CpG Methylation Changes G-Quadruplex Structures Derived from Gene Promoters and Interaction with VEGF and SP1.
G-quadruplex (G4) is a DNA/RNA conformation that consists of two or more G-tetrads resulting from four-guanine bases connected by Hoogsteen-type hydrogen bonds, which is often found in the telomeres of chromatin, as well as in the promoter regions of genes. The function of G4 in the genomic DNA is being elucidated and some G4-protein interactions have been reported; these are believed to play a role in vital cellular functions. In this study, we focused on CpG methylation, a well-known epigenetic modification of the genomic DNA, especially found in the promoter regions. Although many G4-forming sequences within the genomic DNA harbor CpG sites, the relationship between CpG methylation and the binding properties of associated proteins remains unclear. We demonstrated that the binding ability of vascular endothelial growth factor (VEGF) G4 DNA to VEGF165 protein was significantly decreased by CpG methylation. We identified the binding activity of G4 DNA oligonucleotides derived from gene promoter regions to SP1, a transcription factor that interacts with a G4-forming DNA and is also altered by CpG methylation. The effect of methylation on binding affinity was accompanied by changes in G4 structure and/or topology. Therefore, this study suggested that CpG methylation might be involved in protein binding to G4-forming DNA segments for purposes of transcriptional regulation.


Contrary results on mouse hepatitis virus type 3 susceptibility in A/J mouse hepatocytes of phosphatidylserine treatment and of a hypercholesterolaemic diet: no correlation with membrane fluidity levels.
The aim of this study was to examine whether or not membrane fluidity directly influences infection by enveloped viruses, and, more precisely here, the susceptibility of A/J mouse hepatocytes to Mouse Hepatitis Virus type 3 (MHV3). We therefore studied, in parallel, the effects on hepatocyte membrane fluidity and on intracellular viral titre of two treatments, i) a hypercholesterolaemic diet to increase the hepatocyte membrane cholesterol content, ii) direct phosphatidylserine incorporation into hepatocyte membrane. Membrane fluidity was monitored on isolated hepatocytes by fluorescence anisotropy with TMA-DPH, and the viral titre was determined by plaque assay. The results clearly demonstrate that membrane fluidity is not directly involved in viral infection mechanisms.


Allograft cytotoxicity co-operation between alloimmune T cells and macrophages.
T cells from the spleens of C57BL 10 (H-2b) mice 7-12 days after immunization with P815Y (H-2d) mastocytoma cells have been shown to co-operate synergistically with an adherent component of non-immune starch induced peritoneal cells in the cytostasis of target cells. Although significant values for synergy could be obtained using the (125I) UdR incorporation assay to measure cytostasis, normal peritoneal cells were incapable of co-operating with T cells in cytolysis as measured by 51Cr release from pre-labelled target cells. Initially, the synergistic interaction was immunologically specific, but non-specific activity could be induced by challenge with specific antigen.


Efficacy of Psychosocial Interventions for Survivors of Intimate Partner Violence: A Systematic Review and Meta-Analysis.
Survivors of intimate partner violence (IPV) face serious health-related, social and economic consequences. Prior meta-analyses indicate efficacy of psychosocial interventions for support of IPV survivors, but their results are affected by methodological limitations. Extensive subgroup analyses on the moderating effects of intervention and study characteristics are lacking. To address these limitations in an up-to-date and comprehensive meta-analytic review, four literature databases (PsycInfo, Medline, Embase, and CENTRAL, March 23, 2022) were searched for randomized-controlled trials examining the efficacy of psychosocial interventions compared to control groups in improving safety-related, mental health, and psychosocial outcomes in IPV survivors. Weighted effects on IPV, depression, posttraumatic stress disorder (PTSD), and psychosocial outcomes were calculated under random-effects assumption. Subgroup analyses were performed to investigate moderating effects of predefined intervention and study characteristics. Study quality was rated. In all, 80 studies were included in qualitative synthesis, and 40 studies in meta-analyses. Psychosocial interventions significantly reduced symptoms of depression (SMD: -0.15 [95% confidence interval, CI [-0.25, -0.04]; p = .006], I2 = 54%) and PTSD (SMD: -0.15 [95% CI [-0.29, -0.01]; p = .04], I2 = 52%), but not IPV reexperience (SMD: -0.02 [95% CI [ -0.09, 0.06]; p = .70], I2 = 21%) compared to control conditions at post. High-intensive and integrative interventions, combining advocacy-based and psychological components, were favorable subgroups. Yielded effects were modest and not maintained long term. The quality of evidence was low and potential harms remain unclear. Future research should adopt higher standards of research conduct and reporting and must account for the complexity and diversity of IPV experiences.


The Balancing of Peroxynitrite Detoxification between Ferric Heme-Proteins and CO2: The Case of Zebrafish Nitrobindin.
Nitrobindins (Nbs) are all-β-barrel heme proteins and are present in prokaryotes and eukaryotes. Although their function(s) is still obscure, Nbs trap NO and inactivate peroxynitrite. Here, the kinetics of peroxynitrite scavenging by ferric Danio rerio Nb (Dr-Nb(III)) in the absence and presence of CO2 is reported. The Dr-Nb(III)-catalyzed scavenging of peroxynitrite is facilitated by a low pH, indicating that the heme protein interacts preferentially with peroxynitrous acid, leading to the formation of nitrate (~91%) and nitrite (~9%). The physiological levels of CO2 dramatically facilitate the spontaneous decay of peroxynitrite, overwhelming the scavenging activity of Dr-Nb(III). The effect of Dr-Nb(III) on the peroxynitrite-induced nitration of L-tyrosine was also investigated. Dr-Nb(III) inhibits the peroxynitrite-mediated nitration of free L-tyrosine, while, in the presence of CO2, Dr-Nb(III) does not impair nitro-L-tyrosine formation. The comparative analysis of the present results with data reported in the literature indicates that, to act as efficient peroxynitrite scavengers in vivo, i.e., in the presence of physiological levels of CO2, the ferric heme protein concentration must be higher than 10-4 M. Thus, only the circulating ferric hemoglobin levels appear to be high enough to efficiently compete with CO2/HCO3- in peroxynitrite inactivation. The present results are of the utmost importance for tissues, like the eye retina in fish, where blood circulation is critical for adaptation to diving conditions.


DIAMAP: a road map for diabetes research in Europe.
The DIAMAP Project, which has drawn up a road map for diabetes research in Europe, has now concluded, and the results are available in the form of a report and searchable databases. The DIAMAP road maps provide strategic guidance for diabetes research activity and investment in Europe, with the person with diabetes and a broad approach to research being integral to the process.


Mortality from Parkinson's disease and other causes among a workforce manufacturing paraquat: a retrospective cohort study.
Objective To assess the risk of Parkinson's disease (PD) and update information on mortality from major causes of death among a UK workforce who manufactured paraquat (PQ) between 1961 and 1995. There have been no previous studies of the incidence of PD among PQ production workers, although much epidemiological literature exists concerning the relationship between pesticides and PD, and interest has focused on PQ and its users. Methods The cohort included all employees who had ever worked on any of the four plants at Widnes where PQ was manufactured between 1961 and 1995, and 926 male and 42 female workers were followed through 30 June 2009. Mortalities for males were compared with national and local rates, including rates for PD as a mentioned cause of death. Results Overall, 307 workers had died by 30 June 2009. One male death was due to PD, and no other death certificate mentioned PD. At least 3.3 death certificates of male employees would have been expected to have mentioned PD (standardised mortality ratio=31; 95% CI 1 to 171). Personal monitoring results were indicative that the exposure of a PQ production worker on a daily basis was at least comparable with that of a PQ sprayer or mixer/loader. Reduced mortalities compared with local rates were found for major causes of death. Conclusions The study provided no evidence of an increased risk of PD, or increased mortalities from other causes.


Intra-lesional low-dose interferon alpha2a therapy for primary cutaneous marginal zone B-cell lymphoma.
Primary cutaneous marginal zone lymphomas (pcMZL) belong to the primary cutaneous B-cell lymphoma (pCBCL) group. They are characterized by their restriction to the skin and a high likelihood of recurrence after various treatment modalities. First-line therapy consists of surgery and radiotherapy. These therapies may not always be indicated in young patients or in patients with pCBCL located in the face, where surgery or radiotherapy may leave disfiguring scars or radioderma. Eight patients with pcMZL were treated with intra-lesional injections of 3 million units of recombinant IFNalpha2a three times per week. The patients either did not want to undergo or did not qualify for surgical excision or radiotherapy due to inappropriate localization or age. All patients experienced complete tumor regression after a mean of 8.5 weeks (range 3 - 20). Two patients relapsed 4 and 12 months after treatment, respectively, but tumor regression was repeated after additional cycles of intra-lesional IFNalpha2a. All other patients remained free of disease. Thus, intra-lesional IFNalpha2a may represent a valuable alternative to surgery and radiotherapy as first-line treatment of pcMZL.


