Chirality dependent electromechanical properties of single-layer MoS2 under out-of-plane deformation: a DFT study.
2D transition metal dichalcogenides (TMDs) demonstrate significant promise in logic circuits and optoelectronic devices because of their unique structures and excellent semiconductor properties. However, they inevitably undergo out-of-plane deformation during practical applications due to their ultra-thin structures. Recent experiments have shown that out-of-plane deformation significantly affects the electronic structures of 2D TMDs. However, the underlying physical mechanism is largely unknown. Therefore, it is critical to have a deeper understanding of out-of-plane deformation in 2D TMDs to optimize their applications in different fields. Currently, one of the most pressing matters that requires clarification is the chirality dependence of out-of-plane deformation in tuning the electromechanical properties of 2D TMDs. In this work, using single-layer MoS2 as a probe, we systematically investigate the effects of out-of-plane deformation along different chirality directions on the bond length, bending stiffness, electric polarization, and band structure of 2D TMDs by employing first-principles calculations based on density functional theory. Our results indicate that the bond length, bending energy, polarization strength, and band gap size of single-layer MoS2 are isotropic under out-of-plane deformation, while the band gap type is closely related to the direction of deformation. Our study will provide an essential theoretical basis for further revealing the structure-performance relationship of 2D TMDs.


Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and Structure Activity Relationships of Inhibitors.
Inflammation is an initial response of the body to a harmful stimuli and it is achieved by the increased movement of leukocytes (especially granulocytes) from blood into injured tissues. It is required for healing wounds and infections. Despite their indispensable role in microbial killing, the inflammation reactions may also cause diseases to a host such as hay fever, atherosclerosis, and rheumatoid arthritis. The enzymes and oxidizing species released during the inflammatory process can cause damages to the host tissues which lead to inflammatory syndromes. The role of myeloperoxidase (MPO) in the inflammatory reactions is well documented. It contributes in killing the pathogens but it is also implicated in several inflammatory syndromes such as Parkinson's disease, Alzheimer's disease and atherosclerosis. Thus, this enzyme has attracted more attention of the scientists and it has become a target for drug designing. In the last decade, several reversible and irreversible MPO inhibitors were identified as very high potent inhibitors such as fluoroalkylindole, aromatic hydroxamic acid, thioxanthine and benzoic acid hydrazide derivatives. In this review, we tried to illustrate the MPO inhibitors and highlight their structure activity relationship (SAR). In this paper we also discussed the mechanism of the inhibitory effect of the most potent compounds.


The positive feedback loop of furin and TGFβ1 enhances the immune responses of Tregs to hepatocellular carcinoma cells and hepatitis B virus in vitro.
Regulatory T cells (Tregs) can exert immunosuppressive activity. Furin can regulate Treg functions, hepatitis B virus (HBV) persistent infection, and hepatocellular carcinoma (HCC) development. However, it remains unknown whether furin can regulate the immune responses of Tregs to HBV and HCC cells. Here, coculture systems of HBV1.3P-HepG2.3P-HepG2 cells and Tregs transduced with or without lentiviral particles that could overexpress furin or knockdown furin/transforming growth factor β1 (TGFβ1) were established to investigate the regulatory relationship between furin and TGFβ1 and the effect of furin/TGFβ1 on Treg activity. Also, the effects of furin overexpression or furin/TGFβ1 knockdown in Tregs on the immunological activity of effector T cells (Teffs)/cytotoxic T lymphocytes (CTLs) and HBV replication/expression were explored in the coculture system of Teff/CTL, Treg, and HBV1.3P-HepG2 cells. Our results showed that furin expression and TGFβ1 secretion were notably increased in Tregs, and Furin and TGFβ1 formed a positive feedback loop to activate Tregs in the coculture system of Tregs and HBV1.3P-HepG2 cells. Furin or TGFβ1 knockdown in Tregs promoted Teff cell proliferation, stimulated interleukin-2 and interferon-γ secretion, and inhibited HBV replication/gene expression in the coculture system of Teff, Treg, and HBV1.3P-HepG2 cells. Moreover, furin or TGFβ1 depletion in Tregs enhanced the killing activity of CTLs against HBV1.3P-HepG2 cells and curbed HBV replication/gene expression in the coculture system of Tregs, CTLs, and HBV1.3P-HepG2 cells. In conclusion, the positive feedback loop of furin and TGFβ1 enhanced the immune responses of Tregs to HCC cells and HBV in vitro.


Clinical use of FFP: results of a retrospective process and outcome audit.
An audit has been carried out on the usage of 216 units of fresh frozen plasma (FFP) issued to 41 patients. This involved the systems of FFP issue, the appropriateness of prescription as well as the recorded benefits. Sixty-six per cent of the initial requests for FFP appeared to satisfy criteria for appropriate use. Review of the case notes resulted in some changes to earlier decisions and a slight increase to 73% of those accepted as valid. Only 94% of the FFP issued could be proved to have been given to identified patients and only 88% of case notes showed the reason for treatment. Pre- and post-treatment coagulation results were available for all patients. In 15% of cases, pretreatment results were not significantly abnormal, and consequently no post-treatment improvement found. Coagulation improvement was documented in 78% of cases, and clinical statements on patient progress noted in 40%. In 80% of cases, the patient received other blood products carrying a potential virus risk. Six of the remaining eight patients were treated to stabilize oral anticoagulation. For these patients, virus-inactivated prothrombin concentrates could have been used, resulting in almost the same reduction in virus transmission risk for the group of 41 patients as could be obtained by using virus-inactivated FFP.


[Deaths from asthma, bronchitis and pulmonary heart disease in Warsaw in the years 1993-1994].
By the regular checking the death certificates in the municipal offices in 7 districts of Warsaw, the morality rate from asthma has been established as 2.98/100.000, from chronic bronchitis as 8.71/100.000 and from pulmonary heart disease as 6.27/100.000. During one year of this survey only 15 deaths (4.7%) from these diseases were below age of 50.67% of patients died in hospitals and 22 (7%) died suddenly (at home). In general, deaths reported as the results of COLD were only 1.59% of the total number of deaths in Warsaw (21.530). 6.9% of all death certificates were without clinical diagnosis (Number 798 of ICD)-described as "natural death", "death before doctor's arrival" or "noncriminal death". Authors discuss the problem of over- and under-diagnosis of asthma as the cause of death, the historical background of asthma mortality and also put the question of the righteousness of regard the pulmonary heart disease as the primary cause of death.


Adolescent romantic relationships.
In this article, we review theoretical and empirical advances in research on romantic relationships between age 10 and the early twenties. First, we describe key themes in this area of research. Next, we briefly characterize the most influential theoretical formulations and distinctive methodological issues. We then describe research findings regarding pertinent social and developmental processes. We summarize the extensive findings on relationships with parents and peers as a context for romantic relationships. Finally, we characterize the growing evidence that adolescent romantic relationships are significant for individual adjustment and development, and we note promising directions for further research.


Proteomic profiling and bioinformatics analysis identify key regulators during the process from fanconi anemia to acute myeloid leukemia.
Fanconi anemia (FA) is a congenital aplastic anemia, characterized as congenital bone marrow failure, developmental malformation, and the malignant tendency, which may develop into acute myeloid leukemia (AML). However, few studies have been conducted on the progression from FA to AML. In this study, we used proteomic profiling, together with bioinformatics analyses, to explore the molecular mechanisms by which FA progresses to AML. Quantitative proteomic analyses of bone marrow samples identified 168 differentially expressed proteins (DEPs), including 7 upregulated proteins and 161 downregulated proteins in the bone marrow of the FA patient compared with the healthy people. The upregulated proteins were enriched in response to stress, oxygen transport, and hydrogen peroxide catabolic process. The downregulated proteins were enriched in myeloid leukocyte mediated immunity, response to interleukin-12, platelet degranulation and regulation of ATPase activity. Based on these results, we discovered 155 DEPs (142 upregulated and 13 downregulated) in the bone marrow samples between FA and AML patients, of which HIST1H1D, HIST1H3A, PSME1 and THRAP3 may play important roles in the progression of FA to AML and may be used as markers for AML early diagnosis. Finally, cell-line based experiments confirmed that PSME1 had an important effect on the proliferation of leukemia cells.


Polyubiquitination of lysine-48 is an essential but indirect signal for MHC class I antigen processing.
Peptides presented on major histocompatibility complex (MHC) class I molecules are generated via cytosolic proteolysis. However, the nature of the endogenous peptide precursors and the intracellular processing steps preceding protein degradation remain poorly defined. Here, we assessed whether ubiquitination is an essential signal for proteasomal cleavage of antigen substrates in human cells. Conversion into antigenic peptides occurred in the absence of any detectable N-terminal ubiquitination of the model antigens, and did not require the presence of any of the four types, nor a minimum number of ubiquitinatable amino acids within the antigen substrate. However, the knockdown of ubiquitin, expression of a lysine 48 (K48) ubiquitin mutant, or inhibition of proteasome-associated deubiquitinases significantly impaired antigen presentation. The results presented here are consistent with a model in which the binding of the antigen substrate by an adaptor protein leads to its K48-polyubiquitination and the subsequent delivery of the antigen cargo for degradation by the 26S proteasome. Altogether, these findings show an important but indirect role of K48-polyubiquitination in preproteasomal antigen sampling.


Peritoneal Recurrence of Cecal Cancer with Specific Imaging Findings and Shrinkage after Treatment with Pembrolizumab.
Pembrolizumab is one of the treatment options for treatment-refractory unresectable advanced or metastatic colorectal cancer with microsatellite instability-high (MSI-H) or deficiencies in DNA mismatch repair (dMMR). Herein, we report a case in which a recurrent cecal cancer lesion showed specific imaging findings and local inflammatory findings during treatment with pembrolizumab, followed by marked shrinkage. The patient was an 80-year-old woman. Postoperative peritoneal recurrence of cecal cancer of approximately 7 cm in size was observed. The patient had MSI-H and was treated with pembrolizumab. After five courses of treatment, the patient presented to our hospital with a chief complaint of abdominal pain. A blood test showed a strong inflammatory reaction, and computed tomography (CT) showed diffuse low-density area in the tumor. Under the suspicion of an abscess, conservative treatment was initiated and the patient quickly recovered. A CT at 1 month showed a marked reduction in size at the same site, and a CT at 3 months showed that the recurrent foci had almost disappeared. The inflammatory reaction before shrinkage in this case may have been caused by tumor immune response to pembrolizumab.


