined whether the regenerative failure is due to failure of chronically axotomized motoneurons to express and sustain the expression of these regeneration associated genes (RAGs). Chronically axotomized facial motoneurons were subjected to a second axotomy to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to nerve repair. Expression of α1-tubulin, actin and GAP-43 was analyzed in axotomized motoneurons using in situ hybridization followed by autoradiography and silver grain quantification. The expression of these RAGs by acutely axotomized motoneurons declined over several months. The chronically injured motoneurons responded to a refreshment axotomy with a re-increase in RAG expression. However, this response to a refreshment axotomy of chronically injured facial motoneurons was less than that seen in acutely axotomized facial motoneurons. These data demonstrate that the neuronal RAG expression can be induced by injury-related signals and does not require acute deprivation of target derived factors. The transient expression is consistent with a transient inflammatory response to the injury. We conclude that transient RAG expression in chronically axotomized motoneurons and the weak response of the chronically axotomized motoneurons to a refreshment axotomy provides a plausible explanation for the progressive decline in regenerative capacity of chronically axotomized motoneurons.


Comparative first principles-based molecular dynamics study of catalytic mechanism and reaction energetics of water oxidation reaction on 2D-surface.
The study of the water-splitting process, which can proceed in 2e- as well as 4e- pathway, reveals that the process is entirely an uphill process, and the third step, that is, the oxooxo bond formation is the rate-determining step. The kinetic barrier of the oxygen evolution reaction (OER) on the 2D material catalysts in the presence of explicit solvents is scarcely studied. Here, we investigate the dynamics of the OER on the undoped graphene and the activation energy barrier of each step using first principles molecular dynamics simulations. Here we provide a detailed analysis of the kinetics of all the 4e- transfer steps of OER on the graphene surface. We also compare the accuracy of one of the density functional theory (DFT) functionals and density functional based tight binding (DFTB) method in explaining the OER steps. The comparative study reveals that DFTB can be used for performing metadynamics simulations quipped with much less computational cost than DFT functionals. By both Perdew-Burke-Ernzerhof and DFTB methods, the third step is revealed to be the rate-determining step with an energy barrier of 21.19 ± 0.51 and 20.23 ± 0.20 kcal mol-1 , respectively. DFTB gives an impression of being successful in predicting the energy barriers of OER in 4e- transfer pathway and comparable to the DFT method, and we would like to extend the use of DFTB for further studies with a sizable and complex system.


Novel treatments for autism spectrum disorder based on genomics and systems biology.
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic architecture. There are currently no known pharmacologic treatments for the core ASD symptoms of social deficits and restricted/ repetitive behavior. However, there are dozens of clinical trials currently underway that are testing the impact of novel and existing agents on core and associated symptoms in ASD. We present a narrative synthesis of the historical and contemporary challenges to drug discovery in ASD. We then provide an overview of novel treatments currently under investigation from a genomics and systems biology perspective. Data driven network and cluster analyses suggest alterations in transcriptional regulation, chromatin remodelling, synaptic transmission, neuropeptide signalling, and/or immunological mechanisms may contribute to or underlie the development of ASD. Agents and upcoming trials targeting each of the above listed systems are reviewed. Identifying effective pharmacologic treatments for the core and associated symptom domains in ASD will require further collaboration and innovation in the areas of outcome measurement, biomarker research, and genomics, as well as systematic efforts to identify and treat subgroups of individuals with ASD who may be differentially responsive to specific treatments.


Coronary revascularisation with Genous stent helps reduce the waiting time for lung resection.
Patients suitable for lung resection for primary lung cancer and with myocardial ischaemia due to significant coronary artery stenosis, despite optimal medical therapy, are considered for either percutaneous or surgical revascularisation prior to thoracic surgery. Percutaneous coronary intervention (PCI) with bare metal stent (BMS) requires patients to initially receive dual anti-platelet therapy of clopidogrel and aspirin for at least 6 weeks, which delays the waiting time for curative lung resection. We report the successful use of the Genous endothelial progenitor cell (EPC) capture stent in two patients requiring PCI for significant coronary artery disease prior to lung resection. Following PCI with Genous stent implantation, both patients received dual anti-platelet therapy for 1 week. Clopidogrel was then discontinued and a week later both safely underwent curative lung resection receiving aspirin alone. At 6 months' follow-up, neither patient had symptoms or electrocardiograph changes suggestive of angina. Our report suggests that in patients requiring PCI prior to lung resection the Genous EPC capture stent is suitable and reduces their waiting time for surgical resection to 2 weeks instead of 6.


