LncRNA MIR22HG/microRNA-9-3p/IGF1 in nonalcoholic steatohepatitis, the ceRNA network increases fibrosis by inhibiting autophagy and promoting pyroptosis.
Nonalcoholic steatohepatitis (NASH) is known to progress due to the impact of long non-coding RNAs (lncRNAs), which have been linked to autophagy, pyroptosis, and fibrosis in NASH cells. However, the exact mechanisms underpinning these processes remain unclear. This study focuses on the role of lncRNA MIR22HG (MIR22HG) in NASH. The expression of differentially expressed lncRNA was analyzed by RNA sequencing. Mouse models of NASH induced by MCD and HFD were validated. The expression of MIR22HG in HFD and MCD mouse liver tissue samples, FFA cells constructed with HepG2 and Huh7, and human liver tissue samples were detected by QRT-PCR. In addition, We used RNA immunoprecipitation, luciferase reporting, miRNA transfection, plasmid construction, immunofluorescence, Western blot, qRT-PCR, ELISA, and hybridization techniques to elucidate the relationship between MIR22HG, microRNA-9-3p (miR-9-3p), and IGF1. In addition, the mechanism of MIR22HG and PTEN/AKT was explored by Western blot analysis. RNA-seq found that 3751 mRNAs and 23 lncRNAs were differentially expressed, which constituted a lncRNA-miRNA-mRNA regulatory network. Studies demonstrated the downregulation of MIR22HG in HFD and MCD mouse liver tissue samples (p = 1.00E-04 and p = 4.6E-03). Our results showed that overexpression of MIR22HG promoted autophagy and inhibited pyroptosis and fibrosis through the miR-9-3p/IGF1 pathway, thus slowing the occurrence and development of NASH. Further, we observed a low expression of MIR22HG and IGF1, but a high expression of miR-9-3p in NASH patients, a finding in alignment with our in vivo and in vitro results. Using MIR22HG as a biomarker and therapeutic target for NASH patients, we found that it plays a pivotal role in detecting autophagy, pyroptosis, and fibrosis through the ceRNA pathway.


Interleukin-12 and tumor necrosis factor alpha mediate innate production of gamma interferon by group B Streptococcus-treated splenocytes of severe combined immunodeficiency mice.
The existence of interleukin-12-mediated innate immune responses to group B streptococci (GBS) was tested by examining T-lymphocyte-independent gamma interferon (IFN) production in cultured splenocytes from severe combined immunodeficiency mice. Splenocytes were cultured with killed or living GBS for 48 h, and then IFN was measured by enzyme-linked immunosorbent assay. Type III GBS as well as other extracellular bacterial agents of neonatal sepsis (staphylococci and enterococci) induced IFN production, which was enhanced by interleukin-2 and was inhibited by neutralizing antibodies to tumor necrosis factor alpha and to mouse interleukin-12. Interleukin-12 bioactivity was present in conditioned medium from GBS-treated adherent macrophages. Adherent peritoneal macrophages and bone marrow-derived natural killer cells from severe combined immunodeficiency mice cultured separately with GBS did not produce IFN, whereas cocultures did produce IFN. Functional macrophage activation was evident by nitric oxide production in GBS-treated splenocyte cultures. The results show that extracellular pathogens such as GBS, similarly to intracellular microbes, induce macrophage interleukin-12 and tumor necrosis factor alpha, which promote natural killer cell secretion of IFN, which then enhances innate phagocyte resistance mechanisms.


IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype.
The chemokine thymus- and activation-regulated chemokine (TARC) induces selective migration of Th2, but not Th1, lymphocytes and is upregulated in the airways of asthmatic patients. The purpose of this study was to determine whether human airway smooth muscle (HASM) cells produce TARC. Neither IL-4, IL-13, IL-1beta, IFN-gamma, nor TNF-alpha alone stimulated TARC release into the supernatant of cultured HASM cells. However, both IL-4 and IL-13 increased TARC protein and mRNA expression when administered in combination with TNF-alpha but not IL-1beta or IFN-gamma. Macrophage-derived chemokine was not expressed under any of these conditions. TARC release induced by TNF-alpha + IL-13 or TNF-alpha + IL-4 was inhibited by the beta-agonist isoproterenol and by other agents that activate protein kinase A, but not by dexamethasone. To determine whether polymorphisms of the IL-4Ralpha have an impact on the ability of IL-13 or IL-4 to induce TARC release, HASM cells from multiple donors were genotyped for the Ile50Val, Ser478Pro, and Gln551Arg polymorphisms of the IL-4Ralpha. Our data indicate that cells expressing the Val50/Pro478/Arg551 haplotype had significantly greater IL-13- or IL-4-induced TARC release than cells with other IL-4Ralpha genotypes. These data indicate that Th2 cytokines enhance TARC expression in HASM cells in an IL-4Ralpha genotype-dependent fashion and suggest that airway smooth muscle cells participate in a positive feedback loop that promotes the recruitment of Th2 cells into asthmatic airways.


DnaJB6 is present in the core of Lewy bodies and is highly up-regulated in parkinsonian astrocytes.
DnaJ/Hsp40 chaperones determine the activity of Hsp70s by stabilizing their interaction with substrate proteins. We have predicted, based on the in silico analysis of a brain-derived whole-genome transcriptome data set, an increased expression of DnaJ/Hsp40 homologue, subfamily B, member 6 (DnaJB6) in Parkinson's disease (PD; Moran et al. [2006] Neurogenetics 7:1-11). We now show that DnaJB6 is a novel component of Lewy bodies (LBs) in both PD substantia nigra and PD cortex and that it is strongly up-regulated in parkinsonian astrocytes. The presence of DnaJB6 in the center of LBs suggests an early and direct involvement of this chaperone in the neuronal disease process associated with PD. The strong concomitant expression of DnaJB6 in astrocytes emphasizes the involvement of glial cells in PD and could indicate a route for therapeutic intervention. Extracellular alpha-synuclein originating from intravesicular alpha-synuclein is prone to aggregation and the potential source of extracellular aggregates (Lee [2008] J. Mol. Neurosci. 34:17-22). The observed strong expression of DnaJB6 by astrocytes could reflect a protective reaction, so reducing the neuronal release of toxic alpha-synuclein and supporting the astrocyte response in PD might limit the progression of the disease process.


Growth deceleration in Japanese schoolchildren with special reference to those in the city of Sendai.
From the national and regional statistics on the body dimensions of schoolchildren at the 6th year grade in primary schools (i.e., 11-year-olds) and at the 3rd year grade in junior high schools (i.e., 14-year-olds), the secular gains in height and weight by the children of the same age were calculated for the three periods of 1960-4, 1972-76 and 1976-81. Compared with the first period (i.e., 1960-4) when the growth acceleration was maximal, the secular gain was apparently reduced in the second and third study periods (i.e. 1970's) to the level of 1/2 to 1/3 of that in the first period, and was next to nil in some districts. Such deceleration was coupled with changes in seasonal growth patterns and diminution of urban-rural gaps both in the body size and the secular gain. For example, the body dimensions of the children in the City of Sendai did not differ in 1981 between the core part of the city and the surroundings, while the difference had been observed till late 1970's. The 1979 measurements of height and weight of Japanese children are compared with counterpart values observed in other countries.


Why (some) immigrants resist assimilation: US racism and the African immigrant experience.
Scholarship shows that Black immigrants to the US resist assimilation to reduce exposure to racial discrimination faced by native-born African Americans. But, not all Black immigrants are equally likely to be (mis)perceived as African American. We argue that immigrants who are likely to be misidentified as African American have incentives to reify ethnic boundaries as a form of protection against racial discrimination. We develop this argument from interviews and focus groups with African immigrants. We then use a lab experiment to measure rates of miscategorization and identify its correlates among African immigrants. Finally, we test our argument with a novel survey of Somalis, an immigrant population with two ethnic subgroups who differ in their likelihood of being miscategorized as African Americans. We show that this difference shapes the degree of resistance to assimilation. These findings improve our understanding of the relationship between racial discrimination and incentives for Black immigrants to resist assimilation.


Coronary CT Angiography Versus Standard Emergency Department Evaluation for Acute Chest Pain and Diabetic Patients: Is There Benefit With Early Coronary CT Angiography? Results of the Randomized Comparative Effectiveness ROMICAT II Trial.
Cardiac computed tomography angiography (CCTA) reduces emergency department length of stay compared with standard evaluation in patients with low- and intermediate-risk acute chest pain. Whether diabetic patients have similar benefits is unknown. In this prespecified analysis of the Rule Out Myocardial Ischemia/Infarction by Computer Assisted Tomography (ROMICAT II) multicenter trial, we randomized 1000 patients (17% diabetic) with symptoms suggestive of acute coronary syndrome to CCTA or standard evaluation. The rate of acute coronary syndrome was 8% in both diabetic and nondiabetic patients (P=1.0). Length of stay was unaffected by the CCTA strategy for diabetic patients (23.9 versus 27.2 hours, P=0.86) but was reduced for nondiabetic patients compared with standard evaluation (8.4 versus 26.5 hours, P<0.0001; P interaction=0.004). CCTA resulted in 3-fold more direct emergency department discharge in both groups (each P≤0.0001, P interaction=0.27). No difference in hospital admissions was seen between the 2 strategies in diabetic and nondiabetic patients (P interaction=0.09). Both groups had more downstream testing and higher radiation doses with CCTA, but these were highest in diabetic patients (all P interaction≤0.04). Diabetic patients had fewer normal CCTAs than nondiabetic patients (32% versus 50%, P=0.003) and similar normalcy rates with standard evaluation (P=0.70). Notably, 66% of diabetic patients had no or mild stenosis by CCTA with short length of stay comparable to that of nondiabetic patients (P=0.34), whereas those with >50% stenosis had a high prevalence of acute coronary syndrome, invasive coronary angiography, and revascularization. Knowledge of coronary anatomy with CCTA is beneficial for diabetic patients and can discriminate between lower risk patients with no or little coronary artery disease who can be discharged immediately and higher risk patients with moderate to severe disease who warrant further workup. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01084239.