[Clinicopathologic characteristics and prognosis of rectal neuroendocrine neoplasms].
To study the clinicopathologic characteristics and prognosis of rectal neuroendocrine neoplasms (NENs). From January 2000 to May 2017, 84 patients were diagnosed as NENs by pathology and underwent surgical treatment in Peking University First Hospital. Their clinicopathological characteristics, surgial options and prognosis were analyzed retrospectively. Among these 84 cases, 67 cases were NET G1, 6 cases were NET G2, 10 cases were NEC G3 and 1 case was MANEC G3. The median size was 0.8 (0.2 to 18.0) cm. There were 60 cases of stage I(, 2 cases of stage II(, 12 cases of stage III(, 10 cases of stage IIII(. Forty-nine patients accepted examinations because of non-specific symptoms, including altered bowel habits(22/49), bloody stool (19/49) and abdominal pain(10/49); the other 35 cases including 2 patients with liver metastasis were diagnosed by endoscopy or CT during routine physical examination. Forty-four patients received endoscopic ultrasonography(EUS) with 100% of sensitivity and 90.9% of accuracy. Among 20 cases (23.8%) with lymph node metastasis (all ≥T2 stage), 12 cases were NET G1 and G2 (1 case of multiple NET G1) and 8 cases were NEC G3 and MANEC G3. The lymph node metastasis rate of stage T1 NET G1 and G2 was lower than that of stage T2 to T4 NET G1 and G2, also lower than that of NEC G3 and MANEC G3 (all P=0.000), however, stage T2 to T4 NET G1 and G2 showed the similar rate of lymph node metastasis with NEC G3 and MANCE G3(P>0.05). Synchronously distant metastasis was found in 10 (11.9%) patients at the first diagnosis, and ovarian metastasis was found in 1 case 9 years after curative resection of rectal NEN. Among 81 patients receiving operation, 57 patients underwent endoscopic mucosal resection (56 patients of stage T1 NET G1 and G2); 3 patients local excision without lymph node dissection; 13 patients curative resection; 1 patient curative resection with liver metastasis resection; 6 patients palliative surgery and 1 patient metastatic lesion resection only. Overall follw-up time was 1 month to 169 months, and the 3- and 5-year survival rates were 87.7% and 79.7% respectively. No recurrence or metastasis was observed in all the 62 patients with T1 G1 and G2, including 56 cases of ESD, 3 cases of local excision, 3 cases of curative resection, whose 3-year and 5-year survival rates were both 96%. The prognosis was closely associated with grade and stage of NENs (all P=0.000). The early symptoms of rectal NENs are insidious and atypical, therefore some patients are diagnosed as stage II( or higher at their first consultation. ESD is safe and effective for NET G1 and G2. The prognosis depends on grade and stage of NENs.


Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (I).
Gut-associated lymphoid tissue (GALT) is the largest lymphoid organ in the body. This is not surprising considering the huge load of antigens (Ags) from food and commensal bacteria with which it interacts on a daily basis. Gut-associated lymphoid tissue has to recognise and allow the transfer of beneficial Ags whilst concurrently dealing with and successfully removing putative and overtly harmful Ags. This distinctive biological feature of GALT is believed to be crucial to good health. Deregulation or dysfunction of GALT is thought to predispose to inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The exact mechanism(s) underlying the pathogenesis of IBD is (are) poorly understood and the immunological defects in GALT are poorly documented. Advances in immunology have highlighted the importance of dendritic cells (DCs), which are the key Ag presenting cells in tissues and lymphoid compartments. Their crucial role in GALT, in health and disease is discussed in this review. Interaction of DCs with T cells in the gut produces a subset of T lymphocytes, which have immunosuppressive function. Inappropriate Ag uptake and presentation to naïve T cells in mesenteric lymph nodes may lead to T cell tolerance in GALT. These various complex factors in the gut are discussed and their possible relevance to IBD evaluated.


Transcutaneous oximetry in obstetrics and gynecology.
Transcutaneous methods of assessing patient oxygenation are gaining acceptance in many areas of both obstetrics and gynecology. As these techniques move from research protocols to daily practice, some understanding of the underlying technology is necessary. This will allow the clinician to make maximal use of the information possible and avoid pitfalls due to artifacts and equipment limitations. Most of the transcutaneous oximeters in use today rely on either electrochemical or photometric principles for their determinations. Each of these techniques offers unique advantages and disadvantages which help to determine their applicability in various clinical settings.


Molecular Dynamics Study of the Nanoindentation Behavior of Cu64Zr36/Cu Amorphous/Crystalline Nanolaminate Composites.
Amorphous/crystalline nanolaminate composites have aroused extensive research interest because of their high strength and good plasticity. In this paper, the nanoindentation behavior of Cu64Zr36/Cu amorphous/crystalline nanolaminates (ACNLs) is investigated by molecular dynamics (MD) simulation while giving special attention to the plastic processes occurring at the interface. The load-displacement curves of ACNLs reveal small fluctuations associated with shear transformation zone (STZ) activation in the amorphous layer, whereas larger fluctuations associated with dislocations emission occur in the crystalline layer. During loading, local STZ activation occurs and the number of STZs increases as the indentation depth in the amorphous layer increases. These STZs are mostly located around the indenter, which correlates to the high stresses concentrated around the indenter. When the indenter penetrates the crystalline layer, dislocations emit from the interface of amorphous/crystalline, and their number increases with increasing indentation depth. During unloading, the overall number of STZs and dislocations decreases, while other new STZs and dislocations become activated. These results are discussed in terms of stress distribution, residual stresses, indentation rate and indenter radius.


LiDAR Point Cloud Generation for SLAM Algorithm Evaluation.
With the emerging interest in the autonomous driving level at 4 and 5 comes a necessity to provide accurate and versatile frameworks to evaluate the algorithms used in autonomous vehicles. There is a clear gap in the field of autonomous driving simulators. It covers testing and parameter tuning of a key component of autonomous driving systems, SLAM, frameworks targeting off-road and safety-critical environments. It also includes taking into consideration the non-idealistic nature of the real-life sensors, associated phenomena and measurement errors. We created a LiDAR simulator that delivers accurate 3D point clouds in real time. The point clouds are generated based on the sensor placement and the LiDAR type that can be set using configurable parameters. We evaluate our solution based on comparison of the results using an actual device, Velodyne VLP-16, on real-life tracks and the corresponding simulations. We measure the error values obtained using Google Cartographer SLAM algorithm and the distance between the simulated and real point clouds to verify their accuracy. The results show that our simulation (which incorporates measurement errors and the rolling shutter effect) produces data that can successfully imitate the real-life point clouds. Due to dedicated mechanisms, it is compatible with the Robotic Operating System (ROS) and can be used interchangeably with data from actual sensors, which enables easy testing, SLAM algorithm parameter tuning and deployment.


Angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis.
Angina pectoris has long been recognised as one of the principal symptoms of severe aortic valve stenosis (AS), even in patients without significant coronary artery disease (CAD). However, controversy exists concerning the prevalence of angina pectoris and associated CAD in such patients. To determine the prevalence of CAD detectable by angiography and its relation to angina pectoris and coronary risk factors in patients with severe AS. All patients with symptomatic AS who had undergone aortic valve replacement and preoperative cardiac catheterisation at the Austin and Repatriation Medical Centre between 1 January 1986 and 31 May 1996 were retrospectively analysed. Those patients with multiple valve disease, aortic regurgitation of grade 2 or more in severity, or who had had prior coronary artery or valve surgery were excluded from this analysis. A total of 328 consecutive patients with severe AS (242 men and 86 women; mean age 72 years, range 39-84 years) were studied. Significant CAD (reduction in luminal diameter > or = 50%) was found in 162 patients (49.4%). Typical angina was present in 74.7% of these 162 patients but it was also found in 44.6% of the 166 patients without obstructive CAD. Of the patients without angina (n = 133), 30.8% had significant CAD. By multivariate logistic regression, we have identified seven significant predictors for CAD among severe AS patients. Five factors increased risk. Expressed as odds ratio with 95% confidence interval, these included: (i) age in years (1.07; 1.04-1.11, P = 0.001); (ii) male gender (2.09; 1.14-3.80, P = 0.016); (iii) angina pectoris (3.19; 1.89-5.37, P < 0.001); (iv) history of myocardial infarction (2.87; 1.38-5.97, P = 0.005); and (v) peripheral vascular disease (2.28; 1.28-4.05, P = 0.005). Factors associated with decreased likelihood of CAD were serum high density lipoprotein (HDL) cholesterol (0.58; 0.34-0.71, P = 0.002) and peak systolic gradient across the aortic valve (0.97; 0.95-0.99, P = 0.0113). Coronary arteriography can probably be omitted for a patient with severe AS if that patient has no symptoms of angina and has no risk factors known to increase its incidence.


PKD at the crossroads of necrosis and autophagy.
Reactive oxygen species (ROS) that accumulate under oxidative pressure cause severe damage to cellular components, and induce various cellular responses, including apoptosis, programmed necrosis and autophagy, depending on the cellular setting. Various studies have described ROS-induced autophagy, but only a few direct factors that regulate autophagy under oxidative stress are known to date. We have identified DAPK and PKD as such regulators by demonstrating their role in the process of autophagy in general, and specifically during oxidative stress. PKD acts as a downstream effector of DAPk in the regulation of autophagy. Furthermore, PKD functions within the autophagic network as an activator of VPS34, by associating with and phosphorylating VPS34, leading to its activation. Significantly, PKD is recruited to the autophagosomal membranes, placing it within proximity of its autophagic target.


Hydroxylase inhibition abrogates TNF-alpha-induced intestinal epithelial damage by hypoxia-inducible factor-1-dependent repression of FADD.
Hydroxylase inhibitors stabilize hypoxia-inducible factor-1 (HIF-1), which has barrier-protective activity in the gut. Because the inflammatory cytokine TNF-α contributes to inflammatory bowel disease in part by compromising intestinal epithelial barrier integrity, hydroxylase inhibition may have beneficial effects in TNF-α-induced intestinal epithelial damage. The hydroxylase inhibitor dimethyloxalylglycin (DMOG) was tested in a murine model of TNF-α-driven chronic terminal ileitis. DMOG-treated mice experienced clinical benefit and showed clear attenuation of chronic intestinal inflammation compared with that of vehicle-treated littermates. Additional in vivo and in vitro experiments revealed that DMOG rapidly restored terminal ileal barrier function, at least in part through prevention of TNF-α-induced intestinal epithelial cell apoptosis. Subsequent transcriptional studies indicated that DMOG repressed Fas-associated death domain protein (FADD), a critical adaptor molecule in TNFR-1-mediated apoptosis, in an HIF-1α-dependent manner. Loss of this FADD repression by HIF-1α-targeting small interfering RNA significantly diminished the antiapoptotic action of DMOG. Additional molecular studies led to the discovery of a previously unappreciated HIF-1 binding site in the FADD promoter, which controls repression of FADD during hypoxia. As such, the results reported in this study allowed the identification of an innate mechanism that protects intestinal epithelial cells during (inflammatory) hypoxia, by direct modulation of death receptor signaling. Hydroxylase inhibition could represent a promising alternative treatment strategy for hypoxic inflammatory diseases, including inflammatory bowel disease.