The accumulation of non-replicative, non-functional, senescent T cells with age is avoided in calorically restricted mice by an enhancement of T cell apoptosis.
Peripheral blood lymphocytes of elderly humans show an increased percentage of T cells with characteristics of replicative senescence. Similarly, the overall decrease in T cell proliferation in aged mice reflects a progressively increasing proportion of non-functional cells rather than a uniform decline in function by all cells. The improved immune function of calorically restricted (CR) animals is, paradoxically, accompanied by a relative lymphopenia. To test whether the reduction in lymphocyte number in the CR mice might reflect more efficient elimination of T cells, we measured apoptosis in young, old and CR old mice. T cell apoptosis induced by irradiation, Staurosporine, anti-CD3, and heat shock was reduced by 62, 42, 32, and 30%, respectively, in old compared with young mice. Caloric restriction normalized apoptosis in T cells from aged mice. Enhanced elimination of non-functional T cells in CR mice may be, at least in part, responsible for their improved immune functional status relative to non-CR mice of the same age.


Prognostic Value of Hematologic Prealbumin/Fibrinogen Ratio in Patients with Glioma.
Hematologic biomarkers that reflect host nutritional and inflammation status have been identified to be independent prognostic factors in various malignancies. The aim of the present study was to determine the predictive value of preoperative albumin, fibrinogen, prealbumin, albumin/fibrinogen ratio, and prealbumin/fibrinogen ratio (PFR) for the prognosis of patients with glioma. X-tile software was used to identify cutoff values of these parameters. Kaplan-Meier survival analysis and univariate and multivariate analyses based on a Cox proportional hazards regression model were used to determine whether these markers were associated with the prognosis of patients with glioma. In addition, the Harrell concordance index with variables was used to evaluate the prognostic accuracy. The results indicated that PFR (hazard ratio, 2.827; 95% confidence interval, 1.353-6.122; P = 0.006) is the only independent prognostic factor in patients of glioma along with clinicopathologic grade and age. c-index of predicted nomogram including PFR (0.719) for patients with glioma was higher than that without PFR (0.699). Our findings show that circulating preoperative PFR might be a potential negative independent prognostic biomarker for individuals with glioma.


Insulin resistance, inflammation, and vascular disease in nondiabetic predialysis chronic kidney disease patients.
Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate. IR and inflammation are related to vascular disease in nondiabetic predialysis CKD patients. We studied carotid-artery intima-media thickness (IMT) and endothelial function (brachial artery flow mediated dilation [FMD]) in 35 nondiabetic predialysis patients with stage 3-5 CKD and 35 age- and gender-matched controls. Insulin resistance was measured using the homeostasis model assessment for insulin resistance score (HOMA-IR), inflammation by high-sensitivity CRP (hsCRP), and their relationship with FMD and IMT. Patients with CKD showed reduced FMD (3.34 ± 2.14% vs. 5.27 ± 1.78%, P<0.001) and increased IMT (0.78 ± 0.22 mm vs. 0.64 ± 0.16 mm, P = 0.003) compared with controls. The CKD patients had a higher HOMA-IR (2.20 ± 1.08 vs. 1.13 ± 0.64, P<0.001) and hsCRP (3.25 ± 5.47 mg/L vs. 1.10 ± 1.85 mg/L [median ± interquartile range], P = 0.02). In the study population, HOMA-IR was directly related to hsCRP. After adjusting for traditional risk factors, high HOMA-IR and hsCRP were significantly related to decreased FMD (adjusted β = -0.44, 95% confidence interval [CI]: -1.55 to -0.08, P = 0.003 and adjusted β = -0.51, 95% CI: -0.51 to -0.15, P = 0.001) and increased IMT (adjusted β = 0.62, 95% CI: 0.54-1.90, P = 0.001 and adjusted β = 0.43, 95% CI: 0.08-0.57, P = 0.011), respectively. Subjects with systemic inflammation were more insulin-resistant, and in nondiabetic predialysis CKD, IR and systemic inflammation were independently associated with endothelial dysfunction and atherosclerosis.


