Quantum Mechanics/Extremely Localized Molecular Orbital Method: A Fully Quantum Mechanical Embedding Approach for Macromolecules.
The development of methods for the quantum mechanical study of macromolecules has always been an important challenge in theoretical chemistry. Nowadays, the techniques proposed in this context can be used to investigate very large systems and can be subdivided into two main categories: fragmentation and embedding strategies. In this paper, by modifying and improving the local self-consistent field approach originally proposed for quantum mechanics/molecular mechanics techniques, we introduce the new multiscale embedding quantum mechanics/extremely localized molecular orbital (QM/ELMO) method. The new strategy enables treatment of chemically relevant regions of large biological molecules through usual methods of quantum chemistry while describing the remaining parts of the systems by means of frozen extremely localized molecular orbitals transferred from properly constructed libraries. Test calculations have shown the correct functioning and the high reliability of the new approach, thus anticipating its possible applications to different fields of physical chemistry, such as rational drug design and structural refinements of proteins.


Interaction between cisplatin and gemcitabine in vitro and in vivo.
Both gemcitabine (2',2'-difluorodeoxycytidine; dFdC) and cisplatin (cis-diammine dichloroplatinum; CDDP) are active against several solid malignancies, including ovarian cancer and head and neck squamous cell carcinoma. Because of differences in mechanisms of action and toxicity profiles, combination of the two drugs has enormous clinical potential. We studied possible synergism between the drugs: in vitro using three variants of the human ovarian cancer cell line A2780, and in vivo using gemcitabine- and cisplatin-sensitive and -resistant tumors, the head and neck cancer xenografts HNX-22B and HNX-14C and the murine syngeneic colon 26-10 tumor. In vitro, cells were cultured for 72 hours and exposed to the drugs for 1 to 72 hours; synergy was evaluated by multiple drug-effect analysis. In wild-type A2780 and cisplatin-resistant ADDP cells, simultaneous exposure for 24 and 72 hours was synergistic, as well as preincubation with cisplatin for 4 hours followed by gemcitabine. Preincubation with gemcitabine for 4 hours followed by gemcitabine and cisplatin was synergistic in ADDP and A2780 cells. Cisplatin did not enhance the accumulation of gemcitabine triphosphate in A2780 and ADDP cells. Cisplatin caused a marginal decrease of the number of double strand breaks in the DNA caused by gemcitabine. In vivo, gemcitabine at the maximum tolerated dose of 100 or 120 mg/kg could be combined with cisplatin at 4 mg/kg. When injected simultaneously this resulted in at least additive anti-tumor activity in HNX-22B, but not in HNX-14C and colon 26-10 tumors. Cisplatin, injected 4 hours before or after gemcitabine, was equally active as the simultaneous schedule in HNX-22B tumors, but more toxic. In conclusion, the combination of gemcitabine and cisplatin can be synergistic in vitro and at least additive in vivo; this synergism is schedule dependent. The mechanism cannot be explained by gemcitabine triphosphate accumulation or DNA damage studies.


Fluorescent immunolabeling of cancer cells by quantum dots and antibody scFv fragment.
Semiconductor quantum dots (QDs) coupled with cancer-specific targeting ligands are new promising agents for fluorescent visualization of cancer cells. Human epidermal growth factor receptor 2/neu (HER2/neu), overexpressed on the surface of many cancer cells, is an important target for cancer diagnostics. Antibody scFv fragments as a targeting agent for direct delivery of fluorophores offer significant advantages over full-size antibodies due to their small size, lower cross-reactivity, and immunogenicity. We have used quantum dots linked to anti-HER2/neu 4D5 scFv antibody to label HER2/neu-overexpressing live cells. Labeling of target cells was shown to have high brightness, photostability, and specificity. The results indicate that construction based on quantum dots and scFv antibody can be successfully used for cancer cell visualization.


Organization, feasibility and patient appreciation of a follow-up consultation in surgical critically ill patients with favorable baseline quality of life and prolonged ICU-stay: a pilot study.
Intensive care unit (ICU) survivors are often left with impairments in physical, mental and cognitive functioning (Post-Intensive Care Syndrome (PICS)). We evaluated the organization, the feasibility for caregivers and patients and the patients' appreciation of a post-ICU consultation aiming to detect these PICS-symptoms. A single-center prospective observational pilot study was conducted during an 18 month-period in the surgical ICU of a tertiary care hospital. Consecutive adult patients with an ICU-stay of ≥8 days and a favorable baseline quality of life (utility index ≥0.6 on EQ-5D-3 L) were eligible for inclusion. A post-ICU follow-up consultation consisting of a structured interview was scheduled 3 months after hospital discharge. Characteristics of the consultation (CG) and no consultation group (NCG) were compared. P-values <0.05 were considered significant. Of 133 eligible patients, 85 (64%) consented for the study and 42 (49%) attended the consultation. A total of 148 phone calls were made to schedule the consultations. Consultations took a median of 68 (61-74) minutes. Compared to CG-patients, NCG-patients were more often discharged to a care facility (P = 0.003) and had more problems with mobility (P = 0.014), self-care (P < 0.001) and usual activities (P = 0.005) after 3 months. At least one PICS-related problem was documented in all patients in the CG and NCG. Thirty-four CG-patients (81%) appreciated the initiative. Organizing an ICU-follow-up consultation was difficult and feasibility was low, but most attending patients appreciated the initiative. Better developed structures for ICU-follow-up are needed in view of the high number of PICS-related problems documented.


Protective effect of lycopene on oxidative stress and antioxidant status in Cyprinus carpio during cypermethrin exposure.
The aim of this study was to investigate the ameliorative properties of lycopene against the toxic effects of cypermethrin (CYP) by examining oxidative damage markers such as lipid peroxidation and the antioxidant defense system components in carp (Cyprinus carpio). The fish were divided into seven groups of 10 fish each and received the following treatments: group 1, no treatment; group 2, orally administered corn oil; group 3, oral lycopene (10 mg/kg body weight); group 4, exposure to 0.202 μg/L CYP; group 5, exposure to 0.202 μg/L CYP plus oral administration of 10 mg/kg lycopene; group 6, exposure to 0.404 μg/L CYP; and group 7, exposure to 0.404 μg/L CYP plus oral administration of 10 mg/kg lycopene. Treatment was continued for 28 days, and at the end of this period, blood and tissue (liver, kidney, and gill) samples were collected. Levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were determined in blood and tissues for measurement of oxidant-antioxidant status. MDA level, as an index of lipid peroxidation, increased in blood and tissues. Antioxidant enzyme activities in blood and tissues were modified in CYP groups compared with controls. Administration of lycopene ameliorated these parameters. The present results suggest that administration of lycopene might alleviate CYP-induced oxidative stress.


Babesia microti Aldo-keto Reductase-Like Protein Involved in Antioxidant and Anti-parasite Response.
The intraerythrocytic apicomplexan Babesia microti is the primary causative agent of human babesiosis, which is an infectious disease that occurs in various regions around the world. Although the aldo-keto reductases (AKRs) of this parasite have been sequenced and annotated, their biological properties remain unknown. AKRs are a superfamily of enzymes with diverse functions in the reduction of aldehydes and ketones. In the present study, we cloned the full-length cDNA of a B. microti aldo-keto reductase-like protein (BmAKR) and analyzed the deduced amino acid sequence of the BmAKR protein. This protein has a conserved AKR domain with an N-terminal signal sequence. Bmakr was upregulated on the 8th day after infection, whereas it was downregulated during the later stages. The recombinant protein of BmAKR was expressed in a glutathione S-transferase-fused soluble form in Escherichia coli. Western blot analysis showed that the mouse anti-BmAKR antibody recognized native BmAKR from a parasite lysate. Immunofluorescence microscopy localized BmAKR to the cytoplasm of B. microti merozoites in mouse RBCs in this study. Bmakr expression was significantly upregulated in the presence of oxidant stress. Atovaquone, a known anti-babesiosis drug, and robenidine, a known anti-coccidiosis drug, induced upregulation of Bmakr mRNA, thereby suggesting that Bmakr may be involved in anti-parasite drug response.


Kinetic Isotope Effects Provide Experimental Evidence for Proton Tunneling in Methylammonium Lead Triiodide Perovskites.
The occurrence of proton tunneling in MAPbI3 hybrid organic inorganic perovskites is demonstrated through the effect of isotopic labeling of the methylammonium (MA) component on the dielectric permittivity response. Deuteration of the ammonium group results in the acceleration of proton migration (inverse primary isotope effect), whereas deuteration of the methyl group induces a normal secondary isotope effect. The activation energies for proton migration are calculated to be 50 and 27 meV for the tetragonal and orthorhombic phases, respectively, which decrease upon deuteration of the ammonium group. The low activation barrier and the deviation from unity of the ratio of the pre-exponential factors (AH/AD = 0.3-0.4) are consistent with a tunneling mechanism for proton migration. Deuteration of the PEDOT:PSS hole transport layer results in a behavior that is intermediate between that of the deuterated and undeuterated perovskite, due to extrinsic ion migration between the two materials.


The (decision) tree of fertility: an innovative decision-making algorithm in assisted reproduction technique.
Several mathematical models have been developed to estimate individualized chances of assisted reproduction techniques (ART) success, although with limited clinical application. Our study aimed to develop a decisional algorithm able to predict pregnancy and live birth rates after controlled ovarian stimulation (COS) phase, helping the physician to decide whether to perform oocytes pick-up continuing the ongoing ART path. A single-center retrospective analysis of real-world data was carried out including all fresh ART cycles performed in 1998-2020. Baseline characteristics, ART parameters and biochemical/clinical pregnancies and live birth rates were collected. A seven-steps systematic approach for model development, combining linear regression analyses and decision trees (DT), was applied for biochemical, clinical pregnancy, and live birth rates. Of fresh ART cycles, 12,275 were included. Linear regression analyses highlighted a relationship between number of ovarian follicles > 17 mm detected at ultrasound before pick-up (OF17), embryos number and fertilization rate, and biochemical and clinical pregnancy rates (p < 0.001), but not live birth rate. DT were created for biochemical pregnancy (statistical power-SP:80.8%), clinical pregnancy (SP:85.4%), and live birth (SP:87.2%). Thresholds for OF17 entered in all DT, while sperm motility entered the biochemical pregnancy's model, and female age entered the clinical pregnancy and live birth DT. In case of OF17 < 3, the chance of conceiving was < 6% for all DT. A systematic approach allows to identify OF17, female age, and sperm motility as pre-retrieval predictors of ART outcome, possibly reducing the socio-economic burden of ART failure, allowing the clinician to perform or not the oocytes pick-up.


