Nurses' and nurse assistants' beliefs, attitudes and actions related to role and function in an inpatient stroke rehabilitation unit-A qualitative study.
To explore nurses' and nurse assistants' beliefs, attitudes and actions related to their function in an inpatient stroke rehabilitation unit. Several attempts have been made to describe nurses' roles and functions in inpatient neurorehabilitation. However, current understandings of the contributions that nurses and nurse assistants make to neurorehabilitation remain sparse. Descriptive, interpretive qualitative study. Participant observations were conducted during 1 month in a stroke rehabilitation unit at a university hospital in the Capital Region of Denmark. The observations were audiorecorded and field notes were taken on the spot. Semistructured interviews with nurses (N = 8) and nurse assistants (N = 6) were performed. The audiorecorded observations, field notes and interviews were transcribed for inductive and deductive content analysis. Three main categories with underlying subcategories were identified: (i) the importance of professionalism, (ii) striving for visibility, (iii) the importance of structure. This study contributes to present understandings of nurses' and nurse assistants' roles and functions in inpatient stroke rehabilitation. We obtained insights into nursing staff's beliefs and attitudes about rehabilitation-as well as their own role and function-and furthermore how the latter affects their actions in daily practice. The nursing role and function are still not clearly defined. Further education is needed to strengthen the contribution of nursing staff to patients' rehabilitation. Furthermore, focus on developing a professional language and a framework that supports continuity within daily care and rehabilitation is needed.


Prostaglandin production by melanocytic cells and the effect of alpha-melanocyte stimulating hormone.
Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.


Magnetic resonance-based attenuation correction for PET/MR hybrid imaging using continuous valued attenuation maps.
Attenuation correction of positron emission tomographic (PET) data is critical in providing accurate and quantitative PET volumes. Deriving an attenuation map (μ-map) from magnetic resonance (MR) volumes is a challenge in PET/MR hybrid imaging. The difficulty lies in differentiating cortical bone from air from standard MR sequences because both these classes yield little to no MR signal and thus shows no distinguishable information. The objective of this contribution is 2-fold: (1) to generate and evaluate a continuous valued computed tomography (CT)-like attenuation map (μ-map) with continuous density values from dedicated MR sequences and (2) to compare its PET quantification accuracy with respect to a CT-based attenuation map as the criterion standard and other segmentation-based attenuation maps for studies of the head. Three-dimensional Dixon-volume interpolated breath-hold examination and ultrashort echo time sequences were acquired for each patient on a Siemens 3-T Biograph mMR PET/MR hybrid system and the corresponding patient CT on a Siemens Biograph 64. A pseudo-CT training was done using the epsilon-insensitive support vector regression ([Latin Small Letter Open E]-SVR) technique on 5 patients who had CT/MR/PET triplets, and the generated model was evaluated on 5 additional patients who were not included in the training process. Four μ-maps were compared, and 3 of them derived from CT: scaled CT (μ-map CT), 3-class segmented CT without cortical bone (μ-map no bone), 4-class segmented CT with cortical bone (μ-map bone), and 1 from MR sequences via [Latin Small Letter Open E]-SVR technique previously mentioned (ie, MR predicted [μ-map MR]). Positron emission tomographic volumes with each of the previously mentioned μ-maps were reconstructed, and relative difference images were calculated with respect to μ-map CT as the criterion standard. For PET quantification, the proposed method yields a mean (SD) absolute error of 2.40% (3.69%) and 2.16% (1.77%) for the complete brain and the regions close to the cortical bone, respectively. In contrast, PET using μ-map no bone yielded 10.15% (3.31%) and 11.03 (2.26%) for the same, although PET using μ-map bone resulted in errors of 3.96% (3.71%) and 4.22% (3.91%). Furthermore, it is shown that the model can be extended to predict pseudo-CTs for other anatomical regions on the basis of only MR information. In this study, the generation of continuous valued attenuation maps from MR sequences is demonstrated and its effect on PET quantification is evaluated in comparison with segmentation-based μ-maps. A less-than-2-minute acquisition time makes the proposed approach promising for a clinical application for studies of the head. However, further experiments are required to validate and evaluate this technique for attenuation correction in other regions of the body.


GeneView: a comprehensive semantic search engine for PubMed.
Research results are primarily published in scientific literature and curation efforts cannot keep up with the rapid growth of published literature. The plethora of knowledge remains hidden in large text repositories like MEDLINE. Consequently, life scientists have to spend a great amount of time searching for specific information. The enormous ambiguity among most names of biomedical objects such as genes, chemicals and diseases often produces too large and unspecific search results. We present GeneView, a semantic search engine for biomedical knowledge. GeneView is built upon a comprehensively annotated version of PubMed abstracts and openly available PubMed Central full texts. This semi-structured representation of biomedical texts enables a number of features extending classical search engines. For instance, users may search for entities using unique database identifiers or they may rank documents by the number of specific mentions they contain. Annotation is performed by a multitude of state-of-the-art text-mining tools for recognizing mentions from 10 entity classes and for identifying protein-protein interactions. GeneView currently contains annotations for >194 million entities from 10 classes for ∼21 million citations with 271,000 full text bodies. GeneView can be searched at http://bc3.informatik.hu-berlin.de/.


Morphofunctional modifications associated with the inhibition by estradiol of MtTF4 rat pituitary tumor growth.
The MtTF4 pituitary tumor has been induced in Fischer rats by chronic estrogen administration. Recently, we reported that sustained pharmacological treatment of Fischer rats with 17 beta-estradiol inhibited the growth of the MtTF4 tumor transplanted s.c. The present work describes the associated morphofunctional changes occurring in the tumor during 17 beta-estradiol inhibition. It is shown that a 7-day 17 beta-estradiol treatment resulted in an increase of the surface area of cells, nuclei, nucleoli, Golgi complexes, and rough endoplasmic reticulum and an increase in the number of euchromatin-rich nuclei. Flow cytometry analysis of DNA distribution suggested that estradiol affects the cell progression through the early S phase. The ratio of RNA to DNA increased significantly, reflecting cell hypertrophy. Moreover, there was a significant increase in tumor prolactin concentration and a marked enhancement in the intensity of the immunocyto-chemical reaction with rat prolactin antiserum. On the other hand, cell mitoses were dramatically decreased. These morphofunctional changes indicate that the inhibition of the tumor growth by estradiol is accompanied by an evolution of the tumor cell population towards a more differentiated state. However, it cannot be decided whether 17 beta-estradiol induces a shift from a proliferative state to a differentiated state or whether 17 beta-estradiol treatment results in a selection of a subpopulation of tumor cells that are slow growing and more differentiated.


Localization of somatostatin receptor subtype mRNA in the rat gastrointestinal tract and regulation of SSTR1 gene expression.
Somatostatin and its receptors are widely distributed in the central nervous system and peripheral tissues including those of the gastrointestinal tract (GI tract). The expression patterns of the five known SSTR genes have been analysed in detail by reverse transcription polymerase chain reaction amplifications and in situ hybridizations using tissues dissected from different parts of rat stomach and gut. While SSTR1 mRNA is present at relatively high amounts throughout the gastrointestinal tract, the levels of SSTR2, 3 and 4 mRNAs vary in different regions and SSTR5 mRNA has not been detected. In situ hybridizations revealed the presence of SSTR3 mRNA in enterocytes and in neurons of the myenteric and submucous plexus. These findings are consistent with a role of SSTR3 in the observed somatostatin-mediated inhibition of acetylcholine release from myenteric neurons and of secretomotor neuron activity in the submucous plexus. Sequence analyses of the SSTR1 gene promoter revealed the absence of the canonical TATA and CAAT motifs and the presence of a variety of potential binding sites for transcriptional regulators. Among these are binding sites for GCF, AP-2, AP-4, response elements for somatostatin (SOM-RE), epidermal growth factor (EGF-RE) and cytocines (GAS and NFIL) as well as for tissue-specific factors such as Pit-1 (pituitary) and IDX-1 (pancreatic cells). Mobility shift assays have confirmed that nuclear proteins of pancreatic RIN1046-38 and pituitary GH3 tumour cells bind to oligonucleotides containing the overlapping Pit-1 and IDX-1 binding sites. Thus, the Pit-1/IDX-1 sites may be critical for the activation of the SSTR1 gene in these cell-types.


Immunotherapy for non-Hodgkin's lymphoma: monoclonal antibodies and vaccines.
Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.


Activity of Epigenetic Inhibitors against Plasmodium falciparum Asexual and Sexual Blood Stages.
Earlier genetic and inhibitor studies showed that epigenetic regulation of gene expression is critical for malaria parasite survival in multiple life stages and a promising target for new antimalarials. We therefore evaluated the activity of 350 diverse epigenetic inhibitors against multiple stages of Plasmodium falciparum We observed ≥90% inhibition at 10 μM for 28% of compounds against asexual blood stages and early gametocytes, of which a third retained ≥90% inhibition at 1 μM.


[COVID-19 in transplant recipients: Multicentric report of Mexican experience].
Solid Organ Transplant recipients (SOTR) appear to be at particular high risk for critical COVID-19 due to immunosuppressive drugs and comorbidities. We report the first description of clinical course and short-term outcomes of kidney and liver transplant recipients with confirmed COVID-19 in Mexico. The objective of this paper was evaluate the clinical course of transplant patients with COVID-19 infection. We retrospectively evaluated SOTR (kidney and liver) over 18 years of age with confirmed diagnosis of COVID-19 from tertiary care centers in Mexico. Data from 45 kidney transplant recipients were recorded. Median (IQR) age was 43 (IQR 25-70) years. Admission to hospital was required in 37 (75.5 %) patients, of which 8 (16.3%) were hospitalized at Intensive Care Unit (ICU). Acute kidney injury (AKI) stage was documented in 33 (67%) patients. The time of hospitalization was 8 (IQR 6-12) days. Six patients died (12.2%). Additionally, data from 10 liver transplant recipients were included. During their evolution, 5 / 10 required hospital admission and there were no deaths in this group. Transplant recipients show a higher fatality rate and complications from SARS-CoV-2 infection; more studies are needed to identify prognostic factors and effective anti-SARS-CoV-2 therapies.