[Diagnosis and treatment of pancreatic trauma].
Pancreatic trauma is a rare but potentially lethal entity which requires a high level of clinical suspicion. Early diagnosis and assessment of the integrity of the pancreatic duct are essential since ductal injury is a crucial predictor of morbimortality. Overall mortality is 19%, which can rise to 30% in cases of ductal injury. The diagnostic and therapeutic approach is multidisciplinary and guided by a surgeon, imaging specialist and ICU physician. Laboratory analysis shows that pancreatic enzymes are frequently elevated, which is a low specificity finding. In hemodynamically stable patients, the posttraumatic condition of the pancreas is firstly evaluated by the multidetector computed tomography. Moreover, in case of suspicion of ductal injury, more sensitive studies such as Endoscopic Retrograde Cholangiopancreatography or cholangioresonance are needed. This narrative review aims to analyze the etiopathogenesis and pathophysiology of pancreatic trauma and discuss its diagnosis and treatment. Also, the most clinically relevant complications will be summarized.


Development of a serum-free medium which supports the long-term growth of human and nonhuman primate lymphoid cells.
The ability to grow lymphoid cells in serum-free media affords the advantage of separately analyzing those components found to be involved in proliferation and differentiation. Iscove's medium (IMDM) supplemented with bovine serum albumin or casein, cholesterol, ferrous chloride, insulin, beta-mercaptoethanol, L-alpha-phosphatidylcholine, and transferrin supported the long-term proliferation of a gibbon ape lymphoma T-cell line, MLA144. These cells continue to produce interleukin 2 (IL-2, T-cell growth factor) constitutively in the serum-free medium. IL-2-dependent human T cells initiated and maintained in culture in serum-free medium containing IL-2 have continued to replicate for over 3 months with two population doublings every 3 to 4 days. A normal, IL-2-dependent marmoset T-cell line, OH-1, also proliferated on the serum-free medium when supplemented with IL-2. Several established primate B-cell lines which do not require IL-2 for growth were able to proliferate in the serum-free medium. These B-cell lines included B95-8, an Epstein-Barr virus (EBV)-transformed marmoset cell line, HuCo/R-H, a human cord B-lymphocyte line transformed with EBV, and Namalwa, an EBV-positive B-cell line established from a Burkitt's lymphoma. B95-8 cells grown on serum-free medium showed high levels of EBV antigen-positive cells after induction with 12-O-tetradecanoyl-phorbol-13-acetate (TPA).


[Will ultrasound replace the stethoscope?: a case report on neonatal one-lung ventilation].
One-lung ventilation and selective intubation in neonates can be challenging due to intrinsic physiological specificities and material available. Ultrasound (US) is being increasingly used in many extents of anaesthesiology including confirmation of endotracheal tube position. We present a case report of a neonate proposed for pulmonary lobectomy by thoracoscopy in which lung exclusion was confirmed by ultrasound. US is a rapid, more sensitive and specific method than auscultation to evaluate tracheal intubation and lung exclusion.


Encapsulation of eukaryotic cells in alginate microparticles: cell signaling by TNF-alpha through capsular structure of cystic fibrosis cells.
Entrapment of mammalian cells in natural or synthetic biomaterials represents an important tool for both basic and applied research in tissue engineering. For instance, the encapsulation procedures allow to physically isolate cells from the surrounding environment, after their transplantation maintaining the normal cellular physiology. The first part of the current paper describes different microencapsulation techniques including bulk emulsion technique, vibrating-nozzle procedure, gas driven mono-jet device protocol and microfluidic based approach. In the second part, the application of a microencapsulation procedure to the embedding of IB3-1 cells is also described. IB3-1 is a bronchial epithelial cell line, derived from a cystic fibrosis (CF) patient. Different experimental parameters of the encapsulation process were analyzed, including frequency and amplitude of vibration, polymer pumping rate and distance between the nozzle and the gelling bath. We have found that the microencapsulation procedure does not alter the viability of the encapsulated IB3-1 cells. The encapsulated IB3-1 cells were characterized in term of protein secretion, analysing the culture medium by Bio-Plex strategy. The analyzed factors include members of the interleukin family (IL-6), chemokines (IL-8 and MCP-1) and growth factors (G-CSF). The experiments demonstrated that most of the analyzed proteins, were secreted both by the free and encapsulated cells, even if in a different extent.