Hydrogen sulfide regulates intracellular Ca2+ concentration in endothelial cells from excised rat aorta.
Hydrogen sulphide (H2S) is a recently discovered gasotransmitter that may regulate a growing number of endothelial functions, including nitric oxide (NO) release, proliferation, adhesion and migration, which are the key steps of angiogenesis. The mechanism whereby H2S impacts on endothelial physiology is still unclear: however, the aforementioned processes are driven by an increase in intracellular Ca2+ concentration ([Ca2+]i). In the present study, we exploited the excised rat aorta to gain insights into the regulation of [Ca2+]i by H2S within in situ endothelial cells (ECs). Sodium hydrosulphide (NaHS), a H2S donor, caused an elevation in [Ca2+]i, which disappeared in absence of extracellular Ca2+. NaHSinduced Ca2+ inflow was sensitive to high doses of Gd3+, but not BTP-2. Inhibition of the reverse-mode of the Na+-Ca2+ exchanger (NCX), with KB-R7943 or upon removal of extracellular Na+, abrogated the Ca2+ response to NaHS. Moreover, NaHS-elicited Ca2+ entry was significantly reduced by TEA and glybenclamide, which hinted at the involvement of ATP-dependent K+ (KATP) channels. Conversely, NaHS-evoked Ca2+ signal was not affected by the reducing agent, dithiothreitol. Acute addition of NaHS hindered both Ca2+ release and Ca2+ entry induced by ATP, a physiological agonist of ECs. Consistently, inhibition of endogenous H2S synthesis with DL-propargylglycine impaired ATP-induced Ca2+ inflow, whereas it did not affect Ca2+ mobilization. These data provide the first evidence that H2S may stimulate Ca2+ influx into ECs by recruiting the reverse-mode of NCX and KATP channels. In addition, they show that such gasotransmitter may modulate the Ca2+ signals elicited by physiological stimuli in intact endothelium.


Ulcerative dermatitis in C57BL/6 mice exhibits an oxidative stress response consistent with normal wound healing.
Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds.


Ghrelin Protects the Thymic Epithelium From Conditioning-Regimen-Induced Damage and Promotes the Restoration of CD4+ T Cells in Mice After Bone Marrow Transplantation.
The delay in immune reconstitution after hematopoietic stem cell transplantation (HSCT), especially a delay in central immune reconstitution, leads to opportunistic infections and disease relapse after transplantation and affects the long-term outcome of HSCT. This delay is mainly attributable to thymic damage after myeloablative chemotherapy and radiotherapy. We established a model of allogeneic bone marrow transplantation (BMT) in mice and administered ghrelin (GRL) 7 days before the conditioning regimen or the day after BMT to explore the effect of GRL on thymus. All the GRL-treated mice, especially those administered GRL before the conditioning regimen, exhibited more intact thymic architecture and a more rapid restoration of CD4 T lymphocytes after BMT than those of the corresponding control mice. Moreover, the levels of T cell receptor excision circles were significantly higher in the mice treated with GRL before the conditioning regimen than in the control mice at 28 days after BMT. Our findings suggest that GRL may be a novel potential therapeutic approach to protecting the thymic epithelium from conditioning regimen-induced damage and promoting rapid and durable thymic and peripheral CD4 T cell recovery after HSCT.


Automated spectrophotometric analysis of mitochondrial respiratory chain complex enzyme activities in cultured skin fibroblasts.
Mitochondrial respiratory chain complex (RCC) disorders may occur as commonly as 1 in 8500 individuals. Because of the great variability of phenotypic presentations, measurement of individual RCC enzyme activities is a crucial diagnostic process. Current assay methods are time-consuming and labor-intensive and thus constitute a major impediment to clinical practice. A method with a faster turnaround time would therefore be beneficial. We developed an automated spectrophotometric method for measuring the respiratory chain enzyme activities of complex I, complex II + III, and complex IV with the Hitachi 912, an automated spectrophotometer. Mitochondrial citrate synthase was also determined for normalization of the RCC activities. A blinded method comparison with samples from an external testing center yielded a 91% concordance of interpretations. Mean intraassay imprecision (as CV; n = 20) in a single batch analysis of each RCC was 5.9%. Interassay imprecision, evaluated on 2 samples harvested and analyzed 3 times each, gave mean CVs of 10%-18%. With this automated method, a panel of RCC enzyme activities can be determined in <2 h. In addition, an immunoblot assay using monoclonal antibodies against specific subunits of RCC enzyme complexes can be informative in cases of borderline enzyme activity. Our results suggest that in vitro diagnosis of RCC enzyme deficiencies in skin fibroblasts is an effective alternative to invasive muscle biopsy.


Statistical mechanics of protein structural transitions: Insights from the island model.
The so-called island model of protein structural transition holds that hydrophobic interactions are the key to both the folding and function of proteins. Herein, the genesis and statistical mechanical basis of the island model of transitions are reviewed, by presenting the results of simulations of such transitions. Elucidating the physicochemical mechanism of protein structural formation is the foundation for understanding the hierarchical structure of life at the microscopic level. Based on the results obtained to date using the island model, remaining problems and future work in the field of protein structures are discussed, referencing Professor Saitô's views on the hierarchic structure of science.


Effects of recovery method after exercise on performance, immune changes, and psychological outcomes.
Randomized controlled trial using a repeated-measures design. To examine the effects of commonly used recovery interventions on time trial performance, immune changes, and psychological outcomes. The use of cryotherapy is popular among athletes, but few studies have simultaneously examined physiological and psychological responses to different recovery strategies. Nine active men performed 3 trials, consisting of three 50-kJ "all out" cycling bouts, with 20 minutes of recovery after each bout. In a randomized order, different recovery interventions were applied after each ride for a given visit: rest, active recovery (cycling at 50 W), or cryotherapy (cold tub with water at 10°C). Blood samples obtained during each session were analyzed for lactate, IL-6, total leukocyte, neutrophil, and lymphocyte cell counts. Self-assessments of pain, perceived exertion, and lower extremity sensations were also completed. Time trial performance averaged 118 ± 10 seconds (mean ± SEM) for bout 1 and was 8% and 14% slower during bouts 2 (128 ± 11 seconds) and 3 (134 ± 11 seconds), respectively, with no difference between interventions (time effect, P≤.05). Recovery intervention did not influence lactate or IL-6, although greater mobilization of total leukocytes and neutrophils was observed with cryotherapy. Lymphopenia during recovery was greater with cryotherapy. Participants reported that their lower extremities felt better after cryotherapy (mean ± SEM, 6.0 ± 0.7 out of 10) versus active recovery (4.8 ± 0.9) or rest (2.8 ± 0.6) (trial effect, P≤.05). Common recovery interventions did not influence performance, although cryotherapy created greater immune cell perturbation and the perception that the participants' lower extremities felt better.


Controversy and progress for treatment of acute cholangitis after Tokyo Guidelines (TG13).
Tokyo Guideline 2013 (TG13) is an international guideline for the diagnosis, classification and treatment of acute cholangitis. Progress and controversy for the two years after TG13 was summarized. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are both effective imaging tests for common bile duct (CBD) stones. More factors e.g. obesity may be involved in severity assessment. Initiation of broad-spectrum antibiotics addressing the typical Gram-negative enteric bacteria spectrum and early biliary drainage are the mainstay therapeutic options. Early laparoscopic exploration is also an option for stone-related nonsevere acute cholangitis besides endoscopic retrograde cholangial or percutaneous transhepatic cholangial drainage. Surgical biliary drainage should be avoided in severe cholangitis.


Allergic contact dermatitis: novel mechanisms and therapeutic perspectives.
Allergic contact dermatitis is a common eczematous skin disease that occurs in sensitized individuals at the site of contact with small chemicals penetrating the skin barrier. The onset of the disease is mostly due to the rapid recruitment of chemical-specific CD8+ T cells, which induce apoptosis of keratinocytes. Additionally, CD4+ Th1 and Th17 contribute to the extension of the inflammatory reaction by releasing pro-inflammatory cytokines that activate keratinocytes and other skin resident cells. The immune reaction is tightly regulated through multiple mechanisms. In particular, T cell population with regulatory function, such as T regulatory cells 1 and CD4+CD25+ T regulatory cells have a critical role in preventing the development of allergic reactions to innocuous chemicals contacting the skin, and in limiting the magnitude of the inflammatory process in already sensitized individuals. Allergic contact dermatitis is a chronic disease, which lasts, in most cases, for the entire life of the affected individual. Thus, prevention and avoidance of contact with the sensitizer are critical factors in the management of affected patients. The gold standard therapeutic approach for the disease remains the local and/or systemic immunosuppression, aimed to block T cell functions and keratinocyte responsiveness to pro-inflammatory stimuli. However, alternative approaches that aim at preventing T cell accumulation in peripheral tissues are under investigation. Most recently, disclosure of mechanisms regulating allergic contact dermatitis have provided new therapeutic perspectives for the disease, mostly based on immunomodulatory interventions, as in the case of induction of specific oral tolerance to the causative allergen.


Fracture surface energy of the Punchbowl fault, San Andreas system.
Fracture energy is a form of latent heat required to create an earthquake rupture surface and is related to parameters governing rupture propagation and processes of slip weakening. Fracture energy has been estimated from seismological and experimental rock deformation data, yet its magnitude, mechanisms of rupture surface formation and processes leading to slip weakening are not well defined. Here we quantify structural observations of the Punchbowl fault, a large-displacement exhumed fault in the San Andreas fault system, and show that the energy required to create the fracture surface area in the fault is about 300 times greater than seismological estimates would predict for a single large earthquake. If fracture energy is attributed entirely to the production of fracture surfaces, then all of the fracture surface area in the Punchbowl fault could have been produced by earthquake displacements totalling <1 km. But this would only account for a small fraction of the total energy budget, and therefore additional processes probably contributed to slip weakening during earthquake rupture.