Advances in pharmacotherapy: treatment of hypertensive crisis.
A hypertensive crisis can be caused by many factors. Frequently, the mechanism involved is complex and highly variable among patients. Without drug therapy, this condition is associated with very high mortality and morbidity. There are a number of oral and intravenous hypotensive agents available, which can effectively control blood pressure in a hypertensive crisis. The relative advantages and disadvantages of each treatment option is discussed.


Cell proliferation and protein synthesis as initial factors in determination of axial polarity.
The rate of cell proliferation relative to that of protein synthesis appears to have an initial role in establishment of axial polarities in developing animal embryos. An increase in this ratio leads to anterior or dorsal differentiation, while reduction allows posterior or ventral differentiation in a number of organisms. The role that various growth factors play in the regulation of proliferation and protein synthesis is examined.


Programmable and Shape-Memorizing Information Carriers.
Shape memory polymers (SMPs) are expected to play more and more important roles in space-deployable structures, smart actuators, and other high-tech areas. Nevertheless, because of the difficulties in fabrication and the programmability of temporary shape recovery, SMPs have not yet been widely applied in real fields. It is ideal to incorporate the different independent functional building blocks into a material. Herein, we designed a simple method to incorporate four functional building blocks: a neat epoxy-based shape memory (neat SMEP) resin, an SMEP composited with Fe3O4 (SMEP-Fe3O4), an SMEP composited with multiwalled carbon nanotubes, and an SMEP composited with p-aminodiphenylimide into a multicomposite, in which the four region surfaces could be programmed with different language code patterns according to a preset command by imprint lithography. Then, we aimed to reprogram the initially raised code patterns into temporary flat patterns using programming mold that, when triggered by a preset stimulus process such as an alternating magnetic field, radiofrequency field, 365 nm UV, and direct heating, could transform these language codes into the information passed by the customer. The concept introduced here will be applied to other available SMPs and provide a practical method to realize the information delivery.


Aortic valve replacement with or without coronary artery bypass graft surgery: the risk of surgery in patients > or =80 years old.
The purpose of this study was to evaluate the outcomes for elderly (> or =80 years) patients undergoing aortic valve replacement (AVR) with or without coronary artery bypass graft surgery (AVR/CABG). The authors hypothesized that the mortalities of AVR and AVR/CABG are lower than that predicted by published risk scores. A retrospective analysis of data from a single-hospital database. Single tertiary care, private practice. Consecutive patients undergoing AVR or AVR/CABG. Two hundred sixty-one elderly (> or =80 years) patients undergoing isolated AVR (145) or AVR/CABG (116) were evaluated. The majority (94.6%) underwent AVR for aortic valve stenosis. Outcomes were recorded and compared between the 2 surgical procedures with predicted mortalities based on published risk assessment scoring systems. The overall short-term mortality for the elderly group was 6.1% (AVR 5.5% and AVR/CABG 6.9%). The median long-term survival was 6.8 years. There were no significant differences in either morbidity or mortality between the AVR and AVR/CABG groups. Although predicted mortalities were similar for each surgical procedure, they overestimated observed outcome by up to 4-fold. Short- and long-term mortality was low for this group of elderly patients undergoing AVR or AVR/CABG and not significantly different between the 2 surgical groups. Predicted outcomes were worse than that observed, consistent with the hypothesis, and supportive of a more aggressive surgical treatment for aortic valve disease in the elderly patient.


Radiolabeled interleukin-8: specific scintigraphic detection of infection within a few hours.
Several small receptor-binding agents have been tested for imaging of infection and inflammation. The potential of chemotactic peptides and of interleukins is promising and superior to that of conventional agents. In this study, we investigated the potential of interleukin-8 (IL-8) to image infection in rabbits. IL-8 was labeled with 123I using the Bolton-Hunter method. Twenty-fours hours after induction of Escherichia coli abscesses in the left thigh muscle, rabbits were injected intravenously with 18.5 MBq 123I-IL-8. Gamma camera images were obtained at 5 min and at 1, 4, and 8 h after injection. Biodistribution was determined 8 h after injection. 123I-IL-8 rapidly cleared from the blood. Accumulation of 123I-IL-8 in the abscess was visible as early as 1 h after injection. The highest abscess uptake was obtained 4 h after injection (2.6+/-0.2 percentage injected dose [%ID]), whereas 123I-IL-8 rapidly cleared from all other tissues. This resulted in increases in abscess-to-background ratios to 13.0+/-0.7 (8 h after injection), as determined by quantification of the images. In tissue biodistribution (8 h after injection), the abscess uptake was 0.057+/-0.011 %ID/g with abscess-to-contralateral muscle ratios of 114.7+/-23.0. The radioiodination method clearly affected the in vivo biodistribution of IL-8 because IL-8 iodinated using the lodo-Gen method cleared significantly slower from the blood and most other organs, resulting in poor visualization of the abscess. The superior characteristics of IL-8 radioiodinated using the Bolton-Hunter method--i.e., high abscess uptake and rapid background clearance within a few hours--make IL-8 a promising agent to image infection and inflammation.


Evolution rate of hepatitis delta virus RNA isolated in Taiwan.
The complete RNA sequences of hepatitis delta viruses (HDV) isolated at 3 years apart from a chronic delta hepatitis patient in Taiwan were determined. The sequence analysis showed an overall evolution rate of 3.18 x 10(-3) substitutions/nucleotide/year. The evolution rates in different parts of HDV RNA varied. The hypervariable region evolved faster (4.55 x 10(-3) substitutions/nucleotide/year) than the hepatitis delta antigen (HDAg)-coding region (2.60 x 10(-3) substitutions/nucleotide/year) and the autocatalytic region (1.11 x 10(-3) substitutions/nucleotide/year). These data are compatible with the previous finding that the hypervariable region is more divergent than the HDAg-coding region and the autocatalytic regions among the HDV isolates from different geographic areas. No substitution was found in the four previously identified conserved domains of HDV RNA, further confirming their functional importance in viral replication. The evolution rate of this HDV RNA is higher than that determined from the partial RNA sequences of two Japanese HDV isolates and similar to that found in a Lebanon isolate. Further, it was found that this HDV RNA retained the same microheterogeneities at 15 nucleotide positions detected in the RNA 3 years earlier. It is concluded that HDV RNA in patients' serum is extremely heterogeneous, and that the nucleotide substitutions in certain nucleotide positions likely have conferred evolutionary advantages for HDV. Viral sequence evolution is a possible mechanism for chronic HDV infection.


The Basel Institute for Immunology.
At the Centennial Exhibition of the Nobel Prize, the Nobel Foundation called it one of the ten cradles of creativity. The journal Nature likened its ideals to those of the French revolution--Liberté, Egalité, Fraternité--and called it a paradise devoted to the science of immune systems: the Basel Institute for Immunology (BII). Founded by Roche in 1968, inaugurated in 1971, and closed in 2000, it was home to almost 450 scientific members, over 1,000 scientific visitors, and nearly 100 scientific advisors from more than 30 countries who worked in complete academic freedom and without commercial motives on over 3,500 projects, publishing more than 3,200 scientific papers, almost all of them on the structure and functions of immune systems of different species. This review contains a first collection of historical facts and dates that describe the background of the exceptionally successful performance and the strong scientific impact of the institute on the field of immunology.


Exploring the mental health of Mexican migrant farm workers in the Midwest: psychosocial predictors of psychological distress and suggestions for prevention and treatment.
The purposes of the present study were threefold: (a) to assess the prevalence levels of anxiety and depression in a sample of Mexican migrant farm workers in the midwestern United States; (b) to explore the relationships among acculturative stress, anxiety, and depression; and (c) to examine the variables that best predict anxiety and depression. The overall sample revealed elevated levels of anxiety and depression. Migrant farm workers with heightened levels of acculturative stress were more likely to report high levels of anxiety and depression. Family dysfunction, ineffective social support, low self-esteem, lack of agreement with the decision to migrate, high education levels, high levels of acculturative stress, and high levels of anxiety were significantly associated with high depression levels. The overall findings suggest that migrant farm workers who experience elevated levels of acculturative stress may be at risk for experiencing high levels of anxiety and depression. The findings highlight the importance of establishing prevention and treatment services for migrant farm workers that aim to increase levels of emotional support, self-esteem, and coping skills.


Ring-Opening Polymerization of l-Lactide to Cyclic Poly(Lactide) by Zeolitic Imidazole Framework ZIF-8 Catalyst.
The catalytic activity of ZIF-8 in the ring-opening polymerization of l-lactide without solvents or cocatalysts is presented for the first time. Two different synthetic strategies have been applied for synthesizing ZIF-8, either under solvothermal condition or by spray-drying procedure. Their catalytic activities are found to be correlating with the presence of open active sites in ZIF-8 structure. The structural defects that afford active acid and basic sites are supposed to cooperatively catalyze the reaction. ZIF-8 assembled by spray-drying technique, displays a superior catalytic activity at temperature of 160 °C, leading to the formation of high molecular weight cyclic polylactide. The ZIF-8 catalysts could be recycled and reused without any significant loss of catalytic activity.


Comprehensive Profiling of Zika Virus Risk with Natural and Artificial Mitigating Strategies, United States.
Zika virus is transitioning to become a long-term public health challenge, and countries should remain informed of the risk for emergence. We developed a stochastic epidemiologic model to profile risk for Zika virus emergence, including trimester-specific fetal risk across time, in all 3,208 counties in the United States, including Puerto Rico. Validation against known transmission in North America demonstrated accuracy to predict epidemic dynamics and absolute case counts across scales (R2 = 0.98). We found that, although sporadic single transmission events could occur in most US counties, outbreaks will likely be restricted to the Gulf Coast region and to late spring through autumn. Seasonal fluctuations in birth rates will confer natural population-level protection against early-trimester infections. Overall, outbreak control will be more effective and efficient than prevention, and vaccination will be most effective at >70% coverage. Our county-level risk profiles should serve as a critical resource for resource allocation.


