Technical Note: Vendor miscalibration of preclinical orthovoltage irradiator identified through independent output check.
Accurate radiation dosimetry in radiobiological experiments is crucial for preclinical research in advancement of cancer treatment. Vendors of cell irradiators often perform calibration for end-users. However, calibration accuracy remains unclear due to missing detailed information on calibration equipment and procedures. In this study, we report our findings of a vender miscalibration of the radiation output and our investigation on the root cause of the discrepancy. Independent calibration verification for a commercial preclinical orthovoltage irradiator was conducted. Initially, in the absence of ionization chambers calibrated at kV energy, radiochromic films (EBT3) was first calibrated at MV energy. Energy correction factors from literature were used to create an in-house kV dosimetry system. The miscalibration identified with the in-house kV EBT3 dosimetry was later confirmed by ADCL calibrated ionization chambers (Exradin A1SL and PTW 30013) at kV energy. Ionization chambers were suspended in-air following TG-61 recommendation for output calibration. To investigate the root cause of the miscalibration, additional measurements were performed with ionization chambers placed on the shelf. A validated Monte Carlo simulation code was also used to investigate the impact of placing the ionization chamber on the shelf instead of suspending it in air during the vendor-performed calibration process. Up to a 6% dosimetry error was observed when comparing the vendor calibrated output of the preclinical irradiator with our independent calibration check. Further investigation showed incorrect setups in the vendor's calibration procedure which may result in dose errors up to 11% from the backscatter of the shelf board during calibration, and up to 5% from omitting temperature and pressure corrections to ionization chamber readings. Our study revealed large dose calibration errors caused by incorrect setup and the omission of temperature/pressure correction in the vendor's calibration procedure. The findings also highlighted the importance of performing an independent check of the dose calibration for preclinical kV irradiators. More absolute dosimetry training is needed for both vendors and end users for establishing accurate absolute dosimetry.


The effect of vocational rehabilitation on return-to-work rates post stroke: a systematic review.
Returning to work has been identified as an important rehabilitation goal following stroke. Twenty percent of stroke survivors are of working age. The purpose of this systematic review was to determine the effect of vocational rehabilitation programs on return-to-work rates post stroke. Searches were performed in electronic databases and Web-based sites. Studies were eligible for inclusion if they included an adult population of working age (18 to 65 years) who had survived a stroke and had participated in a vocational rehabilitation program. The exclusion criteria included any other type of rehabilitation that did not specifically address vocation, other diagnostic groups or studies where stroke population results were not reported independently, as well as publications not translated to English. The primary outcome was return-to-work rates. Six studies, involving a total of 462 participants, were included in this review. All studies were a retrospective single cohort design. The rates of employment following these vocational rehabilitation programs ranged from 12% to 49%. There was not an adequate number of high-quality trials to make recommendations that support or refute the use of specific vocational rehabilitation programs to increase return-to-work rates following a stroke. Standardized terminology definitions as well as quality, randomized controlled trials are required before conclusions can be made about the effect of vocational rehabilitation programs on the return-to-work rates for stroke survivors.


Investigation of Anaplasma marginale Seroprevalence in a Traditionally Managed Large California Beef Herd.
Recent observations by stakeholders suggested that ecosystem changes may be driving an increased incidence of bovine erythrocytic anaplasmosis, resulting in a reemerging cattle disease in California. The objective of this prospective cohort study was to estimate the incidence of Anaplasma marginale infection using seroconversion in a northern California beef cattle herd. A total of 143 Black Angus cattle (106 prebreeding heifers and 37 cows) were enrolled in the study. Serum samples were collected to determine Anaplasma marginale seroprevalence using a commercially available competitive enzyme-linked immunosorbent assay test kit. Repeat sampling was performed in seronegative animals to determine the incidence density rate from March through September (2013). Seroprevalence of heifers was significantly lower than that of cows at the beginning of the study (P < 0.001) but not at study completion (P = 0.075). Incidence density rate of Anaplasma marginale infection was 8.17 (95% confidence interval: 6.04, 10.81) cases per 1000 cow-days during the study period. Study cattle became Anaplasma marginale seropositive and likely carriers protected from severe clinical disease that might have occurred had they been first infected as mature adults. No evidence was found within this herd to suggest increased risk for clinical bovine erythrocytic anaplasmosis.


Augmentation of hepatoprotective potential of Aegle marmelos in combination with piperine in carbon tetrachloride model in wistar rats.
The current study investigated hepatoprotective and antioxidant effects of Aegle marmelos leaves extract. The major constituent present in the extract i.e. rutin was quantified by using HPLC. Further, the study explored hepatoprotective effect of A. marmelos (70% ethanol extract) in combination with piperine. The normal control and carbon tetrachloride (CCl4) administered rats were divided into 7 groups. Hepatic damage biomarkers were determined in serum samples and oxidative stress biomarkers (malondialdehyde, reduced glutathione, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase), pro-inflammatory and anti-inflammatory cytokines were determined in liver homogenates. CCl4 caused marked liver damage as evident by significant increased activities of serum alkaline phosphatase, bilirubin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, Interleukin 10 and Tumor necrosis factor-α levels compared to normal control. The oxidative stress parameters also significantly modulated in CCl4 group as compared to normal control. Treatment with A. marmelos reduced the severity of toxicity in a dose dependent fashion and the results of A. marmelos extract 50 mg/kg group were comparable to silymarin group. The low dose of A. marmelos extract (25 mg/kg) per se did not significantly reversed the hepatotoxicity but low dose of A. marmelos in combination with piperine showed significant reversal of hepatotoxicity. In conclusion, A. marmelos exerts potential hepatoprotective activity through its antioxidant and anti-inflammatory properties which was enhanced by co-treatment with piperine.


Where's my entourage? The curious case of 2-oleoylglycerol, 2-linolenoylglycerol, and 2-palmitoylglycerol.
2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid in the brain and an agonist at two cannabinoid receptors (CB1 and CB2). The synthesis, degradation and signaling of 2-AG have been investigated in detail but its relationship to other endogenous monoacylglycerols has not been fully explored. Three congeners that have been isolated from the CNS are 2-linoleoylglycerol (2-LG), 2-oleoylglycerol (2-OG), and 2-palmitoylglycerol (2-PG). These lipids do not orthosterically bind to cannabinoid receptors but are reported to potentiate the activity of 2-AG, possibly through inhibition of 2-AG degradation. This phenomenon has been dubbed the 'entourage effect' and has been proposed to regulate synaptic activity of 2-AG. To clarify the activity of these congeners of 2-AG we tested them in neuronal and cell-based signaling assays. The signaling profile for these compounds is inconsistent with an entourage effect. None of the compounds inhibited neurotransmission via CB1 in autaptic neurons. Interestingly, each failed to potentiate 2-AG-mediated depolarization-induced suppression of excitation (DSE), behaving instead as antagonists. Examining other signaling pathways we found that 2-OG interferes with agonist-induced CB1 internalization while 2-PG modestly internalizes CB1 receptors. However in tests of pERK, cAMP and arrestin recruitment, none of the acylglycerols altered CB1 signaling. Our results suggest 1) that these compounds do not serve as entourage compounds under the conditions examined, and 2) that they may instead serve as functional antagonists. Our results suggest that the relationship between 2-AG and its congeners is more nuanced than previously appreciated.


Chinese Medicine as an Adjunctive Treatment for Gastric Cancer: Methodological Investigation of meta-Analyses and Evidence Map.
Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs. Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005). Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (β = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (β = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis. Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.


20(S)-Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway.
20(S)-ginsenoside Rg3 [20(S)-Rg3)], one of the main constituents isolated from Panax ginseng, has been shown to have an anti-cancer effect and to induce apoptosis by interfering with several signaling pathways. However, the molecular mechanisms of AMP-activated protein kinase (AMPK) associated with apoptosis in HT-29 colon cancer cells remain unclear. In the present study, we investigated whether 20(S)-Rg3 exerts an anti-proliferative effect and induces apoptosis by modulating the AMPK signaling pathway in HT-29 cells. 20(S)-Rg3-treated cells displayed several apoptotic features, including DNA fragmentation, proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) and morphological changes. 20(S)-Rg3 down-regulated the expression of anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl2), up-regulated the expression of pro-apoptotic protein of p53 and Bcl-2-associated X protein (Bax), and caused the release of mitochondrial cytochrome c, PARP, caspase-9 and caspase-3. However, 20(S)-Rg3-induced apoptosis was completely abolished in the presence of compound C (AMPK inhibitor) or small interfering RNA for AMPK (siAMPK). In addition, STO-609 (CaMKKβ inhibitor) attenuated 20(S)-Rg3-induced AMPK activation and apoptosis. These results suggest that 20(S)-Rg3-induced apoptosis in HT-29 cells is mediated via the AMPK signaling pathway, and that 20(S)-Rg3 is capable of inducing apoptosis in colon cancer.


Is hybrid cardiac rehabilitation superior to traditional cardiac rehabilitation?
The current COVID-19 pandemic imposes changes in the management of cardiac pathologies. Cardiac rehabilitation needs to define new protocols to welcome patients back. In connection with the observations of the European Association of Preventive Cardiology, the choice of cardiac tele-rehabilitation appeared to be unavoidable. This retrospective research based on data from the Program for the Medicalisation of Information Systems (PMSI) and the electronic medical record analyzes the effect of Hybrid Cardiac Rehabilitation. One hundred and ninety-two patients (29 females and 163 males) with an average of 56.9 years old (±10.3) were able to benefit from a Hybrid Cardiac Rehabilitation program. The data concerning the Stress Test and the Wall Squat Test were collected. We have noticed that patients had improved their cardiorespiratory capacity on the initial and final Stress Test 6.6 (±1.8) MET to 8.2 (±1.9) MET (p < 0.0001). We also found that patients improved lower limb muscle strength 75.1 (±44.8) seconds to 105.7 (±49.7) seconds (p < 0.0001). Hybrid Cardiac Rehabilitation protocols can be set up in this pandemic situation. The programme effectiveness appears to be comparable to the traditional model. However, additional studies are needed to determine the effectiveness of this programme in the long term.