A comparison of 3-D data correlation methods for fractionated stereotactic radiotherapy.
Stereotactic radiosurgery is currently used to treat patients who are not good candidates for conventional neurosurgical procedures. For treatments of nonvascular tumor cells, it appears that fractionation offers a radiobiological advantage between tumor and normal tissues. Therefore, fractionated stereotactic radiotherapy (FSR) is preferred because it minimizes normal tissue complications and maximizes local tumor control probability. We have implemented a methodology clinically to perform the noninvasive patient repositioning technique. The 3-D data correlation method for high-precision and multiple fraction stereotactic treatments has been presented. Three different optimization algorithms (Hooke and Jeeves optimization, simplex optimization, and simulated annealing optimization) are evaluated to calculate the transformation parameters necessary for FSR. A least-square object function is created to perform the 3-D data matching process. By minimizing the unconstrained object function value the best fit can be approached for the reference 3-D data sets. Simulation shows that these algorithms deliver results that are comparable to the previously published correlation algorithm (1,2) (singular value decomposition [SVD] method). The advantage for optimization algorithms is easily understood and can be readily implemented by using a personal computer (PC). The mathematical framework provides a tool to calculate the transformation matrix which can be used to adjust patient position for fractionated treatments. Therefore, using these algorithms for a high-precision fractionated treatment is possible without an invasive repeat fixation device and has been implemented clinically. A bite plate system was incorporated to acquire 3-D patient data. With a 3-D digital camera localization device, the patient motion can be followed in real time with the system calibrated to the isocenter. Two types of data sets are utilized to study the correlation results. One is using the digitized patient data which were retrieved clinically. The other is using the randomly generated data sets. Simulation errors for the optimization algorithms are all less than 1 mm in translation and less than 1 degree in rotation. Currently, FSR is performed using special designed repeat fixation devices which assure reproducible patient position for multiple fractions of radiation treatment. Clinical results indicated that this technique provided excellent treatment results. Three optimization algorithms have been applied and evaluated in calculating the transformation parameters between two 3-D contours or digitized data points. The mathematical functions behind these optimization algorithms are straightforward and can be easily implemented. When incorporated with the proper CT/MR image data with an electronic portal imaging (EPI) system, this process can possibly verify the patient's treatment position whenever there is doubt about the movement during the treatment procedure.


Risk of Tuberculosis Infection among Healthcare Workers in a Tertiary Care Hospital in Bengaluru City.
Tuberculosis (TB) is an airborne communicable disease caused by Mycobacterium tuberculosis. Infection is most likely to occur when an individual is exposed to someone with pulmonary TB on a day-to-day basis, such as by living or working in close quarters with someone who has an active disease. This study was undertaken using reliable screening and investigation tools for assessing the incident latent tuberculosis infection (LTBI) among healthcare workers (HCWs). This descriptive longitudinal study was conducted among 600 HCWs at a tertiary care hospital in Bengaluru city for a period of 1 year 4 months (March 2016-June 2017). All HCWs were stratified according to their work profile as doctors, nurses, laboratory technicians, nursing aides, pharmacists, laundry workers (only those who come in contact with patients), dietary workers (only those who come in contact with patients), and workers from housekeeping department. Study subjects were enrolled in proportion to their population size. The data were collected by administering TB screening questionnaire and performing tuberculin skin test (TST). All the subjects who had negative TST reaction were followed up after 1 year from March 2017 to June 2017. The study subjects consisted of 600 HCWs with a mean age of 27.8 ± 7.1 years. Initially, 600 study subjects underwent TST, 2 of whom were not contactable between 48 and 72 h of test administration. Of the remaining 598 subjects, 120 (20.1%) had a positive TST reaction. After 1 year, of the 478 subjects who tested negative, 345 study subjects underwent the repeat TST and 67 (19.4%) of the study subjects had a positive TST reaction. The prevalence of LTBI was 20.1% and it was significantly associated with age, place of residence, education, work commute time, and mode of transport. The incidence of LTBI was 19.4% and it was significantly associated with gender, place of residence, education, work commute time, and marital status.


Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination.
To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.


The effect of retroviral transformation on DNA replication and DNA polymerase-gamma activity in chick embryo fibroblast mitochondria.
The effect of transformation by oncogenic Rous sarcoma viruses on the replication of mitochondrial DNA (mtDNA) in chick embryo fibroblasts (CEF) was investigated, extending our previous report of a three- to five-fold increase in the rate of mtDNA replication, which is strictly linked to the expression of the transformed state, is mitochondria-specific, and is not attributable to virus production per se or different growth rates between normal and transformed CEF. In this paper, in vivo pulse-label and pulse-chase analysis shows an increased specific activity in all the replicative and topological forms of transformed cell mtDNA I, labeled within a 10-min pulse, 30-min chase period, reflecting about the same proportion of total label incorporated into D-loop strands (approximately 9S) relative to full-length closed circular forms (approximately 37S) of mtDNA from both cell types. In contrast to the concomitant changes observed in many other systems with elevated DNA synthesis, neither the estimated intramitochondrial pool size of the labeled DNA precursor (dTTP), nor the total level of the mtDNA-replicating enzyme (mt gamma-polymerase) is increased in the transformed cells. Notably, however, in both cell types the mitochondrial dTTP pools relative to the mtDNA complement are significantly larger than whole-cell pools relative to the nuclear DNA complement, confirming recent reports in HeLa cells. The solubilized mt gamma-polymerases from normal and transformed CEF, respectively, are both precipitated by 50% ammonium sulfate, inhibited by N-ethylmaleimide, have similar sedimentation coefficients, and exhibit optimal activity when poly(rA) . d(pT)10 is used as the template-primer. On the other hand, the transformed cell enzyme demonstrates an altered response to thiol compounds, a decreased tendency to aggregate during sedimentation, and is significantly less tightly attached to the mitochondria than the normal cell enzyme. We conclude that, as a result of transformation, an increased fraction of mtDNA molecules replicate at a given time, and that this increased replication rate in vivo is correlated with the expression of several altered endogenous properties, which possibly include a modified intramitochondrial structural attachment of the mt gamma-polymerase in situ. This experimental system may be well suitable for use in the identification of regulatory factors which function during the replication of the mitochondrial genome in vivo.


The mediating role of child-teacher dependency in the association between early mother-child attachment and behavior problems in middle childhood.
This study examines child-teacher dependency in preschool as a pathway through which mother-child attachment is associated with children's behavior problems across middle childhood. Data include direct assessments of attachment security and styles, teacher reports of child-teacher dependency, and maternal reports of behavior problems from the NICHD SECCYD (N = 769 children). Children with more secure attachments at 24 months were less likely to exhibit child-teacher dependency at 54 months. Children with ambivalent, controlling, or insecure/other attachments at 36 months had higher levels of child-teacher dependency at 54 months. Results from multi-level models showed that child-teacher dependency at 54 months was associated with higher levels of internalizing, but not externalizing, behavior problems across middle childhood. Child-teacher dependency partially mediated the association between insecure/other mother-child attachment and internalizing behaviors in middle childhood. Supporting preschool teachers to reduce child-teacher dependency may help ameliorate risk for internalizing behaviors posed by insecure/other attachment.


Hypothesis: antiphospholipid antibodies associated with congenital anomalies?
Antiphospholipid antibodies have been associated with pregnancy loss. We now present a possible association between antiphospholipid antibodies, recurrent spontaneous abortion and congenital anomalies. L.M. is a 32-year-old woman, gravida 6, para 2023, whose obstetric history includes three spontaneous abortions and two infants with congenital anomalies including kidney atresia and oromandibular hypogenesis. The only normal offspring are twins born after receiving treatment of aspirin 80 mg daily during the pregnancy. Laboratory evaluation revealed the presence of circulating antiphospholipid antibodies. Antiphospholipid antibodies cause endothelial cell activation which has been proposed as a cause of congenital malformations. This case suggests the risk of not only recurrent spontaneous abortion but also congenital anomalies in the offspring of a women with antiphospholipid antibodies. The congenital anomalies are 'regional' and could result from embryonic vascular accidents as a result of antiphospholipid antibody interaction with endothelial cells. The only 'successful' pregnancy was with treatment with aspirin. If the associations illustrated in this obstetric history can be substantiated by population-based studies, it may be concluded that antiphospholipid antibodies are a risk factor for embryo teratogenicity as well as mortality.


Facial artery and atherosclerosis.
We have performed a study about the incidence of the atherosclerotic phenomenon in the human facial artery, having observed an increase with aging. We also have researched the role of the smooth muscle cells in its genesis, with morphological, ultrastructural and immunohistochemical techniques.


Genetic variability of metabolic characteristics in chickens selected for their ability to digest wheat.
Improving feed efficiency remains crucial for poultry production. Birds have previously been selected on their ability to digest their diet, as assessed by AMEn (Apparent ME corrected for 0 nitrogen). Such selection, for either a high (D+) or a low AMEn (D-), affects energy, nitrogen, lipid, and starch digestibility. The aim of this study was to establish whether selection on the digestive ability of birds modified metabolic traits. A total of 630 broiler chickens of the eighth generation of a divergent selection experiment on AMEn were used for this purpose. A balance trial was performed to determine energy, nitrogen, and phosphorus retention. Growth performance was recorded and body protein and lipid deposition assessed by breast and abdominal fat yields. Tibia development and mineralization were also studied and heat production was indirectly assessed through the measurement of body temperature during fasting and feeding. Phenotypic correlations estimated within line showed that an increased efficiency was associated to fatter birds and more solid bones in D- but not in D+ line, whereas increased consumption was associated with more solid bones in D+ but not in D- line. The heritability estimates for metabolic traits were relatively high, except for temperature traits (from 0.08 to 0.12), ranging from 0.28 to 0.56 for body composition, and from 0.38 to 0.77 for bone characteristics. Breast meat yield did not differ between the 2 lines whereas a slight increase in abdominal fat yield was observed in the high-digestion line (D+). The relative dry tibia weights and ash weights were greater in D+ birds (+6.56 and +8.06%, respectively) but the lengths and the diameters of the tibia were lower (-7.89 and -3.77%, respectively). Finally, AMEn was poorly correlated with almost all metabolic traits (ranging from -0.10 to 0.20), indicating that the ability of the animal to digest its diet is genetically independent of post-digestion metabolic traits.