Improving patient safety through a clinical audit spiral: prevention of wrong tooth extraction in orthodontics.
Introduction With an increasing demand to improve patient safety within the NHS, it is important to ensure that measures are undertaken to continually improve patient care. Wrong site surgery has been defined as a 'never event'. This article highlights the importance of preventing wrong tooth extraction within orthodontics through an audit spiral over five years investigating the accuracy and clarity of orthodontic extraction letters at the University Dental Hospital of Manchester.Aims To examine compliance with the standards for accuracy and clarity of extraction letters and the incidence of wrong tooth extractions, and to increase awareness of the errors that can occur with extraction letters and of the current guidelines.Method A retrospective audit was conducted examining extraction letters sent to clinicians outside the department.Results It can be seen there has been no occurrence of a wrong site tooth extraction. The initial audit highlighted issues in conformity, with it falling below expected standards. Cycle two generally demonstrated a further reduction in compliance. Cycle three appeared to result in an increase in levels of compliance. Cycles 4 and 5 have demonstrated gradual improvements. However, it is noteworthy that in all cycles the audit standards were still not achieved, with the exception of no incidences of the incorrect tooth being extracted.Conclusion This audit spiral demonstrates the importance of long term re-audit to aim to achieve excellence in clinical care. There has been a gradual increase in standards through each audit.


[Glaucoma after congenital cataract extraction in children].
The clinical material comprised 45 eyes in 33 children aged from 5 months to 8 years. In the period of 5 days to 7 years after congenital cataract surgery, an increased intraocular pressure has been observed. Antiinflammatory treatment, optic, cyclocryotherapy, synechia-lysis, anterior vitrectomy, YAG-laser and trabeculectomy were applied, depending on the mechanisms that caused the increase of intraocular pressure. In 1-5 years follow-up, the control of intraocular pressure, using the pharmacological treatment and/or surgery, was obtained in 88.4% of the cases. On admission, the enlargement of the eyeball was observed in 26.6% of children, whereas in every fifth of them the cupping of the optic disc was recorded.


Evolutionary dynamics of cellular automata-based self-replicators in hostile environments.
In this paper we investigate population dynamics, genealogy and complexity-increase of locally interacting populations of cellular automata-based evolving self-replicating loops (evoloops). We outline experiments indicating that the evolutionary growth in complexity, known to be achievable in principle given the complete genetic accessibility granted by universal construction, may be achievable in practice using much simpler replicating structures. By introducing evoloop populations to hostile environments, we demonstrate that selection pressures toward smaller species can be mediated to enable evolutionary accessibility to larger species, which themselves roam a much more vast portion of genetic state-space. We show that this growth in size results from intrinsically biased genealogy inherent in the rules of the evoloop CA, normally suppressed by selection pressures from direct competition favouring the smallest species. This shows that, in populations of simple self-replicating structures, a limited form of complexity-increase may result from a process which is driven by biased genealogical connectivity--a purely emergent property arising out of bottom-up evolutionary dynamics--and not just by adaptation . Implications of this result are discussed and contrasted with other self-replication studies in Artificial Life and Biology.


Quantitative analysis of pesticide residues in vegetables and fruits by liquid chromatography quadrupole time-of-flight mass spectrometry.
The applicability of liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) for the quantitative analysis of pesticide residues in vegetables and fruits was demonstrated. The LC-QTOF-MS parameters, such as cone voltage, capillary voltage, collision energy and mass extraction window, were carefully optimised for the analysis of pesticide residues. The LC-QTOF-MS method was validated for 149 pesticides in four vegetables and fruits, i.e. apple, potato, cabbage and spinach, at a spiking level of 0.01 mg kg(-1). The samples were prepared according to the Japanese official multi-residue method with a modification to the column clean-up procedure. Of the 149 pesticides, recoveries in the range of 70-120% were achieved for 147 pesticides in apple, 145 in potato, 141 in cabbage and 131 in spinach, with intra-day precisions (RSDs) of < 25% and inter-day precisions (RSDs) of < 30%, which are within the acceptable range given in the Japanese method validation guideline. Matrix effects were negligible for the majority of the target pesticides. Except for spiroxamine in spinach, no interfering peaks were observed in the blank samples. The target pesticides, except those with low sensitivity, achieved calibration curves with satisfactory linearity, with correlation coefficients (r) greater than 0.995 in the concentration range of 0.002-0.1 μg ml(-1). Furthermore, the majority of the target pesticides provided more than one fragment ion or isotope ion that could be used for confirmation. The overall results suggest that LC-QTOF-MS is a powerful tool for the quantification of pesticide residues in vegetables and fruits at the level of 0.01 mg kg(-1).


Synchrotron-radiation-induced formation of salt particles on an X-ray lithography mask.
The suppression and removal of contaminants on X-ray masks are required for the application of X-ray lithography to practical semiconductor production, because contamination is easily transferred to the replicated resist patterns and degrades the LSI patterns. In order to study contamination of a Ta/SiN X-ray mask, its growth process was investigated using an atmospheric reaction chamber and in situ observation apparatus for gases at atmospheric pressure. It was found that the contamination particles were ammonium sulfate and oxalate. The sources of the salt particle were also identified.


Biomechanical Comparative Study for Osteosynthesis of Pauwels Type III Femoral Neck Fractures: Conventional Devices versus Novel Fixed Angle Devices.
Osteosynthesis has been recommended for treatment of Pauwels type III femoral neck fractures in young patients. However, no implant of choice has been reported so far. This study was conducted in order to compare the fixation stability of two conventional fixation methods with three different novel fixed angle devices in this type of fracture. A total of 25 composite femurs (4th Generation Saw bone; Pacific Research Laboratories, USA) corresponding to human bone were used. Pauwels type III fracture type was uniformly reproduced. Specimens were fixed with a cannulated screw, cannulated screw with cable, and Intertan nail, dynamic hip screw, and IKEY nail. Measurement of failure loads and the rotational change of the femoral head fragment was performed for evaluation of fixation stability. All implants were compared with cannulated screw and dynmaic hip screw. No meaningful improvement was observed for the cannulated screw with cable compared with the cannulated screw and dynamic hip screw. Meaningful improvement in load-to-failure and y-rotation and z-rotation was observed for both the Intertan nail and IKEY nail compared with the cannulated screw. However, compared with the dynamic hip screw, only the IKEY nail showed improvement in the same profile but the Intertan nail did not. Among novel fixed angle devices, meaningful improvement was observed for the IKEY nail compared with conventional implants. Strengths of this implant include biomechanical stability and simplicity of surgical technique, indicating that it may be another good option for osteosynthesis of Pauwels type III femoral neck fractures.


Haemophilus influenzae increases the susceptibility and inflammatory response of airway epithelial cells to viral infections.
Nontypeable Haemophilus influenzae (NTHI), a common colonizer of lungs of patients with chronic obstructive pulmonary disease (COPD), can enhance expression of the cellular receptor intercellular adhesion molecule 1 (ICAM-1), which in turn can be used by major group human rhinoviruses (HRVs) for attachment. Here, we evaluated the effect of NTHI-induced up-regulation of ICAM-1 on viral replication and inflammatory responses toward different respiratory viruses. Therefore, human bronchial epithelial cells were pretreated with heat-inactivated NTHI (hi-NTHI) and subsequently infected with either HRV16 (major group), HRV1B (minor group), or respiratory syncytial virus (RSV). Pretreatment with hi-NTHI significantly up-regulated ICAM-1 in BEAS-2B cells and primary bronchial epithelial cells. Concomitantly, release of infectious HRV16 particles was increased in cells pretreated with hi-NTHI. Pretreatment with hi-NTHI also caused a significant increase in HRV16 RNA, whereas replication of HRV1B and RSV were increased to a far lesser extent and only at later time points. Interestingly, release of IL-6 and IL-8 after RSV, but not HRV, infection was synergistically increased in hi-NTHI-pretreated BEAS-2B cells. In summary, exposure to hi-NTHI significantly enhanced sensitivity toward HRV16 but not HRV1B or RSV, probably through ICAM-1 up-regulation. Furthermore, hi-NTHI pretreatment may enhance the inflammatory response to RSV infection, suggesting that preexisting bacterial infections might exaggerate inflammation during secondary viral infection.


Total and Free Sugar Content of Pre-Packaged Foods and Non-Alcoholic Beverages in Slovenia.
Scientific evidence of the association between free sugar consumption and several adverse health effects has led many public health institutions to take measures to limit the intake of added or free sugar. Monitoring the efficiency of such policies and the amount of free sugar consumed requires precise knowledge of free sugar content in different food products. To meet this need, our cross-sectional study aimed at assessing free sugar content for 10,674 pre-packaged food items available from major Slovenian food stores during data collection in 2015. Together, 52.6% of all analyzed products contained free sugar, which accounted for an average of 57.5% of the total sugar content. Food categories with the highest median free sugar content were: honey and syrups (78.0 g/100 g), jellies (62.9 g/100 g), chocolate and sweets (44.6 g/100 g), jam and spreads (35.9 g/100 g), and cereal bars (23.8 g/100 g). Using year-round sales data provided by the retailers, the data showed that chocolate, sweets, and soft drinks alone accounted for more than 50% of all free sugar sold on the Slovenian market. The results of this study can be used to prepare more targeted interventions and efficient dietary recommendations.


