Diagnostic value of plasma asymmetric and symmetric dimethylarginine levels in liver transplant recipients.
Nitric oxide is an important factor in the pathogenesis of liver cirrhosis. Its synthesis depends on the availability of L‑arginine and is inhibited by asymmetric dimethylarginine (ADMA). Symmetric dimethylarginine (SDMA) seems to be a good marker of multiorgan failure, especially renal failure. The aim of the present study was to evaluate the diagnostic significance of dimethylarginines in patients after liver transplantation. The study included 30 cadaver liver donors and 30 recipients with liver cirrhosis. The following parameters were estimated in donors and in liver recipients before and at days 1 and 3 after transplantation: serum alanine transaminase (ALT), aspartate transaminase (AST), and γ‑glutamyltranspeptidase (GGT) activity, international normalized ratio (INR), concentrations of bilirubin, albumin, creatinine, electrolytes, ADMA, SDMA, and L‑arginine. Before transplantation cirrhotic patients showed higher bilirubin concentrations, higher ALT and GGT activity, and lower sodium and albumin levels compared with donors. At day 3 after transplantation, we observed a significant increase in ALT, AST, creatinine, sodium, ADMA, SDMA, and L‑arginine, and a decrease in bilirubin levels. A significant positive correlation between SDMA and creatinine was found in donors (P <0.001), recipients before transplantation (P <0.0005), and at days 1 (P <0.004) and 2 after transplantation (P <0.0005). A significant positive correlation was also observed before transplantation between ADMA and bilirubin concentrations (P = 0.0264), ADMA and albumin concentrations at day 1 after transplantation (P = 0.02), while a negative correlation was observed between ADMA and INR before transplantation (P = 0.008) and at day 3 after transplantation (P = 0.03) in recipients. An increase in dimethylarginine levels after liver transplantation seems to be due not only to the dysfunction of the transplanted liver, but also to impaired kidney function caused by the surgery itself and/or the use of a nephrotoxic calcineurin inhibitor--tacrolimus. A significant correlation between serum creatinine and SDMA concentrations both in liver donors and recipients suggests that SDMA renal clearance may have diagnostic value to evaluate the glomerular filtration rate in these patients.


A model of experimental post-traumatic osteomyelitis in guinea pigs.
A model of experimental post-traumatic osteomyelitis is described in which the femur of guinea pigs was fractured and infected with E. coli (10(5)) or Staphylococcus aureus (10(4)). Traumatized uninfected animals served as controls. The animals were further divided within each group by treating the fractured site with an intramedullary wire in one half. Osteomyelitis developed and became chronic in all guinea pigs infected with Staph. aureus, and in nine of 12 infected with E. coli. All animals infected with E. coli treated with an intramedullary wire developed chronic osteomyelitis; only four of seven from E. coli-infected animals with fractures developed this disease. Moreover, Staph. aureus could be recovered from the osseous tissue in the chronic stage of the disease regularly, while E. coli was only present in the early weeks after operation, but not in the chronic stage.


Value of bispectral index monitoring during cardiopulmonary resuscitation.
A 67-yr-old man, undergoing pulmonary metastasis resection, experienced a postoperative cardiopulmonary arrest as a result of severe bleeding. Cardiopulmonary resuscitation (CPR) was initiated, then bispectral index (BIS) monitoring was used which reassured the medical team of the adequacy of the resuscitation.


Plant species differ in their ability to reduce allocation to non-beneficial arbuscular mycorrhizal fungi.
Theory suggests that cheaters threaten the persistence of mutualisms, but that sanctions to prevent cheating can stabilize mutualisms. In the arbuscular mycorrhizal symbiosis, reports of parasitism suggest that reductions in plant carbon allocation are not universally effective. I asked whether plant species differences in mycorrhizal responsiveness would affect both their susceptibility to parasitism and their reduction in allocation to non-beneficial arbuscular mycorrhizal fungi (AMF) in high-phosphorus soils. In a greenhouse experiment, I found that two C3 grasses, Bromus inermis and Elymus repens, effectively suppressed root colonization and AMF hyphal abundance. Increases in soil phosphorus did not reduce the degree to which AMF increased plant biomass. In contrast, two C4 grasses, Andropogon gerardii and Schizachyrium scoparium, more weakly reduced root colonization and failed to suppress AMF hyphal abundance. Consequently, they experienced strong declines in their response to AMF, and one species suffered parasitism. Thus, species differ in susceptibility to parasitism and their reduction in allocation to non-beneficial AMF. These differences may affect the distribution and abundance of plants and AMF, as well as the stability of the mutualism.


Skeletal Muscle Involvement in B-Cell Lymphoma: Two Cases Illustrating the Contribution of Imaging to a Clinically Unsuspected Diagnosis.
Skeletal muscle lymphoma is rare, comprising only a very small subset of lymphoma cases. There are characteristic imaging features which, if recognized, can prevent delay in diagnosis and treatment, particularly when not suspected clinically. Herein, we report two cases of skeletal muscle lymphoma with nearly identical imaging features; the first is an example of primary muscle lymphoma in a 17-year-old boy with back and thigh pain, and the second represents lymphoma recurrence in a 55-year-old man with HIV. Characteristic features seen on MRI were key in raising suspicion for the disease and helped prevent a delay in pathologic diagnosis.


Bioavailability of dapsone on oral administration of Dapsomine--a comparative evaluation.
This study describes a comparative evaluation of dapsone kinetics in humans on administration of Dapsomine, a capsule containing dapsone 100 mg dispersed in oily-base suspension of clofazimine 50 mg. Seven untreated lepromatous leprosy patients were given one capsule of Dapsomine a day for seven days and the pharmacokinetics parameters in this group were compared with those from another group of seven patients who received dapsone 100 mg and clofazimine 50 mg separately. There were no statistically significant differences in parameters such as peak dapsone plasma concentration (Cmax), basal plasma level (C24h), time to peak level (tmax), absorption half-life (t1/2 alpha), elimination half-life t1/2 beta) and areas under plasma concentration-time curves (AUC0-8h) and AUC0-24h) between the two groups.


The effects of an ASA-like hydroperoxide compound on adenosine diphosphate induced platelet aggregation.
A hydroperoxide compound structurally related to acetylsalicylic acid, 3-hydroperoxy-3-methylphthalide, inhibits both the first and second phases of adenosine diphosphate induced, biphasic, human platelet aggregation. This occurs over the same concentration range (0.05-0.5 mM) that acetylsalicylic acid inhibits second phase aggregation and the release reaction only. The complete inhibition of adenosine diphosphate induced aggregation is a unique pharmacological property for an acetylsalicylic-acid-like compound.


Mechanism of the generation of autonomous activity of Ca2+/calmodulin-dependent protein kinase IV.
Ca2+/calmodulin-dependent protein kinase IV (CaM-KIV) is phosphorylated at Thr196 by Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), resulting in induction of both autonomous activity and a high level of Ca2+/CaM-dependent activity. We have shown that the kinetics of Thr196 phosphorylation of CaM-KIV by CaM-KK is well correlated with the generation of its autonomous activity, although Thr177 phosphorylation of CaM-KI does not induce its autonomous activity. The activities of CaM-KI chimera mutants fused with C-terminal regions (residues 296-469 and 296-350) of CaM-KIV are completely dependent on Ca2+/CaM, which is also the case for CaM-KI. Unlike wild-type CaM-KI, however, phosphorylation of Thr177 in the chimera mutants by CaM-KK resulted in generation of significant autonomous activities, indicating that the phosphorylation of Thr in the activation loop is sufficient to partially release the autoinhibitory region of CaM-KIV from the catalytic core. Indeed, the CaM-KIV peptide (residues 304-325) containing minimum autoinhibitory sequences (residues 314-321) suppressed the activity of non-phosphorylated CaM-KIV with an IC50 of approximately 50 microm, and this suppression was competitive with respect to the peptide substrate; however, the CaM-KIV peptide was not capable of inhibiting Thr196-phosphorylated CaM-KIV. Taken together, these results indicated that the Thr196 phosphorylation of CaM-KIV by CaM-KK reduced the interaction of the catalytic core with the autoinhibitory region, resulting in generation of the autonomous activity.


Zr(7)Sb(4): a new binary zirconium-rich antimonide.
Zr(7)Sb(4) has been prepared by arc-melting of the elemental components and annealing at 1000-1150 degrees C. Its crystal structure was determined by X-ray diffraction (Pearson symbol mP44, monoclinic, space group P2(1)/c, Z = 4, a = 8.4905(6) A, b = 11.1557(8) A, c = 11.1217(8) A, beta = 111.443(2) degrees at 295 K). Zr(7)Sb(4) is isotypic to Hf(6)TiSb(4), a compound stabilized by differential fractional site occupancy. It is the first binary group-4 antimonide with this metal-to-antimony ratio, but it differs from the corresponding phosphides and arsenides M(7)Pn(4) (M = Ti, Zr, Hf; Pn = P, As), which adopt the Nb(7)P(4)-type structure. Zr(7)Sb(4) is built up from layers excised from the tetragonal W(5)Si(3)-type structure; these layers are displaced relative to each other to maximize interlayer Zr-Zr and Zr-Sb bonding, as confirmed by band structure calculations.


Pattern of medication selling and self-medication practices: A study from Punjab, Pakistan.
Access to medicines without prescription is a major contributing factor for self-medication practices. This study was designed to examine the ratio of non-prescribed medicines sales and self-medication practices in Punjab, Pakistan. This study also evaluates the reasons for self-medication within its communities. An observational study was conducted in 272 systemically selected pharmacies to analyze medicines-related sales, with or without prescription. A cross-sectional survey was performed between June 2015 and November 2016. Consumers were interviewed about their self-medication practices. Of the pharmacies surveyed, 65.3% participated in the study. A total of 4348 medicines were purchased for self-medication by 3037 consumers (15.2% of all study participants), of which 873 (28.7%) participated in an interview. Majority (81.2%) medicine purchaser, (90.9%) interview participants, and (59.4%) drug users were male. On average, each community pharmacy sold 7.9 medicines without prescription each day, to an average of 5.5 customers. Many participants (28.9%) had matriculation in their formal education. The medicines most often sold for self-medication were analgesics and antipyretics(39.4%). More than 25% of participants reported fever symptoms and 47.8% assumed their illness was too trivial to consult a doctor. Media advertisements were the most common source of information for participants (46.7%). Many types of medicines were often sold without prescription from community pharmacies. Self-medication was common practice for a wide range of illnesses. Pakistan also needs effective implementation of policies to monitor medication sales. Public education about rational medication and limits to advertising medicine are very necessary.