Recurrence of extreme serum analytes in consecutive pregnancies and association with obstetrical outcomes.
To evaluate if presence of extreme maternal serum biochemical analytes recurs in consecutive pregnancies. We hypothesized that presence of >1 extreme analyte in prior pregnancy is associated with increased risk of adverse pregnancy outcome in subsequent pregnancy. Retrospective cohort study of singleton pregnancies evaluated and delivered in 2 consecutive pregnancies (2011-2015). Adverse outcomes were defined as indicated preterm delivery before 37 completed weeks due to preeclampsia, fetal growth restriction or other complications. First and second trimester maternal serum analytes were assessed in 1434 patients in 2 consecutive pregnancies. The presence of >1 extreme serum analyte in prior pregnancy significantly increased likelihood of >1 extreme analyte in subsequent pregnancy. The likelihood increased as number of prior extreme markers increased. In patients with normal outcomes and 2 or more extreme serum analytes in prior pregnancy, there was an increased incidence of adverse pregnancy outcomes in subsequent pregnancy with relative risk (RR) of 5.42 [95% CI 1.6-18.3]. The presence of more than 1 extreme serum marker in one pregnancy increases likelihood of recurrence in subsequent pregnancies. Risk of adverse outcomes in subsequent pregnancy can be evaluated based on biochemistry results as well as prior pregnancy outcomes.


Adult retrospective report of child abuse and prospective indicators of childhood harm: a population birth cohort study.
We aim to determine whether adult retrospective report of child abuse is associated with greater risk of prospectively assessed harmful environments in childhood. We assessed possible recall basis by adult depression status. At 45 years, participants of the 1958 British birth cohort (N = 9308) reported a range of abuse types (by 16 years). Prospective data, ages 7-16 years, were obtained for impoverished upbringing, hazardous conditions, anti-social behaviours and 16 years poor parent-child relationships. We estimated associations between retrospective report of child abuse and prospectively measured harm using (i) odds ratios (ORs, 95% confidence intervals) and (ii) positive predictive values (PPVs). PPVs were calculated stratified by adult depression status. Prevalence of retrospectively reported abuse ranged from 10.7% (psychological) to 1.60% (sexual) and 14.8% reported ≥ 1 type; prospectively recorded harm ranged from 10% (hazardous conditions/poor parent-child relationships) to 20% (anti-social behaviours). Adults retrospectively reporting abuse were more likely to have had harmful childhood environments: 52.4% had ≥ 1 indicator of harm (vs. 35.6% among others); ORsex-adjusted for poor relationships with parents was 2.98 (2.50, 3.54). For retrospectively reported (vs. none) abuse, there was a trend of increasing relative risk ratio with number of harms, from 1.75 (1.50, 2.03) for 1 to 4.68 (3.39, 6.45) for 3/4 childhood harms. The PPV of ≥ 1 prospectively recorded harm did not differ between depressed (0.58 (0.52, 0.64)) and non-depressed (0.58 (0.55, 0.61)) groups. In a population cohort, adult retrospective report of child abuse was associated with several harms, prospectively measured from childhood to adolescence, providing support for the validity of retrospective report-based research. Findings suggest retrospectively reported child abuse is not biased by depression in adulthood.


Immunodeficiency in Down's syndrome: low levels of serum thymic factor in trisomic children.
The activity of thymus-dependent serum factor SF was significantly lower in 18 children wit Down's syndrome (DS) than in 14 matched controls. The percentage of circulating T lymphocytes forming E-rosettes was also low in DS. Together with the previous finding of immature of T lymphocytes in peripheral blood, the present data suggest that the basic immune defect of DS is failure in differentiation of peripheral post-thymic precursors to fully immunocompetent T lymphocytes resulting from lack of thymic hormonal factors.


Radiation and concurrent carboplatin administration in locally advanced head and neck cancer. A Hellenic Cooperative Oncology Group Study.
To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation. Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n = 10), hypopharynx (n = 5), larynx (n = 12), oral cavity (n = 2), paranasal sinuses (n = 3), salivary glands (n = 1) and unknown (n = 1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42. Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received > 66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25). Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.


Cardiac magnetic resonance imaging.
All four cardiac valves can be imaged using MRI. Gradient-echo imaging is the preferred mode of imaging. Valvular regurgitation seen as an area of signal loss in the more proximal chamber can be diagnosed with a high degree of accuracy when compared with 2-D Doppler echocardiography and catheterization angiography. Aortic and mitral stenosis can be semiquantitatively diagnosed, but no method for determining valve areas is currently available. Cardiac prosthetic valves can be imaged but appear only as localized signal loss. Prosthetic valve regurgitation can be diagnosed in the same way as native valve regurgitation. At present, MRI, though not a widely used modality, can contribute significantly to the diagnosis of cardiac valve disorders. With the addition of fast magnetic resonance scanning, which can eliminate the need for electrocardiographic gating, it will be possible for patients with cardiac rhythm irregularities to be scanned, thus broadening the base of patients with valve disease who can be diagnosed.


Evidence that nitric oxide can act centrally to stimulate vasopressin release.
Nitric oxide (NO) is the endothelium-derived relaxing factor, which causes relaxation of vascular smooth muscle. NO synthetase, the enzyme for the synthesis of NO from its precursor L-arginine, is also widely distributed in neurons in the brain, and it has been suggested that NO may serve as an important neuromodulator. Because NO synthetase is present in the hypothalamus in relatively high concentration, we have determined whether NO can affect the release of vasopressin in conscious, chronically prepared rats. The intracerebroventricular (i.c.v.) injection of S-nitroso-N-acetylpenicillamine (12.5 and 25 micrograms; SNAP), that spontaneously breaks down to form NO, caused transient dose-related increases in the plasma vasopressin concentration of 1 and 2 microU/ml (p < 0.01), respectively. In control experiments in which N-acetylpenicillamine (25 micrograms), the precursor for the preparation of SNAP, was injected i.c.v. there was a small, 0.4 microU/ml, increase (p < 0.01) in the plasma vasopressin level. The i.c.v. injection of L-arginine (0.5 and 1 mg), also the precursor for the biosynthesis of NO, resulted in dose-dependent increases in the plasma vasopressin concentration similar in magnitude to those caused by SNAP. When D-arginine (1 mg), which cannot serve as a substrate for NO synthetase, was injected i.c.v., there was only a slight delayed increase in the plasma vasopressin concentration. Thus, NO can act centrally to stimulate vasopressin release and may serve as a neuromodulator in the control of vasopressin release.


First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection.
There is evidence that schizophrenia is characterized by activation of the immune-inflammatory response (IRS) and compensatory immune-regulatory systems (CIRS) and lowered neuroprotection. Studies performed on antipsychotic-naïve first episode psychosis (AN-FEP) and schizophrenia (FES) patients are important as they may disclose the pathogenesis of FES. However, the protein-protein interaction (PPI) network of FEP/FES is not established. The aim of the current study was to delineate a) the characteristics of the PPI network of AN-FEP and its transition to FES; and b) the biological functions, pathways, and molecular patterns, which are over-represented in FEP/FES. Toward this end, we used PPI network, enrichment, and annotation analyses. FEP and FEP/FES are strongly associated with a response to a bacterium, alterations in Toll-Like Receptor-4 and nuclear factor-κB signaling, and the Janus kinases/signal transducer and activator of the transcription proteins pathway. Specific molecular complexes of the peripheral immune response are associated with microglial activation, neuroinflammation, and gliogenesis. FEP/FES is accompanied by lowered protection against inflammation, in part attributable to dysfunctional miRNA maturation, deficits in neurotrophin and Wnt/catenin signaling, and adherens junction organization. Multiple interactions between reduced brain derived neurotrophic factor, E-cadherin, and β-catenin and disrupted schizophrenia-1 (DISC1) expression increase the vulnerability to the neurotoxic effects of immune molecules, including cytokines and complement factors. In summary: FEP and FES are systemic neuro-immune disorders that are probably triggered by a bacterial stimulus which induces neuro-immune toxicity cascades that are overexpressed in people with reduced anti-inflammatory and miRNA protections, cell-cell junction organization, and neurotrophin and Wnt/catenin signaling.


Effects of a 6 Week Yoga Intervention on Executive Functioning in Women Screening Positive for Adult ADHD: A Pilot Study.
Little is known about the effects of yoga training in adults with ADHD symptoms. This pilot study sought to determine the feasibility and selected psychological effects of 6 weeks of yoga training in women screening positive for adult ADHD compared to a wait-list control group. A randomized trial was conducted with 32 adult women (18-24 years) who volunteered after screening positive for adult ADHD as assessed by the Adult ADHD Self-Report Scale (ASRS). Participants were randomized to 6 weeks of Bikram yoga training or to a wait-list control group. The yoga intervention consisted of two 90-min classes per week. Multilevel models were used to test hypothesized interactions of yoga-induced improvements compared to controls across time (baseline, 3 weeks, and 6 weeks). The primary outcomes assessed inhibitory control, cognitive flexibility and working memory using the NIH Toolbox. Separate models with trait mindfulness, trait anxiety and expectations for change in either attention or working memory as covariates tested whether these variables mediated the changes in the three measures of executive function. Secondary outcomes included mood, perceived functional impairment and motivation for, and hyperactivity during, the cognitive tests. No adverse events were observed. Attendance averaged 91.7% among the 69% of the sample that did not dropout. No significant Group X Time interactions were found for any of the psychological outcomes and the null executive function findings were unchanged when including the covariates. Six-weeks of yoga training twice per week is potentially feasible for women experiencing ADHD symptoms, but an exercise stimulus of this duration and magnitude yields no beneficial cognitive or mood outcomes.