Early gestational hemolytic uremic syndrome: case report and review of literature.
Hemolytic uremic syndrome (HUS) is a rare condition which most frequently follows gastrointestinal or respiratory infection episodes in young children, but it can also occur in other settings such as the postpartum period and during use of drugs such as oral contraconceptives, immunosuppressors, and antineoplastics. In early pregnancy, however, its frequency is thought to be very low. The authors report a case of a 30-year-old woman who developed HUS early in her first pregnancy. She had persistent aqueous diarrhea from the beginning of the pregnancy. At the 21st week she developed hypertension which in 2 weeks was followed by seizures, oliguria, and acute pulmonary edema despite intensive medical efforts to control her blood pressure. Surgical intervention for fetal delivery was performed. The patient was initially kept on continuous hemodialysis (CVVHD) followed by an alternate-day conventional hemodialysis schedule. A peripheral blood analysis showed a microangiopathic hemolytic anemia with thrombocytopenia; blood coagulation tests were completely normal. A brain CT scan and an abdominal MRI showed no major abnormalities. HUS was confirmed by a percutaneal kidney biopsy, performed at the 21st day of anuria. Techniques for identification of verotoxin-producing E. coli were not available. Renal function did not recover and the patient has been undergoing regular maintenance hemodialysis for a year.


Trichloroethylene degradation by persulphate with magnetite as a heterogeneous activator in aqueous solution.
Iron oxide-magnetite (Fe3O4) as a heterogeneous activator to activate persulphate anions (S2O8(2-)) for trichloroethylene (TCE) degradation was investigated in this study. The experimental results showed that TCE could be completely oxidized within 5 h by using 5 g L(-1) magnetite and 63 mM S2O8(2-), indicating the effectiveness of the process for TCE removal. Various factors of the process, including. (S2O8(2-) and magnetite dosages, and initial solution pH, were evaluated, and TCE degradation fitted well to the pseudo-first-order kinetic model. The calculated kinetic rate constant was increased with increasing S2O8(2-) and magnetite dosages, but it was independent of solution pH. In addition, the changes of magnetite morphology examined by scanning electron microscopy and X-ray powder diffraction, respectively, confirmed the slight corrosion with α-Fe2O3 coated on the magnetite surface. The probe compounds tests clearly identified the generation of the reactive oxygen species in the system. While the free radical quenching studies further demonstrated that •SO4- and •OH were the major radicals responsible for TCE degradation, whereas •O2- contributed less in the system, and therefore the roles of reactive oxygen species on TCE degradation mechanisms were proposed accordingly. To our best knowledge, this is the first time the performance and mechanism of magnetite-activated persulphate oxidation for TCE degradation are reported. The findings of this study provided a new insight into the heterogeneous catalysis mechanism and showed a great potential for the practical application of this technique in in situ TCE-contaminated groundwater remediation.


Retinopathy of prematurity: causation.
The incidence of ROP is birth weight dependent and restricting therapeutic oxygen levels has dramatically reduced the incidence of ROP in infants of birth weight >1000 g. However, the incidence of ROP has remained high in very low birth weight (VLBW) infants and this appears to be related to these babies being more ill. Several risk factors have been identified in this group, however oxygen variability, rather than high levels, has been correlated with severity of disease in recent clinical and animal studies. Difficulties in defining 'normal' oxygen in this group has meant the optimal range of oxygen therapy has not yet been defined. Clinical studies are now underway using even lower oxygen therapy ranges. The impact this may have on ROP, neurological and respiratory outcomes will require further study.


Chemoprevention strategies in the prostate: an overview.
Chemoprevention is the administration of agents (drugs, biologics, and nutrients) to prevent induction, inhibit, or delay the progression of cancers. Prostate cancer is an important target for chemoprevention because of its long latency and high prevalence. The development of rational chemopreventive strategies requires knowledge of the mechanisms of prostate carcinogenesis and identification of agents that interfere with these mechanisms. Because of the long time period for prostate carcinogenesis and the large size of the cohort required for an evaluable study, identification and characterization of early intermediate biomarkers and their validation as surrogate endpoints for cancer incidence are essential for chemopreventive agent development. Finally, suitable populations with appropriate risk factors, including the presence of premalignant lesions and genetic predispositions, need to be well characterized for future chemopreventive interventions.


Differential effects of antioxidants on the in vitro invasion, growth and lung metastasis of murine colon cancer cells.
We conducted a comparative study of 20 antioxidants including antioxidative vitamins and polyphenols to examine their inhibitory activities against the in vitro invasion, growth and experimental lung metastasis of murine colon 26-L5 carcinoma cells. Among the compounds tested, epigallocatechin gallate (EGCG), gallocatechin gallate and genistein exhibited significant reductions at 77%, 46% and 44% in tumor metastasis by an intraperitoneal administration for 5 d beginning at 3 d before tumor inoculation, respectively. Quercetin also showed a slight but not statistically significant inhibition. Alpha-tocopherol, beta-carotene, ascorbic acid and 2 EGCG-related compounds of epicatechin gallate and epigallocatechin had no effect. EGCG also inhibited tumor metastasis dose-dependently with 98% suppression at 2 micromol; and an almost equivalent inhibition was also produced by only pre-administration of EGCG at the same dose before tumor inoculation. EGCG significantly inhibited tumor cell invasion and proliferation, but its inhibition of these activities was much less effective than that of other compounds which did not show any antimetastatic effect. No statistically significant relationship was observed between the radical scavenging activities of the test compounds and their rates of inhibition of tumor metastasis. The antimetastatic mechanism of EGCG thus seems to be independent of its inhibition of tumor invasion and growth, as well as its radical scavenging activity. Our results suggest that EGCG is potentially beneficial for tumor metastasis inhibition.


Sensitization of mice with olive pollen allergen Ole e 1 induces a Th2 response.
Olive pollen is one of the main causes of allergy in Mediterranean countries, where it is widely distributed. One inconvenience in studying new immunotherapies for olive pollen allergy is the lack of suitable animal models. The aim of this study was to develop a murine model of IgE sensitization to Ole e 1, the major allergen of olive pollen, which mimics the immunological features of olive pollinosis in humans and to investigate the in vivo antigenicity of the recombinant form of the allergen. BALB/c mice were sensitized by intraperitoneal administration of natural Ole e 1 (nOle e 1) and recombinant Ole e 1 (rOle e 1) in Al(OH)(3), respectively. Serum levels of specific IgE, IgG1 and IgG2a, cytokine production and the proliferative response of splenocytes after in vitro stimulation with nOle e 1 were analyzed by ELISA and flow cytometry. The binding capacity of rOle e 1-specific IgG1 was examined by ELISA and immunoblotting. Sensitization with nOle e 1 or rOle e 1 induced high levels of specific IgE and IgG1 versus low IgG2a antibody levels. Splenocytes from sensitized mice exhibited a proliferative response to nOle e 1. In vitro stimulated splenic cells from nOle e 1-primed mice produced IL-4 and low or nondetectable levels of IFN-gamma. Specific IgE and IgG1 antibodies of immunized mice bound to the same Ole e 1 isoforms and showed a similar degree of cross-reactivity as observed for human IgE. Mouse specific nOle e 1 IgG1 was strongly inhibited by IgE from allergic patients. The IgG1 antibodies elicited by rOle e 1 reacted with both the recombinant and natural forms of the allergen. A murine model of Ole e 1 sensitization has been established. rOle e 1 shows similar allergenicity and antigenicity to its natural form. This model should provide a useful tool for evaluating antigenic molecules and exploring new therapeutic approaches in order to treat IgE-mediated olive pollinosis.


Effect of Intermittent versus Continuous Light Exposure on Pupillary Light Response, As Evaluated by Pupillometry.
Continuous and intermittent stimuli with green light affect the pupillary light response (PLR) differently. Since the majority of pupillometric studies use blue and red lights, we investigated the effect of continuous and intermittent stimulations on the PLR using red and blue lights. Seventeen healthy subjects underwent continuous- and intermittent light stimuli, using red (643 nm) and blue light (463 nm). To avoid the influence of pupil size on the amount of light entering the eye, the procedures were repeated with the stimulus-eye in dilated condition. The maximal pupillary constriction and the early redilation phase of post-illumination pupillary response (PIPREarly) represented the mixed response of melanopsin and rod-cone photoreceptors. The late redilation phase of PIPR (PIPRLate) was the marker of melanopsin-containing retinal ganglion cells. Intermittent stimuli with blue light elicited significantly larger maximal contraction during dilated condition (P = 0.001), and larger sustained pupillary contraction under dilated as well as undilated condition (P < 0.001) compared to continuous light exposure. Except the PIPREarly during undilated condition, none of the PIPR metrics were significantly different between intermittent and continuous blue light stimuli. Intermittent red light stimuli elicited also a more sustained pupillary contraction regardless of mydriatic instillation (P ≤ 0.02). In addition, intermittent red light exposure resulted in a slightly larger PIPREarly under undilated condition (P = 0.02) and a slightly larger PIPRLate under dilated condition (P = 0.049). Except the PIPRLate to continuous red light stimulus, all PIPR parameters were larger when the light was presented after induction of unilateral mydriasis. PLR parameters during and after light exposures depend on both the light stimulation mode and the entrance pupillary size.


Microarray based analysis of gene expression patterns in pancreatic neuroendocrine tumors.
Pancreatic neuroendocrine tumors (PanNETs) are a small subgroup of tumors with a variety of biological behaviors. We sought to identify the specially expressed genes and characterize significant pathways in PanNETs compared with non-neoplastic samples. Gene expression profile GSE43795 was obtained from Gene Expression Omnibus database, which included 6 PanNETs and 5 non-neoplastic samples. The differentially expressed genes (DEGs) were identified using Limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions and pathways of DEGs. Transcription factors (TFs) and tumor-associated genes (TAGs) were also identified. Finally, a protein-protein interaction (PPI) network was constructed, and hub proteins and functional module were screened out. Total of 821 DEGs (421 down-regulated, 400 up-regulated) were selected. GO and KEGG enrichment analyses showed that up-regulated DEGs were related to several pathways, including type 2 diabetes mellitus, Ca2+ signaling pathway, long-term potentiation, and long-term depression pathways. Down-regulated DEGs were enriched in several pathways, such as pancreatic secretion, protein digestion and absorption, and metabolic pathway. Interferon-stimulated gene protein 15 (ISG15), somatostatin (SST), and synaptosomal-associated protein 25 kDa (SNAP25) were identified as hub proteins. The genes involved in type 2 diabetes mellitus pathway may play important roles in the development of PanNETs. SNAP25, SST, and ISG15 may be used as potential targets for treatment of PanNETs.