Apoptosis in the pancreatic islet cells of the neonatal rat is associated with a reduced expression of insulin-like growth factor II that may act as a survival factor.
Islet cell ontogeny will define adult beta-cell mass and will consist of a balance of islet cell birth and death. We have investigated the ontogeny of factors that may be related to developmental apoptosis in the islets, insulin-like growth factor II (IGF-II) and inducible nitric oxide synthase (iNOS), in pancreata of young Wistar rats. Pancreata were collected from rats of 21 days gestation to 29 days postnatal age. In situ hybridization and immunohistochemistry showed that IGF-II was expressed and present in fetal and neonatal islet cells, but declined rapidly 2 weeks after birth. Little IGF-I was associated with fetal or postnatal islets. Apoptosis in islet cells was visualized by molecular histochemistry for DNA breakage in tissue sections. Apoptosis was low in the fetus, but increased in incidence postnatally so that 13% of islet cells were undergoing apoptosis on postnatal day 14, with the incidence declining thereafter. Immunohistochemistry for iNOS showed that it was expressed within beta-cells and was most abundant 12 days after birth. When islets were isolated from rat pancreata 20-22 days after birth, islet cell viability, DNA synthetic rate, and insulin release were reduced after incubation with interleukin-1beta, tumor necrosis factor, or interferon-gamma. An increased rate of islet cell survival was found after simultaneous incubation with IGF-I or -II. Cytokine-mediated islet cell death involved the induction of apoptosis. Islets isolated from neonatal rats were not killed after exposure to these cytokines at the same concentrations, but cytokine-induced cell death was seen when neonatal islets were incubated with a neutralizing antibody against IGF-II. These experiments show that a peak of islet cell apoptosis that is maximal in the rat pancreas 14 days after birth is temporally associated with a fall in the islet cell expression of IGF-II. IGF-II was shown to function as an islet survival factor in vitro. The induction of islet cell apoptosis in vivo may involve an increased expression of iNOS within beta-cells.


Process Improvement Approaches for Increasing the Response of Emergency Departments against the COVID-19 Pandemic: A Systematic Review.
The COVID-19 pandemic has strongly affected the dynamics of Emergency Departments (EDs) worldwide and has accentuated the need for tackling different operational inefficiencies that decrease the quality of care provided to infected patients. The EDs continue to struggle against this outbreak by implementing strategies maximizing their performance within an uncertain healthcare environment. The efforts, however, have remained insufficient in view of the growing number of admissions and increased severity of the coronavirus disease. Therefore, the primary aim of this paper is to review the literature on process improvement interventions focused on increasing the ED response to the current COVID-19 outbreak to delineate future research lines based on the gaps detected in the practical scenario. Therefore, we applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform a review containing the research papers published between December 2019 and April 2021 using ISI Web of Science, Scopus, PubMed, IEEE, Google Scholar, and Science Direct databases. The articles were further classified taking into account the research domain, primary aim, journal, and publication year. A total of 65 papers disseminated in 51 journals were concluded to satisfy the inclusion criteria. Our review found that most applications have been directed towards predicting the health outcomes in COVID-19 patients through machine learning and data analytics techniques. In the overarching pandemic, healthcare decision makers are strongly recommended to integrate artificial intelligence techniques with approaches from the operations research (OR) and quality management domains to upgrade the ED performance under social-economic restrictions.


Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids.
We evaluated the accuracy of nicotine concentration labeling on electronic cigarette refill products. The nicotine concentration of 71 electronic cigarette refill fluid products and 1 related do-it-yourself (DIY) product was quantified using high-performance liquid chromatography. Quantified data were compared with manufacturers labeled concentrations. Duplicate refill fluid products purchased at different times were evaluated by visual comparison of fluid coloration and quantified nicotine concentration. Thirty-five of the 54 nicotine-containing fluids had quantified nicotine concentrations that deviated by more than ± 10% from the manufacturer labels, with 46 of 50 being in excess of labeled values. Refill fluids labeled as 0 nicotine had no detectable nicotine. Of the 5 products that were unlabeled for nicotine concentration, 3 contained no detectable nicotine, whereas the remaining 2 contained nicotine in excess of 100mg/ml and may have been intended for DIY use. Sixteen of the 18 duplicate bottles of refill fluid varied greatly in their nicotine concentrations. One of the 5 companies showed significant improvement in labeling accuracy among the most recently purchased products. Of the 23 total duplicate pairs, 15 of 23 varied in coloration from their mates. Nicotine concentration labeling on electronic cigarette refill products was often inaccurate but showed improvement recently in products from 1 company. To ensure the safety of refill fluids and DIY products, it is necessary to establish quality control guidelines for the manufacturing and labeling and to monitor products longitudinally.


Advance care planning for people with dementia: a review.
Few people with dementia have made advance plans for their health care. Advance care planning (ACP) is a process of discussion between an individual and their care providers that takes account of wishes and preferences for future care. We aimed to examine the facilitators and inhibitors to ACP in people with dementia. We also aimed to identify key themes in the literature and critically review the methodologies used. We systematically searched the English language literature including PubMed, CINAHL, AMED, PsychINFO, EMBASE and BNI. We included empirical studies which reported the characteristics of the patient population, the type of advance care planning used and the study setting, and which involved people with dementia, family members or professional carers. We identified 17 studies (11 quantitative methods, one qualitative and five mixed methods). We found one ACP intervention which changed outcomes for people with dementia. Key themes were identified: there is a point at which cognition decreases critically so that an advanced care plan can no longer be made; factors present in family carers and professionals can influence decision-making and the ACP process; ACPs are affected by preferences for life sustaining treatments; ACP in dementia may differ from other illness groups; and there is a need for education relating to ACP. The current evidence base for ACP in dementia is limited. Since UK government policy recommends that all people should engage in ACP, more evidence is needed to understand the feasibility and acceptability of advanced care plans for people with dementia.


Ultrathin Mixed Ionic-Electronic Conducting Interlayer via the Solution Shearing Technique for High-Performance Lithium-Sulfur Batteries.
The commercialization of lithium-sulfur (Li-S) batteries has been hampered by diverse challenges, including the shuttle phenomenon and low electrical/ionic conductivity of lithium sulfide and sulfur. To address these issues, extensive research has been devoted to developing multifunctional interlayers. However, interlayers capable of simultaneously suppressing the polysulfide (PS) shuttle and ensuring stable electrical and ionic conductivity are relatively uncommon. Moreover, the use of thick and heavy interlayers results in an unavoidable decline in the energy density of Li-S batteries. We developed an ultrathin (750 nm), lightweight (0.182 mg cm-2) interlayer that facilitates mixed ionic-electronic conduction using the solution shearing technique. The interlayer, composed of carbon nanotube (CNT)/Nafion/poly-3,4-ethylenedioxythiophene:tetracyanoborate (PEDOT:TCB), effectively suppresses the shuttle phenomenon through the synergistic segregation and adsorption effects on PSs by Nafion and CNT/PEDOT, respectively. Furthermore, the electrical/ionic conductivity of the interlayer can be improved via counterion exchange and homogeneous Li+ ion flux/good wettability from SO3- functional group of Nafion, respectively. Enhanced sulfur utilization and reaction kinetics through polysulfide shuttle inhibition and facilitated electron/ion transfer by interlayer enable a high discharge capacity of 1029 mA h g-1 in the Li-S pouch cell under a high sulfur loading of 5.3 mg cm-2 and low electrolyte/sulfur ratio of 5 μL mg-1.


What characterises smokers who quit without using help? A study of users and non-users of cessation support among successful ex-smokers.
A variety of smoking cessation aids are available; however, the majority of smokers quit unaided. We know little of the differences between users and non-users of cessation support. A cross-sectional study based on the Danish Health Examination Survey (DANHES) conducted in 2007-2008. In all, 6445 persons reporting quitting successfully within the last 5 years were included in analyses. Users and non-users of cessation aid (medical or behavioural support) were compared with regards to age, education, years smoked, tobacco amount, tobacco type and smoking-related disease using logistic regression analysis. Quitting unaided was reported by 63%. Adjusted analyses showed that men were more likely to quit unaided than women, and younger compared with older were more likely to quit unaided (eg, OR among women age 45-59 versus age 14-29 were 0.18, 95% CI 0.12 to 0.20). Additionally, those who had smoked for 15 years or more also had lower odds of quitting unaided. Smoking 15 or more grams of tobacco daily was inversely associated with quitting unaided (eg, OR among men were 0.38, 95% CI 0.31 to 0.46). Quitting smoking without the use of formalised aid was the most common cessation approach. Quitting unaided was more likely among men, younger age groups, those with a shorter history of smoking and those who were light smokers. These results indicate that awareness of unaided cessation in general and to those for whom it is especially relevant should be increased. This could lead to a more efficient use of resources for cessation support.


Empirical validation and psychometric evaluation of the Brief Fear of Negative Evaluation Scale in patients with social anxiety disorder.
The Brief Fear of Negative Evaluation Scale (BFNE; M. R. Leary, 1983a) is often used to assess fear of negative evaluation, the core feature of social anxiety disorder. However, few studies have examined its psychometric properties in large samples of socially anxious patients. Although the BFNE yields a single total score, confirmatory factor analysis indicated a 2-factor solution to be more appropriate, with the 1st factor consisting of all straightforwardly worded items (BFNE-S) and the 2nd of all reverse-scored items (BFNE-R). Support was obtained for the convergent and discriminant validity of the BFNE and BFNE-S, but not the BFNE-R. These results suggest that standard scoring of the BFNE may not be optimal for patients with social anxiety disorder.