Ammonium recruitment and ammonia transport by E. coli ammonia channel AmtB.
To investigate substrate recruitment and transport across the Escherichia coli Ammonia transporter B (AmtB) protein, we performed molecular dynamics simulations of the AmtB trimer. We have identified residues important in recruitment of ammonium and intraluminal binding sites selective of ammonium, which provide a means of cation selectivity. Our results indicate that A162 guides translocation of an extraluminal ammonium into the pore lumen. We propose a mechanism for transporting the intraluminally recruited proton back to periplasm. Our mechanism conforms to net transport of ammonia and can explain why ammonia conduction is lost upon mutation of the conserved residue D160. We unify previous suggestions of D160 having either a structural or an ammonium binding function. Finally, our simulations show that the channel lumen is hydrated from the cytoplasmic side via the formation of single file water, while the F107/F215 stack at the inner-most part of the periplasmic vestibule constitutes a hydrophobic filter preventing AmtB from conducting water.


Insulin during in vitro oocyte maturation has an impact on development, mitochondria, and cytoskeleton in bovine day 8 blastocysts.
Insulin is a key metabolic hormone that controls energy homeostasis in the body, including playing a specific role in regulating reproductive functions. Conditions associated with hyperinsulinemia can lower developmental rates in bovine in vitro embryo production and are linked to decreased fertility in humans, as in cases of obesity or type 2 diabetes. Embryo quality is important for fertility outcome and it can be assessed by choosing scoring standards for various characteristics, such as developmental stage, quality grade, cell number, mitochondrial pattern or actin cytoskeleton structure. Changes in the embryo's gene expression can reflect environmental impacts during maturation and may explain morphological differences. Together with morphological evaluation, this could enable better assessment and possibly prediction of the developmental potential of the embryo. The aim of this study was to use a bovine model to identify potential gene signatures of insulin-induced changes in the embryo by combining gene expression data and confocal microscopy evaluation. Bovine embryos were derived from oocytes matured in two different insulin concentrations (10 µg mL-1 and 0.1 µg mL-1), then stained to distinguish f-Actin, DNA and active mitochondria. The total cell number of the embryo, quality of the actin cytoskeleton and mitochondrial distribution were assessed and compared to an insulin-free control group. A microarray-based transcriptome analysis was used to investigate key genes involved in cell structure, mitochondrial function and cell division. Our results indicate that insulin supplementation during oocyte maturation leads to lower blastocyst rates and a different phenotype, characterised by an increased cell number and different actin and mitochondrial distribution patterns. These changes were reflected by an up-regulation of genes involved in cell division (MAP2K2; DHCR7), cell structure (LMNA; VIM; TUBB2B; TUBB3; TUBB4B) and mitochondrial activation (ATP5D; CYP11A1; NDUFB7; NDUFB10; NDUFS8). Taken together, we hypothesise that the increased proliferation in the insulin-treated groups might impair the developmental potential of the embryos by inducing metabolic stress on the molecular level, which could be detrimental for the survival of the embryo.


Social value orientation and cooperation in social dilemmas: a review and conceptual model.
Social psychologists have long recognized that people fundamentally differ with respect to their social value orientation (SVO), that is, self-regarding versus other regarding preferences, and that these differences affect cooperative behaviour in situations of interdependence. In this paper, we systematically review the vast number of findings on SVO and cooperation, and synthesize the state of the art by presenting an integrated conceptual model that may explain why and when people with different social values select different behavioural strategies in social dilemmas. Specifically, building on Pruitt and Kimmel's (1977) goal/expectation theory and our review of the literature, we suggest that the relationship between SVO and cooperative behaviour is mediated by (1) a cooperative goal and (2) the specific expectations concerning alters' behaviour. We also propose that trust and goal alignment are important contextual moderators of this relationship: for prosocials, cues signalling trust are necessary to generate positive expectations regarding alters' behaviour, whereas proselfs need external incentives to align their personal interest with a cooperative goal. We conclude this review by pointing to several avenues for future research that would help to deepen our understanding of the role of SVO in human cooperation.


Broadband linear high-voltage amplifier for radio frequency ion traps.
We developed a linear high-voltage amplifier for small capacitive loads consisting of a high-voltage power supply and a transistor amplifier. With this cost-effective circuit including only standard parts sinusoidal signals with a few volts can be amplified to 1.7 kVpp over a usable frequency range at large-signal response spanning four orders of magnitude from 20 Hz to 100 kHz under a load of 10 pF. For smaller output voltages the maximum frequency shifts up to megahertz. We test different capacitive loads to probe the influence on the performance. The presented amplifier is sustained short-circuit proof on the output side, which is a significant advantage over other amplifier concepts. The amplifier can be used to drive radio frequency ion traps for single charged nano- and microparticles, which will be presented in brief.


Role of immunotherapy in gastro-enteropancreatic neuroendocrine neoplasms (gep-nens): Current advances and future directions.
Neuroendocrine neoplasms (NENs) are heterogeneous tumours originating from neuroendocrine cells (Pearse & Polak, Gut, 1971, 12,783). They were once considered as rare tumours, although their annual incidence has increased significantly and now exceeds seven cases in 100 000 in the USA (Dasari, et al., JAMA oncology, 2017, 3, 1335). They are a group of highly diverse neoplasms and can be classified into the spectrum of well-differentiated neuroendocrine tumours to poorly differentiated neuroendocrine carcinomas. This is entirely based on the tumour differentiation and grade (low, intermediate, high), which is determined by the Ki-67/mitotic index. The lower grades (G1/2) of the well-differentiated group are characterised by a relative indolent clinical course and the ability to secrete a variety of peptide hormones (Kloppel, Visceral medicine, 2017, 33, 324). Higher grades and poorly differentiated tumours tend to be more aggressive and have limited therapeutic options (Sorbye et al., Neuroendocrinology, 2019, 108, 54). In the modern era of immuno-oncology, immune checkpoint inhibitors (ICPIs) that target programmed cell death 1 (pembrolizumab, nivolumab), programmed cell death-ligand1 (avelumab, atezolizumab and durvalumab) or cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) have revolutionised the management of many solid tumours. In patients with gastro-enteropancreatic (GEP)-NENs, there is a limited data regarding the role of ICPIs either as a single agent or in combination regimens. Here, we review the current advances for ICPIs and where they fit in the management of GEP-NENs.


Ochrobactrum anthropi: a rare cause of pneumonia.
Ochrobactrum anthropi, a Gram-negative bacillus, is an unusual human pathogen. It has been implicated primarily in catheter-related bloodstream infections. Sporadic cases of infection at other body sites have been reported. Pneumonia, however, is an exceedingly rare clinical manifestation; only one case has been reported in the medical literature so far. We present another case of lower respiratory tract infection secondary to O. anthropi in a patient who was critically ill, but recovered with a favorable outcome. We have provided an overview of clinical manifestations, diagnosis, and treatment of infections due to this rare microorganism.


The molecular epidemiology of lung cancer.
Lung cancer is the leading cause of cancer mortality worldwide. There have been only slight improvements in early diagnosis and survival, reflecting limited advances in screening and treatment for lung cancer. The identification of host differences in susceptibility to lung carcinogens, in particular to cigarette smoke, is essential in predicting who is at highest risk. Susceptibility differences in the form of rare, high-penetrance genes are suggested from studies of familial aggregation of lung cancer and a linkage study. Studies focused on more common, low-penetrance genes in the tobacco smoke metabolism pathways (phase I and phase II enzymes) and DNA repair pathways are reviewed, as are inflammation and cell cycle-related genes and DNA adducts as intermediate biomarkers. Also reviewed are studies of epigenetic mechanisms, such as methylation, as alternative sources of variation in host susceptibility. Studies of molecular epidemiology in lung cancer survival are discussed briefly. In the future, studies that focus on complex interactions between multiple genes and environmental exposures within pertinent pathways are needed. New technological advances in genotyping will help move the field forward.


Use of Two-Dimensional Ultrasonographically Guided Access to Reduce Access-Related Complications for Transcatheter Aortic Valve Replacement.
Major vascular complications have been associated with increased mortality and morbidity in patients undergoing transcatheter aortic valve replacement (TAVR). Our objective was to compare vascular and bleeding outcomes with the routine use of 2-dimensional ultrasonography (2D-US) guided femoral artery access in percutaneous transfemoral TAVR compared with traditional anatomic landmark palpation with angiographically-guided access. This single-centre retrospective cohort study was conducted in Ontario, Canada. We enrolled patients from January 1, 2012-June 30, 2016. Routine 2D-US was used in all transfemoral TAVR after January 1, 2014; before this, all cases were performed with angiographic guidance alone. The primary outcome of interest was the composite of any access-related red blood cell transfusion or vascular/bleeding complications. Definitions were based on the Valve Academic Research Consortium (VARC-2) criteria. Fully adjusted multivariable regression models were developed to determine the impact of 2D-US. The study cohort included 387 patients, 109 (28%) of whom underwent femoral artery puncture guided by anatomic and angiographic landmarks, whereas 278 (72%) patients had 2D-US guidance. After adjusting for baseline differences in our multivariable models, we found that 2D-US-guided access was associated with an odds ratio of 0.42 (95% confidence interval, 0.25-0.70; P < 0.01) for the composite end point of access-related vascular or bleeding complications and red blood cell transfusion. The routine use of 2D-US in transfemoral TAVR was associated with substantial reductions in access-related vascular and bleeding complications.


Spontaneous atlantoaxial osteomyelitis: no longer a rare case? Case report.
The number of case reports concerning anterior atlantoaxial osteomyelitis has increased in the past decade. Although previously considered rare, this particular disease has become more prevalent for several reasons, including the increase in the elderly population, which is generally more susceptible to infectious problems. It is, therefore, imperative for physicians in general and neurosurgeons in particular to become aware of the existence of this problem and of the therapeutic options available.