Experimental evaluation of the FluChip diagnostic microarray for influenza virus surveillance.
Global surveillance of influenza is critical for improvements in disease management and is especially important for early detection, rapid intervention, and a possible reduction of the impact of an influenza pandemic. Enhanced surveillance requires rapid, robust, and inexpensive analytical techniques capable of providing a detailed analysis of influenza virus strains. Low-density oligonucleotide microarrays with highly multiplexed "signatures" for influenza viruses offer many of the desired characteristics. However, the high mutability of the influenza virus represents a design challenge. In order for an influenza virus microarray to be of utility, it must provide information for a wide range of viral strains and lineages. The design and characterization of an influenza microarray, the FluChip-55 microarray, for the relatively rapid identification of influenza A virus subtypes H1N1, H3N2, and H5N1 are described here. In this work, a small set of sequences was carefully selected to exhibit broad coverage for the influenza A and B viruses currently circulating in the human population as well as the avian A/H5N1 virus that has become enzootic in poultry in Southeast Asia and that has recently spread to Europe. A complete assay involving extraction and amplification of the viral RNA was developed and tested. In a blind study of 72 influenza virus isolates, RNA from a wide range of influenza A and B viruses was amplified, hybridized, labeled with a fluorophore, and imaged. The entire analysis time was less than 12 h. The combined results for two assays provided the absolutely correct types and subtypes for an average of 72% of the isolates, the correct type and partially correct subtype information for 13% of the isolates, the correct type only for 10% of the isolates, false-negative signals for 4% of the isolates, and false-positive signals for 1% of the isolates. In the overwhelming majority of cases in which incomplete subtyping was observed, the failure was due to the nucleic acid amplification step rather than limitations in the microarray.


Conformational Change from U- to I-Shape of Ion Transporters Facilitates K+ Transport across Lipid Bilayers.
We have investigated, at the atomic level, the ion-fishing mechanism underlying the ion transport across membranes mediated by an artificial ion transporter composed of a hydroxyl-rich cholesterol group, a flexible alkyl chain, and a crown ether. Our results show that the transporter can spontaneously insert into the membrane and switch between the folded (U-shaped) and extended (I-shaped) conformations. The free-energy profile associated with the conformational transition indicates that compared with the U-shaped conformation of the transporter, the I-shaped one is thermodynamically more favorable. Furthermore, the free-energy profiles describing the ion translocation reveal that the transporter capturing the ion in U-shape on one side of the membrane and releasing it in I-shape on the other side constitutes a key way for the highly efficient transport of K+ ions. We present herewith a rigorous and rational framework to decipher the detailed ion-fishing mechanism of transmembrane ion transport with exceptionally high activity.


[Surgical treatment of Essex-Lopresti injury].
To summarize operative procedure and the effectiveness of open reduction with internal fixation or radial head replacement for the treatment of Essex-Lopresti injury. Between November 2002 and October 2010, 10 patients with Essex-Lopresti injury were treated. There were 8 males and 2 females with a mean age of 36 years (range, 20-56 years). Eight cases were fresh closed fracture within 2 days. According to Mason classification, 5 fracture were type II, 3 were type III. The other 2 cases were old fracture within 3 months. Wrist joint X-ray revealed that all the patients had distal radioulnar joint dislocation. Open reduction with internal mini-plate or absorbable screw fixation was performed in 5 cases, and radial head replacement in 5 cases; meanwhile, the distal radioulnar joint was reduced and fixed. All incisions healed by first intention without infection or bone nonunion. The patients were followed up 7 to 24 months with an average of 14.7 months. The X-ray films showed fracture healing at 9-20 weeks (mean, 16.3 weeks); distal radioulnar joint was stable without shortening or shift of proximal radius. According to elbow clinical evaluation system, the results were excellent in 5 cases, good in 3 cases, and fair in 2 cases. According to wrist clinical evaluation, the results were excellent in 7 cases, good in 2 cases, and fair in 1 case. All patients had good elbow stability, and recovered quickly. Early diagnosis, operation, and functional exercises are important to obtain an excellent result in treating Essex-Lopresti injury.


Horner's Syndrome: A Case Report and Review of the Pathophysiology and Clinical Features.
Tumours of the superior sulcus of the lung, commonly referred to as Pancoast tumours, present with characteristic clinical symptoms and signs. An interesting case of a patient who presented with such a tumour is presented. The pathophysiology, clinical features and approach to management are reviewed.


CoBold: a method for identifying different functional classes of transient RNA structure features that can impact RNA structure formation in vivo.
RNA structure formation in vivo happens co-transcriptionally while the transcript is being made. The corresponding co-transcriptional folding pathway typically involves transient RNA structure features that are not part of the final, functional RNA structure. These transient features can play important functional roles of their own and also influence the formation of the final RNA structure in vivo. We here present CoBold, a computational method for identifying different functional classes of transient RNA structure features that can either aid or hinder the formation of a known reference RNA structure. Our method takes as input either a single RNA or a corresponding multiple-sequence alignment as well as a known reference RNA secondary structure and identifies different classes of transient RNA structure features that could aid or prevent the formation of the given RNA structure. We make CoBold available via a web-server which includes dedicated data visualisation.


Old world monkeys and new age science: the evolution of nonhuman primate systems virology.
Nonhuman primate (NHP) biomedical models are critical to our understanding of human health and disease, yet we are still in the early stages of developing sufficient tools to support primate genomic research that allow us to better understand the basis of phenotypic traits in NHP models of disease. A mere 7 years ago, the limited NHP transcriptome profiling that was being performed was done using complementary DNA arrays based on human genome sequences, and the lack of NHP genomic information and immunologic reagents precluded the use of NHPs in functional genomic studies. Since then, significant strides have been made in developing genomics capabilities for NHP research, from the rhesus macaque genome sequencing project to the construction of the first macaque-specific high-density oligonucleotide microarray, paving the way for further resource development and additional primate sequencing projects. Complete published draft genome sequences are now available for the chimpanzee ( Chimpanzee Sequencing Analysis Consortium 2005), bonobo ( Prufer et al. 2012), gorilla ( Scally et al. 2012), and baboon ( Ensembl.org 2013), along with the recently completed draft genomes for the cynomolgus macaque and Chinese rhesus macaque. Against this backdrop of both expanding sequence data and the early application of sequence-derived DNA microarrays tools, we will contextualize the development of these community resources and their application to infectious disease research through a literature review of NHP models of acquired immune deficiency syndrome and models of respiratory virus infection. In particular, we will review the use of -omics approaches in studies of simian immunodeficiency virus and respiratory virus pathogenesis and vaccine development, emphasizing the acute and innate responses and the relationship of these to the course of disease and to the evolution of adaptive immunity.


Advanced Control Synthesis for Reverse Osmosis Water Desalination Processes.
In this study, robust control synthesis has been applied to a reverse osmosis desalination plant whose product water flow and salinity are chosen as two controlled variables. The reverse osmosis process has been selected to study since it typically uses less energy than thermal distillation. The aim of the robust design is to overcome the limitation of classical controllers in dealing with large parametric uncertainties, external disturbances, sensor noises, and unmodeled process dynamics. The analyzed desalination process is modeled as a multi-input multi-output (MIMO) system with varying parameters. The control system is decoupled using a feed forward decoupling method to reduce the interactions between control channels. Both nominal and perturbed reverse osmosis systems have been analyzed using structured singular values for their stabilities and performances. Simulation results show that the system responses meet all the control requirements against various uncertainties. Finally the reduced order controller provides excellent robust performance, with achieving decoupling, disturbance attenuation, and noise rejection. It can help to reduce the membrane cleanings, increase the robustness against uncertainties, and lower the energy consumption for process monitoring.


The prevalence and management of low back pain across adulthood: results from a population-based cross-sectional study (the MUSICIAN study).
The aim of the current study was to determine: the prevalence of low back pain (LBP) and associated disability; the frequency of consultation to general practice; whether there were differences in management by age. We conducted a cross-sectional population study in Aberdeen city and Cheshire County, UK. Participants were 15,272 persons aged 25 years and older. The 1-month period prevalence of LBP was 28.5%. It peaked at age 41-50 years, but at ages over 80 years was reported by 1 in 4 persons. Older persons were more likely to consult, and the prevalence of severe LBP continued to increase with age. Management by general practitioners differed by age of the patient. Older persons (> 70 vs ≤ 40 years) were more likely to only have been prescribed painkillers (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.28-2.35) or only pain killers with other medications (OR 1.45, 95% CI 1.07-1.98). They were less likely to be prescribed physiotherapy or exercise (OR 0.63, 95% CI 0.46-0.85) or to be referred to a specialist (OR 0.77, 95% CI 0.57-1.04). Older persons were more likely to have previously received exercise therapy for pain, were less likely to be enthusiastic about receiving it now (P<0.0001), and were less likely to think it would result in improved symptoms (P<0.0001). It is important that older persons, who have the highest prevalence of LBP with disability and are most likely to consult, are receiving optimal pharmacological and nonpharmacological management.


Vaginismus in peri- and postmenopausal women: a pragmatic approach for general practitioners and gynaecologists.
Vaginismus is generally described as an involuntary contraction of the vaginal musculature, which usually results in the failure of penetration. Despite a lack of consensus as to the exact definition, prevalence rates vary between 4.2% and 42%. It is commonly diagnosed at both gynaecological and psychosexual clinics. The majority of studies and treatment options concentrate on the premenopausal age group. It is accepted that even within this age group, the diagnosis is often incorrect as symptoms can be confused with dyspareunia and other sexual pain disorders. There is no literature discussing vaginismus in the postmenopausal patient, despite evidence that an active sex life is important to the majority of women, irrespective of age. It is known that the majority of women do not report difficulties in their sex life and it may be that the older patient is more embarrassed at disclosing any such difficulties. This review aims to highlight the possible causes of vaginismus in this older age group and to aid the clinician in asking the appropriate questions, performing the appropriate examination and suggesting possible treatment options.