Aromatase and testosterone fatty acid esters: the search for a cryptic biosynthetic pathway to estradiol esters.
The estradiol fatty acid esters (lipoidal derivatives, LE2) are extremely potent estrogens that accumulate in fat, including fat of menopausal women. These steroidal esters are protected from metabolism and are converted to the free, biologically active steroid through the action of esterases. Previous studies have shown that biosynthetic pathways in the adrenal gland exist in which steroid fatty acid esters are substrates. This led us to determine whether a cryptic aromatase pathway exists in which testosterone esters could be converted directly into LE2. We tested a representative fatty acid ester, testosterone stearate, both as an inhibitor and as a substrate for the aromatase enzyme from human placental microsomes. This ester had neither activity. In addition, we tested [1 beta-3H]testosterone acetate as a substrate for this enzyme complex, measuring the production of 3H2O as evidence of aromatization. Although the rate of reaction was considerably slower than that of testosterone, 3H2O was produced. However, when [2, 4, 6, 7-3H]testosterone acetate was incubated and the steroidal products isolated, we found that hydrolysis of the substrate had occurred. Both [3H]-labeled testosterone and estradiol were found, and very little if any [3H]estradiol acetate was formed. Thus, we conclude that an aromatase pathway involving testosterone esters does not exist and that the sole source of LE2 is through direct esterification of estradiol.


The burden of insomnia on individual function and healthcare consumption in Australia.
To determine the extent to which insomnia poses an independent burden on individual function and healthcare use in Australia. Cross-sectional data from 8,841 respondents and representative of the Australian population aged 16 to 85 in the 2007 National Mental Health and Wellbeing Survey were analysed. Insomnia was defined as 'sleeping only in short bursts and being awake most of the night' during the past week. This measure was validated against common epidemiological indicators of insomnia. Associations between insomnia, disability and healthcare consumption were explored using multivariate logistic regression. Insomnia was reported by 5.6% of adults and was associated with older age, female gender, pain and psychological distress. Controlling for these and other a priori confounders, insomnia was associated with greater odds of (Adjusted Odds Ratio; 95% CI): disability days (1.62; 1.20-2.18), difficulties in daily activities (1.60; 1.10-2.31), life dissatisfaction (2.34; 1.11-4.93), use of sleep medication (1.78; 1.12-2.82) and a higher number of visits to general practitioners (1.57; 1.06-2.33). Insomnia was not significantly associated with the use of medications for mental health (1.17; 0.82-1.67), hospital admissions (1.31; 0.82-1.67), the use of complementary and alternative medicine (1.10; 0.73-1.67) or unmet need for healthcare (1.22; 0.84-1.77). One in twenty adult Australians experience a level of insomnia that is independently associated with impairments in functioning and increased use of healthcare. Increasing public and clinician awareness of the impact of insomnia, and promotion of available insomnia treatments may be warranted.


SARS-CoV-2 seroprevalence in the urban population of Qatar: An analysis of antibody testing on a sample of 112,941 individuals.
The study objective was to the assess level of detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in the urban population of Qatar. Antibody testing was performed on residual blood specimens for 112,941 individuals (∼10% of Qatar's urban population) attending for routine/other clinical care between May 12 and September 9, 2020. Seropositivity was 13.3% (95% confidence interval [CI] = 13.1-13.6%) and was independently associated with sex, age, nationality, clinical care encounter type, and testing date. Median optical density (antibody titer) among antibody-positive persons was 27.0 (range = 1.0-150.0), with higher values associated with age, nationality, clinical care encounter type, and testing date. Seropositivity by nationality was positively correlated with the likelihood of having higher antibody titers (Pearson correlation coefficient = 0.85; 95% CI = 0.47-0.96). Less than two in every 10 individuals in Qatar's urban population had detectable antibodies against SARS-CoV-2, suggesting this population is still far from herd immunity and at risk of subsequent infection waves. Higher antibody titer appears to be a biomarker of repeated exposures to the infection.


Smooth and Discrete Cone-Nets.
Cone-nets are conjugate nets on a surface such that along each individual curve of one family of parameter curves there is a cone in tangential contact with the surface. The corresponding conjugate curve network is projectively invariant and is characterized by the existence of particular transformations. We study properties of that transformation theory and illustrate how several known surface classes appear within our framework. We present cone-nets in the classical smooth setting of differential geometry as well as in the context of a consistent discretization with counterparts to all relevant statements and notions of the smooth setting. We direct special emphasis towards smooth and discrete tractrix surfaces which are characterized as principal cone-nets with constant geodesic curvature along one family of parameter curves.