Alteration of the secondary structure of newly synthesized DNA from murine bone marrow cells by 5-fluorouracil.
The present study evaluates the effects of 5-fluorouracil (FUra) on the structure of newly synthesized DNA purified from bone marrow cells. DNA synthesis was decreased by 30 and 45% of control in the presence of 19 and 100 microM FUra, respectively. Furthermore at these concentrations of FUra, the DNA strand sizes were smaller as determined by alkaline sucrose gradients. Enzymatic digestion of the DNA demonstrated that most of the FUra (greater than 90%) was localized in the internucleotide linkage and not at the chain terminus. As the concentration of FUra was varied, the percentage of FUra at the chain terminus was unchanged, suggesting that the decrease in chain size as well as inhibition of DNA synthesis was not due to chain termination. DNA that had been synthesized in the presence of FUra was shown to fragment after increasing time as demonstrated by alkaline sucrose gradient analysis. This time-dependent fragmentation was associated with an increased number of strand breaks as determined by neutral and alkaline sucrose gradient analysis. A parallel study demonstrated a time-dependent excision of FUra from DNA over this same time period. In summary, these studies demonstrate an association between the excision of FUra from DNA and the changes in secondary structure of newly synthesized DNA.


Affinity capture using vancomycin-bound magnetic nanoparticles for the MALDI-MS analysis of bacteria.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides a straightforward means to differentiate microorganism species based on mass spectral fingerprinting. The pathogen cell concentration in an infected sample, however, is generally lower than that capable of being detected directly by MALDI-MS. Furthermore, the presence of proteins or metabolites in biological fluids always causes unavoidable interference for the identification of microorganism species. Vancomycin, which binds to D-Ala-D-Ala moieties on the cell walls of Gram-positive bacteria and, therefore, inhibits peptidoglycan synthesis, is one of the most potent antibiotics. Thus, we have employed vancomycin-modified magnetic nanoparticles as affinity probes to selectively trap Gram-positive pathogens from sample solutions; i.e., these bacteria can be isolated from sample solutions by applying a magnetic field. The isolated cells could then be characterized by MALDI-MS. This approach effectively reduces the interference of protein and metabolite signals in the mass spectra of Gram-positive bacteria because vancomycin has such high specificity for the D-Ala-D-Ala units of the cell walls. The lowest cell concentration we detected for both Staphylococcus saprophyticus and Staphylococcus aureus in a urine sample (3 mL) was approximately 7 x 10(4) cfu/mL.


[Bilateral tonsillar hypertrophy as the first manifestation of B cell-small lymphocytic lymphoma with interfolicular pattern].
B-cell small lymphocytic lymphoma typically involves nodal or extranodal tissues as a diffuse proliferation with proliferation centers (pseudofollicules) obliterating normal architecture. But there are unusual patterns of involvement including interfollicular pattern that can be difficult to recognize histologically and probably represent partial or early involvement by neoplasm. Tonsillar lymphoma usually presents either as a unilaterally enlarged palatine tonsil or as an ulcerative and fungating lesion over the tonsillar area. Most lymphomas that involve the tonsil are diffuse large B cell lymphomas and primary low-grade lymphomas are exceptional. We present a primary B-cell small lymphocytic lymphoma affecting palatine tonsils with interfollicular pattern in a 54 year-old man that clinically presented with symmetric / bilateral tonsillar enlargement and sleep apnea.


Mephedrone (methylmethcathinone) in toxicology casework: a Northern Ireland perspective.
Mephedrone (4-methylmethcathinone) is the beta-keto analogue of 4-methylmethylamphetamine. Before its control in April 2010, it became popular as a legal high in the United Kingdom, displacing methylenedioxymethylamphetamine as the stimulant drug of choice. The drug has stimulant and psychoactive properties, and therefore has forensic significance in criminal and morbid toxicology. The purpose of this study was to survey casework involving the drug (impaired driving and sudden death). The cases were received in the laboratory for analysis between late 2009 and the end of 2010. Analysis of blood samples for mephedrone was conducted by liquid chromatography-mass spectrometry (LC-MS). Routine screening for alcohol and a range of other pharmaceuticals and drugs of abuse was conducted using a combination of enzyme-linked immunoassay, gas chromatography (GC) headspace, GC-MS and high-performance liquid chromatography with diode array detection. Mephedrone was detected in a total of 12 fatal cases. Most of these cases involved death by mechanical means; in two cases, death was attributed directly to mephedrone intoxication (blood concentrations of 2.1 and 1.94 mg/L). Mephedrone was detected in a total of 32 impaired driving cases. Blood concentrations ranged up to 0.74 mg/L (mean 0.21, median 0.10). The casework evidence in this study indicated that recreational use of the drug can produce to blood levels as high as 0.74 mg/L, although the most common value encountered is likely to lie between 0.2 and 0.3 mg/L.


Low vision services for vision rehabilitation in the United Kingdom.
Little is known about the distribution and methods of delivery of low vision services across the United Kingdom. The purpose of this study was to determine the type and location of low vision services within the UK. Survey by means of a 29 point postal questionnaire, followed when necessary by a five point telephone questionnaire. All known potential providers of low vision services (n = 2539) including hospitals (n = 277), optician/optometry practices (n = 1683), social services (n = 177), voluntary groups (n = 190), specialist teachers (n = 205), and universities (n = 6) were surveyed. For each service provider, the type, magnitude, and geographical location were determined. The distribution of services across the United Kingdom and the ratio of providers to population density of people with a visual impairment were mapped using the Geographic Information System (GIS). Data were obtained on 1945 (77%) service providers: 1679 (66%) responded to the postal questionnaire and 266 (11%) to the telephone questionnaire. Of all respondents, 59% (n = 1135) offer some form of help to people with a visual disability, of which 26% (n = 497) only sell magnifiers and 33% (n = 638) provide low vision services. It is estimated that in total just under 155,000 low vision consultations are offered annually, the bulk of which are provided by hospital eye departments. The distribution was geographically uneven and there appears to be scarcity in some areas. When compared to the probable number of people with a visual impairment in the UK there are apparent inadequacies in service provision in terms of distribution, magnitude, and coordination. The results highlight a need to review current services.


Nucleation and growth of the Naica giant gypsum crystals.
The Cave of Giant Crystals in the Naica mine (Mexico) is one of the most amazing displays of mineral beauty ever created in nature. In addition to the colossal crystals of gypsum, which in some cases exceed eleven meters in length and one meter in thickness, the scenery fashioned by the crystalline beams that thrust through the darkness of the cave from floor to ceiling with a luster like moonlight is a unique example of harmony based on crystal symmetry. We review the crystallogenesis of this remarkable and challenging phenomenon of mineralization near equilibrium that can be used to teach the basics of nucleation and crystal growth.


Efficient expression of membrane-bound water channel protein (Aquaporin Z) in Escherichia coli.
In order to explore the possibility of preparing a high-efficiency aquaporin-based biofilter, an efficient approach for expression of membrane-bound Aquaporin Z (AqpZ) in E. coli was proposed. The AqpZ gene was amplified by means of PCR, and two expression vectors (pET28-AqpZ and pET32-AqpZ) were constructed. The channel protein of interest was synthesized in E. coli BL21(DE3)/pET32-AqpZ as an insoluble fusion protein linked with trxA. However, with BL21(DE3)/pET28-AqpZ, significant amount of AqpZ fused only with 6-His (6-His-AqpZ) could be expressed, correctly folded and targeted into the membrane. Under the optimized culture conditions, the highest expression level (9.05 mg/l) of membrane-bound 6-His-AqpZ was achieved with BL21(DE3)/pET28-AqpZ, and an additional amount (2.35 mg/l) was expressed concomitantly as the inclusion body form. This expression result was 3.5 times higher than that in the previous studies.


Isolation of Lamina Propria Mononuclear Cells from Murine Colon Using Collagenase E.
The intestine is the home to the largest number of immune cells in the body. The small and large intestinal immune systems police exposure to exogenous antigens and modulate responses to potent microbially derived immune stimuli. For this reason, the intestine is a major target site of immune dysregulation and inflammation in many diseases including but, not limited to inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, graft-versus-host disease (GVHD) after bone marrow transplantation (BMT), and many allergic and infectious conditions. Murine models of gastrointestinal inflammation and colitis are heavily used to study GI complications and to pre-clinically optimize strategies for prevention and treatment. Data gleaned from these models via isolation and phenotypic analysis of immune cells from the intestine is critical to further immune understanding that can be applied to ameliorate gastrointestinal and systemic inflammatory disorders. This report describes a highly effective protocol for the isolation of mononuclear cells (MNC) from the colon using a mixed silica-based density gradient interface. This method reproducibly isolates a significant number of viable leukocytes while minimizing contaminating debris, allowing subsequent immune phenotyping by flow cytometry or other methods.


LI-RADS Treatment Response versus Modified RECIST for Diagnosing Viable Hepatocellular Carcinoma after Locoregional Therapy: A Systematic Review and Meta-Analysis of Comparative Studies.
To systematically compare the performance of liver imaging reporting and data system treatment response (LR-TR) with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for diagnosing viable hepatocellular carcinoma (HCC) treated with locoregional therapy (LRT). Original studies of intra-individual comparisons between the diagnostic performance of LR-TR and mRECIST using dynamic contrast-enhanced CT or MRI were searched in MEDLINE and EMBASE, up to August 25, 2021. The reference standard for tumor viability was surgical pathology. The meta-analytic pooled sensitivity and specificity of the viable category using each criterion were calculated using a bivariate random-effects model and compared using bivariate meta-regression. For five eligible studies (430 patients with 631 treated observations), the pooled per-lesion sensitivities and specificities were 58% (95% confidence interval [CI], 45%-70%) and 93% (95% CI, 88%-96%) for the LR-TR viable category and 56% (95% CI, 42%-69%) and 86% (95% CI, 72%-94%) for the mRECIST viable category, respectively. The LR-TR viable category provided significantly higher pooled specificity (p < 0.01) than the mRECIST but comparable pooled sensitivity (p = 0.53). The LR-TR algorithm demonstrated better specificity than mRECIST, without a significant difference in sensitivity for the diagnosis of pathologically viable HCC after LRT.