[Research on the recombinant plasmid pDJH2 of L. interrogans serovar lai: sequencing and alignment with other known bacterial Omp sequence].
The Leptospira whole cell vaccine (LWCV) currently used in China is safe and effective, out the immunity following vaccination with two doses of the fluid medium vaccine is of low order. The duration of immunity conferred by this vaccine is rather short, six months or at most one year. Therefore, it is necessary to develop new generation vaccines against Leptospirosis for the developing world. In this paper we report the sequencing of the insert fragment of pDJH2 from genomic DNA of L. interrogans sevovar lai strain 017 and its alignment with other bacterial omp sequences. A genomic library of Leptospira interrogaans serovar lai strain 017 was constructed with the plasmid vector pUC18. A recombinant plasmid designated pJDH2 was screened from the genomic library. Inserted fragment of pDH2 is 1.9 kb by gel electrophoresis. Immunization/protection was studied in BALB/c mice model. The results showed highly significant difference between pDJH2 and pUC18 (control). Inserted fragment of pDJH2 DNA sequencing was performed by Dr Yan Zhengxin (Max-Planck-Institut for Biology. Tubingen, Germany). Insert fragment was cloned into pBluescript II KS-(stratagene) and sequenced by using AB1 (Applied Bio Systems, Model 373A). Two open reading frames of 565 and 662 nucleotides were identified. There were identifiable initiation codons, terminators, Shine-Dalgano ribosome combining site, Pribnow boxes and Sextama boxes within the 2 sequenced regions. Nucleotide sequences were analysed using Gene Work, a suit of computer program developed by Department of Biochemistry St. Jude Children's Research Hospital Memphis. U.S.A. The results of formatted alignment showed the predicted nucleotide sequence of ORF1 of the serovar lai had significant similarity with ORF2 (49.36%). L. kirschneri ompL1 (49.26%), Borrelia burgdoferi omp (48.97%), Treponema phagedenis omp (47.3%); Salmonella typhimurium ompC(46.87%), Yersinia enterocolitica ompH (46.7%), Leptospira borgpeterseni pfap (46.3%), and Serratia marcescens omp (43.3%). The close relationship of the pDJH2 ORF1 and ORF2 nucleotide sequences from Leptospira kirschneri ompL 1 is apparent. Whether the recombinant pDJH2 will prove useful for vaccine development remains to be tested.


MdMADS6 Recruits Histone Deacetylase MdHDA19 to Repress the Expression of the Carotenoid Synthesis-Related Gene MdCCD1 during Fruit Ripening.
Fruit ripening is regulated by epigenetic modifications and transcription factors, which may function independently or as protein complexes. Our previous study showed that the apple histone deacetylase19 (MdHDA19) suppresses fruit ripening through the deacetylation of histones in related genes. Here, a MADS-box transcription factor (MdMADS6) was identified using a yeast two-hybrid (Y2H) assay as a candidate protein that interacts with MdHDA19 during apple fruit ripening. Furthermore, Y2H, bimolecular fluorescence complementation (BiFC) and pull-down assays were used to confirm the interaction between MdHDA19 and MdMADS6. Agrobacterium-mediated transient transformation and yeast one-hybrid assays showed that MdMADS6 promoted carotenoid accumulation in apple fruit by acting on the downstream target genes related to carotenoid biosynthesis. In summary, we conclude that, in the early stages of fruit development, the expression of MdMADS6 was maintained at lower levels, where it interacted with MdHDA19 to form a protein complex that inhibited the expression of the downstream genes. At the late stages of fruit development, active expression of MdMADS6 dissociated the protein complex of MdMADS6 and MdHDA19 and consequently promoted the expression of carotenoid biosynthesis genes as well as carotenoid accumulation.


The neuroprotective and anti-inflammatory effects of diltiazem in spinal cord ischaemia-reperfusion injury.
The protective effects of diltiazem were examined in a rabbit model of spinal cord ischaemia-reperfusion induced by infrarenal aortic occlusion for 30 min. In the diltiazem group (n = 6), an intravenous infusion (2 microg/kg per min) was started 10 min before ischaemia induction; normal saline solution was infused in the control group (n = 6). Neurological function was assessed using modified Tarlov criteria 24 h after surgery. Plasma samples were analysed for interleukin (IL)-6 and IL-10. Spinal tissue was analysed for malondialdehyde, nitric oxide and reduced glutathione activities. Tarlov scores of the diltiazem-treated rabbits indicated significantly improved hind-limb motor function compared with the control group. The diltiazem group also had better quantitative and qualitative histopathological findings. Diltiazem infusion significantly reduced IL-6 levels 3 and 24 h after reperfusion compared with the control group. The mean IL-10 level in the diltiazem group was significantly higher than in the control group 24 h after reperfusion. It is concluded that diltiazem has cytoprotective and anti-inflammatory properties, leading to reduced spinal cord injury.


Dental hygienists' knowledge, opinions, and use of pit and fissure sealants: a comparison of two states.
This article reports results of a study of 563 practicing Minnesota and Wisconsin dental hygienists' knowledge, opinions, and use of pit and fissure sealants. The study was carried out six months prior to the 1983 NIH Consensus Development Conference on Dental Sealants in the Prevention of Tooth Decay. It therefore provides baseline information for two states prior to the initiation of widespread public information about the positive value of sealants that occurred as a result of that conference. Such baseline information is relevant for future studies of the diffusion of adoption of this caries-preventive technology by dental hygienists. Two independent samples were selected randomly from the populations of licensed dental hygienists residing in the two states. Data were collected using a 42-item mailed questionnaire, with an 84 percent response. Data were analyzed for both interstate and intrastate comparisons. Respondents were generally knowledgeable and had favorable opinions about sealants, although they had low levels of training in their use. Sealants were being used in 54 percent of the offices in which respondents practiced, with the dentist placing them most often. Among hygienists who applied sealants at all, more than two-thirds did so three or fewer times per week. Eighty-four percent indicated they would like to apply sealants more often. The most frequent reasons given for nonuse were lack of acceptance by the dentist-employer and nondelegation.


Mortality and Disease in Wild Turkeys ( Meleagris gallopavo silvestris) in Ontario, Canada, from 1992 to 2014: A Retrospective Review.
Wild turkeys ( Meleagris gallopavo silvestris) were extirpated from Ontario, Canada, in the early 1900s due to unregulated over-hunting and habitat loss. Despite a successful reintroduction program and strong population numbers, information regarding the health of wild turkeys in Ontario is scarce. A 22-yr (1992-2014) retrospective study was performed to evaluate diagnostic data, including the cause(s) and contributors to death, in wild turkeys submitted to the Ontario-Nunavut node of the Canadian Wildlife Health Cooperative (n = 56). Noninfectious diagnostic findings (39/56; 69.6%) were more common than infectious, with emaciation recognized most frequently (n = 19; 33.9%) followed by trauma (n = 11, 19.6%). The majority of deaths due to emaciation occurred in winter and spring (17/18; 94.4%), which is consistent with lack of access to or availability of food resources. Morbidity and mortality due to infectious diseases was diagnosed in 16 (28.6%) wild turkeys. Avian poxvirus was the most common infectious cause of disease (n = 7; 12.5%), followed by bacterial infections (n = 5; 8.9%), the most common of which was Pasteurella multocida . Zinc phosphide toxicosis (n = 7; 12.5%) occurred in two incidents involving multiple birds. This study aims to provide baseline data that can be used for reference and comparison in future wild turkey disease surveillance and population monitoring studies.


Expression of cytokine receptors on follicular dendritic cells.
Follicular dendritic cells (FDCs) in the lymphoid follicle (LF) are essential to the sequential processes of B-cell proliferation, selection, and differentiation. Although the importance of some cytokines in these processes has been pointed out, there is little information about the follicular localization of their receptors. We investigated, with special reference to FDCs, the localization of cytokine receptors as well as cytokines themselves in human tonsils by several means, including immunochemistry, immunoelectron microscopy, reverse transcriptase polymerase chain reaction, and in situ hybridization. FDCs in the follicular apical light zone expressed transforming growth factor-beta receptor II (TGF-betaR II), granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFRalpha; CDw116), tumor necrosis factor receptor I (TNFR I; CD120a), interleukin-1 receptor II (IL-1R II; CDw121b), IL-2 receptor beta (IL-2Rbeta; CD122), IL-4 receptor (IL-4R; CDw124), and IL-6 receptor (IL-6R; CD126), among the 10 receptors examined. Those in the basal light zone expressed strongly TNFR I and weakly GM-CSFR alpha, IL-1R II, IL-2Rbeta, IL-4R, and IL-6R, and often those in the outer and mantle zones expressed GM-CSFR alpha, IL-4R, and IL-6R. FDCs in the apical light zone expressed only TGF-beta among the 7 cytokines examined. On the other hand, follicular lymphocytes mainly in the light zone expressed 9 kinds of receptors, with the exception being TGF-betaR II; expression was rather frequent for TNF-alpha, IL-1alpha, and IL-2 and less frequent for TGF-beta, GM-CSF, IL-4, and IL-6. These data indicate that only FDCs mainly in the light zone express many cytokine receptors, although FDCs may produce the cytokine, TGF-beta. Cytokines may act not only on some follicular lymphocytes but also on most FDCs in the light zone expressing cytokine receptors.


RASSF2 methylation is a strong prognostic marker in younger age patients with Ewing sarcoma.
Ras-association domain family of genes consist of 10 members (RASSF1-RASSF10), all containing a Ras-association (RA) domain in either the C- or the N-terminus. Several members of this gene family are frequently methylated in common sporadic cancers; however, the role of the RASSF gene family in rare types of cancers, such as bone cancer, has remained largely uninvestigated. In this report, we investigated the methylation status of RASSF1A and RASSF2 in Ewing sarcoma (ES). Quantitative real-time methylation analysis (MethyLight) demonstrated that both genes were frequently methylated in Ewing sarcoma tumors (52.5% and 42.5%, respectively) as well as in ES cell lines and gene expression was upregulated in methylated cell lines after treatment with 5-aza-2'-deoxcytidine. Overexpression of either RASSF1A or RASSF2 reduced colony formation ability of ES cells. RASSF2 methylation correlated with poor overall survival (p = 0.028) and this association was more pronounced in patients under the age of 18 y (p = 0.002). These results suggest that both RASSF1A and RASSF2 are novel epigenetically inactivated tumor suppressor genes in Ewing sarcoma and RASSF2 methylation may have prognostic implications for ES patients.