The impact of genetic hypertension on insulin secretion and glucoregulatory control in vivo: studies with the TGR(mRen2)27 transgenic rat.
To examine the associations among hypertension, insulin secretion, glucose tolerance and insulin resistance in vivo. Glucose tolerance and insulin secretion during an intravenous glucose tolerance test and action of insulin on whole-body glucose kinetics in the post-absorptive state and during hyperinsulinaemia were examined in conscious, unrestrained TGR(mRen2)27 rats and age-matched transgene-negative controls. Glucose tolerance and insulin secretion were examined after intravenous administration of 500 mg glucose/kg body weight. Endogenous glucose production and whole-body glucose disposal were estimated using [3-3H]-glucose during euglycaemic-hyperinsulinaemic clamping. Muscle glucose utilization was estimated using 2-deoxy-[1-3H]-glucose. Despite there being higher insulin levels, whole-body glucose turnover was significantly lower in post-absorptive TGR(mRen2)27 rats than it was in transgene-negative controls. This was associated with significant suppression of glucose uptake/phosphorylation by oxidative skeletal muscles. TGR(mRen2)27 rats also exhibited significantly lower blood glucose levels, higher plasma insulin levels and higher rates of disappearance of glucose after intravenous administration of glucose. During hyperinsulinaemia, steady-state glucose infusion rates required to maintain euglycaemia in TGR(mRen2)27 rats were significantly greater, indicating that an increase in whole-body action of insulin had occurred. This was due to significantly greater suppression of endogenous production of glucose: insulin-stimulated glucose disposal rates did not differ significantly between the two groups. The results indicate that TGR(mRen2)27 rats have an enhanced and sensitized insulin-secretory response to glucose, together with a greater than normal hepatic action of insulin. Insulin-mediated glucose disposal was not impaired. The results therefore do not support the hypothesis that hypertension plays a primary role in the development of insulin resistance.


Staphylococcal enterotoxin M induced inflammation and impairment of bovine mammary epithelial cells.
Staphylococcus aureus is one of the major etiological pathogens of bovine mastitis. Its invasion into mammary epithelial cells has been proven to be a key event in the pathogenesis of mastitis. However, the specific pathogenic factors have not been clearly identified. Staphylococcus aureus often triggers infections by releasing virulence factor. Recent several studies reported that staphylococcal enterotoxin M was one of the most frequently found enterotoxin genes associated with bovine mastitis. Thus, the effect of staphylococcal enterotoxin M on inflammation and damage of the bovine mammary epithelial bovine mammary gland epithelial cell line (MAC-T) cells with 48 h treatment was explored in the present study. First, staphylococcal enterotoxin M protein was purified by a Ni-NTA spin column (GE Life Science, Westborough, MA). The levels of tumor necrosis factor-α, IL-6, and monocyte chemoattractant protein 1 (MCP-1) secretion were measured with the corresponding ELISA kits (R&D Systems, Abingdon, UK). Second, cell viability was assessed with a Cell Counting Kit-8 (Bioswamp, Wuhan, China) and the apoptotic percentage of cells was determined by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI; Beyotime, Nanjing, China) staining. Third, ATP concentration, reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release were assayed with commercial kits, then mitochondrial membrane potential (ΔΨm) was estimated using fluorescent probe JC-1 (Beyotime). Finally, the production intercellular cell adhesion molecule-1 (ICAM-1), microtubule-associated protein 1A/1B-light chain 3 I/II (LC3 I/II), p62 (Proteintech, Rosemont, IL), and phosphorylation of IκBα, caspase 3, and mammalian target of rapamycin were detected by Western blot. The results showed that staphylococcal enterotoxin M induced inflammation of epithelial cells (upregulating tumor necrosis factor-α, IL-6, MCP-1, and ICAM-1 production) and activated NF-κB (promoting phosphorylation of IκBα). Furthermore, staphylococcal enterotoxin M impaired MAC-T cells via cell necrosis (enhancing LDH release), apoptosis (annexin V-FITC/PI stain, exacerbating oxidative stress, decreasing ΔΨm and intracellular ATP concentration, and activating caspase 3), but independent of autophagy (nonsignificantly increasing LC3-II, decreasing p62 expression, and activating mammalian target of rapamycin). Thereby, staphylococcal enterotoxin M induced the inflammatory property of bovine mammary epithelial cells by boosting cytokine, chemokine, and adhesion molecule production. Furthermore, it caused epithelial cell dysfunction via depressing cell viability and initiating cell necrosis and apoptosis. Because epithelial cells played important roles in orchestrating the inflammatory response and protecting bovine mammary tissue from mastitis, our results indicated that staphylococcal enterotoxin M may be associated with mastitis.


Myocardial infarction and oral contraceptives.
The study presented investigated 448 cases of myocardial infarction and 1728 controls to determine possible relationships between oral contraceptives and AMI. The study found that the use of any type of low-dose oral contraceptive does not appear to increase AMI risk. Health-care practitioners are in a good position to collect research data using lay language.


Management of hepatitis C virus/HIV coinfection among people who use drugs in the era of direct-acting antiviral-based therapy.
Where active antiretroviral therapy (ART) is accessible, human immunodeficiency virus (HIV) is a survivable illness and effective ART can reduce HIV transmission. Chronic hepatitis C virus (HCV) has emerged as a threat to the survival of individuals harboring both HCV and HIV, due to high prevalence and aggressive disease course. The HCV/HIV coinfection epidemic has been driven by people who inject drugs (PWID), although incident HCV is rising among HIV-infected men who have sex with men in the absence of drug injection. Coinfected individuals warrant aggressive treatment of both viruses; although early ART initiation is recommended to reduce the rate of liver disease progression, the most effective way to decrease HCV-related morbidity and mortality in coinfection is to achieve HCV viral eradication. Direct-acting antiviral (DAA) agents will soon revolutionize HCV treatment. Clinical data are needed regarding the efficacy of DAAs in coinfected PWID. Drug-drug interaction studies between ART, DAAs, and opiate substitution therapy must be expedited. Coinfected PWID should have equitable and universal access to HIV/AIDS, HCV, and addiction prevention, care, and treatment. Essential basic steps include improving screening for both infections and engaging coinfected PWID in HIV and HCV care early after diagnoses. Developing strategies to expand access to HCV therapy for coinfected PWID is imperative to stem the HCV epidemic and limit the morbidity and mortality of those at greatest risk for HCV disease progression. The ultimate goal must be the elimination of HCV from all coinfected PWID.


n-type Ge/Si antennas for THz sensing.
Ge-on-Si plasmonics holds the promise for compact and low-cost solutions in the manipulation of THz radiation. We discuss here the plasmonic properties of doped Ge bow-tie antennas made with a low-point cost CMOS mainstream technology. These antennas display resonances between 500 and 700 GHz, probed by THz time domain spectroscopy. We show surface functionalization of the antennas with a thin layer of α-lipoic acid that red-shifts the antenna resonances by about 20 GHz. Moreover, we show that antennas protected with a silicon nitride cap layer exhibit a comparable red-shift when covered with the biolayer. This suggests that the electromagnetic fields at the hotspot extend well beyond the cap layer, enabling the possibility to use the antennas with an improved protection of the plasmonic material in conjunction with microfluidics.


[LOCKED INTRAMEDULLARY NAlLlNG OF HUMERAL SHAFT FRACTURES].
Clinical and radiological results ofthe patients with humeral shaftfractures who underwent Iocked intramedullary nailing are retrospectively evaluated in this study. 29 patients (17 males, 12 females; mean age 43.6; range 26 to 68 years) who underwent Iocked intramedullary nailing were evaluated retrospectively. 17 patients had major and seven patients had minor traumas. ln three patients the fractures were, pathological and also two patients had additional hypertrophic non-union. Closed intramedullary nailing was performed in 21 patients. Three patients (two with non-union) were treated by using autogenous graft. Nine patients were nailed antegradely and 20 retrogradely. The meanfollow-up period was 16.2 months (range 8 to 47 months). The mean time ofunion was 18 weeks (range 8 to 36 weeks) in 26 patients (% 90) but non-union occured in three patients.Functional end results ofshoulderand elbow were excellent in 23 (%79) patients, moderate infour (%13) patients and bad in two %8) patients. Postoperative complications included radial nerve palsy, breakaie of the distal locking screw and superficial infection in one patient each. Nail migration also occured in an osteoporotic patient. Locked intramedullary nailing is the treatment ofchoicefor humeral shaftfractures in osteopenic bone, pathological fractures, comminuted or segmentalfractures and also for humeral shaftfractures in polytraumatised patients who may need to use the injured armfor early rehabilitation and mobilization.


Dual suppressive effect of MTORC1 on autophagy: tame the dragon by shackling both the head and the tail.
The lysosome is a key subcellular organelle that receives and degrades macromolecules from endocytic, secretory and autophagic pathways. Lysosomal function is thus critical for an efficient autophagic process. However, the molecular mechanisms mediating lysosomal function upon autophagic induction are largely unknown. Our laboratory recently discovered that upon autophagy activation, the lysosome is activated, and this functional activation is dependent on MTORC1 suppression, suggesting that MTORC1 exerts a suppressive effect on lysosomal function. Therefore, data from our study demonstrate that MTORC1 exerts a dual inhibitory effect on autophagy, blocking autophagy not only at the initiation stage via suppression of the ULK1 complex, but also at the degradation stage via inhibition of lysosomal function. We think that understanding the negative regulatory effect of MTORC1 on lysosomal function expands the functional scope of MTORC1 in autophagy regulation, and offers new clues for developing novel interventional strategies in autophagy- and lysosome-related diseases.


INFLUENCE OF THE ENVIRONMENT ON THE UNBORN.
EMBRYONIC DEVELOPMENT IS INFLUENCED BY THREE ENVIRONMENTS: the intra-uterine, the maternal body and the maternal surroundings. Factors present in one or other may cause abnormal development.Usually environmental factors act in association with genetic factors but they can be the dominant or sole cause of birth defects. Many malformation-producing agents exist in the maternal environment and some cause abnormalities in man. Use of such agents in experimental animals yields valuable information on how malformations develop. Different species and strains of animals often react differently to the same teratogenic agent, leading to difficulties in screening substances which may be harmful to human embryos. Laboratory experimentation, detailed study of human abortion material and the vigilance of the physician are all essential in the search for human teratogens.


From coordination chemistry to biological chemistry of aluminium.
The paper gives a review on the importance of distribution of Al in biological fluids, primarily in the lights of the works of the author in Al chemistry. It starts with studies of interactions of Al(III) with small biomolecules, such as aliphatic and aromatic hydroxycarboxylic acids, and inorganic and organic phosphates. A significant part of this review deals with the problems of description of the biospeciation of Al(III) in serum, where besides the thermodynamic conditions the role of time is also considered in the case of this sluggish metal ion. The Al(III) complexes of the other large group of biomolecules, proteins and their building blocks (oligo)peptides and amino acids are also discussed, where the role of the type of the side chain donors and the extent of preorganisation are considered in the efficiency of metal ion binding. The application of low molecular mass chelator molecules in restoring the dysfunctioning metal ion (including Al(III)) homeostasis in the treatment of Alzheimer's disease is also discussed in the paper.