The use of traditional medicine by Ghanaians in Canada.
Research into health and health-care seeking behaviour amongst immigrant populations suggests that culturally-based behaviours change over time towards those prevalent in the host culture. Such acculturation of immigrant groups occurs as part of the interaction of immigrants with mainstream culture. This study examined the acculturation of Ghanaian immigrants in Greater Toronto Area (Canada) focusing particularly on attitudes towards and usage of Ghanaian traditional medicine (TRM). The study used both quantitative and qualitative methods. Structured questionnaire interviews were conducted with a sample of Ghanaians in active collaboration with the Ghanaian-Canadian Association in the Greater Toronto Area (GTA). A total of 512 questionnaire interviews were conducted. In addition, three focus groups of nine participants each were conducted with a sub-sample of Ghanaians in Canada. Both the questionnaire and the focus groups indicated that nearly 73% of the Ghanaian immigrants in Canada have a positive attitude toward Ghanaian TRM. This is in comparison with less than 30% who have changed their attitude for various reasons. Some of the attraction of TRM lies in its holistic origin. Ghanaians in the GTA have been pursuing 'integration' and 'assimilation' in their acculturation in Canada. Some have given up or modified some of their attitudes and opinions toward TRM to embrace the 'modern' or 'civilized' way of living. There is the need for health care providers and other stakeholders to be aware of the influence of religion on African immigrants during their acculturation process. Although modernity is said to be founded on the 'ruthless undermining of tradition', there is no evidence to suggest that Ghanaian traditional religion has been undermined to such an extent that there is a major change in attitudes towards TRM.


The study on expression of CIAPIN1 interfering hepatocellular carcinoma cell proliferation and its mechanisms.
Liver cancer is one of the common gastrointestinal cancers. This study was designed to investigate the effect of the cytokine-induced apoptosis inhibitor 1 (CIAPIN1) on hepatocellular carcinoma cell proliferation and invasion. To establish a low and high expression of CIAPIN1 in hepatoma cell lines, pGPU6/GFP/Neo and CIAPIN1 siRNA vectors were constructed. The growth curve of liver cancer cells with a low and high expression of CIAPIN1 was measured by MTT assay and colony formation in soft. The effect of overexpression and inhibition of CIAPIN1 on the expressions of cell cycle proteins Cyclin D1, CDK2, CDK4, and Cyclin E were detected by western blot. As compared with the low expression group, the cells in CIAPIN1 high expression group showed a significant decrease in proliferation (p < 0.05). In addition, the colony-forming ability of cells with high expression of CIAPIN1 was decreased significantly (p < 0.01). Furthermore, the expressions of Cyclin D1 CDK2, CDK4, and Cyclin E in high expression group were significantly increased (p < 0.01). CIAPIN1 played an important role in the proliferation of liver cancer cells through increasing the expressions of cell cycle related proteins Cyclin D1, CDK2, CDK4, and Cyclin E.


Identification of three prolactin-related hormones as markers of invasive trophoblasts in the rat.
An expressed-sequence tag database search has identified three rat cDNA clones in the prolactin/growth hormone family, including a homologue of mouse proliferin-related protein (PRP). The encoded proteins of the two novel clones, designated prolactin-like proteins L (PLP-L) and M (PLP-M), are predicted to be synthesized as precursors of 229 and 227 amino acids, modified by N-linked glycosylation, and secreted as mature glycoproteins of 199 and 200 residues, respectively. Murine homologues to PLP-L and PLP-M were also identified. The open reading frame of rat PRP encodes a precursor protein of 245 amino acids and predicts a secreted 215-amino acid glycoprotein with 81% identity to mouse PRP. All three rat mRNAs are expressed in the placenta, and expression is not detected in other tissues. PLP-L mRNA expression is observed from Days 11-20, with highest levels at Day 13; highest levels of PLP-M are observed from Day 11 until parturition, with peak levels also on Day 13; and highest levels of PRP are also observed from Day 11 until term, with maximal expression on Day 17. All three genes are most highly expressed in invasive trophoblast cells lining the central placental vessel. The identification of molecular markers for endovascular trophoblasts serves to highlight the invasive nature of rodent placentation and may prove useful for future studies of placental function.


[Mechanisms of the joint action of cortisol and adenosine on peripheral blood lymphocytes in bronchial asthma].
The effect of adenosine (10(-6) M) on the cyclic AMP production in lymphocytes of peripheral blood of patients with bronchial asthma and healthy donors was studied. Cells response to adenosine-induced stimulation was significantly decreased for asthmatic patients as compared to normal subjects. Cortisol (3 x 10(-6) M) was shown to be able to normalize suppressed function of cells of the patients. Adenosine (10(-6) M) changed the distribution of hormone-receptor complexes in lymphocytes of the healthy donors to cause increment of the number of 3H cortisol-receptor complexes bound by nucleus. The treatment of lymphocytes of patients with adenosine didn't give any change in specific nuclear 3H cortisol binding. The obtained results may be used for a rational choice of hormonal therapy.


Preparation of Superhydrophobic Film on Ti Substrate and Its Anticorrosion Property.
Superhydrophobic films were fabricated on a titanium substrate with or without anodizing by using a self-assembling method. Firstly, the pretreatments of mechanical polishing/anodizing or mechanical polishing only were conducted, respectively. Subsequently, the preparation of polydopamine film layer, deposition of nano-silver particles, and post modification of 1H,1H,2H,2H-perfluorodecanethiol were performed on the surface of the pretreated substrate. The surface morphologies, compositions, wettability, and corrosion resistance of the films were investigated with scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), water contact angle measurements, and electrochemical tests, respectively. Meanwhile, the effect of the deposition time in the silver nitrate solution on the hydrophobicity of the specimen surface was investigated. The result showed that with the increase of deposition time, the hydrophobic property enhanced gradually. The surface deposited for 7 h exhibited an optimum hydrophobic effect, which was characterized with a large water contact angle (WCA) of 154°, and the surface was rather rough and covered by a relatively uniform layer of micro-nano silver particles. The excellent hydrophobicity was attributed to a rough stratified microstructure along with the low surface energy. The electrochemical measurements showed that the existence of the superhydrophobic film can effectively enhance the corrosion resistance of Ti samples.


The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.
To fulfill the bioenergetic and biosynthetic demand of proliferation, T cells reprogram their metabolic pathways from fatty acid β-oxidation and pyruvate oxidation via the TCA cycle to the glycolytic, pentose-phosphate, and glutaminolytic pathways. Two of the top-ranked candidate transcription factors potentially responsible for the activation-induced T cell metabolic transcriptome, HIF1α and Myc, were induced upon T cell activation, but only the acute deletion of Myc markedly inhibited activation-induced glycolysis and glutaminolysis in T cells. Glutamine deprivation compromised activation-induced T cell growth and proliferation, and this was partially replaced by nucleotides and polyamines, implicating glutamine as an important source for biosynthetic precursors in active T cells. Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines. Therefore, a Myc-dependent global metabolic transcriptome drives metabolic reprogramming in activated, primary T lymphocytes. This may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.


Diverse Roles of PUF Proteins in Germline Stem and Progenitor Cell Development in C. elegans.
Stem cell development depends on post-transcriptional regulation mediated by RNA-binding proteins (RBPs) (Zhang et al., 1997; Forbes and Lehmann, 1998; Okano et al., 2005; Ratti et al., 2006; Kwon et al., 2013). Pumilio and FBF (PUF) family RBPs are highly conserved post-transcriptional regulators that are critical for stem cell maintenance (Wickens et al., 2002; Quenault et al., 2011). The RNA-binding domains of PUF proteins recognize a family of related sequence motifs in the target mRNAs, yet individual PUF proteins have clearly distinct biological functions (Lu et al., 2009; Wang et al., 2018). The C. elegans germline is a simple and powerful model system for analyzing regulation of stem cell development. Studies in C. elegans uncovered specific physiological roles for PUFs expressed in the germline stem cells ranging from control of proliferation and differentiation to regulation of the sperm/oocyte decision. Importantly, recent studies started to illuminate the mechanisms behind PUF functional divergence. This review summarizes the many roles of PUF-8, FBF-1, and FBF-2 in germline stem and progenitor cells (SPCs) and discusses the factors accounting for their distinct biological functions. PUF proteins are conserved in evolution, and insights into PUF-mediated regulation provided by the C. elegans model system are likely relevant for other organisms.


Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances.
This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway.


The effect of scan parameters on cone beam CT trabecular bone microstructural measurements of human mandible.
The objective of this study was to investigate the effect of different cone beam CT scan parameters on trabecular bone microstructure measurements. A human mandibular cadaver was scanned using a cone beam CT (3D Accuitomo 170; J.Morita, Kyota, Japan). 20 cone beam CT images were obtained using 5 different fields of view (4×4 cm, 6×6 cm, 8×8 cm, 10×10 cm and 10×5 cm), 2 types of rotation steps (180° and 360°) and 2 scanning resolutions (standard and high). Image analysis software was used to assess the trabecular bone microstructural parameters (number, thickness and spacing). All parameters were measured twice by one trained observer. Intraclass correlation coefficients showed high intraobserver repeatability (intraclass correlation coefficient, 0.95–0.97) in all parameters across all tested scan parameters. Trabecular bone microstructural measurements varied significantly, especially in smaller fields of view (p = 0.001). There was no significant difference in the trabecular parameters when using different resolutions (number, p = 0.988; thickness, p = 0.960; spacing, p = 0.831) and rotation steps (number, p = 1.000; thickness, p = 0.954; spacing, p = 0.759). The scan field of view significantly influences the trabecular bone microstructure measurements. Rotation steps (180° or 360°) and resolution (standard or high) selections are not relevant.