[Comparison of percutaneous manual and endoscopic laser diskectomy with chemonucleolysis and automated nucleotomy].
The combination of percutaneous manual and endoscopic Ho:YAG laser discectomy (PELD) is a new minimal intervention technique in treating patients with herniated lumbar discs that do not penetrate the posterior longitudinal ligament. The results in 100 patients treated with PELD were compared randomly with those in 100 patients treated by chemonucleolysis with chymopapain (CN) and 100 patients treated by automated percutaneous lumbar discectomy (APLD) at the same hospital. We followed the 300 patients postoperatively for 1 year, with physical examination, postoperative plain lumbosacral radiography, CT, MRI and a self-assessment questionnaire. Some 68% of the patients in the PELD group considered the outcome as excellent or good and 23% as fair; the corresponding figures were 55% and 27% in the CN group, and 48% and 32% in the APLD group. Nine percent of the patients in the PELD group underwent open microdiscectomy or were suffering from back pain with sciatica, compared with 18% in the CN group and 20% in the APLD group. PELD showed better extraction of the hernia mass than APLD and a lower rate of low back pain and less decrease in disc height than CN.


Structural characteristics of goat (Capra hircus) parotid salivary glands.
The structural characteristics of the parotid glands in small ruminants (goat, sheep) were observed and compared to those of a major laboratory animal, the mouse. Their parotid glands consist of the purely serous type. Ultrastructurally, the serous acini of goats and sheep were characterized by the presence of well-developed basolateral expansions of folds, which are characteristics of electrolyte- and water-transporting epithelium. Moreover in ruminants, unlike the mouse, the presence of numerous intercellular canaliculi as well as microvilli projecting into both the intercellular canaliculi and the lumina of the serous acini provided a large surface area for osmotic equilibrium and isotonic saliva secretion. Most of the secretory granules in goats and sheep contained peripherally located inclusions that showed dense reaction products for acid phosphatase. This indicates that most of the secretory granules undergo lysosomal degradation rather than secretion. An apocrine mode of secretion of some secretory granules was occasionally observed in some acini of goats and sheep but only exocytotic features were observed in mice. In the goat, the serous acini showed three morphologically different types, which might be an indication of different activity phases. Furthermore, alpha-smooth muscle actin-, and vimentin-positive myoepithelial cells were observed only around the serous acini and the intercalated ducts. From these findings, we consider that the structural characteristics of ruminant parotid glands might reflect their physiological role in the copious isotonic saliva secretion with a low protein concentration.


The Ectodermal Dysplasias-Burden of Disease Score: Development and Validation of an Ectodermal Dysplasia Family/Parental Burden Score.
Ectodermal dysplasias are genetic conditions affecting the development and/or homeostasis of 2 or more ectodermal derivatives, including hair, teeth, nails, and certain glands. No tool is available to assess the burden of ectodermal dysplasias and its multidimensional impact on patients and their families. This study developed and validated a familial/parental 19-item burden questionnaire designed specifically for ectodermal dysplasias. Each group of questions was linked to 1 of the following dimensions: (i) Impact of the disease on social life and hobbies; (ii) Future prospects; (iii) Restraint of the disease on outdoor activities; (iv) Financial burden of the disease; (v) Acceptance of the disease. Cronbach's alpha was 0.91 for the entire Ectodermal Dysplasias-Burden of Disease (ED-BD) scale, confirming excellent internal coherence. Intradimensional coherences all demonstrated excellent reliability (α > 0.76). The ED-BD questionnaire was highly correlated with the Short Form-12 and Psychological General Well Being Index validated questionnaires. Cultural and linguistic validation in US English was conducted. Development and validation of the questionnaire was based on data from patients with the 2 main ectodermal dysplasias subtypes. This ED-BD questionnaire represents the first specific assessment tool for evaluating the familial/parental burden of ectodermal dysplasias.


Bacillus subtilis functional genomics: genome-wide analysis of the DegS-DegU regulon by transcriptomics and proteomics.
The DegS-DegU two-component regulatory system of Bacillus subtilis controls various processes that characterize the transition from the exponential to the stationary growth phase, including the induction of extracellular degradative enzymes, expression of late competence genes and down-regulation of the sigma(D) regulon. The degU32(Hy) mutation stabilizes the phosphorylated form of DegU (DegU-P), resulting in overproduction of several extracellular degradative enzymes. In this study, the pleiotropic DegS-DegU regulon was characterized by combining proteomic and transcriptomic approaches. A comparative analysis of wild-type B. subtilis and the degU32(Hy) mutant grown in complex medium was performed during the exponential and in the stationary growth phase. Besides genes already known to be under the control of DegU-P, novel putative members of this regulon were identified. Although the degU32(Hy) mutant is assumed to contain high levels of phosphorylated DegU in the exponential as well as in the stationary growth phase, many genes known to be positively regulated by DegU-P did not show enhanced expression in the mutant strain during exponential growth. This is consistent with the fact that most genes belonging to the DegS-DegU regulon are subject to multiple regulation; this is also reflected in the strong stationary-phase induction of these genes in the mutant strain. As expected, during the exponential growth phase, the sigma(D) regulon was expressed at significantly lower levels in the degU32(Hy) mutant than in the wild type.


Comparison of peritoneal dialysis solutions.
The composition of peritoneal dialysis solutions to a great extent, determine their effectiveness and safety. Many of the factors that determine the bioincompatibility of peritoneal dialysis fluids have been recently identified. This knowledge is essential to modify the manufacturing processes and in the quest for more biocompatible solutions. A description of the available peritoneal dialysis fluids in the United States and a comparison of their formulations are provided.


Disparities in prescription drug insurance coverage.
This article examines socioeconomic differences in supplementary insurance for prescription drugs among Canadians aged 15 or older and how the availability of such insurance affects prescription drug use. The data on prescription drug insurance coverage and drug use are from the cross-sectional Health file of the 1996/97 National Population Health Survey (NPHS) conducted by Statistics Canada. The sample size of the population aged 15 or older was 70,884. Rates of insurance coverage for prescription drug services were calculated. All summary estimates were age-adjusted using the 1996/97 population of Canada (both sexes). Among people aged 15 or older, 61% were covered for prescription medications in 1996/97. Sixty-five percent of workers reported coverage, while those who were not working were less likely to have benefits (52%). Only 38% of lower income groups had insurance compared with 74% of the highest income group. Regardless of the number of chronic diseases individuals had, those with drug insurance were more likely to report taking medication.


Role of rapid urease test and histopathology in the diagnosis of Helicobacter pylori infection in a developing country.
The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection. One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard test for the diagnosis of H. pylori infection was histopathology. Sixty-one percent (66/109) patients were males with mean age of 43 +/- 14.1 years and age range 17-80 years. Fifty-two percent (57/109) were not on any medications while 48% (52/109) used PPI before presentation to the outpatients. Pronto Dry was positive in 40% (44/109) and negative in 60% (65/109). Histopathology was positive for H. pylori in 57% (62/109) and negative in 43% (47/109). The sensitivity, specificity, PPV, NPV and like-hood ratio of a positive and negative Pronto Dry test with and without PPI were 43.3%, 86.4%, 81.3%, 3.18, 0.656 and 52.8% vs 71.9%, 80%, 82.1%, 69%, 3.59 and 0.35. This study shows that the sensitivity, specificity, NPV and PPV of rapid urease test was reduced in patients who are on PPI. The exclusive use of the rapid urease test for the diagnosis of Helicobacter pylori cannot be recommended in patients with prior PPI use.


Is accuracy of weight perception associated with health risk behaviors in a diverse sample of obese adolescents?
Current evidence is equivocal as to whether adolescent's perception of weight status is linked to both healthy and risky behaviors. This study examined the association between accurate and inaccurate perception of weight and self-reported health and risk behaviors among a diverse sample of obese, urban adolescents. Data were analyzed from 1,180 participants in the 2009 Philadelphia Youth Risk Behavior Survey. Health behaviors of obese students self-identifying as very or slightly overweight were compared to obese students who underestimated their weight status. Accurate self-identifiers of weight status were significantly more likely to report trying to lose weight, bullying victimization, and suicide attempts as compared to obese students underestimating their weight status. Findings suggest that it is important for school nurses to understand that perceived weight status confers distinct risk profiles and differing needs for health-related services related to the physical, mental, and social health of adolescents.


Outcome in Children Operated for Membranous Subaortic Stenosis: Membrane Resection Plus Aggressive Septal Myectomy Versus Membrane Resection Alone.
The optimal surgical procedure for treatment of fibromembranous subaortic stenosis has been a subject of debate. We report our experience with patients treated for membranous subaortic stenosis using membrane resection alone and membrane resection plus aggressive septal myectomy. Patients followed in the pediatric cardiology clinic of a university hospital, who had undergone surgery for subaortic stenosis between 2002 and 2013 were reviewed. Recurrence of subaortic membrane, residual left ventricular outflow gradient, and aortic valve function were analyzed. Forty-six patients underwent surgery for subaortic membrane. Of these, 19 had membrane resection plus aggressive septal myectomy, while 27 had membrane resection alone. Mean age at surgery for the membrane resection group was 7.7 ± 3.9 years and 10.9 ± 3.6 years for the membrane resection plus aggressive myectomy group. Preoperative subaortic gradient for the membrane resection group was 75.5 ± 26.7 mm Hg and 103.2 ± 39.7 mm Hg for the membrane resection plus aggressive myectomy group. The mean follow-up left ventricular outflow tract gradient was 42.3 ± 31.3 mm Hg in the membrane resection group, while it was 11.6 ± 6.3 mm Hg in the aggressive septal myectomy group. Nine patients from the membrane resection group had significant regrowth of the subaortic membrane during the follow-up period, while none of the aggressive septal myectomy group had detectable membrane on echocardiography. Seven of the nine patients with recurrence of the subaortic membrane underwent subsequent membrane resection plus aggressive septal myectomy. Intraoperative finding in all these redo cases was recurrence (growth) of a subaortic membrane. Aggressive septal myectomy offers less chance of recurrence, freedom from reoperation, and an improved aortic valve function. This is especially important in sub-Saharan settings where a chance of getting a second surgery is unpredictable.