Lysophosphatidic acid stimulates epidermal growth factor-family ectodomain shedding and paracrine signaling from human lung fibroblasts.
Lysophospatidic acid (LPA) is a bioactive lipid mediator implicated in tissue repair and wound healing. It mediates diverse functional effects in fibroblasts, including proliferation, migration and contraction, but less is known about its ability to evoke paracrine signaling to other cell types involved in wound healing. We hypothesized that human pulmonary fibroblasts stimulated by LPA would exhibit ectodomain shedding of epidermal growth factor receptor (EGFR) ligands that signal to lung epithelial cells. To test this hypothesis, we used alkaline phosphatase-tagged EGFR ligand plasmids transfected into lung fibroblasts, and enzyme-linked immunosorbent assays to detect shedding of native ligands. LPA induced shedding of alkaline phosphatase-tagged heparin-binding epidermal growth factor (HB-EGF), amphiregulin, and transforming growth factor-a; non-transfected fibroblasts shed amphiregulin and HBEGF under baseline conditions, and increased shedding of HB-EGF in response to LPA. Treatment of fibroblasts with LPA resulted in elevated phosphorylation of extracellular signal-regulated kinase 1/2, enhanced expression of mRNA for c-fos, HB-EGF and amphiregulin, and enhanced proliferation at 96 hours. However, none of these fibroblast responses to LPA required ectodomain shedding or EGFR activity. To test the ability of LPA to stimulate paracrine signaling from fibroblasts, we transferred conditioned medium from LPA-stimulated cells, and found enhanced EGFR and extracellular signal-regulated kinase 1/2 phosphorylation in reporter A549 cells in excess of what could be accounted for by transferred LPA alone. These data show that LPA mediates EGF-family ectodomain shedding, resulting in enhanced paracrine signaling from lung fibroblasts to epithelial cells.


Distribution of Vibrio vulnificus phage in oyster tissues and other estuarine habitats.
Phages lytic to Vibrio vulnificus were found in estuarine waters, sediments, plankton, crustacea, molluscan shellfish, and the intestines of finfish of the U.S. Gulf Coast, but no apparent relationship between densities of V. vulnificus and its phages was observed. Phage diversity and abundance in molluscan shellfish were much greater than in other habitats. V. vulnificus phages isolated from oysters did not lyse other mesophilic bacteria also isolated from oysters. Both V. vulnificus and its phages were found in a variety of oyster tissues and fluids with lowest densities in the hemolymph and mantle fluid. These findings suggest a close ecological relationship between V. vulnificus phages and molluscan shellfish.


The Role of Eicosanoids in Gynecological Malignancies.
Eicosanoids, bio-active lipid molecules, evoke a multitude of biological effects that directly affect cancer cells and indirectly affect tumor microenvironment. An emerging role has been shown for eicosanoids in the pathogenesis of gynecological malignancies which include cancers of the vulva, vagina, cervix, uterine, and ovary. Eicosanoid biosynthesis pathways start at the metabolism of phospholipids by phospholipase A2 then proceeding to one of three pathways: the cyclooxygenase (COX), lipoxygenase (LOX), or P450 epoxygenase pathways. The most studied eicosanoid pathways include COX and LOX; however, more evidence is appearing to support further study of the P450 epoxygenase pathway in gynecologic cancers. In this review, we present the current knowledge of the role of COX, LOX and P450 pathways in the pathogenesis of gynecologic malignancies. Vulvar and vaginal cancer, the rarest subtypes, there is association of COX-2 expression with poor disease specific survival in vulvar cancer and, in vaginal cancer, COX-2 expression has been found to play a role in mucosal inflammation leading to disease susceptibility and transmission. Cervical cancer is associated with COX-2 levels 7.4 times higher than in healthy tissues. Additionally, HPV elevates COX-2 levels through the EGFR pathway and HIV promotes elevated COX-2 levels in cervical tissue as well as increases PGE2 levels eliciting inflammation and progression of cancer. Evidence supports significant roles for both the LOX and COX pathways in uterine cancer. In endometrial cancer, there is increased expression of 5-LOX which is associated with adverse outcomes. Prostanoids in the COX pathway PGE2 and PGF2α have been shown to play a significant role in uterine cancer including alteration of proliferation, adhesion, migration, invasion, angiogenesis, and the inflammatory microenvironment. The most studied gynecological malignancy in regard to the potential role of eicosanoids in tumorigenesis is ovarian cancer in which all three pathways have shown to be associated or play a role in ovarian tumorigenesis directly on the tumor cell or through modulation of the tumor microenvironment. By identifying the gaps in knowledge, additional pathways and targets could be identified in order to obtain a better understanding of eicosanoid signaling in gynecological malignancies and identify potential new therapeutic approaches.


Insights into the Recognition of Phosphate Groups by Peptidic Arginine from Action Spectroscopy and Quantum Chemical Computations.
The side group of the amino acid arginine is typically in its guanidinium protonated form under physiological conditions and participates in a broad range of ligand binding and charge transfer processes of proteins. The recognition of phosphate moieties by guanidinium plays a particularly key role in the interactions of proteins with ATP and nucleic acids. Moreover, it has been recently identified as the driving force for the inhibition of kinase phosphorilation activity by guanidinium derivatives devised as potential anticancer agents. We report on a fundamental investigation of the interactions and coordination arrangements formed by guanidinium with phosphoric, phosphate, and pyrophosphate groups. Action vibrational spectroscopy and ab initio quantum chemical computations are employed to characterize the conformations of benchmark positively charged complexes isolated in an ion trap. The multidentate structure of guanidinium and of the phosphate groups gives rise to a rich conformational landscape with a particular relevance of tweezer-like configurations, where phosphate is effectively trapped by two guanidinium cations. The pyrophosphate complex incorporates a Na+ cation, which serves to compare the interactions associated with the localized versus diffuse charge distributions of the alkali cation and guanidinium, respectively, within a common supramolecular framework.


Osteochondral lesions of the talus: a new magnetic resonance grading system with arthroscopic correlation.
The purpose of this study was to show that magnetic resonance imaging (MRI) can accurately and noninvasively evaluate the articular cartilage overlying osteochondral lesions of the talus, using arthroscopy as the standard, and provide information about lesion stability. A classification system applicable to both MRI and arthroscopy is proposed. Retrospective review with MRI and arthroscopy correlation. A retrospective analysis involving 26 men and 28 women who underwent MRI of the ankle and in whom arthroscopy had been performed. The talar dome cartilage was evaluated using the following grading system: 0, normal cartilage; 1, abnormal signal but intact; 2, fibrillation or fissures not extending to bone; 3, flap present or bone exposed; 4, loose undisplaced fragment; 5, displaced fragment. There was a history of trauma in 80% of cases. At surgery, 14 ankle joints had intact cartilage and 40 showed osteochondral lesions. MRI correctly identified all 40 osteochondral lesions and all 14 normal ankles. MRI correctly graded 33 of 40 (83%) of the osteochondral lesions using the described 5-point scale. Of the remaining 7 lesions, all were identified within 1 grade. Collapsing all grades into disease-negative status (grades 0 and 1) and disease-positive status (grades 2, 3, 4, and 5) yielded sensitivity of 95%, specificity of 100%, negative predictive value of 88%, and positive predictive value of 100%. This study shows that MRI can be used to evaluate the articular cartilage covering osteochondral lesions of the talus with a high degree of accuracy and thus may aid in identifying patients who would benefit from definitive arthroscopic treatment.


The efficient capture of polysaccharides in Tetradesmus obliquus of indole-3-acetic acid coupling sludge extraction.
Polysaccharide is an important biomass of algae. The sludge extract is rich in organic substances, which can be used by algae for biomass growth and high-value biomass synthesis, but its organic toxicity has an inhibitory effect on algae. To overcome inhibition and improve polysaccharide enrichment, Tetradesmus obliquus was cultured with sludge extract with different indole-3-acetic acid (IAA) concentrations. Within 30 days of the culture cycle, T. obliquus showed in good condition at the IAA dosage content of 10-6 M, the maximum cell density and dry weight were respectively (106.78 ± 2.20) × 106 cell/mL and 2.941 ± 0.067 g/L while the contents of chlorophyll-a, chlorophyll-b, and carotenoid were 1.79, 1.91 and 2.80 times that of the blank group, respectively. The highest polysaccharide accumulation was obtained under this culture condition, reaching 533.15 ± 21.11 mg/L on the 30th day, which was 2.49 times that in the blank group. By FT-IR and NMR analysis, it was found that the polysaccharides of T. obliquus were sulfated polysaccharide with glucose and rhamnose as the main monosaccharides. Proteomic showed that the up-regulation of A0A383WL26 and A0A383WLM8 enhanced the light trapping ability, and A0A383WMJ2 enhanced the accumulation of NADPH. The up-regulation of A0A383WHD5 and A0A383WAY6 indicated that IAA culture could repair the damage caused by sludge toxicity, thus promoting the accumulation of biomass. The above findings provided new insights into the mechanism of sludge toxicity removal of T. obliquus and the enhancement of the polysaccharide accumulation effect under different concentrations of IAA.