Effects of bronchial obstruction on lower esophageal sphincter motility and gastroesophageal reflux in patients with asthma.
The relationship between gastroesophageal reflux and asthma remains unclear. The aim of this study was to analyze the effect of bronchial obstruction on lower esophageal sphincter (LES) motility and reflux in patients with asthma. LES motility and esophageal pH were assessed in eight subjects with intermittent asthma and eight healthy volunteers during three consecutive 30-minute periods: baseline, methacholine-induced bronchospasm, and after inhalation of the beta2-agonist salbutamol. Healthy subjects inhaled 2 mg of methacholine, whereas subjects with asthma inhaled the dose of methacholine causing a 15% fall in FEV(1), as determined by a previous methacholine challenge. LES motility, esophageal pH, and FEV(1) were not significantly different between the three periods in healthy subjects. In patients with asthma, methacholine induced a 21.9 +/- 2.6% decrease in FEV(1) and a concomitant increase in the rate of transient LES relaxation (TLESR) and reflux episodes. Inhalation of salbutamol decreased the rate of TLESRs but not the number of reflux episodes. We conclude that in patients with asthma, methacholine-induced bronchospasm increases the rate of TLESR and the number of reflux episodes. These results support the belief that, in asthma, bronchial obstruction may be responsible for reflux or may aggravate reflux through a mechanism that remains to be further clarified.


Hairy cell leukemia cells are relatively NK-insensitive targets.
The hypothesis that interferon alpha (IFN alpha) has its beneficial effects in hairy cell leukemia by activating natural killer cells against hairy cells was examined. Leukemic cells from patients with hairy cell leukemia were tested for their susceptibility to lysis by fresh and IFN alpha activated peripheral blood mononuclear (PBMC) cells from normal donors. All hairy cells tested were relatively insensitive to cytolysis by PBMC and IFN alpha activated PBMC. The low levels of 51Cr release obtained with a few donors was due to lysis of leukemic cells, not residual normal cells, and was mediated by a natural killer cell (T cell receptor independent) mechanism. Chronic lymphatic leukemic cells before and after treatment with phorbol ester were also resistant to cytolysis. Hairy cells were not susceptible to lymphokine activated killer (LAK) cells but were sensitive to lysis by antibody and complement. The insensitivity to cell mediated cytolysis against hairy cells was shown by cold target inhibition to be a lack of target recognition by NK cells.


Comparison and Validation of Force Fields for Deep Eutectic Solvents in Combination with Water and Alcohol Dehydrogenase.
Deep eutectic solvents (DESs) have become popular as environmental-friendly solvents for biocatalysis. Molecular dynamics (MD) simulations offer an in-depth analysis of enzymes in DESs, but their performance depends on the force field chosen. Here, we present a comprehensive validation of three biomolecular force fields (CHARMM, Amber, and OPLS) for simulations of alcohol dehydrogenase (ADH) in DESs composed of choline chloride and glycerol/ethylene glycol with varying water contents. Different properties (e.g., protein structure and flexibility, solvation layer, and H-bonds) were used for validation. For two properties (viscosity and water activity) also experiments were performed. The viscosity was calculated with the periodic perturbation method, whereby its parameter dependency is disclosed. A modification of Amber was identified as the best-performing model for low water contents, whereas CHARMM outperforms the other models at larger water concentrations. An analysis of ADH's structure and interactions with the DESs revealed similar predictions for Amber and CHARMM.


Increasing prevalence of gastrointestinal colonization with ceftazidime-resistant gram-negative bacteria among intensive care unit patients.
The occurrence of nosocomial infections due to third-generation cephalosporin-resistant gram-negative bacteria is increasing. Gastrointestinal colonization is an important reservoir for antibiotic-resistant bacteria, and it often precedes clinical infection. To estimate the prevalence of gastrointestinal colonization with ceftazidime-resistant gram-negative bacteria among intensive care unit (ICU) patients at a university-affiliated tertiary-care hospital during 2 distinct periods and to assess whether, at any time during the index hospitalization, colonized patients had a clinical culture positive for the same organism that was recovered from surveillance culture. Two ICUs at the University of Maryland Medical Center, a 656-bed tertiary-care hospital located in Baltimore, Maryland. Both ICUs provide care to adult patients. We performed a cross-sectional study of adult patients admitted to the medical ICU or the surgical ICU from June 14 to July 14, 2003, and from June 14 to July 14, 2006. Perirectal swab samples were obtained for surveillance culture on admission to the intensive care unit, weekly thereafter, and at discharge. Each culture sample was plated onto MacConkey agar supplemented with ceftazidime. In 2003, a total of 33 (18.8%) of 176 patients were colonized with ceftazidime-resistant gram-negative bacilli; in 2006, 60 (31.4%) of 191 patients were (P<.01). This increase was largely driven by an increase in ceftazidime-resistant Klebsiella isolates (which accounted for 6.4% of isolates in 2003 and for 22.8% in 2006; P<.01). In 2003, a total of 16 (48.5%) of 33 colonized patients had a clinical culture positive for the same organism that was recovered from the perirectal surveillance culture, compared with 22 (36.6%) of 60 colonized patients in 2006 (P=.28). Our data suggest that gastrointestinal colonization with ceftazidime-resistant gram-negative bacilli is common, that its prevalence is increasing, and that colonization may result in clinical cultures positive for these bacilli.


Formulation of nanoparticles ribosome inactivating proteins from Mirabilis jalapa L. (RIP MJ) conjugated AntiEpCAM antibody using low chain chitosan-pectin and cytotoxic activity against breast cancer cell line.
Ribosome Inactivating Proteins (RIPs) isolated from Mirabilis jalapa L. (MJ protein) leaves showed high cytotoxic effect on malignant. Chitosan nanoparticles have frequently been used in protein delivery applications. The aim of this study was to develop targeted drug delivery system of RIP MJ for breast cancer therapy with chitosan nanoparticles conjugated antiEpCAM antibody. RIP MJ nanoparticles were prepared using low viscous chitosan and pectin using polyelectrolit complex method, followed by conjugation process with antiEpCAM antibody. Characterization of this formula was then carried out for its entrapment efficiency, particles size, zeta potential, morphology using transmission electron microscope (TEM) and cytotoxic assay against T47D and Vero cell line. The optimal concentration of MJ protein; low viscous chitosan; pectin for preparing AntiEpCAM conjugated of RIP MJ nanoparticles was 0.1%; 0.01%;1% (m/v) respectively and showed satisfactory formula with the average particle size of 376.8±105.2nm, polydispersity index (PI) 0.401, zeta potential 43,71 mV, high entrapment efficiency 98,97±0,12%. Transmission electron microscope (TEM) imaging showed a spherical and homogenous structure for nanoparticles. The in vitro cytotoxicity analysis showed that RIP MJ nanoparticle had more cytotoxic effect compared to unformulated RIP against T47D cell-lines. AntiEpCAM conjugated RIP MJ nanoparticles however, increased cytotoxic effect of RIPs on Vero cell-lines not for T47D cell-lines. Chitosan-Pectin nanoparticles suitable for delivering protein to target cancer cells.


Can recent chronic pain techniques help with acute perioperative pain?
This article discussed how the knowledge and technique of a few chronic pain procedures benefited the perioperative clinicians in their care of patients receiving specific orthopaedic surgical procedures. Recent emerging interest in hip and knee denervation for chronic pain management secondary to osteoarthritis stimulates publications on the new understanding of hip and knee joint innervation. The improved understanding of the anatomy allows better precision in targeting the articular branches. The procedures for chronic joint pain such as radiofrequency ablation, chemical neurolysis and neuromodulation procedure have recently been applied to the perioperative care in orthopaedic procedures because of the potential long-lasting analgesia, opioid-sparing effect and consequent improvement in physical function and health-related quality of life after surgery. Despite the widespread use of regional anaesthesia and multimodal analgesia in the perioperative pain management, more than two-third of the patients reported severe postoperative pain. Therefore, other therapeutic strategies used in chronic pain management such as radiofrequency ablation and neuromodulation have been proposed to optimize acute postsurgical pain. The early experience with those techniques is encouraging, and more studies are required to explore the incorporation of these procedures in the perioperative care.


Flexible loop of beta 2-glycoprotein I domain V specifically interacts with hydrophobic ligands.
Beta2-glycoprotein I (beta2-GPI), which consists of four complement control protein modules and a distinctly folded fifth C-terminal domain, is an essential cofactor for the binding to phospholipids of anti-cardiolipin antibodies, isolated from patients with anti-phospholipid antibody syndrome, and its fifth domain has attracted attention as a specific phospholipid-binding site. We focused on the fifth domain of beta2-GPI (Domain V) and examined the interaction of intact Domain V, Domains IV-V, and nicked Domain V with various hydrophobic ligands, as a model molecule of phospholipid. We found that electrostatic and hydrophobic interactions are important for Domain V binding to the ligand molecules. We also found that, while Domain IV has no significant effect on the interactions with ligands, the nicked Domain V with cleavage in the flexible loop decreases the affinity, indicating that the flexible loop region is the binding site of the hydrophobic ligands. The synthetic peptide corresponding to the loop region was disordered and interacted with bis-ANS, confirming the critical role of the loop region. To clarify the nature of the interaction between the loop region and hydrophobic compounds, we prepared the reduced and alkylated Domain V, which was denatured but was assumed to be a collapsed state. Alkylation by iodoacetic acid decreased the interaction of Domain V with bis-ANS, probably because the protein net charge was decreased by the six introduced carboxyl groups and consequently the electrostatic interactions were decreased. In contrast, Domain V alkylated by iodoacetamide, therefore retaining a high positive net charge, bound bis-ANS more strongly than the intact Domain V. These results suggested that the interaction of Domain V with hydrophobic compounds through the flexible loop is similar to the binding of hydrophobic compounds to the protein folding intermediate.