Neuroprotective effects of curdione against focal cerebral ischemia reperfusion injury in rats.
Curdione is one of the most highly concentrated component of the active constituents in E-zhu, which has been reported to possess a variety of activities. However, the pharmacologic neuroprotective activity of curdione has not been evaluated. The present study aimed to investigate the protective effect of curdione on focal cerebral ischemia reperfusion-induced injury in rats and further exploring the underlying mechanisms. Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO) surgery for 2 h, followed by reperfusion stage. All animals received treatment once a day for 7 days before surgery and 14 days from 4 h after the reperfusion started. The neurological deficit test and Morris water maze test were performed at 1, 4, 7 and 14 days after MCAO. The infarct size of animals was determined by the 2,3,5-triphenyltetrazolium chloride staining, and pathological brain damage was estimated by hematoxylin-eosin staining. The malonaldehyde (MDA) levels and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay. Expression of apoptotic proteins was measured by Western blot. Our results showed that curdione could significantly reduce the infarct size and neurological deficits, promote cognitive function recovery and recover neuronal morphologic damages in MCAO rats. It also blocked the increase of MDA content and elevated the activities of SOD, CAT and GSH-PX. Moreover, curdione attenuated the expression of Cyt-C, c-caspase-3 and c-caspase-9 increased the Bcl-2/Bax ratio and hence decreased the cellular apoptosis. Curdione possessed potential neuroprotective effect on rats in the MCAO model. The anti-oxidative and anti-apoptotic properties may be involved in the underlying mechanisms.


[Invasive cholesteatoma of the old radical mastoidectomy].
The aim of this study is to show the importance of computed tomography scanning (CT) and magnetic resonance imaging (MRI) in ancient radical cavities and to determinate the risk factors of an invasive cholesteatoma recurrency. We present 4 cases of medial invasion in the petrous bone of a cholesteatoma without specific symptomatology which appeared many years after undergoing radical mastoidectomy for an acquired cholesteatoma. The analysis of this series allowed to put in evidence the factors of suspicion of an underlying cholesteatoma. They are: the age, an aural discharge, numerous surgical interventions, immunodeficiency, cholesteatoma in childhood and antecedent of facial nerve palsy. This trial emphasizes the importance of imaging (CT and MRI) in front of an ancient radical cavity which presents one or some of these factors in order to eliminate a recurrence of an invasive cholesteatoma. Let us note that the demand of the patients is sometimes aesthetic or functional.


The in vitro characterization of the iterative avermectin glycosyltransferase AveBI reveals reaction reversibility and sugar nucleotide flexibility.
The glycosyltransferase AveBI, which is involved in the biosynthesis of the macrolide antihelmintic avermectin (AVM), was characterized in vitro. AveBI was confirmed to catalyze two separate iterative additions of l-oleandrose, and the reversibility of AveBI-catalyzed reaction was also demonstrated. Investigation of sugar nucleotide specificity revealed 10 unique sugar nucleotide substrates which, in combination with five distinct aglycones, led to the production of 50 differentially glycosylated AVM variants.


Antimicrobial polypeptide multilayer nanocoatings.
A multilayer coating (or film) of nanometer-thick layers can be made by sequential adsorption of oppositely charged polyelectrolytes on a solid support. The method is known as layer-by-layer assembly (LBL). No special apparatus is required for LBL and nanofilms can be prepared under mild, physiological conditions. A multilayer nanofilm in which at least one of the constituent species is a polypeptide is a polypeptide multilayer nanofilm. The present work was aimed at assessing whether polypeptide multilayer nanofilms with specific antimicrobial properties could be prepared by incorporation of a known antimicrobial agent in the film structure, in this case the edible protein hen egg white lysozyme (HEWL). The chicken enzyme is widely employed as a human food preservative. An advantage of LBL in this context is that the nanofilm is fabricated directly on the surface of interest, eliminating the need to incorporate the antimicrobial in other packaging materials. Here, nanofilms were made of poly(L-glutamic acid) (PLGA), which is highly negatively charged in the mildly acidic pH range, and HEWL, which has a high net positive charge at acidic pH. We show that PLGA/HEWL nanofilms inhibit growth of the model microbe Microccocus luteus in the surrounding liquid medium. The amount of HEWL released from PLGA/HEWL films depends on the number of HEWL layers and therefore on the total quantity of HEWL in the films. This initial study provides a sketch of the scope for further development of LBL in the area of antimicrobial polypeptide multilayer films. Potential applications of such films include strategies for food preservation and coatings for implant devices.


Plasmonic-coupled quantum dot photodetectors for mid-infrared photonics.
A plasmonic-coupled, InAs-based quantum dot photodetector fabricated for mid-wave infrared photonics is reported. The detector is designed to provide a broadband absorption [full width at half maximum (FWHM) ≳ 2 µm] peaked at ∼5.5 µm, corresponding to transitions from the ground state of the quantum dot to the quasi-continuum resonance state above the quantum well. From the coupling of this transition to the surface plasma wave (SPW) excited by an Au film atop the detector, fabricated with a 1.5 µm-period, 2-dimensional array of square holes, a narrowband SPW enhancement peaked at 4.8 µm with an FWHM less than 0.5 µm is achieved. At ∼90 K, a peak responsivity enhanced ∼5× by the plasmonic coupling is observed. Simulation reveals that this enhancement corresponds to collecting ∼6% of the incident light; ∼40% of the total absorption by the SPW excitation at the peak wavelength.


Influence of aneurysm wall stiffness and the presence of intraluminal thrombus on the wall movement of an aneurysm - an in vitro study.
The purpose of this in vitro study was to investigate the influence of aneurysm wall stiffness and of the presence of intraluminal thrombus (ILT) on aneurysm wall movement. Three latex aneurysms were used with different wall stiffness. The aneurysms, equipped with 20 tantalum markers, were attached to an in vitro circulation model. Fluoroscopic roentgenographic stereo photogrammetric analysis was used to measure marker movement during six cardiac cycles at three different systemic pressures. To investigate the influence of ILT on wall movement, we repeated the same experiment with one of the aneurysms. The aneurysm sac was then filled with one of two E-moduli differing thrombus analogues (Novalyse 8 and 20) or with perfusate as a control. It was noted that the amplitude of the wall movement (mm) increased significantly (P < 0.05) as the compliance of the wall increased. The mean amplitude of the wall movement decreased (P < 0.05) as the stiffness (E-modulus) of the ILT increased. In conclusion, ILT has a 'cushioning effect'. Wall movement (and theoretically wall stress) diminishes when the stiffness of the ILT increases. Compliance of the aneurysm wall influences wall movement. When the stiffness of the wall increases, the wall movement diminishes.


The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation.
Ubiquitination is a reversible post-translational modification that has emerged as a critical regulator of synapse development and function. However, the mechanisms that regulate the deubiquitinating enzymes (DUBs) responsible for the removal of ubiquitin from target proteins are poorly understood. We have previously shown that the DUB ubiquitin-specific protease 46 (USP-46) removes ubiquitin from the glutamate receptor GLR-1 and regulates its trafficking and degradation in Caenorhabditis elegans We found that the WD40-repeat proteins WDR-20 and WDR-48 bind and stimulate the catalytic activity of USP-46. Here, we identified another mechanism by which WDR-48 regulates USP-46. We found that increased expression of WDR-48, but not WDR-20, promotes USP-46 abundance in mammalian cells in culture and in C. elegans neurons in vivo Inhibition of the proteasome increased USP-46 abundance, and this effect was nonadditive with increased WDR-48 expression. We found that USP-46 is ubiquitinated and that expression of WDR-48 reduces the levels of ubiquitin-USP-46 conjugates and increases the t1/2 of USP-46. A point-mutated WDR-48 variant that disrupts binding to USP-46 was unable to promote USP-46 abundance in vivo Finally, siRNA-mediated knockdown of wdr48 destabilizes USP46 in mammalian cells. Together, these results support a model in which WDR-48 binds and stabilizes USP-46 protein levels by preventing the ubiquitination and degradation of USP-46 in the proteasome. Given that a large number of USPs interact with WDR proteins, we propose that stabilization of DUBs by their interacting WDR proteins may be a conserved and widely used mechanism that controls DUB availability and function.


Age-related health stereotypes and illusory correlation.
This experiment investigated how age-related health stereotypes affect people's judgments of younger and older patients' medical compliance. Previous research has shown that stereotypes of young adults include healthy components, but stereotypes of older adults include both healthy and unhealthy components (Hummert, 1990). We predicted that younger patients in poor health would violate people's expectations about health in younger individuals. As a result of this violation, people would perceive younger patients to be more non-cooperative than older patients. On the other hand, because people's stereotypes of older patients contain both good and poor health components, non-cooperative older patients would be no more memorable than cooperative older patients. These hypotheses were supported by data showing that both younger and older participants formed illusory correlations between younger patients and non-cooperative behavior, but not between older patients and non-cooperative behavior. Implications for how age-related health stereotypes might affect beliefs about compliance and healthcare policy are discussed.


CHILDHOOD PSYCHOSIS OR MENTAL RETARDATION: A DIAGNOSTIC DILEMMA. I. PSYCHIATRIC AND PSYCHOLOGICAL ASPECTS.
A relatively large percentage of children seen at a mental retardation clinic demonstrated psychotic symptoms. The entire group with psychotic manifestations, 62 in all, were reviewed in order to clarify the diagnosis of childhood psychosis or mental retardation. The 1961 British criteria for childhood psychosis were used and are advocated by the authors. Childhood psychosis was the primary diagnosis in 38 cases, and psychosis secondary to brain damage in 24 cases. Onset of the condition under the age of three years and a poor prognosis for social recovery were characteristic of the entire group.Obvious emotional disorder was present in 21 mothers and 14 fathers. There was a continuum in terms of number of psychotic symptoms, level of intelligence and presence of organic signs. It is concluded that there is an overlap between the entities of childhood psychosis and mental retardation.