Preventative diabetes self-care management practices among individuals with diabetes and mental health stress.
The study purpose examines diabetes self-care management practices among individuals diagnosed with diabetes with and without mental health stress. Pooled cross-sectional data (2011-2016) from the Household Component of the Medical Expenditure Panel Survey (HC-MEPS) were used. The sample consisted of individuals ages 25-85 years (n = 13,193; weighted n = 23,559,975). Dependent variables were engagement in moderate/vigorous physical exercise five times weekly, receiving dilated eye exams, foot checks, treating diabetes with diet modification or insulin injections, and eating fewer high fat/cholesterol foods. The independent variable was diabetes with and without mental health stress. The study controlled for predisposing, enabling, and need factors. Compared with individuals with diabetes without mental health stress, findings indicate individuals with diabetes and low or mild/moderate mental health stress were more likely to treat diabetes with diet modification and to restrict high fat/cholesterol food. Individuals with diabetes and severe mental health stress were more likely to restrict high fat/cholesterol. Additionally, individuals with mild/moderate to severe mental health stress were less likely to engage in diabetes care behavior. Mental health stress is represented as a non-specific psychological distress index summary during the past 30 days and may not be an actual representation of overall distress in a person's life. There were no variables distinguishing diabetes type or severity. The study uses self-reported data and is cross-sectional. Mental health stress may contribute to individuals not engaging in self-management practices. It would be beneficial to incorporate psychosocial services for individuals with diabetes and mental health stress.


Overexpression of WNT2 and TSG101 genes in colorectal carcinoma.
Colorectal carcinoma (CRC) arises as a result of mutational activation of oncogenes coupled with inactivation of tumour suppressor genes. Mutations in APC, K-ras and p53 have been commonly reported. In a previous study by our group, the tumour susceptibility gene 101 (TSG101) were found to be persistently upregulated in CRC cases. TSG101 was reported to be closely related to cancers of the breast, brain and colon, and its overexpression in human papillary thyroid carcinomas and ovarian carcinomas had previously been reported. The wingless-type MMTV integration site family member 2 (WNT2) is potentially important in the Wnt/beta-catenin pathway and upregulation of WNT2 is not uncommon in human cancers. In this study, we report the investigation for mutation(s) and expression pattern(s) of WNT2 and TSG101, in an effort to further understand their role(s) in CRC tumourigenesis. Our results revealed no mutation in these genes, despite their persistent upregulation in CRC cases studied.


[Unsafe abbreviations in medical prescriptions and their association with medication errors: a review].
The prescription of medications is a weak link in the therapeutic chain of a drug. Medication errors can be associated with the use of so-called unsafe abbreviations in medical prescription. When they are mistakenly interpreted by the person who reads the prescription, error becomes imminent. We herein review the literature about the use of unsafe abbreviations in medical prescriptions and their association with medication errors. PubMed and Lilacs were reviewed, and 29 studies were analyzed, extracting information about the use of abbreviations, common abbreviations, reasons for their use and tools to reduce this conduct. A list with the main risky health abbreviations adapted to Chile was generated. It became clear that the use of abbreviations has increased, appearing in almost all medical prescriptions. The most commonly used abbreviations are the acronym "u" referring to units, followed by "sc" referring to subcutaneous. One of the causes for the use of acronyms the limited time that doctors have at the time of prescription. One way to reduce the use of these abbreviations, is to remind constantly about those that may have the greatest risk in each health institution. A list of unsafe abbreviations, to be used by Chilean health services, is proposed.


Liver-first approach of colorectal cancer with synchronous hepatic metastases: A reverse strategy.
Recently, there has been a change in the strategy of how synchronous colorectal hepatic metastases are attributed to the development of more valuable protocols of chemotherapy and radiotherapy for neoadjuvant treatment of colorectal neoplasms and their hepatic metastases. There is a consensus that patients with synchronous colorectal hepatic metastases have lower survival than those with metachronous colorectal hepatic metastases. Currently, controversy remains concerning the best approach is sequence in a patient with colorectal cancer and synchronous hepatic metastases resection. To obtain a better patient selection, the authors have suggested the initial realization of systemic chemotherapy in the circumstance of patients with colorectal tumor stage IV, since these patients have a systemic disease. The rationale behind this liver-first strategy is initially the control of synchronous hepatic metastases of colorectal carcinoma, which can optimize a potentially curative hepatic resection and longstanding survival. The liver-first strategy procedure is indicated for patients with colorectal hepatic metastases who require downstaging therapy to make a curative liver resection possible. Thus, the liver-first strategy is considered an option in cases of rectal carcinoma in the early stage and with limited or advanced synchronous colorectal hepatic metastases or in case of patients with asymptomatic colorectal carcinoma, but with extensive liver metastases. Patients undergoing systemic chemotherapy and with progression of neoplastic disease should not undergo hepatic resection, because it does not change the prognosis and may even make it worse. To date, there have been no randomized controlled trials on surgical approach of colorectal synchronous hepatic metastases, despite the relatively high number of available manuscripts on this subject. All of these published studies are observational, usually retrospective, and often non-comparative. The patient selection criteria for the liver-first strategy should be individualized, and the approach of these patients should be performed by a multidisciplinary team so its benefits will be fully realized.


LONGITUDINAL CORRELATION OF ELLIPSOID ZONE LOSS AND FUNCTIONAL LOSS IN MACULAR TELANGIECTASIA TYPE 2.
To compare ellipsoid zone (EZ) loss and functional loss in macular telangiectasia (MacTel) type 2 longitudinally. Prospective natural history study. Ellipsoid zone loss was measured in en-face images created from spectral domain optical coherence tomography. Functional loss was assessed by best-corrected visual acuity and microperimetry, counting the number of test points with impaired function. A total of 56 eyes of 31 participants were followed for 4.5 ± 1.2 years. Ellipsoid zone loss was 18,600 ± 3,917.3 pixel at baseline (≈0.59 mm) and increased 2,627.8 ± 427.9 pixel (≈0.08 mm) per year. Best-corrected visual acuity decreased 2.2 ± 0.9 letters per year. Change in EZ loss correlated significantly with change in relative and absolute scotomas (r = 0.62; P-value < 0.0001 and r = 0.72; P-value < 0.0001), but not with loss of best-corrected visual acuity. Functional loss showed a similar frequency of progression as EZ loss, but a higher rate of "regression," likely due to higher variability of the measurement, assuming a progressive neurodegenerative disease. The results of the authors support EZ loss as surrogate measure for visual function in MacTel type 2. Being objective, EZ loss might be considered more suitable than microperimetry as primary end point in future interventional trials.


Sex Ratio of Parental Investment in Colonies of the Social Wasp Polistes fuscatus.
Field estimates of parental investment in the two sexes in the social paper wasp Polistes fuscatus indicate that the mother's interests, rather than those of her worker offspring, are realized. Local competition for mates seemed to be absent, and the population investment ratio was not significantly different from 1:1. Workers are not more closely related to the brood they tend than they would be to their own offspring. The 3/4 relationship between sisters in haplodiploid species cannot account for the maintenance of eusociality in this case.


Comprehensive, structurally-informed alignment and phylogeny of vertebrate biogenic amine receptors.
Biogenic amine receptors play critical roles in regulating behavior and physiology in both vertebrates and invertebrates, particularly within the central nervous system. Members of the G-protein coupled receptor (GPCR) family, these receptors interact with endogenous bioamine ligands such as dopamine, serotonin, and epinephrine, and are targeted by a wide array of pharmaceuticals. Despite the clear clinical and biological importance of these receptors, their evolutionary history remains poorly characterized. In particular, the relationships among biogenic amine receptors and any specific evolutionary constraints acting within distinct receptor subtypes are largely unknown. To advance and facilitate studies in this receptor family, we have constructed a comprehensive, high-quality sequence alignment of vertebrate biogenic amine receptors. In particular, we have integrated a traditional multiple sequence approach with robust structural domain predictions to ensure that alignment columns accurately capture the highly-conserved GPCR structural domains, and we demonstrate how ignoring structural information produces spurious inferences of homology. Using this alignment, we have constructed a structurally-partitioned maximum-likelihood phylogeny from which we deduce novel biogenic amine receptor relationships and uncover previously unrecognized lineage-specific receptor clades. Moreover, we find that roughly 1% of the 3039 sequences in our final alignment are either misannotated or unclassified, and we propose updated classifications for these receptors. We release our comprehensive alignment and its corresponding phylogeny as a resource for future research into the evolution and diversification of biogenic amine receptors.