Yeast Starter as a Biotechnological Tool for Reducing Copper Content in Wine.
Copper is widely used in agriculture as a traditional fungicide in organic farming to control downy mildew on grapes, consequently it is possible to find this metal during all stages of the vinification process. Low amounts of copper play a key role on the function of key cell enzymes, whereas excess quantities can exert amount-dependent cytotoxicity, resulting in general cellular damage. Nowadays the excessive copper ions in wines is removed by addition of adsorbents, but these additives can influence the sensory characteristics of wine, as well as detrimental to the health of consumers. It is well known that high concentrations of Cu2+ can be toxic to yeasts, inhibiting growth and activity, causing sluggish fermentation and reducing alcohol production. In this study, 47 S. cerevisiae strains were tested for copper tolerance by two different tests, growth on copper added medium and fermentative activity in copper added grape must. The results obtained by the two different tests were comparable and the high strain variability found was used to select four wild strains, possessing this characteristic at the highest (PP1-13 and A20) and the lowest level (MPR2-24 and A13). The selected strains were tested in synthetic and natural grape must fermentation for ability to reduce copper content in wine. The determination of copper content in wines and yeast cells revealed that at the lowest copper residual in wine corresponded the highest content in yeast cells, indicating a strong strain ability to reduce the copper content in wine. This effect was inversely correlated with strain copper resistance and the most powerful strain in copper reduction was the most sensitive strain, MPR2-24. This wild strain was finally tested as starter culture in cellar pilot scale fermentation in comparison to a commercial starter, confirming the behavior exhibited at lab scale. The use of this wild strain to complete the alcoholic fermentation and remove the copper from wine represents a biotechnological sustainable approach, as alternative to the chemical-physical methods, ensuring at the same time a completed alcoholic fermentation and organoleptic quality of wine.


Potential risk of re-emergence of urban transmission of Yellow Fever virus in Brazil facilitated by competent Aedes populations.
Yellow fever virus (YFV) causing a deadly viral disease is transmitted by the bite of infected mosquitoes. In Brazil, YFV is restricted to a forest cycle maintained between non-human primates and forest-canopy mosquitoes, where humans can be tangentially infected. Since late 2016, a growing number of human cases have been reported in Southeastern Brazil at the gates of the most populated areas of South America, the Atlantic coast, with Rio de Janeiro state hosting nearly 16 million people. We showed that the anthropophilic mosquitoes Aedes aegypti and Aedes albopictus as well as the YFV-enzootic mosquitoes Haemagogus leucocelaenus and Sabethes albiprivus from the YFV-free region of the Atlantic coast were highly susceptible to American and African YFV strains. Therefore, the risk of reemergence of urban YFV epidemics in South America is major with a virus introduced either from a forest cycle or by a traveler returning from the YFV-endemic region of Africa.


Heterogeneity of O blood group in India: Peeping through the window of molecular biology.
Molecular genotyping of ABO blood group system has identified more than 60 "O" group alleles based on the single-nucleotide polymorphisms present in the ABO gene. Heterogeneity of O group alleles has been observed in various countries from South America, Europe, Middle East, and Asia. India is a vast country with more than 1300 million population which is divided into various ethnic and tribal groups. However, very little is known about the heterogeneity of O alleles in Indians. A total of 116 O group individuals from the mixed population of Mumbai, India, were enrolled in the present study. DNA was extracted using the standard phenol-chloroform method. The exons 6 and 7 of the ABO gene were genotyped by polymerase chain reaction-single-strand conformation polymorphism and/or DNA sequencing. The genotyping results were compared with our earlier findings. Overall, ten different genotypes were identified. Three rare alleles, namely, O05, O11, and O26 were seen in the mixed group category. These results suggest that there is an internal heterogeneity in the mixed group while Dhodias and Parsis, the groups which were screened earlier, seem to be more homogenous groups. An important piece of information emerges out from this study, that is, O01O02 genotype is expressing some selective force in population groups screened in India as well as many other groups worldwide. In the future, molecular genotyping of the ABO blood group system among different ethnic and tribal Indian groups would help in generating data to fill up the gaps in the molecular ABO map of the world.


Characterization of a polyvinyl alcohol-hydrogel artificial articular cartilage prepared by injection molding.
We have developed a hip hemi-arthroplasty using polyvinyl alcohol-hydrogel (PVA-H) as the treatment for hip joint disorders in which the lesion is limited to the joint surface. In previous studies, we characterized the biocompatibility and the mechanical properties of PVA-H as an arthroplasty material. To fix PVA-H firmly to the bone, we have devised an implant composed of PVA-H and porous titanium fiber mesh (TFM). However, because of poor infiltration of the PVA solution into the pores of the TFM when using the low temperature crystallization method, the strength of the PVA-H-TFM interface was insufficient. Consequently, the infiltration method was improved by adopting high-pressure injection molding. With this improved method, the bonding strength of the interface increased remarkably. However, as this injection molding requires high temperature, various mechanical properties of the PVA-H might change with this treatment in comparison with the previous method. The purpose of this study was to investigate the effect of high temperature treatment on the mechanical properties of PVA-H as artificial articular cartilage, the tensile test and friction test were performed about new PVA-H. The results showed no significant mechanical deterioration of the PVA-H. This certified that the injection-molding method did not induce the change of the mechanical properties of PVA-H and indicated the potential of hemi-arthroplasty using PVA-H by this method in the future.


The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity.
The EMPA-REG OUTCOME study revealed that a sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, can remarkably reduce cardiovascular (CV) mortality and heart failure in patients with high-risk type 2 diabetes. Recently, the CANVAS program also showed that canagliflozin, another SGLT2 inhibitor, induces a lower risk of CV events. However, the precise mechanism by which an SGLT2 inhibitor elicits CV protective effects is still unclear. Possible sympathoinhibitory effects of SGLT2 inhibitor have been suggested, as significant blood pressure (BP) reduction, following treatment with an SGLT2 inhibitor, did not induce compensatory changes in heart rate (HR). We have begun to characterize the effects of SGLT2 inhibitor on BP and sympathetic nervous activity (SNA) in salt-treated obese and metabolic syndrome rats, who develop hypertension with an abnormal circadian rhythm of BP, a non-dipper type of hypertension, and do not exhibit a circadian rhythm of SNA. Treatment with SGLT2 inhibitors significantly decreased BP and normalized circadian rhythms of both BP and SNA, but did not change HR; this treatment was also associated with an increase in urinary sodium excretion. Taken together, these data suggest that an SGLT2 inhibitor decreases BP by normalizing the circadian rhythms of BP and SNA, which may be the source of its beneficial effects on CV outcome in high-risk patients with type 2 diabetes. In this review, we briefly summarize the effects of SGLT2 inhibitors on BP and HR, with a special emphasis on SNA.


User Models for Personalized Physical Activity Interventions: Scoping Review.
Fitness devices have spurred the development of apps that aim to motivate users, through interventions, to increase their physical activity (PA). Personalization in the interventions is essential as the target users are diverse with respect to their activity levels, requirements, preferences, and behavior. This review aimed to (1) identify different kinds of personalization in interventions for promoting PA among any type of user group, (2) identify user models used for providing personalization, and (3) identify gaps in the current literature and suggest future research directions. A scoping review was undertaken by searching the databases PsycINFO, PubMed, Scopus, and Web of Science. The main inclusion criteria were (1) studies that aimed to promote PA; (2) studies that had personalization, with the intention of promoting PA through technology-based interventions; and (3) studies that described user models for personalization. The literature search resulted in 49 eligible studies. Of these, 67% (33/49) studies focused solely on increasing PA, whereas the remaining studies had other objectives, such as maintaining healthy lifestyle (8 studies), weight loss management (6 studies), and rehabilitation (2 studies). The reviewed studies provide personalization in 6 categories: goal recommendation, activity recommendation, fitness partner recommendation, educational content, motivational content, and intervention timing. With respect to the mode of generation, interventions were found to be semiautomated or automatic. Of these, the automatic interventions were either knowledge-based or data-driven or both. User models in the studies were constructed with parameters from 5 categories: PA profile, demographics, medical data, behavior change technique (BCT) parameters, and contextual information. Only 27 of the eligible studies evaluated the interventions for improvement in PA, and 16 of these concluded that the interventions to increase PA are more effective when they are personalized. This review investigates personalization in the form of recommendations or feedback for increasing PA. On the basis of the review and gaps identified, research directions for improving the efficacy of personalized interventions are proposed. First, data-driven prediction techniques can facilitate effective personalization. Second, use of BCTs in automated interventions, and in combination with PA guidelines, are yet to be explored, and preliminary studies in this direction are promising. Third, systems with automated interventions also need to be suitably adapted to serve specific needs of patients with clinical conditions. Fourth, previous user models focus on single metric evaluations of PA instead of a potentially more effective, holistic, and multidimensional view. Fifth, with the widespread adoption of activity monitoring devices and mobile phones, personalized and dynamic user models can be created using available user data, including users' social profile. Finally, the long-term effects of such interventions as well as the technology medium used for the interventions need to be evaluated rigorously.


Factors associated with stress impacting academic success among post-secondary students: A systematic review.
Objective: To synthesize peer-reviewed primary research exploring factors associated with perceived stress impacting post-secondary students' academic success. Methods: A systematic review identified research conducted in North America, Europe, and Australia in the last ten years across 12 databases. Results: Of the 6,214 references screened, 14 English articles published between 2011 and 2018 were deemed relevant. Subsequent analysis characterized articles by study design, location, population, factors with a statistically significant relationship with both perceived stress and academic success, and future research directions. Findings reveal a complex relationship among overlapping factors associated with perceived stress on academic success at both the intrapersonal (eg, academic, demographic, psychological, attitudinal, and behavioral characteristics) and interpersonal levels (eg, social capital). Conclusions: Further research should measure the association of the identified factors to inform areas where resources could be targeted within post-secondary institutions to prevent stress from unduly impacting students' educational outcomes.