Activation of Aryl Carboxylic Acids by Diboron Reagents towards Nickel-Catalyzed Direct Decarbonylative Borylation.
The Ni-catalyzed decarbonylative borylation of (hetero)aryl carboxylic acids with B2 cat2 has been achieved without recourse to any additives. This Ni-catalyzed method exhibits a broad substrate scope covering poorly reactive non-ortho-substituted (hetero)aryl carboxylic acids, and tolerates diverse functional groups including some of the groups active to Ni0 catalysts. The key to achieve this decarbonylative borylation reaction is the choice of B2 cat2 as a coupling partner that not only acts as a borylating reagent, but also chemoselectively activates aryl carboxylic acids towards oxidative addition of their C(acyl)-O bond to Ni0 catalyst via the formation of acyloxyboron compounds. A combination of experimental and computational studies reveals a detailed plausible mechanism for this reaction system, which involves a hitherto unknown concerted decarbonylation and reductive elimination step that generates the aryl boronic ester product. This mode of boron-promoted carboxylic acid activation is also applicable to other types of reactions.


Aerobactin synthesis genes iucA and iucC contribute to the pathogenicity of avian pathogenic Escherichia coli O2 strain E058.
Aerobactin genes are known to be present in virulent strains and absent from avirulent strains, but contributions of iucC and iucA, which are involved in aerobactin synthesis, to the pathogenicity of avian pathogenic Escherichia coli (APEC) have not been clarified. In this study, effects of double mutants (iucA/iutA or iucC/iutA) compared to those of single mutants (iucA, iucC or iutA) of aerobactin genes on the virulence of APEC strain E058 were examined both in vitro (aerobactin production, ingestion into HD-11 cells, survival in chicken serum) and in vivo (competitive growth against parental strain, colonization and persistence). In competitive co-infection assays, compared to the E058 parental strain, the E058ΔiucA mutant was significantly reduced in the liver, kidney, spleen (all P<0.01), heart and lung (both P<0.001). The E058ΔiutA mutant also was significantly reduced in the liver, lung, kidney (all P<0.01), heart and spleen (both P<0.001). The E058ΔiucC mutant was significantly attenuated in the heart and kidney (both P<0.05) and showed a remarkable reduction in the liver, spleen and lung (P<0.01); meanwhile, both E058ΔiucAΔiutA and E058ΔiucCΔiutA double mutants were sharply reduced as well (P<0.001). In colonization and persistence assays, compared with E058, recovered colonies of E058ΔiucA were significantly reduced from the lung, liver, spleen and kidney (P<0.01) and significantly reduced in the heart (P<0.001). E058ΔiutA was significantly reduced from the heart, lung, liver, spleen and kidney (P<0.01). E058ΔiucC, E058ΔiucAΔiutA and E058ΔiucCΔiutA were significantly decreased in all organs tested (P<0.001). These results suggest that iutA, iucA and iucC play important roles in the pathogenicity of APEC E058.


Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax.
Bacillus anthracis infection is associated with severe hemostatic disturbances but their roles and contribution to fatality remain incompletely characterized. We undertook analyses of circulating antithrombin levels during the course of infection using a comparison of lethal and nonlethal murine anthrax models. Plasma samples were obtained from DBA/2 mice challenged intraperitoneally with the spores of either toxigenic B. anthracis Sterne strain or nontoxigenic, avirulent delta Sterne strain. We found that plasma antithrombin levels were rapidly depleted in Sterne spore-challenged mice, concomitant with elevation of neutrophil elastase (NE) and massive syndecan shedding from the liver into circulation. The shed syndecan bound with antithrombin accelerated NE-mediated antithrombin proteolysis. The liver response to infection demonstrated strain-specific compensatory increases of antithrombin and syndecan gene transcription. Both bacterial strains induced changes in blood coagulation parameters consistent with the onset of disseminated intravascular coagulation. We propose that antithrombin depletion proceeding through activation of neutrophils and massive shedding of heparin-like syndecan from the liver into circulation contribute to anthrax coagulopathy.


Primary hyperparathyroidism detected by gingival biopsy.
This case of primary hyperparathyroidism presented several unusual features: (1) The only presenting symptoms were two gingival giant cell lesions (brown tumors), (2) Bone changes occurred early in the disease, but apparently affected only the mandible and maxilla, (3) No renal disease could be detected. The diagnosis, treatment and postoperative course of this unusual case has been described.


Comparative toxicity of size-fractionated airborne particulate matter obtained from different cities in the United States.
Hundreds of epidemiological studies have shown that exposure to ambient particulate matter (PM) is associated with dose-dependent increases in morbidity and mortality. While early reports focused on PM less than 10 microm (PM10), numerous studies have since shown that the effects can occur with PM stratified into ultrafine (UF), fine (FI), and coarse (CO) size modes despite the fact that these materials differ significantly in both evolution and chemistry. Furthermore the chemical makeup of these different size fractions can vary tremendously depending on location, meteorology, and source profile. For this reason, high-volume three-stage particle impactors with the capacity to collect UF, FI, and CO particles were deployed to four different locations in the United States (Seattle, WA; Salt Lake City, UT; Sterling Forest and South Bronx, NY), and weekly samples were collected for 1 mo in each place. The particles were extracted, assayed for a standardized battery of chemical components, and instilled into mouse lungs (female BALB/c) at doses of 25 and 100 microg. Eighteen hours later animals were euthanized and parameters of injury and inflammation were monitored in the bronchoalveolar lavage fluid and plasma. Of the four locations, the South Bronx coarse fraction was the most potent sample in both pulmonary and systemic biomarkers, with a strong increase in lung inflammatory cells as well as elevated levels of creatine kinase in the plasma. These effects did not correlate with lipopolysaccharide (LPS) or total zinc or sulfate content, but were associated with total iron. Receptor source modeling on the PM2.5 samples showed that the South Bronx sample was heavily influenced by emissions from coal fired power plants (31%) and mobile sources (22%). Further studies will assess how source profiles correlate with the observed effects for all locations and size fractions.


[Gonadal toxicity of cancer therapies in children].
Numerous cytotoxic drugs used to treat childhood cancers, as well as pelvic or hypothalamo- pituitary irradiation and gonadal surgery, can affect subsequent hormonal function and fertility. Prevention of these adverse consequences is based primarily on therapeutic de-escalation when possible, and now also on gonad or gamete preservation. These patients and their parents must receive thorough information, taking into account the child's age, the proposed treatments, and the length of follow-up. Teams treating childhood cancers must receive appropriate training, and access to innovative fertility-preserving techniques must be guaranteed at the national level.


Proteomic analysis of human tears: defensin expression after ocular surface surgery.
Human tear protein profiles were monitored by surface enhanced laser desorption/ionization-time-of-flight mass spectrometry ProteinChip technology (SELDI-TOF ProteinChip) and liquid chromatography-mass spectrometry (LC-MS). Tears were collected from 21 patients scheduled for surgery to remove an ocular surface neoplasm prior to surgery (day 0) and on days 1, 3, and 30 postoperatively. Using this proteomic approach, we verified that three human alpha-defensins (HNP-1, HNP-2, and HNP-3) were significantly up-regulated in their expression after surgery and that their levels decreased to approximately normal by day 30 by which time healing was complete. Further confirmation of the identity of the alpha-defensins in human tears was made by LC purification, trypsin digestion, and ESI-MS/MS analysis of their tryptic digests. The concentrations of HNP-1 and HNP-2 were determined and shown to be markedly increased after ocular surface surgery. The results of the study suggest that human alpha-defensins HNP-1, HNP-2, and HNP-3 are up-regulated after surgery, and may in addition to their antimicrobial properties have an important role in wound healing.


Spontaneous Coronary Artery Dissection: Pitfalls of Angiographic Diagnosis and an Approach to Ambiguous Cases.
Spontaneous coronary artery dissection (SCAD) is a pathophysiologically distinct cause of acute coronary syndromes (ACS). It is increasingly recognized that optimal management is different from that for atherosclerotic ACS and that a SCAD diagnosis has specific long-term prognostic and therapeutic implications. Accurate diagnosis is therefore essential to ensure the best treatment of patients. At present this relies on the recognition of typical features of SCAD identified on invasive coronary angiography. Although most SCAD can be readily distinguished angiographically from alternative causes of ACS, false positive and false negative diagnoses remain common. In particular, sometimes non-SCAD presentations, including atherothrombosis, takotsubo cardiomyopathy, coronary embolism, coronary vasospasm, contrast streaming, and myocardial infarction with nonobstructive coronary arteries, can mimic angiographic features usually associated with SCAD. The authors present the combined experience from European and US SCAD referral centers reviewing the classical angiographic appearances of SCAD, presenting potential diagnostic pitfalls and exemplars of SCAD mimickers. The authors further review the benefits and limitations of intracoronary imaging in the context of SCAD. Finally, the authors discuss the investigation of ambiguous cases and an approach to minimize misdiagnosis in difficult cases.


Numerical study of the transverse diffusion coefficient for a one component model of plasma.
In this paper, we discuss the results of some molecular dynamics simulations of a magnetized one component plasma, targeted to estimate the diffusion coefficient D⊥ in the plane orthogonal to the magnetic field lines. We find that there exists a threshold with respect to the magnetic field strength |B→|: for weak magnetic field, the diffusion coefficients scale as 1/|B→|2, while a slower decay appears at high field strength. The relation of this transition with the different mixing properties of the microscopic dynamics is investigated by looking at the behavior of the velocity autocorrelation.


Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosa cystic fibrosis bacterial isolates.
Recent years have seen renewed interest in phage therapy--the use of viruses to specifically kill disease-causing bacteria--because of the alarming rise in antibiotic resistance. However, a major limitation of phage therapy is the ease at with bacteria can evolve resistance to phages. Here, we determined whether in vitro experimental coevolution can increase the efficiency of phage therapy by limiting the resistance evolution of intermittent and chronic cystic fibrosis Pseudomonas aeruginosa lung isolates to four different phages. We first pre-adapted all phage strains against all bacterial strains and then compared the efficacy of pre-adapted and nonadapted phages against ancestral bacterial strains. We found that evolved phages were more efficient in reducing bacterial densities than ancestral phages. This was primarily because only 50% of bacterial strains were able to evolve resistance to evolved phages, whereas all bacteria were able to evolve some level of resistance to ancestral phages. Although the rate of resistance evolution did not differ between intermittent and chronic isolates, it incurred a relatively higher growth cost for chronic isolates when measured in the absence of phages. This is likely to explain why evolved phages were more effective in reducing the densities of chronic isolates. Our data show that pathogen genotypes respond differently to phage pre-adaptation, and as a result, phage therapies might need to be individually adjusted for different patients.