Danggui buxue tang--a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells.
Danggui buxue tang (DBT), a Chinese herbal decoction used to treat ailments in women, contains radix Astragali (Huangqi; RA) and radix Angelicae Sinensis (Danggui; RAS). The weight ratio of RA to RAS used in DBT must be 5:1 as stipulated as early as AD 1247; however, DBT's mechanism of action has never been described. Here, the estrogenic effects of DBT were investigated by determining the phosphorylations of estrogen receptor alpha (ER alpha) and extracellular signal-regulated kinase 1/2 (Erk1/2) in cultured MCF-7 cells. The application of DBT triggered the phosphorylation of ER alpha and Erk1/2 in a time-dependent manner. In contrast to the effect of estrogen, DBT triggered ER alpha phosphorylation at both S118 and S167. This DBT-specific phosphorylation was not triggered by an extract of one of the individual herbs, or by mixing the extracts of RA and RAS. DBT-induced downstream signals are described here. These signals suggest the uniqueness of this Chinese herbal decoction that requires a well-defined formulation.


Efficiency and optimal size of hospitals: Results of a systematic search.
National Health Systems managers have been subject in recent years to considerable pressure to increase concentration and allow mergers. This pressure has been justified by a belief that larger hospitals lead to lower average costs and better clinical outcomes through the exploitation of economies of scale. In this context, the opportunity to measure scale efficiency is crucial to address the question of optimal productive size and to manage a fair allocation of resources. This paper analyses the stance of existing research on scale efficiency and optimal size of the hospital sector. We performed a systematic search of 45 past years (1969-2014) of research published in peer-reviewed scientific journals recorded by the Social Sciences Citation Index concerning this topic. We classified articles by the journal's category, research topic, hospital setting, method and primary data analysis technique. Results showed that most of the studies were focussed on the analysis of technical and scale efficiency or on input / output ratio using Data Envelopment Analysis. We also find increasing interest concerning the effect of possible changes in hospital size on quality of care. Studies analysed in this review showed that economies of scale are present for merging hospitals. Results supported the current policy of expanding larger hospitals and restructuring/closing smaller hospitals. In terms of beds, studies reported consistent evidence of economies of scale for hospitals with 200-300 beds. Diseconomies of scale can be expected to occur below 200 beds and above 600 beds.


Avoiding the Personhood Issue: Abortion, Identity, and Marquis's 'Future-Like-Ours' Argument.
One reason for the persistent appeal of Don Marquis' 'future like ours' argument (FLO) is that it seems to offer a way to approach the debate about the morality of abortion while sidestepping the difficult task of establishing whether the fetus is a person. This essay argues that in order to satisfactorily address both of the chief objections to FLO - the 'identity objection' and the 'contraception objection' - Marquis must take a controversial stand on what is most essential to being the kind of entity that an adult human being is. Such a stand amounts to a controversial account of personhood. To the extent that FLO's success depends on accepting such a controversial metaphysical view, one apparent attraction of FLO proves illusory.


Critical review and rethinking of USEPA secondary standards for maintaining organoleptic quality of drinking water.
Consumers assess their tap water primarily by its taste, odor, and appearance. Starting in 1979, USEPA promulgated Secondary Maximum Contaminant Levels (SMCLs) as guidance for contaminants with organoleptic effects and also to maintain consumers' confidence in tap water. This review assesses the basis for the 15 SMCLs (aluminum, chloride, color, copper, corrosivity, fluoride, foaming agents, iron, manganese, odor, pH, silver, sulfate, total dissolved solids, zinc) and summarizes advances in scientific knowledge since their promulgation. SMCLs for aluminum, color, pH, silver, sulfate, total dissolved solids, and zinc are appropriate at current values and remain consistent with sensory science literature. Recent advances in sensory and health sciences indicate that SMCLs for chloride, copper, fluoride, iron, and manganese are too high to minimize organoleptic effects. The SMCLs for corrosivity and foaming agents may be outdated. The SMCL for odor requires rethinking as the test does not correlate with consumer complaints. Since current stresses on source and treated waters include chemical spills, algal blooms, and increased salinization, organoleptic episodes that negatively impact consumer confidence and perception of tap water still occur and may increase. Thus, adherence to SMCLs can help maintain production of palatable water along with consumers' confidence in their water providers.


[The main aspects of symptomatic therapy of chronic heart failure].
The main aims of the treatment of chronic heart failure are to improve and to maintain the quality of life, to increase duration of life, to decrease mortality, to prevent diseases leading to the heart failure development, and to prevent the progression of heart failure. Diuretics are the drugs of first choice for the treatment of congestive heart failure. They can improve the quality of patient's life quite quickly. Noncompliance to methodological diuretic use can cause a serious damage such as metabolic disorders, arrhythmias, and even sudden death. Loop diuretics are the drugs of choice. Resistance to diuretics occurs in 10-20% of the cases during the course of treatment; therefore, drug combination as well as dose modification is required. Diuretics are not recommended to use alone for a symptomatic relief. They are prescribed in combination with beta-blockers, angiotensin-converting-enzyme inhibitors, and/or angiotensin receptor blockers for a continuous pathogenetic therapy of congestive heart failure. Digoxin in combination with diuretics is the drug of choice for treatment of heart failure when tachyarrhythmia or severe systolic left ventricular dysfunction appears or it is impossible to administer beta-blockers. In this article, the guidelines of European Society of Cardiology and also American College of Cardiology and American Heart Association for the symptomatic management of congestive heart failure, updated in 2005, are reviewed.


Droxidopa Persistence in Neurogenic Orthostatic Hypotension May Be Affected by Titration Approach.
Droxidopa is approved for the treatment of neurogenic orthostatic hypotension (nOH) symptoms and requires patients to be titrated to individualized effective doses (100-600 mg, three times daily) based on symptomatic response. As per the product label, droxidopa should be titrated every 24-48 hours to an optimum maintenance dose (maximum daily dosage 1,800 mg). In an examination of patients with nOH treated in clinical practice settings (n=4,506) using data from the central Northera specialty-pharmacy hub, titration schedules, daily titration dosage (ie, dosage during first dispensation, the assumed titration period), and daily maintenance dosage (dosage during subsequent dispensations) were characterized. It was found that customized titration schedules (ie, different from the product-label recommendation) had been used in 53% of patients, and these patients had had an average daily titration dosage of 567 mg. In contrast, patients who were titrated as per the label schedule (48 hours, 37%; 24 hours, 10%) had daily titration dosages of 1,500-1,650 mg. A relationship between treatment persistence (measured by number of refills) and maintenance dosage was identified. Average daily maintenance doses in patients who received 2, 3-6, 7-24, and >25 dispensations were 938, 969, 1,069, and 1,167 mg, respectively (P<0.0001). In summary, our data suggest that more than half the patients treated with droxidopa in clinical practice settings are not titrated using the schedule recommended on the product label (ie, not 24-48 hours), and as a result receive lower daily dosages of droxidopa than those treated using the recommended titration schedules. Lower daily maintenance dosages of droxidopa were associated with shorter treatment persistence (ie, fewer dispensations). Reasons for discontinuation could not be examined in this study, but further investigation of these persistence data is warranted.


Rat small-intestinal beta-galactosidases. Influence of pH on the hydrolysis of different substrates.
1. The influence of pH and the kind of buffer on the hydrolysis of lactose and four hetero-beta-galactosides (phenyl beta-galactoside, o-nitrophenyl beta-galactoside, p-nitrophenyl beta-galactoside and 6-bromo-2-naphthyl beta-galactoside) by homogenates of rat small-intestinal mucosa has been studied. 2. There are at least two beta-galactosidases present in the homogenates, one with optimum pH3-4 and another with optimum pH5-6. 3. The enzyme with the lower pH optimum is mainly a heterogalactosidase. It hydrolyses lactose slowly. The other enzyme is mainly a disaccharidase, since it hydrolyses lactose much more rapidly than the heterogalactosides. 4. Under the conditions used, citrate had an inhibitory effect on the 6-bromo-2-naphthyl beta-galactosidase activity at pH3-4, but did not influence the 6-bromo-2-naphthyl beta-galactosidase activity at pH5-6 or the hydrolysis of the other substrates at any pH.


Effect of supination versus pronation in the non-operative treatment of pediatric supracondylar humerus fractures.
Supracondylar fracture of the humerus is the most common elbow injury that requires reduction and immobilization in the proper position to union. There are a few reports regarding the position of the forearm immobilization on elbow cosmetic outcome. This study aimed to compare two modes of the forearm, supination and pronation in elbow deformity incidence after closed reduction and casting of this fracture. This prospective and descriptive study was carried out on children with supracondylar fracture of the humerus treated with closed reduction and cast immobilization in one of the two modes of either supination or pronation for a period of three weeks. Twenty-nine patients were immobilized in supination and 35 in pronation. Follow-up lasted for 8 months. Re-displacement was defined as the criteria and subsequent deformities of the elbow in patients, were assessed by clinical and radiographic examination. A total of 64 patients, 50 boys and 14 girls, with the mean age of 4.8 years (3.1 to 8.5 years) participated. All fractures were closed and of the extension type. Forty-five cases had Gartland type II and 19 had type III fracture. Deformity of the elbow had occurred in seven cases (10.94%). Four cases of cubitus varus (CA 5 º - 16º) were observed in the supination group, of these, three patients had type III and one other had a type II fracture. In the pronation group, two cases of cubitus varus (CA 6 º - 14º) and one case of cubitus valgus (CA 17º) were observed, with type III initial fracture in all 3 cases. In regard to elbow malunion deformity, no obvious difference was observed between the two methods of supination and pronation in the closed treatment of supracondylar humerus fracture. However, as cubitus varus and valgus had occurred in both groups with unstable type III fractures, to prevent this complication, operative fixation is advised rather than closed reduction and position of the forearm immobilization.


Non-Melanocytic Skin Cancers of the Head and Neck: A Clinical Study in Jeju Province.
Jeju Island is geographically and socioeconomically distinct from the mainland of South Korea. Thus, the presentation and management of non-melanocytic skin cancers (NMSC) of the head and neck may differ from those in other regions of the country. We compared the clinical characteristics and treatment modalities of NMSC on Jeju Island with the findings of similar regional studies. Patient data, including age, sex, diagnosis, tumor site, treatment, and recurrence, were obtained from the medical and pathology records of patients diagnosed with NMSC between January 2010 and June 2015. In total, 190 patients (57 men) with a mean age of 75 years (range, 42-97) were assessed. Overall, 203 NMSCs were diagnosed, including 123 basal cell carcinomas and 80 squamous cell carcinomas. The tumor sites included the nose, cheeks, periorbital area, and lips (n=55, 54, 25, and 20, respectively). We identified 92 T1-stage and 60 T2-stage tumors, and 120 cases were treated with wide surgical resection and 17 cases were treated with radiation therapy at the medical center. Of the 120 cases treated surgically, 69 required reconstructive surgery using a local skin flap, 22 required full-thickness skin grafting, and 12 underwent primary closure. Basal and squamous cell carcinomas recurred in 2 and 1 cases, respectively. Compared to the reports from other regions, the average patient age was 10 years higher, with a marked female preponderance. While the proportion of squamous cell carcinoma was higher than in other regions, the tumor distribution and surgical management profiles were similar.