Unplanned return to operating room after lower extremity endovascular intervention is an independent predictor for hospital readmission.
Hospital readmissions after surgical operations are preventable and are now counted as a quality metric. Patients with peripheral arterial disease often have several serious medical comorbidities. With advancements in endovascular technology and increasing comfort level of vascular surgeons, more and more patients with peripheral arterial disease are being treated with endovascular therapy. Most of these interventions are done as same-day operations. This study retrospectively reviewed the factors associated with hospital readmission after lower extremity endovascular interventions. This study used the 2013 endovascular repair-targeted American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database and generalized 2013 general and vascular surgery Program User Files. Patient, diagnosis, and procedure characteristics of patients undergoing lower extremity endovascular surgery were assessed. Multivariate logistic regression analysis was used to determine independent risk factors for hospital readmission ≤30 days after surgery. During 2013, 1096 patients (61% men, 39% women) underwent lower extremity endovascular interventions. Indications for operations included claudication (40%), critical limb ischemia with rest pain (19%), critical limb ischemia with tissue loss (35%), and others (6%) Among these patients, 147 (13.4%) were readmitted to the hospital ≤30 days after surgery, and ∼46% of all readmissions were ≤2 weeks after the discharge The following factors had significant associations with readmission: smoking (odds ratio [OR], 0.52, 95% confidence interval [CI], 0.3-0.9), noninsulin-dependent diabetes mellitus (OR, 1.65; 95% CI, 0.9-3.2), dyspnea (OR, 1.9; 95% CI, 1-3.7), insulin-dependent diabetes mellitus (OR, 2.1; 95% CI, 1.2-3.6), body mass index >30 kg/m2 (OR, 2.5; 95% CI, 1.3-5.1), dependent functional status (OR, 2.6; 95% CI, 1.4-4.8), emergent surgery (OR, 4.3; 95% CI, 1.9-9.6), and unplanned return to the operating room (OR, 8.3; 95% CI, 4.7-14.7). Readmission after lower extremity endovascular intervention is a serious complication. Various factors place a patient at a high risk for readmission. High body mass index, unplanned return to the operating room, insulin-dependent diabetes mellitus, noninsulin-dependent diabetes mellitus, nonsmoking status, dyspnea, dependent functional status, and emergency operation are independent risk factors for hospital readmission. Return to operating room is associated with an 8.3-fold increase in hospital readmission.


Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule.
Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH), active vitamin D 3, and fibroblast growth factor 23 (FGF23). The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms responsible for phosphate reclamation are well described, and emerging work is delineating the molecular identity of the paracellular shunt wherein calcium permeates the proximal tubular epithelium. Significant experimental work has delineated the molecular effects of PTH and FGF23 on these processes as well as their regulation of active vitamin D 3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms of calcium and phosphate reabsorption from the proximal tubule and how they are influenced by the phospho- and calciotropic hormones acting on this segment and then consider the implications on both renal calcium and phosphate handling as well as whole body mineral balance.


Endovascular management of a mandibular arteriovenous malformation in a patient with severe hemophilia a.
The unusual case of a mandibular arteriovenous malformation in a patient with severe hemophilia A and hepatitis C is reported. Supplementary substitution of various coagulation factors allowed direct puncture and intralesional injection of a liquid adhesive, resulting in complete anatomic and clinical cure without peri- or postoperative bleeding. Replacement therapy providing normal levels of relevant coagulation factors enables endovascular treatment in a safe and effective manner in hemophiliac patients.


A method to calculate the centre of the ankle joint: a comparison with the Vicon Plug-in-Gait model.
In gait analysis, calculation of the ankle joint centre is a difficult task. The conventional way to calculate the ankle joint centre is using the Vicon Plug-in-Gait model. The present study proposes a new model, which calculates the joint centre from two markers positioned over the medial and lateral malleoli (i.e. Two-marker-model). In order to compare the proposed model with Plug-in-Gait model, gait data from healthy and patient subjects were captured using a motion capture system. The ankle joint centres were calculated by the two models. A test-retest experiment was carried out to check reliability and repeatability for Two-marker-model. Two ankle joint centres produced by two models were significantly different. The distances between two ankle joint centres were approximately 16.8 (mm), and the differences in the posterior-anterior, medial-lateral and inferior-superior directions were approximately 6.3, 7.7 and 8.2 (mm). Further error analysis highlighted that the probability of producing errors in Two-marker-model is lower than that in Plug-in-Gait model due to the Two-marker-model's simple and reliable marker positioning. The reliability and repeatability coefficients for the new model were greater than 0.9. In principle, the Plug-in-Gait model is more likely to produce errors than the Two-marker-model, because the former employs multiple markers from the pelvis to calf to define the ankle joint centre with marker positions being very user-dependent. The results suggest that the Two-marker-model can be considered an alternative to Plug-in-Gait model for calculating ankle joint centre.


T-cell recognition of mycobacterial antigens.
T-cells play a dominant role in the immune response to mycobacterial infections. Most recognized mycobacterial antigens have been identified by monoclonal antibody techniques and, subsequently, sequenced and isolated by molecular cloning. Both CD4+ and CD8+ alpha beta T-cells, as well as gamma delta T-cells have been shown to participate in anti-mycobacterial host responses. The antigens recognized by CD4+ T-cells have been studied in most detail, with particular interest on proteins actively secreted by tubercle bacilli, on lipoproteins and on heat shock or stress proteins. Peptide mapping of T-cell epitopes of several mycobacterial proteins has suggested that many of their epitopes are recognized permissively in the context of multiple human and mouse major histocompatibility complex (MHC) class II alleles. This finding is encouraging for the development of subunit vaccines and diagnostic reagents.


Polarisation stabilisation of vertical cavity surface emitting lasers by minimally invasive focused electron beam triggered chemistry.
Local electron triggered reactions of functional surface adsorbates were used as a maskless, dry, and minimally invasive nanolithography concept to stabilize the polarisation of individual vertical cavity surface emitting lasers (VCSELs) on a wafer in a post-processing step. Using a 30 keV focused electron beam of a scanning electron microscope and injecting volatile organo-metallic (CH(3))(2)Au(tfa) molecules, polarisation gratings were directly written on VCSELs by dissociating the surface adsorbed molecules. The electron triggered adsorbate dissociation resulted in electrically conductive Au-C nano-composite material, with gold nanocrystals embedded in a carbonaceous matrix. A resistivity of 2500 µΩcm was measured at a typical composition of 30 at.% Au. This material proved successful in suppressing polarisation switching when deposited as line gratings with a width of 200 nm, a thickness of 50 nm, and a pitch of 500 nm and 1 µm. Refractive index measurements suggest that the optical attenuation by the deposited Au-C material is much lower than by pure Au thus giving a low emission power penalty while keeping the polarisation stable.


The clinical efficacy of consolidation chemotherapy for resectable esophageal squamous cell cancer after trimodality therapy.
We aimed to assess the clinical outcome of consolidation chemotherapy for resectable esophageal squamous cell cancer (ESCC) after trimodality therapy. From January 2005 to December 2012, a total of 192 consecutive locally advanced ESCC patients who underwent trimodality therapy successfully was included. Grouping was based on the degree of myelosuppression occurred during preoperative chemoradiotherapy. Of the 192 patients, 120 patients underwent trimodality therapy only (TT group), while 72 patients received consolidation chemotherapy additionally after trimodality therapy (TC group). Preoperative chemoradiotherapy included two cycles of chemotherapy concurrently with radiotherapy. The chemotherapy regimen consisted of cisplatin 20 mg/m2/day and fluorouracil 400 mg/m2/day administered intravenously infusion on days 1-5 of a 21 days cycle. Concurrent radiotherapy was delivered in a total of 40 Gy in 20 fractions. All patients underwent surgery successfully. For 72 patients in TC group, additional 1-4 cycles of consolidation chemotherapy were administered, and chemotherapy regimen was as before. The 5-year survival rate was 43.5% in TT group, as compared with 48.8% in TC group. (P = 0.238). The 5.year progression.free survival. (PFS) rates were 34.0% in TT group and 38.8% in TC group. (P = 0.049). Risk reduction in PFS was remarkable for males and those who did not achieve pathologic complete response. (pCR). The incidence rate of disease progression did not differ significantly. (P = 0.200). The addition of consolidation chemotherapy demonstrates no survival benefit for patients with locally advanced ESCC, but PFS is significantly improved, especially for males and those who did not achieve pCR.


Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury.
A major portion of individuals affected by traumatic spinal cord injury (SCI) experience one or more types of chronic neuropathic pain (NP), which is often intractable to currently available treatments. The availability of reliable behavioral assays in pre-clinical models of SCI-induced NP is therefore critical to assess the efficacy of new potential therapies. Commonly used assays to evaluate NP-related behavior in rodents, such as Hargreaves thermal and von Frey mechanical testing, rely on the withdrawal response to an evoked stimulus. However, other assays that test spontaneous/non-evoked NP-related behavior or supraspinal aspects of NP would be highly useful for a more comprehensive assessment of NP following SCI. The Mouse Grimace Scale (MGS) is a tool to assess spontaneous, supraspinal pain-like behaviors in mice; however, the assay has not been characterized in a mouse model of SCI-induced chronic NP, despite the critical importance of mouse genetics as an experimental tool. We found that beginning 2 weeks after cervical contusion, SCI mice exhibited increased facial grimace features compared to laminectomy-only control mice, and this grimace phenotype persisted to the chronic time point of 5 weeks post-injury. We also found a significant relationship between facial grimace score and the evoked forepaw withdrawal response in both the Hargreaves and von Frey tests at 5 weeks post-injury when both laminectomy-only and SCI mice were included in the analysis. However, within only the SCI group, there was no correlation between grimace score and Hargreaves or von Frey responses. These results indicate both that facial grimace analysis can be used as an assay of spontaneous NP-related behavior in the mouse model of SCI and that the information provided by the MGS may be different than that provided by evoked tests of sensory function.


Repurposed agents in the Alzheimer's disease drug development pipeline.
Treatments are needed to address the growing prevalence of Alzheimer's disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the pharmaceutical development process is both time-consuming and costly. Drug repurposing provides an opportunity to accelerate this process by investigating the AD-related effects of agents approved for other indications. These drugs have known safety profiles, pharmacokinetic characterization, formulations, doses, and manufacturing processes. We assessed repurposed AD therapies represented in Phase I, Phase II, and Phase III of the current AD pipeline as registered on ClinicalTrials.gov as of February 27, 2020. We identified 53 clinical trials involving 58 FDA-approved agents. Seventy-eight percent of the agents in trials had putative disease-modifying mechanisms of action. Of the repurposed drugs in the pipeline 20% are hematologic-oncologic agents, 18% are drugs derived from cardiovascular indications, 14% are agents with psychiatric uses, 12% are drug used to treat diabetes, 10% are neurologic agents, and the remaining 26% of drugs fall under other conditions. Intellectual property strategies utilized in these programs included using the same drug but altering doses, routes of administration, or formulations. Most repurposing trials were supported by Academic Medical Centers and were not funded through the biopharmaceutical industry. We compared our results to a European trial registry and found results similar to those derived from ClinicalTrials.gov. Drug repurposing is a common approach to AD drug development and represents 39% of trials in the current AD pipeline. Therapies from many disease areas provide agents potentially useful in AD. Most of the repurposed agents are generic and a variety of intellectual property strategies have been adopted to enhance their economic value.