Anti-proliferation effects of ethanolic extracts from Sophora moorcroftiana seeds on human hepatocarcinoma HepG2 cell line.
Previous studies have shown that the ethanolic extracts from Sophora moorcroftiana seeds (ee-Sms) have in vitro anticancer properties. The anti-proliferation effects of ee-Sms on HepG2 cells were assessed by MTT assay and cell cycle analysis. Total cell proteins were separated by two-dimensional electrophoresis (2-DE), and protein spots with more than two-fold difference were analysed by MALDI-TOF/TOF-MS. MTT assay showed that the anti-proliferation of ee-Sms demonstrates dose- and time dependently. HepG2 cells were treated with ee-Sms at 1.30 mg/mL for 48 h induced cell cycle arrest in S phase. The differentially-expressed proteins were involved in DNA repair, cell proliferation, cell metabolism and immunoreaction. This study sheds new insights into the molecular mechanisms underlying the anti-proliferation properties of ee-Sms in HepG2 cells.


Micro-RNA-451 Reduces Proliferation of B-CPAP Human Papillary Thyroid Cancer Cells by Downregulating Expression of Activating Transcription Factor 2.
BACKGROUND MicroRNAs (miRNAs) are novel biomarkers that are important in tumorigenesis and cancer treatment resistance. miR-451 is expressed in human papillary thyroid carcinoma (PTC) tissues and is associated with tumor progression. This study investigated the molecular mechanism associated with the effects of miR-451 on B-CPAP human PTC cells in vitro. MATERIAL AND METHODS Binding of miRNAs to the 3' untranslated region (3'UTR) of messenger RNA (mRNA) was determined with a luciferase reporter assay. miRNAs and plasmids were transfected into human PTC B-CPAP cells with Lipofectamine 2000 Transfection Reagent. Cell viability was tested with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. The levels of miRNAs and mRNA were determined with quantitative polymerase chain reaction and protein levels were analyzed with immunoblotting. RESULTS miR-451 bound to wild-type but not mutant 3'-UTR of activating transcription factor 2 (ATF2). MiR-451 mimics inhibited the growth of B-CPAP cells and reduced mRNA and protein levels in ATF2, whereas miR-451 inhibitors promoted the growth of B-CPAP cells and increased mRNA and protein levels in ATF2. CONCLUSIONS miR-451 directly bound to the 3'UTR of ATF2, decreased mRNA and protein levels in ATF2, and inhibited growth of B-CPAP cells. Our findings suggest that miR-451 may be a potential therapeutic target for PTC.


D-β-hydroxybutyrate stabilizes the hippocampal CA3-CA1 circuit during acute insulin resistance.
1.The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KB) during low glucose availability. Neuronal KB uptake, which does not rely on the glucose transporter 4 (GLUT4) and insulin, has shown promising clinical applications in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of the exogenous KB D-β-hydroxybutyrate (D-βHb) on mouse brain metabolism during acute insulin resistance (AIR). We found the impacts of AIR and D-βHb to be qualitatively distinct across neuronal compartments: AIR decreased synaptic activity and LTP, and impaired axonal conduction, synchronization, and action potential (AP) properties. D-βHb rescued neuronal functions connected to axonal conduction and synchronization but did not rescue synaptic activity. While DβHb failed to rescue synaptic activity, it successfully rescued neuronal functions associated with axonal conduction and synchronization.


The role of mitochondrial dysfunction in macrophages on SiO2 -induced pulmonary fibrosis: A review.
Several epidemiologic and toxicological studies have widely regarded that mitochondrial dysfunction is a popular molecular event in the process of silicosis from different perspectives, but the details have not been systematically summarized yet. Thus, it is necessary to investigate how silica dust leads to pulmonary fibrosis by damaging the mitochondria of macrophages. In this review, we first introduce the molecular mechanisms that silica dust induce mitochondrial morphological and functional abnormalities and then introduce the main molecular mechanisms that silica-damaged mitochondria induce pulmonary fibrosis. Finally, we conclude that the mitochondrial abnormalities of alveolar macrophages caused by silica dust are involved deeply in the pathogenesis of silicosis through these two sequential mechanisms. Therefore, reducing the silica-damaged mitochondria will prevent the potential occurrence and fatality of the disease in the future.


Interlimb coordination during a cooperative bimanual object manipulation task.
This experiment examined asymmetries in the execution of an object manipulation task that requires the coordinated use of both hands. To this end, twenty right-hand-dominant participants performed a bimanual object manipulation task, which required that they reach for and grasp two objects located on a tabletop, fit the two objects through a hole in a horizontally or vertically oriented fitting board, and then rotate the objects 180° to produce a "beep" tone. Overall, the two hands were highly synchronized at the start, but not at end, of each movement phase. The decrease in interlimb coupling at later stages of the movement phase was primarily driven by the shorter movement time values for the dominant right hand. In addition, degree of left object rotation was greater than the right object, irrespective of board orientation. In sum, the results suggest that manual asymmetries and role assignment are not hardwired constraints, but depend on the overall task constraints and the manner in which the task is conceptualized.


Enhancement of hepatocarcinogenesis in female rats by ethinyl estradiol and mestranol but not estradiol.
The effect of dietary exposure to synthetic estrogens on hepatocarcinogenesis was evaluated. Diethylnitrosamine-initiated and 0.85% NaCl solution-treated noninitiated female Sprague-Dawley rats were transferred to semisynthetic diets containing mestranol (0, 0.1, or 0.5 ppm), ethinyl estradiol (0.5 ppm), estradiol (0.6 ppm), or mestranol plus beta-methasone (0.5 and 0.2 ppm, respectively). gamma-Glutamyl transferase (GGT)-positive transections and hematoxylin and eosin-detectable nodules and carcinomas were scored at 9 and 12 months. Quantitative stereological calculations were performed to determine GGT lesion number and size. At 9 months, in diethylnitrosamine-initiated rats, ethinyl estradiol and mestranol caused 3.5- and 4.4-fold increases, respectively, in the number of GGT lesions per liver and an increased incidence of hepatocellular carcinomas while estradiol had no enhancing effect. Addition of beta-methasone to the mestranol-containing diet caused a significant decrease in GGT lesion number but not carcinoma incidence compared to mestranol alone. At 12 months, in diethylnitrosamine-initiated rats, mestranol caused a dose-dependent increase in GGT lesion number. The hepatocellular carcinoma incidence was significantly increased at the high mestranol dose. Small increases in the numbers of larger GGT lesions were also observed in noninitiated animals treated with mestranol and ethinyl estradiol and are most probably due to promotion of spontaneously initiated hepatocytes. These results indicated that the synthetic estrogens cause dramatic increases in the number of presumptive preneoplastic GGT lesions. Carcinoma incidence is also enhanced. Thus, these results confirm and extend our previous studies which together with the results of others have shown that synthetic estrogens can act as promoters of hepatocarcinogenesis.


Differential regulation of human aortic smooth muscle cell proliferation by monocyte-derived macrophages from diabetic patients.
Macrophage accumulation in the arterial wall and smooth muscle cell (SMC) proliferation are features of type 2 diabetes mellitus (DM) and its vascular complications. However, the effects of diabetic monocyte-derived macrophages on vascular SMC proliferation are not clearly understood. In the present study, we investigated the pro-proliferative effect of macrophages isolated from DM patients on vascular SMCs. Macrophage-conditioned media (MCM) were prepared from macrophages isolated from DM patients. DM-MCM treatment induced HASMC proliferation, decreased p21(Cip1) and p27(Kip1) expressions, and increased microRNA (miR)-17-5p and miR-221 expressions. Inhibition of either miR-17-5p or miR-221 inhibited DM-MCM-induced cell proliferation. Inhibition of miR-17-5p abolished DM-MCM-induced p21(Cip1) down-regulation; and inhibition of miR-221 attenuated the DM-MCM-induced p27(Kip1) down-regulation. Furthermore, blocking assays demonstrated that PDGF-CC in DM-MCM is the major mediators of cell proliferation in SMCs. In conclusion, our present data support the hypothesis that SMC proliferation stimulated by macrophages may play critical roles in vascular complications in DM patients and suggest a new mechanism by which arterial disease is accelerated in diabetes.


Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors.
Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone with physiological roles in adipose tissue, the central nervous system and bone metabolism. While selective ligands for GIP receptor (GIPR) have not been advanced for disease treatment, dual and triple agonists of GIPR, in conjunction with that of glucagon-like peptide-1 (GLP-1) and glucagon receptors, are currently in clinical trials, with an expectation of enhanced efficacy beyond that of GLP-1 receptor (GLP-1R) agonist monotherapy for diabetic patients. Consequently, it is important to understand the pharmacological behavior of such drugs. In this study, we have explored signaling pathway specificity and the potential for biased agonism of mono-, dual- and tri-agonists of GIPR using human embryonic kidney 293 (HEK293) cells recombinantly expressing human GIPR or GLP-1R. Compared to GIP(1-42), the GIPR mono-agonists Pro3GIP and Lys3GIP are biased towards ERK1/2 phosphorylation (pERK1/2) relative to cAMP accumulation at GIPR, whereas the triple agonist at GLP-1R/GCGR/GIPR is biased towards pERK1/2 relative to β-arrestin2 recruitment. Moreover, the dual GIPR/GLP-1R agonist, LY3298176, is biased towards pERK1/2 relative to cAMP accumulation at both GIPR and GLP-1R compared to their respective endogenous ligands. These data reveal novel pharmacological properties of potential therapeutic agents that may impact on diversity in clinical responses.