EnDuo, a novel derivative of Endostar, inhibits the migration of colon cancer cells, suppresses matrix metalloproteinase-2/9 expression and impedes AKT/ERK activation.
Colon cancer remains a life-threating disease with increasing morbidity and mortality worldwide despite the advancement in modern medical treatment. Therefore, novel and effective anti-colon cancers drugs are urgently needed. In this study, we investigated the anti-metastatic property EnDuo, a modified version of Endostar, and the underlying mechanisms. Colon cancer cells were treated with different concentrations of EnDuo (50 μg/mL, 100 μg/mL, 200 μg/mL), and Endostar (100 μg/mL) as positive control. Cell Counting Kit-8 assay was performed to test the effect of EnDuo on cell viability. A scratch wound assay and transwell assay were employed to evaluate the relocation and motility of malignant colon cells following treatment with EnDuo. Western blot analysis was used to determine inhibitory effects of EnDuo by detecting the phosphorylation level of AKT and ERK proteins, and the expression of MMP-2 and MMP-9 proteins. Our results showed that EnDuo impedes the migration of colon cancer cells in a dose-dependent manner. At the molecular level, EnDuo induced a significant reduction in the phosphorylation of AKT and ERK proteins, and inhibited the expression of MMP-2 and MMP-9 proteins. Collectively, these results demonstrate that EnDuo exhibits a comparable anti-metastatic effect by suppressing the migration of colon cancer cells. Possibly, EnDuo interrupts the PI3K/AKT/ERK signaling pathway to arrest cell migration. Our study provides a novel insight to the potential clinical applications of EnDuo against colon cancers in the future.


Dimethylthiourea protects rats against gram-negative sepsis and decreases tumor necrosis factor and nuclear factor kappaB activity.
The thiol-containing compound dimethylthiourea (DMTU) is a known protectant in various models of oxidant-mediated tissue damage. Protective effects of DMTU have also been reported in studies on endotoxin-induced (LPS-induced) tissue injury. DMTU may exert this protective effect by reducing oxidative stress. In this study we investigated the effect of DMTU on survival, oxidative stress, and tumor necrosis factor (TNF) activity in two rat models of gram-negative bacterial sepsis. Intraperitoneal injection of 500 mg DMTU/kg protected against the lethal effects of intraperitoneally injected LPS (5 mg/kg) and live Salmonella typhimurium (3.3 x 10(10) CFU/kg). LPS injection resulted in oxidative stress, as indicated by an elevated concentration of hydrogen peroxide (H(2)O(2)) in normal and carbon monoxide-treated deproteinized blood. We also observed increased H(2)O(2) levels in animals injected with live Salmonella typhimurium. Although DMTU improved survival in both models, H(2)O(2) concentrations were not affected by it. This is consistent with our in vitro observation that DMTU is a weak H(2)O(2) scavenger. Serum TNF activity, however, was substantially decreased by DMTU, and this was associated with a reduced activation of nuclear factor kappaB in the peritoneal cells of LPS-treated rats. In addition, LPS-induced TNF production in vitro by rat peritoneal macrophages was inhibited by DMTU (p < 0.05). These results suggest that the protective effect of DMTU in gram-negative bacterial sepsis may be the result of a reduction in TNF activity. DMTU does not exert this effect by H(2)O(2) scavenging but may inactivate toxic H(2)O(2) metabolites.


Double Deprotonation of CH3 CN by an Iron-Aluminium Complex.
Herein we present the first double deprotonation of acetonitrile (CH3 CN) using two equivalents of a bimetallic iron-aluminium complex. The products of this reaction contain an exceeding simple yet rare [CHCN]2- dianion moiety that bridges two metal fragments. DFT calculations suggest that the bonding to the metal centres occurs through heavily polarised covalent interactions. Mechanistic studies reveal the intermediacy of a monomeric [CH2 CN]- complex, which has been characterised in situ. Our findings provide an important example in which a bimetallic metal complex achieves a new type of reactivity not previously encountered with monometallic counterparts.[1, 2] The isolation of a [CHCN]2- dianion through simple deprotonation of CH3 CN also offers the possibility of establishing a broader chemistry of this motif.


Serum Zinc Levels in Apparently Healthy Children in Nigeria: Are They Acceptable.
Despite the importance of zinc in the human body, there is paucity of data on the zinc status of Nigerian children. The aim of this study was to determine the serum zinc levels of children attending the pediatric outpatient clinic of a tertiary hospital in South East Nigeria and to assess their need for routine zinc supplementation. One hundred children aged 5-60 months were recruited consecutively from the pediatric outpatient clinic. Their socioeconomic class (SEC) was assessed using the tool developed by Oyedeji. Physical examination was carried out to exclude malnutrition and/or liver disease. Samples were collected in the morning from nonfasting subjects and were analyzed using atomic absorption spectrophotometer. Serum zinc deficiency was defined as zinc level <80 μg/dl. The overall median (range) serum zinc level was 83.3ug/dl (60-105 μg/dl) while the median (mean rank) serum zinc levels among male and female subjects were 83.4 μg/dl and 84.2ug/dl, respectively (U = 1071.00; P = 0.228). A total of 26 (26%) apparently healthy children had low serum zinc levels. There was no association between gender and serum zinc levels (χ2 = 2.163; P = 0.141). A significant positive but weak relationship was found between SEC and zinc levels (r = 0.208, P = 0.038) but not between serum zinc levels and age of the children (r = 0.185, P = 0.065). A significant proportion of Under-5s could have low serum zinc levels. Routine zinc supplementation may be necessary among this age group in Nigeria.