The nature and regulation of the receptors for insulin-like growth factors.
Two subtypes of IGF receptors have been identified. Type I IGF receptors have a Mr greater than 300,000 and are composed of disulfide-linked 130,000-dalton (alpha) and approximately 90,000-dalton (beta) subunits. The alpha subunit binds hormone; the beta subunit appears to have intrinsic tyrosine kinase activity and to be autophosphorylated. Type I receptors preferentially bind IGF-I but also bind IGF-II and, more weakly, insulin. Type II IGF receptors consist of a 250,000-dalton protein that contains internal disulfide bonds but is not linked to other membrane components. Type II receptors bind IGF-II with higher affinity than IGF-I. They do not interact with even very high concentrations of insulin. Type I IGF receptors and insulin receptors are homologous structures. They have similar subunit structure. Both receptors bind IGFs and insulin. They have similar (but not identical) antigenic determinants. Both receptors are downregulated by IGFs and insulin. Both receptors are affected in certain patients with genetically determined insulin resistance. Type II IGF receptors do not appear to be homologous to type I receptors. They differ in structure, peptide binding specificity, and antigenic determinants. Type II receptors do not appear to be downregulated. Although type II receptors appear to be phosphorylated in intact cells, they do not possess intrinsic tyrosine protein-kinase activity. Insulin acutely upregulates type II IGF receptors in intact rat adipose cells by effecting a redistribution of receptors cycling between a large intracellular pool and the plasma membrane. Insulin and the IGFs elicit the same biological responses, either by cross-reacting with one of the receptors for the heterologous ligand or by concurrent activation of convergent effector pathways by binding to the homologous receptor. Which mechanism is utilized appears to depend more on the tissue than on the biological response. Insulin desensitizes rat hepatoma cells to the actions of insulin and IGFs, mediated by both insulin and IGF receptors, by mechanisms distal to hormone binding and possibly common to IGF and insulin effector pathways.


Lime burns resulting in total conjunctival defect, enucleation, and fused eyelids.
A rare case of right eye lime burns resulting in total conjunctival defect, enucleation, and fused eyelids is reported. This article describes total conjunctival sac reconstruction using a split-thickness skin graft combined with a spherical orbital implant, which may be a good choice for treating such a disorder.


Adrenal crises in children treated with high-dose inhaled corticosteroids for asthma.
Three children presented with adrenal crises, manifested by vomiting and hypoglycaemia, after protracted courses of high-dose inhaled corticosteroids for asthma. Significant dose reduction was possible in all three without loss of asthma control, emphasising the importance of back-titration to minimise dose. Parents of children taking high doses of inhaled corticosteroids should be alerted to the clinical features of adrenal insufficiency. If suspected, prompt medical assessment should be arranged, including serum glucose and cortisol measurement.


Identification and evaluation of quercetin as a potential inhibitor of naphthoate synthase from Enterococcus faecalis.
Enterococcus faecalis is a gram-positive, rod-shape bacteria responsible for around 65% to 80% of all enterococcal nosocomial infections. It is multidrug resistant (MDR) bacterium resistant to most of the first-line antibiotics. Due to the emergence of MDR strains, there is an urgent need to find novel targets to develop new antibacterial drugs against E. faecalis. In this regard, we have identified naphthoate synthase (1,4-dihydroxy-2-naphthoyl-CoA synthase, EC: 220.127.116.11; DHNS) as an anti-E. faecalis target, as it is an essential enzyme for menaquinone (vitamin K2 ) synthetic pathway in the bacterium. Thus, inhibiting naphtholate synthase may consequently inhibit the bacteria's growth. In this regard, we report here cloning, expression, purification, and preliminary structural studies of naphthoate synthase along with in silico modeling, molecular dynamic simulation of the model and docking studies of naphthoate synthase with quercetin, a plant alkaloid. Biochemical studies have indicated quercetin, a plant flavonoid as the potential lead compound to inhibit catalytic activity of EfDHNS. Quercetin binding has also been validated by spectrofluorimetric studies in order to confirm the bindings of the ligand compound with EfDHNS at ultralow concentrations. Reported studies may provide a base for structure-based drug development of antimicrobial compounds against E. faecalis.


Dental caries and tooth loss in adults in the United States, 2011-2012.
Among adults aged 20-64, 91% had dental caries and 27% had untreated tooth decay. Untreated tooth decay was higher for Hispanic (36%) and non-Hispanic black (42%) adults compared with non-Hispanic white (22%) and non-Hispanic Asian (17%) adults aged 20-64. Adults aged 20-39 were twice as likely to have all their teeth (67%) compared with those aged 40-64 (34%). About one in five adults aged 65 and over had untreated tooth decay. Among adults aged 65 and over, complete tooth loss was lower for older Hispanic (15%) and non-Hispanic white (17%) adults compared with older non-Hispanic black adults (29%).


Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells.
Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer's disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD.


E-Cadherin/HMR-1 Membrane Enrichment Is Polarized by WAVE-Dependent Branched Actin.
Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical-basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.


Schedule for rating disabilities: disabilities of the liver. Final rule.
This document amends the Department of Veterans Affairs (VA) Schedule for Rating Disabilities (38 CFR part 4) by revising the portion of the Digestive System that addresses disabilities of the liver. The intended effect of this action is to update this portion of the rating schedule to ensure that it uses current medical terminology and unambiguous criteria, and that it reflects medical advances that have occurred since the last review.


Drug-induced glomerulopathies.
Normal renal function depends upon an intact glomerular apparatus. Many drugs and chemicals are capable of damaging the glomerulus, causing its increased permeability to large molecules. Glomerular lesions are usually responsible for proteinuria and the nephrotic syndrome. This also holds true for the drug-induced glomerulopathies, of which membranous glomerulo-nephritis is the most frequent type of lesion encountered. Apart from this, several cases of different glomerular changes such as focal segmental glomerulosclerosis and crescentic glomerulonephritis have also been reported. The drug-induced glomerulopathies are probably immune mediated. This is, for instance, reflected in the fact that patients with drug-induced nephritic syndrome frequently have the HLA-B8 and DR3 antigens. In depth information is provided for the previously mentioned disorders.


2'‑Hydroxyflavanone inhibits epithelial‑mesenchymal transition, and cell migration and invasion via suppression of the Wnt/β‑catenin signaling pathway in prostate cancer.
Despite the availability of a number of treatment options, certain cases of primary prostate cancer (PCa) will develop into metastatic PCa, in which epithelial‑mesenchymal transition (EMT) serves an important role. Recently, a natural flavonoid known as 2'‑hydroxyflavanone (2HF) exerts remarkable anticancer activity on various types of cancer. Our previous study demonstrated that 2HF could promote apoptosis and inhibit the proliferation of PCa cells, but whether 2HF is involved in the regulation of EMT, and cell migration and invasion in metastatic PCa remains unknown. The present study used two different metastatic PCa cell lines (PC‑3 and DU145) to investigate the effects of 2HF on EMT, and cell migration and invasion. The results demonstrated that 2HF could inhibit EMT, and cell migration and invasion through the Wnt/β‑catenin signaling pathway by suppressing GSK‑3β phosphorylation, β‑catenin expression and transactivation. In conclusion, the present study revealed a novel function of 2HF, which may be used to prevent or treat PCa metastasis.


Structure and Antibacterial Activity of Chitosan from the American Cockroach, the German Cockroach and the Mealworm Beetle.
Owing to chitosan properties such as biocompatibility and antimicrobial activities, and several applications in biomedical field, some physicochemical and anti-bacterial properties, and the level of chitosan from three species of American cockroach, Periplaneta americana (Dictyoptera: Blattidae), the German cockroach, Blattella germanica (Dictyoptera: Ectobiidae) and the Mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae) were investigated. The cuticle of adults derived from specimens was dried and grounded. The powders were demineralized as well as deproteinized after deacetylation via NaOH. At last, the chitosan yields from insects were studied for antibacterial activity on Gram-positive bacteria (Proteus mirabilis, Klebsiella pneumoniae), and Gram-negative bacteria (Enterococcus faecalis and Staphylococcus epidermidis). The Fourier transform infrared spectroscopy (FTIR) was used to analyze the chitosan composition. The chitosan ratios of the American and German cockroaches and the mealworm beetle were 5.80, 2.95, and 1.70% per 3 g of the dried bodies respectively. The chitin DD's for the American cockroach, the German cockroach and the mealworm beetle were 36.8%, 31.5% and 27.3%, respectively. The bactericidal activity of chitosan obtained from the American cockroach at a concentration of 1% had the greatest effect on P. mirabilis compared to other concentrations, while chitosan obtained from the German cockroach at a concentration of 0.01% had the greatest effect on K. pneumoniae compared to other concentrations. According to the results, the anti-bacterial influence of the chitosan is based upon the insect species and chitosan concentration. Probably, the variation relates to the changes in the chitin structure among the three insect species.


Overexpression of CDCA8 promotes the malignant progression of cutaneous melanoma and leads to poor prognosis.
Cutaneous melanoma is very aggressive and results in high mortality rates for cancer patients. Determining molecular targets is important for developing novel therapies for cutaneous melanoma. Cell division cycle associated 8 (CDCA8) is a putative oncogene that is upregulated in multiple types of cancer. The present study aimed to examine the role of CDCA8 in cutaneous melanoma, with a focus on the association of its expression to prognosis and metastasis. First, the mRNA expression of CDCA8 in cutaneous melanoma tissues was investigated using the ONCOMINE and Gene Expression Omnibus (GEO) databases. Furthermore, the relationship between the expression of CDCA8 and cutaneous melanoma patient survival was analyzed using a Kaplan‑Meier plot and Log Rank test. In addition, the effects of CDCA8 on proliferation, migration and invasion of cutaneous melanoma cell lines were investigated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), Cell Counting kit‑8, colony formation assay, wound healing and Matrigel assay. Finally, the expression levels of key proteins related to the Rho‑associated coiled‑coil‑containing protein kinase (ROCK) signaling pathway were measured by western blot assay. The results demonstrated that CDCA8 was overexpressed in cutaneous melanoma tissues and cells lines compared with normal tissues, and high expression of CDCA8 was significantly associated with poorer prognosis in patients with cutaneous melanoma. In in vitro experiments, CDCA8 knockdown inhibited A375 and MV3 cell proliferation, migration and invasion. In addition, CDCA8 knockdown reduced the phosphorylation levels of ROCK1 and myosin light chain, two downstream effector proteins of the ROCK pathway. In summary, the present findings suggested that CDCA8 may be a promising therapeutic target for the treatment of cutaneous melanoma.