Increased cell proliferation and differential protein expression induced by low-level Er:YAG laser irradiation in human gingival fibroblasts: proteomic analysis.
Erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment has demonstrated favorable wound healing effect after periodontal therapy. One of the reasons may be the positive biological effect of the low-level laser on the irradiated tissues, although the mechanism remains unclear. The aim of this study was to investigate the effect of low-level Er:YAG laser irradiation on cell proliferation and laser-induced differential expression of proteins in human gingival fibroblasts (HGFs) by proteomic analysis. In the first experiment, HGFs were exposed to low-level Er:YAG laser irradiation and the laser-induced cell proliferation and damage were evaluated on day 3. In the second experiment, proteomic analysis was performed on day 1 after irradiation. The peptides prepared from HGFs were analyzed by a hybrid ion trap-Fourier transform mass spectrometer, Mascot search engine, and UniProtKB database. A significant increase in cell proliferation without cell damage after irradiation was observed. Among the total identified 377 proteins, 59 proteins, including galectin-7, which was associated with the process of wound healing, were upregulated and 15 proteins were downregulated in laser-treated HGFs. In the third experiment, the increase in messenger RNA (mRNA) and protein expression of galectin-7 in the irradiated HGFs was validated by various analytical techniques. In addition, the effect of recombinant human galectin-7 on the modulation of HGFs proliferation was confirmed. The results indicate that low-level Er:YAG laser irradiation can promote HGF proliferation and induce a significant change in protein expression and the upregulation of galectin-7 expression may partly contribute to the increase in cell proliferation.


Allogenic Acellular Dermal Matrix and Xenogeneic Dermal Matrix as Connective Tissue Graft Substitutes for Long-Term Stability Gingival Recession Therapy: A Systematic Review and Meta-Analysis.
Connective tissue graft (CTG) serves as a gold standard for gingival recession therapy. Yet the availability of CTG is limited, and it increases patient morbidity. Allogenic acellular dermal matrix (AADM) and xenogeneic dermal matrix (XDM) have been proven to be effective substitutes of CTG although the long-term stability is unclear. The aim of this study was to analyze the long-term stability outcome of gingival recession therapy using AADM and XDM compared to CTG. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted independently from several online databases (PubMed, Scopus, and Embase). Five of 233 publications were included for final qualitative analysis and meta-analysis focusing on the mean difference of clinical parameters such as recession depth (RD), recession width (RW), probing depth (PD), clinical attachment loss (CAL), tissue thickness (TT), keratinized tissue width (KTW), and mean root coverage (MRC). Meta-analyses of RD, RW, CAL, TT, KTW, and MRC display an overall mean of 0.2 mm (95% confidence interval [CI]: -0.45 to -0.05), 0.29 mm (95% CI: -0.65 to 0.08), 0.2 mm (95% CI: -0.69 to 0.29), 0.25 mm (95% CI: -0.53 to 0.03), 0.26 mm (95% CI: -0.5 to 0.02), and 9.19% (95% CI: -13.95 to -4.43]), respectively, favoring the CTG. PD was the only parameter that favored the AADM or XDM with an overall mean of 0.03 mm (95% CI: -0.05 to 0.11). In all, if the long-term stability is the goal, the CTG is considered superior for gingival recession therapy. However, if it is contraindicated, the AADM and XDM might be considered as alternatives.


ACE gene insertion/deletion polymorphism associated with 1998 World Health Organization definition of metabolic syndrome in Chinese type 2 diabetic patients.
Because ACE insertion/deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and because plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes, the goal of this study was to investigate whether ACE gene I/D polymorphism is associated with metabolic syndrome in Chinese subjects with type 2 diabetes. A total of 711 patients with type 2 diabetes and 750 control subjects were studied. The ACE I/D polymorphism was determined by PCR. The definition and criteria of metabolic syndrome used in this study matched those proposed in the 1998 World Health Organization classification. Of 711 patients with type 2 diabetes, 534 (75.1%) fulfilled the criteria for metabolic syndrome. The prevalence of metabolic syndrome in control subjects with II, ID, and DD genotype was 9.4, 11.5, and 15.4%, respectively, and in patients with type 2 diabetes, it was 68.6, 79.2, and 86.1%, respectively. The ACE I/D polymorphism was significantly associated with the syndrome in patients with type 2 diabetes (P = 0.001). When pooling the control subjects with diabetic patients, the prevalence of metabolic syndrome in the whole study group with II, ID, and DD genotype was 37.9, 44.5, and 51.0%, respectively, and ACE I/D polymorphism was still significantly associated with metabolic syndrome (P = 0.003). Diabetic patients with DD genotype were also found to have a higher prevalence of dyslipidemia (II/ID/DD = 43.1/53.1/65.8%, P < 0.001) and albuminuria (36.0/44.6/50.6%, P = 0.018) and to have higher serum triglyceride levels (II, ID, and DD = 155 +/- 114, 170 +/- 140, and 199 +/- 132 mg/dl, respectively, P < 0.05). Control subjects with DD genotype were also found to have a higher prevalence of albuminuria or more advanced nephropathy (II/ID/DD = 5.7/14.0/15.4%, P = 0.001), whereas the prevalence of dyslipidemia was not found to be statistically different in the control group. When pooling control with diabetic subjects, ACE genotype could still be significantly associated with dyslipidemia (II/ID/DD = 34.7/41.3/52.2%, P < 0.001) and albuminuria or more advanced nephropathy (20.3/28.9/33.1%, P < 0.001). Diabetic patients with metabolic syndrome were found to have higher serum uric acid levels than those without metabolic syndrome (6.4 +/- 1.8 vs. 5.3 +/- 1.4 mg/dl, P < 0.01). The ACE I/D polymorphism was found to be associated with metabolic syndrome in Chinese patients with type 2 diabetes. This finding may provide genetic evidence to explain the clustering of metabolic syndrome and suggests that the renin-angiotensin system is involved in the pathophysiology of metabolic derangement in patients with type 2 diabetes.


CROSS-RESISTANCE FOLLOWING ARTIFICIAL SELECTION FOR INCREASED DEFENSE AGAINST PARASITOIDS IN DROSOPHILA MELANOGASTER.
An increase in resistance to one natural enemy may result in no correlated change, a positive correlated change, or a negative correlated change in the ability of the host or prey to resist other natural enemies. The type of specificity is important in understanding the evolutionary response to natural enemies and was studied here in a Drosophila-paxasitoid system. Drosophila melanogaster lines selected for increased larval resistance to the endoparasitoid wasps Asobara tabida or Leptopilina boulardi were exposed to attack by A. tabida, L. boulardi and Leptopilina heterotoma at 15°C, 20°C, and 25°C. In general, encapsulation ability increased with temperature, with the exception of the lines selected against L. boulardi, which showed the opposite trend. Lines selected against L. boulardi showed large increases in resistance against all three parasitoid species, and showed similar levels of defense against A. tabida to the lines selected against that parasitoid. In contrast, lines selected against A. tabida showed a large increase in resistance to A. tabida and generally to L. heterotoma, but displayed only a small change in their ability to survive attack by L. boulardi. Such asymmetries in correlated responses to selection for increased resistance to natural enemies may influence host-parasitoid community structure.


Global Composition of the Bacteriophage Community in Honey Bees.
The microbial communities in animal digestive systems are critical for host development and health. They stimulate the immune system during development, synthesize important chemical compounds like hormones, aid in digestion, competitively exclude pathogens, etc. Compared to the bacterial and fungal components of the microbiome, we know little about the temporal and spatial dynamics of bacteriophage communities in animal digestive systems. Recently, the bacteriophages of the honey bee gut were characterized in two European bee populations. Most of the bacteriophages described in these two reports were novel, harbored many metabolic genes in their genomes, and had a community structure that suggests coevolution with their bacterial hosts. To describe the conservation of bacteriophages in bees and begin to understand their role in the bee microbiome, we sequenced the virome of Apis mellifera from Austin, TX, and compared bacteriophage compositions among three locations around the world. We found that most bacteriophages from Austin are novel, sharing no sequence similarity with anything in public repositories. However, many bacteriophages are shared among the three bee viromes, indicating specialization of bacteriophages in the bee gut. Our study, along with the two previous bee virome studies, shows that the bee gut bacteriophage community is simple compared to that of many animals, consisting of several hundred types of bacteriophages that primarily infect four of the dominant bacterial phylotypes in the bee gut. IMPORTANCE Viruses that infect bacteria (bacteriophages) are abundant in the microbial communities that live on and in plants and animals. However, our knowledge of the structure, dynamics, and function of these viral communities lags far behind our knowledge of their bacterial hosts. We sequenced the first bacteriophage community of honey bees from the United States and compared the U.S. honey bee bacteriophage community to those of samples from Europe. Our work is an important characterization of an economically critical insect species and shows how bacteriophage communities can contain highly conserved individuals and be highly variable in composition across a wide geographic range.