Magnesium ion inner sphere complex in the anticodon loop of phenylalanine transfer ribonucleic acid.
The binding of Ca2+ and Mg2+ to tRNAPhe is analyzed by equilibrium titrations and temperature-jump measurements using the Wye base fluorescence as a label. Titration experiments starting with the folded structure of the tRNA (high salt and low temperature) show that Ca2+ and Mg2+ binding detected by Wye base fluorescence changes is associated with equilibrium constants between 1 x 10(3) and 3 x 10(3) M-1. The binding of Ca2+ leads to an increase of the relaxation time associated with a conformation change of the anticodon loop and to a decrease of the corresponding amplitude. These data are represented quantitatively by a two-step reaction scheme with a preferential binding of Ca2+ to one of the anticodon conformations. When Mg2+ is added, an extra relaxation process is observed with time constants around 1 ms. This process demonstrates the formation of a Mg2+ inner sphere complex. Relaxation time constants and amplitudes are represented quantitatively by a three-step reaction scheme. Mg2+ binds preferentially to one of the anticodon conformations. In the absence of Mg2+, these conformations are populated almost equally with a transition rate constant around 5 x 10(3) s-1. The Mg2+ inner sphere complex is formed with a relatively low rate constant of (1--2) x 10(3) s-1, indicating a conformational barrier. These data strongly suggest that the Mg2+ site analyzed in the present investigation corresponds to the anticodon site with a distorted octahedral coordination characterized by X-ray analysis. The results are discussed in terms of the anticodon function and also with respect to their implications upon Mg2+ binding to nucleic acids in general.


Rare cause of deranged liver profile in pregnancy.
We present the case of a 33-year-old pregnant woman with an abnormal liver profile secondary to liver metastases from colon cancer. The patient presented in her third trimester with non-specific symptoms. Blood tests revealed a cholestatic liver picture, initially attributed to prurigo gravidarum. However, following a normal vaginal delivery, her symptoms persisted and the liver profile failed to return to baseline. This led to further investigations including a CT scan of the abdomen-revealing a transverse colonic tumour with extensive liver involvement. Biopsy of the liver confirmed an adenocarcinoma of colonic origin, and subsequently the patient underwent a right hemicolectomy followed by systemic chemotherapy.


MicroRNAs Encoded by Bovine Leukemia Virus (BLV) Are Associated with Reduced Expression of B Cell Transcriptional Regulators in Dairy Cattle Naturally Infected with BLV.
Bovine leukemia virus (BLV) is estimated to infect over 83% of dairy herds and over 40% of all dairy cows in the United States. While, BLV only causes leukemia in a small proportion of animals, research indicates that BLV+ cattle exhibit reduced milk production and longevity that is distinct from lymphoma development. It is hypothesized that BLV negatively affects production by interfering with cattle immunity and increasing the risk of secondary infections. In particular, BLV+ cows demonstrate reduced circulating levels of both antigen-specific and total IgM. This study investigated possible mechanisms by which BLV could interfere with the production of IgM in naturally infected cattle. Specifically, total plasma IgM and the expression of genes IGJ, BLIMP1, BCL6, and PAX5 in circulating IgM+ B cells were measured in 15 naturally infected BLV+ and 15 BLV- cows. In addition, BLV proviral load (PVL) (a relative measurement of BLV provirus integrated into host DNA) and the relative expression of BLV TAX and 5 BLV microRNAs (miRNAs) were characterized and correlated to the expression of selected endogenous genes. BLV+ cows exhibited lower total plasma IgM and lower expression of IGJ, BLIMP1, and BCL6. While, BLV TAX and BLV miRNAs failed to correlate with IGJ expression, both BLV TAX and BLV miRNAs exhibited negative associations with BLIMP1 and BCL6 gene expression. The results suggest a possible transcriptional pathway by which BLV interferes with IgM production in naturally infected cattle.


Non-alcoholic Steatohepatitis in Asians: Current Perspectives and Future Directions.
Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease (NAFLD), which, apart from excess fat in the liver, may be characterised by some level of inflammatory infiltration and fibrogenesis, occasionally progressing to liver cirrhosis or hepatocellular carcinoma (HCC). The objective of the current review is to elucidate the rising prevalence, the role of microbiome and genetics in pathogenesis, diagnostic challenges, and novel treatment alternatives for NASH. Newer diagnostic techniques are being developed since using liver biopsy in a larger population is not a reasonable option and is primarily restricted to clinical research, at least in developing countries. Besides these technical challenges, another important factor leading to deviation from guideline practice is the lack of health insurance coverage in countries like India. It leads to reluctance on the part of physicians and patients to delay required tests to curb out-of-pocket expenditure. There is no cure for NASH, with liver transplantation remaining the last option for those who progress to end-stage liver disease (ESLD) or are detected with early-stage HCC. Thus, lifestyle modification remains the only viable option for many, but compliance and long-term adherence remain major challenges. In obese individuals, bariatric surgery and weight reduction have shown favourable results. In patients with less severe obesity, endoscopic bariatric metabolic therapies (EBMT) are rapidly emerging as less invasive therapies. However, access and acceptability remain poor for these weight reduction methods. Therefore, intense research is being conducted for potential newer drug classes with several agents currently in phase II or III of clinical development. Some of these have demonstrated promising results, such as a reduction in hepatic fat content, and attenuation of fibrosis with an acceptable tolerability profile in phase II studies. The developments in the management of NASH have been fairly encouraging. Further well-designed long-term prospective studies should be undertaken to generate evidence with definitive results.


Borderline personality pathology and chronic health problems in later adulthood: the mediating role of obesity.
Borderline personality disorder (BPD) is associated with many negative physical health outcomes, including increased risk for serious chronic diseases such as diabetes, heart disease, and arthritis. BPD is also linked with obesity, a condition that is strongly related to many of the same physical health problems. Although research has shown that BPD is related to these physical conditions, there is limited evidence of whether body mass mediates the relation between BPD and serious physical health problems. The present study examined the associations among BPD features, body mass index (BMI), and six major physical health problems in an epidemiologically based sample (n = 1051) of Saint Louis residents, ages 55-64. Using interviewer-, self-, and informant-report of personality pathology, we found that BPD features were significantly related to reported presence of heart disease, arthritis, and obesity. BMI was also significantly related to heart disease and arthritis. Sobel mediation models showed that BMI fully mediated the relation between BPD features and arthritis. These results suggest that borderline pathology is an important risk factor for serious health problems in later adulthood. Obesity appears to be one pathway that leads to more health problems among individuals with BPD symptoms and may be a useful starting point when thinking about future intervention strategies.


A novel monospecific IgG2/lambda-autoantibody with specificity for a mitochondrial antigen: evidence for an antigen-driven pathogenetic B-cell response in rheumatoid synovial tissue, induced by tissue alteration.
To elucidate the pathogenic role of synovial B cells in rheumatoid arthritis (RA), nine human IgG/lambda-secreting B-cell hybridomas from rheumatoid synovial tissue of a patient with definite RA were screened by enzyme-linked immunosorbent assay and indirect immunofluorescence on tissue cryosections for detection of antibodies against autoantigens. One IgG2/lambda monoclonal antibody (mAb) from the B-cell hybridoma ELG211/15/63 (= hybr63) exhibited intense immunofluorescence reactivity in the cytoplasm of chondrocytes and epithelial cells of the gastrointestinal tract, especially in parietal cells of gastric mucosa (human and mouse tissue), representing a mitochondrial pattern. This result was confirmed by morphometric analysis of immunoelectron microscopy data, exhibiting a significantly higher labeling density in mitochondria (p < or = 0.001) than in the cytoplasmic background, with predominant staining in the inner mitochondrial membrane and mitochondrial matrix (p < or = 0.05). Immunoblotting experiments carried out with gastric mucosa, and a mitochondrial protein preparation revealed two major proteins of 38 and 50 kd under reducing conditions. The analysis of the IgV(H) genes from this B-cell hybridoma showed highest homology to the human germline gene DP53 (96%). The IgV(L) region gave highest homology to the human germline gene DP5 (93%). In the complementarity-determining regions, residues of the H- and L-chain variable regions replacement mutations only indicated that this B-cell clone had been antigen-selected for its affinity (ratio of replacement to silent mutations: > or = 7). To analyze the in vivo expansion of the B-cell clone, primers specific for the V(H) to D to J(H) rearrangement of this B-cell hybridoma were used. Specific amplifications could be detected within part of the synovial tissue but not within the cells of the synovial fluid and peripheral blood of the patient. The ability of the IgG2/lambda mAb to induce an inflammatory reaction was tested by intraperitoneal application in severe combined immunodeficiency (SCID) mice, which resulted in an inflammatory, predominantly granulocytic infiltration of the peritoneum. Consequently, intrasynovial cell death or cartilage destruction seems to be a possible source of liberation of mitochondrial antigens, inducing a local, antigen-driven IgG2/lambda B-cell response with the ability to induce an inflammatory reaction. These data suggest that tissue destruction may serve as a source of arthritogenic antigens that perpetuate and amplify the local pernicious inflammatory process in RA synovialitis.