Comparative Evaluation of Two Different Ultrasonic Liquid Coolants on Dental Aerosols.
Dentists are more prone for developing infectious diseases especially related to respiratory system. The ultrasonic scaler which is a major source of dental aerosol production is most frequently used contrivance in a dental set up. The aim of this study was to evaluate the effect of povidone iodine and chlorhexidine gluconate as an ultrasonic liquid coolant on aerosols in comparison with distilled water. The objectives of this study were to compare the potency of povidone iodine and chlorhexidine gluconate on reducing dental aerosols and quantitative assessment of microbial content of dental aerosols at right, left and behind the dental chair. In this study 30 subjects were selected who fulfilled the inclusion criteria and were divided into three groups. Group 1 (Control group): Ultrasonic scaling with distilled water (10 subjects), Group 2 (Test group): Ultrasonic scaling with 2% povidone iodine (10 subjects), Group 3 (Test group): Ultrasonic scaling with 0.12% chlorhexidine (10 subjects). At the baseline one blood agar plate was kept for 10 minutes in the fumigated chamber before ultrasonic scaling, thereafter three blood agar plates were kept at a distance of 0.4 meters away on either side of the patient and 2 meters behind the patient's mouth during ultrasonic scaling. Blood agar plates were kept for gravitometric settling of dental aerosols. At baseline, no significant numbers of Colony-Forming Units (CFU) were detected. It is found that Group 3 (chlorhexidine gluconate) showed effective CFU reduction (27.17 ±12.5 CFU) when compared to distilled water (124.5 ± 30.08 CFU) and povidone iodine (60.43 ± 33.33 CFU). More CFU were found on blood agar plates which were kept on right side in all the three groups. The results obtained were statistically significant (p< 0.001). Chlorhexidine gluconate is more effective in reducing dental aerosols when compared to povidone iodine and distilled water. Povidone iodine showed better CFU reduction when compared with distilled water. Hence, chlorhexidine or povidone iodine can also be used as an ultrasonic liquid coolant for reducing the number of dental aerosols during ultrasonic scaling.


Feature-based activation and suppression during binocular rivalry.
In the past decade, effects of pattern coherence have indicated that perception during binocular rivalry does not result solely from reciprocal inhibitory competition between monocular channels. In this study we were interested in feature selectivity both during dominance and during suppression. The first experiment shows that a suppressed stimulus perceptually appears earlier when it shares features with a visible stimulus than when it does not. Subsequently, our second experiment suggests a reversal of this effect when similarity is exhibited with a suppressed stimulus. These findings hint at a role for both selective enhancing (Experiment 1) and selective inhibitory cortical mechanisms (Experiment 2) in causing image rivalry. From a phenomenological perspective these results suggest that we are not only selectively aware but also selectively unaware of specific features in the visual scene.


Continuity in a VA patient-centered medical home reduces emergency department visits.
One major goal of the Patient-Centered Medical Home (PCMH) is to improve continuity of care between patients and providers and reduce the utilization of non-primary care services like the emergency department (ED). To characterize continuity under the Veterans Health Administration's PCMH model--the Patient Aligned Care Team (PACT), at one large Veterans Affair's (VA's) primary care clinic, determine the characteristics associated with high levels of continuity, and assess the association between continuity and ED visits. Retrospective, observational cohort study of patients at the West Haven VA (WHVA) Primary Care Clinic from March 2011 to February 2012. The 13,495 patients with established care at the Clinic, having at least one visit, one year before March 2011. Our exposure variable was continuity of care--a patient seeing their assigned primary care provider (PCP) at each clinic visit. The outcome of interest was having an ED visit. The patients encompassed 42,969 total clinic visits, and 3185 (24%) of them had 15,458 ED visits. In a multivariable logistic regression analysis, patients with continuity of care--at least one visit with their assigned PCP--had lower ED utilization compared to individuals without continuity (adjusted odds ratio [AOR] 0.54; 95% CI: 0.41, 0.71), controlling for frequency of primary care visits, comorbidities, insurance, distance from the ED, and having a trainee PCP assigned. Likewise, the adjusted rate of ED visits was 544/1000 person-year (PY) for patients with continuity vs. 784/1000 PY for patients without continuity (p = 0.001). Compared to patients with low continuity (<33% of visits), individuals with medium (33-50%) and high (>50%) continuity were less likely to utilize the ED. Strong continuity of care is associated with decreased ED utilization in a PCMH model and improving continuity may help reduce the utilization of non-primary care services.


A defect late in stimulus-secretion coupling impairs insulin secretion in Goto-Kakizaki diabetic rats.
A widely accepted genetically determined rodent model for human type 2 diabetes is the Goto-Kakizaki (GK) rat; however, the lesion(s) in the pancreatic islets of these rats has not been identified. Herein, intact islets from GK rats (aged 8-14 weeks) were studied, both immediately after isolation and after 18 h in tissue culture. Despite intact contents of insulin and protein, GK islets had markedly deficient insulin release in response to glucose, as well as to pure mitochondrial fuels or a non-nutrient membrane-depolarizing stimulus (40 mmol/l K+). In contrast, mastoparan (which activates GTP-binding proteins [GBPs]) completely circumvented any secretory defect. Basal and stimulated levels of adenine and guanine nucleotides, the activation of phospholipase C by Ca2+ or glucose, the secretory response to pertussis toxin, and the activation of selected low-molecular weight GBPs were not impaired. Defects were found, however, in the autophosphorylation and catalytic activity of cytosolic nucleoside diphosphokinase (NDPK), which may provide compartmentalized GTP pools to activate G-proteins; a deficient content of phosphoinositides was also detected. These studies identify novel, heretofore unappreciated, defects late in signal transduction in the islets of our colony of GK rats, possibly occurring at the site of activation by NDPK of a mastoparan-sensitive G-protein-dependent step in exocytosis.


LncRNA SNHG12 ameliorates bupivacaine-induced neurotoxicity by sponging miR-497-5p to upregulate NLRX1.
Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has been reported to participate in the regulation of various nervous system disorders. Bupivacaine (BV), a commonly used local anesthetic, could generate neurotoxicity in neurons. This work intended to investigate the role and specific mechanism of SNHG12 in BV-induced neurotoxicity. In this study, we established an in vitro cell model of BV-induced neurotoxicity by exposing human neuroblastoma cells (SH-SY5Y) to BV. It was found that SNHG12 and NLRX1 levels were gradually downregulated, while miR-497-5p enrichment was upregulated accordingly with the increase of BV concentration. As indicated by functional assays, SNHG12 overexpression promoted cell viability but inhibited cell apoptosis and oxidative stress in BV-treated SH-SY5Y cells. In addition, it was identified that SNHG12 directly targeted miR-497-5p and attenuated BV-induced neurotoxicity via interaction with miR-497-5p. Besides, it was confirmed that SNHG12 could upregulate NLRX1 expression by absorbing miR-497-5p. Moreover, miR-497-5p decreased cell viability and induced cell apoptosis and oxidative stress, which was partly reversed by NLRX1 upregulation. In conclusion, our findings indicated that SNHG12 might relieve BV-associated neurotoxicity by upregulating NLRX1 via miR-497-5p in vitro, providing novel clues and biomarkers for the treatment and prevention of BV-associated neurotoxicity.


Addressing food insecurity: An exploration of wheat production expansion.
Wheat plays a crucial role in global food security, serving as a vital food crop that feeds billions of people worldwide. Currently, Russia and Ukraine are responsible for exporting approximately 25% of the world's wheat, making any issues in these regions a cause for concern regarding global wheat supply. The problems faced in these areas have led to a surge in wheat prices worldwide. Consequently, it becomes necessary to explore alternative regions that can compensate for the decline in wheat production and supply. This study focuses on wheat production and yield in major producing countries, utilizing the GYGA (Global Yield Gap Atlas) protocol for predictions. The findings reveal a global wheat production gap of 270,378,793 tons. Notably, the largest gap in irrigated wheat production exists in countries like China, India, Pakistan, Turkey, Iran, Afghanistan, Uzbekistan, Egypt, and Azerbaijan. Additionally, the rainfed wheat production gap on a global scale amounts to 545,215,692 tons, with Russia, the USA, Kazakhstan, Australia, Ukraine, China, Turkey, Canada, India, and France having the most significant production gaps. Through boundary line analysis, specific criteria were identified for suitable areas of irrigated and rainfed wheat cultivation. For irrigated conditions, the temperature range of 3000 to 7000 GDD (Growing Degree Days) and a temperature seasonality of 3 were determined as favorable. Under rainfed conditions, the suitable areas encompass a temperature range of 2000 to 4000 GDD, an aridity index exceeding 600, and a temperature seasonality of 2. Thirteen countries possess extensive agricultural land within the climatic codes favorable for irrigated wheat cultivation. Approximately 50% of the agricultural lands within these countries, corresponding to the total arable area for irrigated wheat, fall within the climatic codes 3403, 5403, 5303, 4303, 5503, 5203, 3503, 3303, and 4103. China, the United States, Ukraine, Russia, and Iran are the top five countries with favorable lands for irrigated wheat cultivation. Similarly, fourteen countries have significant agricultural lands within the favorable climatic codes for rainfed wheat cultivation. Around 52% of the agricultural lands within these countries are within the climatic codes 3702, 2702, 2802, and 4602. France, Germany, Britain, Poland, and Denmark possess the highest potential to expand rainfed wheat cultivation areas within these favorable climate codes, with respective areas of 2.7, 2.6, 1.6, and 0.9 million hectares. According to the study, the North China Plain emerges as a primary region for increasing irrigated wheat production, both in terms of cultivated area and yield potential. For rainfed conditions, the European continent stands out as a significant region to enhance wheat production.


Hyperphosphatemia of chronic kidney disease.
Observational studies have determined hyperphosphatemia to be a cardiovascular risk factor in chronic kidney disease. Mechanistic studies have elucidated that hyperphosphatemia is a direct stimulus to vascular calcification, which is one cause of morbid cardiovascular events contributing to the excess mortality of chronic kidney disease. This review describes the pathobiology of hyperphosphatemia that develops as a consequence of positive phosphate balance in chronic kidney disease and the mechanisms by which hyperphosphatemia acts on neointimal vascular cells that are stimulated to mineralize in chronic kidney disease. The characterization of hyperphosphatemia of chronic kidney disease as a distinct syndrome in clinical medicine with unique disordered skeletal remodeling, heterotopic mineralization and cardiovascular morbidity is presented.