Comparative Study of Soybean Oil and the Mixed Fatty Acids as Acyl Donors for Enzymatic Preparation of Feruloylated Acylglycerols in Ionic Liquids.
Feruloylated acylglycerols (FAGs) are the lipophilic derivatives of ferulic acid. In this work, soybean oil (SBO) and the mixed fatty acids (MFA) were selected as fatty acyl donors, and reacted with glyceryl monoferulate (GMF) to prepare FAGs in ionic liquids (ILs). Effect of various reaction parameters (time, temperature, enzyme concentration, and substrate ratio) and ILs on the GMF conversion and the reaction selectivity for FAGs formation were investigated. Response surface methodology (RSM) based on a 3-level-4-factor Box-Behnken experimental design was employed to evaluate the inactive effect of reaction parameters. For the esterification of GMF with MFA, the maximum GMF conversion (98.9 ± 0.9%) and FAG yield (88.9 ± 0.6%) were achieved in [C10mim]PF6. However, for the transesterification of GMF with SBO, the maximum GMF conversion (94.3 ± 0.7%) and FAG yield (83.8 ± 1.0%) were obtained in [C12mim]PF6. High FAG selectivities (∼0.90) were also obtained using SBO or MFA as acyl donors.


Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes.
The aim of this study was to evaluate the significance of endothelial cell-derived microparticles (EDMP), angiopoietin-2 (Ang-2) and adiponectin in hyperlipidemic patients with and without type 2 diabetes mellitus, and to compare the two for the effects of eicosapentaenoic acid (EPA) on these markers. One hundred and twenty-six hyperlipidemic patients with and without type 2 diabetes mellitus received EPA 1,800 mg daily, and 50 of the patients were non-diabetic. EDMP and Ang-2 levels prior to treatment were higher in diabetic patients than in non-diabetic patients, whereas adiponectin levels were lower in diabetics. When diabetic patients were classified into two groups on the basis of Ang-2 levels, the levels of all markers remained unchanged in those without a high Ang-2 level after EPA treatment. In contrast, all markers except for adiponectin were decreased significantly in diabetic patients with high Ang-2 levels after 6 months of EPA treatment. These diabetic patients with high Ang-2 levels displayed a more significant increase in adiponectin levels after EPA treatment than those who did not. These results suggest that EPA possesses an adiponectin-dependent anti-atherosclerotic effect and may be beneficial for the prevention of vascular complications in diabetic patients with high Ang-2 levels.


Promotion of physical activity-related health competence in physical education: study protocol for the GEKOS cluster randomized controlled trial.
One central goal of physical education in many countries is to empower students to be physically active throughout their lifespan. Physical activity-related health competence (PAHCO) encompasses physical, cognitive, and motivational elements associated with the individuals' ability to be physically active in a health-enhancing way. To date, there is a lack of empirical evidence concerning effective programs and methods to promote PAHCO in physical education. The purpose of this study is to examine to what extent a health and physical fitness-related program that includes learning tasks integrating theoretical and practical elements promotes students' PAHCO in physical education. This study is a cluster randomized controlled trial that compares two physical education intervention programs on health and physical fitness (IG-run, IG-game play) with regular physical education lessons (CG-run, CG-game play) in secondary schools in Germany. Forty-eight physical education classes (ninth grade) were recruited and randomly allocated to the four study groups. The intervention programs include six physical education lessons on health and physical fitness and only differ in the type of physical activity that is executed (running and jumping vs. small-sided games). The students' PAHCO is examined both pre- and post-intervention and after 8-12 weeks of follow-up. We also determine various process variables during the intervention period to analyze the intervention fidelity. The results of this study provide evidence on whether a combination of theoretical and practical elements in physical education can enhance students' PAHCO. Beyond that, our process analyses will allow differentiated insights into the mechanism of how the intervention programs work. German Clinical Trials Register (DRKS), DRKS-ID: DRKS00016349 . Retrospectively registered on 10 January 2019.


The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor.
Inhibition of P300 acetyltransferase activity by specific inhibitor C646 has been shown to improve insulin signaling. However, the underlying molecular mechanism of this improvement remains unclear. In this study, we analyzed P300 levels of obese patients and found that they were significantly increased in liver hepatocytes. In addition, large amounts of P300 appeared in the cytoplasm. Inhibition of P300 acetyltransferase activity by C646 drastically increased tyrosine phosphorylation of the insulin receptor protein substrates (IRS1/2) without affecting the tyrosine phosphorylation of the beta subunit of the insulin receptor (IRβ) in hepatocytes in the absence of insulin. Since IRS1/2 requires membrane translocation and binding to inositol compounds for normal functions, we also examined the role of acetylation on binding to phosphatidylinositol(4,5)P2 and found that IRS1/2 acetylation by P300 reduced this binding. In contrast, we show that inhibition of IRS1/2 acetylation by C646 facilitates IRS1/2 membrane translocation. Intriguingly, we demonstrate that C646 activates IRβ's tyrosine kinase activity and directly promotes IRβ interaction with IRS1/2, leading to the tyrosine phosphorylation of IRS1/2 and subsequent activation of insulin signaling even in the absence of insulin. In conclusion, these data reveal the unique effects of C646 in activating insulin signaling in patients with obesity and diabetes.


Implication of sphingosin-1-phosphate in cardiovascular regulation.
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite generated by phosphorylation of sphingosine catalyzed by sphingosine kinase. S1P acts mainly through its high affinity G-protein-coupled receptors and participates in the regulation of multiple systems, including cardiovascular system. It has been shown that S1P signaling is involved in the regulation of cardiac chronotropy and inotropy and contributes to cardioprotection as well as cardiac remodeling; S1P signaling regulates vascular function, such as vascular tone and endothelial barrier, and possesses an anti-atherosclerotic effect; S1P signaling is also implicated in the regulation of blood pressure. Therefore, manipulation of S1P signaling may offer novel therapeutic approaches to cardiovascular diseases. As several S1P receptor modulators and sphingosine kinase inhibitors have been approved or under clinical trials for the treatment of other diseases, it may expedite the test and implementation of these S1P-based drugs in cardiovascular diseases.


Niacin treatment of stroke increases synaptic plasticity and axon growth in rats.
Niacin is the most effective medication in current clinical use for increasing high-density lipoprotein cholesterol. We tested the hypothesis that niacin treatment of stroke promotes synaptic plasticity and axon growth in the ischemic brain. Male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion and treated with or without Niaspan (a prolonged-release formulation of niacin, 40 mg/kg) daily for 14 days starting 24 hours after middle cerebral artery occlusion. The expression of synaptophysin, Nogo receptor, Bielschowsky silver, brain-derived neurotrophic factor, and its receptor tropomyosin-related kinase B were measured by immunohistostaining and Western blot, respectively, in the ischemic brain. Complementing in vivo studies, primary cultured neurons were used to test the effect of niacin and high-density lipoprotein on neurite outgrowth and brain-derived neurotrophic factor/tropomyosin-related kinase B expression. Niaspan treatment of stroke significantly increased synaptophysin, Bielschowsky silver, brain-derived neurotrophic factor/tropomyosin-related kinase B expression, and decreased Nogo receptor expression in the ischemic brain compared with middle cerebral artery occlusion control animals (P<0.05, n=8/group). Niacin and high-density lipoprotein treatment significantly increased neurite outgrowth and brain-derived neurotrophic factor/tropomyosin-related kinase B expression in primary cultured neurons. Tropomyosin-related kinase B inhibitor attenuated niacin-induced neurite outgrowth (P<0.05, n=6/group). Niacin treatment of stroke promotes synaptic plasticity and axon growth, which is mediated, at least partially, by the brain-derived neurotrophic factor/tropomyosin-related kinase B pathways.


Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies.
Ellagic acid as a polyphenol or micronutrient, which can be naturally found in different vegetables and fruits, has gained considerable attention for cancer therapy due to considerable biological activities and different molecular targets. Ellagic acid with low hydrolysis and lipophilic and hydrophobic nature is not able to be absorbed in circulation. So, accumulation inside the intestinal epithelial cells or metabolization to other urolithins leads to the limitation of direct evaluation of EA effects in clinical studies. This review focuses on the studies which supported anticancer activity of pure or fruit-extracted ellagic acid through in vitro, in vivo, in silico, and drug delivery methods. The results demonstrate ellagic acid modulates the expression of various genes incorporated in the cancer-related process of apoptosis and proliferation, inflammation related-gens, and oxidative-related genes. Moreover, the ellagic acid formulation in carriers composed of lipid, silica, chitosan, iron- bovine serum albumin nanoparticles obviously enhanced the stable release and confident delivery with minimum loss. Also, in silico analysis proved that ellagic acid was able to be placed at a position of cocrystal ADP, in the deep cavity of the protein target, and tightly interact with binding pocket residues leading to suppression of substrate availability of protein and its activation inhibition.


Orientation of adsorbed polar molecules (dipoles) in external electrostatic field.
A model is proposed in the framework of classical electrostatics to describe the behavior of an adsorbed polar molecule near the plane interface between two insulators under the action of an external electrostatic field. The molecule is considered as a permanent point dipole that polarizes the interface and interacts with it through electrostatic image forces. The latter and the applied field try to reorient the dipole in a competitive manner. The system behavior turns out to be rather complicated: it may show a bistable character with a hysteresis (a switch). Such a switch can serve as an element in a memory network made of adsorbed molecules.


Oxidation and assimilation of carbohydrates by Micrococcus sodonensis.
Perry, Jerome J. (North Carolina State University, Raleigh), and James B. Evans. Oxidation and assimilation of carbohydrates by Micrococcus sodonensis. J. Bacteriol. 91:33-38. 1966.-Micrococcus sodonensis is a biotin-requiring strict aerobe that cannot utilize carbohydrates as sole sources of carbon and energy. However, addition of mannose, glucose, sucrose, or maltose to a medium on which the organism can grow resulted in an increase in total growth. M. sodonensis oxidized these sugars without induction, thus indicating the presence of constitutive enzymes for their transport, activation, and metabolism. Under appropriate nonproliferating cell conditions, glucose was readily incorporated into essential constituents of the cell. When glucose-1-C(14) and glucose-6-C(14) were oxidized by nonproliferating cells, the label was found in both the protein and nucleic acid fractions of the cell. The respiratory quotients of cells oxidizing glucose in saline and in phosphate buffer indicated assimilation of sugar carbon in buffer and virtually no assimilation in saline. The ability of M. sodonensis to completely oxidize glucose and to grow on intermediates of glucose oxidation but not on glucose suggests that glucose may suppress or repress some reaction(s) necessary for growth, and that growth substrates either derepress or circumvent this block.