A Proximity Ligation-Based Method for Quantitative Measurement of D-Loop Extension in S. cerevisiae.
Homologous recombination faithfully restores the sequence information interrupted by a DNA double-strand break by referencing an intact DNA molecule as a template for repair DNA synthesis. DNA synthesis is primed from 3'-OH end of the invading DNA strand in the displacement loop (D-loop). Here, we describe a simple and quantitative proximity ligation-based assay to study the initiation of homologous recombination-associated DNA synthesis initiated at the D-loop and final product formation. The D-loop extension assay overcomes the semiquantitative nature and some limitations of the current PCR-based technique and facilitates the study of the recombination-associated DNA synthesis.


Postmortem evaluation of serum and urine neopterin concentrations.
Cellular immune response is accompanied by the release of neopterin. Increased neopterin levels in urine and serum are observed in patients during viral infections, autoimmune diseases, and allograft rejections and certain malignant diseases. We investigated postmortem neopterin concentrations in urine and serum samples taken from 32 corpses 3 to 69 h (mean 19.3 h) after death. Urine neopterin concentrations in corpses are similar to those of healthy live controls and are independent of the time after death. In contrast, serum neopterin concentrations are frequently greatly increased in corpses, and the levels are higher in sera collected more than 10 h after death in comparison with samples obtained earlier. Neopterin measurement in urine and serum samples of corpses is feasible. It appears likely that urine neopterin concentrations could aid the diagnosis of inflammatory diseases in corpses.


Oxidative stress in fungi: its function in signal transduction, interaction with plant hosts, and lignocellulose degradation.
In this review article, we want to present an overview of oxidative stress in fungal cells in relation to signal transduction, interaction of fungi with plant hosts, and lignocellulose degradation. We will discuss external oxidative stress which may occur through the interaction with other microorganisms or plant hosts as well as internally generated oxidative stress, which can for instance originate from NADPH oxidases or "leaky" mitochondria and may be modulated by the peroxiredoxin system or by protein disulfide isomerases thus contributing to redox signaling. Analyzing redox signaling in fungi with the tools of molecular genetics is presently only in its beginning. However, it is already clear that redox signaling in fungal cells often is linked to cell differentiation (like the formation of perithecia), virulence (in plant pathogens), hyphal growth and the successful passage through the stationary phase.


The candidate neuroprotective agent artemin induces autonomic neural dysplasia without preventing peripheral nerve dysfunction.
Artemin (ART) signals through the GFR alpha-3/RET receptor complex to support sympathetic neuron development. Here we show that ART also influences autonomic elements in adrenal medulla and enteric and pelvic ganglia. Transgenic mice over-expressing Art throughout development exhibited systemic autonomic neural lesions including fusion of adrenal medullae with adjacent paraganglia, adrenal medullary dysplasia, and marked enlargement of sympathetic (superior cervical and sympathetic chain ganglia) and parasympathetic (enteric, pelvic) ganglia. Changes began by gestational day 12.5 and formed progressively larger masses during adulthood. Art supplementation in wild type adult mice by administering recombinant protein or an Art-bearing retroviral vector resulted in hyperplasia or neuronal metaplasia at the adrenal corticomedullary junction. Expression data revealed that Gfr alpha-3 is expressed during development in the adrenal medulla, sensory and autonomic ganglia and their projections, while Art is found in contiguous mesenchymal domains (especially skeleton) and in certain nerves. Intrathecal Art therapy did not reduce hypalgesia in rats following nerve ligation. These data (1) confirm that ART acts as a differentiation factor for autonomic (chiefly sympathoadrenal but also parasympathetic) neurons, (2) suggest a role for ART overexpression in the genesis of pheochromocytomas and paragangliomas, and (3) indicate that ART is not a suitable therapy for peripheral neuropathy.


Masked Isolated Nocturnal Hypertension in Children and Young Adults.
Isolated nocturnal hypertension (INH) is characterized by normal daytime blood pressure (BP) and elevated nighttime BP diagnosed by ambulatory BP monitoring. Masked isolated nocturnal hypertension (MINH) is a subtype of INH in which office BP is normal. We studied the frequency and characteristics of INH and MINH in children and young adults. One hundred and ninety-eight subjects seen by the pediatric nephrology service were studied retrospectively. Isolated nocturnal hypertension (INH) and MINH were diagnosed according to daytime and nighttime ABP and office BP in the case of the latter. One hundred and eighteen subjects (60%) had normotension, 6 (3%) had isolated daytime hypertension, 32 (16%) had INH, and 42 (21%) had day-night hypertension. Sixteen subjects had MINH (8.1%). The underlying diseases of MINH were as follows: no underlying disease 9 (56%), renal disease 6 (38%), and endocrine disease 1 (6%). There was no significant difference in the underlying disease, gender, age, and BMI between MINH and INH with elevated office BP. In conclusion, MINH is present in children and young adults. Since there were no specific features for MINH, screening with ambulatory or home BP monitoring during sleep may be appropriate.


The validity of the Supports Intensity Scale for adults with psychiatric disabilities.
Although the Supports Intensity Scale (SIS) was developed for persons with intellectual and developmental disabilities, we argue for its applicability for people with psychiatric disabilities. Previous empirical evidence for the criterion-related validity of SIS for this population is limited, based on only two studies with participants from the same Mexican state. In a nationwide study we found that SIS explained between 48 and 51% of the variance in the dependent measure, indicating very good validity. The profile of individual support needs showed sensitivity to activities relatively specific to people with psychiatric disabilities, further indicating the validity of the scale. Overall, we find SIS to be valid and appropriate instrument for assessing the support needs of this population.


Structure-activity relationships for the hypertensinogenic activity of ouabain: role of the sugar and lactone ring.
Elevated levels of an endogenous ouabain circulate in many patients with essential hypertension. However, in contrast to ouabain, digoxin does not induce hypertension. This study investigated the hypothesis that within a single cardiac glycoside, the structural elements that induce hypertension differ from those responsible for high potency as a sodium pump inhibitor. Normal male Sprague-Dawley rats received infusions of vehicle (VEH), rhamnose (RHA), ouabain (OUA), ouabagenin (OGN), dihydro-ouabain (DHO), iso-ouabain (ISO), and a lactone ring opened analog (ORO) at 30 microgram. kg(-1). 24 h(-1) for 5 weeks via subcutaneous osmotic pumps. Cuff pressures were taken weekly. At the end of the study, trunk blood was harvested, extracted by C18 column, and subjected to high-performance liquid chromatography. Fractions were analyzed for OUA, OGN, and DHO by immunoassay. In OUA-, OGN-, and DHO-infused rats, 1 main peak of immunoreactivity corresponding to the infused agent was found. No evidence of in vivo conversion to OUA or DHO was found for any analog except ORO. At 5 weeks, systolic blood pressures in VEH, RHA, OUA, OGN, DHO, ISO, and ORO were 132+/-2.5, 133+/-1.5, 159+/-2.6,* 154+/-4,* 167+/-4,* 171+/-2.2,* and 169+/-2.4* mm Hg, respectively (*P<0.01 versus VEH and RHA, P<0.05 versus OUA). The hypertensinogenic activity was greater than OUA in 3 analogs (DHO, ISO, and ORO) in which the lactone was saturated, conformationally restrained by linkage with the oxygen at C14, or opened, respectively. These compounds were weak inhibitors of dog kidney Na,K-ATPase. Thus, RHA and the unsaturated lactone ring are crucial to the high potency of OUA as an inhibitor of the sodium pump but appear to be unrelated to its ability to induce hypertension. The conclusion that this form of hypertension is mediated primarily by the steroid nucleus suggests also that OUA may have a mechanism of action independent of the sodium pump.


A case-control study of skin conductance biofeedback on seizure frequency and emotion regulation in drug-resistant temporal lobe epilepsy.
This study investigates the physiological basis of effects of skin conductance biofeedback on anxiety disorders, depressive disorders and stress in drug-resistant temporal lobe epilepsy (TLE). This method presents an interest in seizure reduction and improvement in psychiatric comorbidities frequently associated with TLE. Our goal was to better understand the impact of biofeedback on seizure control and on emotional regulation. Fifteen patients with TLE were treated with 12 skin conductance biofeedback sessions and compared with 15 control TLE patients on a waiting list. They were evaluated in terms of seizure frequency, clinical evaluations of anxiety and depression and skin conductance responses (SCR) to five emotions: fear, disgust, sadness, happiness and peacefulness induced by short films. Biofeedback training significantly reduced seizure frequency with a mean reduction of -47.42% in the biofeedback group, while the control group did not differ at the two time measures. A significant improvement was found for depression and trait-anxiety in the biofeedback group but not in the control group. There were no differences on SCR on any emotion after biofeedback treatment. A correlation was found between mean change in SCR over the biofeedback treatment and the reduction of seizure frequency, but not between SCR changes and scores on psychiatric comorbidities. These results show independent effect of biofeedback on mood and seizure control. Improvements in anxiety and depressive symptoms were not related to SCR, whereas improved seizure control was, suggesting differential mechanisms underlying these two phenomena.