Modulation of hepatic transcription and translation during early stages of aflatoxin B1 carcinogenesis.
Isolated rat hepatocytes have been used to study the transcription and translation processes at varied time intervals after administration of a single dose (6 mg/kg) of hepatocarcinogen aflatoxin B1 (AFB1). The effects of AFB1 during the first 24 h of drug treatment show a characteristic inhibition followed by periods of rapid recovery and also a hyperactive state when both heterogeneous nuclear RNA (HnRNA) transcription and cytoplasmic translation processes reach about 200% of control. Analysis of [3H]orotic acid pulse-labeled HnRNA and cytoplasmic polyadenylic acid(poly (A)) containing mRNA on sucrose gradients under conditions which prevent aggregation show a stepwise reduction in the total isotopic incorporation as well as in the size distribution during the first 9 h of AFB1 treatment. Between 9 and 24 h after AFB1 treatment, there is a recovery in the total incorporation as well as in the size of HnRNA and poly (A) containing mRNA. Analysis of translation products by a two-dimensional procedure shows loss of some high molecular weight products in AFB1-treated cells. At 24 h after AFB1 treatment (hyperactive stage) there is a total recovery of activity. Also, several new translation products not detected in the control hepatocytes are synthesized at this stage. The hyperactive stage might represent gene-derepression or reprogramming of gene expression.


Differential Clinical Significance of Neurotrophin-3 Expression according to MYCN Amplification and TrkC Expression in Neuroblastoma.
Neurotrophin-3 (NT-3), a member of the NT family, has only been considered an ancillary compound that provides anti-apoptotic benefits by inactivating tropomyosin receptor kinase C (TrkC)-induced apoptotic signals. However, little is known about the clinical relevance of NT-3 expression itself in neuroblastoma. The purpose of this study was to assess NT-3 expression in patients with neuroblastoma and its relevance to clinicopathologic findings and treatment outcomes. In this study, expression of NT-3 and TrkC was analyzed using immunohistochemistry in 240 patients with newly diagnosed neuroblastoma. The results of the study revealed that NT-3 expression was associated with older age at diagnosis, localized tumors, and more differentiated tumors but was not associated with early treatment response (degree of residual tumor volume after three cycles of chemotherapy) and progression-free survival (PFS). However, when analysis was confined to patients with MYCN amplified tumors, NT-3 expression was associated with better early treatment response with borderline significance (P = 0.092) and higher PFS (86.9% vs. 58.2%; P = 0.044). In multivariate analysis in patients with MYCN amplified tumors, NT-3 was independent prognostic factor (hazard ratio, 0.246; 95% confidence interval, 0.061-0.997; P = 0.050). In another subgroup analysis, the early treatment response was better if NT-3 was expressed in patients without TrkC expression (P = 0.053) while it was poorer in patients with TrkC expression (P = 0.023). This study suggests that NT-3 expression in neuroblastoma has its own clinical significance independent of TrkC expression, and its prognostic significance differs depending on the status of MYCN amplification and/or TrkC expression.


The action of β-hydroxybutyrate on the growth, metabolism and global histone H3 acetylation of spontaneous mouse mammary tumours: evidence of a β-hydroxybutyrate paradox.
Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth of some cancer cells and accelerates it in others. This "butyrate paradox" is thought to be due to butyrate mediating histone acetylation and thus inhibiting cell proliferation in cancers that preferentially utilise glucose (the Warburg effect); whereas in cells that oxidise butyrate as a fuel, it fails to reach inhibitory concentrations and can stimulate growth. We treated transgenic mice bearing spontaneous MMTV-NEU-NT mammary tumours with the ketone body β-hydroxybutyrate (β-OHB) and monitored tumour growth, metabolite concentrations and histone acetylation. In a cell line derived from these tumours, we also measured uptake of β-OHB and glucose, and lactate production, in the absence and presence of β-OHB. β-OHB administration accelerated growth of MMTV-NEU-NT tumours, and their metabolic profile showed significant increases in ATP, glutamine, serine and choline-related metabolites. The β-OHB concentration within the treated tumours, 0.46 ± 0.05 μmol/g, had no effect on histone acetylation as shown by western blots. Cultured tumour cells incubated with 0.5 mM β-OHB showed β-OHB uptake that would be equivalent to 54% of glycolytic ATP phosphorylation and no significant change in glucose consumption or lactate production. These results suggest that a β-OHB paradox may occur in these mammary tumours in a manner analogous to the butyrate paradox. At low β-OHB concentrations (<1 mM, as observed in our tumour model post-treatment), and in the absence of a Warburg effect, β-OHB is consumed and thus acts as an oxidative energy source and not as an epigenetic factor. This would explain the increase in tumour growth after treatment, the metabolic profiles and the absence of an effect on histone H3 acetylation.


Effects of organisational and patient factors on doctors' burnout: a national survey in China.
To measure the burnout of doctors affiliated with western medicine (WM) and traditional Chinese medicine (TCM) hospitals and to evaluate its relationships with organisational and patient factors. A national cross-sectional study in China. By convenience sampling, this study was conducted in 64 general hospitals from six provinces and Beijing between July 2014 and April 2015. There were a total of 2576 eligible participants, including 1766 WM doctors and 810 TCM doctors in this study. Burnout symptoms of emotional exhaustion, job involvement and personal accomplishment were measured. In total, 73.6% of doctors reported emotional exhaustion, the core component of burnout. In multivariable models, emotional exhaustion was significantly associated with organisational factors, including salary fairness [WM: odds ratio (OR)=2.36, 95% confidence interval (CI): 1.80 to 3.09; TCM: OR=1.59, 95% CI: 1.08 to 2.33], participation in organisational decision-making (WM: OR=1.58, 95% CI: 1.21 to 2.08; TCM: OR=1.84, 95% CI: 1.23 to 2.74), professional value (WM: OR=1.74, 95% CI: 1.35 to 2.25), frequency of participation in full-time training (TCM: OR=1.48, 95% CI: 1.01 to 2.16) and frequency of participation in clinical meetings (WM: OR=1.53, 95% CI: 1.11 to 2.10; TCM: OR=2.48, 95% CI: 1.57 to 3.92). Patient factors are also associated with burnout among both WM and TCM doctors, including respect (WM: OR=1.73, 95% CI: 1.31 to 2.28; TCM: OR=1.65, 95% CI: 1.10 to 2.45) and unreasonable demands (WM: OR=2.31, 95% CI: 1.68 to 3.20; TCM: OR=3.44, 95% CI: 2.15 to 5.49). Moreover, job involvement and personal accomplishment among both WM and TCM doctors were significantly associated with organisational and patient factors. Our results suggest that improving organisational management and patient behaviours may be beneficial to reduce doctors' burnout. Our findings require further validation in different organisational settings.


Levels of Occupational Exposure to Solar Ultraviolet Radiation in Vancouver, Canada.
Outdoor workers are at high risk of exposure to solar ultraviolet radiation (UVR), a known human carcinogen. In Canada, no objective measures of UVR exposure are available for occupational settings. The Outdoor Workers Project collected UVR exposure data among outdoor workers in Vancouver, Canada during the summer of 2013. Objective measures of exposure were taken for one week using calibrated electronic UVR dosimeters. Additional data was collected from workers on skin cancer risk factors, family history of skin cancer, and job type; as well as meteorological data for sampling days. Marginal models were constructed to examine the worker, job and meteorological determinants of UVR exposure levels, as measured in standard erythemal dose (SED). Seventy-eight workers were recruited, of which 73 had at least 1 day of measured UVR exposure for this analysis. Participants were mostly male, young and Caucasian. Mean exposure (corrected for repeated measures) was 1.08 SED. Exposure measures were highly variable even in the same workplace, ranging from 0.01 SED to 19.2 SED. Younger age, working in land-based construction, and sunnier weather forecasts led to higher levels of UVR exposure. Exposure levels capable of causing sunburn were common in this study of outdoor workers, in a location not typically associated with high sun exposure.


Predictors of COVID-19 Vaccine Uptake and Reasons for Vaccine Hesitancy Among New York State Refugees.
Resettled refugees in the U.S. face a disproportionately high risk of COVID-19 exposure, infection, and death. This study examines COVID-19 vaccination status among adult participants and their minor children, reasons for vaccine hesitancy, and predictors of vaccine uptake, as well as sources of COVID-19 news and information and trust in those sources. The data in this study were drawn from the Telehealth and COVID-19 Knowledge, Attitudes, and Practices in New York Refugee Communities Survey (N = 353), conducted March-May, 2022. The multivariate results indicate that in this sample of resettled refugees, those who reported higher levels of educational attainment, were from Afghanistan, and those who had fewer concerns about the vaccine were more likely to accept vaccination. The participants in this study identified local health workers, clinics, and community organizations - places where social workers are present - as both the largest source of nonsocial media COVID-19 news and information and the most trusted source of COVID-19 news and information. The implications from this study provide social workers with an understanding of the social and behavioral factors impacting vaccine uptake in refugee communities. According to the NASW Code of Ethics, social workers must challenge inequalities that persist against marginalized groups, such as racial and ethnic health disparities. Social work practitioners can play an essential role in decreasing unjust health disparities by providing accurate, culturally appropriate information on public health concerns such as COVID-19 to their refugee clients and within interprofessional collaboration.


Effects of Hyul-Bu-Chuke-Tang on Erythrocyte Deformability and Cerebrovascular CO(2) Reactivity in Normal Subjects.
Aim. Hyul-bu-chuke-tang (HCEt) is a well-known traditional herbal medicine that is used for the treatment of ischemic cerebrovascular disorders. We investigated the acute effects of HCEt on erythrocyte deformability and cerebrovascular CO(2) reactivity (CVR) in healthy male subjects. Materials and Methods. We examined erythrocyte deformability in an HCEt group (n = 14) and a control group (n = 10). CVR was measured using hyperventilation-induced CO(2) reactivity of the middle cerebral artery and transcranial Doppler (TCD) in the HCEt group (n = 11). A historical control group (n = 10) of CVR measurements was also created from our previous study. All measurements were performed prior to and 1, 2, and 3 hours after HCEt administration. Results. HCEt significantly improved erythrocyte deformability 1 hour after administration compared to the control group (2.9 ± 1.1% versus -0.6 ± 1.0%, P = 0.034). HCEt significantly improved the CVR 2 hours after administration compared to the historical control group (9.1 ± 4.0% versus -8.1 ± 4.1%, P = 0.007). The mean blood pressure and pulse rate did not vary from baseline values in either group. Conclusions. We demonstrated that HCEt improved erythrocyte deformability and CVR. Our findings suggest that an improvement in erythrocyte deformability contributes to HCEt's effect on cerebral microcirculation.


An overview of low disease activity and remission in psoriatic arthritis.
Psoriatic arthritis (PsA) is a complex, multisystem and potentially disabling disease with musculoskeletal and skin manifestations. In PsA, as well as in the other chronic rheumatic conditions, a state of low disease activity or remission should be the target of treatment but to reach this objective, in the assessment of PsA patients, is still an unmet need due to the heterogeneity of disease manifestations. With the introduction of anti-TNF treatment, low disease activity or remission become an achievable and suitable state that could be reached by 50%-60% of PsA patients. The aim of this paper is to briefly summarise the concept of low disease activity and remission in PsA, with particular focus on anti-TNF therapy.