Practical Bayesian Inference in Neuroscience: Or How I Learned To Stop Worrying and Embrace the Distribution.
Typical statistical practices in biological sciences have been increasingly called into question due to difficulties in replication of an increasing number of studies, much of which is confounded by the relative difficulty of null significance hypothesis testing designs and interpretation of p-values. Bayesian inference, representing a fundamentally different approach to hypothesis testing, is receiving renewed interest as a potential alternative or complement to traditional null significance hypothesis testing due to its ease of interpretation and explicit declarations of prior assumptions. Bayesian models are more mathematically complex than equivalent frequentist approaches, which have historically limited applications to simplified analysis cases. However, the advent of probability distribution sampling tools with exponential increases in computational power now allows for quick and robust inference under any distribution of data. Here we present a practical tutorial on the use of Bayesian inference in the context of neuroscientific studies. We first start with an intuitive discussion of Bayes' rule and inference followed by the formulation of Bayesian-based regression and ANOVA models using data from a variety of neuroscientific studies. We show how Bayesian inference leads to easily interpretable analysis of data while providing an open-source toolbox to facilitate the use of Bayesian tools.


[Expression and significance of p120ctn isoforms in lung squamous cell carcinomas and adenocarcinomas.].
It has been proven that p120ctn plaied an important role in cell adhesion and correlates with tumorigenesis significantly, the aim of this work is to investigate the expression of p120ctn (p120 catenin) isoform proteins in lung squamous cell carcinomas and adenocarcinomas, and analyze the correlations between p120ctn and clinicopathological parameters. Immunofluorescence and Westren Blot were used to detect the expression of p120ctn isoforms in lung cancer tissues and the corresponding normal lung tissues. Compared to normal epithelium of lung, lung cancer tissues show reduction or absence of membrane expression or cytoplasmic accumulation of p120ctn. In normal lung tissues, the total levels of p120ctn proteins were significantly higher than that in lung cancer tissues (P <0.001). The isoform 1 (120KD) and isoform 3 (100KD) proteins were the major isoforms of p120ctn expressed in normal lung tissues, which were significantly reduced in lung cancer samples (P =0.001 and P <0.001, respectively). Furthermore, the changes in isoform 3 protein levels was negatively associated with lymph node metastasis (P =0.005). Reductions of p120ctn isoform 1 and 3 is a common phenomenon in lung cancer tissues and may play a role in metastasis progression in human lung cancer.


Platinum-Based Chemotherapy and Immunotherapy in Early Triple-Negative Breast Cancer: A Meta-Analysis and Indirect Treatment Comparison.
Triple-negative breast cancer (TNBC) comprises 15% of invasive breast cancers. Platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) have been extensively researched in recent years as promising treatments in the neoadjuvant setting. However, clinical data is lacking in direct comparisons of these two treating regimens. We conducted an online search on PubMed, Embase, Cochrane Online Library and key oncological meetings for available randomized controlled trials (RCTs) investigating ICIs or platinum drugs versus anthracyclines and taxane-based neoadjuvant chemotherapy (AT-based NACT). Conventional meta-analyses were conducted separately, and then indirect comparisons for clinical efficacy and safety profile were performed between ICIs and platinum drugs using AT-based NACT as a common comparator. Seven random controlled trials (RCTs) with 1,647 patients were included in the meta-analysis. The indirect comparison demonstrated that ICIs plus chemotherapy significantly improved pathological complete response (pCR) rate (p = 0.00445, OR, 1.78; 95%CI, 0.70-4.53), and decreased the adverse effect (AE) related discontinuance versus platinum-based chemotherapy (P = 0.00015; OR 0.46; 95%CI, 0.26-0.82). ICIs plus chemotherapy showed increased pCR rate and decreased adverse effects compared with platinum-based chemotherapy in early TNBC. However, subgroup analysis and survival data to explore the proper patients for each treatment remains scarce. Therefore, further studies with powered direct comparisons of these two treating regimens are required.


[Controlled clinical trials of initial observation on therapeutic effects of moxibustion for osteoarthritis of the knee: multi-center clinical effect].
To compare therapeutic effects between moxibustion and infrared therapy for the treatment of knee osteoarthritis. From January 2007 to June 2008 period, 65 patients with knee osteoarthritis were divided into treatment and control groups randomly uniform random number table generated from SAS statistical software. Among 35 patients in the treatment group, 17 patients were male and 18 patients were female, ranging in age from 45 to 75 years, with an average of (61.2+/-6.4) years; the course of disease ranged from 9 to 43 months, with a mean of (23.6+/-13.8) months; the preoperative Lysholm score ranged from 19 to 28 scores, averaged (24.3+/-3.3) scores. In the control group, there were 30 patients, including 13 males and 17 females, ranging in age from 47 to 79 years, with an average of (62.5+/-9.3) years; the course of disease ranged from 8 to 45 months, with a mean of (24.6+/-16.6) months; the preoperative Lysholm score ranged from 20 to 29 scores, averaged (25.9+/-3.0) scores. The patients in the treatment group were treated with moxibustion, and the patients in control group were treated with infrared therapy. All the patients were followed up for 4 weeks. The Lysholm scores were compared between the two groups. According to Lysholm score for clinical efficacy, treatment group got (87.5+/-5.6) scores and the control group were (85.9+/-3.5) scores, the Lysholm score of the treatment group was higher than that of the control group (P<0.05). Among pain score, joint flexion and extension score, joint stability score, and up and down stairs score, the pain and joint stability scores of patients in the treatment group were higher than those of control group (P<0.05). Compared with infrared therapy, moxibustion treatment for knee osteoarthritis can get better joint function, which is effect to alleviate the patient's pain, improve joint stability, improve the efficacy, and is valued to be promoted.


Paediatric diarrhoea--rehydration therapy revisited.
Acute infective diarrhoea remains one of the most common causes of morbidity and mortality in children under 5 years of age. This paper reports on a 7-year experience of management of paediatric diarrhoea at King Edward VIII Hospital, Durban, in which an inpatient case-fatality rate of nearly 25% was reduced to less than 7%, and the admission rate was reduced by 60% by a cumulative effect of the following measures: one of four paediatric wards was converted into a diarrhoea ward; improved attention to protocol resulted in a rapid reduction in the inpatient case-fatality rate, but further improvement resulted from a strong commitment to an efficient outpatient oral rehydration protocol to reduce the pressure on inpatient beds, as well as a simplified approach to fluid therapy; and a formula was developed based on units of 5 ml/kg/h, and applicable to both oral and intravenous routes. The most important assessment of dehydrated patients is determination of a need for resuscitation. In less severely ill patients it is not necessary to calculate rehydration fluid requirements by a 'percent dehydration' formula.


Nifuroxazide Mitigates Angiogenesis in Ehlrich's Solid Carcinoma: Molecular Docking, Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling.
Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich's mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich's solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.


SARS-CoV-2 infection is associated with increased odds of insomnia, RLS and dream enactment behavior.
Literature suggests that the COVID-19 pandemic has resulted in poor sleep quality, especially among the infected population. However, literature regarding the effect of COVID-19 pandemic and SARS-CoV-2 infection on occurrence of insomnia, restless legs syndrome and dream enactment behavior is either scarce or unavailable. This study was planned to assess the effect of SARS-CoV-2 infection on the occurrence of insomnia, restless legs syndrome (RLS) and dream enactment behavior (DEB). For this cross-sectional study, a questionnaire comprising of items related to demographic details, past medical history, and information related to SARS-CoV-2 infection was distributed through social media. Insomnia was diagnosed using clinical criteria. RLS, DEB, sleep quality, depression and anxiety were assessed using a validated questionnaire. Information regarding the use of hypnotic medications was also gathered. Of the 1596 respondents, 37.2% reported disturbed sleep while insomnia was reported by 22.6% respondents. 27.3% of respondents reported RLS and 17.4% suffered DEB. The odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03-1.58; P < 0.02) and among those who had SARS-CoV-2 infection (OR = 1.76; 95% CI = 1.42-2.19; P < 0.001). Similarly, SARS-CoV-2 infection was also associated with increased odds of RLS (OR = 2.48; 95% CI = 1.98-3.11; P < 0.001) and DEB (OR = 1.58; 95%CI = 1.21-2.06; P < 0.001). Insomnia, RLS and DEB were more frequent among respondents who required oxygen therapy, those who experienced loss of taste and/or smell, depression and anxiety. Prevalence of insomnia, DEB and RLS was higher than said prevalence among respondents with no history of SARS-CoV-2 infection, but lower than that of those with positive history of SARS-CoV-2 infection. 5.3% of respondents reported taking hypnotic medications before infection, 7% during infection and 5.3% after infection. SARS-CoV-2-infection-related factors in association with environmental factors have increased the prevalence of insomnia, DEB and RLS among subjects having infection. SARS-CoV-2-associated immunological changes, hypoxia and neurotropism may play a role in occurrence of insomnia, DEB and RLS.


Purification of gamma-glutamyltransferase by phenyl boronate affinity chromatography. Studies on the acceptor specificity of transpeptidation by rat kidney gamma-glutamyltransferase.
gamma-Glutamyltransferase has been purified from rat kidney by a novel procedure using phenyl boronate affinity chromatography. The highly purified enzyme has been studied with respect to acceptor specificity for a number of amino acids, amino acid analogues, dipeptides and tripeptides. The acceptor activity is specific for L-amino acids. The amino acids and the majority of the essential amino acids are poor acceptors while the sulphur-containing amino acids are the best acceptors. The acceptor activity is modulated by the substitution of the amino acid side chain. Substitution of the side chain at the delta, gamma or beta positions results in a proportionally decreasing ability to act as acceptor. The carbonyl moiety of the gamma-carboxy group of the acceptor appears to be essential for acceptor activity, absence of an alpha-carboxy carbonyl group increases the Kappm of the acceptor approximately 100-fold.