Clozapine Management in Schizophrenia Inpatients: A 5-Year Prospective Observational Study of Its Safety and Tolerability Profile.
Clozapine is well known for its efficacy and clinical superiority compared to other antipsychotics in treatment-resistant schizophrenia (TRS). However, it is frequently underutilized worldwide because of its acute adverse events, as well as for its long-term cardiometabolic and hematological consequences. The aim of the study was to evaluate 5-year safety in chronic TRS inpatients with continuous clozapine use. Patients with TRS and clozapine treatment were evaluated for 5 years. All participants were assessed using the Brief Psychiatric Rating Scale (BPRS), Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C), Social Performance Scale (PSP) and Short Portable Mental Status Questionnaire (SPMSQ). Clinical, cardiometabolic and hematological data were collected periodically. General linear models (GLM) repeated measures controlling for CLZ dose were utilized to determine differences in variables across the time. Overall, 189 inpatients were screened for study participation. The final sample included twenty-one TRS patients (16 males, 76%) with an average age of 57.6 years, all with 5-year continuous use of clozapine (mean dose 266 mg/day). There was not a significant effect of time on BPRS (p=0.774), PSP (p=0.855) and SPMSQ (p=0.066); differences remained not significant after controlling for CLZ dose (p=0.585, p=0.467 and p=0.105, respectively). No changes were found in blood and clinical parameters except for red blood cell count, which decreased over time (p=0.024; η2= 0.952). Patients reported a significant BMI decrease (-8.98 kg, p=0.008) between baseline and 5 years last observation. The findings show how the application of a structured dietary, clinical and therapeutic monitoring program in psychiatric care facilities could allow the safe and effective long-term cardiometabolic and hematological management of clozapine. The unique role that clozapine plays in the current treatment of patients with TRS requires greater clinical awareness. Although its acute and chronic side effects are notorious, its safety management is feasible and broadens its potential practical application.


Comparative studies of O2 and N2 in pure, mixed and layered CO ices.
We present laboratory data on pure, layered and mixed CO and O2 ices relevant for understanding the absence of gaseous O2 in space. Experiments have been performed on interstellar ice analogues under ultra high vacuum conditions by molecular deposition at 14 K on a gold surface. A combination of reflection absorption infrared spectroscopy (RAIRS) and temperature programmed desorption (TPD) is used to derive spectroscopic and thermodynamic properties of the ices. It is found that for pure ices the desorption energy of O2 is larger than that of CO and N2. TPD spectra reveal similar desorption processes for all examined CO-O2 ice morphologies. The different amorphous and crystalline components of pure 13CO RAIR spectra are analyzed. The RAIRS data of the 13CO stretching vibration show a significant difference between layered and mixed CO-O2 ices: layered CO-O2 ices resemble that of pure 13CO whereas the spectra of mixed ices are broadened. The experiments also show that the sticking probabilities of O2 on CO and O2 on O2 are close to unity. These new results are compared with recently analyzed data of CO-N2 ices. The differences in the TPD and RAIRS spectra of the CO-N2 and CO-O2 ice systems are explained by differences in quadrupole intermolecular interactions and by different crystallization processes of these ices.


Network of microRNA, transcription factors, target genes and host genes in human mesothelioma.
Significant progress has been made into the elucidation of the etiology of mesothelioma at the level of the genes and miRNA. Nevertheless, researchers in this field remain unable to systematically construct a network that demonstrates the specific relationships between genes, miRNA and transcription factors (TFs). TFs are key regulatory elements that control gene expression. In the present study, according to the transcriptional regulatory rule, three regulatory networks were constructed using experimentally validated elements to explore the pathogenesis of mesothelioma. We focused on the regulatory relationship between the miRNA and its host gene, the miRNA and its target gene, and the miRNA and TFs. Expressed, related and global networks were constructed, and the similarities and differences between them were analyzed. Notably, the differentially expressed network used in the present study, which was based on experimentally validated data, contained numerous incorrect expression signal pathways for the pathogenesis of mesothelioma. In theory, if these errors are corrected, this cancer may be prevented or cured. Subsequent analysis of the differentially expressed nodes and pathways may help to explain the pathogenesis of mesothelioma. Notably, some of these exhibited a self-adaption relationship, which was detected by listing the upstream and downstream elements in a table with differentially expressed genes and miRNA. The findings of the present study demonstrated detailed transcriptional regulation, which may serve as a reference to aid further elucidation of the pathogenesis of mesothelioma.


Non-invasive assessment of liver fibrosis in C282Y homozygous HFE hemochromatosis.
C282Y homozygotes with serum ferritin (SF) levels >1000 μg/L and/or increased serum transaminase levels are at risk of severe F3/F4 fibrosis. Current practical guidelines recommend liver biopsy in such individuals. This prospective observational cohort study aimed to evaluate non-invasive alternative means such as hyaluronic acid (HA) and transient elastography (TE) for the assessment of severe fibrosis in patients with SF >1000 μg/L or elevated transaminases. Between September 2005 and April 2013, 77 patients diagnosed C282Y homozygotes underwent a liver biopsy because of SF >1000 μg/L and/or increased transaminases according to current guidelines, with concomitant TE. All of them had clinical and biological evaluation, including HA measurement in 52 cases. A total of 19.5% of patients had F3-F4 severe fibrosis. HA was higher in patients with severe fibrosis, but did not accurately predict severe fibrosis. TE was significantly higher in patients with severe fibrosis (17.2 vs. 4.9 kPa; P < 0.05) and was able to accurately predict fibrosis stage in 47/61 (77%) patients with valid measurement using a lower threshold of 6.4 kPa and an upper threshold of 13.9 kPa. Efficient assessment of severe fibrosis was not possible in patients with intermediate TE values. An algorithm that successively employed SF and TE can accurately classify severe fibrosis in 61% of patients, restricting the need for liver biopsy to the 39% of patients with intermediate or unvalid TE values. This algorithm should be validated in independent cohorts before extended use.


Standardized assessment of reading performance: the New International Reading Speed Texts IReST.
There is a need for standardized texts to assess reading performance, for multiple equivalent texts for repeated measurements, and for texts equated across languages for multi-language studies. Paragraphs are preferable to single sentences for accurate speed measurement. We developed such texts previously in 6 languages. The aim of our current study was to develop texts in more languages for a wide range of countries and users, and to assess the reading speeds of normally-sighted readers. Ten texts were designed for 17 languages each by a linguist who matched content, length, difficulty, and linguistic complexity. The texts then were used to assess reading speeds of 436 normally-sighted native speakers (age 18-35 years, 25 per language, 36 in Japanese), presented at a distance of 40 cm and size 1 M, that is 10-point Times New Roman font. Reading time (aloud) was measured by stopwatch. For all 17 languages, average mean reading speed was 1.42 ± 0.13 texts/min (±SD), 184 ± 29 words/min, 370 ± 80 syllables/min, and 863 ± 234 characters/min. For 14 languages, mean reading time was 68 ms/character (95% confidence interval [CI] 65-71 ms). Our analysis focussed on words per minute. The variability of reading speed within subjects accounts only for an average of 11.5%, between subjects for 88.5%. The low within-subject variability shows the equivalence of the texts. The IReST (second edition) can now be provided in 17 languages allowing standardized assessment of reading speed, as well as comparability of results before and after interventions, and is a useful tool for multi-language studies (for further information see www.amd-read.net).


Novel Semisynthetic Derivatives of Bile Acids as Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.
An Important task in the treatment of oncological and neurodegenerative diseases is the search for new inhibitors of DNA repair system enzymes. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is one of the DNA repair system enzymes involved in the removal of DNA damages caused by topoisomerase I inhibitors. Thus, reducing the activity of Tdp1 can increase the effectiveness of currently used anticancer drugs. We describe here a new class of semisynthetic small molecule Tdp1 inhibitors based on the bile acid scaffold that were originally identified by virtual screening. The influence of functional groups of bile acids (hydroxy and acetoxy groups in the steroid framework and amide fragment in the side chain) on inhibitory activity was investigated. In vitro studies demonstrate the ability of the semisynthetic derivatives to effectively inhibit Tdp1 with IC50 up to 0.29 µM. Furthermore, an excellent fit is realized for the ligands when docked into the active site of the Tdp1 enzyme.


KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression.
Hepatic lipid metabolism is controlled by integrated metabolic pathways. Excess accumulation of hepatic TG is a hallmark of nonalcoholic fatty liver disease, which is associated with obesity and insulin resistance. Here, we show that KH-type splicing regulatory protein (KSRP) ablation reduces hepatic TG levels and diet-induced hepatosteatosis. Expression of period 2 (Per2) is increased during the dark period, and circadian oscillations of several core clock genes are altered with a delayed phase in Ksrp(-/-) livers. Diurnal expression of some lipid metabolism genes is also disturbed with reduced expression of genes involved in de novo lipogenesis. Using primary hepatocytes, we demonstrate that KSRP promotes decay of Per2 mRNA through an RNA-protein interaction and show that increased Per2 expression is responsible for the phase delay in cycling of several clock genes in the absence of KSRP. Similar to Ksrp(-/-) livers, both expression of lipogenic genes and intracellular TG levels are also reduced in Ksrp(-/-) hepatocytes due to increased Per2 expression. Using heterologous mRNA reporters, we show that the AU-rich element-containing 3' untranslated region of Per2 is responsible for KSRP-dependent mRNA decay. These findings implicate that KSRP is an important regulator of circadian expression of lipid metabolism genes in the liver likely through controlling Per2 mRNA stability.


QSAR studies applied to the prediction of antigen-antibody interaction kinetics as measured by BIACORE.
The objective of this work was to investigate the potential of the quantitative structure-activity relationships (QSAR) approach for predictive modulation of molecular interaction kinetics. A multivariate QSAR approach involving modifications in peptide sequence and buffer composition was recently used in an attempt to predict the kinetics of peptide-antibody interactions as measured by BIACORE. Quantitative buffer-kinetics relationships (QBKR) and quantitative sequence-kinetics relationships (QSKR) models were developed. Their predictive capacity was investigated in this study by comparing predicted and observed kinetic dissociation parameters (k(d)) for new antigenic peptides, or in new buffers. The range of experimentally measured k(d) variations was small (300-fold), limiting the practical value of the approach for this particular interaction. However, the models were validated from a statistical point of view. In QSKR, the leave-one-out cross validation gave Q(2) = 0.71 for 24 peptides (all but one outlier), compared to 0.81 for 17 training peptides. A more precise model (Q(2) = 0.92) could be developed when removing sets of peptides sharing distinctive structural features, suggesting that different peptides use slightly different binding modes. All models share the most important factor and are informative for structure-kinetics relationships. In QBKR, the measured effect on k(d) of individual additives in the buffers was consistent with the effect predicted from multivariate buffers. Our results open new perspectives for the predictive optimization of interaction kinetics, with important implications in pharmacology and biotechnology.