Particulate matter air pollution: individual choices for improving cardiometabolic well-being.
Exposure to small particulate matter (PM2.5) has become the 5th highest ranking risk factor for death, responsible for 4.2 million deaths worldwide. PM pollution is also associated with cardiovascular disease and type 2 diabetes, and may contribute to deteriorate the already poor cardiometabolic outlook of the diabetic patient. Although most sources of outdoor air pollution are well beyond the control of individuals, there is still room for personal action. Health behaviors (smoking cessation, avoiding obesity, and increasing physical activity) may increase the poor life expectancy of individuals in the lowest income quartile of the Western population; moreover, a favorable lifestyle, (no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern), may cut by nearly 50% the risk of coronary heart disease among people at high genetic risk. Things seem not immutable, as individual healthy choices do matter.


Corticosterone Excess-Mediated Mitochondrial Damage Induces Hippocampal Neuronal Autophagy in Mice Following Cold Exposure.
Cold stress can induce autophagy mediated by excess corticosterone (CORT) in the hippocampus, but the internal mechanism induced by cold stress is not clear. In vivo, male and female C57BL/6 mice were stimulated in 4 °C, 3 h per day for 1 week to build the model of cold sress. In vitro, hippocampal neuronal cell line (HT22) cells were incubated with or without mifepristone (RU486) for 1 h, then treated with 400 μM cortisol (CORT) for 3 h. In vivo, autophagy was measured by western blotting. In vitro, monodansylcadaverine staining, western blotting, flow cytometry, transmission electron microscopy, and immunofluorescence were used to characterize the mechanism of autophagy induced by excess CORT. Autophagy was shown in mouse hippocampus tissues following cold exposure, including mitochondrial damage, autophagy, and 5' AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway activation after CORT treatment. Autophagy did not rely on the glucocorticoid receptor. In addition, autophagy in male mice was more severe. The study would provide new insight into the mechanisms and the negative effect of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia.


Cognition in mania and depression: psychological models and clinical implications.
Affective disorders, including bipolar disorder and major depressive disorder, are highly prevalent throughout the world and are extremely disabling. Diagnostic and Statistical Manual criteria and psychological models strongly implicate cognitive dysfunctions as being integral to our understanding of these disorders. We review the findings from studies that have used neurocognitive tests and functional imaging techniques to explore abnormal cognition in affective disorders. In particular, we highlight the evidence for cognitive dysfunctions that persist into full clinical remission, and the recent trend toward the use of "hot" processing tasks, involving emotionally charged stimuli, as a means of differentiating between the cognitive underpinnings of mania and depression. The clinical relevance of these developments is discussed.


Exploratory Analysis of Glycemic Control and Variability Over Gestation Among Pregnant Women with Type 1 Diabetes.
In exploratory analyses, we evaluated glycemic variability (GV) and gestational outcomes in pregnant women (n = 28) with type 1 diabetes (T1D). Gestational age at delivery was higher for women with lower glycemic measures, including estimated HbA1c (eHbA1c) (0.14% decrease in HbA1c per 1-week greater gestational age, P = 0.0035), mean sensor glucose (-3.9 mg/dL P = 0.0039), time spent >140 mg/dL (-3.1%, P = 0.0029), and higher time in range (TIR) of 63-140 mg/dL (3.2%, P = 0.0029). Third trimester measured HbA1c was significantly associated with gestational age at delivery (P = 0.0081). Preeclampsia was associated with less TIR in first (50.5% vs. 69.9%, P = 0.0034) and second trimesters (47.1% vs. 66.7%, P = 0.0025), but not with measured HbA1c. There were significant differences in other markers of GV (continuous overall net glycemic action, high blood glucose index, J-index, mean amplitude of glycemic excursions) with infant birth weight and gestational age at delivery. Thus, multiple markers of glycemia and GV were associated with gestational health outcomes in T1D pregnancies in this pilot study. Clinical Trial Registration number: NCT02556554.