Patterns and Prognostic Importance of Hepatic Involvement in Patients with Serous Ovarian Cancer: A Single-Institution Experience with 244 Patients.
Purpose To evaluate the frequency, patterns, and prognostic importance of metastatic hepatic involvement in serous ovarian cancer. Materials and Methods This institutional review board-approved retrospective study, with waived informed consent, included 244 patients with pathologically proven serous ovarian cancer (mean age ± standard deviation, 59 years ± 10.7; range 19-93 years). Electronic medical records and all available imaging studies over a median follow-up of 44 months (interquartile range [IQR], 27-70) were reviewed to identify the frequency of liver parenchymal invasion (LPI) from perihepatic peritoneal metastasis and hematogenous liver metastases. The associations and prognostic importance of LPI and hematogenous metastases were studied by using univariate and multivariate Cox proportional analysis. Results Eighty-four of 244 patients (34%) developed perihepatic metastases, of whom 55 (23%) developed LPI after median of 43 months (IQR, 25-63). Hematogenous hepatic metastases developed in 38 of 244 patients (16%) after median of 42 months (IQR, 26-64). At multivariate analysis, age (P = .008; hazard ratio [HR]: 1.03; 95% confidence interval [CI]: 1.009, 1.07) and suboptimal cytoreduction (P = .03; HR, 2.13; 95% CI: 1.12, 4.07) were associated with LPI. Increasing age (P = .01; HR, 1.04; 95% CI: 1.008, 1.08), high-grade tumor (P = .01; HR, 6.75; 95% CI: 1.44, 120.5), and advanced stage (P = .03; HR, 3.16; 95% CI: 1.94, 4.56) were associated with hematogenous metastases. Overall survival with and without LPI was similar (median, 80 months; IQR, 50-not reached vs 123 months; IQR, 49-279; P = .6). Hematogenous metastases were associated with significantly shorter survival at univariate (median 63 months, IQR 43-139 vs 145 months, IQR 50-not reached; P = .006) and multivariate analyses (P = .03; HR, 1.88; 95% CI: 1.14, 3.28). Conclusion Differentiating hematogenous metastases and LPI is important for radiologists; hematogenous metastases are associated with shorter survival, while LPI does not adversely affect survival and prognostically behaves like peritoneal disease. © RSNA, 2016.


Recent advances in extracorporeal life support as a bridge to lung transplantation.
Invasive mechanical respiratory support in candidate bridging to transplant (BTT) has become common practice in recent years. This usually consists of mechanical ventilation, extracorporeal life support (ECLS) or a combination of both techniques. Areas covered: This review covers epidemiology, technical considerations, indications and outcome of ELCS as BTT. Published literature was identified by searching the MEDLINE bibliographic database (1946-present) and appropriate papers were reviewed. In a retrospective analysis of the period 2010-2016 (n = 92 cases of ECLS bridging, 62% ECLS only) at our institution, bridging success was 73%, with 1-year survival among patients surviving to transplant 78%, surpassing our previously published results between 2005-2009 (bridging success 58%, 1-year survival 58%, p = 0.002 and p = 0.02, respectively). Expert commentary: While ECLS success has influenced lung transplant selection criteria, bridging remains technically and ethically challenging. Candidate selection and organ allocation are crucial to achieving acceptable results.


Electron transport dynamics in redox-molecule-terminated branched oligomer wires on Au(111).
Dendritic bis(terpyridine)iron(II) wires with terminal ferrocene units were synthesized on a Au(111) surface by stepwise coordination using a three-way terpyridine ligand, a ferrocene-modified terpyridine ligand, and Fe(II) ions. Potential-step chronoamperometry, which applied overpotentials to induce the redox of the terminal ferrocene, revealed an unusual electron-transport phenomenon. The current-time profile did not follow an exponential decay that is common for linear molecular wire systems. The nonexponentiality was more prominent in the forward electron-transport direction (from the terminal ferrocene to the gold electrode, oxidation) than in the reverse direction (from the gold electrode to the terminal ferrocenium, reduction). A plateau and a steep fall were observed in the former. We propose a simple electron transport mechanism based on intrawire electron hopping between two adjacent redox-active sites, and the numerical simulation thereof reproduced the series of "asymmetric" potential-step chronoamperometry results for both linear and branched bis(terpyridine)iron(II) wires.


Fine structure of micropylar regions of Cobitis hankugensis, Iksookimia longicorpa and their unisexual natural hybrids.
Iksookimia longicorpa and Cobitis hankugensis are two species of fish distributed only on the Korean Peninsula. They have a unique reproductive ecology that naturally hybridizes into three widely known unisexual types, maintaining populations of almost all females. In this study, the fine structure of the micropyles of I. longicorpa, C. hankugensis and their hybrids was analyzed to find out how egg-sperm interaction, a common interspecies isolation mechanism, is possible between heterogeneous species. Analysis of 30 eggs from five females of each species revealed that all had one funnel-shaped micropylar region and a manhole-shaped micropyle canal. With the exception of C. hankugensis, which had no spiral grooves or ridges, the rest had counterclockwise spiral grooves and ridges on the micropylar region. All five species, however, showed identical groove patterns for the micropyle canal. The egg size was the largest in HL (one from the C. hankugensis locus with one from the I. longicorpa locus) and the smallest in C. hankugensis. In the hybrids, the HL type had the largest egg and HHL (two from the C. hankugensis locus with one from the I. longicorpa locus) type the smallest. For the diameter of the micropylar region and micropyle canal, the diploid I. longicorpa, C. hankugensis and HL were smaller than those of the triploid. In addition, as the ratio of the canal diameter to the eggs was lower in I. longicorpa than in C. hankugensis, it was confirmed that I. longicorpa has a relatively small micropyle canal compared with C. hankugensis.


Spatiotemporal pattern of gross primary productivity and its covariation with climate in China over the last thirty years.
The uncertainties of China's gross primary productivity (GPP) estimates by global data-oriented products and ecosystem models justify a development of high-resolution data-oriented GPP dataset over China. We applied a machine learning algorithm developing a new GPP dataset for China with 0.1° spatial resolution and monthly temporal frequency based on eddy flux measurements from 40 sites in China and surrounding countries, most of which have not been explored in previous global GPP datasets. According to our estimates, mean annual GPP over China is 6.62 ± 0.23 PgC/year during 1982-2015 with a clear gradient from southeast to northwest. The trend of GPP estimated by this study (0.020 ± 0.002 PgC/year2 from 1982 to 2015) is almost two times of that estimated by the previous global dataset. The GPP increment is widely spread with 60% area showing significant increasing trend (p < .05), except for Inner Mongolia. Most ecosystem models overestimated the GPP magnitudes but underestimated the temporal trend of GPP. The monsoon affected eastern China, in particular the area surrounding Qinling Mountain, seems having larger contribution to interannual variability (IAV) of China's GPP than the semiarid northwestern China and Tibetan Plateau. At country scale, temperature is the dominant climatic driver for IAV of GPP. The area where IAV of GPP dominated by temperature is about 42%, while precipitation and solar radiation dominate 31% and 27% respectively over semiarid area and cold-wet area. Such spatial pattern was generally consistent with global GPP dataset, except over the Tibetan Plateau and northeastern forests, but not captured by most ecosystem models, highlighting future research needs to improve the modeling of ecosystem response to climate variations.


Determination of the nonlinear dielectric increment in the Cole-Davidson model.
The problem of the nonlinear dielectric relaxation of complex liquids is tackled in the context of the Cole-Davidson [J. Chem. Phys. 19, 1484 (1951)] model. By using an appropriate time derivative of noninteger order, an infinite hierarchy of differential-recurrence relations for the moments (expectation values of the Legendre polynomials) is obtained. The solution is established for the stationary regime of an ensemble of polar and symmetric-top molecules acted on by a strong dc bias electric field superimposed on a weak ac electric field. The results for the first three nonlinear harmonic components of the electric susceptibility are analytically established and illustrated with the help of Argand diagrams for the nonlinear dielectric increment and three-dimensional dispersion and absorption spectra for the second and the third harmonic components as a function of the anomalous exponent beta</=1, the value of which gives rise to skewed arcs (Argand plots) and asymmetric shapes (loss spectra) in the high-frequency domain.


[Effect of combined application of psoralen and ultraviolet A for inducing NB4 cell apoptosis and its impact on Fas/FasL gene expressions].
To explore the effect of combined application of psoralen (PSO, an extract from psoralea) and ultraviolet A (UVA) for inducing the apoptosis of human leukemic cell line NB4 and its impact on the Fas/FasL gene expressions. According to factorial design, changes of apoptosis rate and ultrastructure of NB4 cells, as well as the gene and protein expressions of Fas/FasL were observed after cells were treated with PSO in different concentrations and irradiated by UVA of 360 nm wavelength for different times, using flow cytometry, transmission electron microscopy and quantitative polymerase chain reaction (PCR), and the outcomes were treated with variable analysis. (1) After treatment of PSO in concentration of 10, 20, 40, 80 microg/mL combined with a 5-min exposure of UVA, the NB4 cells apoptosis rate induced were 26.57% +/- 0.42%, 30.67% +/- 0.11%, 34.90% +/- 0.30% and 24.63% +/- 0.38% respectively. The effects were dose- and time-dependent, and an interaction was shown between the two actors. (2) After being treated by PSO plus UVA, obvious ultrastructure changes with apoptosis characteristics were shown in NB4 cell under electron microscope. (3) PSO plus UVA showed up-regulatory effect on gene and protein expressions of Fas, and down-regulatory effect on gene and protein expressions of FasL in a dose- and time-dependent manner, with the interaction between the two actors in altering Fas gene expression, also in altering FasL gene and protein expressions. Combined application of PSO and UVA can induce the apoptosis of NB4 cells, and the Fas/FasL system is one of the pathways for apoptosis inducing.


[Intensity modulated radiotherapy for cancers of the upper aerodigestive tract].
Intensity-modulated radiotherapy (IMRT) is a new high precision radiotherapy technique, allowing to protect some normal tissues without compromising the tumour cure probability. This is a more complex and more costly technique, compared to conventional radiotherapy, which needs increased quality assurance programs. The early results obtained in head-and-neck carcinomas have been very promising but would need to be confirmed in randomised trials to determine whether these results can be transposed to the majority of these cancers and especially to locally advanced cases, which are the most frequently occurring forms of these cancers.


Studies of 13C-urea breath test for diagnosis of Helicobacter pylori infection in patients after partial gastrectomy.
Many of the reports on the diagnostic efficacy of the 13C-urea breath test (13C-UBT) for the detection of Helicobacter pylori in the residual stomach have shown negative results. We conducted an evaluation to establish a standardized protocol and an appropriate cutoff value for 13C-UBT in partial gastrectomy patients. Forty-two patients undergoing partial gastrectomy were included. Three gastric biopsies from the anastomotic site and mid-to-high body were taken at panendoscopy for histology, culture and rapid urease test (RUT). The 13C-UBT protocol included ingestion of 100 mg 13C-urea, use of mouthwash, and the body in a horizontal position on the left side. Six breath samples were taken after ingestion. The Delta 13CO2 values were significantly elevated in infected patients at all time points, and values were higher at 20 min and thereafter than at an earlier time point. The sensitivity of 13C-UBT was 96.3% with the cutoff of 2.0 per thousand at 40 min. The accuracy rates were highest with 13C-UBT, culture, RUT and histological tests, in that order. Forty minutes and a cutoff of 2.0 per thousand were found to be optimal for the test, with the body position horizontal on the left side. In the present protocol 13C-UBT appears to be a reliable tool with the same accuracy rate as other routine tests in patients with a remnant stomach.