Optoelectronic Artificial Synaptic Device Based on Amorphous InAlZnO Films for Learning Simulations.
Neuromorphic computing, which mimics brain function, can address the shortcomings of the "von Neumann" system and is one of the critical components of next-generation computing. The use of light to stimulate artificial synapses has the advantages of low power consumption, low latency, and high stability. We demonstrate amorphous InAlZnO-based light-stimulated artificial synaptic devices with a thin-film transistor structure. The devices exhibit fundamental synaptic properties, including excitatory postsynaptic current, paired-pulse facilitation (PPF), and short-term plasticity to long-term plasticity conversion under light stimulation. The PPF index stimulated by 375 nm light is 155.9% when the time interval is 0.1 s. The energy consumption of each synaptic event is 2.3 pJ, much lower than that of ordinary MOS devices and other optical-controlled synaptic devices. The relaxation time constant reaches 277 s after only 10 light spikes, which shows the great synaptic plasticity of the device. In addition, we simulated the learning-forgetting-relearning-forgetting behavior and learning efficiency of human beings under different moods by changing the gate voltage. This work is expected to promote the development of high-performance optoelectronic synaptic devices for neuromorphic computing.


Assessment of the antiviral properties of recombinant surfactant protein D against influenza B virus in vitro.
The armamentarium of antiviral drugs against influenza viruses is limited. Furthermore, influenza viruses emerge that are resistant to existing antiviral drugs like the M2 and NA inhibitors. Therefore, there is an urgent need for the development of novel classes of antiviral drugs. Here we investigated the antiviral properties of recombinant porcine surfactant protein D (RpSP-D), an innate defense molecule with lectin properties, against influenza B viruses. We have previously shown that porcine SP-D has more potent neutralizing activity against influenza A viruses than human SP-D. Here we show that RpSP-D neutralizes influenza B viruses efficiently and inhibited the binding of these viruses to epithelial cells of the human trachea.


Operative treatment of displaced intra-articular fractures of Calcaneum: Is it worthwhile?
To compare the results of operative treatment for displaced intra-articular fractures of calcaneum with conservative treatment. The retrospective non-randomised comparative study using. purposive non-probability convenient sampling was conducted at the Combined Military Hospital, Rawalpindi, and comprised treatment records from March 2010 to October 2013 of patients who had been treated either by Plaster of Paris casting (Group A) or managed by open reduction internal fixation (Group B). Functional outcome was assessed using Foot and Ankle Disability Index. Of the 42 records in the study, 20(47.6%) related to Group A and 22(52.4%) to Group B. The mean age was 41±7.82 years (range: 28-55 years) in Group A, and 31±6.35 years (range: 21-43) in Group B. Male-to-female ratio was 10:1 in Group A; 9:1 in Group B. Union was achieved in all (100%) cases. Bone substitute was used in 16(72.7%) in Group B to fill void during reconstruction of collapsed calcaneum. Wound complications were noted in 2(9.1%) Group B patients. There was loss of reduction in 1(4.5%). Mean Foot and Ankle Disability Index score in Group A was 45±10.68.4 compared to 67.9±10.04 in Group B (p=1.99). For displaced intra-articular fractures, operative treatment is associated with better functional outcome in terms of absolute functional scores and should be the treatment of choice although factors such as age, soft tissue injury and surgical expertise may influence the decision.


Development of a qPCR assay for specific quantification of Botrytis cinerea on grapes.
The aim of this study was to develop a system for rapid and accurate real-time quantitative PCR (qPCR) identification and quantification of Botrytis cinerea, one of the major pathogens present on grapes. The intergenic spacer (IGS) region of the nuclear ribosomal DNA was used to specifically detect and quantify B. cinerea. A standard curve was established to quantify this fungus. The qPCR reaction was based on the simultaneous detection of a specific IGS sequence and also contained an internal amplification control to compensate for variations in DNA extraction and the various compounds from grapes that inhibit PCR. In these conditions, the assay had high efficiency (97%), and the limit of detection was estimated to be 6.3 pg DNA (corresponding to 540 spores). Our method was applied to assess the effects of various treatment strategies against Botrytis in the vineyard. Our qPCR assay proved to be rapid, selective and sensitive and may be used to monitor Botrytis infection in vineyards.


The Mitochondrial Lon Protease: Novel Functions off the Beaten Track?
To maintain organellar function, mitochondria contain an elaborate endogenous protein quality control system. As one of the two soluble energy-dependent proteolytic enzymes in the matrix compartment, the protease Lon is a major component of this system, responsible for the degradation of misfolded proteins, in particular under oxidative stress conditions. Lon defects have been shown to negatively affect energy production by oxidative phosphorylation but also mitochondrial gene expression. In this review, recent studies on the role of Lon in mammalian cells, in particular on its protective action under diverse stress conditions and its relationship to important human diseases are summarized and commented.


Thyroxine-binding globulin, triiodothyronine, thyroxine and thyrotropin in newborn infants and children.
Thyroxine-binding globulin (TBG), triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) have been determined by radioimmunoassay in plasma of newborn infants and throughout childhood until puberty. Mean maternal TBG concentration was 1.65 +/- 0.09 mg/100 ml (SEM) and significantly higher (p less than 0.01) than cord blood levels of TBG (1.16 +/- 0.08 mg/100 ml (SEM). Throughout infancy and childhood TBG remained significantly elevated (p less than 0.01) compared to a middle age control group of healthy blood donors. T3, T4 and TSH concentrations behaved postnatally as known from previous studies. The T3 and T4 increase observed immediately after birth was not a secondary phenomenon due to changes in TBG concentration since this globulin did not change significantly during this period.


Changes in the activity of some metabolic enzymes in the heart of SHR rat incurred by transgenic expression of CD36.
Hypertension, dyslipidemia, and insulin resistance in the spontaneously hypertensive rat (SHR) can be alleviated by rescuing CD36 fatty acid translocase. The present study investigated whether transgenic rescue of CD36 in SHR could affect mitochondrial function and activity of selected metabolic enzymes in the heart. These analyses were conducted on ventricular preparations derived from SHR and from transgenic strain SHR-Cd36 that expresses a functional wild-type CD36. Our respirometric measurements revealed that mitochondria isolated from the left ventricles exhibited two times higher respiratory activity than those isolated from the right ventricles. Whereas, we did not observe any significant changes in functioning of the mitochondrial respiratory system between both rat strains, enzyme activities of total hexokinase, and both mitochondrial and total malate dehydrogenase were markedly decreased in the left ventricles of transgenic rats, compared to SHR. We also detected downregulated expression of the succinate dehydrogenase subunit SdhB (complex II) and 70 kDa peroxisomal membrane protein in the left ventricles of SHR-Cd36. These data indicate that CD36 may affect in a unique fashion metabolic substrate flexibility of the left and right ventricles.


Double-barreled gun: Combination of PARP inhibitor with conventional chemotherapy.
DNA repair pathways are evolutionarily conserved molecular mechanisms that maintain the integrity of genomic DNA. In cancer therapies, the integrity and activity of DNA repair pathways predict therapy resistance and disease outcome. Members of the poly (ADP-ribose) polymerase (PARP) family initiate and organize the biologic process of DNA repair, which counteracts many types of chemotherapies. Since the first development in approximately 3 decades ago, PARP inhibitors have greatly changed the concept of cancer therapy, leading to encouraging improvements in tumor suppression and disease outcomes. Here we summaries both pre-clinical and clinical findings of PARP inhibitors applications, particularly for combination therapies.


Progress in Biosensors for the Point-of-Care Diagnosis of COVID-19.
Coronavirus disease 2019 (COVID-19) is a highly virulent infection that has caused a pandemic since 2019. Early diagnosis of the disease has been recognized as one of the important approaches to minimize the pathological impact and spread of infection. Point-of-care tests proved to be substantial analytical tools, and especially lateral flow immunoassays (lateral flow tests) serve the purpose. In the last few years, biosensors have gained popularity. These are simple but highly sensitive and accurate analytical devices composed from a selective molecule such as an antibody or antigen and a sensor platform. Biosensors would be an advanced alternative to current point-of-care tests for COVID-19 diagnosis and standard laboratory methods as well. Recent discoveries related to point-of-care diagnostic tests for COVID-19, the development of biosensors for specific antibodies and specific virus parts or their genetic information are reviewed.


The emerging role for CAR T cells in solid tumor oncology.
In recent years, treatment with chimeric antigen receptor (CAR) T-cells has revolutionized the outcomes of patients with relapsed or refractory hematological malignancies with long-term remissions in >30% of patients. Similarly, the introduction of immune checkpoint inhibitor therapy changed the therapeutic landscape for several solid malignancies also leading to impressive long-term remission in patients. However, so far CAR T-cell therapy in solid tumors has shown low response rates and especially a lack of long-term remissions. This review focuses on the latest clinical advances and discusses promising results seen with CAR T-cells exploring new target antigens. We then review relevant challenges limiting long-term responses with CAR T-cell therapy in solid tumors like CAR T-cell persistence and target antigen expression. In addition, there is an increasing understanding on T-cell function and dysfunction within the immunosuppressive tumor microenvironment. This comprises of inhibitory cytokines and checkpoint molecules limiting the killing capacity of CAR T-cells. Finally, we will discuss how this deeper knowledge can be used to develop CAR T-cell therapies overcoming these inhibitory factors and results in CAR T-cell products with higher efficacy and safety. These technological developments will hopefully lead to enhanced clinical activity and improved solid tumor patient outcomes in the near future.