Overexpression of cyclin D1 is associated with poor survival in epithelial ovarian cancer.
In order to assess the prognostic role of the cell-cycle regulator cyclin D1 in epithelial ovarian cancer, 70 patients have been studied during an observation period of 8 years. The cyclin D1 protein content was analyzed by Western blotting, and classed as negative, positive and highly positive by densitometric scanning. The relationship between cyclin D1 expression and clinicopathological variables was determined. Univariate and multivariate survival analyses were also carried out. Patients with highly positive cyclin D1 tumors had shorter overall survival than patients with positive cyclin D1 (median survival 31 vs. 49 months; p = 0.058). Furthermore, in patients with stage III/IV tumors and residual disease greater than 2 cm, cyclin D1 expression significantly influenced clinical outcome (p = 0.047 and 0.040, respectively). In the Cox's regression model, cyclin D1 expression and residual disease were identified as the most important predictors of survival (p = 0.016 and 0.002, respectively). In patients with high cyclin D1 expression and residual disease after debulking surgery greater than 2 cm, the relative risks of death were to 2.48 and 3.7, respectively, compared to their correspondent counterparts. The overexpression of cyclin D1 is significantly related to a more aggressive tumor phenotype and poor prognosis in ovarian carcinoma.


AT1 receptor expression in glomeruli from NO-deficient rats.
Chronic inhibition of nitric oxide synthase promotes renin-dependent hypertension and renal injury. The present study examines how renal angiotensin II receptors are expressed in this model. N(G)-nitro-L-arginine methyl ester (L-NAME) was given orally to rats for 1 month and was associated or not with captopril during the 4 last days of the administration. 125I-[Sar1, Ile8]-Ang II binding, AT1)mRNA and cytosolic calcium were studied in isolated glomeruli from L-NAME and control rats and in cultured mesangial cells from normal rats. Renal injury was marked in rats receiving L-NAME. Type I angiotensin II (AT1) receptor number and mRNA expression were decreased (p < 0.05) in glomeruli isolated from L-NAME-treated rats compared with controls, unless they received captopril in combination. The low level of AT1 receptor expression was associated with an attenuated rise of cytosolic calcium in response to angiotensin II. Angiotensin-converting enzyme activity in glomeruli and angiotensin II concentration in renal cortex were increased (p < 0.05) in rats receiving L-NAME alone, whereas aminopeptidase A activity was not modified. To better discriminate between the direct and indirect effects of nitric oxide deficiency, rat mesangial cells were exposed or not for 24 h to S-nitroso-N-acetyl penicillamine, a nitric oxide donor. Angiotensin II binding, AT1 mRNA expression and calcium response to angiotensin II were decreased in presence of the nitric oxide donor (p < 0.01). These results suggest that the decrease of AT1 receptor expression after 1 month of L-NAME treatment does not depend on a direct effect of nitric oxide deficiency but results from the high local angiotensin II concentration due to the stimulated angiotensin-converting enzyme activity. They also show that the renin-angiotensin dependence of this model of hypertension does not result from the overexpression of AT1 receptors.


Monitoring the removal of carbonate from alkali metal hydroxide solutions using gas diffusion flow injection.
Monitoring the removal of carbonate from alkali metal hydroxide (MOH, M = K, Na) solutions with calcium oxide (CaO) was studied using a newly developed method for the determination of trace amounts of total carbonate (TC) in alkaline solutions based on a flow injection (FI) technique coupled with a gas diffusion system. The optimized conditions of the FI system were as follows: the flow rate of each carrier, reaction solution (H2SO4) and receptor solution (Cresol Red, pH 8.9) was 0.25 ml min(-1), the sample size was 0.1 ml and the concentration of H2SO4 in the reaction solution was 0.09 M. The limit of detection of TC by the proposed method was 4 x 10(-7) M. The removal efficiency of carbonate was affected by the amount of CaO added, the shaking time of the solutions and the concentration of MOH. For 1 M NaOH and KOH solution, the removal efficiency of carbonate was about 99% and the concentration of residual carbonate was 4 x 10(-5) and 1.2 X 10(-4) M, respectively, when the amount of CaO added was 2 g l(-1) and the shaking time was 16 h.


[The social rehabilitation of neurosurgical patients].
The authors analyze the theoretical problems of estimating the effectiveness of rehabilitation of patients with brain lesions. Describe an original scale for assessing social rehabilitation of neurosurgical patients. Relate the results of the follow-up of a group of patients after brain surgery. Analyze the dependence of the effectiveness of social rehabilitation on some demographic, clinical and neuropsychological criteria.


Anti-Müllerian hormone and its role in ovarian function.
Anti-Müllerian hormone (AMH) is expressed after birth in the ovary in the granulosa cells of healthy, small growing follicles. We have shown that AMH affects two important regulatory steps during folliculogenesis. At initial recruitment, AMH inhibits recruitment of primordial follicles into the growing pool, while at cyclic recruitment AMH lowers the FSH-sensitivity of follicles. In these ways, AMH plays an important role in regulation of ovarian follicle growth. AMH serum level is a strong candidate marker for ovarian reserve in women. In normo-ovulatory women, AMH serum levels correlated strongly with the number of antral follicles. In addition, AMH is a strong predictor for the number of oocytes retrieved in patients undergoing IVF treatment. The convenience of determination and its relative stable expression during the menstrual cycle indicate that further validation of the use of serum AMH is recommended as a clinical measure of ovarian reserve.


No association between gender inequality and peak HIV prevalence in developing countries - an ecological study.
The prevalence of both gender inequality and HIV prevalence vary considerably both within all developing countries and within those in sub-Saharan Africa. We test the hypothesis that the extent of gender inequality is associated with national peak HIV prevalence. Linear regression was used to test the association between national peak HIV prevalence and three markers of gender equality - the gender-related development index (GDI), the gender empowerment measure (GEM), and the gender inequality index (GII). No evidence was found of a positive relationship between gender inequality and HIV prevalence, either in the analyses of all developing countries or those limited to Africa. In the bivariate analyses limited to Africa, there was a positive association between the two measures of gender "equality" and peak HIV prevalence (GDI: coefficient 28, 95% confidence interval (CI) 9.1-46.8; GEM: coefficient 54.8, 95% CI 20.5-89.1). There was also a negative association between the marker of gender "inequality" and peak HIV prevalence (GII: coefficient -66.9, 95% CI -112.8 to -21.0). These associations all disappeared on multivariate analyses. We could not find any evidence to support the hypothesis that variations in the extent of gender inequality explain variations in HIV prevalence in developing countries.


[Comparison of the results of stenting ans balloon angioplasty of coronary arteries in relation to the type of stenosis].
Based on the comparison of the immediate and late results of stenting and balloon angioplasty (BA), the authors consider whether it is expedient to perform stenting of coronary arteries (CA) in all cases of BA in patients with coronary heart disease (CHD) and different types of CA stenosis. The study included 410 patients: a group of stenting (n = 197) and a group of traditional BA (n = 213). All the patients in both groups were divided into four subgroups in relation to the type of detected stenosis according to the classification of the American Association of Cardiologists (ACC/AHA). The positive angiographic and clinical results were observed in all 197 patients after stenting. This was associated neither with the type of dilated stenosis nor with the design of an implanted stent. In dilation of types A and B1 stenoses, a stent-like result was significantly more frequently observed than in dilation of types B2 and C stenoses. There was no significant difference in the development of restenosis in patients after routine BA and stenting of types A and B1 stenoses. At the same time, after BA of types B2 and C stenoses, restenosis developed significantly more frequently than in stenting. Thus, on the basis of this study, it may be stated that the traditional BA yields the so-called stent-like result significantly more frequently in patients with uncomplicated forms of CA stenoses than in those with complicated ones. Once the stent-like result is achieved in patients with type A stenoses, stenting should not be performed since the latter fails to improve the immediate and late results of angioplasty. Despite that the stent-like result is achieved in patients with complicated forms of CA stenoses, it is expedient to make stenting. Our findings indicate that the obtained good immediate result reduces the incidence of restenosis.


Molecular genetics of the RNA polymerase II general transcriptional machinery.
Transcription initiation by RNA polymerase II (RNA pol II) requires interaction between cis-acting promoter elements and trans-acting factors. The eukaryotic promoter consists of core elements, which include the TATA box and other DNA sequences that define transcription start sites, and regulatory elements, which either enhance or repress transcription in a gene-specific manner. The core promoter is the site for assembly of the transcription preinitiation complex, which includes RNA pol II and the general transcription fctors TBP, TFIIB, TFIIE, TFIIF, and TFIIH. Regulatory elements bind gene-specific factors, which affect the rate of transcription by interacting, either directly or indirectly, with components of the general transcriptional machinery. A third class of transcription factors, termed coactivators, is not required for basal transcription in vitro but often mediates activation by a broad spectrum of activators. Accordingly, coactivators are neither gene-specific nor general transcription factors, although gene-specific coactivators have been described in metazoan systems. Transcriptional repressors include both gene-specific and general factors. Similar to coactivators, general transcriptional repressors affect the expression of a broad spectrum of genes yet do not repress all genes. General repressors either act through the core transcriptional machinery or are histone related and presumably affect chromatin function. This review focuses on the global effectors of RNA polymerase II transcription in yeast, including the general transcription factors, the coactivators, and the general repressors. Emphasis is placed on the role that yeast genetics has played in identifying these factors and their associated functions.


In vitro antioxidant activities of the fractions of Coccinia grandis L. leaf extract.
The present study was aimed at investigating the antioxidant activities of the various fractions of the hydromethanolic extract of the leaves of Coccinia grandis L. Voigt. (Cucurbitaceae). The antioxidant activities of the fractions have been evaluated by using nine in vitro assays and were compared to standard antioxidants such as ascorbic acid, alpha-tocopherol, curcumin and butylated hydroxyl toluene (BHT). All the fractions showed effective H-donor activity, reducing power, free radical scavenging activity, metal chelating ability and inhibition of beta-carotene bleaching. None of the fractions exerted an obvious pro-oxidant activity. The antioxidant property depends upon concentration and increased with increasing amount of the fractions. The free radical scavenging and antioxidant activities may be attributed to the presence of phenolic and flavonoid compounds present in the fractions. The results obtained in the present study indicate that the leaves of C. grandis are a potential source of natural antioxidant.