Surgical treatment of 102 tendo achillis ruptures-- suture or tenontoplasty?
A series of 102 patients with total subcutaneous rupture of the achilles tendon treated surgically from 1944 to 1972 is presneted. All patients were treated early after the acute event, and the diagnosis was made on clinical examination. Group I comprises 54 patients treated over the first part of the period by simple tendon suture, and group II comprises 48 patients from the second part of the period treated by tenontoplasty ad modum Silfverskjöld. The results in the two groups are compared and also contrasted with the results following conservative treatment more recently reported. Operative treatment is recommended rather than conservative bandaging. There were no recurrent ruptures in group II, but 2 patients in group I had rupture recurrence. The functional results were not statistically significantly different in the two groups. There was no operative mortality. Surgical complications were infrequent, and, in general, did not affect the period of treatment, nor the duration of incapacity. Recent studies reported in the literature cast doubt on frequent previous reports of pathological changes in the tendon predisposing to rupture. Some constitutional weakness would appear to be etiological from this study where some familial incidence was noted, and particularly there was an incidence of not simultaneous bilateral rupture. The risk of contralateral rupture if patients returned to sporting activity to the same extent as before the primary injury was 26% (12-45%).


Prevalence and Antimicrobial Properties of Lactic Acid Bacteria in Nigerian Women During the Menstrual Cycle.
The composition of vagina lactic acid bacteria (LAB) differs within the different ethnic group. This study is aimed at determining the prevalence of LAB with their antimicrobial properties in Nigerian women's vagina during different stages of the menstrual cycle. Microorganisms were isolated from vaginal swabs of ten Nigerian women during different stages of the menstrual cycle and identified by partial sequencing of the 16S rRNA gene. The antimicrobial properties of the LAB were tested against the multidrug-resistant uropathogens. The prevalence of LAB was higher during ovulation period while during menstruation period, it declined. Twenty-five LAB isolates were identified as three species, namely: Lactobacillus plantarum (15), Lactobacillus fermentum (9), Lactobacillus brevis (1) and one acetic acid bacteria - Acetobacter pasteurianus. The LAB had antimicrobial activities against the three uropathogens with zones of inhibition from 8 to 22 mm. The presence of LAB inhibits the growth of Staphylococcus sp. GF01 also in the co-culture. High LAB counts were found during ovulation period with L. plantarum as a dominant species while during menstruation, there was a decrease in the LAB counts. The isolated LAB has antimicrobial properties against the urogenital pathogens tested thus exhibiting their potential protective role against uropathogens. The composition of vagina lactic acid bacteria (LAB) differs within the different ethnic group. This study is aimed at determining the prevalence of LAB with their antimicrobial properties in Nigerian women's vagina during different stages of the menstrual cycle. Microorganisms were isolated from vaginal swabs of ten Nigerian women during different stages of the menstrual cycle and identified by partial sequencing of the 16S rRNA gene. The antimicrobial properties of the LAB were tested against the multidrug-resistant uropathogens. The prevalence of LAB was higher during ovulation period while during menstruation period, it declined. Twenty-five LAB isolates were identified as three species, namely: Lactobacillus plantarum (15), Lactobacillus fermentum (9), Lactobacillus brevis (1) and one acetic acid bacteria – Acetobacter pasteurianus. The LAB had antimicrobial activities against the three uropathogens with zones of inhibition from 8 to 22 mm. The presence of LAB inhibits the growth of Staphylococcus sp. GF01 also in the co-culture. High LAB counts were found during ovulation period with L. plantarum as a dominant species while during menstruation, there was a decrease in the LAB counts. The isolated LAB has antimicrobial properties against the urogenital pathogens tested thus exhibiting their potential protective role against uropathogens.


Prolongation of segmental pancreatic allografts in dogs receiving cyclosporin A.
This study showed that a heterotopic autotransplant of the tail of the pancreas was capable of maintaining adequate glucoregulatory function in pancreatectomized dogs, glucose tolerance test curves, and K values not differing from normal dogs 4 months after transplantation. Hyperinsulinemia in the fasting state was observed in the absence of hypoglycemia in autograft and allograft recipients. Intraductal Ethibloc injection produced total replacement of the exocrine gland at 4 months by fibrosis but with the preservation of islets. Cyclosporin A (Cy A, oral drinking solution) in a dose of 25 mg/kg/day given to recipients of heterotopic segmental allografts produced a slight but significant prolongation of graft survival, but a dose of 40 mg/kg/day resulted in indefinite graft survival (greater than 100 days) in five of eight allograft recipients. During intravenous glucose tolerance tests (IVGTTs), fasting hyperinsulinemia and significantly impaired glucose degradation (K values) was observed in long-term surviving allograft recipients 4 months after transplantation. In four long-term surviving pancreatic allograft recipients initially given 40 mg/kg/day, the dose of Cy A was gradually reduced after 4 months to a maintenance dose of 5 mg/kg/day by 6 months. On a dose of 5 mg/kg/day, three dogs rejected their grafts between 18 and 28 days after this schedule had commenced. Successful reversal of the hyperglycemia in two of three dogs that rejected their grafts was achieved by i.v. methylprednisolone and increased doses of Cy A. These results indicate that Cy A alone could significantly prolong the survival of canine pancreatic segmental allografts, but initially higher doses were required than that found to be effective in prolonging renal allograft survival in the dog.


The relationship and predictive value of dementia and frailty for mortality in patients with surgically managed hip fractures.
Both dementia and frailty have been associated with worse outcomes in patients with hip fractures. However, the interrelation and predictive value of these two entities has yet to be clarified. The current study aimed to investigate the predictive relationship between dementia, frailty, and in-hospital mortality after hip fracture surgery. All patients registered in the 2019 National Inpatient Sample Database who were 50 years or older and underwent emergency hip fracture surgery following a traumatic fall were eligible for inclusion. Logistic regression (LR) models were constructed with in-hospital mortality as the response variables. One model was constructed including markers of frailty and one model was constructed excluding markers of frailty [Orthopedic Frailty Score (OFS) and weight loss]. The feature importance of all variables was determined using the permutation importance method. New LR models were then fitted using the top ten most important variables. The area under the receiver-operating characteristic curve (AUC) was used to compare the predictive ability of these models. An estimated total of 216,395 patients were included. Dementia was the 7th most important variable for predicting in-hospital mortality. When the OFS and weight loss were included, they replaced dementia in importance. There was no significant difference in the predictive ability of the models when comparing the model that included markers of frailty [AUC for in-hospital mortality (95% CI) 0.79 (0.77-0.81)] with the model that excluded markers of frailty [AUC for in-hospital mortality (95% CI) 0.79 (0.77-0.80)]. Dementia functions as a surrogate for frailty when predicting in-hospital mortality in hip fracture patients. This finding highlights the importance of early frailty screening for improvement of care pathways and discussions with patients and their families in regard to expected outcomes.


Evaluating Real-World Adherence and Effectiveness of the "Reboot Online" Program for the Management of Chronic Pain in Routine Care.
Chronic pain is a prevalent and disabling condition. Reboot Online was developed as a multidisciplinary and widely accessible online treatment program for chronic pain. It has been shown to be effective in clinical trials, but the effectiveness of this program in routine care settings remains unknown. This study aimed to examine program adherence and effectiveness in a real-world sample of participants completing Reboot Online in the community. A retrospective cohort study was conducted using real-world data from participants referred the Reboot Online program by clinicians as part of their routine care, from April 2017 to April 2019. Routinely collected data on program adherence, participant demography and clinical outcomes were included in the analyses. Measures included the Pain Self Efficacy Questionnaire, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain-Disability Index, and Patient Health Questionnaire 9-item (depression). Logistic regression was used to investigate whether certain factors predict program adherence (completion versus noncompletion), and linear mixed models were used to examine effectiveness. In total, 867 participants were included in the analyses, and 583 engaged with at least one Reboot Online lesson. Of these, 42% (n = 247) completed the course in its entirety, with rurality and lower Tampa scores being significant predictors of adherence. Completers demonstrated significant improvements across all outcome measures (effect sizes ranging from 0.22 to 0.51). Reboot Online is an effective treatment for chronic pain in the routine care setting. Adherence was variable (overall 42%), and could be predicted by rurality and less fear of movement at baseline.


Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript.
The first step in the decay of some eukaryotic mRNAs is the shortening of the poly(A) tail. To examine how the transcript body was degraded after deadenylation, we followed the decay of a pulse of newly synthesized MFA2 transcripts while utilizing two strategies to trap intermediates in the degradation pathway. First, we inserted strong RNA secondary structures, which can slow exonucleolytic digestion and thereby trap decay intermediates, into the MFA2 5' UTR. Following deadenylation, fragments of the MFA2 mRNA trimmed from the 5' end to the site of secondary structure accumulated as full-length mRNA levels decreased. In addition, in cells deleted for the XRN1 gene, which encodes a major 5' to 3' exonuclease in yeast, the MFA2 transcript is deadenylated normally but persists as a full-length mRNA lacking the 5' cap structure. These results define a mRNA decay pathway in which deadenylation leads to decapping of the mRNA followed by 5'-->3' exonucleolytic degradation of the transcript body. Because the poly(A) tail and the cap structure are found on essentially all mRNAs, this pathway could be a general mechanism for the decay of many eukaryotic transcripts.


Assessing beef carcass tissue weights using computed tomography spirals of primal cuts.
More than 800 beef primal cuts from 44 Aberdeen Angus and Limousin-cross steers carcasses were scanned using spiral computed tomography (CT) and dissected. Thresholds for the segmentation of fat, muscle and bone in the CT spirals were estimated with the objective of assessing the weight of these tissues in the primal cuts and in the entire carcasses. Thresholds were estimated using half of the dataset (DBE) and then validated in the other half (DBV). Automatic image analysis procedures were used to assess tissue weights. The R(2) of the regression between primal tissue weight by dissection and CT were high in both datasets for fat (DBE, 0.89; DBV, 0.92), muscle (DBE, 0.99; DBV, 0.99) and bone (DBE, 0.95; DBV, 0.97). The estimation of total carcass tissue weights were also very accurate for the three tissues (R(2) values of 0.95 to 0.96), indicating that CT scanning may deliver very accurate information on beef carcass composition faster and with lower cost than physical dissection and without damaging or depreciating the primal joints.


CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity.
Mesenchymal stem cells (MSC) are not universal and may be subject to dynamic changes upon local milieus in vivo and after isolation and cultivation in vitro. Here, we demonstrate that MSC derived from murine pericardial adipose tissue (pMSC) constitute two cohorts of population distinguished by the level of CD73 expression (termed as CD73high and CD73low pMSC). Transplantation of two types of cells into mouse hearts after myocardial infarction (MI) revealed that the CD73high pMSC preferentially brought about structural and functional repair in comparison to the PBS control and CD73low pMSC. Furthermore, the CD73high pMSC displayed a pronounced anti-inflammatory activity by attenuating CCR2+ macrophage infiltration and upregulating several anti-inflammatory genes 5 days after in vivo transplantation and ex vivo cocultivation with peritoneal macrophages. The immunomodulatory effect was not seen in cocultivation experiments with pMSC derived from CD73 knockout mice (CD73-/-) but was partially blocked by pretreatment of the A2b receptor antagonist, PSB603. The results highlight a heterogeneity of the CD73 expression that may be related to its catalytic products on the modulation of the local immune response and thus provide a possible explanation to the inconsistency of the regenerative results when different sources of donor cells were used in stem cell-based therapy.


A 5-year follow-up of primary seminal vesicle adenocarcinoma: A case report.
Primary seminal vesicle adenocarcinoma (PSVA) is an extremely rare malignancy that should be carefully differentiated from cancer originating in the prostate, colon or bladder. Without standard guidelines, radical resection is considered a mainstay treatment, providing the best prognosis. However, as manifestations of PSVA are not detected in early stages, the majority of cases of PSVA are diagnosed at late stages, contributing to poor prognosis. We described the case of a PSVA patient confirmed by histopathology and immunohistochemistry (IHC) staining positive for carbohydrate antigen-125 (CA-125) and negative for prostate specific antigen (PSA). Primary seminal vesicle adenocarcinoma. Surgery was carried out at the beginning, however, residual tumor was verified; thus 3 cycles of chemotherapy with a regimen of paclitaxel and cis-platinum were performed, followed by radical pelvic radiotherapy with a dose of 60 Gray in 30 fractions; then, another 3 cycles of the same chemotherapy were carried out. At the moment, the patient is still under follow-up and has been disease-free for more than 5 years. Our manuscript describes a patient with PSVA with long-term survival and supplies a successful management strategy for this malignancy.


Puerarin inhibits amyloid β-induced NLRP3 inflammasome activation in retinal pigment epithelial cells via suppressing ROS-dependent oxidative and endoplasmic reticulum stresses.
Amyloid β (Aβ) is a critical stimulator that promotes the progression of age-related macular degeneration (AMD). NLRP3 inflammasome activation induced by Aβ is estimated to be responsible for retinal pigment epithelium (RPE) dysfunction in such disease. Puerarin, one of the major active constituents of Kudzu root, has been widely used in the clinical treatment of AMD in China for decades; however, the detailed molecular mechanism remains far from clear. In this study, we investigated the protective effect and underlying mechanism of puerarin against Aβ1-40-induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells. The results showed that Aβ1-40 induced NLRP3 inflammasome activation mainly via triggering ROS-dependent oxidative stress, particularly lipid peroxidation, and endoplasmic reticulum stress in LPS-primed ARPE-19 cells; however, such effect could be significantly reversed by puerarin in a dose-dependent manner. Furthermore, the effect of puerarin was potentially mediated through activating Nrf2/HO-1 antioxidant signaling pathway and inhibiting Aβ1-40-induced phosphorylation of IRE1 and PERK as well as nuclear expression of ATF6α. Therefore, the significance of the current study is to reveal the novel mechanism of puerarin in the prevention of AMD.


21st century glaucoma care.
Glaucoma care has evolved dramatically over the past generation, with changes that have incorporated new technology and improved understanding of the disease process. A major need is to construct a useful definition of glaucomatous optic neuropathy that can be used to compare data across clinical research studies. The treatment of glaucoma should now be based on achievement of a goal target for intraocular pressure, unique to each patient. Adherence with eye drop treatment is far from ideal and can be improved using reminder systems. Sustained delivery of glaucoma medication is on the horizon. New surgical approaches to glaucoma are being actively studied but have not as yet found their place in its care, with rigorous testing against present treatments needed.


Highly Stable Bimetallic AuIr/TiO₂ Catalyst: Physical Origins of the Intrinsic High Stability against Sintering.
It has been a long-lived research topic in the field of heterogeneous catalysts to find a way of stabilizing supported gold catalyst against sintering. Herein, we report highly stable AuIr bimetallic nanoparticles on TiO2 synthesized by sequential deposition-precipitation. To reveal the physical origin of the high stability of AuIr/TiO2, we used aberration-corrected scanning transmission electron microscopy (STEM), STEM-tomography, and density functional theory (DFT) calculations. Three-dimensional structures of AuIr/TiO2 obtained by STEM-tomography indicate that AuIr nanoparticles on TiO2 have intrinsically lower free energy and less driving force for sintering than Au nanoparticles. DFT calculations on segregation behavior of AuIr slabs on TiO2 showed that the presence of Ir near the TiO2 surface increases the adhesion energy of the bimetallic slabs to the TiO2 and the attractive interactions between Ir and TiO2 lead to higher stability of AuIr nanoparticles as compared to Au nanoparticles.


Nanotechnology and Health.
: Potential adverse health effects associated with exposure to engineered or synthesized nanomaterials have not been reported in humans; however, there is accumulating evidence from animal studies that exposure to some nanomaterials is harmful. While there is uncertainty as to the likelihood, frequency, and intensity of exposures experienced by those working around engineered nanoparticles, the American College of Occupational and Environmental Medicine has developed this guidance document for occupational medicine physicians and their colleagues to offer prudent preventive recommendations on the topics of exposure monitoring, exposure controls, and medical surveillance.


Lower prevalence of non-reproductive system cancers among female former college athletes.
Lower prevalence of non-reproductive system cancers among former college athletes. Med. Sci. Sports Exerc., Vol. 21, No. 3, pp. 250-253, 1989. The prevalence (lifetime occurrence) rates of cancers of nonreproductive organs and tissues were determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 who had been nonathletes, from data on medical history, reproductive history, athletic training, and diet. The non-reproductive system cancers were divided into two classes: class I, which included cancers of the digestive system, thyroid, bladder, lung, and other sites and hematopoietic cancers (lymphoma, leukemia, myeloma, and Hodgkin's disease), and class II, which included skin cancers and cutaneous melanoma. The former college athletes had a significantly lower prevalence of class I cancers compared to the nonathletes; the age-adjusted relative risk (RR) equals 3.34, 95% confidence limits (1.35, 8.33), P = 0.009. In contrast, the prevalence rates of malignant melanomas and skin cancers did not differ significantly between the former athletes and nonathletes. The age-adjusted RR did not differ from 1.0. The lower prevalence rate of class I cancers among the former athletes is in accord with previous findings of a significantly lower prevalence rate of breast cancer and cancers of the reproductive system among former college athletes compared to nonathletes.


Phase retrieval with unknown sampling factors via the two-dimensional chirp z-transform.
We derive the analytic gradient of a phase retrieval error metric with respect to the sampling factor or the f-number that produced the measured point-spread function. This allows us to efficiently optimize over the sampling factor, thereby improving the accuracy of the phase estimate. Computer simulation results show its effectiveness.


[Assessment of disease burden related to non-optimal temperature across China].
Objective: To estimate the excess mortality attributed to non-optimal ambient temperature in China. Methods: Mortality data and meteorological data from 239 counties in 2013-2018 were collected to simulate the quantitative exposure-response relationship between the temperature and mortality using distributed lag nonlinear models for time series studies. Then the number of non-optimal-temperature-related excess deaths was assessed and the spatial distribution was explored. Results: There were averagely (12±8) cases of all-cause deaths per day per county from 2013 to 2018. The average daily temperature was (14.98±10.31)℃, and the daily average relative humidity was (68.79±17.25)%. The daily average O3 concentration was (58.95±34.96) μg/m³, and the daily average PM2.5 concentration was (54.97±45.56) μg/m³. The exposure-response curve between daily average temperature and all-cause mortality showed a "U" shape, and the theoretical minimum mortality temperature (MMT) corresponding to the minimum number of deaths was 21.60 ℃. When the temperature was higher than MMT, the heat-related health effect increased with the temperature rising. When the temperature was lower than MMT, the cold-related effect increased with the temperature decreasing. The attributable fraction (AF) of death caused by non-optimal temperature was 8.76% (95%CI: 8.07%-9.10%), and the AF of death caused by cold effect and heat effect was 7.21% (95%CI: 6.51%-7.57%) and 1.55% (95%CI: 1.46%-1.61%), respectively. The excess deaths from non-optimal temperature in 2015 were 519 122, 72.98% of which could be attributed to low temperature. The number of excess deaths caused by non-optimal temperature mainly showed a decreasing trend from the east to the west, relatively high (117 522) in East China. Heilongjiang Province (in Northeast China) had the most excess deaths (26 924) caused by low temperature, and Guangdong Province(in South China) had the most excess deaths (27 763) caused by high temperature. Conclusion: The non-optimal temperature has a significant impact on health and causes a considerable burden of disease in China with obvious spatial heterogeneity.


Serologic therapy of tetanus in the United States, 1965-1971.
To study the influence of tetanus antitoxins on the outcome of human tatanus, we analyzed data on 545 cases reported to the Center for Disease Control from 1965 through 1971. Patients treated with antitoxin had a significantly lower case-fatality ratio than untreated patients, and the effect of serotherapy was not modified significantly by the age or race of the subjects. Antitoxin of equine origin and human tetanus immune globulin (TIG) were equally effective. The data on the effect of different doses of TIG suggest that 500 units may be as effective as the currently recommended therapeutic dose of 3,000 to 10,000 units. The importance of possible bias introduced by unmeasured factors such as quality of supportive therapy could not be determined, but confounding by 11 recorded potentially confounding factors was minimal.