Influential factors of long-term care in a Japanese rural community examined through interviews of family caregivers.
Recent increases in the number of those with health care needs who live at home in Japan highlight the importance of maintaining a healthy community environment for long-term care. This study characterized continuing long-term home-based care for patients with health care needs in a rural community through an examination of influential factors, as perceived by family caregivers of patients with care needs. Semistructured interviews revealed self-reliance as the most important factor. Promoting the quality of a family caregiver's life was also found to be important. Family caregiver support is required considering the character of a rural community and residents' ideologies.


High-Resolution Atomic Absorption Spectrometry Combined With Machine Learning Data Processing for Isotope Amount Ratio Analysis of Lithium.
An alternative method for lithium isotope amount ratio analysis based on a combination of high-resolution atomic absorption spectrometry and spectral data analysis by machine learning (ML) is proposed herein. It is based on the well-known isotope shift of approximately 15 pm for the electronic transition 22P←22S at around the wavelength of 670.8 nm, which can be measured by the state-of-the-art high-resolution continuum source graphite furnace atomic absorption spectrometry. For isotope amount ratio analysis, a scalable tree boosting ML algorithm (XGBoost) was employed and calibrated using a set of samples with 6Li isotope amount fractions, ranging from 0.06 to 0.99 mol mol-1, previously determined by a multicollector inductively coupled plasma mass spectrometer (MC-ICP-MS). The calibration ML model was validated with two certified reference materials (LSVEC and IRMM-016). The procedure was applied toward the isotope amount ratio determination of a set of stock chemicals (Li2CO3, LiNO3, LiCl, and LiOH) and a BAM candidate reference material NMC111 (LiNi1/3Mn1/3Co1/3O2), a Li-battery cathode material. The results of these determinations were compared with those obtained by MC-ICP-MS and found to be metrologically comparable and compatible. The residual bias was -1.8‰, and the precision obtained ranged from 1.9 to 6.2‰. This precision was sufficient to resolve naturally occurring variations, as demonstrated for samples ranging from approximately -3 to +15‰. To assess its suitability to technical applications, the NMC111 cathode candidate reference material was analyzed using high-resolution continuum source atomic absorption spectrometry with and without matrix purification. The results obtained were metrologically compatible with each other.


Photochromism of diarylethene single molecules in polymer matrices.
Robust fluorescent photoswitching molecules, having perylene bisimide as the fluorescent unit and diarylethene as the switching unit, were prepared, and their photochromic reactions were measured at the single-molecule level in various polymer matrices. The histograms of the fluorescent on and off times were found to deviate from normal exponential distribution and showed a peak when the molecules are embedded in rigid polymer matrices, such as Zeonex or poly(methyl methacrylate) (PMMA). In soft polymer matrices, such as poly(n-buthyl methacrylate) (PnBMA), exponential distribution was observed for the on and off times. The abnormal distribution suggests that the quantum yields of the photoreactions are not constant and the molecules undergo the reactions after absorbing a certain number of photons. A multilocal minima model was proposed to explain the environmental effect.


Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes.
Hepatitis B virus (HBV) infection and alcoholism are major public health problems worldwide, contributing to the development of end-stage liver disease. Alcohol intake affects HBV infection pathogenesis and treatment outcomes. HBV-specific cytotoxic T lymphocytes (CTLs) play an important role in HBV clearance. Many previous studies have focused on alcohol-induced impairments of the immune response. However, it is not clear whether alcohol alters the presentation of HBV peptide-major histocompatibility complex (MHC) class I complexes on infected hepatocytes resulting in escape of its recognition by CTLs. Hence, the focus of this study was to investigate the mechanisms by which ethanol metabolism affects the presentation of CTL epitope on HBV-infected hepatocytes. As demonstrated here, although continuous cell exposure to acetaldehyde-generating system (AGS) increased HBV load in HepG2.2.15 cells, it decreased the expression of HBV core peptide 18-27-human leukocyte antigen-A2complex (CTL epitope) on the cell surface. Moreover, we observed AGS-induced suppression of chymotrypsin- and trypsin-like proteasome activities necessary for peptide processing by proteasome as well as a decline in IFNγ-stimulated immunoproteasome (IPR) function and expression of PA28 activator and immunoproteasome subunits LMP7 and LMP2. Furthermore, IFNγ-induced activation of peptide-loading complex (PLC) components, such as transporter associated with antigen processing (TAP1) and tapasin, were suppressed by AGS. The attenuation of IPR and PLC activation was attributed to AGS-triggered impairment of IFNγ signaling in HepG2.2.15 cells. Collectively, all these downstream events reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, which may suppress CTL activation and the recognition of CTL epitopes on HBV-expressing hepatocytes by immune cells, thereby leading to persistence of liver inflammation.NEW & NOTEWORTHY Our study shows that in HBV-expressing HepG2.2.15 cells, acetaldehyde alters HBV peptide processing by suppressing chymotrypsin- and trypsin-like proteasome activities and decreases IFNγ-stimulated immunoproteasome function and expression of PA28 activator and immunoproteasome subunits. It also suppresses IFNγ-induced activation of peptide-loading complex (PLC) components due to impairment of IFNγ signaling via the JAK-STAT1 pathway. These acetaldehyde-induced dysfunctions reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, thereby leading to persistence of HBV infection.


An EIT image reconstruction method based on DenseNet with multi-scale convolution.
Electrical impedance tomography (EIT) is an imaging technique that non-invasively acquires the electrical conductivity distribution within a field. The ill-posed and nonlinear nature of the image reconstruction process results in lower quality of the obtained images. To solve this problem, an EIT image reconstruction method based on DenseNet with multi-scale convolution named MS-DenseNet is proposed. In the proposed method, three different multi-scale convolutional dense blocks are incorporated to replace the conventional dense blocks; they are placed in parallel to improve the generalization ability of the network. The connection layer between dense blocks adopts a hybrid pooling structure, which reduces the loss of information in the traditional pooling process. A learning rate setting achieves reduction in two stages and optimizes the fitting ability of the network. The input of the constructed network is the boundary voltage data, and the output is the conductivity distribution of the imaging area. The network was trained and tested on a simulated dataset, and it was further tested using actual measurement data. The images reconstructed via this method were evaluated by employing root mean square error, structural similarity index measure, mean absolute error and image correlation coefficient in comparison with conventional DenseNet and Gauss-Newton. The results show that the method improves the artifact and edge blur problems, achieves higher values on the image metrics and improves the EIT image quality.


A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy.
The low efficiency of photodynamic therapy (PDT) is caused by tumor hypoxia and the adaptive immune resistance/evasion of tumor cells, while the currently emerging immune checkpoint therapy restores the intrinsic immune capacities but can't directly attack the tumor cells. Methods: Herein we report an integrated nanoplatform that combines PDT with immunotherapy to enhance photodynamic therapeutic effects and simultaneously inhibit tumor cells resistance/evasion. To achieve this, we fabricated Mn@CaCO3/ICG nanoparticles and loaded them with PD-L1-targeting siRNA. Results: Thanks to the protection of CaCO3 on the loaded ICG and the oxygen produced by MnO2, an enhanced photodynamic therapeutic effect in vitro was observed. In vivo experiments demonstrated that the nanoplatform could efficiently deliver the loaded drug to the tumor tissues and significantly improve tumor hypoxia, which further contributes to the therapeutic effect of PDT in vivo. Moreover, the synergistic benefits derived from the siRNA, which silenced the checkpoint gene PD-L1 that mediates the immune resistance/evasion, resulted in a surprising therapeutic effect to rouse the immune system. Conclusions: The combination treatment strategy has great potential to be developed as a new and robust method for enhanced PDT therapy with high efficiency and a powerful antitumor immune response based on PD-L1 blockade.


[How successful is inpatient treatment in child and adolescent psychiatry? Preliminary results of the Marburg Evaluation Project].
From 1999 to 2006, the inpatient treatment of a complete clinical sample in a child and adolescent psychiatric hospital was evaluated in a naturalistic effectiveness study in order to obtain detailed information about the outcome of the therapies. The project was realized as a longitudinal 1-sample design with measurements at three points in time (admission assessment; discharge assessment and 6-week follow-up; 1 1/2 year follow-up). An essential part of the assessments was conducted using standardized telephone interviews with the parents of the inpatients. The project included 1,321 inpatients; the 1 1/2 year follow-up was accomplished for 776 cases. In all repeated measurements, there were highly significant effects. The pre-post effect sizes were higher than 1. The effects which were achieved during inpatient treatment were stable over time with a slight improvement after treatment. The outcome of different diagnostic groups showed significant differences at the 1 1/2 year follow-up. The results should be used in the counselling of patients and their parents prior to starting therapy. It should be investigated whether the favourable results can be generalized for inpatient treatments in other hospitals of child psychiatry.


The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.
Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. https://clinicaltrials.gov/ct2/show/NCT00588731.


[Vascular risk factors and Alzheimer disease risk: epidemiological studies review].
Etiology of Alzheimer's disease (AD) is still undefined in its most frequent sporadic type, but a role of vascular risk factor is more and more evocated in its pathophysiology. This role enables to hope that preventive or curative care of vascular risk factors could decrease AD incidence. Among these factors, high blood pressure, diabetes, hypercholesterolemia and tobacco consumption were the most studied. We review the risk for AD, which had been associated with each of these factors in epidemiological studies. High blood pressure is associated with an increased risk of AD in most studies while the results are more controversial for the others factors. All these four vascular risk factors have variable interaction with the presence of cerebrovascular diseases and of the epsilon 4 allele of the apolipoprotein E gene which is a predisposition factor for sporadic AD.


Proton-Activated Chloride Channel: Physiology and Disease.
The maintenance of intracellular and extracellular pH relies on multiple ion transporters/channels. Proton-activated chloride channel (PAC) precisely regulates extracellular and early/late endosomal pH by transporting chloride ion (Cl-) across membranes and has been shown to be implicated in pH imbalance under hypoxic conditions, such as the acidic microenvironments of cancer and ischemia. In this article, the phenotypic characteristics, molecular mechanisms, physiology of PAC and its role in cancer, ischemic stroke and hypoxia will be discussed in order to provide some clues for developing potential therapeutic strategies.