Evidence of validity of an inhalant-craving questionnaire.
Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach's Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users.


Lifetime Observation of Cognition and Physiological Parameters in Male Mice.
Laboratory mice are predominantly used for one experiment only, i.e., new mice are ordered or bred for every new experiment. Moreover, most experiments use relatively young mice in the range of late adolescence to early adulthood. As a consequence, little is known about the day-to-day life of adult and aged laboratory mice. Here we present a long-term data set with three consecutive phases conducted with the same male mice over their lifetime in order to shed light on possible long-term effects of repeated cognitive stimulation. One third of the animals was trained by a variety of learning tasks conducted up to an age of 606 days. The mice were housed in four cages with 12 animals per cage; only four mice per cage had to repeatedly solve cognitive tasks for getting access to water using the IntelliCage system. In addition, these learner mice were tested in standard cognitive tests outside their home-cage. The other eight mice served as two control groups living in the same environment but without having to solve tasks for getting access to water. One control group was additionally placed on the test set-ups without having to learn the tasks. Next to the cognitive tasks, we took physiological measures (body mass, resting metabolic rate) and tested for dominance behavior, and attractivity in a female choice experiment. Overall, the mice were under surveillance until they died a natural death, providing a unique data set over the course of virtually their entire lives. Our data showed treatment differences during the first phase of our lifetime data set. Young learner mice showed a higher activity, less growth and resting metabolic rate, and were less attractive for female mice. These effects, however, were not preserved over the long-term. We also did not find differences in dominance or effects on longevity. However, we generated a unique and valuable set of long-term behavioral and physiological data from a single group of male mice and note that our long-term data contribute to a better understanding of the behavioral and physiological processes in male C57Bl/6J mice.


Hydrated-ion ordering in electrical double layers.
In this work we revisit the surface forces measured between two atomically flat mica surfaces submerged in a reservoir of potassium nitrate (KNO(3)) solution. We consider a comprehensive range of concentrations from 0.08 mM to 2.6 M. The significantly improved resolution available from the extended surface force apparatus (eSFA) allows the distinction of hydration structures and hydrated-ion correlations. Above concentrations of 0.3 mM, hydrated-ion correlations give rise to multiple collective transitions (4 ± 1 Å) in the electrical double layers upon interpenetration. These features are interpreted as the result of hydrated-ion ordering (e.g. layering), in contrast to the traditional interpretation invoking water layering. The hydrated-ion layer adjacent to the surface (i.e. outer Helmholtz layer) is particularly well defined and plays a distinctive role. It can be either collectively expelled in a 5.8 ± 0.3 Å film-thickness transition or collectively forced to associate with the surface by external mechanical work. The latter is observed as a characteristic 2.9 ± 0.3 Å film-thickness transition along with an abrupt decrease of surface adhesion at concentrations above 1 mM. At concentrations as low as 20 mM, attractive surface forces are measured in deviation to the DLVO theory. The hydration number in the confined electrolyte seems to be significantly below that of the bulk. A 1-3 nm thick ionic layer solidifies at the surfaces at concentrations >100 mM, i.e. below bulk saturation.


Phenomenological Study on Mothering Experiences of the Married Immigrant Women in Urban Areas.
This study was done to explore the lived experience of pregnancy, childbirth, postpartum and early child rearing in married immigrant women in urban areas. Data were collected from February to April, 2011 through in-depth interviews. Nine immigrant women were selected in a metropolitan area through the purposive and snowball sampling method. After obtaining IRB permission and informed consent from the participants, all interviews were recorded with MP3 recorder and transcribed for analysis. Using the phenomenological approach, data collected through in-depth interviewing were analyzed following Colaizzi style. Data analysis revealed 4 categories and 10 themes related to pregnancy, childbirth, postpartum and early child rearing of married immigrant women in urban areas. These four categories were 'A clumsy foreigner's life with nostalgia', 'Crisis in the crisis', 'Unprepared for motherhood', and 'Living together with new family without regrets'. It was a common finding that they were not ready to be mothers because of the very short time for adjustment in Korea. Compared to rural, immigrant women urban women had various in social support systems. The results indicate that adequate education is needed for immigrant women regarding motherhood, and that this education should be culturally appropriate for these women.


Effect of dietary fat and the circadian clock on the expression of brain-derived neurotrophic factor (BDNF).
Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the brain and its decreased levels are associated with the development of obesity and neurodegeneration. Our aim was to test the effect of dietary fat, its timing and the circadian clock on the expression of BDNF and associated signaling pathways in mouse brain and liver. Bdnf mRNA oscillated robustly in brain and liver, but with a 12-h shift between the tissues. Brain and liver Bdnf mRNA showed a 12-h phase shift when fed ketogenic diet (KD) compared with high-fat diet (HFD) or low-fat diet (LFD). Brain or liver Bdnf mRNA did not show the typical phase advance usually seen under time-restricted feeding (RF). Clock knockdown in HT-4 hippocampal neurons led to 86% up-regulation of Bdnf mRNA, whereas it led to 60% down-regulation in AML-12 hepatocytes. Dietary fat in mice or cultured hepatocytes and hippocampal neurons led to increased Bdnf mRNA expression. At the protein level, HFD increased the ratio of the mature BDNF protein (mBDNF) to its precursor (proBDNF). In the liver, RF under LFD or HFD reduced the mBDNF/proBDNF ratio. In the brain, the two signaling pathways related to BDNF, mTOR and AMPK, showed reduced and increased levels, respectively, under timed HFD. In the liver, the reverse was achieved. In summary, Bdnf expression is mediated by the circadian clock and dietary fat. Although RF does not affect its expression phase, in the brain, when combined with high-fat diet, it leads to a unique metabolic state in which AMPK is activated, mTOR is down-regulated and the levels of mBDNF are high.


Selective upregulation of the flip-flop splice variants of AMPA receptor subunits in the rat spinal cord after hindpaw inflammation.
Glutamate receptors are involved in spinal nociceptive transmission and the development of persistent inflammatory hyperalgesia. It is unclear, however, whether there are changes in glutamate receptor gene expression associated with tissue injury. In the present study, we used reverse transcription-polymerase chain reaction (RT-PCR) to examine the modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor gene expression in the rat spinal cord by inflammation. Inflammation was introduced into the hindpaw by intraplantar injection of 0.2 ml of complete Freund's adjuvant (CFA). At 2 h-14 d after inflammation, total RNAs from L4,5 spinal cord were used for RT-PCR with primers targeted at eight flip-flop splice variants of the AMPA receptor subunits. It was found that the GluR1-flop mRNA was up-regulated at 2 h-5 h (P<0.05), down-regulated at 3 d (P=0.05), and returned to control levels at 7 d following inflammation. The GluR2-flip and GluR3-flop mRNAs were up-regulated at 5 h-1 d (P<0.05) and returned to control levels at 3 d after inflammation. The GluR1-flip mRNA was not detected in the samples and the mRNAs for other splice variants did not exhibit significant changes. Immunocytochemical analysis of GluR1 and GluR2 subunits indicate that the protein translation products of these subunits were also increased in the spinal cord. These results demonstrate an increased expression of AMPA receptor subunits that correlates with the acute phase of CFA-induced inflammation and hyperalgesia. Selective changes in the expression of the flip-flop splice variants of the AMPA receptor suggest a reorganization of the composition of the AMPA receptor complex and its involvement in the development of inflammatory hyperalgesia.


A simple test for synergy for a small number of combinations.
A method for detecting deviations from the Loewe additive drug combination reference model for in vitro drug combination experimentation is described. It is often difficult to fit a response surface model to drug combination data, especially in situations where the experimental design contains a sparse set of combinations. The literature does contain good response surface modeling approaches, but they tend to be complex and can be difficult to execute. It is especially difficult to check model quality when fitting to more than two combined agents. A simple method based on sound statistical principles is proposed that examines the mean response deviation of each combination from the predicted response under Loewe additivity. The method can readily handle any number of combined agents, does not require sophisticated modeling, and can even be programmed into Microsoft Excel without the use of macros. Several potential extensions to the method are discussed in detail. Computer-generated simulations demonstrate the statistical capabilities of the approach, and a real-data example is given to illustrate the method.


Chronic severe pyloric lesions in horses: 47 cases.
The clinical findings and outcome associated with chronic severe equine pyloric lesions have not been well described previously. To describe the history, clinical signs, endoscopic and ultrasound results, laboratory data, treatment, pathological findings and survival of horses with chronic severe pyloric lesions. Retrospective case series. Medical records from horses treated at clinics in Czech Republic and Germany in which chronic severe pyloric lesions were confirmed endoscopically and/or on post-mortem examination were reviewed. Forty-seven horses were identified, median age 3 years (range 0.8-16 years). There were 3 geldings, 23 mares and 19 stallions and the majority were Warmbloods (60%). The most common presenting signs were poor body condition (40; 87%), slow eating (39; 83%), recurrent colic (35; 74%) and selective appetite (30; 64%). The most consistent laboratory abnormality was hypoalbuminaemia (10; 36%). Slow gastric emptying was confirmed in 29 individuals during gastroscopy and/or ultrasonography. Endoscopy revealed distal oesophagitis in 9 of 47 horses, and severe equine squamous gastric disease in all cases. Pyloric lesions were depressed, flat or raised fibrinosuppurative pyloric ulcers and were seen in 45 (2 pylori were not seen endoscopically). Thirty-two cases were treated, with 28 responding well initially. All treated cases received anti-ulcer medication and four underwent gastrojejunostomy. Clinical signs recurred after medical treatment in at least 11 cases. Only 18 of 44 cases (41%) survived long term (3 were lost to follow-up). Horses diagnosed at 3 years of age or younger were significantly less likely to survive more than 6 months than older horses (27.8% vs. 72.2%, P<0.001). The study is retrospective, some records were incomplete and case identification was subjective. Chronic severe pyloric lesions can be associated with delayed gastric emptying identified with ultrasonography and/or endoscopy. The prognosis is poor in young horses.