The neuropathology of schizophrenia.
Insofar as schizophrenia is a neuropsychiatric syndrome involving the brain, neuropathology is a promising, if not essential investigative approach. Although traditional neuropathology has yet to yield a pathognomonic lesion in schizophrenia, there have been no shortages of findings. Unfortunately, many of these findings have not only failed to be pathognomonic, but they have not been consistently replicated. Fortunately, newer neuropathological techniques, such as post-mortem neurochemistry, have resulted in findings among the most reproducible in schizophrenia research. Although one of these, increased dopamine receptors in the basal ganglia of schizophrenic patients, has been replicated many times, it suffers from doubts as to its clinical relevance. Are these increases in dopamine receptors primary to the illness or a side effect of the treatment? This article discusses the relevance of this finding, reviews other highlights of post-mortem neurochemistry and traditional neuropathology, and discusses new horizons such as autoradiography, immunocytochemistry, and neuronal morphometrics.


Angiomatoid malignant fibrous histiocytoma with extensive lymphadenopathy simulating Castleman's disease.
We report the association in a 10-year-old boy of an angiomatoid malignant fibrous histiocytoma (AMFH) of the left thigh with ipsilateral inguinal, pelvic and extensive retroperitoneal lymphadenopathy, and severe systemic manifestations. These include growth retardation, fever, severe anemia, hypergammaglobinemia, and hypoalbuminemia. At ultrastructural level the tumor was characterized by an abundance of myofibroblasts, occasional histiocytes, and small vessels with marked reduplication of the basal lamina. Biopsies of the inguinal and abdominal lymph nodes showed follicular hyperplasia and massive plasmacytosis indistinguishable from Castleman's disease (giant lymph node hyperplasia) of plasma cell type. The radical surgical excision of the primary tumor in the thigh resulted in the disappearance of the abdominal lymphadenopathy and a marked reduction in size of the pelvic lymph nodes with marked decrease of the gammaglobulins, thus proving that the nodal lesions were the expression of a reactive process to the tumor rather than a coincidental independent lymphoproliferative disorder. Retroperitoneal and pelvic node dissection was performed 1 year after the radical excision of the thigh tumor because of persistent pelvic lymphadenopathy and failure of serum immunoglobulins M and A to return to normal level, with a recent peak of IgA to twofolds that of normal value. Metastatic AMFH was found in the three pelvic nodes. One month postoperatively IgA returned to near normal level whereas IgM remained slightly elevated.


A highly selective, organocatalytic route to chiral dihydro-1,2-oxazines.
[reaction: see text] The organocatalyzed asymmetric synthesis of chiral dihydro-1,2-oxazines from achiral starting materials proceeds in moderate to excellent yields and excellent enantioselectivity. This sequential reaction gives the desired products in a single pot.


[Computation and experimental examination of an implant structure made by a fibre-reinforced building method for the bypass of continuity defects of the mandible].
A partial resection of the lower jaw often has to be carried out in the context of the surgical removal of tumours in the lower jaw, mouth and tongue-floor space and lower jaw fractures with loss of substance, benign bone lesions and extensive difficult inflammation of bone tissue, respectively. The primary reconstruction of the lower jaw after partial resection with loss of continuity is mainly important for functional and aesthetic reasons. The defects of lower jaw continuity are often bridged with metal plates to reconstruct the masticatory function of the lower jaw, temporarily or permanently. Functional as well as aesthetic disadvantages arise in the case of the application of such plates as a result of a high stiffness jump between reconstruction plate and bone and their insufficiently individual design. The employment of biocompatible, carbon-fibre-reinforced Polyetheretherketon (CF-PEEK) permits the development of a geometry- and stiffness-adapted carrying structure for the mandible. For the demand-adapted dimensioning and the test of a CF-PEEK bandage, the application of optical methods, such as the grey value correlation method, is suited as well as numeric methods, such as the finite element method. In an initial analysis of deformation behaviour, the various osteosynthesis configurations are comparatively investigated on a model jaw. The calculations and tests of the lower jaw model show that the use of the new CF-PEEK bandage compared to the use of conventional titanium osteosynthesis plates shows a mechanical behaviour which is much better adapted to the natural lower jaw.


High levels of tumor-infiltrating lymphocytes showed better clinical outcomes in FOLFOX-treated gastric cancer patients.
Background: Tumor-infiltrating lymphocytes (TILs) and postoperative chemotherapeutics interact in the tumor micro-environment. This interaction has not been well investigated in gastric cancer. Materials & methods: A total of 129 patients were divided into high or low TILs based on the median number of positive CD3+ and FoxP3+ T cells, which was assessed by immunocytochemistry. Results: Cox regression analysis showed that the stage III disease with shorter overall survival was significant. The analysis showed that high numbers of CD3+ or FoxP3+ T cells have better clinical outcomes in FOLFOX-treated patients. Conclusion: High CD3+ and FoxP3+ T-cell infiltration was associated with better clinical outcomes in patients with gastric cancer treated with FOLFOX, suggesting TILs incorporated into algorithms to improve the therapeutic efficacy of optimal chemotherapy.


Fumitremorgins and Relatives - From Tremorgenic Compounds to Valuable Anti-Cancer Drugs.
Fumitremorgins are mycotoxins but can also inhibit cancer cells and reverse their drug resistance. The bioactivity of prenylated cyclo-Trp-Pro dipeptides and their derivatives concerning their application in anti-cancer therapies will be discussed. Reports on the discovery and assessment of this class of fungal compounds are compiled from literature using Google Scholar and PubMed. The bioactivities of the natural compounds are discussed with the aim of their improvement for cancer therapy. Although a number of compounds of this class have been found, only a minority of them showed bioactivity in the applied bioassays. Fumitremorgins and related compounds are active against various cancer cells but they are also mycotoxins. Some of these natural compounds can arrest cancer cells in their cell cycle and some can block ABC-transporters and reverse resistance in chemotherapy. Structure activity relationships have been deduced leading to the prediction of highly active compounds. Several easily accessible derivatives of these natural products have been discovered being highly selective and non-toxic. Sophisticated screening methods, high throughput screening, metabolic engineering, and synthetic biology are novel and promising technologies for the search for highly active drugs. Rapid gene sequencing in combination with engineered biosynthetic pathways should contribute substantially to novel pharmaceutics.


Using an experiment among clinical experts to determine the cost and clinical impact of rapid whole exome sequencing in acute pediatric settings.
Evaluate the cost and clinical impacts of rapid whole-exome sequencing (rWES) for managing pediatric patients with unknown etiologies of critical illnesses through an expert elicitation experiment. Physicians in the intervention group (n = 10) could order rWES to complete three real-world case studies, while physicians in the control group (n = 8) could not. Costs and health outcomes between and within groups were compared. The cost incurred in the intervention group was consistently higher than the control by 60,000-70,000 THB. Fewer other investigation costs were incurred when rWES could provide a diagnosis. Less cost was incurred when an rWES that could lead to a change in management was ordered earlier. Diagnostic accuracy and the quality of non-pharmaceutical interventions were superior when rWES was available. In acute pediatric settings, rWES offered clinical benefits at the average cost of 60,000-70,000 THB. Whether this test is cost-effective warrants further investigations. Several challenges, including cost and ethical concerns for assessing high-cost technology for rare diseases in resource-limited settings, were potentially overcome by our study design using expert elicitation methods.


Identification and expression of a host-recognized antigen, FspA, from Flavobacterium psychrophilum.
Flavobacterium psychrophilum is the aetiological agent of rainbow trout fry syndrome, an economically important disease of immature salmonid fish for which there is no vaccine. Convalescent serum from the host, rainbow trout (Oncorhynchus mykiss), reacted strongly with a approximately 20 kDa, Flavobacterium-specific protein antigen (subsequently named FspA) from F. psychrophilum. Protein-enriched, detergent-partitioned samples were separated by two-dimensional gel electrophoresis and the protein target was excised, proteolytically cleaved and the resulting peptides analysed by MS. Quadrupole-time-of-flight MS was used to generate a fragmented peptide spectrum. The resulting peptide sequences were then used to design degenerate PCR primers to amplify the gene (fspA) of interest: 612 bp encoding 203 aa, including a putative 19 aa N-terminal signal sequence which predicted a processed 19 303.6 Da protein. FspA proved to be unique and only homologous to two unspecified sequences reported from Flavobacterium johnsoniae, although weakly homologous to a Yersinia pseudotuberculosis adhesin. An amplified gene fragment (537 bp, encoding 179 aa) was further cloned into an expression vector, expressed as a approximately 30 kDa N-terminal fusion protein and found to retain its strong reactivity with host serum antibodies. These results suggest that the surface-localized FspA may be an important subunit vaccine candidate antigen against F. psychrophilum.


[Examination of dust generated from a workplace where steel wire coil are unwound].
Analyses of constituents, measurement of concentrations, research of size distributions and scanning electron microscopic examinations were carried out to determine the type and amount of dust generated in a working environment where steel wire coils are unwound. In about a 700 m2 work area unit, stationary samplings, including A-sampling (24 points) and B-sampling (1 point), which are defined by the law, were carried out. The dust concentration was measured by a digital dust indicator. A low volume air sampler was used to determine the conversion factor of the values obtained by the digital dust indicator. Because the result of the dust level by A-sampling and B-sampling were 0.64 mg/m3 and 0.82 mg/m3 respectively, they can both be classified as Control Class 1. A proportion of less than 7 microns of the airborne dust made up about 15 to 20% (volume %) of the total dust in the working environments. Metallic dust and white dust were identified in the accumulated dust. By measuring with a X-ray diffractometry, it was determined that the metal dust constituent was Zn and the white dust constituent was Zn4CO3(OH)6.H2O. By a scanning electron microscopic examination, the scope of the particles was proven to be non-fibrous.


Hostility, social support, and perceptions of work.
The aim of this study was to determine whether hostility and perceived availability of social support are related to perceptions of the work environment. The W.W. Cook and D.M. Medley (1954) Hostility (Ho) scale; the Interpersonal Support Evaluation List (S. Cohen, R. Mermelstein, T. Kamarck, & H. Hoberman, 1985); and measures of collegiality, time pressure, and job dissatisfaction were completed by 204 attorneys (159 men and 45 women). After controlling for age, gender, and other job characteristics, high Ho scores were related to lower perceived supportive collegiality at work. Low perceived availability of social support was related to greater job dissatisfaction. Neither hostility nor social support was associated with perceptions of time pressure at work. These findings suggest that hostility and availability of social support may be an important pathway linking certain job characteristics to cardiovascular disease and other illnesses.