[Cerebral hemorrhage after carotid endarterectomy in a young adult].
Cerebral haemorrhage after carotid endarterectomy is a rare complication. It follows 0.5% to 20% of all endarterectomies, but should be borne in mind because of the morbidity and mortality seen in most cases. We describe the case of a 42 year old man in whom carotid endarterectomy had been done 7 days before to treat a stenosis of 80%. He complained of a sudden onset of weakness of the right half of his body and changes in his speech. Physical examination showed right inferior facial paresia, right hemiparesia and right extensor cutaneous plantar reflex. On admission to the Emergency Department, before treatment, blood pressure was 80/60. Carotid auscultation and palpation were normal. Cerebral TRC showed a left lenticular haematoma. The patient progressed satisfactorily. We review the literature on the subject as well as the factors which should be considered as possibly predisposing to bleeding after carotid endarterectomy, such as arterial hypertension and occlusion or severe stenosis of the contralateral carotid artery. The detection of patients with the risk of postendarterectomy bleeding by simple noninvasive investigations, such as the transcranial doppler and the acetazolamide test, and early diagnosis of a clinical picture compatible with a hyperperfusion syndrome may contribute to the relief and prevention of sequelae in these patients.


Diencephalic seizures: responsiveness to bromocriptine and morphine.
Two patients with posttraumatic diencephalic seizures, characterized by autonomic dysfunction and extensor posturing, had partial responses to bromocriptine and complete responses to morphine. Probable synergism between the two agents was noted. These 2 cases suggest the potential effectiveness of this regimen for the treatment of diencephalic seizures, raise questions regarding the role of the dopaminergic and opioid systems in this disease entity, and support the hypothesis that diencephalic seizures represent a release phenomenon in the brain.


Evidence of the Role of R-Spondin 1 and Its Receptor Lgr4 in the Transmission of Mechanical Stimuli to Biological Signals for Bone Formation.
The bone can adjust its mass and architecture to mechanical stimuli via a series of molecular cascades, which have been not yet fully elucidated. Emerging evidence indicated that R-spondins (Rspos), a family of secreted agonists of the Wnt/β-catenin signaling pathway, had important roles in osteoblastic differentiation and bone formation. However, the role of Rspo proteins in mechanical loading-influenced bone metabolism has never been investigated. In this study, we found that Rspo1 was a mechanosensitive protein for bone formation. Continuous cyclic mechanical stretch (CMS) upregulated the expression of Rspo1 in mouse bone marrow mesenchymal stem cells (BMSCs), while the expression of Rspo1 in BMSCs in vivo was downregulated in the bones of a mechanical unloading mouse model (tail suspension (TS)). On the other hand, Rspo1 could promote osteogenesis of BMSCs under CMS through activating the Wnt/β-catenin signaling pathway and could rescue the bone loss induced by mechanical unloading in the TS mice. Specifically, our results suggested that Rspo1 and its receptor of leucine-rich repeat containing G-protein-coupled receptor 4 (Lgr4) should be a novel molecular signal in the transmission of mechanical stimuli to biological signal in the bone, and this signal should be in the upstream of Wnt/β-catenin signaling for bone formation. Rspo1/Lgr4 could be a new potential target for the prevention and treatment of disuse osteoporosis in the future.


(2-Amino-3-nitro-benzoato-κO)triphenyl-tin(IV).
The asymmetric unit of the title compound, [Sn(C(6)H(5))(3)(C(7)H(5)N(2)O(4))], consists of two independent mol-ecules. In each mol-ecule, the four-coordinated Sn(IV) atom exists in a distorted tetra-hedral geometry and two intra-molecular N-H⋯O hydrogen bonds with S(6) ring motifs are present. In one mol-ecule, the benzene ring of the 2-amino-3-nitro-benzoate ligand makes dihedral angles of 42.74 (11), 89.66 (13) and 53.04 (10)° with the three phenyl rings. The corresponding dihedral angles for the other mol-ecule are 6.29 (11), 66.55 (11) and 62.33 (10)°. In the crystal, a weak inter-molecular C-H⋯π inter-action and a π-π stacking inter-action with a centroid-centroid distance of 3.5877 (12) Å are observed.


Acute rheumatic carditis causing sudden death.
An 18-year-old male died suddenly while running a confidence course in basic training. Past medical history was negative for acute rheumatic fever. At autopsy he had acute rheumatic mitral valvulitis with extensive myocarditis. Multiple Aschoff bodies were seen in perivascular regions in the right and left ventricle. Review of recent literature of the various causes of sudden cardiac death failed to reveal acute rheumatic valvulitis and myocarditis as reported causes of sudden death.


Safety and reliability of tattooing colorectal neoplasms prior to laparoscopic resection.
Accurate tumor localization is critical to performing minimally invasive colorectal resection. This study reviews the safety and reliability of tattooing colorectal neoplasms prior to laparoscopic resection. We retrospectively reviewed 50 consecutive patients with colorectal neoplasms who underwent endoscopic tattooing prior to laparoscopic resection. Data were obtained from medical charts, endoscopy records, and pathology reports. No complications related to endoscopy or tattooing were incurred. Five neoplasms (10%) were in the ascending colon, five (10%) were in the transverse colon, eight (16%) were in the descending colon, 23 (46%) were in the sigmoid colon, and nine (18%) were in the rectum. Tattoos were visualized intraoperatively and accurately localized the neoplasm in 44 patients (88%). Six patients (12%) did not have tattoos visualized laparoscopically and required intraoperative localization. On average, the pathology specimens in this series had a 15 cm proximal margin, a 12 cm distal margin, and 15 lymph nodes. In the context of laparoscopic colorectal resection, preoperative endoscopic tattooing is a safe and reliable method of tumor localization in most cases. Localizing colon and proximal rectal lesions with tattoos may be preferable to other localization techniques including intraoperative endoscopy.


An Epidemiologic Approach to the Study of Aerosolized Florida Red Tides.
Very little has been published in the scientific literature on the human health effects of Florida red tide, either as human clinical case reports or formal epidemiologic studies. In addition to the health effects associated with the ingestion of contaminated shellfish, there have been multiple anecdotal reports of respiratory irritation and possible immunologic effects associated with the inhalation of aerosolized Florida red tide. To investigate the human health effects from environmental exposure to red tide toxins, we have formed an interdisciplinary team of scientists. We have created a network of public and environmental health workers who periodically report local conditions as a red tide develops. In addition, we have access to environmental monitoring data as well as data from a surveillance program supported through the Florida Poison Information Network. When a red tide moves onshore where people might be exposed, the team rapidly assembles at the site to collect environmental samples and epidemiologic data. To assess the more long-term effects from environmental exposure to red tide toxins, we are conducting epidemiologic studies involving occupational and sensitive populations who live in areas that are regularly impacted by red tides. Other scientists are evaluating the acute and chronic respiratory effects of red tides and brevetoxins in both rat and sheep models as well as refinement of toxin measurement methodology. These models are being used to refine and validate the biomarkers of brevetoxins exposure as well as explore the pathophysiology of health effects from brevetoxins respiratory exposure. Bolstered by the additional research in rat and sheep models, this interdisciplinary scientific team is exploring the acute and chronic exposures and health effects of aerosolized Florida red tides in animal models and various human populations. In the future, this research can be applied to the understanding of exposure and effects of other aerosolized natural toxins such as cyanobacterial toxins.


[Treatment of prostato-rectal fistulae. Apropos of 5 cases].
The authors report 5 cases of prostato-rectal fistulae. Two men were treated by a posterior approach and two by an abdominal approach because of associated lesions. They review all of the techniques of approaching the prostato-rectal fistulas. The transsphincteric approach provides excellent exposure and reliable closure of prostato-rectal fistulas: the concern for possible anal incontinence is unfounded. Additional security can be obtained by performing a colostomy beforehand.


Radionuclide therapy for prostate cancer lumbar metastasis prolongs symptom-free survival in a rat model.
The present study was initiated to explore the effects of hydroxyethylidene diphosphonate labeled with rhenium 186(186Re-HEDP) treatment on the progression of lumbar skeletal metastasis in an animal model and to correlate the eventual treatment efficacy with the radioisotope tissue distribution. The effect of 186Re-HEDP on the progression of lumbar metastasis from prostate cancer was investigated in the Copenhagen rat model. Metastatic prostate tumor deposits were induced in male rats by tail vein injection of R3327-MATLyLu prostate tumor cells under concomitant clamping of the inferior caval vein. The development of clinical symptoms such as onset of hind leg paralysis and urinary bladder swelling was monitored and related to the presence of tumor cells within histologic sections of L-5 and L-6 vertebrae. The 186Re-HEDP administration, given either 1 day or 8 days after surgical induction of lumbar metastasis, could significantly increase the symptom-free survival of the animals. These results were confirmed by a significant decrease in the presence of histologically detectable tumor tissue. Biodistribution studies demonstrated the uptake of the major part of the radioisotope within bone tissue. Uptake of radioactivity within the lumbar vertebrae on a microscopic scale, as shown by phosphor screen autoradiography, was concentrated in areas of bone formation and turnover. Signs of radiotoxicity, such as bone marrow replacement by fat cells and the absence of megakaryocytes, were observed. The results show that radionuclide treatment using 186Re-HEDP is a potentially efficacious treatment option in prostate cancer disseminated to the skeleton. The optimal treatment dose should be determined carefully and aimed at acceptable levels of myelotoxicity.


The quantum-confined Stark effect in layered hybrid perovskites mediated by orientational polarizability of confined dipoles.
The quantum-confined Stark effect (QCSE) is an established optical modulation mechanism, yet top-performing modulators harnessing it rely on costly fabrication processes. Here, we present large modulation amplitudes for solution-processed layered hybrid perovskites and a modulation mechanism related to the orientational polarizability of dipolar cations confined within these self-assembled quantum wells. We report an anomalous (blue-shifting) QCSE for layers that contain methylammonium cations, in contrast with cesium-containing layers that show normal (red-shifting) behavior. We attribute the blue-shifts to an extraordinary diminution in the exciton binding energy that arises from an augmented separation of the electron and hole wavefunctions caused by the orientational response of the dipolar cations. The absorption coefficient changes, realized by either the red- or blue-shifts, are the strongest among solution-processed materials at room temperature and are comparable to those exhibited in the highest-performing epitaxial compound semiconductor heterostructures.