Comparability issues of survival data.
This study examines the level of homogeneity in cancer registration and follow up techniques adopted by each registry, in order to ensure a correct evaluation of the data and of the geographical differences observed within Italy. A quality check was performed on the registration techniques, assuring that they met the international standards and yielded correct data, and on follow up methods. Difficulties concerning the assessment of certain tumours emerged from international debates. Thus, registries were requested to fill in a questionnaire to thoroughly examine differences in the management of tumour cases with difficult biological and clinical assessment (e.g. in situ and urinary bladder tumours). Some discrepancies in registration methods were observed. The most significant problems concern urinary bladder tumours, especially in coding procedures of in situ and uncertain behaviour tumours and the proportion of short-term survivors proportions for some geographical areas. Good quality and comparability indices were generally observed (microscopic verification, follow up management). In conclusions, quality standards in cancer registration appear good and allow for a correct geographical comparability. Some important problems regard only a small number of cancer sites (namely urinary bladder), whose results should be examined with caution.


ADHD Symptoms in Pathological and Problem Gamblers in Singapore.
Background: There is relatively little research examining the relationship between Attention-Deficit/Hyperactivity Disorder (ADHD) and gambling addiction. This study seeks to explore for ADHD symptoms in adult gambling addiction patients and to evaluate their gambling-related cognitions. Materials and Methods: A cross-sectional survey was conducted at National Addictions Management Service, Institute of Mental Health, in Singapore. Patients presenting for gambling treatment were screened for ADHD symptoms and assessed for severity of gambling-related cognitions. The primary objective was to observe the rate of patients screening positive for ADHD. Results: 20% of the sample screened positive for ADHD. These individuals also had lower levels of gambling-related cognitions. No significant correlation was noted between ADHD symptoms and gambling-related cognition scores. Conclusions: Positive screening results for ADHD occurred frequently in our sample of Pathological Gambling (PG) and Problem Gambling patients and these affected individuals also exhibited lower levels of gambling-related cognitions. This finding may suggest that the gambling behavior in patients with ADHD-PG comorbidity is driven by impulsivity rather than gambling-related cognitions, which has implication on treatment considerations. Further research with a larger sample size is indicated.


The effect of ionic strength on the electron-transfer rate of surface immobilized cytochrome C.
Horse heart cytochrome c was immobilized on four different self-assembled monolayer (SAM) films. The electron tunneling kinetics were studied in the different assemblies as a function of the ionic strength of the buffer solution using cyclic voltammetry. When cytochrome c is electrostatically immobilized, the standard electron exchange rate constant k0 decreases with the increase of the solution's ionic strength. In contrast, the protein covalently attached or ligated has a rate constant independent of the ionic strength. The inhomogeneity of electrostatically immobilized cytochrome c increases with the increase of the solution's ionic strength whereas that of the covalently attached protein is independent of the ionic strength. A comparison of these different electron-transfer behaviors suggests that the thermodynamically stable geometry of cytochrome c in the electrostatic assemblies is also an electron transfer favorable one. It suggests that the surface charges of cytochrome c are capable of guiding it into geometries in which its front surface faces the electron-transfer partner. The inhomogeneity observed in this study indicates that a distribution of cytochrome c orientations and thus a distribution of electron transfer rate constants exists.


A novel diagnostic tool for detecting oesophageal pathology: the PillCam oesophageal video capsule.
Gastro-oesophageal reflux disease is a common entity. Erosive oesophagitis, ulcers and Barrett's oesophagus, which is found in up to 10% of gastro-oesophageal reflux disease patients, characterize severe gastro-oesophageal reflux disease. Patients with Barrett's oesophagus have 0.5% per patient-year risk of developing oesophageal adenocarcinoma. Currently, it appears that a minority of those at risk for Barrett's oesophagus undergo screening in part because of the costs associated with endoscopy as well as risks of sedation. A new ingestible PillCam oesophageal capsule developed may offer an alternative office-based approach to visualize the oesophagus without sedation. To compare the oesophageal capsule to conventional upper endoscopy for detection of oesophageal pathologies. A newly developed capsule, which acquires video images from both ends of the device at a 4 frame/s rate, was ingested by 17 fasting patients with suspected oesophageal disorders. An ingestion procedure aimed to lengthen capsule transit time in the oesophagus was utilized. Subsequently, a standard upper endoscopy was carried out. The investigator interpreting the capsule findings was blinded to the endoscopy results and vice versa. Patients with dysphagia, known Zenker's diverticulum, intestinal obstruction, cardiac pacemaker or pregnancy were excluded. Twelve of the 17 patients examined had oesophageal findings using the endoscope as the gold standard. Capsule endoscopy identified oesophageal pathology in all 12 of these patients and an additional pathology in one patient that was missed during endoscopy. For the purpose of this study, this finding was regarded as a false-positive. The mean oesophageal passage time was 189 +/- 280 s. The positive predictive value of the oesophageal capsule for any oesophageal pathology was 92% and the negative predictive value was 100%. Oesophageal capsule sensitivity was 100% and specificity 80%. There were neither swallowing difficulties nor complications subsequent to ingestion in any subjects. Seventy-three percentage of patients preferred the oesophageal capsule procedure on conventional endoscopy. Only one patient preferred oesophagogastroduodenoscopy. This pilot study has shown that oesophageal capsule endoscopy is an accurate, convenient, safe and well-tolerated method to screen patients for significant oesophageal disorders. No sedation is required, which may allow simple, office-based screening and assessment. Further, large-scale studies are necessary to more fully assess this novel diagnostic tool.


A new Paramyxovirus isolated from cynomolgus monkeys.
A new virus was isolated from cynomolgus monkeys for laboratory use imported from Indonesia in July, 1973. The virus agglutinated erythrocytes of some avian and mammalian species and hemolyzed chick erythrocytes. The virus was eluted from the surface of chick red blood cells by its neuraminidase activity. The virus was inactivated by ether; its nucleic acid was RNA. On electron micrographs, the particles varied from 250 to 400 nm in diameter, being covered with envelopes in which the surface projections were embedded. The diameter of inner helical structure was about 18 nm. These observations indicate that the virus belongs to a group of paramyxoviruses. On the basis of serological examinations, this virus can be identified as a new virus having some relations with Yucaipa or Bangore viruses. This virus is designated as "Murayama virus" from the name of the place where it was isolated.


The COVID-19 Pandemic - A Diagnostic Industry Perspective.
The COVID-19 pandemic has brought about unprecedented changes to all facets of the healthcare system, including the diagnostic industry. The pandemic has highlighted both the challenges and strengths of the industry and has also provided valuable insights on how to be better prepared for future pandemics. In this perspective article, we describe the challenges faced by the diagnostic industry in general, particularly the difficulties encountered by Luminex Corporation, a diagnostic assay development and manufacturing company located in Austin, Texas, USA, as well as the mitigation strategies employed. In addition to discussion of the key challenges, the article provides insights on the lessons learned and steps that can be undertaken to better prepare for future outbreaks.


Comparison of self and proxy ratings for motor performance of individuals with Parkinson disease.
The impact of Parkinson disease (PD) has been examined in recent years by comparing self-ratings by individuals with PD and proxy ratings by caregivers, communication partners, and/or health care providers. However, the existing evidence is mixed with some researchers suggesting perfect agreement between rater groups while others suggesting differences among rater groups for motor performance of individuals with PD. The current study examined self and proxy perception of performance of individuals with PD for six motor characteristics (gait, rigidity, right and left bradykinesia, rest tremors, and perception of physical effort) based on Unified Parkinson Disease Rating Scale (UPDRS) motor tasks. Participants included 20 individuals with PD, 20 communication partners, and a trained rater. The study compared perceptual ratings and corresponding UPDRS scores as well as rater group differences for perceptual motor ratings. A series of Pearson Product Moment Correlations indicated significant relationship only between self-ratings for gait and rest tremors by individuals with PD and corresponding UPDRS scores (p<.05). Further, a multivariate analysis of variance was completed to compare rater group differences. Results indicated significant overestimation of rest tremors by both individuals with PD and communication partners when compared to corresponding ratings by the trained rater. Overall, the study provided evidence for perception deficits among individuals with PD and communication partners regarding motor performance of individuals with PD. Additional studies are needed to further explore the changes in perception abilities of individuals with PD and communication partners with respect to disease duration, disease severity, and other co-morbid factors.


Chronic Pain in Young People With Cerebral Palsy: Activity Limitations and Coping Strategies.
To describe the effect of chronic pain on the activities of children and adolescents with cerebral palsy, to describe coping strategies, and to examine associations between effect of pain on activities, coping strategies, and level of pain. Using an online survey, 27, 8- to 18-year-olds with cerebral palsy and chronic pain or their parents reported pain intensity, distribution, activity limitations (using the Child Activity Limitations Interview-21), and coping strategies (using the Pediatric Pain Coping Inventory). Pain intensity ranged from 3 to 10, and 89% reported pain in multiple areas, principally the lower limbs. Individuals reporting higher pain intensity had more activity limitations and were more likely to use catastrophizing coping strategies. Coping strategies may be an important mediator between pain and its effect on activities in children with cerebral palsy. Individualized pain management should be based on routine pain assessment.


Arrhythmia occurring as the sole presenting feature in Covid-19.
Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection is observed to be associated with several cardiac complications. Cardiac arrhythmias are frequently observed in critically ill patients and are usually associated with myocarditis. We report two patients with Covid-19, in whom serious arrhythmias were the sole presenting feature, in the absence of any of the known manifestations of the disease. Further research is required into this yet unknown mechanism of the effect of Covid-19 on the conduction system. Thus, managing patients with acute-onset arrhythmias of unexplained aetiology, even when they present without known clinical features of Covid-19, should be done with care.