Investigating the exon 6 sequence changes of interleukin 7 receptor A (IL7RA) gene in patients with relapsing-remitting multiple sclerosis.
Interleukin 7 receptor alpha (IL7RA) gene that encodes a subunit of IL7 receptor has been reported to be associated with different immunologic disease. Multiple Sclerosis (MS) patients have shown an aberrant blood level of soluble form of IL7R protein. The genomic changes in the sequence of this gene have been suggested to be correlated with its altered splicing specially, variants in the exon 6 of the gene have been reported to influence the maintenance or skipping of this exon and control the soluble or insoluble form of the final product. In order to evaluate this changes in the IL7RA gene and to determine a possible correlation between these changes and the MS susceptibility the whole sequence of the exon 6 and 7 and their flanking sequences were analyzed. In this regard, we investigate the sequence changes of the exon 6 and 7 of the IL7RA gene in 75 relapsing-remitting MS patients and compare the results with 75 healthy control using sequence analyzing. The results of the sequence analysis were used in two aspects. The allelic and genotypic estimated frequencies of a reported risk variant rs6897932 in patients and controls in our population confirmed its association with the disease (P= 0.009, OR = 6.273, for TT genotype). Also, we report a possible hazardous cutoff for changes in a potential exon splicing silencer element (ESS (nt. 20-24)) and its correlation with rs6897932 to confer the risk of developing MS. In conclusion our results confirm the association between IL7RA exon 6 sequence changes and increased susceptibility for multiple sclerosis.


The association between social media use and body dysmorphic symptoms in young people.
Social media use (SMU) is highly prevalent amongst young people and previous research suggests an association with mental health problems, including poor body image. However, the potential relationship between SMU and body dysmorphic disorder (BDD) has received little attention. Furthermore, little is known about the factors that moderate the potential association between SMU and body dysmorphic symptoms. The current study tested the associations between three facets of SMU and body dysmorphic symptoms and explored perfectionism as a moderator in a non-clinical sample. Two-hundred and nine 16-18-year-olds (mean age = 16.5 years, 37% male) recruited from schools in London completed an online survey measuring aspects of SMU, including: frequency of image-and text-based SMU; motivations for SMU (appearance, popularity, connection or values and interests); and active and passive SMU. Participants additionally completed validated measures of body dysmorphic symptoms, perfectionism, and anxiety/depressive symptoms. Linear regression models tested the association of body dysmorphic symptoms with different facets of SMU, with and without adjustment for age, sex and anxiety/depressive symptoms. Frequency of use of image-based, but not text-based, platforms was significantly and positively associated with body dysmorphic symptoms, and this association remained significant in the adjusted models. Appearance-based motivation for SMU was the only motivator uniquely associated with body dysmorphic symptoms across the unadjusted and adjusted models. Passive, not active, SMU was associated with body dysmorphic symptoms in unadjusted models, but this association became non-significant in the adjusted models. Self-oriented perfectionism moderated the association between frequency of image-based SMU and body dysmorphic symptoms. Image-based SMU, and appearance-based motivations for SMU, are positively associated with body dysmorphic symptoms. Self-oriented perfectionism may amplify the relationship between SMU and body dysmorphic symptoms. Our findings highlight the importance of a nuanced approach to examining SMU, and the need for further research to determine whether specific facets of SMU contribute to the development and/or maintenance of body dysmorphic symptoms.


Phase I combining a P-glycoprotein inhibitor, MS209, in combination with docetaxel in patients with advanced malignancies.
The purpose of this study was to investigate the safety and tolerability of MS209, a potent inhibitor of P-glycoprotein, when given in combination with docetaxel and to determine whether MS209 affects docetaxel pharmacokinetics. Patients with advanced solid malignancies were eligible for this phase I trial. Docetaxel as 1-hour infusion was given alone during the first cycle. MS209 was introduced as of cycle 2 and given orally 30 minutes after docetaxel infusion. The dose escalation scheme followed a modified Fibonacci model with six steps (docetaxel, 60-100 mg/m2 and MS209, 300-1,200 mg per body). A total of 30 patients were treated at five dose levels. Dose-limiting toxicities were febrile neutropenia, infection, stomatitis, dysphagia, and fatigue. The maximum tolerated dose was reached at level 5 (docetaxel, 80-MS: 1,200). Pharmacokinetic analysis failed to show a strong pharmacokinetic interaction between the two compounds, but at the highest dose levels, there is a trend to an increase of docetaxel AUC when this agent is given in combination with MS209. MS209 can be given in combination with docetaxel, with limited effect on docetaxel toxicity or pharmacokinetics.


Diabetes Education as a Career Choice.
The purpose of the study was to examine the field of diabetes education along with identifying facilitators and barriers for future health care professionals entering the specialty field of diabetes education. Faculty members who were currently teaching in a health-related discipline, the students of those faculty members, and nursing students who were members of the National Student Nursing Association were surveyed to gather descriptive data. While faculty members reported they are promoting diabetes education to their health professions students, many nursing students are not aware of this career path. Nursing students understand that diabetes is a significant problem and will be something they encounter in all areas of their careers, but many were not sure they wanted to specialize in it. There is a gap between what faculty members and students report as far as awareness of the diabetes education specialty. In addition, misinformation about diabetes and people living with diabetes may be a deterrent for potential future diabetes educators. American Association of Diabetes Educators, health professions faculty members, and practicing diabetes educators can do more to clear up misconceptions and promote diabetes education as a career path for students in the health professions.


In vivo studies on the dynamics of histone-DNA interaction: evidence for nucleosome dissolution during replication and transcription and a low level of dissolution independent of both.
Histones have been both radiolabeled and density-labeled with amino acids in vivo to determine the dynamics of histone-DNA and histone-histone interactions at the replication fork and on active genes. Proteins were uniformly labeled and subsequently chased for three cell generations. During the chase period, H3,H4 tetramers dissociated from the H2A,H2B dimers to re-form nucleosomes with the corresponding nondense histones synthesized during the chase period. These data suggest that the prereplicative nucleosomes are dissolved during advancement of the replication fork with release of associated histones in the form of the H3,H4 tetramers and H2A,H2B dimers. Experiments that involve density labeling of cells in the presence of actinomycin D indicate that the dynamic exchange of H2A,H2B that has been previously described [Jackson, V. (1987) Biochemistry 26, 2315-2324] is partially dependent on RNA polymerase movement. These results provide indirect evidence that nucleosome dissolution occurs during transcription. When deposition during replication and transcription is inhibited by simultaneous treatment of cells with cytosine arabinoside and actinomycin D, the majority of the newly synthesized histones are unable to deposit into nucleosome structure. The low level of deposition that is observed has characteristics similar to the deposition of uH2A and uH2B, and it is proposed that conjugation of H2A and H2B by ubiquitin occurs when these proteins are in a free pool within the nucleus. The new H3,H4 tetramers and new H2A,H2B dimers when prevented from depositing are not stable. New and old H3 and H4 intermix to form hybrid tetramers, and a similar intermixing is observed for the H2A,H2B dimers. A model is presented to describe the dynamics of histone-DNA interactions during replication and transcription.


[Application of delta-shaped anastomosis in totally laparoscopic distal gastrectomy].
To explore the technical feasibility, safety, and clinical efficacy of delta-shaped anastomosis in totally laparoscopic distal gastrectomy (TLDG). Clinical data of 18 patients with gastric cancer who received TLDG with delta-shaped anastomosis from November 2012 to December 2012 were retrospectively analyzed. The delta-shaped anastomosis is a new method of intraabdominal Billroth I anastomosis using only linear stapler. The posterior wall of the stomach and that of the duodenum were put together using linear stapler, and the common stab incision was also closed with linear stapler. The anastomosis was finished with a delta-shaped. TLDG with delta-shaped anastomosis was successfully carried out in all the patients. The mean operation time and mean time for anastomosis were (156.3 ± 38.5) minutes and (24.6 ± 11.2) minutes. The lengths of upper and lower segment of resection form gastric cancer were (5.8 ± 2.4) cm and (4.1 ± 2.7) cm. Blood loss was (70.7 ± 43.8) ml and number of dissected lymph nodes was 32.4 ± 12.0 per patient. The average time to ground activities, time to flatus, time to fluid diet and length of hospital stay were (1.8 ± 0.9) days, (3.1 ± 1.2) days, (3.6 ± 1.7) days, and (9.6 ± 2.5) days, respectively. Only one patient developed chylus leak with intraabdominal infection. There was no mobility related to the anastomosis in all the patients. The delta-shaped anastomosis is a safe and feasible procedure for totally laparoscopic distal gastrectomy and provides satisfactory short-term efficacy.


Rheological bases for empirical rules on shear viscosity of lubrication oils.
The shear relaxation spectra of various lubrication oils were measured at 5-205 MHz and 10-70 °C, and the variation of the steady-state shear viscosity (η0) was divided into the contributions of the high-frequency shear modulus (G∞) and relaxation time (τ). The temperature dependence of η0 was dominated by that of τ. The increase in molecular weight accompanies both increase in τ and decrease in G∞, and the increase in η0 results from the larger effect of the former. The flexibility of the chain reduced τ, while its effect on G∞ was rather small. The introduction of phenyl or cyclohexyl groups enhanced G∞. Oils of larger G∞ tend to exhibit a larger temperature dependence of η0.


Optimizing antithrombotic therapy after coronary stent implantation in patients on chronic oral anticoagulation.
Most patients on chronic oral anticoagulation have a lifelong indication. When these patients undergo percutaneous coronary interventions with stent implantation, they also have an indication for dual antiplatelet therapy (aspirin and a P2Y12 inhibitor). However, this so-called triple therapy results in increased bleeding risks which in turn is associated with increased mortality. Furthermore, emerging stronger antiplatelet drugs (prasugrel and ticagrelor) are associated with increased bleeding, making triple therapy even more hazardous. This created a clinical treatment dilemma for this subset of patients, and new trials have been designed to explore new treatment strategies. This review summarizes the available evidence regarding the optimal treatment of patients on chronic oral anticoagulation undergoing percutaneous coronary interventions with stent implantation.


Vasovasostomy in rabbits after vasectomy or vas occlusion by tantalum clip.
Vasovasostomy was performed in rabbits that had been vasectomized or had the vas occluded by a tantalum clip for 6 or 15 months. Vasovasostomy restored fertility to 40-50% in vasectomized rabbits and 60-70% in the tantalum clip-occluded animals. Any changes that occurred due to vasectomy and tantalum clip occlusion (e.g. testicular weight, enzyme concentrations in the testis) returned to normal within 3-6 months of vasovasostomy. We suggest that vas occlusion with tantalum clips is a good method of surgical male sterilization and has a high success rate for restoration of fertility.