Forecasting the effects of obesity and smoking on U.S. life expectancy.
Although increases in obesity over the past 30 years have adversely affected the health of the U.S. population, there have been concomitant improvements in health because of reductions in smoking. Having a better understanding of the joint effects of these trends on longevity and quality of life will facilitate more efficient targeting of health care resources. For each year from 2005 through 2020, we forecasted life expectancy and quality-adjusted life expectancy for a representative 18-year-old, assuming a continuation of past trends in smoking (based on data from the National Health Interview Survey for 1978 through 1979, 1990 through 1991, 1999 through 2001, and 2004 through 2006) and past trends in body-mass index (BMI) (based on data from the National Health and Nutrition Examination Survey for 1971 through 1975, 1988 through 1994, 1999 through 2002, and 2003 through 2006). The 2003 Medical Expenditure Panel Survey was used to examine the effects of smoking and BMI on health-related quality of life. The negative effects of increasing BMI overwhelmed the positive effects of declines in smoking in multiple scenarios. In the base case, increases in the remaining life expectancy of a typical 18-year-old are held back by 0.71 years or 0.91 quality-adjusted years between 2005 and 2020. If all U.S. adults became nonsmokers of normal weight by 2020, we forecast that the life expectancy of an 18-year-old would increase by 3.76 life-years or 5.16 quality-adjusted years. If past obesity trends continue unchecked, the negative effects on the health of the U.S. population will increasingly outweigh the positive effects gained from declining smoking rates. Failure to address continued increases in obesity could result in an erosion of the pattern of steady gains in health observed since early in the 20th century.


Determination of tissue-type plasminogen-activator mRNA in human and non-human cell lines by dot-blot hybridization.
A labelled cDNA clone was used in DNA-RNA hybridization on nitrocellulose filter paper (dot-blot technique) to detect and quantify mRNA for endogenous tissue plasminogen activator (PA) in cell extracts and samples of RNA purification runs. Although, for detection purposes, the assay was less sensitive than translation in Xenopus oocytes, it was at least as reliable and much more convenient for the purpose of quantitative determination. In particular, the technique was used to study the kinetics of PA mRNA formation in a human melanoma cell line (Bowes) after exposure to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Incubation of the cells with TPA resulted in a 15-20-fold increase in cellular PA mRNA content. The effect was time- and dose-dependent: the increase in PA-specific mRNA was clearly visible as early as 4 h after initiation of TPA treatment in Bowes cells. It was blocked completely by pretreatment of the cells with actinomycin D, indicating that TPA caused enhancement of synthesis of PA mRNA rather than inhibition of PA mRNA degradation. The use of the nitrocellulose dot-blot technique also revealed that two non-human cell lines produce mRNAs which cross-react with the human PA mRNA, namely the mouse melanoma cell line B16 and the rat brain-tumour cell line, RT4-71-1. TPA was found to exert similar stimulatory effects on the synthesis of mRNAs in these cell lines as in Bowes cells.


A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity.
Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals. Successful propagation in an infected host by this obligate intracellular parasite depends on its ability to enter and exit host cells. Egress from the cell can be artificially induced by causing fluxes of calcium within the parasite with the use of calcium ionophores. While this ionophore-induced egress (IIE) has been characterized in detail, it is not known whether it mimics a normal physiological process of the parasite. This is underscored by the fact that mutants in IIE do not exhibit strong defects in any of the normal growth characteristics of the parasite in tissue culture. We have isolated and characterized a T. gondii mutant that along with a delay in IIE exhibits a severe defect in establishing a successful infection in vivo. In tissue culture this mutant displays normal ability to invade, divide within cells and convert into the latent encysted bradyzoite form. Nevertheless, mice infected with this mutant are less likely to die and carry less brain cysts than those infected with wild type parasites. Thus, our results suggest that normal response to calcium fluxes plays an important role during in vivo development of T. gondii.


From brain determination to testis determination: evolution of the mammalian sex-determining gene.
In mammals, sex is determined by an XY male:XX female sex chromosome system in which a male-dominant gene on the Y chromosome (SRY) determines testis formation. Sex chromosomes evolved from an ordinary autosome pair as the Y chromosome was progressively degraded. The Y chromosome has lost nearly all of its 1500 original genes, and those that survived did so because they evolved a critical role in male determination or differentiation. SRY is typical of Y-borne genes. Comparative gene mapping and sequencing shows that SRY arose quite recently as a degraded version of the SOX3 gene on the X chromosome. SOX3 is expressed predominantly in brain, and so is more likely to be a brain-determining than a testis-determining gene. The male-dominant action of SRYmay be an illusion, as its structure suggests that it works by interfering with the action of a related gene, which in turn inhibits testis development. This hypothesis can give a good account of how a brain-determining gene acquired a role in testis determination via differential dosage of SOX3. SRYhas no central role in sex determination and it can be replaced as a trigger and loft, as have many other Y-borne genes in recent evolutionary history. The absence of SRY in two species of the mole vole (Ellobius) suggests that its useful life is already running out.


The effect of Bacillus Calmette-Guerin-induced macrophage activation on the in vivo clearance of sensitized erythrocytes.
The clearance of (51)Cr-labeled guinea pig erythrocytes, sensitized with a known amount of IgM or IgG antibody, was examined in normal and BCG-infected guinea pigs. In normal animals, IgM-coated cells were rapidly sequestered in the liver. Most of these cells were then slowly released into the circulation where they survived normally as Coombs-positive erythrocytes. Neither the site nor extent of initial clearance showed major alterations in BCG-infected animals; however, there was no return of the sequestered erythrocytes into the circulation. This pattern of clearance was only seen in normals at very high levels of sensitization. In contrast to the IgM studies, the pattern of clearance of IgG-sensitized erythrocytes was not altered, but the rate and magnitude was markedly increased at all levels of sensitization. In addition, complement-independent clearance of IgG-sensitized erythrocytes was augmented in BCG-infected guinea pigs lacking classical complement pathway function. The spleen remained the organ primarily responsible for this increased clearance of IgG-sensitized erythrocytes. Sensitized cells in BCG-infected animals were removed from the circulation as if they were coated with several times the amount of antibody. Serum factors were shown not to be responsible for the increased clearance. These data suggest that increased macrophage activation in BCG-infected animals plays a critical role in determining the consequences of cell sensitization in vivo. These studies may help to explain exacerbations of hemolytic anemias and related states after intercurrent infections.


Cyclosporine decreases prostaglandin E2 production in mouse medullary thick ascending limb cultured cells.
Intrarenal vasoconstriction is thought to be the major pathogenesis of cyclosporine (CsA) nephrotoxicity. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two of the major intrarenal vasodilators, which protect kidney from ischemia. CsA inhibited NO production in renal epithelial cells. The interaction between CsA and intrarenal PGE2 and NO production is still unclear. The aim of the study is to evaluate the interaction of CsA with intrarenal PGE2 and NO production in renal epithelial cells. Models of cultured mouse thick ascending limb (TAL) cells are chosen to perform the experiments, as TAL cells are the major site of intrarenal PGE2 production and target of CsA nephrotoxicity. We investigated the PGE2 production by enzyme-linked immunosorbent assay, and cyclooxygenase (COX-1 and COX-2) mRNA expression by RT-PCR in cultured cells treated with or without CsA. TAL cells maintained the main characteristics of their parental cells. TAL cells produce PGE2 mainly by COX-1 in steady state and by COX-2 in stimulated state by lipopolysaccharide (LPS). CsA (100 ng/ml) significantly reduced the PGE2 production up to 43% in TAL cells in LPS stimulated status (control versus CsA: 375.1 +/- 15.5 vs. 187.2 +/- 12.2 nm/mg protein, n = 7, P < 0.001). The effects were dose-dependent. The mRNA expression of COX1 is not affected and COX-2 is decreased in CsA-treated TAL cells. NO donor could prevent the inhibitory effects of CsA. We concluded that CsA decreased intrarenal PGE2 production in stimulated status mainly by decreasing COX-2 expression. NO might play a role in the CsA effect. The results suggested the role possible of PGE2 in CsA nephrotoxicity.


Transport anomalies and adaptative pressure-dependent topological constraints in tetrahedral liquids: evidence for a reversibility window analogue.
Topological rigid constraints can be computed rather simply with changing composition and temperature but their estimation remains challenging for other thermodynamic variables. Here, the investigation of densified silicate liquids from molecular dynamics simulations combined with an analysis of radial and angular atomic excursions allows defining a pressure dependence of such constraints. Results show, that for a given composition, the dependence is nonmonotonic as it depends on the interplay between constraints broken by thermal activation and additional constraints arising from the increase of network connectivity under pressure. An anomalous behavior for oxygen bending constraints is obtained in the (P, T) map which connects to reported anomalies in transport properties and is identified as the pressure analogue of the stress-free Boolchand intermediate phase in rigidity driven by composition.


Hot-pressed ceramic Cr(2+):ZnSe gain-switched laser.
The technology of hot-pressed Cr(2+):ZnSe ceramic preparation is reported. Comparative gain-switched lasing of hot-pressed ceramic and CVD grown Cr(2+):ZnSe samples with slope efficiencies up to 10% and output energies up to 2 mJ were demonstrated. This is a milestone in the development of future large scale mid-IR laser systems based on ceramic TM(2+):II-VI materials. This evolving technology has excellent potential as media for practical low cost, high power mid-IR laser applications.


Coherent transfer of an optical carrier over 251 km.
We transfer an optical frequency over 251 km of optical fiber with a residual instability of 6x10(-19) at 100 s. This instability and the associated timing jitter are limited fundamentally by the noise on the optical fiber and the link length. We give a simple expression for calculating the achievable instability and jitter over a fiber link. Transfer of optical stability over this long distance requires a highly coherent optical source, provided here by a cw fiber laser locked to a high finesse optical cavity. A sufficient optical carrier signal is delivered to the remote fiber end by incorporating two-way, in-line erbium-doped fiber amplifiers to balance the 62 dB link loss.