Derivation of induced pluripotent stem cells from orangutan skin fibroblasts.
Orangutans are an endangered species whose natural habitats are restricted to the Southeast Asian islands of Borneo and Sumatra. Along with the African great apes, orangutans are among the closest living relatives to humans. For potential species conservation and functional genomics studies, we derived induced pluripotent stem cells (iPSCs) from cryopreserved somatic cells obtained from captive orangutans. Primary skin fibroblasts from two Sumatran orangutans were transduced with retroviral vectors expressing the human OCT4, SOX2, KLF4, and c-MYC factors. Candidate orangutan iPSCs were characterized by global gene expression and DNA copy number analysis. All were consistent with pluripotency and provided no evidence of large genomic insertions or deletions. In addition, orangutan iPSCs were capable of producing cells derived from all three germ layers in vitro through embryoid body differentiation assays and in vivo through teratoma formation in immune-compromised mice. We demonstrate that orangutan skin fibroblasts are capable of being reprogrammed into iPSCs with hallmark molecular signatures and differentiation potential. We suggest that reprogramming orangutan somatic cells in genome resource banks could provide new opportunities for advancing assisted reproductive technologies relevant for species conservation efforts. Furthermore, orangutan iPSCs could have applications for investigating the phenotypic relevance of genomic changes that occurred in the human, African great ape, and/or orangutan lineages. This provides opportunities for orangutan cell culture models that would otherwise be impossible to develop from living donors due to the invasive nature of the procedures required for obtaining primary cells.


Sparkling Organic Phosphorescence from Fluorinated Tetrathia[7]helicenes: Synthesis and Photophysical, Electrochemical and Computational Studies.
Structure-property correlations in the thiahelicene family are often not trivial beacuse most of the functional groups present on the helical scaffold modify the conjugation size of the π-system. Selecting fluorine-containing groups to provide strong inductive effects without interacting with low-lying orbitals of the system could be the way to overcome the issue. Here we report a study on three fluorine-functionalized tetrathia[7]helicenes, highlighting interesting correlations between the position of the functional groups and the conjugated skeleton properties. Helicenes Heli-F2 and Heli-CF-F2 were prepared by photoinduced isomerization-electrocyclization (the Mallory photocyclization) of the corresponding fluorinated benzodithienyl-ethenes Alk-F2 and Alk-CF-F2, which were prepared in high yields through stereo-conservative Stille reaction. Notably these helicenes were found to display green phosphorescence around 530-550 nm, and the studies suggest an efficient spin-orbit coupling mechanism in these high-energy triplet nonplanar conjugated molecules. Both helicenes and their precursors were thoroughly characterized by means of optical and electrochemical measurements, while DFT calculations enable a rationale on their structure-property correlations to be defined.


Efficacy and Safety of Half-Dose Gadopiclenol versus Full-Dose Gadobutrol for Contrast-enhanced Body MRI.
Background Gadopiclenol is a macrocyclic gadolinium-based contrast agent (GBCA) with higher relaxivity compared with standard GBCAs, potentially allowing gadolinium dose reduction without decreasing efficacy. Purpose To investigate whether gadopiclenol at 0.05 mmol/kg is noninferior to gadobutrol at 0.1 mmol/kg for lesion visualization in body MRI. Materials and Methods A randomized, double-blind, crossover, phase 3 study was conducted between August 2019 and December 2020 at 33 centers in 11 countries. Adults with at least one suspected focal lesion in one of three different body regions (head and neck; breast, thorax, abdomen, or pelvis; or musculoskeletal system) underwent two contrast-enhanced MRI examinations, randomized to start with either gadopiclenol or gadobutrol. MRI examinations were read by three blinded expert readers for each respective body region. Readers rated border delineation, internal morphologic characteristics, and visual contrast enhancement. Three additional blinded readers assessed reader preference. For safety analysis, adverse events were recorded. The differences between gadopiclenol- and gadobutrol-enhanced MRI in terms of lesion visualization were analyzed with a generalized linear mixed model using a two-sided paired t test. Results Among 273 participants (mean age, 57 years ± 13 [SD]; 162 women) who underwent both gadopiclenol- and gadobutrol-enhanced MRI and had at least one correlating lesion, 260 participants without major protocol deviations were analyzed for noninferiority. Gadopiclenol was noninferior to gadobutrol for all qualitative visualization parameters and for all readers (lower limit 95% CI of the difference of at least -0.10, which was above the noninferiority margin [-0.35]; P < .001). For most participants (75%-83% [206-228 of 276]), readers reported no preference between gadopiclenol- and gadobutrol-enhanced images. Adverse events did not differ in frequency, intensity, type, or association with GBCA injection (12 of 288 participants receiving gadopiclenol and 16 of 290 receiving gadobutrol). Conclusion Gadopiclenol at 0.05 mmol/kg was comparable with gadobutrol at 0.1 mmol/kg for lesion evaluation at contrast-enhanced body MRI and had a similar safety profile. Clinical trial registration no. NCT03986138 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Bashir and Thomas in this issue.


Ag(e)ing and Degradation of Supercapacitors: Causes, Mechanisms, Models and Countermeasures.
The most prominent and highly visible advantage attributed to supercapacitors of any type and application, beyond their most notable feature of high current capability, is their high stability in terms of lifetime, number of possible charge/discharge cycles or other stability-related properties. Unfortunately, actual devices show more or less pronounced deterioration of performance parameters during time and use. Causes for this in the material and component levels, as well as on the device level, have only been addressed and discussed infrequently in published reports. The present review attempts a complete coverage on these levels; it adds in modelling approaches and provides suggestions for slowing down ag(e)ing and degradation.


Chronic fatigue syndrome/myalgic encephalomyelitis as a twentieth-century disease: analytic challenges.
The challenges of chronic fatigue syndrome (often called myalgic encephalomyelitis, especially in the UK) (CFS/ME) to analytical and medical approaches are connected with our inability to understand its distressing somatic symptoms in terms of a single identifiable and understandable disease entity. The evidence for the roles of viral aetiologies remains inconclusive, as does our understanding of the involvement of the immune system. The history and social context of CFS/ME, and its relation to neurasthenia and psychasthenia are sketched. A symbolic attitude to the condition may need to be rooted in an awareness of psychoid levels of operation, and the expression and spread of CFS/ME may sometimes be aided by the ravages of projective identification. Psychic denial, sometimes violent, in sufferers (especially children and adolescents) and their families may be important in the aetiology of CFS/ME. We draw out common threads from psychodynamic work with five cases, four showing some symptomatic improvement, analytic discussions of three cases being presented elsewhere in this issue of JAP.


Coexistence of a mature teratoma and mucinous cystadenocarcinoma in the same ovary--a case report.
A case of right sided abdominal lump with pain in a 45 years female was presented. Radiological investigation revealed a multiloculated cystic mass with a few mural nodules arising from right ovary. The tumor was removed by exploratory laparotomy and histopathological examination showed coexistence of dermoid cyst with mucinous cystadenocarcinoma in the same ovary. Left ovary and uterus was healthy and there was no tumor extension or omental deposits. Postoperative period was uneventful.


Microwave de-embedding techniques applied to acoustics.
This paper describes the use of the microwave techniques of time domain reflectometry (TDR) and de-embedding in an acoustical application. Two methods of calibrating the reflectometer are presented to evaluate the consistency of the method. Measured and modeled S-parameters of woodwind instruments are presented. The raw measured data is de-embedded to obtain an accurate measurement. The acoustic TDR setup is described.


Nondisjunction of chromosome 15: origin and recombination.
Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N = 27) and Angelman syndrome patients (N = 5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination are utilized. Standard methods of centromere mapping are employed to determine the level of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, most paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome.


Eucommia ulmoides Oliver leaf extract increases endogenous antioxidant activity in type 2 diabetic mice.
Eucommia ulmoides Oliver (Du-zhong) leaf extract was investigated for its antioxidant effects in type 2 diabetic animals, C57BL/KsJ-db/db mice. Du-zhong extract equivalent to 1% dried whole Du-zhong leaf (0.187 g of extract/100 g of diet) was added to the experimental diets for 6 weeks. The Du-zhong extract supplement significantly lowered blood glucose concentrations and elevated plasma paraoxonase activity compared with the control group. The activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly higher in the Du-zhong group compared with the control group, while glutathione reductase (GR) activity was not different between groups. The activities of SOD, GSH-Px, and GR in liver and kidney were not affected by Du-zhong extract supplementation, whereas the CAT activity was significantly higher in the Du-zhong group than in the control group. Du-zhong extract supplementation resulted in lower levels of hydrogen peroxide and lipid peroxide in erythrocytes, liver, and kidney. These results suggest that the antioxidant activity of Du-zhong extract is potentially beneficial for the prevention and management of complications of type 2 diabetes.


The effect of universal fluorinated nucleobases on the catalytic activity of ribozymes.
Four fluoro modified universal nucleobases have been synthesized. The universal nucleobases 1 and 2, containing a 2,4-difluorobenzene as nucleobase and a 4,6-difluorobenzimidazole, respectively, were chemically incorporated into a selected hammerhead ribozyme sequence which has already been retrovirally expressed as an anti-HIV ribozyme to investigate their effect on the catalytic activity of the ribozymes. The substitution of the natural nucleosides with either 1 or 2 results only in a small decrease of the catalytic activity. The Km value for the monosubstituted ribozyme with a 2,4-difluorobenzene is 309 nM(-1), the corresponding kcat is 2.91 x 10(-3) min(-1). A disubstituted hammerhead ribozyme carrying one of each modification has also been synthesized. For a further stabilization of the ribozyme/substrate complex 2'-(beta-aminoethoxy) modified fluorinated nucleosides 15 and 16 have been developed.