The 4 U's Rule of Fibromyalgia: A Proposed Model for Fatigue in a Sample of Women with Fibromyalgia: A Qualitative Study.
Although fatigue usually goes unnoticed, it is a symptom that poses great challenges to patients with fibromyalgia and is a strong limitation. The aim of this study is to identify and describe the variables involved in fatigue in nine different situations of the Goal Pursuit Questionnaire (GPQ) that may occur in the daily lives of women with fibromyalgia, according to an ABC (Antecedents-Behaviors-Consequences) model. This study followed a qualitative descriptive research method and a deductive-inductive hybrid approach based on a phenomenological paradigm. Twenty-six women with fibromyalgia participated in focus group discussions between February and March of 2018. Thematic content analysis was carried out from transcribed verbatim interviews. We identified nine major themes that emerged from the participants' conversations: self-imposed duties, muscle fatigue, overwhelming feeling of tiredness, difficulty thinking, difficulty concentrating, negative emotions, lifestyle changes, affected everyday activities, and lack of motivation for daily activities and social interactions. We conclude that the ABC model allowed certain elements to emerge regarding the fatigue experience, highlighting its importance as a symptom in fibromyalgia. This additional analysis of the ABC model showed that fatigue can be described through the 4 U's Rule, which is integrated by these four adjectives: (1) Unpredictable, (2) Uncontrollable, (3) Unseen, and (4) Unintelligible. Identifying these characteristics can contribute to a better understanding of fibromyalgia in addition to better treatment for these patients.


Cerrena aurantiopora sp. nov. (Polyporaceae) from eastern Asia.
A new species of polypore in genus Cerrena was discovered in Kangwon Province, Korea. The resupinate basidiocarp and light orange, poroid hymenophore were sufficiently different to be distinguished from previously recorded species of Cerrena, C. consors, C. cystidiata, C. sclerodepsis and C. unicolor. Based on the results of morphological and phylogenetic analyses, we propose this new polypore as Cerrena aurantiopora sp. nov.


Using mass spectrometry to detect buffalo salivary odorant-binding protein and its post-translational modifications.
A large number of mammalian odorant-binding proteins, which are lipocalins, have been studied. These proteins participate in peri-receptor events by selecting and carrying odorant molecules. The present study aimed at identifying the buffalo salivary odorant-binding protein (sOBP), and to determine its post-translational modification using mass spectrometry. The buffalo salivary 21 kDa protein was initially separated adopting sodium dodecyl sulfate-polyacrylamide gel electrophoresis and it was identified as sOBP with high statistical reliability using liquid chromatography/tandem mass spectrometry (LC/MS/MS) and SEQUEST, for the first time. Further, the post-translationally modified peptides were screened adopting MS/MS. A total of four post-translational modifications, namely glycation at lysine-(59), hydroxylation at lysine-(134), ubiquitination at lysine-(121), and dihydroxylation in lysine-(108), were recorded. Moreover, these modifications have not been identified in buffalo salivary odorant-binding protein.


Purification and Some Properties of Chlorella fusca Ribulose 1,5-Diphosphate Carboxylase.
Ribulose 1,5-diphosphate carboxylase has been purified from extracts of autotrophically grown Chlorella fusca by ammonium sulfate precipitation and centrifugation on a linear sucrose density gradient. The enzyme was homogeneous by the criterion of polyacrylamide gel electrophoresis. The molecular weight of the enzyme was 530,000, and it was composed of two types of subunit of molecular weight 53,000 and 14,000. Ribulose 1,5-diphosphate, CO(2), and Mg(2+) had Michaelis constant values of 15 mum, 0.3 mm, and 0.37 mm, respectively. At high bicarbonate concentration (17 mm and 50 mm), 6-phosphogluconate inhibited the enzyme, the inhibition being noncompetitive with respect to ribulose 1,5-diphosphate (Ki 0.065 mm), whereas at low bicarbonate concentration (1 mm), 6-phosphogluconate activated the enzyme. Oxygen was a competitive inhibitor with respect to CO(2), suggesting the enzyme also functions as an oxygenase. This was confirmed by direct assay, a 1: 1 stoichiometry between ribulose 1,5-diphosphate consumed and O(2) uptake being observed.


Understanding the private worlds of physicians, nurses, and parents: a study of life-sustaining treatment decisions in Italian paediatric critical care.
This study's aim was to describe: (a) How life-sustaining treatment (LST) decisions are made for critically ill children in Italy; and (b) How these decisional processes are experienced by physicians, nurses and parents. Focus groups with 16 physicians and 26 nurses, and individual interviews with 9 parents were conducted. Findings uncovered the 'private worlds' of paediatric intensive care unit (PICU) physicians, nurses and parents; they all suffer tremendously and privately. Physicians struggle with the weight of responsibility and solitude in making LST decisions. Nurses struggle with feelings of exclusion from decisions regarding patients and families that they care for. Physicians and nurses are distressed by legal barriers to LST withdrawal. Parents struggle with their dependence on physicians and nurses to provide care for their child and strive to understand what is happening to their child. Features of helpful and unhelpful communication with parents are highlighted, which should be considered in educational and practice changes.


Soybean lecithin-stabilized oil-in-water (O/W) emulsions increase the stability and in vitro bioaccessibility of bioactive nutrients.
This study was proposed to investigate the possibility of co-delivering essential oils and lipophilic nutrients via lecithin stabilized emulsions. Emulsions with different droplet sizes (62.5-105 nm), zeta potentials (-33.7 to -58.6 mV), and PdI values (0.155-0.275) were successfully prepared. Incorporation of curcumin into emulsions significantly improved its water solubility (1700-fold), thermal and photochemical stability. The droplet size of curcumin-loaded emulsions did not change over 30 days of storage at 4 °C. Gastrointestinal tract (GIT) digestion caused significant changes in the droplet size and interfacial properties of curcumin-loaded emulsions. The bioaccessibility of encapsulated curcumin was 4.79-10.6-fold higher than that of free molecule. This is mainly attributed to the different solubility of curcumin in essential oils, which also showed different bioaccessibility. The findings suggested that emulsions can be novel carriers for co-delivering essential oils and lipophilic nutrients with increased stability and bioaccessibility.


Patterns of inheritance in Irish and Italian families with neural tube defects: comparison between high and low rate areas.
Neural tube defects (NTDs) may result from a genetic susceptibility interacting with environmental exposures occurring early in pregnancy. Current research is concerned with enlarging our understanding of the action of folic acid, a B group vitamin, which has been shown to prevent the occurrence of NTDs in clinical trials. Despite the epidemic waves in the incidence of NTDs and the existence of areas with very high rates, there have been few studies that explored the genetic contribution to NTDs in high rates versus low rate areas. We investigated the genetic epidemiologic factors that occur in NTD families and compared their frequency in a high rate area-Ireland-with a low rate area-Italy. We explored the existence of three features indicative of hereditary factors and found that all three factors were higher in Ireland than in Italy. These factors were (i) sibling recurrence risk (3.3% vs 1.6%; p = 0.2), (ii), other malformations in siblings (11.5% vs 3.3%; p < 0.001) and (iii) average number of children in mothers' families vs fathers' families (average difference in Ireland 1.0 vs 0.4 in Italy; p < 0.1). These results support the motion that geographic differences in occurrence of NTDs are due at least in part to differing prevalences of genetic susceptibility factors. Further epidemiological and molecular studies are needed to confirm this observation. In addition, studies of the interactions between environmental agents and genetic susceptibility will be important in determining their relative contributions.


Field-Effect Transistor with a Plasmonic Fiber Optic Gate Electrode as a Multivariable Biosensor Device.
A novel multivariable system, combining a transistor with fiber optic-based surface plasmon resonance spectroscopy with the gate electrode simultaneously acting as the fiber optic sensor surface, is reported. The dual-mode sensor allows for discrimination of mass and charge contributions for binding assays on the same sensor surface. Furthermore, we optimize the sensor geometry by investigating the influence of the fiber area to transistor channel area ratio and distance. We show that larger fiber optic tip diameters are favorable for electronic and optical signals and demonstrate the reversibility of plasmon resonance wavelength shifts after electric field application. As a proof of principle, a layer-by-layer assembly of polyelectrolytes is performed to benchmark the system against multivariable sensing platforms with planar surface plasmon resonance configurations. Furthermore, the biosensing performance is assessed using a thrombin binding assay with surface-immobilized aptamers as receptors, allowing for the detection of medically relevant thrombin concentrations.


The neglected surgery - Hernioscopy - Maybe the best choice for strangulated groin hernias in the COVID-19 pandemic.
Introduction: While elective surgeries have been postponed worldwide due to the COVID-19 pandemic, emergency operations cannot be delayed and are continuously being performed just like before the pandemic outbreak [1].

 Aim: Although elective surgeries have been postponed worldwide due to the COVID-19 pandemic, emergency operations cannot be delayed and are continuously being performed. In general surgery practice, incarcerated / strangulated inguinal hernias take a prominent place among emergency surgeries. In 1% of these patients, the hernia contents retreat spontaneously into the abdomen until the hernia sac is opened. It is strongly recommended that these bowel segments be evaluated for possible intestinal necrosis.

 Results: Patients who underwent emergency surgery and hernioscopy in the Sakarya Training and Research Hospital General Surgery Service due to incarcerated or strangulated inguinal hernia between March 2020 and October 2020 were included in the study. Hernioscopy procedure was performed using the single-port and glove-port methods. For each patient, the following variables were recorded: age, duration of complaints, comorbidities, hernia repair method, operation time, incarcerated organ, postoperative complications and whether ischemia improved after reduction or resection was required.

  Conclusion: Hernioscopy is a procedure performed under spinal anesthesia which prevents unnecessary laparotomies and should be considered as first-line treatment during the COVID-19 pandemic in patients who undergo emergency surgery for strangulated inguinal hernia.