Identification of Porphyromonas gingivalis genes specifically expressed in human gingival epithelial cells by using differential display reverse transcription-PCR.
Porphyromonas gingivalis, one of the causative agents of adult periodontitis, can invade and survive within host epithelial cells. The molecular mechanisms by which P. gingivalis induces uptake and adapts to an intracellular environment are not fully understood. In this study, we have investigated the genetic responses of P. gingivalis internalized within human gingival epithelial cells (GECs) in order to identify factors involved in invasion and survival. We compared the differential display of arbitrarily PCR-amplified gene transcripts in P. gingivalis recovered from GECs with the display of transcripts in P. gingivalis control cultures. Over 20 potential differentially expressed transcripts were identified. Among these, pepO, encoding an endopeptidase, and genes encoding an ATP-binding cassette (ABC) transporter and a cation-transporting ATPase were upregulated in GECs. To investigate the functionality of these gene products, mutants were generated by insertional inactivation. Compared to the parental strain, mutants of each gene showed a significant reduction in their invasion capabilities. In addition, GEC cytoskeletal responses to the mutants were distinct from those induced by the parent. In contrast, adhesion of the mutant strains to GECs was not affected by lack of expression of the gene products. These results suggest that PepO, a cation-transporting ATPase, and an ABC transporter are required for the intracellular lifestyle of P. gingivalis.


Vacuolar Ca2+/H+ transport activity is required for systemic phosphate homeostasis involving shoot-to-root signaling in Arabidopsis.
Calcium ions (Ca(2+)) and Ca(2+)-related proteins mediate a wide array of downstream processes involved in plant responses to abiotic stresses. In Arabidopsis (Arabidopsis thaliana), disruption of the vacuolar Ca(2+)/H(+) transporters CAX1 and CAX3 causes notable alterations in the shoot ionome, including phosphate (P(i)) content. In this study, we showed that the cax1/cax3 double mutant displays an elevated P(i) level in shoots as a result of increased P(i) uptake in a miR399/PHO2-independent signaling pathway. Microarray analysis of the cax1/cax3 mutant suggests the regulatory function of CAX1 and CAX3 in suppressing the expression of a subset of shoot P(i) starvation-responsive genes, including genes encoding the PHT1;4 P(i) transporter and two SPX domain-containing proteins, SPX1 and SPX3. Moreover, although the expression of several PHT1 genes and PHT1;1/2/3 proteins is not up-regulated in the root of cax1/cax3, results from reciprocal grafting experiments indicate that the cax1/cax3 scion is responsible for high P(i) accumulation in grafted plants and that the pht1;1 rootstock is sufficient to moderately repress such P(i) accumulation. Based on these findings, we propose that CAX1 and CAX3 mediate a shoot-derived signal that modulates the activity of the root P(i) transporter system, likely in part via posttranslational regulation of PHT1;1 P(i) transporters.


Phenotypic and molecular analysis of six human cell lines derived from patients with plasma cell dyscrasia.
Cell lines RPMI 8226, JJN3, U266 B1, NCI-H929 (all EBV-) and ARH77 and HS-Sultan (both EBV+) have been extensively characterized in this study. EBV- lines expressed the phenotype (CD138-, CD19+, CD20+) whereas EBV+ were (CD138+, CD19-, CD20-). CD56 expression was restricted to EBV- cell lines, with the exception of U266 B1, whereas PCA-1 was strongly expressed on five of the six cell lines. Only EBV+ cell lines bound peanut-agglutinin (PNA). However, all cell lines bound the lectin Jacalin that binds the same receptor as PNA, irrespective of the receptors sialylation status. By RT-PCR and direct sequencing of their IgH V/D/J domains, ARH77 was demonstrated to use the germline sequence VH4-34/dm1/JH6b, whereas no arrangement was demonstrated for RPMI 8226, suggesting IgH gene deletion or mutation. HLA class I and II antigens were detected using HLA typing on all cell lines warranting their use as suitable targets for HLA-restricted cytotoxic T cells. By sensitive RT-PCR, mRNA for IL-6, IL-6R and TNFbeta was found expressed in all cell lines. IL-1 mRNA expression was predominantly associated with the EBV+ phenotype. Although mRNA for IL-3 and GM-CSF was never detected, transcripts for c-kit ligand and, more commonly, its receptor were. Likewise GM-CSF, M-CSF and erythropoietin mRNA transcripts were detected in the majority of cell lines.


Biomechanical and physiologic processes leading to internal derangement with adhesion.
This article describes the biomechanical and physiologic processes occurring with the insidious development of craniomandibular dysfunction. This explanation uses basic orthopedic concepts and correlates the specific pathophysiologic circumstances that result in internal derangements and adhesive capsulitis. The specific pathophysiologic processes reviewed here include collagen failure, inflammatory response, synovitis, synovial hypertrophy, fibrous adhesion formation, and chondromalacia degenerative changes. Current diagnostic terminology describes internal derangements as being present with or without reduction. In view of the physiologic processes described, a better diagnostic description would be internal derangement with adhesion. Treatment should be directed toward preventing progression of degenerative changes and allowing normal reparative processes to proceed.


Novel Prediction Model for COVID-19 in Saudi Arabia Based on an LSTM Algorithm.
The rapid emergence of the novel SARS-CoV-2 poses a challenge and has attracted worldwide attention. Artificial intelligence (AI) can be used to combat this pandemic and control the spread of the virus. In particular, deep learning-based time-series techniques are used to predict worldwide COVID-19 cases for short-term and medium-term dependencies using adaptive learning. This study aimed to predict daily COVID-19 cases and investigate the critical factors that increase the transmission rate of this outbreak by examining different influential factors. Furthermore, the study analyzed the effectiveness of COVID-19 prevention measures. A fully connected deep neural network, long short-term memory (LSTM), and transformer model were used as the AI models for the prediction of new COVID-19 cases. Initially, data preprocessing and feature extraction were performed using COVID-19 datasets from Saudi Arabia. The performance metrics for all models were computed, and the results were subjected to comparative analysis to detect the most reliable model. Additionally, statistical hypothesis analysis and correlation analysis were performed on the COVID-19 datasets by including features such as daily mobility, total cases, people fully vaccinated per hundred, weekly hospital admissions per million, intensive care unit patients, and new deaths per million. The results show that the LSTM algorithm had the highest accuracy of all the algorithms and an error of less than 2%. The findings of this study contribute to our understanding of COVID-19 containment. This study also provides insights into the prevention of future outbreaks.


Prognostic Autophagy-Related Model Revealed by Integrating Single-Cell RNA Sequencing Data and Bulk Gene Profiles in Gastric Cancer.
Autophagy has been associated with tumor progression, prognosis, and treatment response. However, an autophagy-related model and their clinical significance have not yet been fully elucidated. In the present study, through the integrative analysis of bulk RNA sequencing and single-cell RNA sequencing, an autophagy-related risk model was identified. The model was capable of distinguishing the worse prognosis of patients with gastric cancer (GC), which was validated in TCGA and two independent Gene Expression Omnibus cohorts utilizing the survival analysis, and was also independent of other clinical covariates evaluated by multivariable Cox regression. The clinical value of this model was further assessed using a receiver operating characteristic (ROC) and nomogram analysis. Investigation of single-cell RNA sequencing uncovered that this model might act as an indicator of the dysfunctional characteristics of T cells in the high-risk group. Moreover, the high-risk group exhibited the lower expression of immune checkpoint markers (PDCD1 and CTLA4) than the low-risk group, which indicated the potential predictive power to the current immunotherapy response in patients with GC. In conclusion, this autophagy-associated risk model may be a useful tool for prognostic evaluation and will facilitate the potential application of this model as an indicator of the predictive immune checkpoint biomarkers.


Angioplasty of distal venous bypasses: is it worth the cost?
Saphenous vein is the best graft for long term patency infragenicular bypass. During follow-up, stenoses can appear on the graft. Is angioplasty a good solution for the treatment of these lesions? During the follow-up of 612 saphenous bypass with below-knee distal anastomosis, 90 stenoses (over 70%) were discovered. Among them 36 were treated with transluminal angioplasty (34 bypasses). Stenoses were detected at a mean follow-up of 7 months after bypass realization. They were located 17 times on the graft itself and 19 times near the anastomoses and they were never longer than 5 cm. Percutaneous approach was preferred for 11 cases and surgical for the others. Immediate success was obtained in 33 cases (91%). Among the 3 failed cases 2 needed a new bypass. Mean follow-up was 33 months after the initial bypass and 24 months after angioplasty. Graft patency was ensured by a single angioplasty in 18 cases. Assisted primary patency, cumulative patency, limb salvage rate were respectively 65%, 91%, 100% at one year and 53%, 72%, 96% at 2 years. Transluminal angioplasty can be advised for the treatment of short stenosis of infrainguinal vein graft: this technique has a weak risk, little surgical aggressiveness, short hospitalisation. Results are acceptable and not very different with the location of the stenosis.


Self-assembly of supramolecular nanotubes/microtubes from 3,5-dimethyl-4-iodopyrazole for plasmonic nanoparticle organization.
Hierarchical super-architectures from small molecule self-assembly have interesting properties and play an indispensable role in many fields. In most cases, a self-assembly process refers to multiple intermolecular interactions among intricately designed building blocks. Here, a supramolecular assembly with a tubular morphology with dimensions ranging from nanometers to micrometers was prepared through self-assembly of 3,5-dimethyl-4-iodopyrazole (DMIP), a molecule with an unprecedented simple structure. As predicted by density functional theory (DFT) calculations, the hydrogen bond and halogen bond interaction energy between DMIP molecules can be up to 32.81 kJ mol-1, which effectively drives DMIP molecules to assemble into fibrils, sheets, and finally, tubular architectures. Intriguingly, the formed tubular structure can be easily removed by heating at 100 °C, enabling the material to function as a disposable template to guide linear organization of nanostructures. As a proof of concept, ordered Au or Ag nanochains with diameters ranging from 18 to 120 nm were facilely prepared in high yield.