Overlap among Spatial Memories Triggers Repulsion of Hippocampal Representations.
Across the domains of spatial navigation and episodic memory, the hippocampus is thought to play a critical role in disambiguating (pattern separating) representations of overlapping events. However, it is not fully understood how and why hippocampal patterns become separated. Here, we test the idea that event overlap triggers a "repulsion" among hippocampal representations that develops over the course of learning. Using a naturalistic route-learning paradigm and spatiotemporal pattern analysis of human fMRI data, we found that hippocampal representations of overlapping routes gradually diverged with learning to the point that they became less similar than representations of non-overlapping events. In other words, the hippocampus not only disambiguated overlapping events but formed representations that "reversed" the objective similarity among routes. This finding, which was selective to the hippocampus, is not predicted by standard theoretical accounts of pattern separation. Critically, because the overlapping route stimuli that we used ultimately diverged (so that each route contained overlapping and non-overlapping segments), we were able to test whether the reversal effect was selective to the overlapping segments. Indeed, once overlapping routes diverged (eliminating spatial and visual similarity), hippocampal representations paradoxically became relatively more similar. Finally, using a novel analysis approach, we show that the degree to which individual hippocampal voxels were initially shared across route representations was predictive of the magnitude of learning-related separation. Collectively, these findings indicate that event overlap triggers a repulsion of hippocampal representations-a finding that provides critical mechanistic insight into how and why hippocampal representations become separated.


Incidence rate of hypokalemic and its associated factors for patients undergoing noncardiac surgery: a retrospective analysis.
Hypokalemia is common in hospitalized patients. In fact, untreated hypokalemia is associated with the incidence and mortality of adverse cardiac events. Timely recognition and treatment of these diseases are essential. Indeed, a little research has been conducted on the level of K+ in perioperative patients. In this study, by comparing the changes of K+ from when patients were admitted to hospital and to after they had entered the operating room, we analyzed the related factors of K+ disorder after operating-room entry and identified factors related to the occurrence of perioperative K+ disorder. This single-center retrospective study included non-cardiac surgery patients who underwent admission blood gas analysis and blood gas analysis upon entering the operating room in the China-Japan Union Hospital of Jilin University between June 2019 and September 2020. Among the 258 patients who underwent non-cardiac surgery with anesthesia, 19 cases (7.4%) were hypokalemic on admission, and 102 cases (39.5%) were hypokalemic after admission to the operating room. The K+ levels after operating-room entry were positively correlated with the K+ concentration at admission (r=0.363; P<0.05). Female sex [odds ratio (OR) =0.451; 95% CI: 0.263-0.775; P=0.004], hypertension (OR =0.499; 95% CI: 0.281-0.885; P=0.017), and preoperative bowel preparation (OR =0.471; 95% CI: 0.258-0.860; P=0.014) were risk factors for hypokalemia for patients after operating-room entry. Hypokalemia was found to be common in patients after operating-room entry. Even patients with normal K+ at admission could have hypokalemia due to undergoing an operation, with female sex, hypertension, and bowel preparation being the risk factors for this condition.


The role of cytokines in the pathogenesis of systemic lupus erythematosus - from bench to bedside.
The pathogenesis of systemic lupus erythematosus (SLE) entails a complex interaction between the different arms of the immune system. While autoantibodies production and immune complex deposition are cornered as hallmark features of SLE, there is growing evidence to propose the pathogenic role of cytokines in this disease. Examples of these cytokines include BLys, interleukin-6, interleukin-17, interleukin-18, type I interferons and tumour necrosis factor alpha. These cytokines all assume pivotal functions to orchestrate the differentiation, maturation and activation of various cell types, which would mediate local inflammatory process and tissue injury. The knowledge on these cytokines not only fosters our understanding of the disease, but also provides insights in devising biomarkers and targeted therapies. In this review, we focus on cytokines which have substantial pathogenic significance and also highlight the possible clinical applications of these cytokines.


A Comparison of Ultrasonography, Computerised Tomography, and Conventional MRI Findings for Splenic Nodules Associated with Type 1 Gaucher's Disease with Diffusion-Weighted MRI Findings.
A 26-year-old female patient with Type 1 Gaucher's disease (GD) was admitted to our clinic with complaints of stomachache and signs of anemia. The patient underwent ultrasonography (US), computerised tomography (CT), and magnetic resonance imaging (MRI) scan. Imaging studies revealed massive hepatosplenomegaly, choledocolithiasis, and six nodules in the spleen with a mean size of 14 mm. The nodules appeared hyperechoic, hypoechoic, and of mixed echogenicity on the US and hypodense on the CT. While the nodules were observed to be iso-hypointense in T1-weighted (T1WI) images, they appeared to be hyperintense in the T2-weighted (T2WI) images. There were no diffusion restrictions in these nodules that appeared on the diffusion-weighted magnetic resonance imaging (DWI). A nodule located at the lower pole was observed to be hypointense in the T2WI images. The nodule located at the lower pole, which appeared hypointense in T2WI series, had restricted diffusion upon DWI. In this study, we aimed to present the properties of splenic GD nodules using US, CT, and conventional MRI, together with DWI. This case report is the first to apply US, CT, and conventional MRI, together with DWI, to the splenic nodules associated with Gaucher's disease.


[Experimental model producing global brain ischemia by clamping the aorta in dogs].
Canine cerebral blood flow is supplied not only through carotid and vertebral arteries, but also through rich network of collaterals. Therefore, it is said that total body arrest is requested to assure the global brain ischemia. The global ischemic models, reported previously, were by the simultaneous occlusion of aorta and vena cava. In our model, however, the global cerebral ischemia was produced by clamping only the ascending aorta. Cardiovascular changes such as increases in left ventricular and pulmonary arterial pressure, and decrease in left ventricular dp/dt followed after ceasing of ascending aortic blood stream. The heart continued to beat during 60 minutes of the clamping. Despite of increased central venous pressure, sagittal sinus pressure and intracranial pressure remained unchanged during the aorta clamping. Ten-minutes of total cerebral ischemia was produced in 46 dogs and successful studies on cerebral and systemic variables were carried out in 68% of them. The method of clamping the aorta without occlusion of vena cava seems to be unsuitable for long term survival study because of severe loading of lung circulation. However, we conclude that this simple model is of great use for short term experiment on global brain ischemia.


Annexin A1 Is a Key Modulator of Mesenchymal Stromal Cell-Mediated Improvements in Islet Function.
We have previously demonstrated that coculture of islets with mesenchymal stromal cells (MSCs) enhanced islet insulin secretory capacity in vitro, correlating with improved graft function in vivo. To identify factors that contribute to MSC-mediated improvements in islet function, we have used an unbiased quantitative RT-PCR screening approach to identify MSC-derived peptide ligands of G-protein-coupled receptors that are expressed by islets cells. We demonstrated high expression of annexin A1 (ANXA1) mRNA by MSCs and confirmed expression at the protein level in lysates and MSC-conditioned media by Western blot analysis and ELISA. Preculturing islets with exogenous ANXA1 enhanced glucose-stimulated insulin secretion (GSIS), thereby mimicking the beneficial influence of MSC preculture in vitro. Small interfering RNA-mediated knockdown of ANXA1 in MSCs reduced their capacity to potentiate GSIS. MSCs derived from ANXA1(-/-) mice had no functional capacity to enhance GSIS, in contrast to wild-type controls. Preculturing islets with ANXA1 had modest effects on their capacity to regulate blood glucose in streptozotocin-induced diabetic mice, indicating that additional MSC-derived factors are required to fully mimic the beneficial effects of MSC preculture in vivo. These findings demonstrate the feasibility of harnessing the MSC secretome as a defined, noncellular strategy to improve the efficiency of clinical islet transplantation protocols.


Synchronization on Erdös-Rényi networks.
In this Brief Report, by analyzing the spectral properties of the Laplacian matrix of Erdös-Rényi networks, we obtained the critical coupling strength of the complete synchronization analytically. In particular, for any size of the networks, when the average degree is greater than a threshold and the coupling strength is large enough, the networks can synchronize. Here, the threshold is determined by the value of the maximal Lyapunov exponent of each dynamical unit.


Excessive drinking among African American men: individual and contextual correlates.
In this article, the authors explored associations of multiple domains with regular drinking and getting drunk among adult African American men. Questionnaire-based, computer-assisted interviews were conducted with 484 men in Atlanta, Georgia. Data analysis involved multivariate logistic regression analyses. Findings show that being older increased the odds of both drinking behaviors. Sensation seeking increased the odds of regular drinking, and having experienced childhood sexual and physical abuse increased the odds of getting drunk. Having health insurance reduced the odds of both outcomes. Insurance coverage and the heterogeneity among adult African American men must be considered in risk reduction efforts.


Estimated dietary iodine intake as a predictor of placental size: evidence from the ELSPAC study.
The relationship between low iodine status and pregnancy-associated comorbidities has been known for decades. The relationship between iodine intake and placental pathologies is, however, far less clear. This study was designed to examine the relationship between dietary iodine intake and placental size while also focusing on typical adverse pregnancy outcomes. The dietary iodine intake of 4711 pregnant women enrolled in the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) in 1990-1991 was established using a 145-item food frequency questionnaire. Multivariate linear regression models were used to estimate the relationship between dietary iodine intake during pregnancy and placental weight. Additional models were constructed to investigate the relationship between estimated dietary iodine intake and adverse birth outcomes. The estimated average iodine intake in the ELSPAC cohort was 106.6 μg/day. In the fully adjusted model, estimated dietary iodine intake was found to be significantly negatively associated with placental weight (β = -0.025, 95% CI: -0.044; -0.006, p = 0.011). Moreover, estimated dietary iodine intake was found to be significantly positively associated with the birth weight / placental weight ratio in the fully adjusted model (β = -0.024, 95% CI: 0.004; 0.043, p = 0.016). This study provides evidence of a relationship between estimated dietary iodine intake and placental weight and the birth weight / placental weight ratio. Additional research is warranted to provide more insight into the role of iodine in early as well as late placentation.